Manuel B. Graeber, MD (Neurology)

• Professor of Neuropathology
• Division of Neuropathology
• Department of Pathology and Clinical Laboratory Medicine
• Neurosciences Center
• King Fahd Medical City
• Riyadh, Saudi Arabia
• The Brain and Mind Research Institute
• University of Sydney
• Sydney, Australia

If drowsiness or dizziness occurs symptoms of pneumonia buy coversyl 8mg without prescription, avoid driving and performing tasks that require alertness chi infra treatment discount 4 mg coversyl amex. During therapy with this drug medicine used to treat chlamydia generic coversyl 8 mg on-line, avoid alcoholic beverages and do not take any nonprescription drug unless its use has been approved by the primary health care provider medicine pills order coversyl 8mg overnight delivery. Notify the primary health care provider immediately if symptoms do not improve after 3 or 4 days symptoms 0f ms cheap coversyl 8mg free shipping. Continue therapy for at least 1 week or for 3 days after the urine shows no signs of infection symptoms yellow fever generic 4mg coversyl otc. Notify the primary health care provider immediately if any of the following occur: fever, chills, cough, shortness of breath, chest pain, or difficulty breathing. What instruction would be most important to give a failed to see his primary health care provider for a follow-up urine sample 2 weeks after completing his course of drug therapy. Analyze the situation to determine what points you would stress in a teaching plan for this patient. Discuss specific nursing tasks to include in a nursing care plan for this patient. Drink one to two glasses of cranberry juice daily to promote healing of the urinary tract. This drug comes in a one-dose packet that must be dissolved in 90 mL or more of fluids. What statement(s) would be included in a teaching plan for a patient prescribed phenazopyridine (Pyridium)? Take precautions when out in the sun by wearing sunscreen, a hat, and long-sleeved shirts for protection. This is a normal occurrence that will disappear when use of the drug is discontinued. Discuss the uses, general drug actions, general adverse reactions, contraindications, precautions, and interactions associated with gastrointestinal drugs. Discuss important preadministration and ongoing assessment activities the nurse should perform on the patient taking a gastrointestinal drug. List some nursing diagnoses particular to a patient taking a gastrointestinal drug. Discuss ways to promote an optimal response to therapy, how to manage common adverse reactions, and important points to keep in mind when educating patients about the use of gastrointestinal drugs. Some of the more common preparations are listed in the Summary Drug Table: Drugs Used in the Management of Gastrointestinal Disorders. Antacids (against acids) are drugs that neutralize or reduce the acidity of stomach and duodenal contents by combining with hydrochloric acid and producing salt and water. Examples of antacids include aluminum hydroxide gel (Amphojel), magaldrate (Riopan), and magnesia or magnesium hydroxide (Milk of Magnesia). An additional use for aluminum carbonate is in the treatment of hyperphosphatemia or for use with a low phosphate diet to prevent formation of phosphate urinary stones. Calcium carbonate may be used in treating calcium deficiency states such as menopausal osteoporosis. Magnesium oxide may be used in the treatment of magnesium deficiencies or magnesium depletion from malnutrition, restricted diet, or alcoholism. Some of the less common but more serious adverse reactions include: · Aluminum-containing antacids-constipation, intestinal impaction, anorexia, weakness, tremors, and bone pain · Magnesium-containing antacids-severe diarrhea, dehydration, and hypermagnesemia (nausea, vomiting, hypotension, decreased respirations) · Calcium-containing antacids-rebound hyperacidity, metabolic alkalosis, hypercalcemia, vomiting, confusion, headache, renal calculi, and neurologic impairment · Sodium bicarbonate-systemic alkalosis and rebound hypersecretion Although the antacids have the potential for serious adverse reactions, they have a wide margin of safety, especially when used as prescribed. Calcium-containing antacids are contraindicated in patients with renal calculi or hypercalcemia. Aluminum-containing antacids are used cautiously in patients with gastric outlet obstruction. Magnesium- and aluminum-containing antacids are used cautiously in patients with decreased kidney function. The calciumcontaining antacids are used cautiously in patients with