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HTN is also most prevalent among minorities, specifically non-Hispanic blacks (42.4% men, 44% women) [26].##### b Hypertension HTN, defined as a systolic blood pressure (SBP) greater than 140 and/or a diastolic blood pressure (DBP) greater than 90 is related to increased and elevated BMI.#### 1 Cardiometabolic Disease Risk ##### a Type 2 Diabetes Mellitus T2DM, characterized by hyperglycemia, insulin resistance, and/or impaired insulin sensitivity, affects over 300 million people worldwide and possibly 12–14% of adults in the United States [21]. T2DM may have the greatest association to obesity when compared to any other cardiometabolic disease [22]. The Nurses' Health Study and the National Health and Nutrition Examination Survey III (NHANES III) have provided a great deal of information regarding the relationship between T2DM and obesity. As BMI increases >35 kg/m2, the relative risk for T2DM increases significantly. This increased risk is closely related to the increase in visceral fat, as measured by WC [23]. Like obesity, T2DM is more prevalent among minorities (15.9% American Indian/Alaskan; 13.2% non-Hispanic blacks; 12.8% Hispanics) than non-Hispanic whites (7.6%) [24,25]. Over the past 20 years, both have increased in prevalence. Data collected from the Behavioral Risk Factor Surveillance System shows the rise in obesity and T2DM paralleled each other from 1990 to 2000, both increasing by almost 50% [22]. As HCP we know that diabetes, especially when uncontrolled, leads to poor long-term health outcomes. Given the relationship between the two, it is important that the HCPs (1) recognize this relationship and (2) provide the appropriate counseling to help patients lose weight and decrease their risk for developing diabetes. ##### b Hypertension HTN, defined as a systolic blood pressure (SBP) greater than 140 and/or a diastolic blood pressure (DBP) greater than 90 is related to increased and elevated BMI. HTN is also most prevalent among minorities, specifically non-Hispanic blacks (42.4% men, 44% women) [26].Specifically, HTN is associated with weight at adulthood, weight gain throughout adulthood and obesity [28].The rise in HTN risk as it is associated to weight gain is dose-dependent.This means the greater the weight gain, the greater risk (hazard ratio, 2.52; CI 95%), specifically among men [29].Just as weight gain negatively affects BP, weight loss positively affects BP.

The following list gives you a brief rundown of the symptoms and causes of other types of diabetes: Diabetes due to loss or disease of pancreatic tissue: If you have a disease such as cancer that requires you to have some of your pancreas removed, you lose your pancreas's valuable insulin-producing beta cells, and your body becomes diabetic.After you give birth, the foetus and placenta are no longer in your body, so their anti-insulin hormones are gone and your diabetes disappears. Be aware that, even though your diabetes subsides after you give birth, type 2 diabetes develops within 15 years after the pregnancy in more than half of the women who had gestational diabetes. This high likelihood of type 2 diabetes probably results from a genetic susceptibility to diabetes in these women that is magnified by the large amount of anti-insulin hormones in their bodies during pregnancy. Every time you go for an antenatal check, your midwife or doctor probably wants to check your urine for, among other things, sugar. It may be really tough to wee into that tiny pot when your tummy is so big that you can't see where you're aiming, but the result is well worth the effort! The 'renal threshold' at which glucose passes from your bloodstream into your urine is often lower when you're pregnant. That means that you can have sugar in your urine even if you aren't diabetic. But if you do have sugar in your urine, your midwife or doctor will test your blood for sugar, too. You may also have a blood test done for gestational diabetes around the 24th to the 28th week of your pregnancy. Could You Have Another Type of Diabetes? Cases of diabetes other than type 1, type 2, or gestational are rare and usually don't cause severe diabetes in the people who have them. But occasionally one of these other types of diabetes is responsible for a more severe case of diabetes, so you should be aware that they exist. The following list gives you a brief rundown of the symptoms and causes of other types of diabetes: Diabetes due to loss or disease of pancreatic tissue: If you have a disease such as cancer that requires you to have some of your pancreas removed, you lose your pancreas's valuable insulin-producing beta cells, and your body becomes diabetic.You produce these hormones in glands other than your pancreas.If you get a tumour on one of these hormone-producing glands, the gland sometimes produces excessive levels of the hormones that act in opposition to insulin.This can give you either simple glucose intolerance or diabetes.

Hydration is the primary treatment.The disease is self-limiting, and the primary anticipated problem is shock from dehydration.Symptoms are usually limited to gastrointestinal upset including cramps, diarrhea, and vomiting.The bacteria are usually destroyed by stomach acid or cooking, but the toxin survives to be absorbed by the gut.Drug overdose is another common source of ingested toxin. You should know the risks associated with overdose of any drug that you carry in quantity. The likely source of a problem will be overuse of pain medication like acetaminophen, ibuprofen, or opioids like hydrocodone. This often happens when patients are confused about generic and trade names used for drugs. For example, a patient may take full doses of two different brands of pain reliever, hoping for a better result, not realizing that both are trade names for the same medication, such as acetaminophen. The effects of a mild unintentional overdose are usually limited to accentuated side effects like stomach upset or drowsiness. Discontinuing the medication usually solves the problem. Intentional overdose is much more serious. Even common over-the-counter medications such as acetaminophen or iron tablets can be toxic in high doses. Immediate generic treatment followed by emergency evacuation is indicated. In opioid or antihistamine overdose, the immediate threat to life will be respiratory failure due to loss of respiratory drive. Oxygen and positive pressure ventilation can be lifesaving. **Ingested Toxins** Treatment * Basic life support (BLS), PROP * Remove and dilute: oral hydration * Evacuate with advanced life support (ALS) assistance as needed * Contact poison control **American Association of Poison Control Centers** www.aapcc.org (800) 222–1222 Food poisoning is another form of accidental toxic ingestion. The toxin is produced by bacteria such as staphylococci growing in poorly refrigerated food. The bacteria are usually destroyed by stomach acid or cooking, but the toxin survives to be absorbed by the gut. Symptoms are usually limited to gastrointestinal upset including cramps, diarrhea, and vomiting. The disease is self-limiting, and the primary anticipated problem is shock from dehydration. Hydration is the primary treatment.You should suspect infection in any gastrointestinal illness that lasts longer than that.A bacterial infection of the gut should be considered serious and aggressively treated with antibiotics and evacuation.It may be impossible to distinguish between a mild gastroenteritis caused by a viral infection and food poisoning because the signs and symptoms are often the same.

B, The truncus arteriosus, now divided into the pulmonary trunk and aorta, is presented between the right and left atria, which expand lateral to it.The purple part of the interventricular ring will give rise to the atrioventricular bundle and bundle branches, whereas the yellow part of the interventricular ring will not participate in the formation of the adult conducting system.In order to produce powerful synchronous contractions, the working myocardium of the chambers must also, of necessity, conduct rapidly, whereas to act as a pacemaker, the cells of the nodes need to be poorly coupled, and hence display slow conduction. The vertebrate heart is myogenic, implying that all cardiomyocytes have the capacity to generate and conduct the depolarizing impulse. Because cardiac myocytes are electrically coupled, the cells with the highest pacemaking activity take the lead. In the formed normal heart, the leading pacemaker is always within the sinus node. In embryonic hearts, the leading pacemaker is always found at the venous pole (Fig. 52.12). Thus, it is the most recently recruited cells at the venous pole that always have the highest pacemaking activity. All regions of the early embryonic heart tube possess poorly coupled cells and display intrinsic automaticity, thus permitting slow propagation of the depolarizing impulses along the cardiac tube, and producing matching peristaltic waves of contraction that push the blood in an antegrade direction. The myocytes of a developing heart do not have well-developed sarcomeric structures, and have a poorly developed sarcoplasmic reticulum. This tissue has been called primary myocardium, distinguishing it from the rapidly conducting and well-developed working myocardium of the atrial and ventricular chambers. Fig. 52.12 Development of the conduction system of the heart. A, At stage 13 with the truncus arteriosus reflected to the right, the interventricular ring marks the region of the primary heart tube. The purple part of the interventricular ring will give rise to the atrioventricular bundle and bundle branches, whereas the yellow part of the interventricular ring will not participate in the formation of the adult conducting system. B, The truncus arteriosus, now divided into the pulmonary trunk and aorta, is presented between the right and left atria, which expand lateral to it.C, The position of the original primary heart tube ring indicated in the formed heart.The pulmonary trunk has been removed.As development proceeds, the ventricular chambers develop in the cranial part of the heart tube, by ventral expansion, and the atrial chambers in the caudal part by dorsolateral expansion (see Fig.52.8).

In both instances, the new event must meet clinical criteria for ADEM, including the presence of encephalopathy [5].The distinction between multiphasic and recurrent rests on whether the second ADEM illness involves new brain regions (multiphasic) or whether the second event is a recapitulation of the prior illness (recurrent).Table 17.2 ADEM MRI appearance White matter > gray matter, but usually both affected --- Bilateral asymmetric white matter involvement Bilateral symmetric gray matter involvement Deep/juxtacortical white matter > periventricular white matter Both supratentorial and infratentorial lesions, but more supratentorial Small>medium>large, but often all sizes are present in same patient Variable contrast enhancement Spinal cord involvement in ADEM has been described in 11–28 % of patients. Typical spinal cord lesions are large and swollen, show variable enhancement, and predominantly affect the thoracic region. Skip lesions with intervening segments of cord that appear normal are typical (Fig. 17.1) [2]. ### Imaging Follow-Up Sequential MRI scanning during the follow-up period plays an important role in establishing the diagnosis of ADEM. Monophasic ADEM is not associated with development of new lesions. Complete resolution of MRI abnormalities after treatment has been described in 37–75 % of patients and partial resolution in 25–53 % of them. There are no clear criteria documenting how long to continue to image patients after a single ADEM episode. Some authors suggest reassessing patients with at least two additional MRI studies after the first normal MRI over a period of 5 years from the initial episode as the best way to confirm the absence of ongoing lesions [2]. The 2007 consensus (see above) also defined recurrent and multiphasic ADEM in children who experience subsequent events after an initial ADEM illness not associated with a lifelong disorder characterized by an ongoing demyelinating process. The distinction between multiphasic and recurrent rests on whether the second ADEM illness involves new brain regions (multiphasic) or whether the second event is a recapitulation of the prior illness (recurrent). In both instances, the new event must meet clinical criteria for ADEM, including the presence of encephalopathy [5].A diagnosis of meningoencephalitis can be suggested by leptomeningeal enhancement on postcontrast MRI or CT (which is an unusual feature of ADEM) or the typical involvement of limbic structures in herpes encephalitis [1, 2].When the MRI shows large focal tumorlike lesions, one should consider brain tumors, brain abscesses, or tumefactive demyelinating disease [2, 10].

### 15.4.5 Dissection of Sylvian Fissure To expose an MCA aneurysm , the surgeon must open the sylvian fissure widely.After the semicircular dural incision, dura is opened and reflected over the sphenoid wing and temporal muscle to prevent blood from running into the operative field.15.3) The dura mater is tacked to the bone margins.### 15.4.4 Dural Incision (Fig.Fig. 15.3 Skin incision, craniotomy incision, and dural incision. Skin incision ( _arrow head_ ) is from the front of ear to midline of forehead. With two burr hole, cosmetic osteotomy is performed by electric craniotomy. The pterion is cut by chisel and hammer with minimum bone defect ( _arrow_ ). Superficial temporal artery (STA) should be preserved during skin incision. Semicircular dural incision ( _open arrow_ ) Fig. 15.4 Transcranial motor-evoked potential. Hair is shaved partially even in the case of SAH, and cork screw electrodes for transcranial motor-evoked potential (MEP) are placed in both sides of the head ### 15.4.3 Craniotomy (Fig. 15.3) With two burr holes, cosmetic osteotomy is performed by electric craniotomy. The pterion is cut by chisel and hammer with minimum bone defect as much as possible. After removing the bone flap, the outer sphenoid wing is removed down to the meningo-orbital band . The outer sphenoid wing is removed with a rongeur. However, if a patient has a large or giant aneurysm or has a tight brain following SAH, the surgeon may also perform wide osteotomy, which entirely removes the pterion from the surgical field and thus increases the workspace. In the case of severe brain swelling due to SAH and sylvian hematoma, external decompression is performed. ### 15.4.4 Dural Incision (Fig. 15.3) The dura mater is tacked to the bone margins. After the semicircular dural incision, dura is opened and reflected over the sphenoid wing and temporal muscle to prevent blood from running into the operative field. ### 15.4.5 Dissection of Sylvian Fissure To expose an MCA aneurysm , the surgeon must open the sylvian fissure widely.We cut the arachnoid membrane with proper tension using fine tip forceps and microscissors.Usually the arachnoid is opened between the large sylvian veins.We can avoid cutting the vein and bleeding by only cutting the arachnoid membrane above the veins.We can preserve any small veins by only cutting the arachnoid membrane even in the case of SAH.

Such impingement can cause excruciating, radiating pain if dorsal roots are involved and can cause loss of motor control of affected muscles if ventral roots are involved.The discs' proximity to the intervertebral foramina provides an anatomical substrate for understanding the possible impingement of a herniated nucleus pulposus on spinal roots.The outer zone, the cerebellar cortex (three-layered), is infolded to form numerous folia. Deep to the folia is the white matter, carrying afferent and efferent fibers associated with the cerebellar cortex. Deep to the white matter are the deep cerebellar nuclei, cell groups that receive most of the output from the cerebellar cortex via Purkinje cell axon projections. The deep cerebellar nuclei also receive collaterals from mossy fiber and climbing fiber inputs to the cerebellum. These direct afferent inputs to the deep nuclei provide a coarse adjustment for their output to upper motor neurons, whereas the loop of afferent input through the cerebellar cortex back to the deep nuclei provides fine adjustments for their output to upper motor neurons. The cerebellar peduncles are interior to the deep nuclei; these massive fiber bundles interconnect the cerebellum with the brain stem and the thalamus. 5 # Spinal Cord 5.1 Spinal Column: Bony Anatomy 5.2 Lumbar Vertebrae: Radiography 5.3 Spinal Cord: Gross Anatomy in Situ 5.4 The Spinal Cord: Its Meninges and Spinal Roots 5.5 Spinal Cord: Cross-Sectional Anatomy in Situ 5.6 Spinal Cord: White and Gray Matter ### 5.1 Spinal Column: Bony Anatomy Anterior, lateral, and posterior views of the bony spinal column show the relationships of the intervertebral discs with the vertebral bodies. The discs' proximity to the intervertebral foramina provides an anatomical substrate for understanding the possible impingement of a herniated nucleus pulposus on spinal roots. Such impingement can cause excruciating, radiating pain if dorsal roots are involved and can cause loss of motor control of affected muscles if ventral roots are involved.### 5.2 Lumbar Vertebrae: Radiography These lumbar radiographs show the lumbar spine in an anteroposterior view and a lateral view.The vertebral bodies, with their spinous and transverse processes, are visible, and the spaces occupied by the intervertebral discs are uniform and symmetrical in a normal radiograph.A herniated disc may show a disruption of that symmetry.

Do not apply to open skin injuries.**A RNICA** **Warning:** For external use only.MUST-HAVE HERBS The herbs in this section are arranged in order of usefulness.Medical herbalists can advise you on both the appropriate herbal remedies and nutritional measures.The need for such supplementation should be individually assessed by a specialist in view of your age, lifestyle and diet.Because the muscular and skeletal systems are so intimately connected it makes sense to discuss them together. SAFETY AND COMPATIBILITY Many common problems associated with joints and muscles can be safely treated at home, and herbs can offer a lot in terms of pain and inflammation control. However, some of the recommended remedies need to be used in a specific way, otherwise they can be potentially harmful (for example, arnica). Some remedies may not be compatible with conventional medication for joint disorders. In the latter case, a medical herbalist may advise you on alternative herbs that can work alongside the orthodox medication –it is generally not safe to try such remedies yourself. Herbalists can also offset the side effects of medication used for the treatment of advanced arthritis. OTHER THERAPIES There are many complementary therapies that deal with joint and muscle problems, especially back problems. Herbal medicine works extremely well in conjunction with such therapies, for example, osteopathy, and I would encourage you to combine herbs with another therapy of your choice to deal with problems that are 'mechanical' in nature, such as strain injuries, misalignment, bad posture and so on. SUPPLEMENTS Both the muscular and skeletal systems often benefit from specific supplementation that aids the rate of healing and reduces inflammatory tendencies. The need for such supplementation should be individually assessed by a specialist in view of your age, lifestyle and diet. Medical herbalists can advise you on both the appropriate herbal remedies and nutritional measures. MUST-HAVE HERBS The herbs in this section are arranged in order of usefulness. **A RNICA** **Warning:** For external use only. Do not apply to open skin injuries.Uses This herb provides the best treatment for bruising and should be used only in cream or ointment form.Any bumps, knocks or sprains, if treated immediately with arnica, will have minimal swelling and bruising and will heal much quicker.

Ethical standards for disclosure of test results must be strictly followed.If the results indicate that the infecting organism is not sensitive to the prescribed antibiotic, the doctor should be informed and an appropriate antibiotic order obtained.#### After the Test Posttest care is an important aspect of total patient care. Attention should be directed to the patient's concerns about possible results or the difficulties of the procedure. Appropriate treatment subsequent to testing must be provided. For example, after a barium test, a cathartic is indicated. However, if a bowel obstruction has been identified, catharsis is contraindicated. Recognition and rapid institution of treatment of complications (e.g., bleeding, shock, bowel perforation) is essential in caring for the patient who has just had a diagnostic procedure. More invasive tests often require heavy sedation or a surgical procedure. In these situations, aftercare is similar to routine postoperative care. ##### Reporting Test Results Although proper patient preparation and skill and accuracy in performing test procedures are vital, timeliness in reporting test results is no less essential. To be clinically useful, results must be reported promptly. Delays in reporting test results can make the data useless. The data must be included in the appropriate medical record and presented in a manner that is clear and easily interpreted. As in all phases of testing, communication among health care professionals is important. Health care providers need to understand the significance of test results. For example, nurses on the evening shift may be the first to see the results of a culture and sensitivity report on a patient with a urinary tract infection. If the results indicate that the infecting organism is not sensitive to the prescribed antibiotic, the doctor should be informed and an appropriate antibiotic order obtained. Ethical standards for disclosure of test results must be strictly followed.Its purpose was to improve the health care of each individual by insuring the ability for each person to obtain reasonable health care, and to allow each individual access to and protection of his or her health care information.

* Caused by unmetabolized ethylene glycol and its toxic metabolites (frequently fatal).* Almost always acute.SIGNALMENT Species Dogs, cats, and many other species, including birds Mean Age and Range * Any age susceptible (3 months–13 years) * Mean—3 years SIGNS General Comments * Dose-dependent.* Toxicity—initially causes CNS depression, ataxia, gastrointestinal irritation, and polyuria or polydipsia; rapidly metabolized in the liver by alcohol dehydrogenase to glycoaldehyde, glycolic acid; glyoxalic acid, and oxalic acid; leads to severe metabolic acidosis and renal epithelial damage. * Minimum lethal dosage—cats, 1.4 mL/kg; dogs, 6.6 mL/kg SYSTEMS AFFECTED * Gastrointestinal—irritated mucosa. * Nervous—inebriation from ethylene glycol and glycoaldehyde owing to inhibition of respiration, glucose metabolism, and serotonin metabolism and alteration of amine concentrations. * Renal/Urologic—initially, osmotic diuresis; later, metabolites, especially calcium oxalate monohydrate crystals, are directly cytotoxic to renal tubular epithelium, resulting in renal failure. The mechanism of toxicity is now thought to involve attachment of oxalate to cell plasma membrane, activation of enzyme activity, and production of free radicals and lipid peroxidation, leading to cell necrosis. INCIDENCE/PREVALENCE * Common in small animals. * Highest fatality rate of all poisons; fatality rates higher for cats than dogs. * Incidence similar in cats and dogs. GEOGRAPHIC DISTRIBUTION Higher incidence in colder areas where antifreeze is more commonly used. SIGNALMENT Species Dogs, cats, and many other species, including birds Mean Age and Range * Any age susceptible (3 months–13 years) * Mean—3 years SIGNS General Comments * Dose-dependent. * Almost always acute. * Caused by unmetabolized ethylene glycol and its toxic metabolites (frequently fatal).* Dogs—with increasing depression, patient drinks less but polyuria continues, resulting in dehydration; CNS signs abate transiently after approximately 12 hours, but recur later.* Cats—usually remain markedly depressed; do not exhibit polydipsia.* Oliguria (dogs, 36–72 hours; cats, 12–24 hours) and anuria (72–96 hours post-ingestion)—often develop if untreated.* May note severe hypothermia.

**b**.Finally, the trifurcation graft is sewn to the proximal portion of the aortic graft.The distal arch anastomosis is constructed and the two aortic grafts are reapproximated.(C) Flow is then restored to the brain with a clamp on the proximal segment of the trifurcation graft.Alternatively, a debranching operation with use of individual trifurcation grafts to the arch vessels may be performed. This should reduce the duration of DHCA and improve cerebral protection, potentially reducing neurologic morbidity (Figure 1.23).226,227 **c**. Distal arch repair can be performed via a left thoracotomy without cardiopulmonary bypass. Use of CPB and a period of DHCA through either a sternotomy or thoracotomy incision may be useful when clamping is not feasible for the proximal anastomosis or for more complex operations. Several creative operations for distal arch aneurysms have been described, such as open transaortic stent endografting of distal arch aneurysms with carotid artery bypass.228 **d**. If it is anticipated that a descending aortic repair may be necessary in the future, a piece of graft material is left dangling from the distal anastomosis and can be retrieved at a subsequent operation through the left chest (the "elephant trunk" procedure).229 **3. Descending thoracic aorta** **a**. Graft replacement of the diseased aorta is performed with reimplantation of intercostal vessels at the level of T8–T12 for more extensive aneurysms. This is performed through a left thoracotomy or thoracoabdominal incision with use of one-lung anesthesia. **Figure 1.23** • Aortic arch replacement using a trifurcation graft (TG). (A) Using axillary cannulation for CPB, the aorta is clamped and the proximal root reconstruction is performed. (B) During DHCA, the arch vessels are divided 1 cm from their origins, and individual anastomoses are sequentially performed to the arch vessels with side limbs off the trifurcation graft. (C) Flow is then restored to the brain with a clamp on the proximal segment of the trifurcation graft. The distal arch anastomosis is constructed and the two aortic grafts are reapproximated. Finally, the trifurcation graft is sewn to the proximal portion of the aortic graft. **b**.A BioMedicus centrifugal pump, which actively returns blood to the patient at a designated rate, can be used with or without oxygenation.Left-heart bypass alone has been shown to reduce the incidence of paraplegia during surgery for thoracoabdominal aneurysms, but not necessarily more limited descending thoracic aneurysms.232,233 **c**.

Of course, not every story is a success story, but the sample does show an improvement rate of 82 percent, a statistic that conventional therapists can only dream of.In _The Conquest of Cancer_ , she listed over 60 cases of patients she treated; these were pulled at random from her files.They have been put to the test in her clinical practice as well as in her laboratory.Dr. Livingston found that the administration of safe, nontoxic antibiotics such as ampicillin and penicillin G can reduce the excessive amount of PC in the bloodstream and thereby cause cancerous tumors to shrink. The term "excessive" is used here because, as has been noted, normal amounts of PC do not cause a problem in the healthy body and in fact contribute to one's well-being. It is only when they become excessive that they contribute to cancerous growth in the body. ## **OTHER PARTS OF THE PROGRAM** Other elements of this safe, nontoxic program include the following: ✅ Transfusions of fresh whole blood, preferably from a healthy family member, to reduce the risk of contamination, increase oxygenation, and replenish the body's enzymes. ✅ Injections of gamma globulin to provide fresh antibodies. ✅ Injection of spleen extract derived from immunized animals to increase the patient's white blood cell count. White blood cells play a critical role in arresting foreign substances and toxic intruders into the blood. ✅ Injections of nonspecific vaccines, such as one containing numerous mixed bacteria, for use in respiratory infections and to increase general resistance. ✅ Supplements and/or injections of vitamins C and B12, plus tablets of vitamins such as A, C, E, B6, and B12, and minerals to stimulate the immune system. ✅ Oral supplementation of hydrochloric acid where needed to correct overly alkaline blood caused by digestive difficulties. **THE PATIENTS** Dr. Livingston's ideas about the treatment and prevention of cancer are not purely academic. They have been put to the test in her clinical practice as well as in her laboratory. In _The Conquest of Cancer_ , she listed over 60 cases of patients she treated; these were pulled at random from her files. Of course, not every story is a success story, but the sample does show an improvement rate of 82 percent, a statistic that conventional therapists can only dream of.By 1980 the patient reported feeling much better, and tests showed that his tumor had shrunk 50 percent.When Dr. Livingston contacted him in 1983 while writing her book, he said that he was still following the program and was in general good health._ _A 12-year-old boy was diagnosed with Hodgkin's disease.

if copious mucus; also tones mucous membranes) Expectorant: thyme; fennel; hyssop; elecampane Antitussive: wild cherry bark (esp.**Mother Earth cough syrup*:** (Cayce product, made from wild cherry bark, horehound, rhubarb, wild ginger, and honey) **Mustard chest plaster*** 1 part mustard, 4 parts flour, white of 1 egg (or 1 tsp. olive oil). Add water to form thin paste. Place between cloth and apply to oil-covered chest. **Botanicals for specific types of cough** Dosage ought to reflect the acuteness of the situation; so small amounts taken more frequently is recommended. **Upper respiratory tract (throat) coughs** Demulcent: mullein; licorice; marshmallow Antiseptic: thyme; elecampane; goldenseal/Indian barberry (berberine); myrrh. Can add 2 to 3 drops of eucalyptus or tea tree oil Anti-inflammatory: skullcap; ginger; white willow bark (salicylic acid); licorice Anticatarrhal: goldenseal (esp. for thick, tenacious, yellow mucus); eyebright (runny, watery mucus); sage Mix appropriate dose in some warm water and gargle, then swallow. **Lower respiratory tract (lung) coughs** Demulcent: as above Expectorant: sundew; grindelia; ginger (if cold) Anticatarrhal: goldenseal, sage, mullein Spasmolytic: thyme; licorice Antitussive: wild cherry; thyme (mild); pleurisy root (also diaphoretic, expectorant) **Hard, croupy cough** Spasmolytic: wild cherry bark; thyme; sundew; black cohosh Soften phlegm: elecampane Bath oil: thyme is good Herbal teas: mullein, anise seed, with honey **Whooping cough** Antispasmodic: sundew (specific); thyme Antiseptic: goldenseal Anticatarrhal: mullein; goldenseal (esp. if copious mucus; also tones mucous membranes) Expectorant: thyme; fennel; hyssop; elecampane Antitussive: wild cherry bark (esp.**Sample formulation** Mix the following, use as a tincture or extract.10 to 15 drops in water, three times per day.