respiratory insufficiency, renal impairment, or cardiac disease. Antacids are classified as Pregnancy Category C drugs and should be used with caution during pregnancy. Sodium-containing antacids are contraindicated in in absorption of weakly acidic drugs and results in a decreased drug effect (eg, digoxin, phenytoin, chlorpromazine, and isoniazid) 2. Absorbing or binding drugs to their surface, resulting in decreased bioavailability (eg, tetracycline) 3. Affecting the rate of drug elimination by increasing urinary pH (eg, the excretion of salicylates is increased, whereas excretion of quinidine and amphetamines is decreased) the following drugs have a decreased pharmacologic effect when administered with an antacid: corticosteroids, digoxin, chlorpromazine, oral iron products, isoniazid, phenothiazines, ranitidine, phenytoin, valproic acid, and the tetracyclines. Dexpanthenol administration may cause itching, difficulty breathing, and urticaria. These drugs have been largely replaced by histamine H2 antagonists, which appear to be more effective and have fewer adverse drug reactions. These drugs are used cautiously in patients with diabetes and cardiovascular disease. Metoclopramide is a Pregnancy Category B drug; dexpanthenol is a Pregnancy Category C drug. The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa. Contraindications, precautions, and interactions of the anticholinergic drugs are discussed in Chapter 25. These drugs inhibit the action of histamine at histamine H2 receptor cells of the stomach, which then reduces the secretion of gastric acid and reduces total pepsin output. Examples of histamine H2 antagonists include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid Pulvules), ranitidine (Zantac). These drugs are used cautiously in patients with renal or hepatic impairment and in the severely ill or debilitated patient. The histamine H2 antagonists are used cautiously in the older adult (causes confusion). Histamine antagonists are Pregnancy Category B (cimetidine, famotidine, and ranitidine) drugs and C (nizatidine) drugs and should be used with caution during pregnancy and lactation. The following discussion does not cover all drugs that may interact with the H2 antagonists but represents some of the more common interactions. Antacids and metoclopramide may decrease absorption of the H2 antagonists if administered concurrently. There may be a decrease in white blood cell count when the H2 antagonists are administered with the alkylating drugs or the antimetabolites. There is an increased risk of toxicity of oral anticoagulants, phenytoin, quinidine, lidocaine, or theophylline when administered with H2 antagonists. Concurrent use of cimetidine and morphine increases the risk of respiratory depression. Diphenoxylate use may result in anorexia, nausea, vomiting, constipation, rash, dizziness, drowsiness, sedation, euphoria, and headache. This drug is a narcotic-related drug that has no analgesic activity but has sedative and euphoric effects and drug dependence potential. To discourage abuse, it is combined with atropine (an anticholinergic or cholinergic blocking drug), which causes dry mouth and other mild adverse effects. Loperamide is not a narcotic-related drug, and minimal adverse reactions are associated with its use. Occasionally, abdominal discomfort, pain, and distention have been seen, but these symptoms also occur with severe diarrhea and are difficult to distinguish from an adverse drug reaction. The antidiarrheal drugs are used cautiously in patients with severe hepatic impairment or inflammatory bowel disease. Antidiarrheals are classified as Pregnancy Category B drugs and should be used cautiously during pregnancy and lactation. There are additive cholinergic effects when administered with other drugs having anticholinergic activity, such as antidepressants or antihistamines. Concurrent use of the antidiarrheals with a monoamine oxidase inhibitor increases the risk of a hypertensive crisis. Examples of these drugs include difenoxin with atropine (Motofen), diphenoxylate with atropine (Lomotil), and loperamide (Imodium). Simethicone has a defoaming action that disperses and prevents the formation of mucus-surrounded gas pockets in the intestine. These drugs are useful as adjunctive treatment of any condition in which gas retention may be a problem (ie, postoperative gaseous distention, air swallowing, dyspepsia, peptic ulcer, irritable colon, or diverticulosis). In addition to its use for the relief of intestinal gas, charcoal may be used in the prevention of