As soon as the machine ceases to milk, the udder should be stripped and the machine removed.For maintenance of a healthy udder, what is first required is a strong stimulus to 'let-down', followed by rapid milking.The basic principles of machine milking are, in fact, vacuum and pulsation, and the way in which these are applied to the teat in the teat-cup assembly.Reluctance to move, stiffness and recumbency are the signs, and deaths may occur. Treatment The intravenous or subcutaneous injection of CALCIUM BOROGLUCONATE solution with or without added MAGNESIUM. When a deficiency of blood PHOSPHORUS complicates milk fever, and there is no response to calcium treatment, phosphorus in the form of 85 g (3 oz) of sodium acid phosphate may be given by mouth twice daily. Prevention Milk fever has proved difficult to prevent. Reducing calcium intake in the later stages of pregnancy, followed by a boost in in-feed calcium two to three days before calving, has been suggested. Acidic diets (DCAB, DCAD) can help control milk fever. VITAMIN D and its derivatives have been used to prevent hypocalcaemia. ## Milking (see also under MASTITIS; MILKING MACHINES). At milking time, the 'milk let-down' mechanism begins to operate; it is actuated by the hormone oxytocin which is secreted in the posterior pituitary gland and which is released into the bloodstream following a nervous stimulus. This stimulus may be caused by the rattling of milk pails, the placing of food in the manger, the washing of the udder, etc. ## Milking Machines Their action simulates that of the sucking calf. The teat-orifice is opened and milk withdrawn by means of a partial vacuum applied to the outside of the teat. As continuous vacuum would restrict circulation of the blood in the teat, cause pain, and inhibit milk ejection, the vacuum is applied intermittently by means of a pulsator. Milk fever: the characteristic posture. The basic principles of machine milking are, in fact, vacuum and pulsation, and the way in which these are applied to the teat in the teat-cup assembly. For maintenance of a healthy udder, what is first required is a strong stimulus to 'let-down', followed by rapid milking. As soon as the machine ceases to milk, the udder should be stripped and the machine removed.Automatic cluster-removal is useful here.To maintain udder health a strong stimulus to 'let down' is required, followed by rapid milking.This is achieved by the herdsman not having too many units to cope with, nor other tasks to perform.Milking machines can be made to milk faster by increasing the degree of vacuum, increasing the pulsator rate, or by widening the pulsator ratio.

Most of the early research suffers from serious methodologic flaws, including use of small biased samples, limited or no statistical analysis, poor (if any) controls, and retrospective designs subject to recall and other biases.The primary focus is on those effects for which there is reasonable evidence from controlled studies.To achieve smoking cessation, bupropion, varenicline, nicotine replacement, behavioral therapies, and other pharmacologic strategies all warrant consideration. Behavioral strategies are also useful in promoting better dietary practices, sleep hygiene, safe sex, and exercise. For some patients, change can be achieved efficiently through support groups, whereas others change more effectively through a one-on-one relationship with a healthcare professional. 28.7.5 Stress-related Physiologic Response Affecting a Medical Condition Biofeedback, relaxation techniques, hypnosis, and other stress management interventions have been helpful in reducing stress-induced exacerbations of medical illness, including cardiac, gastrointestinal, headache, and other symptoms. Pharmacologic interventions have also been useful (e.g., the widespread practice of prescribing benzodiazepines during acute myocardial infarction to prevent stress-induced increase in myocardial work). 28.7.6 Psychological Factors in Specific Medical Disorders A specific discussion on the effects of psychological factors on selected medical disorders are beyond the scope of this book. Readers are encouraged to avail themselves of the readings provided at the end of this chapter. The primary focus is on those effects for which there is reasonable evidence from controlled studies. Most of the early research suffers from serious methodologic flaws, including use of small biased samples, limited or no statistical analysis, poor (if any) controls, and retrospective designs subject to recall and other biases.Clinical Vignette Mrs A, a 46-year-old married attorney, was referred for psychiatric evaluation by her gastroenterologist, who was following her for longstanding irritable bowel syndrome.She had had IBS since the age of 20, with complaints of intermittent constipation, diarrhea, crampy abdominal pain, and bloating.

They say a prayer as a plane lifts off a runway, but they never think twice about the possible health ramifications of sitting still during that multihour flight while they consume highly processed snack foods.They instead focus on the wrong health priorities.Most people don't.But your first step lies in taking this killer seriously.In the past few decades, we've experienced dramatic improvements in medical care. The pharmaceutical industry has brought us miracle medicines capable of halving the amount of blood cholesterol floating around in our arteries. Along with my colleagues, I have perfected ways to thread the tiniest of catheters into a coronary artery and insert medicine-coated stents to hold it open and allow blood to flow. Robots have even been invented to help with the trickiest aspects of open-heart surgery. But despite these advances in medical care, far too many people are dying years or decades before their time. More than one million coronary bypass and angioplasty surgeries are done every single year in the United States and Canada, making these procedures among the most expensive and most common medical procedures offered in North America. Still, no other cause of death has even come close to ousting heart disease from its number one spot on the list of the top 10 killers of men and women worldwide. I tell you none of this to scare you. Rather, as a compassionate cardiologist, I wrote this book because I want you to know something both important and liberating. You do not need to get sick. You also don't need to have your chest cracked open so a surgeon can sew veins onto your diseased coronary arteries. You don't need to suffer from side effects of your medications, and you definitely don't need to be disabled or die from heart disease decades before your time. You have so much more control over this killer than you think—almost total control, in fact. But your first step lies in taking this killer seriously. Most people don't. They instead focus on the wrong health priorities. They say a prayer as a plane lifts off a runway, but they never think twice about the possible health ramifications of sitting still during that multihour flight while they consume highly processed snack foods.Yet not only have they never undergone heart CT calcium scoring or advanced cholesterol testing, had the medial thickness of their carotid arteries measured by ultrasound, or had an EndoPAT, they've never even heard of such tests, and that's because their health care providers haven't mentioned them.

Even a century after its introduction, the structure of Salvarsan remained unknown; that is, though the formula for Salvarsan is well known, Ehrlich's lab never did establish the precise structure of the compound.Like its precursor, it was a blockbuster: a miracle drug.Cassella's partners at Hoechst AG introduced arsphenamine under the trade name Salvarsan. It was the world's first synthetic chemotherapeutic agent. Salvarsan was a huge success, within a year of its introduction the most widely prescribed drug in the world. It was also one of the most challenging, for both doctors and patients. Common side effects included nausea and vomiting. Storage of the compound was a tricky business, requiring vials tightly sealed to avoid oxidation. Treatment entailed weekly injections of the highly diluted compound over the course of a year— _very_ highly diluted; each injection required at least 600 cc of solution per injection, or a pint and a quarter of solvent pumped into a patient's body with every visit to the doctor. Many doctors decided to experiment with different solvents; others to try different injection locations: into the muscle, under the skin, or directly into the bloodstream. Intramuscular and subcutaneous injections tended to be painful; intravenous ones still unfamiliar to physicians, and therefore risky. The dangers of such a regimen, given the needles and syringes available in the first decade of the twentieth century, were very real: Too much seepage from the injection site could result in amputation or even death. Moreover, as would become a familiar theme of every subsequent advance in drug therapy, it was widely used for ailments well outside its arena of effectiveness. In some unfortunate cases, it resulted in death from cerebral hemorrhage. In 1912, Hoechst, Ehrlich, and Hata responded with a new and improved version, marketed as Neosalvarsan, which was soluble in water, and less toxic to boot. Like its precursor, it was a blockbuster: a miracle drug. Even a century after its introduction, the structure of Salvarsan remained unknown; that is, though the formula for Salvarsan is well known, Ehrlich's lab never did establish the precise structure of the compound.The actual structure of Salvarsan, which wasn't discovered until 2005, consists of mixtures of cyclic molecules, which prompted some people to suggest that it wasn't a _Zauberkugel,_ but _Zauberschrot_ : a magic buckshot.Even more mysteriously: As of this writing, no one has yet figured out the mechanism by which Salvarsan and Neosalvarsan target _T.pallidum_ so precisely.

• Zinc: 20 to 30 mg per day • N-acetylcysteine: 200 mg three times per day • One of the following: Bromelain (1,200 to 1,800 MCU): 250 to 500 mg three times per day between meals Serratia peptidase (enteric-coated): 30 to 50 mg three times per day between meals #### Botanical Medicines • Goldenseal (Hydrastis canadensis) or another berberine-containing plant (standardized extracts recommended): Dried root or as infusion (tea): 2 to 4 g three times per day Tincture (1: 5): 6 to 12 ml (1.5 to 3 tsp) three times per day Fluid extract (1: 1): 2 to 4 ml (0.5 to 1 tsp) three times per day Solid (powdered dry) extract (4:1 or 8 to 12% alkaloid content): 250 to 500 mg three times per day • Echinacea species: Fluid extract of the fresh aerial portion of E. purpurea (1:1): 2 to 4 ml (1/2 to 1 tsp) three times per day (preferred form) Juice of aerial portion of E. purpurea stabilized in 22% ethanol: 2 to 4 ml (1/2 to 1 tsp) three times per day (preferred form) Dried root (or as tea): 1 to 2 g three times per day Freeze-dried plant: 325 to 650 mg three times per day Tincture (1:5): 2 to 4 ml (1/2 to 1 tsp) three times per day Fluid extract (1:1): 2 to 4 ml (1/2 to 1 tsp) three times per day Solid (dry powdered) extract (6.5:1 or 3.5% echinacoside): 150 to 300 mg three times per day • South African geranium (Pelargonium sidoides, EPs 7630 or equivalent preparation): adults, 3 ml three times per day or two 20-mg tablets three times per day for up to 14 days; children ages 7 through 12, 30 drops (1.5 ml) three times per day; age 6 years or less, 10 drops (0.5 ml) three times per day #### Physical Medicine • Nasal rinse with warm saline solution once per day, increasing to several times a day during acute attacks Sports Injuries, Tendinitis, and Bursitis • Tendinitis: Acute or chronic pain localized in a tendon Limited range of motion • Bursitis Severe pain in the affected joint, particularly on movement Limited range of motion This chapter deals with sports injuries (e.g., sprains, strains, and bruises), tendinitis, and bursitis.Tendinitis usually results from a strain.Although acute tendinitis usually heals within a few days to two weeks, it may become chronic, in which case calcium salts will typically deposit along the tendon fibers.

However, a good way to increase the kidney and liver purpose, particularly the overall kidney function is by improving the immune function and supporting in the evacuation of the kidneys and liver's waste products by trying RENACARE.This buildup happens in the blood stream because the kidneys can no longer clear the waste products in your body.Also, regulating blood pressure is associated with the kidneys' ability to eject enough sodium chloride (salt) to maintain normal sodium balance, extracellular fluid volume and blood volume. However, kidney disease is the most common hypertension (high blood pressure) that is secondary. The truth is that even minor disruptions in kidney functions play a role in most cases of high blood pressure and increased injury to the kidneys. Yes, this injury can eventually cause stroke or even death. Yes, studies show that in normal people, the body adjusts when there's a higher intake of sodium chloride (salt) by excreting more sodium without raising major pressure. However, many outside influences can decrease the kidneys' ability to send out sodium. The truth is that, if the kidneys are less able to send out salt with regular or higher salt intake, chronic increases in extracellular fluid amount and blood amount will emerge, which will eventually lead to high blood pressure on the long run. Nevertheless, normal working kidneys have other jobs too. They make chemicals called hormones that help you make red blood cells, build strong bones, and keep your blood pressure under control. When kidneys are functioning normally and are healthy, the major kidney functions will continue. However, you must realize that our continued existence depends on these vital organs, even though you can live a normal life with only one kidney. Yes, when kidneys stop working, waste products that are harmful to your body build up and make you feel sick. This buildup happens in the blood stream because the kidneys can no longer clear the waste products in your body. However, a good way to increase the kidney and liver purpose, particularly the overall kidney function is by improving the immune function and supporting in the evacuation of the kidneys and liver's waste products by trying RENACARE.## How to Recognize Kidney Failure Without doubt, we know that Kidneys have a very important function in our bodies.These special organs filter blood to remove fluid waste from the body and control fluid and electrolyte balances.In fact, the role that kidneys have in our lives is vital to keeping us going, moving and basically living as earlier mentioned in the previous chapter.

B.You may be out of bed for breakfast.**Level 2: Modified bed rest** A.Avoid heavy lifting above 20 pounds.You should follow the following activity guidelines: **Level 1: As tolerated** A.**Activity:** Activity at home is based on how significant your PTL has been.Take medications to stop contractions as directed.I.Babies born too soon are at risk for breathing problems, bleeding into their brain, infection, and bowel problems, to name a few. Early recognition is the key to stopping premature labor and delivery. CAUSE * * * There are several predisposing factors for preterm labor (PTL), including previous premature delivery, smoking, incompetent cervix, multiple gestation (twins or triplets), and infection. In most cases, the cause of PTL is unknown. PREVENTION * * * You can decrease your risk for PTL by living a healthy lifestyle with a balanced diet, proper fluid consumption, and no smoking. Please review any previous PTL symptoms with your health care provider. Early recognition is a key to success. TREATMENT PLAN * * * Treatment depends on the clinical picture. In general, you should remember: A. Drink at least 8 to 10 glasses of noncaffeinated liquid a day; dehydration can increase contractions. B. Empty your bladder every 2 to 3 hours. C. Report any bladder infection symptoms, such as burning with urination, to your health care provider. D. Avoid breast stimulation (including showers where the water stream is on your breasts); this can stimulate contractions. E. Rest frequently. Rest means lying down on either side, not on your back. F. Contractions and cramping happen more often in the evening and nighttime after having activity during the day. G. Do not have intercourse or sexual stimulation without asking your nurse practitioner, certified nurse-midwife, or doctor. If intercourse is okay, use a condom to decrease infection. H. Try to arrange for help with housework and childcare to help you maintain your bed-rest schedule. I. Take medications to stop contractions as directed. **Activity:** Activity at home is based on how significant your PTL has been. You should follow the following activity guidelines: **Level 1: As tolerated** A. Avoid heavy lifting above 20 pounds. **Level 2: Modified bed rest** A. You may be out of bed for breakfast. B.C. Rest for 2 hours with only moderate activity until dinner.D. Go to bed by 8 p.m.Moderate activity consists of short periods of cooking, light housework (dusting and sweeping).**Level 3: Strict bed rest** A.You may be out of the bed only to go to the bathroom or to move to the couch.B.You may take a shower, use the toilet, brush your teeth, then return immediately to bed.

Stenting produces significantly better angioplastic results.Angioplasty might reduce the number of antihypertensive medications but does not significantly change the progression of kidney dysfunction in comparison to patients medically managed.Two large randomized trials showed that vascular intervention is no better than optimal medical management in typical patients with renal artery stenosis.A noninvasive procedure, it uses a spiral (helical) CT scan with intravenous contrast injection. The sensitivities from various studies range from 77% to 98%, with specificities in the range of 90–94%. **MRA** is an excellent but expensive way to screen for renal artery stenosis, particularly in those with atherosclerotic disease. Sensitivity is 77–100%, although one flawed study showed a sensitivity of only 62%. Specificity ranges from 71% to 96%. Turbulent blood flow can cause false-positive results. The imaging agent for MRA (gadolinium) has been associated with nephrogenic systemic fibrosis, which occurs primarily in patients with a GFR of less than 15 mL/min/1.73 m2, and rarely in patients with a GFR of 15–29 mL/min/1.73 m2. This fibrosis has also occurred in those with AKI and kidney transplants. **Renal angiography** is the gold standard for diagnosis but it is more invasive than the three screening tests discussed above. Thus, it is performed after a positive screening test. CO2 subtraction angiography can be used in place of dye when the risk of dye nephropathy exists—eg, in diabetic patients with kidney injury. Lesions are most commonly found in the proximal third or ostial region of the renal artery. The risk of atheroembolic phenomena after angiography ranges from 5% to 10%. Fibromuscular dysplasia has a characteristic "beads-on-a-string" appearance on angiography. ### Treatment Treatment of atherosclerotic ischemic renal disease is controversial. Options include medical management, angioplasty with or without stenting, and surgical bypass. Two large randomized trials showed that vascular intervention is no better than optimal medical management in typical patients with renal artery stenosis. Angioplasty might reduce the number of antihypertensive medications but does not significantly change the progression of kidney dysfunction in comparison to patients medically managed. Stenting produces significantly better angioplastic results.Angioplasty is equally as effective as, and safer than, surgical revision.Treatment of fibromuscular dysplasia with percutaneous transluminal angioplasty is often curative, which is in stark contrast to treatments for atherosclerotic disease.Cooper CJ et al; CORAL Investigators.Stenting and medical therapy for atherosclerotic renal-artery stenosis.N Engl J Med.2014 Jan 2;370(1):13–22.

Next to AIDS, Ebola virus—because of its terrifying consequences—has become the virus most imprinted on contemporary consciousness.It attacks the kidneys and can cause lung inflammation, internal bleeding, and death.In 1993, an emerging hantavirus was identified in New Mexico, which caused headline news over an emerging viral threat.It arrived in the Americas by slave ships from West Africa and became one of the most feared of diseases up until the early part of the twentieth century. Yellow fever is a hemorrhagic disease that attacks the liver causing jaundice, necrosis (death of cells), and death. It is still common in tropical Africa, Latin America, and Asia. An effective vaccine is available, but there is no specific treatment other than management of symptoms and blood transfusion. A number of other insect-borne viral illnesses that cause illnesses in America include Venezuelan equine encephalitis, Colorado tick fever, Eastern equine encephalitis, Western equine encephalitis, St. Louis encephalitis, California encephalitis, and West Nile Fever. Most of these viruses cause (or can lead to) inflammation of the central nervous system. Other viruses that also cause central nervous system damage include the herpes viruses, HIV, poliovirus, and the mumps; however, these are not insect-borne illnesses. Rodents, such as squirrels, mice, and rats, spread viruses in their droppings when they forage for food. The contaminated food is then eaten, or dried fecal matter contaminates the air and is then inhaled. The most notorious of rodent-related viruses is hanta. First identified in 1954 during the Korean War, the virus was isolated from samples found near the Hantaan River in 1978. This disease, originally called Korean Hemorrhagic Fever, belongs to the Bunyavirus family and has a genus of its own, _Hantavirus_ , with three types identified. In 1993, an emerging hantavirus was identified in New Mexico, which caused headline news over an emerging viral threat. It attacks the kidneys and can cause lung inflammation, internal bleeding, and death. Next to AIDS, Ebola virus—because of its terrifying consequences—has become the virus most imprinted on contemporary consciousness.It is endemic in parts of Africa, but Ebola has "cousins," all members of the Filovirus family, that occur in other parts of the world including Europe, South America, and Asia.The most notorious of these is the Marburg virus, first identified in South Africa.Other fatal hemorrhagic viral diseases include Lassa, Argentine, and Bolivian fevers.

CABG is most likely to benefit people who have severe angina that is not relieved by drug therapy, a normally functioning heart, no previous heart attacks, and no other conditions that would make surgery hazardous (such as chronic obstructive pulmonary disease).It can improve exercise tolerance, relieve symptoms, and decrease the number or dose of drugs needed.Doctors recommend that most people who have coronary artery disease take both aspirin and clopidogrel daily to reduce the risk of a heart attack. Ticlopidine, which has similar effects but more potential side effects than clopidogrel, may be used if the person is allergic or cannot tolerate clopidogrel. Antiplatelet drugs are given to people with angina unless there is a reason not to. For example, they are not given to people who have a bleeding disorder. Revascularization Procedures These procedures include percutaneous coronary intervention (PCI) procedures (also called angioplasty) and coronary artery bypass grafting (CABG). These invasive techniques are effective, but they are only mechanical measures for correcting the immediate problem. They do not stop the progression of the underlying disease. People still need to modify risk factors. PCI (see Percutaneous Coronary Intervention) is often preferred to CABG because it is less invasive, although it is not appropriate for every situation. PCI is usually preferred when only one or two arteries are affected, and the blocked area is not very long. However, new technology and increasing experience are allowing doctors to use PCI for more and more people. CABG (see Coronary Artery Bypass Grafting) is highly effective for people who have angina and coronary artery disease. It can improve exercise tolerance, relieve symptoms, and decrease the number or dose of drugs needed. CABG is most likely to benefit people who have severe angina that is not relieved by drug therapy, a normally functioning heart, no previous heart attacks, and no other conditions that would make surgery hazardous (such as chronic obstructive pulmonary disease).About 85% of people have complete or dramatic relief of symptoms after surgery.Acute Coronary Syndromes Acute coronary syndromes result from a sudden blockage in a coronary artery.This blockage causes unstable angina or heart attack (myocardial infarction) depending on the location and amount of blockage.

The fact is, however, that these are simply two different ways of approaching the same underlying problems, and there is no reason to believe that one is superior to the other.The problem, though, is that the categories 'biological' and 'psychological' do not refer to different underlying processes, but instead refer to different perspectives on, or ways of talking about, the same processes." As an oft-cited example of this idea, Waterman described studies on obsessive compulsive disorder (OCD) in which researchers used PET scans to track changes in brain metabolism in OCD patients who had been randomly assigned to receive either medication or cognitive behavioral therapy. Among those patients whose symptoms (for example, excessive hand washing and checking) improved with treatments, subsequent PET scans found precisely the same brain metabolism changes—namely, a reduction in the hyperactivity of a certain neural circuit—regardless of whether the treatment was pharmacological or behavioral. As much as it may be convenient and intuitive for us to use the language of dualism, in fact psychopharmacologists and psychotherapists are both treating the same thing—what we might call the mind/brain. As I talked to Waterman about these concepts, I was reminded of a basic disagreement between therapists and psychopharmacologists that still comes up occasionally. Psychiatrists sometimes say that therapy "ignores" the underlying biological problem, while therapists often counter that psychiatric medications simply put a Band-Aid on symptoms without addressing the deeper psychological issues. The fact is, however, that these are simply two different ways of approaching the same underlying problems, and there is no reason to believe that one is superior to the other.Actually accomplishing this on a large scale will be a challenge.The issues are complex and the possible solutions are many, as we will next explore._Chapter 10_ ## Solutions In order to fix the many problems explored in this book, I believe the profession must develop a vision of the ideal psychiatrist.

Physiotherapy or arthroscopy may be required.Bear in mind, too, that patients with a 'weak' ankle following injury or recurrent sprains may be suffering chronic ligament injury or have 'functional instability' caused by painful scar impingement within the ankle joint.Once the diagnosis is suspected, patients should be non-weight bearing and seen in a fracture clinic.If they are white or clear they will be dissolvable, whereas coloured sutures can be dissolvable, but may need removing. 9.A straight leg raise (SLR) can identify quads, knee and hip pathology as well as lumbosacral radiculopathy The SLR commonly identifies lumbosacral radiculopathy (sciatica). A positive test comprises pain radiating down the back of the leg when it is passively raised between 30° and 70°. The SLR is also helpful in various knee extensor mechanism injuries: quadriceps tendon rupture, patella fracture and patellar tendon rupture, which all present with pain and an inability to actively perform an SLR. Management should include knee immobilisation to prevent tendon retraction and fracture clinic assessment for possible surgery. Hip fractures do not always present classically and may not be visible on X-rays. Inability to actively perform a SLR, groin pain and limited hip rotation in combination help identify these occult hip fractures. 10.Beware of unresolving 'ankle sprain' An underdiagnosed injury is the high ankle or syndesmotic sprain – damage to the ligamentous complex between the distal tibia and fibula. Suspect this when the mechanism of injury includes ankle rotation. Signs include toe walking to avoid painful dorsiflexion, pain with combined passive ankle dorsiflexion and external rotation and syndesmotic pain provoked by compressing tibia and fibula at mid-calf. Once the diagnosis is suspected, patients should be non-weight bearing and seen in a fracture clinic. Bear in mind, too, that patients with a 'weak' ankle following injury or recurrent sprains may be suffering chronic ligament injury or have 'functional instability' caused by painful scar impingement within the ankle joint. Physiotherapy or arthroscopy may be required.The patient is often in agony with disturbed sleep.X-ray will reveal calcification in the rotator cuff.Treatment consists initially of an ultrasound guided steroid injection into the calcific deposit.2.Ulnar nerve problems The ulnar nerve can be trapped at the elbow (cubital tunnel syndrome) or at the wrist (Guyon's canal compression).

Acute consequence of the HPA axis activation is mobilization of energy reserves to facilitate coping with stress.Cortisol exerts its action through activation of two types of receptors; type I or mineralocorticoid receptor (MR) with high affinity for endogenous corticosteroids, and type II or glucocorticoid (GR) receptors, with low affinity for cortisol [220].Central to regulating bodily homoeostasis and neuroendocrine response to external and internal stressors is the hypothalamus. Through action of neuropeptides, which it synthesizes and secretes, the hypothalamus controls an immense number of bodily functions, which include stress response, control of body temperature, ingestive behaviours, emotions, sexual activity, circadian cycles, blood pressure, as well as electrolyte balance [214]. Hypothalamic-pituitary-adrenal axis (HPA axis) Disturbance in homoeostatic balance, conveyed to the hypothalamus through the action of numerous neurotransmitters, including acetylcholine, noradrenaline, serotonin and GABA [215], causes activation of the HPA axis resulting in a release of a corticotropin-releasing factor (CRF) into the portal circulation, CRH-mediated release of adrenocortico-tropic hormone (ACTH) from the anterior pituitary, and ACTH-mediated release of the cortisol from the adrenal gland [216–218]. CRF, a 41-amino acid peptide, exerts its action through two types of receptors, CRF1 and CRF2, and it appears that these two receptors mediate opposing effects, with CRFR1 activating and CRFR2 inhibiting, the CRF-mediated stress response. CRFR1 is the predominate subtype in limbic regions and in pituitary regulation of HPA axis activity [219]. Cortisol exerts its action through activation of two types of receptors; type I or mineralocorticoid receptor (MR) with high affinity for endogenous corticosteroids, and type II or glucocorticoid (GR) receptors, with low affinity for cortisol [220]. Acute consequence of the HPA axis activation is mobilization of energy reserves to facilitate coping with stress._Peripheral measures_ of hormones in bodily fluids may not provide a reliable insight into the brain functioning, as a number of associated variables, including hypothalamo/pituitary blood flow, degree of stress, diet, sleep or level of activity, are difficult to control.

The symptoms are very similar to those of a bipolar disorder; however, they are related directly to the use of a substance or a medication and subside when those factors are removed.## __.__ Substance/Medication-Induced Bipolar and Related Disorder (__.__ ) This is a diagnosis that presents with the same essential features as those of manic, hypomanic, and depressive episodes.In addition, counselors should differentiate this disorder from the rapid cycling presentation of Bipolar I and II disorders; because of frequent shifts in rapid cycling, both of these disorders may resemble cyclothymic disorder. A thorough assessment of presenting symptoms and history will assist counselors in determining if full criteria for a depressive episode, manic episode, or hypomanic episode have been met. If at any point the full symptoms of these episodes have been met, the cyclothymic disorder diagnosis can be dropped and the more appropriate mood disorder assigned (APA, 2013a). Because this disorder was originally included in the chapter on personality disorders, referred to as cyclothymic temperament, it can be confused for borderline personality disorder (Van Meter et al., 2012). The APA (2013a) acknowledges this change and suggests that marked shifts in mood can be associated with both disorders, and both disorders can be diagnosed if the full criteria for each have been met. ### Coding, Recording, and Specifiers There is only one diagnostic code for cyclothymic disorder: 301.13 (F34.0). If applicable, coding is recorded along with the specifier of _with anxious distress_. See the end of this chapter for more information on this specifier. Because mood symptoms are considered mild by nature, there is no specifier for mild, moderate, and severe. ## __.__ Substance/Medication-Induced Bipolar and Related Disorder (__.__ ) This is a diagnosis that presents with the same essential features as those of manic, hypomanic, and depressive episodes. The symptoms are very similar to those of a bipolar disorder; however, they are related directly to the use of a substance or a medication and subside when those factors are removed.This may or may not include depressive symptoms.The mood disturbance must occur during or soon after substance intoxication or withdrawal or after taking medications.The substance or medication must be able to cause the symptoms, and the disturbance does not only occur when the individual is experiencing delirium (APA, 2013a).

Nerves that become compressed, however, can produce excruciating pain.The condition may not cause any symptoms if the narrowed spinal canal does not compress nerves that provide sensation to the back and legs.Degenerated discs sometimes collapse so extensively they cause _spinal stenosis_ (table 2.2), a narrowing of the spinal canal, which contains sensitive nerves.Discs degenerate as we age, becoming thinner and drying out until they shrink and no longer provide adequate cushioning between the bones. A _bulging disc_ , which usually develops gradually, protrudes beyond its normal position. _Herniated discs_ (also referred to as _ruptured_ or _slipped discs_ ) occur when a portion of the interior gel leaks into the spinal canal through a crack in the outer layer of the disc (figure 2.1). Herniated discs typically develop suddenly as a result of an injury to the spine, but they are not always painful. In fact, many people are unaware of the problem until it shows up on magnetic resonance imaging (MRI). A protruding disc can press on a nerve root, triggering radiating pain and numbness in the back and down the leg. A herniated disc in the neck acts in the same way, sending pain signals down the arm. If medication or rest does not resolve the problem, it may be appropriate to consider injections of steroids into the surrounding epidural space. Minimally invasive procedures can also remove some or all of the disc material to relieve pressure on the nerve root. **FIGURE** 2.1. Pain can develop in the back, arms, and legs when a damaged or deteriorated disc presses on a nearby nerve root. **LAYERS OF PAIN** People with chronic back disorders frequently feel pain from multiple sources. The origin of the problem may be a bulging disc in the lower back that irritates a nerve. The pain may also cause a secondary layer of discomfort by triggering reactive muscle spasms. Additionally, stress or anxiety can heighten the perception of pain. Degenerated discs sometimes collapse so extensively they cause _spinal stenosis_ (table 2.2), a narrowing of the spinal canal, which contains sensitive nerves. The condition may not cause any symptoms if the narrowed spinal canal does not compress nerves that provide sensation to the back and legs. Nerves that become compressed, however, can produce excruciating pain.Stenosis occurs sooner in people with inherited spinal abnormalities and those who have an injury, tumor, scoliosis, osteoarthritis, or other degenerative spinal condition._Cauda equina syndrome_ is caused by extreme compression of the nerves in the lower spine.This is a serious condition that requires surgery to prevent paralysis and permanent loss of bowel and bladder control.

The medical, legal, and psychiatric impairment associated with Cannabis Dependence appears roughly comparable to that of Cocaine Dependence. Cannabis intoxication The most elemental cannabis-related diagnosis is that of Cannabis Intoxication. In order to make this diagnosis the patient must have used cannabis recently and be having some psychological or behavioral change as a result. In addition, a person must be experiencing two of the following four signs and symptoms: conjunctival injection, increased appetite, dry mouth, and tachycardia. The symptoms also cannot be better accounted for by another medical or mental condition. There is also a specifier, "with perceptual disturbances," if the intoxicated individual is experiencing illusions or hallucinations without losing reality testing or being delirious. In addition, there are a number of other physiological and psychological effects of cannabis described in the literature that do not appear in the _Diagnostic and Statistical Manual of Mental Disorders_ , Fourth Edition, Text Revision (DSM-IV-TR). These are listed in Table 17.2. **Table 17-2** The physiological and psychological effects of Cannabis Intoxication **Physiological effects** Common Tachycardia Increased appetite Dry mouth/thirst Conjunctival injection Constipation Decreased intraocular pressure Mydriasis Mild bronchoconstriction followed by bronchodilation Mild analgesia Mild anti-emetic effects Decreased libido Uncommon Ataxia Ptosis Miosis Drowsiness Bradycardia Hypotension Peripheral vasoconstriction Hypothermia **Psychological effects** Common Euphoria Distortions in perception (e.g.To be diagnosed with Cannabis Abuse, over a 12-month period as a function of cannabis use an individual must have any one of the following: recurrent episodes of failing to fulfill obligations at work, school, or home; recurrent episodes of cannabis use when using results in physical danger; recurrent legal difficulties; or recurrent arguments or disputes with others.

To do this, a vaccine must be able to infect antigen presenting cells.However, most immunologists believe that to protect against HIV-1 a vaccine will need to elicit memory killer T cells.Consequently, non-infectious vaccines that elicit protective antibodies have been made from dead viruses or even a single viral protein.Roughly two million people die every year from malaria, yet there is no vaccine that has been shown to be generally protective against this disease. Likewise, immunologists have not been able to devise an effective vaccine against tuberculosis, a bacterial infection which kills about three million humans each year. And roughly one third of all the people on earth are infected with herpes simplex virus, yet a herpes vaccine does not exist. Indeed, it is the hope of many that in trying to develop an AIDS vaccine, immunologists will discover new strategies that will make it possible to produce vaccines which will protect against some of the other pathogens for which vaccines currently are not available. * * * ### REVIEW Vaccinations take advantage of the ability of B and T cells to remember invaders we have previously encountered. By introducing the immune system to a "safe" version of a microbe, vaccination prepares these adaptable weapons to respond rapidly and powerfully if a real attack occurs at some future time. The potency of a vaccine can be increased by combining the specific antigen that a B or T cell recognizes together with an adjuvant. The purpose of an adjuvant is to "get the attention of the immune system" by providing a danger signal required for activation. The production of memory B and helper T cells does not require that an antigen presenting cell be infected. Consequently, non-infectious vaccines that elicit protective antibodies have been made from dead viruses or even a single viral protein. However, most immunologists believe that to protect against HIV-1 a vaccine will need to elicit memory killer T cells. To do this, a vaccine must be able to infect antigen presenting cells.However, a vaccine intended to protect the general population against HIV-1 must have no possibility of causing AIDS.And because HIV-1 has a very high mutation rate, there are no guarantees that an attenuated AIDS virus will not reactivate.Consequently, an attenuated form of the virus probably cannot be used to protect the public against an HIV-1 infection.

Always give your system a rest after taking DMSA for up to 3 weeks.Give your system a rest from the DMSA for 2 weeks while continuing other remedy support Repeat DMSA cleansing cycle as tolerated and indicated by clinical, diagnostic and/or energetic tests Contraindications Avoid any intense detoxification during pregnancy and lactation.Take smaller doses if senstive generally Take smaller doses if kidneys show stress Watch and support liver function, considering Silymarin Take Chitosan fiber (3 to 15 a day at least 3 hours away from any beneficial oils if possible) to support bowel elimination route and prevent recycling of heavy metals and other toxins Do enemas, implants or colonic irrigation if necessary or helpful Make sure to take extra minerals: a multiple-mineral supplement (StarGold, 1 or 2 capsules twice a day, or Kreb Cycle Minerals, 1 twice a day) plus Magnesium Glycinate (1 capsule twice a day) away from DMSA Take two to four Ester-C Complex three times a day Biofield analysis remedies should be tested and adjusted at least monthly Urine-Testing: 3 days: 500 mg three times a day loading dose 3rd day: 24 hours urine test for heavy metals and creatinine clearance Consider 24-hour urine test for heavy metals again at the end of the second round of the DMSA Cleansing-Dosage: A 50 kg (110 lb) person may take up to 500 mg spread out through the day for up to five days (maximum: 10mg for each kilogram of the body-mass for each day) A 50 kg (110 lb) person may then take up to 1000 mg spread through the day for up to 2 weeks (maximum: 10mg/kg b.i.d.) Give your system a rest from the DMSA for 2 weeks while continuing other remedy support Repeat DMSA cleansing cycle as tolerated and indicated by clinical, diagnostic and/or energetic tests Contraindications Avoid any intense detoxification during pregnancy and lactation. Always give your system a rest after taking DMSA for up to 3 weeks.Vitamin A in retinol and retinal forms, plus precursor Carotenoids (Pro-Vitamin A) including Beta Carotene all contain one or more cyclohexene ring structures that provide some sanctuary for the spirit minerals.

**Clubbing** _(Moll, 1997)_ clubfoot ME, _clubbe_ \+ AS, _fot_ ], a congenital deformity of the foot, sometimes resulting from intrauterine constriction and characterized by unilateral or bilateral deviation of the metatarsal bones of the forefoot.See also [**Schamroth window test**.The nail base angle measures more than 160°.cloxacillin sodium /klok′s sil′in/, a penicillinase-resistant penicillin used for bacterial infections. INDICATIONS: It is prescribed in the treatment of serious bacterial infections, primarily those caused by penicillinase-producing strains of staphylococci. CONTRAINDICATION: Known hypersensitivity to this drug or to any penicillin prohibits its use. ADVERSE EFFECTS: Among the more serious adverse reactions are GI discomfort, rash, and hypersensitivity. CLS/MT, abbreviation for **clinical laboratory scientist/medical technologist**. CLT/MLT, abbreviation for _clinical laboratory technician/medical laboratory technician._ clubbed penis ME, _clubbe_ \+ L, _penis_ ], See **[penile curvature. ** clubbing ME, _clubbe_ ], an abnormal enlargement of the distal phalanges with a flattening of the curvature of the nail margin at the cuticle, where the nail meets the cuticle. It usually is associated with cyanotic heart disease or advanced chronic pulmonary disease but sometimes occurs with biliary cirrhosis, colitis, chronic dysentery, thyrotoxicosis, and sickle cell anemia. Clubbing occurs in all the digits but is most easily seen in the fingers. Advanced clubbing is obvious, but early clubbing may be difficult to diagnose. Clubbing is present if the transverse diameter of the base of the fingernail is greater than the transverse diameter of the most distal joint of the digit. The nail base angle measures more than 160°. See also [**Schamroth window test**. **Clubbing** _(Moll, 1997)_ clubfoot ME, _clubbe_ \+ AS, _fot_ ], a congenital deformity of the foot, sometimes resulting from intrauterine constriction and characterized by unilateral or bilateral deviation of the metatarsal bones of the forefoot.Treatment depends on the extent and rigidity of the deformity.Splints and casts in infancy may produce complete correction.Surgery in several steps may be necessary to achieve normal function.See also [**Denis Browne splint,** **talipes**.

But he also knew that the virus was only very mildly weakened at this point.In truth, he deeply hoped that RA 27/3 was a vaccine in the making.This was because he didn't want Murray and his staff defining the RA 27/3 virus as a vaccine, giving them license to interfere with his trial, require lab and animal testing, and generally slow him down.The committee had been exceedingly cautious in its report published in _Science_ in January 1963, warning that the human diploid cells might harbor hidden viruses that could cause cancer or otherwise harm vaccinees. It had urged that new vaccines made in them should first be put into one or two adult volunteers, who should then be watched carefully for at least six months in case the vaccine was infected with hepatitis or another virus with a long incubation period. Murray added that Plotkin needn't worry about these recommendations if "you already have data from other studies with diploid cells to meet these [committee] suggestions." Plotkin considered that he did have that data. It was just one year earlier that the quiet, determined Yugoslavian vaccinologist, Drago Ikić, had immunized five thousand Croatian preschoolers against polio with a vaccine made using WI-38 cells—to no apparent ill effect. As for summoning an "objective group of advisers" to preapprove the study, Plotkin didn't do that. But it is probable, he wrote in 2016, that he consulted with Hilleman, Merck's vaccine chief, and with Robert Weibel, a pediatrician at the University of Pennsylvania who worked closely with Merck running vaccine trials. When Plotkin wrote to the DBS, he stated that he was using "non-vaccine material." This was because he didn't want Murray and his staff defining the RA 27/3 virus as a vaccine, giving them license to interfere with his trial, require lab and animal testing, and generally slow him down. In truth, he deeply hoped that RA 27/3 was a vaccine in the making. But he also knew that the virus was only very mildly weakened at this point.Rather, it would likely give the toddlers full-fledged rubella.This would prove beyond a doubt that the agent that he had captured from the kidneys of fetus 27 was indeed the rubella virus.Not that he doubted this.But others might.

Here is an analogy: Where there is garbage, there are likely to be flies.My take on this H. pylori link is that it is another instance in which conventional medicine is obsessed with an infective agent rather than focusing on the host's defense factors.Since another study of patients with GERD showed that 20 mg of Prilosec was equal to 20 mg of Nexium, there doesn't seem to be any real difference between the two other than the cost. Substituting OTC Prilosec for Nexium, Prevacid, and other prescription acid-blockers would cut spending on those medicines by about 50 percent, or almost $7 billion nationally—enough money to pay for health coverage for more than 1 million uninsured Americans—according to a study by the University of Arkansas. * * * THE BACTERIAL LINK TO PEPTIC ULCER DISEASE A corkscrew-shaped bacterium, Helicobacter pylori (H. pylori) is now regarded as the most important factor in the development of peptic ulcers and stomach cancer. The bacterium—one of the few that manage to survive in the acidic environment of the upper digestive tract—seems to burrow under the surface of the stomach lining and attach itself to the underlying cells. There it disrupts the production of the thick protective mucin lining the stomach and intestines and triggers localized inflammation that ultimately leads to the formation of ulcers. In 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery, in 1979, that H. pylori is a primary factor in peptic ulcer disease and for their subsequent work. As a result, when doctors suspect that peptic ulcer is associated with H. pylori and is not due to other factors (such as side effects of drugs), they typically consider it an infection and treat it with antibiotics. My take on this H. pylori link is that it is another instance in which conventional medicine is obsessed with an infective agent rather than focusing on the host's defense factors. Here is an analogy: Where there is garbage, there are likely to be flies.The popular treatment of peptic ulcers is antibiotic therapy plus an acid-blocking drug, but the antibiotics are like insect repellent, and taking them in combination with an acid-blocking drug may be extremely dangerous (discussed below).A more rational approach is to focus on eliminating the factors that lead to an overgrowth of H. pylori.

This can cause clumsiness where children with dyspraxia often knock over objects or bump into objects and people.the limbs are.It can also cause difficulties in spatial awareness (proprioception), which is the ability of the brain to process where different parts of the body, e.g.This may cause problems with balance and timing.It affects fine and or gross motor coordination.This knowledge is fairly recent and previously any additional problems a child with Down's syndrome had were seen as part of the Down's syndrome diagnosis. Again, children's abilities with this condition can vary enormously with very different levels of learning difficulty and acquisition of speech in the same way that all children on the autistic spectrum vary. Tuberous Sclerosis Approximately 2–4 per cent of children with autism have Tuberous Sclerosis (TS). This is a genetic disorder in which tubers or lesions grow in various parts of the body, but especially in the brain. Although the majority of children with TS are not diagnosed with autism, around 43–61 per cent of children with TS have symptoms of autism. Autism in these children may be diagnosed at a later age due to the progression of the disease, which may in time cause autism alongside other symptoms. There is a high incidence of epilepsy among the autism population. This is discussed further on page 83. Apart from these known identifiable medical conditions there are also other coexisting disorders that many children with ASD have as well and which are also classified as being autistic spectrum disorders, such as dyspraxia and ADHD. Dyspraxia Dyspraxia is a form of developmental coordination disorder (DCD). It is in the category of neurodevelopmental disorders in the APA's _Diagnostic and Statistical Manual of Mental Disorders_ and is classified as a motor disorder. It is lifelong and cannot be cured, but there are many things that can be done to make life easier for those who have it. It affects fine and or gross motor coordination. This may cause problems with balance and timing. It can also cause difficulties in spatial awareness (proprioception), which is the ability of the brain to process where different parts of the body, e.g. the limbs are. This can cause clumsiness where children with dyspraxia often knock over objects or bump into objects and people.However, there are other unseen issues that children with this condition have problems with.These include problems with planning.They may not be able to follow and remember instructions in sequence.They may have problems in organizing and carrying out everyday movements and procedures.A child with dyspraxia, for example, may need help to dress themselves.

These three genetic elements are readily passed between bacteria of the same as well as different species, allowing intra- and interspecies spread of resistance elements.These genes may also be found in transposons and integrons.In bacteria, genes encoding products that allow bacteria to escape drug actions (resistance genes) often exist on plasmids, circular pieces of extrachromosomal DNA.Introduction The introduction of antibiotics and other antimicrobial compounds revolutionized medical treatment of infectious diseases, leading some observers to declare victory in the lengthy war against these illnesses. The proclamation proved to be premature, for microbes demonstrated impressive abilities to escape killing or inactivation by these drugs. In populations of bacteria and other microbes, various clones exist that are resistant to the actions of different drugs. After exposure or improper exposure to these drugs, the more susceptible organisms are killed and the more resistant organisms tend to survive and may come to dominate the population under certain circumstances due to their increased fitness (greater ability to survive and reproduce). Many bacterial resistance elements are contained either singly or in groups within mobile genetic elements (discussed later in this chapter) that may enable rapid transmission of multiple drug resistance genes. As microbial populations develop resistance to existing drugs, humans have responded by producing new drugs. The microbes subsequently find means of evading these drugs, forcing humans to search for more novel agents in the continuing evolutionary waltz of life. Increased incidence of drug resistance is currently a rapidly growing phenomenon in many types of organisms, including viruses, bacteria, protozoa, and insects. Separate chapters deal with this phenomenon in several organisms, including HIV, tuberculosis, and malaria. In bacteria, genes encoding products that allow bacteria to escape drug actions (resistance genes) often exist on plasmids, circular pieces of extrachromosomal DNA. These genes may also be found in transposons and integrons. These three genetic elements are readily passed between bacteria of the same as well as different species, allowing intra- and interspecies spread of resistance elements.During conjugation in gram-positive bacteria, DNA is exchanged between a mating pair of microbes.In gram-negative bacteria, plasmids are transferred to nearby bacteria in an act that often involves elongated pili that join the microbes together.Transformation involves the acquisition of DNA from other bacteria that have previously lysed and released their DNA into the external environment.

The IGF system features distinctive increases in circulating levels of IGF binding protein 2 and "big" IGF II [77].Gradual, spontaneous remission [76] with decreasing bone density can occur.During active disease, the forearms and legs are painful.Periosteal, endosteal, and trabecular bone thickening occurs throughout the skeleton except the cranium.### Histological findings Nascent periosteal bone roughens cortical bone surfaces while undergoing cancellous compaction with blending to the original cortex. There may also be osteopenia of trabecular bone from quiescent formation. Mild cellular hyperplasia and thickening of blood vessels is found near synovial membranes, but synovial fluid is unremarkable. Electron microscopy shows layered basement membranes. ### Etiology and pathogenesis A controversial hypothesis suggested some circulating factor acts on the vasculature causing hyperemia and soft tissues changes, but later reduced blood flow. In 2008, AR pachydermoperiostosis was explained by loss of function mutation within _HPGD_ that encodes 15‐hydroxyprostaglandin dehydrogenase [72]. Subsequently, _SLCO2A1_ mutation was identified [73]. These defects would increase prostaglandin E2 levels. ### Treatment The treatment has been recently reviewed [74]. Painful synovial effusions may respond to nonsteroidal anti‐inflammatory drugs. Colchicine reportedly helped one patient. Contractures or neurovascular compression by osteosclerotic lesions can require surgical intervention. A variety of treatments may help the hyperhidrosis. ## HEPATITIS C‐ASSOCIATED OSTEOSCLEROSIS In 1992, severe generalized osteosclerosis and hyperostosis was reported in former drug abusers [75]. Approximately 20 cases have been reported, and hepatitis C virus infection proved common to all. Periosteal, endosteal, and trabecular bone thickening occurs throughout the skeleton except the cranium. During active disease, the forearms and legs are painful. Gradual, spontaneous remission [76] with decreasing bone density can occur. The IGF system features distinctive increases in circulating levels of IGF binding protein 2 and "big" IGF II [77].Antiviral therapy improved one patient [78].## OTHER SCLEROSING BONE DISORDERS Table 107.1 lists many additional conditions associated with focal or generalized increases in skeletal mass.Sarcoidosis characteristically causes cysts within coarsely reticulated bone.However, sclerotic areas occasionally appear in the axial skeleton or long bones.

b. Dihydrofolate reductase converts dihydrofolate to FH4.• Thymidylate synthase is irreversibly inhibited by 5-fluorouracil.In the conversion of N5,N10-methylene-FH4 to dihydrofolate reductase (FH2) by thymidylate synthase, the carbon from the methylene group is transferred to deoxyuridine monophosphate (dUMP) to produce deoxythymidine monophosphate (dTMP).a.Methionine synthase removes the methyl group (-CH3) from 5-methyltetrahydrofolate (N5-methyl-FH4), the circulating form of folic acid in the blood, to produce tetrahydrofolate (FH4) and methyl-B12 (methylcobalamin). • Key point—folic acid and folic acid derivatives are important in single carbon transfer reactions from methyl groups (-CH3) and methylene groups (-CH2). Folic acid derivatives: important in single carbon transfer reactions a. Methionine synthase transfers the methyl group of methyl-B12 to homocysteine, which regenerates vitamin B12 (cobalamin) and releases the product methionine. • Deficiency of vitamin B12 traps N5-methyl-FH4 in its circulating form, which falsely increases the serum folic acid in 30% of cases (methyltetrahydrofolate trap). b. Deficiency of folic acid and/or vitamin B12 increases plasma homocysteine. ↑Homocysteine: folic acid deficiency (MC) and vitamin B12 deficiency **Folic acid deficiency** is the most common cause of increased serum homocysteine levels in the United States. Homocysteine acts as an atherogenic factor by converting a stable atherosclerotic plaque into an unstable plaque that leads to thrombosis. 2. Tetrahydrofolate combines with serine to produce N5,N10-methylene-FH4; glycine is a by-product of the reaction. • Tetrahydrofolate receives a methyl group (-CH3) from serine to produce N5,N 10-methylene-tetrahydrofolate and glycine. a. In the conversion of N5,N10-methylene-FH4 to dihydrofolate reductase (FH2) by thymidylate synthase, the carbon from the methylene group is transferred to deoxyuridine monophosphate (dUMP) to produce deoxythymidine monophosphate (dTMP). • Thymidylate synthase is irreversibly inhibited by 5-fluorouracil. b. Dihydrofolate reductase converts dihydrofolate to FH4.Thymidylate synthase: irreversibly inhibited by 5-fluorouracil Dihydrofolate reductase: inhibited by methotrexate (reversible), trimethoprim H **Vitamin B 12 in odd-chain fatty acid metabolism** 1.Vitamin B12 is involved in odd-chain fatty acid (FA) metabolism, which explains the neurologic problems that are unique to vitamin B12 deficiency (Fig.12-17).12-17: Odd-chain fatty acid metabolism.