nonspecific pruritus associated with kidney dialysis treatment and as an antidote in poisoning. Simethicone is in some antacid products, such as Mylanta Liquid and Di-Gel Liquid. The digestive enzymes are used cautiously in patients with asthma (an acute asthmatic attack can occur), hyperuricemia, and during pregnancy and lactation. These drugs are Pregnancy Category C drugs, and safe use in pregnancy has not been established. Calcium carbonate or magnesium hydroxide antacids may decrease the effectiveness of the digestive enzymes. When administered concurrently with an iron preparation, the digestive enzymes decrease the absorption of oral iron preparations. The pregnancy category of simethicone is unknown; charcoal is a Pregnancy Category C drug. The enzymes pancreatin and pancrelipase, which are manufactured and secreted by the pancreas, are responsible for the breakdown of fats, starches, and proteins. Conditions or diseases that may cause a decrease in or absence of pancreatic digestive enzymes include cystic fibrosis, chronic pancreatitis, cancer of the pancreas, There are no apparent adverse reactions to ipecac. Although not an adverse reaction, a danger associated with any emetic is the aspiration of vomitus. Ipecac is a Pregnancy Category C drug, and safe use in pregnancy has not been established. The action of each laxative is somewhat different, yet they produce the same result-the relief of constipation (Display 48-1). Gallstone-solubilizing (gallstone-dissolving) drugs, such as ursodiol (Actigall), suppress the manufacture of cholesterol and cholic acid by the liver. The suppression of the manufacture of cholesterol and cholic acid may ultimately result in a decrease in the size of radiolucent gallstones. They are not effective for all types of gallstones and require many months of usage to produce results. Because of the potential toxic effects associated with long-term use, these drugs are recommended for only carefully selected and closely monitored patients. A laxative is most often prescribed for the short-term relief or prevention of constipation. Certain stimulant, emollient, and saline laxatives are used to evacuate the colon for rectal and bowel examinations. Fecal softeners or mineral oil are used prophylactically in patients who should not strain during defecation, such as after anorectal surgery or a myocardial infarction. Psyllium may be used in patients with irritable bowel syndrome and diverticular disease. Polycarbophil may be prescribed for constipation or diarrhea associated with irritable bowel syndrome and diverticulosis. Ursodiol is used cautiously during pregnancy (Pregnancy Category B) and lactation. Absorption of ursodiol is decreased if the agent is taken with bile acid sequestering drugs or aluminum-containing antacids. Clofibrate, estrogens, and q q q q Bulk-producing laxatives are not digested by the body and therefore add bulk and water to the contents of the intestines. The added bulk in the intestines stimulates peristalsis, moves the products of digestion through the intestine, and encourages evacuation of the stool. Examples of bulk-forming laxatives are psyllium (Metamucil) and polycarbophil (FiberCon). Emollient laxatives lubricate the intestinal walls and soften the stool, thereby enhancing passage of fecal material. One difference between emollient laxatives and fecal softeners is that the emollient laxatives do not promote the retention of water in the stool. Examples of fecal softeners include docusate sodium (Colace) and docusate calcium (Surfak). Hyperosmolar drugs dehydrate local tissues, which causes irritation and increased peristalsis, with consequent evacuation of the fecal mass. Irritant or stimulant laxatives increase peristalsis by direct action on the intestine. Saline laxatives attract or pull water into the intestine, thereby increasing pressure in the intestine, followed by an increase in peristalsis. When the patient has constipation as an adverse reaction to another drug, the primary care provider may prescribe a stool softener or another laxative to prevent constipation during the drug therapy. Display 48-2 lists the names of some drugs and drug classifications that may cause constipation. The following laxatives are Pregnancy Category C drugs: cascara, sagrada, docusate, glycerin, phenolphthalein, magnesium hydroxide, and senna. These drugs are used during pregnancy only when the benefits clearly outweigh the risks to the fetus. When surfactants are administered with mineral oil, surfactants may increase mineral oil absorption.