This information is often suggestive of a unifying diagnosis, but the absence of a "usual" finding should never totally exclude a diagnosis.A person living in the San Joaquin Valley who has pulmonary symptoms may have coccidioidomycosis.A 26-year-old African-American patient with multiple episodes of severe bone pain may be suffering from sickle cell anemia.Chest pain| 6/28/12| 2. Acute inferior myocardial infarction| 1/30/10| 2/15/10 3. Colon cancer| 4/30/08| 6/3/08 4. Diabetes mellitus| 2003| 5. Hypertension| 1997| 6. "Red urine"| 6/10/09| 7/1/09 7. Distress over son's drug abuse| 1/12| The presence of a symptom or sign related to a specific problem is a pertinent positive finding. For example, a history of gout and increased uric acid level are pertinent positive findings in a man suffering from excruciating back pain radiating to his testicle. This patient may be suffering from renal colic secondary to a uric acid kidney stone. The absence of a symptom or sign that, if present, would be suggestive of a diagnosis is a pertinent negative finding. A pertinent negative finding may be just as important as a pertinent positive finding; the fact that a key finding is not present may help rule out a certain diagnosis. For example, the absence of tachycardia in a woman with weight loss and a tremor makes the existence of hyperthyroidism less likely; the presence of tachycardia would strengthen the likelihood of hyperthyroidism. An important consideration in any database is the patient's demographic information: sex, age, ethnicity, and area of residence. A man with a bleeding disorder dating from birth is likely to have hemophilia. A 65-year-old person with exertional chest pain is probably suffering, statistically, from coronary artery disease. A 26-year-old African-American patient with multiple episodes of severe bone pain may be suffering from sickle cell anemia. A person living in the San Joaquin Valley who has pulmonary symptoms may have coccidioidomycosis. This information is often suggestive of a unifying diagnosis, but the absence of a "usual" finding should never totally exclude a diagnosis.This apparently simplistic statement has great merit because it underlines the fact that the observer should not assume an exotic diagnosis if a common one accurately explains the clinical state.(In contrast, if a common diagnosis cannot account for all the symptoms, the observer should look for another, less common diagnosis.)

B Pathology: cause is unknown.Joints most involved are hands, wrists, elbows, knees, and ankles.### MAJOR MEDICAL DIAGNOSES #### Rheumatoid Arthritis A Definition: chronic, systemic disease in which inflammatory changes occur throughout the connective tissue in the body, destroying joints internally.Teach self-care activities.3.Provide self-care aids or devices.2.Assist with ADLs.Avoid use of pillows under knee. 5. To avoid release of emboli, never rub legs. 6. Encourage use of antiembolism stockings. 7. Take daily calf measurements. F Acute pain related to bone fracture or disease 1. Inspect and palpate the painful site, looking for inflammation, edema, bruising, tenderness, and skin warmth; do not rub site, to avoid causing emboli. 2. Support the affected body part. 3. Apply warm, moist compress to affected body part where prescribed. Use ice for injuries within the first 24 to 48 hours. 4. Give prescribed analgesic. 5. Evaluate effectiveness of pain relief measures. 6. Patient teaching for early recognition and reporting of discomfort or pain. G Impaired physical mobility related to cast or traction confinement, joint pain, stiffness, or inflammation 1. Explain the reason for and intended effect of ROM exercises. 2. Have patient maintain body alignment. 3. Provide total exercising of muscles and joints unless severe pain or inflammation is present. Movement is contraindicated if recent surgery was performed on or near the joint. H Acute pain related to cast 1. Massage the area around the cast except for leg casts. 2. Pad rough edges. 3. Elevate extremity to reduce swelling. 4. Inspect the skin for irritation. 5. Observe for cyanosis and assess capillary refill times of the extremity in a cast. 6. Observe for complaints of numbness and tingling of the extremity in a cast. 7. Observe cast for indentations. I Self-care deficits (feeding, bathing, hygiene) related to impaired physical mobility 1. Assist with ADLs. 2. Provide self-care aids or devices. 3. Teach self-care activities. ### MAJOR MEDICAL DIAGNOSES #### Rheumatoid Arthritis A Definition: chronic, systemic disease in which inflammatory changes occur throughout the connective tissue in the body, destroying joints internally. Joints most involved are hands, wrists, elbows, knees, and ankles. B Pathology: cause is unknown.C Signs and symptoms 1.Subjective a. Sore, achy joint or joints b.Fatigue c. Weakness d. Malaise e. Loss of appetite f. Morning stiffness g. Joint pain 2.Objective a. Low-grade fever b.Weakened grip c. Anemia d. Weight loss e. Subcutaneous nodes f. Enlarged lymph nodes g. Joint deformity h. Muscle atrophy i.

It is also thought to be one of those autoimmune disorders whereby the immune system has a homeostatic imbalance and produces certain antibodies that confuse the signals being transmitted.Interruption and interference with this action of acetylcholine on skeletal muscle is the cause of myasthenia gravis.It also transmits messages between the brain and spinal cord.This is the reason that melatonin is referred to as the mood enhancer and known as an antistress, antipanic and antiageing hormone. It is also thought to be helpful in immunity, and to play a part in decreasing pain sensitivity. In many countries it is taken to alleviate jet lag. _Seasonal Affective Disorder syndrome (SAD)._ This is a form of depression, often exacerbated at the onset of winter or by too long a time spent indoors. Again this is linked to disturbance of the light-dark cycle, and seems to be associated with abnormal levels in the production of melatonin. This is thought to be responsible for the many stress-related problems. ( _See_ SAD.) A hypothesis is that by administering melatonin the symptoms are subsequently relieved. The medical profession prescribe melatonin, which sometimes can lead to the exacerbation of symptoms, making the patient even more depressed. It is freely on sale in some countries, but we are not sure of the long-term side-effects. Working on the great toe and brain areas of the foot helps all these disorders without the use of drugs. _Myasthenia gravis._ This disorder affects the muscles of the body, because there is a fault in the transmission of neural impulses to them. Acetylcholine is a most important neurotransmitter and is released by neurons connected to skeletal muscles, often causing them to contract. It also transmits messages between the brain and spinal cord. Interruption and interference with this action of acetylcholine on skeletal muscle is the cause of myasthenia gravis. It is also thought to be one of those autoimmune disorders whereby the immune system has a homeostatic imbalance and produces certain antibodies that confuse the signals being transmitted.The consequence of this is that there is intensifying muscular weakness.The thymus is thought to be the culprit; however, removal of this organ does not guarantee an alleviation of the disorder.Also many of the strong drugs used are only palliative; they do not cure the disorder, and most of them have very debilitating adverse effects.

Elsewhere ACV has long been acclaimed as a hair-conditioning treatment, which produces shinier, less tangled and more manageable locks.Some sufferers report that mixing it with honey improves skin quality and reduces irritation in other areas and that drinking it with honey is also effective, though as yet there is no clinical evidence to support these uses.Dosages may vary depending on whether the herb is being taken during an infection or as a preventive—follow label instructions or take as professionally prescribed. Due to the herb's extremely bitter taste, some people may find it easier to take in capsule or tablet form. ## APPLE CIDER VINEGAR use for ✓ Diabetes and insulin resistance ✓ Psoriasis ✓ Scalp and hair problems A POPULAR FOLK REMEDY, apple cider vinegar (ACV) has played multiple roles over the centuries. It has been a wound-healing agent, preservative, condiment, tonic, deodorant, preventer of scurvy, disinfectant and even an elixir of youth. Today its use as a remedy centers on its ability to help certain skin and scalp disorders when applied topically. It is also being studied for its potential in taming blood glucose levels and its ability to promote weight loss. * * * ### How it works The main constituent of ACV is acetic acid, which has antimicrobial properties. Acetic acid is used topically in conventional medicine to combat antibiotic-resistant bacteria that infect open wounds, and has proved effective against Staphylococcus aureus in patients with leg ulcers. ACV also contains other acids, mineral salts and amino acids, which may have a therapeutic role. The US National Psoriasis Foundation suggests that diluted ACV applied topically can relieve the itch that occurs with scalp psoriasis. Some sufferers report that mixing it with honey improves skin quality and reduces irritation in other areas and that drinking it with honey is also effective, though as yet there is no clinical evidence to support these uses. Elsewhere ACV has long been acclaimed as a hair-conditioning treatment, which produces shinier, less tangled and more manageable locks.One theory is that it does this by deactivating enzymes that break down carbohydrates into glucose, thus slowing the digestive process.A 2007 study of 11 people with type 2 diabetes found that taking 2 tablespoons (30 ml) of ACV in water at bedtime reduced waking glucose levels by 4–6 percent.Other research suggests that taking ACV might encourage weight loss.

A significant compound injury, particularly with associated contamination, tissue loss or devascularisation requires broad-spectrum antibiotic therapy, commencing in the emergency room and maintained perioperatively.If the condition of the limb deteriorates, or is completely ischaemic at presentation with no distal flow demonstrated, the risk of limb loss is significant and exploration and arterial reconstruction is required (Fig. 14.16). Fig. 14.16 Critically ischaemic upper limb with thrombotic occlusion of the brachial artery following cannulation (a). Circulation was restored by excision and vein graft reconstruction of the brachial artery and the limb has been largely preserved (b) ## Complex and Mutilating Hand Injuries A child with a mutilating injury of the upper limb with devascularisation, amputation or a significant complex injury requires a plan formulated for repair or reconstruction of the injury. Fortunately, these injuries are relatively uncommon in children. However, the implications of tissue loss or damage for long term hand function and acceptance, requires the surgeon to, in the words of del Pinal, bring some organization to the chaos of these injuries [84]. Injury outcome scores have been applied in the management and estimation of prognosis of adult lower limb [85] and, more specifically, hand injuries [86]. While these have been applied to the child, the value is arguable and decisions regarding salvage or reconstruction of these complex injuries are made on an individual basis, with the benefit of the doubt in favour of reconstruction rather than amputation. For these complex injuries, preoperative assessment is difficult as exposure of the part will usually be painful but, optimally, some estimate made of whether tissue loss has occurred and, hence, whether the child and parents need to be consented for use of donor sites remote to the injury, or whether the reconstruction is likely to be achieved in a single or multiple stages. A significant compound injury, particularly with associated contamination, tissue loss or devascularisation requires broad-spectrum antibiotic therapy, commencing in the emergency room and maintained perioperatively.The initial operative management is debridement of non-vital tissue, so as to allow a thorough evaluation of the wound.Debridement should be conservative, particularly of tendons and nerves, but foreign material needs to be removed by sharp dissection and lavage to limit the risk of infection in contaminated wounds.

To help you find these doctors, there is a list in the Resources section of complementary medicine associations whose doctors study alternatives to the drug-based medicine they learned in medical school.But cardiologists who are looking for alternatives to drug therapy and to its many side effects, and who read studies thoroughly, are using magnesium successfully.The suggested criteria for magnesium intervention were not followed in a very large trial called ISIS-4, and the outcome did not show the same results as the LIMIT trial. In the ISIS trial, magnesium was given many hours after the onset of symptoms and after blood-clotting had begun and after blood-clotting drugs had been administered. The two trials were as dissimilar as apples and oranges, yet the debate over magnesium's efficacy still rages. Since the LIMIT and ISIS studies, several smaller trials have shown even greater recovery from heart attacks using intravenous magnesium, including a trial of 200 people with a 74 percent lower death rate. Dr. Michael Shechter is a brilliant young magnesium researcher who in his numerous recent clinical trials has proven the benefits of magnesium in treating heart disease. His clinical trials begun in 2000 and continued every year since maintain that magnesium is a viable and necessary treatment for people with heart disease in spite of the ISIS trial and another trial called MAGIC suggesting that it does not., , , , , Pharmaceutical companies, who want to promote their own drug therapies, cite the ISIS trial as proof that magnesium sulfate doesn't work; supporters of magnesium cite the LIMIT trial as proof that it does. Your doctor may be influenced by the ISIS trial and think magnesium is not an important option in your care. But cardiologists who are looking for alternatives to drug therapy and to its many side effects, and who read studies thoroughly, are using magnesium successfully. To help you find these doctors, there is a list in the Resources section of complementary medicine associations whose doctors study alternatives to the drug-based medicine they learned in medical school.Because one of the major side effects of heart medications, especially diuretics, is magnesium deficiency, it is vital that magnesium be tested with a Magnesium RBC test or the EXATest and supplemented in heart patients who are on medication.

Eosinophils are prominent in allergic rhinitis.In the low power view of a nasal polyp in Fig.There is marked oedema and engorgement of mucosal connective tissue and infiltration by chronic inflammatory cells.Simple polyps of this type are generally bilateral and the finding of unilateral involvement suggests alternative diagnoses.12.1 H), commonly infective or allergic in nature.Histologically, there is an inflammatory infiltrate within the interstitium associated with myocyte necrosis. * E) Incorrect. Giant cell myocarditis is a rare entity of unknown cause. Histology demonstrates giant cells and necrotic myocytes. #### Cross-reference: Chapter 11 12 # Respiratory System ## Diseases of the nose and pharynx Allergic rhinitis (hay fever) commonly affects the nose, paranasal sinuses and nasopharynx and can predispose to inflammatory nasal polyps (Fig. 12.1). The sinonasal (Schneiderian) papilloma is particular to the nasal cavity and is usually unilateral (Fig. 12.2). Malignant tumours of the nasal passages and sinuses are rare, but nasopharyngeal carcinoma (Fig. 12.3) is of special interest because of its association with Epstein–Barr virus (EBV) infection. Vocal cord polyps (laryngeal or singer's nodule) arise as smooth nodules on the surface of the true vocal cords, usually as a result of persistent inflammation (Fig. 12.4). The stratified squamous epithelium of the larynx may also contain a low risk HPV infection associated lesion, the benign squamous papilloma. Cigarette smoking and alcohol consumption predispose to the development of dysplasia and invasive squamous cell carcinoma of the larynx . (Fig. 12.5). Fig. 12.1 Nasal polyps. (A) LP; (B) HP.Nasal polyps are a consequence of chronic inflammation of the nasal mucosa (E-Fig. 12.1 H), commonly infective or allergic in nature. Simple polyps of this type are generally bilateral and the finding of unilateral involvement suggests alternative diagnoses. There is marked oedema and engorgement of mucosal connective tissue and infiltration by chronic inflammatory cells. Eosinophils are prominent in allergic rhinitis.In the low power view of a nasal polyp in Fig.As seen in Fig.12.1B, the connective tissue contains an inflammatory cell infiltrate in which eosinophils (Eo) and plasma cells predominate.Eosinophils are also present in the surface respiratory epithelium.Fig.12.2 Sinonasal (Schneiderian) papilloma (MP).There are three main histological types of sinonasal papilloma: exophytic, inverted and oncocytic.

**Can They All Be Right?Dr. Fife's book demonstrates the evidence and explains the research that positively links these diseases to diabetes, metabolic syndrome, and insulin resistance in the brain and other nervous tissues.It was the first book to gather together the pertinent medical research on the health benefits of coconut oil and present it in an understandable format for the general public. Fife's plan recommended optimal dosages of coconut oil that were purported to aid in weight loss, the prevention of heart disease and premature aging, strengthening the immune system, and improving digestion. Interest piqued and soon thereafter _The Coconut Diet_ was written by nutritionist Cherie Calbom, the "Juice Lady." Cherie presented her diet from a cleansing perspective. It employed various detoxification regimens that utilized raw foods and juices while simultaneously incorporating coconut oil into a relatively low-carbohydrate diet. The book cover proclaimed to reveal "the secret ingredient that helps you lose weight while you eat your favorite foods." It especially highlighted the advantages that the medium-chain fatty acids in coconut oil provide for enhanced thyroid function. Most recently, being a prolific author, Dr. Fife has published the _pièce de résistance_ of coconut oil diet books, _Stop Alzheimer's Now!_ Based on serious scientific and medical research and copious case studies, this book takes a profound logical leap forward in explaining that, because of its medium-chain fatty acid makeup, coconut oil is an important key to preventing, mitigating, and even reversing chronic and debilitating neurodegenerative disease states—the dementias, multiple sclerosis (MS), Lou Gehrig's disease (ALS), Parkinson's disease, Huntington's chorea, epilepsy, and others. Dr. Fife's book demonstrates the evidence and explains the research that positively links these diseases to diabetes, metabolic syndrome, and insulin resistance in the brain and other nervous tissues. **Can They All Be Right?For example, the Shilhavys' approach will benefit anyone, but it would not likely be stringent enough to reverse chronic disease states and may not even be enough to normalize weight in some people.

Symptoms include lethargy, depression, social withdrawal, and work difficulties.seasonal affective disorder (SAD) /sē′z n l/, a _DSM-IV_ mood disorder associated with the shorter days and longer nights of autumn and winter.See also **kinesia**.Compare **air sickness,** **car sickness**.Also called **mal de mer**.seasickness, a form of kinesia caused by traveling on an ocean or the sea.SDAT, abbreviation for **senile dementia-Alzheimer type**. SDMS, abbreviation for _Society of Diagnostic Medical Sonographers._ Se, symbol for the element **selenium**. SE, abbreviation for **spin-echo**. S.E., abbreviation for **standard error**. sea-blue histiocyte syndrome, a condition of spleen enlargement and mild thrombocytopenia. Histiocytes in the bone marrow contain cytoplasmic granules that stain bright blue. **Sea-blue histiocyte** _(Carr and Rodak, 2008)_ seaborgium (Sg) /sēbôr′gē· m/ [Glenn T. Seaborg, American chemist and educator, 1912–1999], a synthetic radioactive element, with a half-life of 0.9 second. Its atomic number is 106; its atomic mass is 266. It was first synthesized in 1974 by scientists working independently in the United States and Russia. sealant /sē′l nt/, an agent that protects against access from the outside or leakage from the inside. See also **dental sealant**. sealed source [ME, _seel,_ mark; Fr, _sourdre,_ to spring], a source of radioactivity that is permanently encased in a container or bonding material to prevent leakage. Sealed sources, such as seeds, needles, and specially designed applicators, are used in the implantation of cesium-137, iodine-125, iridium-192, radium-226, and other radionuclides for the treatment of various malignant tumors. sealer cement, a compound used in filling a pulp canal. It is applied as a plastic that fills depressions in the surface of the canal, solidifies after insertion, and helps close the apex of the root canal. seal limbs. See **phocomelia**. seasickness, a form of kinesia caused by traveling on an ocean or the sea. Also called **mal de mer**. Compare **air sickness,** **car sickness**. See also **kinesia**. seasonal affective disorder (SAD) /sē′z n l/, a _DSM-IV_ mood disorder associated with the shorter days and longer nights of autumn and winter. Symptoms include lethargy, depression, social withdrawal, and work difficulties.The symptoms recede in the spring, when days become longer.The condition is associated with the effect of light on melatonin secretion and is treated with light therapy for 5 to 6 hours per day.seasonal allergic rhinitis, hay fever.

The semitendinosus transfer avoids over lengthening of the hamstrings with less effect on anterior pelvic tilt [32].Postoperatively this is associated with improved sagittal plane knee kinematics reduced knee flexion at initial contact, knee extension approximated to normal during loading and reduced peak knee flexion in swing, with increased range of knee movement.The accuracy with regards to the amount of derotation required to normalize gait can be addressed objectively with IGA and is associated with superior postoperative outcomes in comparison to clinical examination alone [27]. The difficulty lies with the surgeon intraoperatively, accurately quantifying the correction. Two studies based on pre- and postoperative IGA data demonstrated that only one- half to two-thirds of the amount of correction was obtained intra-operatively, thereby for a derotation of 20 ° of desired correction on post-operative gait analysis, the surgeon should plan to rotate the femur 30–40 ° at surgery [26, 28]. ## Knee Flexion Deformity Clinical examination and reliance on the popliteal angle is misleading to quantify functional hamstring length. Musculoskeletal modeling of the hamstrings suggests that the hamstring length may be normal or long [29] – thereby a release or lengthening can potentially be detrimental [30]. Surgical options for the hamstrings are numerous. The concept of 'dose of surgery' aims to titrate the amount of surgery on the severity of the flexion deformity [31]. A medial hamstring lengthening is suggested for children with a fixed flexion deformity (FFD) <15 °. Between 15 ° and 25 ° a combined medial hamstring lengthening and semitendinosus transfer to the adductor tubercle is preferred. Postoperatively this is associated with improved sagittal plane knee kinematics reduced knee flexion at initial contact, knee extension approximated to normal during loading and reduced peak knee flexion in swing, with increased range of knee movement. The semitendinosus transfer avoids over lengthening of the hamstrings with less effect on anterior pelvic tilt [32].There are few studies relating to outcomes of anterior stapling (or 8-pating) in children with CP, although there are small case series demonstrating their effectiveness for improving knee flexion deformity in growing children [33].Distal femoral osteotomy can improve knee range of movement and gait indices.

Dogs with chronic ehrlichiosis, however, may very rarely have a monoclonal gammopathy, usually within a polyclonal gammopathy, and a markedly increased concentration of plasma cells in the bone marrow.Two or three of these four features traditionally are considered to be essential for the diagnosis of plasma cell myeloma to be established.15.34).Neoplastic cells may appear to be very well-differentiated, however, in which case they are difficult to distinguish from normal plasma cells. Plasma cells occasionally may have a ruffled eosinophilic cytoplasmic margin that appears similar to a flame; these are termed flaming plasma cells or flame cells (Fig. 15.32). Figure 15.31 Bone marrow aspirate from a dog with plasma cell myeloma. Almost all the cells present are plasma cells. Note the more typical plasma cell with an eccentric nucleus and abundant cytoplasm (arrowhead). Wright stain. Figure 15.32 Left. Bone marrow aspirate from a dog with plasma cell myeloma. These plasma cells have eosinophilic-colored cytoplasm that is ruffled, and they sometimes are referred to as flame cells. The cytoplasm is filled with immunoglobulin. Right. Bone marrow aspirate from a dog with plasma cell myeloma. Note the variation in cell size, ranging from the large, immature plasma cell with loose chromatin (arrow) to the small cells with more condensed chromatin (arrowhead). Wright Stain. An important diagnostic and clinical manifestation of plasma cell myeloma is a monoclonal or biclonal gammopathy, usually immunoglobulin G or A but, occasionally, immunoglobulin M (Fig. 15.33). The immunoglobulins synthesized by malignant plasma cells also are known as paraproteins. Other diagnostic features include Bence-Jones protein (i.e., light chains of immunoglobulins) in the urine and radiographic evidence of osteolysis (Fig. 15.34). Two or three of these four features traditionally are considered to be essential for the diagnosis of plasma cell myeloma to be established. Dogs with chronic ehrlichiosis, however, may very rarely have a monoclonal gammopathy, usually within a polyclonal gammopathy, and a markedly increased concentration of plasma cells in the bone marrow.Figure 15.33 Protein electrophoretogram from a dog with plasma cell myeloma and monoclonal gammopathy.Note the monoclonal immunoglobulin (IgG) spike at the right.Albumin is represented by the smaller spike to the left.Wright stain.Figure 15.34 (A) Lateral lumbar radiograph of a dog with multiple myeloma.