The different types of renal osteodystrophy have only modest relationships with clinical outcomes treatment wax generic coversyl 4 mg without a prescription. Mortality Abnormal bone quality and quantity can lead to increased bone fragility treatment e coli discount coversyl 8 mg amex, resulting in fracture medications joint pain coversyl 8mg low cost. Bone and mineral disorders emerged as one of the most troublesome complications; fractures occurred in 47% of the patients medicine 5325 discount coversyl 8mg with amex. Since then treatment ind 8mg coversyl visa, several studies of fracture prevalence and incidence have been reported medicine effexor cheap 8 mg coversyl free shipping, with a prevalence from 10 to 40% in general dialysis populations and in approximately half of patients older than 50 years (Supplementary Table 4). The incidence rate of hip fractures in all patients who started dialysis in the United States from 1989 to 1996 was 4. This topic represents a comprehensive review of the literature of selected topics by the Work Group with assistance from the evidence review team to formulate the rationale for clinical recommendations. Abnormal bone histology, diagnosed by bone biopsy with histomorphometry, has been the primary tool used to diagnose S33 chapter 3. Although bone biopsy is invasive and thus cannot be performed easily in all patients, it is the gold standard for the diagnosis of renal osteodystrophy. As detailed below, renal osteodystrophy is a complex disorder and biochemical assays do not adequately predict the underlying bone histology. Thus, bone biopsy should be considered in patients in whom the etiology of clinical symptoms and biochemical abnormalities is not certain. Thus, the Work Group encourages the continued training of nephrologists in the performance and interpretation of bone biopsies. Classification of renal osteodystrophy by bone biopsy Bone biopsies are performed to understand the pathophysiology and course of bone disease, to relate histological findings to clinical symptoms of pain and fracture, and to determine whether treatments are effective. The traditional types of renal osteodystrophy have been defined on the basis of turnover and mineralization as follows: mild, slight increase in turnover and normal mineralization; osteitis fibrosa, increased turnover and normal mineralization; osteomalacia, decreased turnover and abnormal mineralization; adynamic, decreased turnover and acellularity; mixed, increased turnover with abnormal mineralization. Other measurements that help to define a low or high turnover (such as eroded surfaces, number of osteoclasts, fibrosis, or woven bone) tend to be associated with the bone-formation rate as measured by tetracycline labeling. This is the most definite dynamic measurement, hence it was chosen to represent bone turnover. It should be noted that an improvement of a bone biopsy cannot be determined on the basis of a simple change in the bone-formation rate, because the restoration of normal bone may require either an increase or a decrease in bone turnover, depending on the starting point. The second parameter is mineralization, which reflects the amount of unmineralized osteoid. Mineralization is measured by the osteoid maturation time or by mineralization lag time, both of which depend heavily on the osteoid width as well as on the distance between tetracycline labels. The classic disease with an abnormality of mineraliS34 zation is osteomalacia, in which the bone-formation rate is low and the osteoid volume is high. Some patients have a modest increase in osteoid, which is a result of high boneformation rates. The overall mineralization, however, is not normal because unmineralized osteoid is increased. Patients with low bone-formation rates and a normal osteoid have adynamic disease (they do not even form the osteoid matrix, hence they do not manifest a problem with mineralization). The final parameter is bone volume, which has not traditionally been included in previous schemes for describing renal osteodystrophy. Bone volume contributes to bone fragility and is separate from the other parameters. The bone volume is the end result of changes in bone-formation and resorption rates: if the overall bone formation rate is higher than the overall bone resorption rate, the bone is in positive balance and the bone volume will increase. Differing prevalences of bone disease types observed between studies are due to differing classification methods, in addition to differences related to geographical areas, genetic background, and treatment modalities. One of the most problematic differences in classification relates to the boneformation rate. This requires tetracycline labeling, and thus normal ranges cannot be determined on autopsy or surgical series. The studies also revealed a decreased aluminum intoxication, from 40% of biopsies carried out before 1995 to 20% in patients biopsied after 1995. The natural history of bone disease evaluated through bone histomorphometry is variable. The overall trend is toward a worsening turnover (either getting too high or too low) and stable mineralization. Bone formation (turnover) is high in those with osteitis fibrosa and mild disease, and low in those with osteomalacia and adynamic bone disease. Most of these patients had been referred for some clinical reason (6505 patients), whereas the remaining patients were apparently asymptomatic (863 patients). There did not seem to be differences in the prevalence of histological types between referred and asymptomatic patients. Most of the studies of bone histomorphometry have not been designed to fully evaluate the relationship between fractures and types of renal osteodystrophy. One study of 31 dialysis patients found that those with lowturnover osteodystrophy had fracture rates of 0. There were no differences in fracture history between those with adynamic bone disease, high bone turnover, or mixed bone disease. However, we could locate no reports of prospective studies of patients with a low bone volume to determine the subsequent fracture rate. They subsequently, with an expanded cohort, reported a significant interaction between the dosage of calcium-containing phosphate binders and bone activity, such that calcium load had a significantly greater influence on aortic calcifications and stiffening in the presence of adynamic bone disease. The trabecular bone is very porous: about 20% of the tissue is bone and the rest is marrow or fat. Certain sites, however, contain higher percentages of trabecular bone (by weight). The forearm is almost all cortical bone, the vertebral body is 42% trabecular bone,121 the proximal femur is about 25% trabecular, and the total body about 80% cortical. In patients with osteoporosis, the degree of trauma and the quality of the bone also determine whether bones will fracture. The graph is a summary of studies arranged in chronological order; each point is the mean value for a study. When more than one skeletal site or gender was measured in a study, the points are connected by a vertical line. If data from men and women were reported separately, the points for women are in a lighter shade. Data from studies that reported g/cm2 were converted to Z-scores (hip and forearm) using the average age of the group of individuals and published normal reference ranges. Abnormal microarchitecture, mineralization density, crystal deposition in the bone matrix, or abnormalities in the matrix itself could all contribute to the loss of bone strength. However, bone biopsy is not practical in the majority of clinical patients, and when these serum markers are above or S39 chapter 3. Several other cross-sectional studies157,175,180,189,191,192,208 have also evaluated this relationship and, in general, were negative. However, a case-controlled cohort study did find a 31% (95% confidence interval 0. As with any diagnostic test, there is a tradeoff between the sensitivity and the specificity of the test. The predictive value depends on the sensitivity and specificity, and on the overall prevalence of the condition. The positive predictive value is the percentage of patients with a positive result on a test who actually have the disease (either high or low turnover), and the sensitivity is the percentage of patients with the disease who have a positive test result. Much of the focus of renal osteodystrophy has been on bone turnover, but bone volume is another important factor in bone physiology. Each point represents a study, and they are arranged in chronological order from 1981 to 2006 from left to right. The small symbols are studies of 20­50 patients, medium symbols 51­100 patients, and large symbols 4100 patients. The collagen molecules are then covalently bonded through pyridinoline cross-linking. These collagen-based markers have been studied in normal populations, wherein there are significant but moderate correlations with bone-formation/resorption rates. These markers, however, may be helpful in identifying those patients who respond to osteoporosis medications. Thus, at this point in time, there is insufficient evidence for the use of these markers. At present, there is no consensus with regard to the clinical utility of markers in individual patients with osteoporosis, but many ongoing studies are examining this issue, especially as anabolic drugs are being developed. On a theoretical basis, bone markers should be able to predict the change in bone volume, which is determined by bone balance. Unfortunately, none of the current serum or urine markers of bone turnover are sensitive enough to allow the calculation of bone balance, and the interpretation of the measurements depends on the clinical situation. The markers of bone formation that depend on the secretion of new collagen would not be able to detect this improved mineralization. The mechanisms of linear growth failure include the presence of chronic metabolic acidosis, renal osteodystrophy, nutrient wasting, chronic inflammation, functional hypogonadism in some adolescents, and dysregulation of the growth hormone­insulin-like growth factor 1 endocrine axis. However, using data from the North American Pediatric Renal Transplant Cooperative Study 2006 data report,252 only 6. This low usage prompted an examination of the benefit and harm of recombinant human growth hormone in children (see Chapter 4. Such abnormalities may include a height below the 3rd percentile of the growth curve for normal children of the same gender; a negative statural growth curve against the genetic potential based on midparental height formulas even when on the normal growth curve; or a negative growth velocity, based on gender-specific curves of normal children. Growth should be assessed at least monthly in infants, quarterly in children below 2 years of age, and at least annually in older children and adolescents, and plotted accurately on the appropriate growth chart for either height, velocity, or ideally, both. K the development of an international standard for the assessment of renal osteodystrophy, particularly for dynamic measurements. It is generally well recognized that the prevalence of calcification increases with progressively decreasing kidney function and is greater than that in the general population. Cardiovascular calcification is associated with, and predictive of, adverse clinical outcomes, including cardiovascular events and death. However, there are some uncertainties with regard to the sensitivity and specificity of the different imaging tests available for detecting cardiovascular calcification. Finally, there is no clear evidencebased protocol or algorithm for the diagnostic and therapeutic strategies that need to be followed after yielding a positive calcification test result. K However, there was consensus that known vascular/ valvular calcification and its magnitude identify patients at high cardiovascular risk. The most threatening