However, less invasive endobronchial ultrasound (EBUS)-guided or endoscopic ultrasound (EUS)-guided biopsies are now being used with increasing frequency both for initial diagnosis and staging of the mediastinum.In the past, the only procedure available to define mediastinal lymph node metastases before surgery was mediastinoscopy.Treatment of NSCLC is significantly influenced by the specific histologic subtype (squamous vs. non-squamous) and the presence of driver genetic alterations, such as EGFR mutation or ALK gene rearrangement (31). Therefore, it is imperative to obtain sufficient tissue to perform these analyses. Generally, biopsy of a metastatic site is preferred over the primary tumor since it also provides conclusive evidence of metastatic spread. In addition, a core biopsy is preferred over a fine needle aspirate since core samples are more likely to yield enough tissue not only for the diagnosis of lung cancer, but also for histologic subtyping and for the analysis of driver genetic alterations. The two most commonly performed diagnostic procedures for suspected lung cancer are image-guided (CT or ultrasound) biopsy of the primary tumor or an accessible metastatic site or bronchoscopic biopsy of the primary with or without biopsy of mediastinal lymph nodes. Thoracentesis with cytologic evaluation of pleural fluid is very helpful in patients with a pleural effusion. Mediastinal Staging Assessment of the mediastinum is an important aspect of staging patients with potentially resectable lung cancer. Metastatic spread to the mediastinal lymph nodes is generally considered a contraindication to primary surgical resection. Initial noninvasive mediastinal assessment is done with both CT and PET. However, since both the false-positive and false-negative rates with PET are about 10%, pathologic confirmation of mediastinal lymph node involvement is crucial in patients with otherwise resectable lung cancer. In the past, the only procedure available to define mediastinal lymph node metastases before surgery was mediastinoscopy. However, less invasive endobronchial ultrasound (EBUS)-guided or endoscopic ultrasound (EUS)-guided biopsies are now being used with increasing frequency both for initial diagnosis and staging of the mediastinum.The lymph nodes that can be accessed by mediastinoscopy include high (levels IIR and IIL) and low (levels IVR and IVL) paratracheal and anterior subcarinal (level VII) lymph nodes.

The concept that non-free fluid (CSF is free fluid) or interstitial edema is bright on FLAIR or DWI would suggest that there may be subtly increased underlying amounts of fluid in these locations relative to other regions that are darker on FLAIR, or the bright signal in these regions could be related to a slightly lesser degree of myelination (i.e., less tightly packed axons).Such cortical hyperintensity also may be diffuse throughout the cerebrum or cerebellum and may simulate early findings of hypoxic-ischemic encephalopathy/injury (HIE/HII); the apparent diffusion coefficient (ADC) maps accompanying the DWI will lack cortical or subcortical white matter abnormalities in such normal cases. (Acute HIE will have a dark cortex on ADC maps, and subacute HIE more than 5–7 days old will have deep white matter dark signal on ADC maps.) Cortical hyperintensity may appear asymmetric and greater in the frontal region (particularly at 3 T) than in posterior regions, a difference that may be exaggerated by the fact that the perirolandic cortices (precentral and postcentral gyri) have normally darker signal at 3 T than the frontal cortices. The reasons for parenchymal FLAIR, T2WI, and DWI pseudolesions are unknown. However, such pseudolesions seem to be noted most commonly in regions that undergo myelination later (e.g., the PVWM posteriorly), at the edge of or within regions of active myelination in children (e.g., PVWM or CST in infants), or in regions of high diffusion anisotropy (e.g., CST or DSCP). The concept of structures with normal, relatively higher anisotropy causing normal hyperintensity focally on DWI is covered in more detail later in the subsection focused on DWI, along with DWI-specific artifact. The concept that non-free fluid (CSF is free fluid) or interstitial edema is bright on FLAIR or DWI would suggest that there may be subtly increased underlying amounts of fluid in these locations relative to other regions that are darker on FLAIR, or the bright signal in these regions could be related to a slightly lesser degree of myelination (i.e., less tightly packed axons).The problem with the theory of the dielectric effect is that cases of cortical hyperintensity are quite common, which is contrary to the concept that deeper structures tend to be more hyperintense.Thus, the cause of hyperintensities in such locations is unknown but may vary depending on the location.

Look for non-stimulating, adaptogenic, botanical American ginseng ( _Panax quinquefolius_ ) to help control cortisol variations and serum blood glucose and insulin levels._Thyroid Support Supplements_ A high-quality thyroid support supplement is an all-in-one thyroid support product that may benefit many thyroid conditions._Glutamine_ Glutamine is a major fuel for the intestines and supports the functioning of the gastrointestinal tract. It aids in tissue growth and is the nutrient of choice for maintaining the intestinal mucosal lining. Glutamine also supports the growth of muscle mass and is known to support the immune system—specifically, the powerful immune system found in the gut. _Digestion Support Supplements_ High-quality digestion support supplements blend digestive enzymes with betaine HCL to support optimal digestion of proteins, fats, and carbohydrates. The best brands contain the protease dipeptidyl peptidase IV (DPP IV), which aids in the breakdown of casomorphin (from casein) and gluteomorphin (from gluten), as well as the enzyme lactase, which helps break down the dairy sugar lactose. By reducing the inflammation associated with digestive dysfunction, a digestion support supplement taken before meals may be helpful for those who experience gas and bloating after eating and who tend toward constipation. But before you buy this supplement, try eating a slice of dried mango with your meal. It might work even better than a supplement. _Adrenal Support Supplements_ High-quality adrenal support supplements combine whole herbs that nutritionally support the adrenal cortex and glands. By enhancing the body's ability to produce certain adrenal hormones, these supplements support the immune system and also relieve mild stress and frustration. _Thyroid Support Supplements_ A high-quality thyroid support supplement is an all-in-one thyroid support product that may benefit many thyroid conditions. Look for non-stimulating, adaptogenic, botanical American ginseng ( _Panax quinquefolius_ ) to help control cortisol variations and serum blood glucose and insulin levels.Hypothyroidism, the name given to low production of thyroid hormone, is vastly underrecognized.Many of my patients have vague complaints that they attribute to aging, yet healing their thyroid frequently resolves their complaints.We know that for optimal health the thyroid must be balanced so that the rest of the hormonal symphony stays in tune.

Not only do food allergies increase the allostatic load and cortisol burden, food allergies themselves are the result of long-term stress.Other behaviors such as early weaning and premature introduction of solid foods to infants and the repetitive nature of most diets have been suggested to increase food intolerances._Candida albicans_ is especially problematic because it adheres to the gut wall and directly contributes to a leaky gut. Acid-blocking medications (Zantac, Prilosec, Tagamet, to name a few) alter the digestive process by reducing stomach acid secretion. (These are important drugs when needed to treat gastritis, gastric reflux, or ulcers but are widely overused by physicians and the public.) With less stomach acid comes reduced pancreatic enzyme secretion, leading to poor digestion of proteins and absorption of substances triggering allergy. These drugs also contribute to nutritional deficiencies (B12, zinc, and other minerals) that affect the immune system as well. Poor nutritional habits lead to greater food allergy incidence through continual exposure to the same foods, fast foods, sugars, and unhealthy oils and fats. The typical American diet, rich in omega-6 fats and simple sugars and lacking omega-3 fats and complex carbohydrates, impacts the digestive process by encouraging abnormal bacterial growth in the gut while not providing the nutrients needed for the health of the gut wall cells, the mucocytes. Poor nutrition can lead to greater likelihood of viral illness that can at times trigger a food allergy problem. The change in food composition of the American diet also plays a role. The number of food additives has skyrocketed over the past fifty years, leading to recurrent exposure to chemicals in foods. Foods containing preservatives, conditioners, and artificial colorings and flavorings, and foods that are contaminated with antibiotics from animal feed and pesticides, add to the impact on the immune system in the digestive tract. Other behaviors such as early weaning and premature introduction of solid foods to infants and the repetitive nature of most diets have been suggested to increase food intolerances. Not only do food allergies increase the allostatic load and cortisol burden, food allergies themselves are the result of long-term stress.High cortisol also increases stomach acid production, leading to more use of acid-blocking drugs, and furthering malabsorption.Chronic stress and allostatic load will eventually change the immune response, leading to more allergies.Managing food allergies is a major part of the dietary control of cortisol and regaining adaptation.

Fibrosis causes ageing muscles to develop increasing amounts of fibrous connective tissue, which results in a loss of flexibility, movement and circulation.This can be attributed to: * Loss of elasticity to skeletal muscle – as muscles age they lose their elasticity due to a process called fibrosis (Martini and Bartholomew, 2012).Common types of body movements include: * extension – a movement that increases the angle or distance between two bones or parts of the body; * hyperextension – an extension angle greater than 180°; * flexion – the opposite of extension, in that it is a movement that decreases the angle or distance between two bones and brings the bones closer together and is a common movement of hinge joints – for example, bending the elbow or knee; * abduction – moving a limb away from the midline of the body; * adduction – (the opposite of abduction) the movement of a limb towards the midline of the body; * rotation – a movement common to ball-and-socket joints and is the movement of a bone around its longitudinal axis; * circumduction – a combination of abduction, adduction, extension and flexion. Table 6.8 provides a summary of the different actions of muscle movement. **Table 6.8** Types of muscle movement ****Action****| ** **Definition**** ---|--- Extension| Increases the angle or distance between two bones or parts of the body Flexion| Decreases the angle of a joint Abduction| Moves away from the midline Adduction| Moves closer to the midline Circumduction| A combination of flexion, extension, abduction and adduction Supination| Turns the palm up Pronation| Turns the palm down Plantar flexion| Lowers the foot (point the toes) Dorsiflexion| Elevates the foot Rotation| Moves a bone around its longitudinal axis ## The effects of ageing Generally, the size and power of all muscle tissues within the body decrease as the body ages. This can be attributed to: * Loss of elasticity to skeletal muscle – as muscles age they lose their elasticity due to a process called fibrosis (Martini and Bartholomew, 2012). Fibrosis causes ageing muscles to develop increasing amounts of fibrous connective tissue, which results in a loss of flexibility, movement and circulation.This tendency for rapid fatigue also means that, with age, there is a lower tolerance for exercise.* Age-related reduction in cardiovascular performance – means that blood flow to muscles does not increase with exercise and the ability to recover from muscular injuries decreases and is likely to result in scar tissue formation.

Although I found some ideas a bit quirky, I still approached TCM teaching with an expectant attitude.I later learned that one TCM principle for treatment of skin diseases is to treat the lung.We know that smoking is associated with premature aging of skin.An insufficiency of heart Qi causes pallor, glassy appearance, anorexia, poor and congested circulation with a black color in the face. "_ The description of heart Qi insufficiency could easily be that of a moribund patient with advanced heart disease. _"An increase in heart fire results in redness of the tip of the tongue, painful mouth, or sores of the mouth, restlessness, and insomnia. "_ The association of the TCM heart with fire and mouth sores was a bit strange until we were introduced in our curriculum to the Five Phases system of TCM (see chapter 4). # Lung Next came the description of the lung. _"The lung governs Qi. The lung is the sea of Qi. It gets Qi from the outside atmosphere and from inside the body when food is transported via the spleen to the lung. The lung is subordinate to the heart. The heart mobilizes the blood but it depends on healthy lung Qi. The nature of lung Qi is descending. If lung Qi rises, there is dyspnea, cough, congestion, edema, and difficult urination. It opens channels for water. It assists water to descend into the bladder. "_ Lung Qi (literally, air that is inhaled) made sense to me as a Western practitioner. At this point, I could not grasp how the lung received Qi from food, but I found the rest acceptable. The description of what happens when lung Qi rises fits that of congestive heart failure, often accompanied by dyspnea, congestion, and fluid retention. _"The lung governs skin and body hair, which depend on lung Qi for moisture and nourishment. If lung Qi is weak, the skin and hair become dry. "_ It is logical that poor lung function would impair oxygenation of blood, and therefore the skin and hair, suffering this loss, would become dry. We know that smoking is associated with premature aging of skin. I later learned that one TCM principle for treatment of skin diseases is to treat the lung. Although I found some ideas a bit quirky, I still approached TCM teaching with an expectant attitude.The description bore no resemblance whatsoever to the organ that I knew as the liver._"The liver is the general of organs; it strategizes, needs to flow, and dislikes obstruction,"_ he said.I could accept calling the liver a _general_ and saying it _strategizes,_ because the liver is actually an organ of metabolism, clearing the body of a multitude of compounds.

The appropriate choice and application of proteomic techniques are important parts of the experimental design.In contrast to SILAC, ICAT and 2D gel electrophoresis can be used on both tumor biopsies and cell culture–based experiments.However, SILAC can be used only for cell culture–based proteomic experiments.This makes SILAC currently the most promising quantitative proteomics approach.Subtractive proteomic mapping of the endothelial surface in lung and solid tumors for tissue-specific therapy. Nature, 429, 629–35. Reproduced by permission of Nature. To overcome some of the limitations of 2D gel–based proteomics, more robust techniques such as SDS-PAGE or gel-free protein separation combined with 1D and 2D HPLC and highly resolving mass spectrometry, or protein arrays which depart completely from the conventional proteomics technologies, have been developed over the past 5 or so years and are increasingly used for the various proteome-related problems addressed in cancer biology. ICAT was one of the first chemical peptide labeling tech­niques that allowed for high-throughput proteomics by liquid chromatography–mass spectrometry (LC-MS). The main disadvantage of ICAT is that the labeling is dependent on a chemical reaction with cysteine, which has to be optimal for successful labeling. However, ICAT can be used on any biological system whether it is cell lines, (human) tissue, yeast, or bacteria. An example of the application of ICAT is the quantitative proteomic analysis of Myc oncoprotein function in mammalian cells (Shiio et al., 2002). SILAC with heavy nitrogen (15N) or carbon (13C) labeled amino acids are the main types of metabolic labeling. Metabolic labeling is a very efficient method of proteome-wide labeling of proteins. Unlike chemical labeling like ICAT, the cell incorporates the heavy isotope form of the amino acids (see Box 20.6). This makes SILAC currently the most promising quantitative proteomics approach. However, SILAC can be used only for cell culture–based proteomic experiments. In contrast to SILAC, ICAT and 2D gel electrophoresis can be used on both tumor biopsies and cell culture–based experiments. The appropriate choice and application of proteomic techniques are important parts of the experimental design.Generally, SILAC protein extracts are mixed with a control in a 1 : 1 ratio, then separated by 1D gel electrophoresis, digested with an endopeptidase, and analyzed by LC-MS.The mass spectra are processed to identify and quantify proteins.

Interestingly, preliminary studies of exercise have shown it can potentially lower the risk of depression, anxiety, and stress and should be added to any treatment regimen.In addition, a lack of physical activity and less than optimal eating habits are more likely with this disorder, which only further impact physical and mental health.** Virtually any lifestyle change found to be heart healthy has been shown to reduce the risk or progression of BPH, including maintaining normal blood pressure, blood sugar, and cholesterol levels and a healthy weight or waist size, eating a healthy diet, and exercising. Alpha-blockers are the top-selling drug class used to treat BPH; they work by relaxing the prostate. They were originally derived from blood pressure–lowering medicines because men reported peeing better when their high blood pressure was reduced. Bam! **Drink in moderation. ** This has been consistently associated with a lower risk of BPH and reduced symptoms associated with BPH, probably due to the anti-inflammatory effects or the heart-healthy benefits of moderate alcohol consumption. Of course, this doesn't mean you should _start_ drinking if you don't currently imbibe. **Work up a sweat. ** One of the best ways to prevent BPH or reduce the progression of it is to exercise regularly, about 30 minutes a day. In a famous Harvard study, regular physical activity was even associated with a lower risk of getting surgery for BPH! Patients tell me all the time that after a good, long aerobic workout, their urinary stream seems stronger, and this is further proof of how exercise relaxes the prostate and helps improve urinary function. ## Bipolar Disorder ### THE JURY'S STILL OUT **Dr. Moyad Secret Heart healthy = bipolar disorder healthy? ** Yes! Individuals with bipolar disorder tend to also have a higher incidence of metabolic syndrome and other cardiovascular risk factors, such as high cholesterol, high blood pressure, obesity, and diabetes. In addition, a lack of physical activity and less than optimal eating habits are more likely with this disorder, which only further impact physical and mental health. Interestingly, preliminary studies of exercise have shown it can potentially lower the risk of depression, anxiety, and stress and should be added to any treatment regimen.A similar percentage have difficulty adhering to medications because of side effects, so you should explore adding anything with a high benefit-to-risk scenario.**NAC (N-acetylcysteine).

Though classified as one of the NSAID's—nonsteroidal anti-inflammatory drugs—which are considered to have milder side effects than steroids, Rimadyl has produced side effects that are very disturbing indeed, and appeared to lead to at least three deaths among dogs in my practice.Along with the usual supplements, I used the homeopathic remedy silicea at high potencies, since I'd heard reports of its success in helping reverse bone cancer. I also added injectable homeopathic bone, "Os Suis" from the German company Heel. Now, I sensed, was also the time for intravenous ozone. In all previous cases of bone cancer for which I'd used ozone, I'd injected ozone gas directly into the tumors. But due to this tumor's location, deep in the musculature of the upper arm, I couldn't reach it directly. Instead, Sassi was given ozone intravenously, and by painless enema into her rectum. For months afterward, Sassi did well. Her tumor remained totally unchanged, as shown by follow-up X rays at VPI—astounding with such an aggressive cancer—and remained small enough not to be painful, enabling her to lead a normal life. A year after her visit, her health appeared to falter. Up she came again for another "pick-me-up" round of intravenous vitamin C and ozone. The bone cancer appeared not to have grown at all. During that period, though, it was clear she had developed some sharp, undefined pain in her neck. The obvious conclusion was that the bone cancer had spread to her upper spine, but a full X-ray series, again at VPI, revealed no evidence of any growth, progression, or spread of the tumor. At VPI, the best guess was that Sassi might have arthritis—by now, she was eleven years old—and so she was put on Rimadyl, a drug I warn against in the "Arthritis" section of Chapter Seven. Though classified as one of the NSAID's—nonsteroidal anti-inflammatory drugs—which are considered to have milder side effects than steroids, Rimadyl has produced side effects that are very disturbing indeed, and appeared to lead to at least three deaths among dogs in my practice.I don't know whether Rimadyl contributed to Sassi's death.Perhaps some other cause is to blame.She was, after all, eleven years old, and her unspecified pain was so acute at times in that last stage that the relief she did get from Rimadyl may have warranted its use.But the last report I received about her, just prior to her death, indicated no spread of the original cancer.

Thrombocytopenia occurs in up to 25% of patients, with extreme thrombocytopenia (<20,000 platelets/mm3) occurring in 5–10% of these patients.20 * _Mucocutaneous disease:_ The cutaneous manifestations of SLE include photosensitive rashes, alopecia (hair loss), periungual telangiectasias (involving the nail folds), and livedo reticularis (purplish networking discoloration of skin).Labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score ≥1 focus/4 mm2. 3. Keratoconjunctivitis sicca with ocular staining score greater ≥3 (assuming that individual is not currently using daily eye drops for glaucoma and has not had corneal surgery or cosmetic eyelid surgery in the last 5 years). ### Medical History and Physical Exam #### Systemic Lupus Erythematosus Medical history and physical assessment reveal the diversity of this multisystem disease that can have phases of stability and exacerbations, called lupus flares. * _Renal disease:_ Localization of immune complexes in the kidney is the precipitating factor in the development of lupus nephritis and can lead to a rapidly progressing glomerulonephritis or a less aggressive form of renal disease resulting from cumulative, chronic tissue injury during previous flares of SLE. Ultimately, cell proliferation, inflammation, necrosis, and fibrosis result in significant impairment of renal function. * _Cardiac disease:_ Cardiac manifestations include pericarditis, pericardial effusion, myocardial infarction, and valvular disease. The most common of all cardiac lesions in these patients is a nonbacterial verrucous valvular lesion, known as Libman–Sacks endocarditis. * _Hematological disease:_ Anemia, leukopenia, and thrombocytopenia are significant complications of SLE and/or its treatment. Anemia in these patients is most commonly associated with hemodialysis therapy, while leukopenia results from the immunosuppressive therapies. Thrombocytopenia occurs in up to 25% of patients, with extreme thrombocytopenia (<20,000 platelets/mm3) occurring in 5–10% of these patients.20 * _Mucocutaneous disease:_ The cutaneous manifestations of SLE include photosensitive rashes, alopecia (hair loss), periungual telangiectasias (involving the nail folds), and livedo reticularis (purplish networking discoloration of skin).1.4).* _Oral conditions:_ Over 75% of SLE patients have oral complaints, including ulcerations, xerostomia, and burning mouth.Ulcerations, erythema, and/or keratosis, commonly affecting the vermilion, gingiva, buccal mucosa, and palate found in patients with SLE, may be confused with lichen planus.

aureus_ or of _S.However, evidence for a similar pathogenesis in humans is lacking; the relationship between the clinical signs of staphylococcal blepharitis and hypersensitivity to subcutaneous injections of either whole _S.epidermidis_.These findings could not be reproduced for _S.Systemic factors that may promote MGD include, among others, androgen deficiency, menopause, ageing, Sjögren syndrome, hypercholesterolaemia, psoriasis, atopy, rosacea, hypertension and benign prostatic hyperplasia (BPH). Medications associated with the pathogenesis of MGD include antiandrogens, medications used to treat BPH, postmenopausal hormone therapy (e.g. oestrogens and progestins), antihistamines, antidepressants and retinoids [6]. ###### Pathology ###### _Staphylococcal blepharitis_ In staphylococcal blepharitis there is an association with _Staphylococcus aureus_ and _S. epidermidis_ colonization of the lid margins, although colonization by _S. aureus_ is often transient and the numbers of either organism are often no greater than in normal controls [14] (see also Chapter 26). Although folliculitis, styes and lid margin ulcers may be due to infection by _S. aureus_ , the persistence of lid inflammation after treatment and the sterile marginal ulcers are not explained by infection alone. The importance of cell-mediated immunity in the pathogenesis of the disease was shown by experimental studies in rabbits; when these were immunized with either whole _S. aureus_ or with cell wall ribitol teichoic acid, both ulcerative keratitis, phlyctenules and marginal corneal ulcers developed after secondary challenge, providing evidence for the hypothesis that these changes were due to the development of hypersensitivity to both viable and killed organisms [15, 16]. These findings could not be reproduced for _S. epidermidis_. However, evidence for a similar pathogenesis in humans is lacking; the relationship between the clinical signs of staphylococcal blepharitis and hypersensitivity to subcutaneous injections of either whole _S. aureus_ or of _S._Staphylococcus epidermidis_ is more often isolated than _S.aureus_ from the lids of patients with staphylococcal blepharitis, but the role of a hypersensitivity response is assumed and not supported by any firm data [17].

1.(Crayhon 1998).**Eleven More Reasons to Cut the Carbs (If You Aren't Already Convinced)** The following list of reasons to cut your carbs is adapted from _The Carnitine Miracle,_ by Robert Crayhon, M.A.Grains (gluten) and dairy (casein) are the most common offenders, followed by soy, peanuts, and corn. Chicken eggs are also commonly problematic for many people. Cyrex Labs (www.cyrexlabs.com) has extremely accurate testing. A stool antigen test by Enterolab (www.enterolab.com) can be reliably diagnostic of several common food sensitivities as well. * Get a good night's sleep. Don't be a night owl. Studies repeatedly show sleep deprivation as strongly correlated with decreased insulin sensitivity and unwanted weight gain, along with other problems. Try to get at least six to eight quality hours of sleep every single night, as we were designed to do! * Exercise daily, or at least three to five times per week. Short bouts of high-intensity interval training or exertion-and-resistance training are most effective. Exercise has been shown to decidedly help improve insulin sensitivity. Exercise such as this immediately following a meal containing carbohydrates also can help burn off some of the sugar. * Give special attention to stress management. Increased levels of stress hormones (e.g., cortisol) may significantly elevate blood sugar levels and insulin production, as well as suppress the immune system. _Actively cultivate stress-reduction habits_ —or else! _Note:_ Cravings for sugar, alcohol, or carbohydrates, as well as cravings for stimulants such as caffeine, may be an indication of serotonin depletion. Chronic use of these substances actually depletes serotonin over time and can lead to low levels of this important neurotransmitter. This lack of serotonin can either generate or exacerbate cognitive deficits, as well as depressive, labile, or anxious states—particularly in susceptible individuals (Schwarzbein and Deville 1999). **Eleven More Reasons to Cut the Carbs (If You Aren't Already Convinced)** The following list of reasons to cut your carbs is adapted from _The Carnitine Miracle,_ by Robert Crayhon, M.A. (Crayhon 1998). 1.2.You are much more likely to have a heart attack following a high-carbohydrate meal than a high-fat meal.3.Carbohydrates raise your level of insulin, which makes you fat and increases your risk for metabolic disorder, diabetes, and worse.4.A high intake of carbohydrates and sweetened beverages is associated with an increased risk of breast cancer (Witte et al.1997).5.

Observation alone is generally recommended after the first episode of diverticular hemorrhage.The pathogenesis is believed to be the rupture to the submucosal branch of the penetrating arteries or vasa recta into the colonic lumen as a result of stretching of the weakened diverticular wall.Among the more common causes for bright blood per rectum or hematochezia (bloody stools) is upper gastrointestinal bleeding (UGIB), which occurs in approximately 10% to 15% of patients with LGIB. An additional 5% to 10% of bleeding may arise from small bowel sources such as Meckel's diverticulum, small bowel tumors, or angiodysplasia. Colonic sources of bleeding include diverticular bleeds, bleeding from neoplasia or polyps, and various types of colitis (Table 1). Approximately 10% to 20% of LGIB do not have a clear etiology and remain obscure despite thorough evaluation. TABLE 1: Bleeding diagnoses in patients discharged with acute lower gastrointestinal bleeding in the National Inpatient Sample, 2002 Adapted from Strate LL, Ayanian JZ, Kotler G, et al: Risk factors for mortality in lower intestinal bleeding, _Clin Gastronenterol Hepatol_ 6(9):1004–1955, 2008. ### Diverticulosis The prevalence of diverticulosis, or colonic outpouching, increases with age; in Western society, approximately two thirds of the population have diverticulosis by age 85 years. Twenty percent of patients with diverticulosis present with abrupt, painless bleeding or hematochezia during their lifetime, and 5% have severe hemorrhage. Although most diverticula are located in the sigmoid and descending colon, diverticular bleeding is fairly equally distributed between the right and left sides of the colon. Risk factors for bleeding diverticulosis include advanced age, the use of nonsteroidal antiinflammatory drugs (NSAIDs) or anticoagulation therapy, diabetes mellitus, and ischemic heart disease. The pathogenesis is believed to be the rupture to the submucosal branch of the penetrating arteries or vasa recta into the colonic lumen as a result of stretching of the weakened diverticular wall. Observation alone is generally recommended after the first episode of diverticular hemorrhage.Surgical intervention consists of resection of the affected segment of colon.### Neoplasia Occult bleeding, bright red blood per rectum, and hematochezia are all potential signs of benign adenomatous polyps and adenocarcinoma of the colon and rectum.Polyps account for 7% to 33% of cases of massive LGIB.

It is well established that genetic factors influence the dose of warfarin required to maintain the INR within the therapeutic range.These data suggest that age should not be considered a contraindication to treatment with warfarin in patients with AF.The annual risk for a major hemorrhagic complication during anticoagulation with warfarin is in the range of 1% to 2%, and a strong predictor of major bleeding events is an INR higher than 3.0. For example, the risk for intracranial bleeding is approximately twice as high at an INR of 4.0 than at 3.0. This emphasizes the importance of maintaining the INR in the range of 2.0 to 3.0. Some studies have indicated that advanced age can be a risk factor for intracranial hemorrhage in patients with AF who are treated with warfarin. The fear of hemorrhagic complications may lead some clinicians to favor the use of aspirin over warfarin in older adults. However, recent data indicate that the risk-to-benefit ratio of warfarin is more favorable than that of aspirin, even in patients older than 75 years. A randomized clinical trial (the Birmingham Atrial Fibrillation Treatment of the Aged Study) enrolled 973 patients older than 75 years (mean age, 82 years) with AF and randomly assigned them to treatment with 75 mg/day of aspirin or with warfarin adjusted to maintain an INR of 2.0 to 3.0.22 The primary endpoint was the composite of stroke (ischemic or hemorrhagic), intracranial hemorrhage, and arterial embolism, and the mean duration of follow-up was 2.7 years. The annual risk for the composite endpoint was significantly higher in the aspirin group (3.8%) than in the warfarin group (1.8%), even when the analysis was limited to patients older than 85 years. These data suggest that age should not be considered a contraindication to treatment with warfarin in patients with AF. It is well established that genetic factors influence the dose of warfarin required to maintain the INR within the therapeutic range.

Most cancer chemotherapeutic agents are immune-suppressants and cytotoxic.Using an Ayurveda-inspired reverse pharmacology approach, bioactive fractions have been developed as potential vaccine adjuvants.This effort led to four Indian and one United States patent in the area of vaccine adjuvant [46–48].In immune-suppressed animals, ashwagandha exhibited significant dose-dependent potentiation of cellular and humoral immune response, comparable to levamisole, and faster recovery of CD4+ T cells percentages compared to the control, and cyclosporin [42]. The study indicated immunostasis activity, and suggests its use where Th1–Th2 modulation is required. This activity has shown significant benefits as immunoadjuvants, when studied on mortality and morbidity associated with DPT, and the potentiating, protective effects of vaccine. Newer vaccines such as subunit and DNA vaccines are weakly immunogenic and require adjuvants. We hypothesized that Rasayana may offer better and safer immunodrugs that can be used as adjuvants in vaccines and cancer treatments [43]. Researchers from our group used a modified Kendrick test that involved the challenge of live pertussis cells intracerebrally, where a significant increase in antibody titer, reduced mortality, and improvement in overall health was observed [44]. This observation has immense importance in the vaccine industry, to obtain more efficient and sustained immunostimulation resulting in increased yield of immune sera, and immunobiologicals [44]. These studies indicate applications of Rasayana as potential immunoadjuvants, that also offer direct therapeutic benefits resulting in lower morbidity and mortality [45]. A project to develop a vaccine adjuvant was successfully completed in collaboration with Savitribai Phule Pune University and the Serum Institute of India. This effort led to four Indian and one United States patent in the area of vaccine adjuvant [46–48]. Using an Ayurveda-inspired reverse pharmacology approach, bioactive fractions have been developed as potential vaccine adjuvants. Most cancer chemotherapeutic agents are immune-suppressants and cytotoxic.Researchers carried out activity-related extractions to identify the best performing candidate drugs.This work resulted in a United States patent in the area of cancer adjuvants.This product will have importance in cancer therapeutics, especially to counter untoward effects of chemotherapy, without compromising the anticancer activity of chemotherapy [49].

Because of rumors about a high breakage rate, many people believe that condoms are not all that effective.Removal must be done carefully to avoid spillage.Condoms may be lubricated or can be used with a variety of water-based lubricants (read the label), but they should not be used with petroleum-based lubricants such as Vaseline.However, that thin rubber membrane may be all that stands between you and pregnancy or a variety of diseases. These latex rubber sheaths that unroll to cover the penis are 90 to 98 percent effective in preventing pregnancy. The effectiveness can be raised to nearly 100 percent by combining them with the cervical cap, diaphragm, vaginal contraceptive film (VCF), or fertility awareness. Condoms also provide the best protection from sexually transmitted diseases (STDs). According to the US Food and Drug Administration, they are "highly effective" in preventing infection from HIV, gonorrhea, Chlamydia, trichomoniasis, and hepatitis B. They are less effective against genital herpes, human papillomavirus, syphilis, and chancroid. Condoms are often thought of as a "male-controlled" method, but actually, the effective use of condoms requires the interest and willingness of both partners. Today both men and women buy condoms and keep them in their backpacks or at the bedside for ready use. Because of low cost and wide availability, condoms are the most commonly used barrier method in the world. They come in a variety of styles, in different sizes, and with various aesthetic embellishments, with or without lubricants and/or spermicide. To be effective, condoms must be used correctly. They should be unrolled along the shaft of the penis with a little space left at the tip to collect the ejaculate. Condoms may be lubricated or can be used with a variety of water-based lubricants (read the label), but they should not be used with petroleum-based lubricants such as Vaseline. Removal must be done carefully to avoid spillage. Because of rumors about a high breakage rate, many people believe that condoms are not all that effective.Condoms that are old or have been exposed to heat are more likely to break.If you are worried about breakage, use two condoms at a time.Also, try to buy them in small quantities and at places where turnover is high, such as large discount drug stores.Female Condom * * * The female condom somewhat resembles the standard male condom and can be bought over the counter.

As survival improves for certain subgroups, attention may be refocused on reduction of treatment morbidity and long-term consequences.Increasing knowledge of tumor biology has allowed recognition of differential sensitivity to chemotherapeutic agents among various phenotypic subgroups and risk group stratification.All were treated with chemotherapy and none received radiation. Clinical regression of testicular involvement was seen in all patients and there were no episodes of testicular relapse. Survival was not influenced by the presence of testicular involvement. The authors concluded that systemic chemotherapy is sufficient for B cell non-Hodgkin's lymphoma in boys and that a careful search should be made for additional sites of disease in boys that present with testicular masses. In rare cases, primary lymphoma arising in the testis will present as testicular enlargement and diagnosis will be made at the time of biopsy or orchiectomy. Both follicular and Burkitt's lymphomas have been reported in children as a primary site [22, 29]. In general, these tumors are treated by orchiectomy and chemotherapy. Successful treatment by orchiectomy alone has been reported in a 3 year old boy with stage I follicular lymphoma of the testis [22]. Fig. 21.10 Ultrasound imaging of testicular infiltration due to non-Hodgkin's lymphoma that manifested as testicular enlargement ### Treatment Non-Hodgkin's lymphoma is considered a systemic disease in all patients and chemotherapy is the cornerstone of successful treatment. As in many other childhood cancers, there has been a remarkable evolution in treatment regimens since the 1960s with continued improvement due to multicenter, cooperative trials. Increasing knowledge of tumor biology has allowed recognition of differential sensitivity to chemotherapeutic agents among various phenotypic subgroups and risk group stratification. As survival improves for certain subgroups, attention may be refocused on reduction of treatment morbidity and long-term consequences.It is important to minimize surgical morbidity so that chemotherapy can begin promptly for these tumors since they have such a rapid growth fraction.Current chemotherapy for NHL is based on attention to histology, immunophenotype, extent of disease and central nervous system prophylaxis.

Observable behavior, including "test behavior," reflects an interaction between the domains of person and environment.A competent neuropsychologist will sample multiple domains of behavior.Such behavior can range from a person's manner of dress to his or her performance on a specific neuropsychological test.Observable behavior is frequently the most sensitive manifestation of brain pathology.Although quantitative data are also important, the patient's route to solving a particular cognitive problem often reveals an underlying process that can be reflective of spared and affected brain regions. In contemporary practice, both of these methods rely on a vast body of knowledge about characteristic syndromes that are known to be associated with underlying disease states. The current practice of clinical neuropsychology concerns itself with the assessment of cognitive functions, through the use of test instruments, for the purpose of understanding the functional integrity of the brain. By relying on knowledge of brain–behavior relationships and characteristic syndromes, the results of assessment are useful for the diagnosis and treatment of brain-related injuries and illness. # II. Fundamental Assumptions The study of clinical neuropsychology is firmly rooted in the larger field of neuroscience and, therefore, rests on the assumption that the nervous system impacts behavior and cognition. Conversely, inferences can be made about the integrity of the brain based on observable behavior. The ability to make accurate and meaningful inferences is predicated on a thorough understanding of two streams of knowledge: (a) the neural infrastructure underlying normal human cognition and behavior and (b) the characteristic profiles of neurocognitive and neurobehavioral syndromes. Observable behavior is frequently the most sensitive manifestation of brain pathology. Such behavior can range from a person's manner of dress to his or her performance on a specific neuropsychological test. A competent neuropsychologist will sample multiple domains of behavior. Observable behavior, including "test behavior," reflects an interaction between the domains of person and environment.Individual tests used in neuropsychological practice focus on measurement of particular cognitive processes.In order to be useful, each test must be constructed according to sound psychometric principles and possess adequate validity and reliability.In addition, there must be appropriate normative data with which to compare a single patient's performance.

Therefore, to produce the maximum reduction in risk, CEA should be performed within 2 weeks of a minor stroke or TIA.The risk of a major stroke is highest in the period immediately following a minor stroke or TIA.Intra-abdominal hypertension is common after surgery for a ruptured AAA. Ideally, the intra-abdominal pressure should be monitored to identify those patients who are developing abdominal compartment syndrome. Summary A ruptured AAA is a vascular surgical emergency that is associated with significant morbidity and mortality. Optimal care requires excellent communication between the different professional groups involved at each stage of the treatment process. The anaesthetist caring for the patient with a ruptured AAA needs to be aware of the potential for profound haemodynamic instability, myocardial ischaemia, coagulopathy, and marked acid–base disturbance. It is crucial that appropriate treatments are instituted in a timely fashion to minimize the impact of these factors. **Further reading** **Roberts K** **,** **Revell M** **,** **Youssef H** **,** **Bradbury AW** **,** **and** **Adam DJ** (2006). Hypotensive resuscitation in patients with ruptured abdominal aortic aneurysm. _European Journal of Vascular and Endovascular Surgery_ , **31** , 339–44. Case 9.2 Carotid endarterectomy # Background Carotid endarterectomy (CEA) is a preventative procedure that aims to reduce the likelihood of a major disabling stroke or death in patients who have experienced a minor stroke or a transient ischaemic attack (TIA) and who also have a significant stenosis of the ipsilateral internal carotid artery. The risk of a major stroke is highest in the period immediately following a minor stroke or TIA. Therefore, to produce the maximum reduction in risk, CEA should be performed within 2 weeks of a minor stroke or TIA.# CPD matrix matches 2A03; 2A10; 2G01 # Case history A 57-year-old male accountant with a 30 pack year smoking history is scheduled for a left-sided CEA.Seven days previously, whilst in a business meeting, he experienced an episode of weakness affecting his right arm, accompanied by expressive dysphasia.His symptoms resolved completely within 20 min.

Patients with respiratory disease, particularly children, often have difficulty handling excessive secretions.The equipment necessary for these interventions is generally not available in low-resource settings and therefore will not be discussed in this chapter.In most low-resource settings, equipment and oxygen capacity is insufficient for these techniques. However, bubble continuous positive airway pressure (CPAP) providing positive end-expiratory pressure (PEEP) can be established using supplies commonly available in most hospitals (Figure 26.2). It is important to note that patients on bubble CPAP are dependent on a steady flow of oxygen; cessation of oxygen flow can quickly lead to suffocation. Therefore, bubble CPAP should only be used in settings where there is close and preferably continuous monitoring of patients and where there is staff trained in using the device. Figure 26.2 Simple bubble CPAP can be made from common hospital supplies (adapted from AdaptAir.org). The PEEP delivered with bubble CPAP can be adjusted by changing the depth the tubing is immersed in water. The above interventions are helpful in supporting patients with impaired oxygenation but are insufficient to treat im­­paired ventilation secondary to lung disease or hypoventilation. Invasive or non-invasive methods, such as bilevel positive airway pressure or mechanical ventilation, may be needed to deliver positive pressure inhalations to patients with impaired ventilation. The equipment necessary for these interventions is generally not available in low-resource settings and therefore will not be discussed in this chapter. Patients with respiratory disease, particularly children, often have difficulty handling excessive secretions.Various pathologies causing respiratory distress, such as asthma or COPD, present with wheezing.Wheezing should be treated with inhaled beta-agonists, frequently salbutamol in low-resource settings.Salbutamol nebulization can be administered every 10–20 min until patient improvement, or continuously.

Occasionally patients may experience severe pain and distension up to several hours after the CT colonogra-phy examination because of excess residual air within the colon.Thus, following retrograde insufflation of the colon with room air, the colon will remain filled until the air is passed distally.Following supine axial image acquisition, the patient is turned prone and another CT scout image is obtained with additional gaseous insuf-flation if segments of colon with suboptimal distension are noted on the scout view. Fig. 5.5 (a) Poor distension of the descending colon limits the diagnostic ability for lesions on this axial image. (b) Endolumi-nal view in the same patient showing suboptimal distension which inhibits navigation through this segment Fig. 5.6 (a) Collapse of a portion of the rectum in the supine position on an axial image. (b) Excellent distension of the rectum with the same patient in a prone position, demon-strating a small polyp along the left posterolateral colonic wall. (c) Three-dimensional cube view of the same polyp seen in the prone position Fig. 5.7 (a) Collapse of a long length of the sigmoid on coronal multiplanar reformatted view simulating annular carcinoma. (b) Occlusion of the lumen on endoluminal view due to collapse of the sigmoid in the same patient. This appearance may also be caused by an occluding carcinoma, and proper colonic distension is essential for differentiation ### 5.3.1 Room Air Currently room air is used most frequently to manually insufflate the colon for CT colonography. Its ease of use and familiarity to radiologists and technologists because of a similar route of administration per rectum for double-contrast barium enema examinations has made it easily adaptable for CT colonography. It is also readily available at no additional cost. A large component of room air is nitrogen, which is inert, so that there is no active diffusion across the bowel wall when the colon is distended with air. Thus, following retrograde insufflation of the colon with room air, the colon will remain filled until the air is passed distally. Occasionally patients may experience severe pain and distension up to several hours after the CT colonogra-phy examination because of excess residual air within the colon.1995).### 5.3.2 Carbon Dioxide Carbon dioxide (CO2) has been used instead of atmospheric air for insufflation of the colon for colonos-copy as well as for barium enema examination because it has been found to decrease patient discomfort.CO2 is readily resorbed through the colonic wall because of a steep diffusion gradient and it is then exhaled from the lungs.

For example, the risk of infection with MDR pathogens for a nursing home resident who has dementia but can independently dress, ambulate, and eat is quite different from the risk for a patient who is in a chronic vegetative state with a tracheostomy and a percutaneous feeding tube in place.Moreover, HCAP is a distillation of multiple risk factors, and each patient must be considered individually.## **CHAPTER 11 PNEUMONIA** **Lionel A. Mandell Richard Wunderink** ### **DEFINITION** Pneumonia is an infection of the pulmonary parenchyma. Despite being the cause of significant morbidity and mortality, pneumonia is often misdiagnosed, mistreated, and underestimated. In the past, pneumonia was typically classified as community-acquired (CAP), hospital-acquired (HAP), or ventilator-associated (VAP). Over the past two decades, however, some persons presenting as outpatients with onset of pneumonia have been found to be infected with the multidrug-resistant (MDR) pathogens previously associated with HAP. Factors responsible for this phenomenon include the development and widespread use of potent oral antibiotics, earlier transfer of patients out of acute-care hospitals to their homes or various lower-acuity facilities, increased use of outpatient IV antibiotic therapy, general aging of the population, and more extensive immunomodulatory therapies. The potential involvement of these MDR pathogens has led to a new category of pneumonia—termed _health care_ — _associated pneumonia_ (HCAP)—distinct from CAP. Conditions associated with HCAP and the likely pathogens are listed in **Table 11–1**. **TABLE 11–1** **CLINICAL CONDITIONS ASSOCIATED WITH AND LIKELY PATHOGENS IN HEALTH CARE–ASSOCIATED PNEUMONIA** Although the new classification system has been helpful in designing empirical antibiotic strategies, it is not without disadvantages. Not all MDR pathogens are associated with all risk factors (Table 11–1). Moreover, HCAP is a distillation of multiple risk factors, and each patient must be considered individually. For example, the risk of infection with MDR pathogens for a nursing home resident who has dementia but can independently dress, ambulate, and eat is quite different from the risk for a patient who is in a chronic vegetative state with a tracheostomy and a percutaneous feeding tube in place.This chapter deals with pneumonia in patients who are not considered to be immunocompromised.### **PATHOPHYSIOLOGY** Pneumonia results from the proliferation of microbial pathogens at the alveolar level and the host's response to those pathogens.Microorganisms gain access to the lower respiratory tract in several ways.The most common is by aspiration from the oropharynx.

Recalling that edema occurs following a fracture and recalling the complications associated with a cast will assist you in answering the question._**Test-Taking Strategy:**_ Focus on the **subject** , a plaster cast.The health care provider is notified immediately if circulatory impairment occurs._**Test-Taking Strategy:**_ Eliminate options 1 and 2 first because they are **comparable or alike** in that either of these options could result in further injury to the victim. Of the remaining options, the more prudent action would be for the nurse to remain with the victim and have someone else call for emergency assistance. _**Review:**_ Immediate care of the victim with a **fracture** **_Level of Cognitive Ability:_** Applying **_Client Needs:_** Physiological Integrity **_Integrated Process:_** Nursing Process—Implementation **_Content Area:_** Adult Health—Musculoskeletal **_Priority Concepts:_** Clinical Judgment; Mobility _**Reference:**_ Ignatavicius, Workman (2013), pp. 1153, 1160. **833. 1, 2, 3** **_Rationale:_** A plaster cast takes 24 to 72 hours to dry (synthetic casts dry in 20 minutes). The cast and extremity should be elevated to reduce edema if prescribed. A wet cast is handled with the palms of the hand until it is dry, and the extremity is turned (unless contraindicated) so that all sides of the wet cast will dry. A cool setting on the hair dryer can be used to dry a plaster cast (heat cannot be used on a plaster cast because the cast heats up and burns the skin). The cast needs to be kept clean and dry, and the client is instructed not to stick anything under the cast because of the risk of breaking skin integrity. The client is instructed to monitor the extremity for circulatory impairment, such as pain, swelling, discoloration, tingling, numbness, coolness, or diminished pulse. The health care provider is notified immediately if circulatory impairment occurs. _**Test-Taking Strategy:**_ Focus on the **subject** , a plaster cast. Recalling that edema occurs following a fracture and recalling the complications associated with a cast will assist you in answering the question.**834.2** **_Rationale:_** A small amount of serous oozing is expected at pin insertion sites.Signs of infection such as inflammation, purulent drainage, and pain at the pin site are not expected findings and should be reported to the health care provider._**Test-Taking Strategy:**_ Focus on the **subject** , a finding that is of least concern.

There are no recommended doses for this supplement as it is not a nutritive element.Another possibility, shown in several lab-based studies, it that chondroitin may block the sprouting on pain-sensing nerves, which may help prevent pain after back injury as a normally vigorous sprouting response contributes to extra pain sensitivity.Think of all the skinny people you know who drink diet soda; now think of all the heavy people you know who drink diet soda: which list is longer? The benefits of drinking water are tremendous, from improving oral hygiene to reducing food consumption. Most diet experts recommend limiting water intake at mealtime to a few sips. It seems that drinking water in between meals and especially 20 minutes before mealtimes is a good strategy. ### Know Your Supplements #### **GLUCOSAMINE AND CHONDROITIN SULFATE FOR JOINTS** Glucosamine and chondroitin sulfate is the most commonly used non-nutritive dietary supplement for the treatment of arthritis. Derived from cow's hooves and shark cartilage, glucosamine and chondroitin sulfate are compounds that are normally found in joints. The supplementation of these compounds in the diet is believed to contribute to joint motions that are smooth and relatively painless. There is some scientific evidence to support their use in osteoarthritis of the knee and hip., A specific benefit for spine arthritis has not yet been shown. Additional mechanisms may explain the beneficial effects of the compounds against pain. One possibility is that glucosamine in particular may block the release of signaling factors that drive inflammation, but this has been shown in laboratory studies only. Another possibility, shown in several lab-based studies, it that chondroitin may block the sprouting on pain-sensing nerves, which may help prevent pain after back injury as a normally vigorous sprouting response contributes to extra pain sensitivity. There are no recommended doses for this supplement as it is not a nutritive element.Factors That Increase Stomach Acid Reflux • Stress • Ibuprofen and other NSAIDs • Lying down soon after meals • CAPS foods • Frequent bending over • Heavy lifting • Obesity • Fatty foods #### **CALCIUM FOR BONES** Calcium is clearly important for bone health.

People with this mutation are at risk for many types of malignancies, some common and some rare, including ovarian cancer like Veronica's.Members of Li Fraumeni syndrome families have an approximately twenty-five-fold increased risk of developing a malignant tumor by age fifty than does the average person.Unfortunately, despite the tremendous wealth of knowledge that we have about TP53's multiple roles in different mechanisms of tumor suppression, finding it mutated is not presently very helpful in terms of pointing to the best treatment option. On the frontier of knowledge, oncologists have to go with their gut instincts about what is best for each patient. This is still personalized oncology as much as precision oncology. I am confident that at some point we will get around this problem and make effective therapies to restore TP53 function. Unfortunately, that day has yet to come. Finding a TP53 mutation in Veronica's tumor also opened up an incidentaloma box. The test had sequenced her tumor and discovered a _bona fide_ TP53 deleterious mutation. Yet we couldn't tell whether the mutation had only recently arisen as the tumor grew and changed (called a _somatic_ mutation), or whether Veronica carried this mutation in all the normal cells in her body (that would be called _constitutional_ mutation). People who carry a TP53 mutation in all the normal cells in their body have a genetic disease called the _Li Fraumeni syndrome_ , named after Fred Li and Joe Fraumeni Jr., the American physicians who first described it. The Li Fraumeni syndrome can be passed on from generation to generation, although about one out of five or ten people with the syndrome have a _de novo_ mutation and are the first affected member of their family. Members of Li Fraumeni syndrome families have an approximately twenty-five-fold increased risk of developing a malignant tumor by age fifty than does the average person. People with this mutation are at risk for many types of malignancies, some common and some rare, including ovarian cancer like Veronica's.If Veronica's mutation was in all of her cells' DNA, that meant it was inheritable and could also affect her two children.I explained to her family that we couldn't tell at this point.Her precise TP53 mutation had not been seen in Li Fraumeni patients in the past.Was that because it was a rare variant?

CD4 counts below 100 cells/µL **Cryptosporidiosis** is a disease that causes typically large-volume watery diarrhoea, and can be life-threatening in individuals who are severely immune suppressed.Common causes at different CD4 counts are described below.The causes of diarrhoea will vary depending on an individual's immune status.Very urgent, watery bowel motions causing pain and/or cramping may be considered severe. Acute diarrhoea Acute diarrhoea usually lasts for less than 14 days (Post, 2006) and, depending on severity, may have little impact on nutritional status. Chronic diarrhoea Chronic diarrhoea has many definitions including 'loose stools occurring three days per week'; or 'two or more loose watery stools per day for at least 30 days'. Many PLHIV have had chronic diarrhoea for several years and often do not report this symptom when seeing their doctor, as it has become 'normal' to have recurrent loose bowel motions. As weight loss and nutrient deficiencies often occur in PLHIV with chronic diarrhoea, clinicians and dietitians should routinely ask PLHIV about stool volume, consistency and frequency, together with gauging the impact these are having on the patient. The volume and frequency of diarrhoea will vary depending on the affected part(s) of the intestines. In diseases of the small intestine, stools are usually voluminous and watery or fatty. In colonic (large intestine) disease, stools are frequent, sometimes small in volume, and possibly accompanied by blood, mucus, pus and abdominal cramping or discomfort (WHO, 2006). 9.4.2 Causes of diarrhoea in PLHIV Parasites, bacteria and viruses may account for up to 80% of diarrhoea experienced by PLHIV. Medications, including ART, may also cause or exacerbate diarrhoea in this population. The causes of diarrhoea will vary depending on an individual's immune status. Common causes at different CD4 counts are described below. CD4 counts below 100 cells/µL **Cryptosporidiosis** is a disease that causes typically large-volume watery diarrhoea, and can be life-threatening in individuals who are severely immune suppressed.A 'Cochrane review' of trials found insufficient evidence to establish whether any drug is able to effectively eliminate the organism amongst symptomatic individuals (Abubakar _et al._ , 2007).**Microsporidiosis** ****typically causes fever, pain, watery stools with or without mal- absorption and wasting.However, microsporidiosis may respond to antimicrobial therapy.

To return the system to a normal, healthy state, whatever caused the problem in the first place must first be dealt with.For example, if a cough suppressant is given at this point, inflammation may develop in the lungs that can lead to pneumonia or even asthma.All natural healing substances and holistic therapies—including herbs, supplements, homeopathy, nosodes, flower essences, acupuncture, and aromatherapy—elicit a detoxification response. In this natural phase of the healing process, things may seem to get worse for a time, even though the body is actually moving forward to restore health and balance. #### THE NATURE OF SYMPTOMS Symptoms are simply the visible manifestation of the body's attempt to heal itself. For instance, when a virus infects the upper respiratory system, the body produces lots of mucus and tears to wash away the virus particles. Inflammation flares as the body's defensive white blood cells rush to the area and release chemicals to kill the invaders. Coughing develops as airway defenses push virus particles and debris away from the lungs. The cat may even develop a fever, since respiratory viruses cannot live at higher-than-normal temperatures. These symptoms may be uncomfortable for the cat, and certainly distressing for you to see, but they are all part of the normal defensive and healing processes of the body. If, however, you give the cat drugs to suppress the symptoms, these normal defenses will be inhibited. The body then has to find another way to combat the infection, which often results in a new symptom. For instance, if a decongestant is used to dry up the mucus and tears, the virus may be able to penetrate deeper into the lungs, and a cough may develop to protect sensitive lung tissues. If we then use another drug to get rid of the new symptom—the cough—the body will continue to search for other ways to deal with the problem. For example, if a cough suppressant is given at this point, inflammation may develop in the lungs that can lead to pneumonia or even asthma. To return the system to a normal, healthy state, whatever caused the problem in the first place must first be dealt with.#### ENVIRONMENTAL CHALLENGES The body—whether human or feline—receives constant challenges from the environment: viruses, bacteria, parasites, and fungi, and also air pollution, water pollution, and chemicals used in the manufacture of flooring, carpeting, furniture, and clothing.

## Inborn Errors of Metabolism and Other Genetic Disorders Inborn errors of metabolism are well-characterized genetic abnormalities that give rise to metabolic disorders.Figure 10-12 Numerous islands of extramedullary hematopoiesis (small blue cells) are scattered among mature hepatocytes in the liver of this infant with nonimmune hydrops fetalis. The most serious threat in fetal hydrops is CNS damage, known as kernicterus (Fig. 10-13). The affected brain is enlarged and edematous and, when sectioned, has a bright yellow color, particularly the basal ganglia, thalamus, cerebellum, cerebral gray matter, and spinal cord. The precise level of bilirubin that induces kernicterus is unpredictable, but neural damage usually requires a blood bilirubin level greater than 20 mg/dL in term infants; in premature infants this threshold may be considerably lower. Figure 10-13 Kernicterus. Note the yellow discoloration of the brain parenchyma due to bilirubin accumulation, which is most prominent in the basal ganglia deep to the ventricles. ###### Clinical Features. The clinical manifestations of fetal hydrops vary with the severity of the disease and can be inferred from the preceding discussion. Minimally affected infants display pallor, possibly accompanied by hepatosplenomegaly (to which may be added jaundice with more severe hemolytic reactions), whereas the most gravely ill neonates present with intense jaundice, generalized edema, and signs of neurologic injury. These infants may be supported by a variety of measures, including phototherapy (visual light oxidizes toxic unconjugated bilirubin to harmless, readily excreted, water-soluble dipyrroles) and, in severe cases, total exchange transfusion of the infant. ## Inborn Errors of Metabolism and Other Genetic Disorders Inborn errors of metabolism are well-characterized genetic abnormalities that give rise to metabolic disorders.Most inborn errors of metabolism are rare diseases that are generally inherited as autosomal recessive or X-linked traits (Chapter 5).Mito­chondrial disorders (Chapter 5) form a distinct entity by themselves.Some of the clinical features that suggest an underlying metabolic disorder in a neonate are listed in Table 10-4.

That's exactly what we've seen happen in these patients."One of the major goals of cancer research has been to identify differences between cancer cells and normal cells so that these differences can be targeted with more effective and less toxic treatments.But on this afternoon in New Orleans, he looked like he was having trouble controlling his excitement. He described the research group's efforts to identify a proper dose and schedule for treatment and months of waiting for results. Finally, as the regimen was refined to three 100-milligram capsules per day, the benefits became apparent. All thirty-one patients experienced what seemed to be complete remission, with their white blood cells returning to normal and their health restored. In some cases, the chromosomal abnormality that caused the disease began to disappear. Indeed, when they studied blood samples, Druker's group couldn't find any evidence of the Philadelphia chromosome in some of their patients. The only side effects reported were fatigue, muscle cramps, and stomach upsets. I think that most of us who listened to Druker's talk reflected on CML patients who had died and others who had suffered the grueling experience of bone marrow transplants, which only worked a quarter of the time. In comparison, STI571 seemed like a miracle, and scientists generally don't believe in miracles. Druker acknowledged this when he spoke with the press. "One of the problems I've had with this project," he said, "is that I oftentimes have difficulty convincing people that this isn't too good to be true. One of the major goals of cancer research has been to identify differences between cancer cells and normal cells so that these differences can be targeted with more effective and less toxic treatments. That's exactly what we've seen happen in these patients."Approval came on May 10, 2001.Novartis, which had been gearing up for the moment, began shipping the drug the very next day.In less than six hours, every advance order for the drug—more than five thousand of them—had been filled and shipped.Soon doctors and patients all over the world were seeing dramatic remissions like the ones recorded in early trials.

**P/OM.Centre point for abdominal pain and any distension.** Apex of ear for any inflammatory problem.**P/AA.** Both large and small intestine points, also the ileocaecal valve.**P/AS._Warning!_ ST-36 must not be used on young children.ST-35 and 36 are ideal for gastritis or diarrhoea.** SP-5 and LIV-1 are good for constipation.**P/LL.(1) Stimulation to the adrenal gland area encourages production of the glucocorticosteroids, which have a very powerful anti-inflammatory effect; this also helps regulation of salt and water balance. There is loss of vital electrolytes with excessive diarrhoea. It also allows the inflamed tissue to heal itself. (2) Stimulation of the spinal area contacts the sympathetic nervous system; this calms the activity in the bowels. The combination of working the whole spinal area helps to balance the stimuli from the vagus nerve and the coeliac plexus that serve the whole abdominal viscera. (3) The spleen is a vital area for both of these problems; this adjusts the quality and quantity of blood in the circulation; we know according to Chinese medicine it is responsible for peristalsis in the colon and it helps remove foreign bodies from the bloodstream. Extra stimulation to this area helps contraction, thus squeezing every little bit of reserve of nutrient-rich blood into the general circulation. Working the whole system correctly enables the eliminating organs to function normally; detoxification then takes place enhancing the immune system and balancing homeostasis. **P/Hs. ** LI-2 and 4, and TB-4 are all very effective for constipation. For intestinal colic, SI-3 and 4. _Warning!_ LI-4 can be used only providing the person is not pregnant, as it is an empirical point to promote delivery during labour. **P/LL. ** SP-5 and LIV-1 are good for constipation. ST-35 and 36 are ideal for gastritis or diarrhoea. _Warning!_ ST-36 must not be used on young children. **P/AS. ** Both large and small intestine points, also the ileocaecal valve. **P/AA. ** Apex of ear for any inflammatory problem. Centre point for abdominal pain and any distension. **P/OM.**P/TCM.** Shenmen for pain relief and also a calming point.**P/HF.** For constipation or diarrhoea a good point on the face is Chengjiang (CV-24) in the depression below the bottom lip.The CV meridian starts in the perineum.( _See also_ Colon problems.)#### Breast problems ##### Symptoms Most breast discomforts are due to hormonal imbalances.

(Courtesy of Professor Dame Janet Husband.)The tumour (arrow) is shown extending posteriorly to the rectum and laterally to the side-walls of the pelvis.**Figure 18.8** CT scan in advanced bladder cancer.To evaluate the degree of extravesical spread MRI and CT are extremely valuable (Figure 18.8).### Clinical features The majority of patients with bladder cancer complain of haematuria, usually painless, although other symptoms such as urgency of micturition, nocturia and frequency or reduction of the urinary stream may also be present. Loin or back pain may occur if tumour obstruction has led to hydronephrosis or if large intra-abdominal lymph node metastases are present. Even single episodes of haematuria should be fully investigated by cystoscopy. Fortunately, the majority of patients with superficial tumours do not develop invasive disease; indeed, it is probably true that superficial and deeply invasive bladder carcinomas are distinctly separate disorders [1]. Definitive diagnosis requires cystoscopy with biopsy, which gives a clear indication of the site, size, general appearance and multiplicity of tumours. This procedure is normally performed under general anaesthesia, permitting a full examination including thorough rectal and bimanual palpation, which is essential for accurate staging. Urinary exfoliative cytology is a valuable addition to diagnosis and is currently being evaluated as a means not only of diagnosis but also of monitoring response to treatment. IVU should be performed, giving essential information regarding the anatomy and functioning of the kidneys and ureters, and often further information as to the site and extent of the primary tumour. Renal function should be assessed by measurement of blood urea and creatinine clearance, or other form of assessment such as diethylenetriaminepenta-acetic acid (DTPA) clearance. To evaluate the degree of extravesical spread MRI and CT are extremely valuable (Figure 18.8). **Figure 18.8** CT scan in advanced bladder cancer. The tumour (arrow) is shown extending posteriorly to the rectum and laterally to the side-walls of the pelvis. (Courtesy of Professor Dame Janet Husband.)Repeated cystoscopy may be required, together with biopsy of any suspicious site.Tumour mapping is an important preliminary and all visible tumours should be removed wherever possible.The aim of treatment is not only to eradicate the initial lesion but also to prevent a superficial relapse and, above all, prevent progression to muscle-invasive disease.

**Is ultrasound safe?With higher frequencies, there is greater resolution but decreased penetration.The transabdominal probes are typically 3 to 7 MHz and the transvaginal probes 5 to 9 MHz.** True.**True or False: The frequencies of the transvaginal transducers are typically higher than the transabdominal.This is known as the piezoelectric effect.**In pregnancies affected with Trisomy 18, the hCG will be _______, and the PAPP-A will be _____. NT will be increased. ** Decreased, decreased. **What NT is greater than the 99th percentile throughout the measured gestational ages? ** 3.5 mm. **While performing NT, what structure shown below may be a useful marker for detection of aneuploidy? ** Nasal bone. **What technique should be utilized for nasal bone (NB) measurements? ** • Fetus magnified so that only the head and upper thorax are in the screen. • Precise midsagittal view of the fetal profile. • Fetal spine down with slight neck flexion. • Transducer parallel to the direction of the fetal nose (45–135 degrees). • Three distinct lines should be seen. **What is the ductus venosus? ** A trumpet-shaped vein connecting the umbilical sinus to the hepatic veins and the IVC, directing high velocity oxygenated blood returning from the placenta to the left atrium via the foramen ovale. **What is the normal Doppler waveform pattern in the ductus venosus? ** Biphasic pulsatile continuously forward flow. **What heart abnormalities may be apparent in the first trimester, but may be resolved by the third trimester? ** Muscular ventricular septal defect. ## **CHAPTER 17 Obstetrical Ultrasound and Fetal Abnormalities** Amelia McLennan, MD **How is ultrasound produced? ** It is the vibrations of crystals in response to electrical current generate sound waves. This is known as the piezoelectric effect. **True or False: The frequencies of the transvaginal transducers are typically higher than the transabdominal. ** True. The transabdominal probes are typically 3 to 7 MHz and the transvaginal probes 5 to 9 MHz. With higher frequencies, there is greater resolution but decreased penetration. **Is ultrasound safe?The level of ultrasound intensity that is defined as safe is <100 mW/cm2.It has been shown to cause thermal effects and mechanical changes via cavitation in animal studies.**What serum analytes are used in conjunction with ultrasound to screen for aneuploidy?

_Phase 1:_ Studies that are usually conducted with healthy volunteers and that emphasize safety.For this purpose, positron emission tomography technologies are particularly useful.This phase aims to select compounds that might be of use in more traditional clinical studies, a selection process sometimes called _screening_ because one of the characteristics that is looked for is target engagement.This is the worst result possible in a study because it implies that the data generated are not informative, and most of the resources invested are lost. Clinical trials usually are described as _positive_ when the results support the hypothesis being tested and _negative_ when they fail to support that hypothesis. However, a negative trial may appear to occur under two different scenarios: either the intervention is truly not efficacious in the situation tested or the trial failed. Only in the first condition should the trial be called negative. To ascertain that this is the case, the analysis of the data must go far beyond the strictly statistical analysis of the hypothesis, which can never tell more than that the null hypothesis is rejected or not. The ascertainment that a trial is truly negative must be determined from thorough analysis of various components, including the characteristics of the population, the dimension of the placebo effect, and the adequacy of the randomization. The stepwise approach is exemplified by the U.S. Food and Drug Administration (FDA) phases of clinical trials. #### Food and Drug Administration Phases of Clinical Trials _Phase 0:_ Exploratory study involving very limited human exposure to the drug, with no therapeutic or diagnostic goals (examples include screening of candidate compounds and microdose studies). Phase 0 is a recent addition to the traditional scheme of four phases (Figure 17.1). This phase aims to select compounds that might be of use in more traditional clinical studies, a selection process sometimes called _screening_ because one of the characteristics that is looked for is target engagement. For this purpose, positron emission tomography technologies are particularly useful. _Phase 1:_ Studies that are usually conducted with healthy volunteers and that emphasize safety._Phase 2:_ Studies that gather preliminary data on effectiveness (whether the drug has efficacy in a parameter relevant to the indication pursued in people who have a certain disease or condition).For example, participants receiving the drug may be compared with similar participants receiving a different treatment, usually an inactive substance (placebo) or a different drug.

Respiratory failure, multiorgan dysfunction, and septic shock are the usual cause of death.Prolonged febrile states and generalized malaise are common.Other systems can also be involved leading to neurologic manifestations (encephalopathy, seizure) and liver impairment.Conjunctivitis is reported in influenza H7 infections.Gastrointestinal symptoms are reported more frequently in H5N1 infections.The primary risk factor for human infection is direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets. Slaughtering and handling carcasses of infected poultry are also risk factors. The emergence of H5, H7, and H9 avian influenza virus subtypes in humans raises concern that the virus may undergo genetic reassortment or mutations in some of the genes and develop greater human-to-human transmissibility with the potential to produce a global pandemic. Human infections with H5N1 viruses have been reported to WHO from 16 countries, the first report in the Americas was in Canada in 2014, and approximately 60% of the cases have died. Infection with avian influenza (H7N9) virus was first reported in China in 2013. Since then, many cases have been reported around the world with an average case fatality rate of 40%. Infections with other H7 avian influenza viruses (H7N2, H7N3, and H7N7) have occurred sporadically around the world. Rare human cases of influenza H9N2 are also reported. ### Clinical Findings #### A. Symptoms and Signs Distinguishing avian influenza from regular influenza is difficult. History of exposure to dead or ill birds or live poultry markets in the prior 10 days, recent travel to Southeast Asia or Egypt, or contact with known cases should be investigated. Patients infected by H5N1 or H7N9 avian influenza A viruses have an aggressive clinical course. The symptoms and signs include fever followed by lower respiratory symptoms (cough, dyspnea). Upper respiratory tract symptoms are less common. Gastrointestinal symptoms are reported more frequently in H5N1 infections. Conjunctivitis is reported in influenza H7 infections. Other systems can also be involved leading to neurologic manifestations (encephalopathy, seizure) and liver impairment. Prolonged febrile states and generalized malaise are common. Respiratory failure, multiorgan dysfunction, and septic shock are the usual cause of death.For human infections with avian influenza A(H7N7) and A(H9N2) viruses, most cases have been mild with a few cases hospitalized and very few reports of deaths resulting from infection.#### B.Laboratory Findings Current commercial rapid antigen tests are not optimally sensitive or specific for detection of H5N1 influenza and should not be the definitive test for influenza.

Do not despair.Furthermore, if your loved one lives long enough in a bed-bound condition, it is likely that you will witness at least one serious skin breakdown known as a bedsore, or decubitus.Coconut oil is excellent for use in light massage to improve circulation, for muscle and nerve stimulation, and as an aid in the prevention of contractures.It is helpful in cleanups, too, when normal soap and water might prove too abrasive to get the job done. Lest you think this idea is a bit far fetched, there is nothing that tears more easily or horrifyingly than the fragile skin of a demented elder. Even the skin of a newborn baby is infinitely more resilient. As an antiseptic cleanser, coconut oil is a gentle and welcome friend. In Lewy body dementia, one of the notable early symptoms is, incredibly, an inconceivably runny nose. My mother would easily go through an entire carton of facial tissues in a day, which sadly is exceedingly rough on a nose. A light application of coconut oil can ease the discomfort of a raw nose and calm inflamed nasal passages, too! With incontinence and constipation come other special problems. Rashes, vaginal yeast infections, and jock itch are notable among the issues that crop up when elders may become damp or soiled overnight, and coconut oil aids in prevention by providing a nourishing barrier on the skin that inhibits fungal and bacterial growth. In the case of constipation, coconut oil in the diet is a good preventative. But after the fact, when an enema may become necessary, coconut oil is an excellent mild lubricant for easy, pain-free insertion of the syringe. Finally, when patients become bedridden, everything becomes far more complicated. Coconut oil is excellent for use in light massage to improve circulation, for muscle and nerve stimulation, and as an aid in the prevention of contractures. Furthermore, if your loved one lives long enough in a bed-bound condition, it is likely that you will witness at least one serious skin breakdown known as a bedsore, or decubitus. Do not despair.**A Coconut Body Balm to Make** Aromatherapy may seem like alchemy to the uninitiated, but therapeutic blends of essential oils really can help elders in the end stages of dementia.Therapeutic essential oils enhance psychological and physical well-being.By utilizing the art and science of blending them to their greatest synergistic effect, elders can be afforded a substantial amount of relief.

Although its cause remains unknown, it is clear that both genetic and environmental factors play a role in pathogenesis.Along with SD and xerosis generalisata, it is by far one of the most commonly seen papulosquamous diseases in the HIV-infected population.The major disease entities falling into this category include psoriasis, 'parapsoriasis', pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica (PLC), lymphomatoid papulosis, pityriasis rosea (PR), pityriasis rubra pilaris (PRP), pityriasis alba (PA), lichen planus (LP), lichen striatus (LS), lichen nitidus (LN), and seborrheic dermatitis (SD). Some clinicians also include xerosis, acquired icthyosis, and asteatotic dermatitis, especially in human immunodeficiency virus (HIV)-positive patients. Many of the aforementioned conditions, in addition to being more prevalent, may display a fulminant or unusual clinical presentation in the setting of HIV infection. This is an important point to remember as it may serve as an important clue to the diagnosis of HIV infection where it might not otherwise be suspected. This is especially true of older individuals in whom HIV infection is less often considered and thus may be diagnosed at advanced stages. As most of these conditions develop unusual characteristics when T cell counts fall below 150 × 106/l, they may guide prognosis and their severity often mirrors immunologic collapse. The fact that these conditions change with the immune status of the host suggests an important role of the immune system in their pathogenesis. ### **PSORIASIS** #### **D EFINITION/OVERVIEW** Psoriasis is a chronic relapsing-remitting cutaneous disease that affects approximately 1–3% of the world's population. Along with SD and xerosis generalisata, it is by far one of the most commonly seen papulosquamous diseases in the HIV-infected population. Although its cause remains unknown, it is clear that both genetic and environmental factors play a role in pathogenesis.The characteristic sharply demarcated erythematous plaques with silver scale on the extensor surfaces tend to follow a bimodal distribution in terms of age of onset, but can appear at any age.Similarly, this disease, though it affects men and women equally, displays a wide range of severity.

C. In the condition called toxic multinodular goiter, the thyroid gland enlarges in response to some bodily need such as puberty, pregnancy, iodine deficiency, and immunologic, viral, and genetic disorders.The resulting increase in the level of circulating thyroid hormone is responsible for the thyrotoxic symptoms.C. Elderly: Toxic multinodular goiter (Plummer disease) occurs in 15% to 20% of patients with thyrotoxicosis. D. Symptomatology incidence 1. Ophthalmopathy is more common in smokers. 2. Atrial fibrillation 10% to 25% incidence and is more common in the elderly. 3. Autoimmune thyroid diseases have a peak incidence in people aged 20 to 40 years. Pathogenesis A. Hyperthyroidism is one form of thyrotoxicosis in which an excess of hormone is excreted by the thyroid gland. The diseases that can cause hyperthyroidism include Graves' disease, toxic multinodular goiter, thyroid cancer, and increased secretion of the TSH. Thyrotoxicosis not related to hyperthyroidism may be subacute thyroiditis, ectopic thyroid tissue, and ingestion of excessive thyroid hormone. Postpartum thyroiditis can precipitate a short-term mild hyperthyroidism, which has an onset at 2 to 6 months postpartum. Severe thyrotoxicosis of any cause is called thyrotoxic crisis or storm. B. In Graves' disease, the normal feedback mechanisms that regulate hormone secretion are taken over by some abnormal thyroid-stimulating mechanism. Thyroid autoantibodies of the immunoglobulin G (IgG) class are present in more than 95% of patients with Graves' disease. The hyperfunctioning of the thyroid gland causes suppression of TSH and thyrotropin-releasing hormone (TRH). There are profound increases in iodine uptake and thyroid gland metabolism, which are believed to be the causes of the gland enlargement. The resulting increase in the level of circulating thyroid hormone is responsible for the thyrotoxic symptoms. C. In the condition called toxic multinodular goiter, the thyroid gland enlarges in response to some bodily need such as puberty, pregnancy, iodine deficiency, and immunologic, viral, and genetic disorders.Predisposing Factors A. Graves' disease 1.Women in the second through fifth decades of life 2.Familial autoimmune thyroid disease 3.Concomitant disorders believed to be autoimmune 4.Increased in Trisomy 21 5.Higher incidence in smokers B.Toxic multinodular goiter 1.Advanced age 2.Recent exposure to iodine-containing medications (amiodarone and/or radio-contrast dye) 3.

This "optimized SPA" maximized penetration rates through a standardized incubation protocol for spermatozoa (4°C for 42 h in test-yolk buffer followed by a rapid warming protocol); as a result, false negative results were decreased, thereby improving sensitivity.26.4) [45, 46].With an effort to improving this test, modifications were made to the routine SPA protocol in our laboratory (see Fig.If further evolution of this line of testing allows for better selection of mature sperm for ICSI, thereby improving ICSI success rates, this would also represent a significant advance over our current practice. ## 26.6 Sperm Penetration Assay (or Zona-Free Hamster Oocyte Penetration Assay) Based upon the observation that human sperm will successfully penetrate zona-free hamster oocytes in vitro, first noted by Yanagamachi et al. in 1976 [41], the sperm penetration assay (SPA), is a test of the ability of spermatozoa to (a) undergo capacitation, (b) fuse with the egg membrane, and (c) disperse sperm DNA content thereby resulting in the formation of the male pronucleus. This complicated test of sperm function was developed in the late 1970s and corresponded with the initial development and utilization of IVF. Practitioners correctly hypothesized that SPA testing might offer useful predictive information regarding IVF success. Numerous series did correlate normal SPA results with IVF success, with an acceptable number of false-positive results [42, 43]. However, a disproportionate number of false negatives were observed, implying that sperm that failed the SPA were actually able to fertilize oocytes with an acceptable success rate in vitro. Ultimately, this difference was attributed to variability in the rate at which spermatozoa undergo capacitation [44]. With an effort to improving this test, modifications were made to the routine SPA protocol in our laboratory (see Fig. 26.4) [45, 46]. This "optimized SPA" maximized penetration rates through a standardized incubation protocol for spermatozoa (4°C for 42 h in test-yolk buffer followed by a rapid warming protocol); as a result, false negative results were decreased, thereby improving sensitivity.Fig.26.4 Hamster ovum sperm penetration assay; phase contrast microscopy, 40×.Lighter regions on surface of ovum are decondensed sperm.

##### Anti-motility Drugs and NSAIDs Cimolai et al.Although there are no separate studies about the effect of morphine in STEC colitis, antimotility drugs in general have been associated with adverse outcome (see below).The risk of fluid overload and cardiopulmonary complications due to saline infusion is minimal, provided the patient is hospitalized and supervised diligently by an experienced team [403]. Hospital admission does not only simplify patient monitoring, it may also alleviate parental anxiety and reduce the spreading of the potentially dangerous organisms from the family and community (see above) [349, 350]. Fig. 26.8 Initial evaluation of STEC infection. (a) Risk of Stx HUS: Age group (>6 months) and diarrhea <4 to 7 days that is frequent, turned bloody after 2–3 days, associated with abdominal cramps, or recent HC/HUS in family of community. (b) Culture stool for (at least): E. coli O157 (SMAC), Campylobacter, Salmonella, Shigella, Yersinia spp. Stx assay and PCR (for Stx sequences) if available (Used with permission of AGA Institute from Holtz et al. [372]) ##### Analgesia Abdominal, typically cramping pain can be severe. Where volume expansion with isotonic saline fails to alleviate the ischemic colitis pain, pharmacological therapy may be warranted. Acetaminophen can be tried, unless there is evidence of hepatopathy. Morphine, found to be effective in children with severe abdominal pain due other etiologies [483], may be administered sparingly, although it tends to worsen post-colitis constipation or ileus. Although there are no separate studies about the effect of morphine in STEC colitis, antimotility drugs in general have been associated with adverse outcome (see below). ##### Anti-motility Drugs and NSAIDs Cimolai et al.A subsequent study of 118 children with STEC colitis (28 with HUS) from the same center revealed that the prolonged use of antidiarrheal agents was associated with development of HUS (multivariate analysis; relative risk 44.1; CI95 % 8.5–229.4) [484].

planned parenthood, a philosophical framework central to the development of contraceptive methods, contraceptive counseling, and family planning programs and clinics.The program can be implemented by collaborative, coercive, or emulative means.Also called [**plane xanthoma,** **xanthoma planum**. See also **xanthelasmatosis**. Planck's constant (h) /plangks/ Max Planck, German physicist, 1858–1947], a fundamental physical constant that relates the energy of radiation to its frequency. It is expressed as 6.63 × 10−27 erg-seconds or 6.63 × 10−34 joule-seconds. See also [**photon**. plane [L, _planum,_ level], **1. ** _n,_ a flat surface determined by three points in space. **2. ** _n,_ an extension of a longitudinal section through an axis, such as the coronal, horizontal, transverse, frontal, and sagittal planes, used to identify the position of various parts of the body in the study of anatomy. **3. ** _v,_ the act of paring or of rubbing away. **4. ** _n,_ a superficial incision in the wall of a cavity or between tissue layers, especially in plastic surgery. **—planar,** _adj._ plane xanthoma. See **planar xanthoma**. -plania, suffix meaning the "deviation from its normal location": _choloplania, pyoplania, spiloplania._ planigraphic principle /plan′igraf′ik/, a rule of tomography in which the fulcrum or axis of rotation is raised or lowered to alter the level of the focal plane but the tabletop height remains constant. plankton /plangk′t n/ [Gk, _planktos,_ wandering], nearly microscopic floating or weakly swimming organisms (both photosynthetic and nonphotosynthetic) found in lakes and oceans that provide the initial level in the food chain for aquatic animals. planned change, an alteration of the status quo by means of a carefully formulated program that follows four steps: unfreezing the present level, establishing a change relationship, moving to a new level, and freezing at the new level. The program can be implemented by collaborative, coercive, or emulative means. planned parenthood, a philosophical framework central to the development of contraceptive methods, contraceptive counseling, and family planning programs and clinics.See also **contraception**.planning L, _planum_ ], (in five-step nursing process) a category of nursing behavior in which a strategy is designed to achieve the goals of care for an individual patient, as established in assessing and analyzing.Planning includes developing and modifying a care plan for the patient, collaborating with other personnel, and recording relevant information.

Fatigue and stress are common causes of lack of interest in sex.The problem can involve both a lack of desire for one's partner and the inability to become sexually aroused during sexual activity.## **Lack of Interest in Sex** A lack of interest in sex is the second most common sexual problem (after erection problems) and affects both men and women.In women, causes of frictional pain at the vaginal opening include inadequate vaginal lubrication, a vaginal or bladder infection, a sexually transmitted disease (STD) such as genital herpes (see page 482), or soreness after childbirth. Deep pelvic pain can result from conditions such as endometriosis (see page 870), a disorder of the ovaries, or allergic reactions. Chronic pain in the lower back also can cause deep pelvic pain during intercourse. Common causes of painful intercourse in men include a tight foreskin, an STD, infection of the prostate gland or bladder, an anatomical abnormality of the penis, or inflammation. Cancer of the penis or testicles and musculoskeletal conditions such as arthritis in the lower back also make thrusting uncomfortable. Some spermicides (see page 471) can cause a burning sensation in both men and women. ### _**Symptoms, Diagnosis, and Treatment**_ In women, symptoms of dyspareunia include pain or discomfort in the external part of the genitals or deep inside the pelvic area. Men usually experience pain in the penis. Your doctor will be able to find the cause of your discomfort by performing a physical examination of your reproductive organs and ordering tests to detect an infection or an underlying medical condition. Treatment of dyspareunia depends on the underlying cause. ## **Lack of Interest in Sex** A lack of interest in sex is the second most common sexual problem (after erection problems) and affects both men and women. The problem can involve both a lack of desire for one's partner and the inability to become sexually aroused during sexual activity. Fatigue and stress are common causes of lack of interest in sex.Disinterest in sex sometimes masks another sexual problem, such as premature ejaculation (see previous page) or a woman's inability to have an orgasm (see previous page).After the birth of a baby, some women feel a lack of desire for sex.

Medications and CBT are not a replacement for an unhealthy lifestyle.In children, CBT is considered the first-line treatment of conventional care for anxiety.BIOCHEMICAL THERAPIES: MEDICATIONS, DIETARY SUPPLEMENTS, AND HERBS Medications In adults, the combination of medications with CBT is more powerful in relieving anxiety than using either therapy alone, though medications alone can help.The combination of cognitive behavioral therapy (CBT) plus medications is more potent than either therapy alone. However, therapy's powerful benefits can last for many months; because it has fewer side effects and benefits last longer, psychotherapy can be a more cost-effective treatment for anxiety than medications, particularly for children. Another proven therapy for anxiety, particularly PTSD, is called Eye Movement Desensitization and Reprocessing (EMDR). Although most studies of EMDR have been done in adults, new studies show significant benefits for children, too. EMDR requires professional training and guidance. Look for someone with extensive pediatric experience and solid credentials. Insurance often covers professional counseling or psychotherapy services. Check with your insurance carrier to make sure what is covered, what percentage of the visit is paid, and how many sessions are covered under your policy. Also be aware that support groups, peer support, workshops, computerized on-line counseling, and Internet-based services are cost-effective ways to help overcome anxiety. A variety of effective approaches are available to meet individual needs for coaching and counseling. BIOCHEMICAL THERAPIES: MEDICATIONS, DIETARY SUPPLEMENTS, AND HERBS Medications In adults, the combination of medications with CBT is more powerful in relieving anxiety than using either therapy alone, though medications alone can help. In children, CBT is considered the first-line treatment of conventional care for anxiety. Medications and CBT are not a replacement for an unhealthy lifestyle.Medications work only as long as the drugs are taken daily.Side effects limit their desirability for long-term use.For example, prenatal use of SSRI medications may lead to irritability, feeding difficulties, and breathing problems in newborns.

In 2006 Dan Chen had accepted a position at Genentech, whose steel-and-glass laboratories fronted the San Francisco Bay.And anyway, he knew Dan was especially busy now, with three kids, a busy oncology practice, and a new job in biotech."Don't want to tempt fate this time!""This marks my 2-year NED anniversary again," Brad noted, but he didn't think they should have a celebration."Brad had just a crazy response to it," Chen remembers. What the anti-CTLA-4 drug unleashed in Brad's immune system was something more like a riot than a precise military operation. Brad got his first injection of the experimental MDX-010 antibody on October 5. Within a week he had an extensive rash on his neck, arms, and face, and a huge welt on his thigh near the injection sites. And every day it got worse. "Brad was really, really sick," Dan says. "He couldn't eat for over a month and ultimately had to get slammed with some of the strongest drugs we have to shut off the immune response." Brad checked into the hospital under Dr. Weber's care the day after Christmas. He had already lost forty-five pounds and endured weeks of misery. The experience of having his own immune system attack his guts was, Brad later said, the most brutal thing he had ever been through. An examination would show that the extreme immune response had decimated his GI tract. Had it been enough to completely wipe out Brad's cancer, too? Only time would tell. Slowly, Brad bounced back from the anti-CTLA-4 trials. He was clear of cancer for 2007, gaining weight back, feeling his old self again into the new year. The family Christmas letter was hopeful, if cautious, and the following August he wrote to tell his friend that the PET/CT scans and brain MRI were all still clear. "This marks my 2-year NED anniversary again," Brad noted, but he didn't think they should have a celebration. "Don't want to tempt fate this time!" And anyway, he knew Dan was especially busy now, with three kids, a busy oncology practice, and a new job in biotech. In 2006 Dan Chen had accepted a position at Genentech, whose steel-and-glass laboratories fronted the San Francisco Bay.This was a place filled with academics, but it wasn't academia.It was a powerhouse of resources for new drug development.Taking care of patients was still hugely important to Chen, and he'd kept his clinical position at the Stanford cancer center.And Brad was still one of his patients, or really a former patient turned friend, a guy who could remain free of cancer.

River/Rec.(1) Erythronium americanum; (2) ADDER'S TONGUE, AMERICAN TROUT-LILY, DOG-TOOTH VIOLET, ERYTHRONIUM, LAMB'S TONGUE, RATTLESNAKE VIOLET, SNAKE LEAF, SNAKE'S TONGUE, YELLOW ERYTHRONIUM, YELLOW SNAKELEAF, YELLOW SNOWDROP; (3) liliaceae; (4) Eastern U.S., U.S., Acadia National Park, Big S. Fork Natl.mesochoreum; (3) liliaceae; (4) Wilson's Creek National Battlefield 10528.(1) Erythrina variegata; (2) CORAL TREE, NGATAE, TIGER'S-CLAW; (3) fabaceae, leguminosae; (4) Dominican Republic, Eastern Polynesia, Haiti, Haleakala National Park, India, Java, Malaya, Moluccas, Nature Preserve of American Samoa, Niue, Philippines, Samoa, Solomon Islands, Tonga, Zanzibar (5) anodyne, astringent, depressant, diuretic, emmenagogue, lactogogue, venereal, vermifuge; (6) abscesses, asthma, bilious, bobo, cancer, common cold, convulsions, cough, dysentery, earache, female ailments, fever, hematemesis, menorrhagia, paralysis, pimples, snake bite, stomach ache, toothache; (8) Santal, Tongan; (9) medicine; (10) eye 10522. (1) Erythrina variegata var. orientalis; (2) TIGER'S-CLAW; (3) fabaceae; (4) Haleakala National Park 10523. (1) Erythrina vespertilio; (2) BAT'S WING CORAL TREE; (4) Australia 10524. (1) Erythrocoma triflora; (3) rosaceae; (4) Black Canyon Of The Gunnison, Rocky Mountain National Park 10525. (1) Erythrodes querceticola; (3) orchidaceae; (4) Everglades National Park 10526. (1) Erythronium albidum; (2) SMALL WHITE FAWN-LILY; (3) liliaceae; (4) Cuyahoga Valley National Recreation Area, Effigy Mounds National Monument, Friendship Hill National Historic Site, Hot Springs National Park, Indiana Dunes National Lakeshore, Lincoln Boyhood National Memorial, Mammoth Cave National Park, Saint Croix National Scenic River 10527. (1) Erythronium albidum var. mesochoreum; (3) liliaceae; (4) Wilson's Creek National Battlefield 10528. (1) Erythronium americanum; (2) ADDER'S TONGUE, AMERICAN TROUT-LILY, DOG-TOOTH VIOLET, ERYTHRONIUM, LAMB'S TONGUE, RATTLESNAKE VIOLET, SNAKE LEAF, SNAKE'S TONGUE, YELLOW ERYTHRONIUM, YELLOW SNAKELEAF, YELLOW SNOWDROP; (3) liliaceae; (4) Eastern U.S., U.S., Acadia National Park, Big S. Fork Natl. River/Rec.

Agonists for a different nicotinic receptor, the α4β2-nicotinic receptor, are discussed in Chapter 14 on substance abuse, and are being tested as well for potential precognitive actions (e.g., varenicline, ABT560, also an α4β2 agonist).Enhancing prefrontal cortex histamine actions by blocking its presynaptic H3 autoreceptor is discussed in Chapter 11 and illustrated in Figure 11-11. Several H3 antagonists are in testing to boost cognitive function in ADHD. Boosting acetylcholine function in prefrontal cortex is another pro-cognitive approach. Muscarinic agonists tend to be poorly tolerated, but there are several emerging approaches to stimulating nicotinic cholinergic receptors. Several α7-nicotinic receptor agonists are being tested (e.g., EVP-6124, TC5619, DMXB-A/GTS21, MEM3454, R4996/MEM63908, AZD0328, ABT560, JN403, RG3487), some with promising early clinical results in ADHD. Ongoing investigations are dealing with the possible development of tolerance to full agonists without allosteric actions, insufficient efficacy in partial agonists, and how to treat smokers who are already stimulating their nicotinic receptors. One multifunctional agent is RG3487, which is both an α7-nicotinic partial agonist and a 5HT3 antagonist, the latter mechanism discussed in Chapter 7 and illustrated in Figure 7-46 as a mechanism to raise acetylcholine levels in the cortex. Vortioxetine, a novel multifunctional antidepressant with 5HT3 antagonist, SERT inhibition, and multiple other pharmacologic actions, discussed in Chapter 7 and illustrated in Figure 7-89, also raises acetylcholine levels in experimental models and has theoretical appeal as a pro-cognitive agent not only in depression but also in other disorders such as ADHD. Agonists for a different nicotinic receptor, the α4β2-nicotinic receptor, are discussed in Chapter 14 on substance abuse, and are being tested as well for potential precognitive actions (e.g., varenicline, ABT560, also an α4β2 agonist).### Summary Attention deficit hyperactivity disorder (ADHD) has core symptoms of inattentiveness, impulsivity, and hyperactivity, linked theoretically to specific malfunctioning neuronal circuits in prefrontal cortex.

However, after 50 years old and, at any age after several years of dialysis, a precise evaluation of arterial status is critical.If the Doppler examination appears abnormal, contrast-enhanced imaging should be performed; the choice between computed tomography angiography (CTA) and magnetic resonance angiography (MRA) depends on residual renal function.## 30.2 Presurgical Evaluations ### 30.2.1 Evaluation of the Graft Recipient The pretransplantation work-up is aimed at determining whether the patient's general condition can tolerate the surgical intervention and whether local conditions permit graft implantation, and the latter orients the choice of the technique to be used. The local status of the lower urinary tract and blood vessels to be attached to the graft is evaluated essentially through imaging explorations. #### 30.2.1.1 The Lower Urinary Tract Retrograde cystography is mandatory to assess bladder morphology and function. The bladder capacity must be assessed because it is often decreased, depending on the degree of urine output before transplantation. Bladder diverticulum and vesicoureteral reflux must be excluded because they could facilitate urinary infection during the posttransplantation period. Such abnormalities should be treated during or before the transplantation. Finally, bladder-output function and urethral morphology during voiding can be examined during cystouretrography. #### 30.2.1.2 Status of the Vasculature For young recipients (<50 years old) who have not been on dialysis for a prolonged period and thus have a low probability of developing arterial lesions, Doppler examination of the lower limbs suffices. If the Doppler examination appears abnormal, contrast-enhanced imaging should be performed; the choice between computed tomography angiography (CTA) and magnetic resonance angiography (MRA) depends on residual renal function. However, after 50 years old and, at any age after several years of dialysis, a precise evaluation of arterial status is critical.The site, the severity, and the degree of extension of these calcifications, and the presence of arterial stenoses directly influence the choice of the implantation site.Today, the best technique to determine arterial wall status is nonenhanced multidetector-row CT (MDCT) with axial sections and coronal reformations.

In many cases, flap coverage is unnecessary as primary closure over the tibial component is possible (13).Never close the wound with the tissues in tension.2.Be mindful to handle the soft tissue flaps with care to avoid necrosis.Patellar tendon reattachment and soft tissue coverage are the major challenges inherent to proximal tibial segmental replacement total knees. In terms of patellar tendon reattachment, no clear solution exists at present. Several designs are available, most of which utilize a sintered surface on the anterior aspect of the tibial component to facilitate soft tissue ingrowth (Fig. 13). This process aids in scar formation and adhesion of the patellar tendon to the surface of the prosthesis. Usually, this is performed in association with drilling holes in the tibial component to allow insertion of large sutures to help stabilize the patellar tendon repair during healing. Protection of this repair is achieved by keeping the knee in extension in a knee immobilizer or cylinder cast for 5–6 weeks following surgery. Most patients treated in this manner regain greater than 90° of flexion with the help of gentle physical therapy. Many patients will eventually develop an extensor lag, though this is usually less than 20° and may be absent altogether. Rarely does this lag cause knee instability, but if it does a drop lock brace can be used to maintain the knee in extension during ambulation. Fig. 13 Proximal tibial segmental prosthesis demonstrating frayed anterior surface to facilitate soft tissue ingrowth In terms of soft tissue coverage for the proximal tibia, there are two important rules: 1. Be mindful to handle the soft tissue flaps with care to avoid necrosis. 2. Never close the wound with the tissues in tension. In many cases, flap coverage is unnecessary as primary closure over the tibial component is possible (13).The other factor that facilitates ease of closure is the use of a downsized tibial component.Some manufacturers include regular and small versions of the rotating hinge tibial component in their sets.This may make closure much simpler and help avoid the need for flap coverage.Finally, appropriate jigs will facilitate proper prosthetic insertion, especially in the hands of the occasional user.

The term circulating RNA refers primarily to microRNA (miRNA) which either travels as small fragments bound to proteins or encapsulated in exosomes [114, 115].## 12.4 Circulating RNA and Exosomes ### 12.4.1 Biology of Exosomes and Circulating RNA Besides the two major topics in liquid biopsies, CTCs and ctDNA, circulating RNA is a small but promising field for clinical applications.In later stages, the analysis of ctDNA allows for a comprehensive therapy monitoring, which allows the physicians to respond as quickly as possible to changes in the tumor. Thus, treatments can be adjusted rapidly, and patients can be spared from expensive treatments with very toxic drugs and side effects from the moment the drug is no longer effective. Moreover, novel therapeutic targets that occur in the course of the disease can be identified and offer new treatment options. ctDNA also provides a unique opportunity to learn more about metastasis processes and the related signaling pathways. Furthermore, ctDNA levels can be used as prognostic markers in order to evaluate whether a patient needs adjuvant treatment after curative surgery in order to eliminate residual cancer cells. Especially in earlier stages, only a subset of patients relapse and therefore profit from adjuvant therapy after a curative resection of the tumor. ctDNA analyses could spare some patients a burdensome and costly therapy. In the near future, ctDNA might also be used as a diagnostic biomarker enabling early detection of cancer. Illumina, the current market leader in the field of NGS, has just founded a 100 million dollar start-up company called GRAIL with the aim to develop a test for early detection of cancer, which would be launched in 2019. Although the detection of cancer in its earliest stage is the "the Holy Grail" in oncology, one has to consider that the detection of specific mutations in the circulation in individuals who do not yet have visible tumor can be problematic. ## 12.4 Circulating RNA and Exosomes ### 12.4.1 Biology of Exosomes and Circulating RNA Besides the two major topics in liquid biopsies, CTCs and ctDNA, circulating RNA is a small but promising field for clinical applications. The term circulating RNA refers primarily to microRNA (miRNA) which either travels as small fragments bound to proteins or encapsulated in exosomes [114, 115].Longer stretches of RNA transcripts outside of cells are considered to derive from dying cells and having no functional role.Furthermore, RNA molecules can originate from viruses and therefore can pose a serious threat to the whole organism.Therefore, it is not surprising that RNase activity is high in serum, as it was shown that >99% of mRNA added to serum is degraded within 15 s [116].

The effect of the rapid entry of chylomicrons into the blood stream after the second meal on the postprandial lipemia occurring as a result of the first meal is very important in view of the potentially adverse effects associated with elevated concentrations of chylomicrons and their remnants in the circulation for most of the day including atherogenesis.52 ### 4.2 Postprandial Glycemia and Insulinemia Postprandial glycemic excursion may be defined as the increase in glycemia immediately following a meal, particularly those meals that contain starchy foods (white bread, pasta, potatoes, etc.). This rise in glycemia occurs 10 to 20 minutes following the beginning of ingestion, increases between 30 minutes and 1 hour post-meal, and returns to basal values from 2 to 5 hours. A numerical index, named the glycemic index (GI), is given to a carbohydrate-rich food based on the average of the increase in blood glucose levels occurring after the food is eaten. The GI may be defined as the incremental area under the blood glucose response curve of a 50 g carbohydrate portion of a test food expressed as a percentage of the response to the same amount of carbohydrate from a standard food taken by the same subject.53 In a fasting condition, the plasma glucose concentration in healthy adults is relatively stable, which indicates that rates of glucose production and utilization are finely regulated, ranging between 1.8 and 2.6 mg/kg/min.54 After a meal, glucose absorption results in rates of exogenous glucose delivery into the circulation that can be more than twice the rate of post-absorptive endogenous glucose production, depending on the carbohydrate content of the meal and the rate and degree of glucose absorption.In fasting conditions, the hormone insulin regulates the plasma glucose concentration by restraining hepatic glucose production; after meals, higher concentrations of insulin are required to stimulate glucose utilization.56 It has been shown that the amount and/or nature of carbohydrates in a meal may alter postprandial lipid metabolism.

The preferred method involves serial cephalometric radiograph at 6-month intervals to assess the relative movement of the mid face or mandible relative to the cranial base.However, surgical objectives include the following: (1) functional reconstruction of the macrostomia; (2) reconstruction of the eyelid soft tissue to prevent globe exposure; (3) separation of the confluent oral, nasal, and orbital cavities; and (4) aesthetic correction of the deformity.26 Attention should be directed first to soft tissue closure and cranial defect correction during the first year of life.49 The scar within the cleft should be excised up to normal tissue followed by layered closure of the soft tissue. Emergent procedure in the neonatal period should be reserved for functional problems such as globe exposure to prevent corneal ulceration. The facial and cranial skeleton frequently requires reconstruction and grafting, which is best performed once the child is older, approximately 6-9 years of age.49 Correction of maxillomandibular anomalies with orthognathic surgery should be initiated once skeletal maturity has been achieved; approximately 15 years of age in female and 17 years of age in male.58 Cessation of growth of the cranio-facial structures can be correlated with axial skeletal growth, by either hand films to determine epiphyseal plate closure or serial cephalometric analysis. The preferred method involves serial cephalometric radiograph at 6-month intervals to assess the relative movement of the mid face or mandible relative to the cranial base.

* * * Wren's story might be different from yours—but most of us can relate to the constant pressures we're under to work more, be more, do more—and the price we're paying for our chronic overwhelm—exhaustion, brain fog, food cravings, frequent illness, stress and anxiety, poor sleep, the hormonal roller coaster, and more.* * * **HPA Axis Quick Review** The HPA axis is the stress response system that starts in your brain, extends to your adrenal glands, and impacts pretty much every system and function in your body. When it's stuck in the ON position, you're wired, overstimulated, irritable, and living as if you're constantly on red alert—your blood sugar, blood pressure, and digestive, nervous, hormonal, and immune systems respond accordingly, and you end up with all of the problems associated with SOS-O. When your brain dials down the reaction to protect you from chronic overload, and with it, dials back your cortisol and adrenaline production, you end up in SOS-E, feeling exhausted, sometimes deeply, and your reactions are low—in everything from your metabolism, mood, and immunity to your mind, blood pressure, and hormones. Your thyroid function gets dialed down, too, so that you save energy, but hypothyroidism leaves you feeling sick and tired. * * * Wren's story might be different from yours—but most of us can relate to the constant pressures we're under to work more, be more, do more—and the price we're paying for our chronic overwhelm—exhaustion, brain fog, food cravings, frequent illness, stress and anxiety, poor sleep, the hormonal roller coaster, and more.Also important to remember is that there are many kinds of overwhelm that can cause SOS—life stress is just one of these.Anything that overwhelms any of your body's systems—your digestive system, your detoxification system, or your immune system, can throw you into SOS.