localization of unwanted calcification is at vascular sites, where it may manifest as both medial and intimal calcification of arteries. In the general population, autopsy and imaging studies have identified calcification in 495% of atherosclerotic plaques. Furthermore, an advanced calcification of the heart valves may lead to dysfunction contributing to heart failure and an increased risk of endocarditis. As mentioned above, two patterns of vascular calcification have been described: predominantly intimal and predominantly medial calcification. Arterial calcification assessed by all the available imaging studies cannot accurately differentiate calcification that is localized to the intima from calcification in the media adjacent to the internal elastic lamina, or in the medial layer. Experimental and ex vivo studies suggest that the vascular smooth muscle cell may be critical in the development of calcification by transforming into an osteoblast-like phenotype. The stimulus for such a transformation may depend on the location of calcification within the artery wall. For example, in intimal lesions, atherosclerosis may be the most important stimulus. In vivo animal studies have shown less arterial calcification with non-calcium-based binders compared to that with calcium-based binders. However, in recent years, it became evident that vascular calcification is also an active cellular process. As already pointed out above, the presence or upregulation of inducers of cellular osteogenic transformation and hydroxyapatite formation (among which high phosphate probably has a central role)262 causes the differentiation of vascular smooth muscle cells into an osteoblast-like phenotype of vascular smooth muscle cells. Newly discovered calcium-regulatory factors, including fetuin-A, matrix Gla protein, osteoprotegerin, and pyrophosphates-all of which possess properties of systemic or local calcification inhibitors-may have a key role in fine-tuning protection against unwanted calcification, and some of these factors may be dysregulated in uremia. As epidemiological studies suggest a direct relationship between calcification and impaired clinical outcomes, cardiovascular calcification is thus regarded as a relevant clinical end point by most investigators mirroring cardiovascular event risk. However, it cannot yet be used as a reliable surrogate marker for interventions, as the link between intervention and S45 chapter 3. Finally, a rare but very severe form of medial calcification of small (cutaneous) arteries is calciphylaxis, also called calcific uremic arteriolopathy. It is characterized by ischemic, painful skin ulcerations followed by superinfections, and is associated with high mortality. Relationships with dysregulated calcification inhibitors (fetuin-A and matrix Gla protein) have been implicated in the pathogenesis of calciphylaxis, but because of the relatively low incidence of the disease, no conclusive data are available to firmly comment on the nature of the disease process or to allow generalizable treatment options to be recommended. This topic represents a comprehensive review of the literature of selected topics by the Work Group with assistance from the evidence review team to formulate a rationale for clinical recommendations. However, these studies were not designed to test sensitivity and specificity in this regard. The Work Group felt that the data to support (i) and (ii) were strong, the data to support (iii) were somewhat inconsistent, and the data to support (iv) were limited. These may include, but are not limited to , patients with significant hyperphosphatemia requiring a differentiated high-dose phosphate-binder therapy, patients on a transplant waiting list, and any patient in whom the caring physician decides that a knowledge of the presence of vascular calcification may impact therapeutic decision making. Prevalence Twenty-five reports including information on the baseline prevalence of vascular or valvular calcification were evaluated (Supplementary Table 10). The studies included a total of Kidney International (2009) 76 (Suppl 113), S22­S49 chapter 3. The prevalence of calcifications was variable at other vascular sites and was dependent on the sensitivity of the method used.

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A 5-year-old girl is brought to the emergency department because of fever and severe abdominal pain medications covered by medicare generic 4 mg coversyl amex. In the examination room treatment refractory best coversyl 8mg, she keeps her right hip flexed and resists active extension of the hip symptoms 8-10 dpo cheap 4mg coversyl with amex. The inflamed structure associated with these symptoms is most likely in contact with which of the following structures? A 61-year-old man comes to the physician because of a 3-month history of episodes of headache medications medicaid covers purchase 8 mg coversyl otc, heart palpitations medicine 219 purchase coversyl 8mg visa, and excessive sweating medications known to cause tinnitus 4mg coversyl sale. A 6-year-old boy has a large intra-abdominal mass in the midline just above the symphysis pubis. During an operation, a cystic mass is found attached to the umbilicus and the apex of the bladder. A 55-year-old man who has alcoholic cirrhosis is brought to the emergency department because he has been vomiting blood for 2 hours. He has a 2-month history of abdominal distention, dilated veins over the anterior abdominal wall, and internal hemorrhoids. A 3-year-old girl with mild craniofacial dysmorphosis has profound hearing deficits. Further evaluation indicates profound sensory auditory deficits and vestibular problems. Altered development of which of the following is most likely to account for these observations? A 19-year-old woman comes to the physician because of a 5-day history of increasingly severe right lower abdominal pain and bloody vaginal discharge. A 22-year-old man is brought to the emergency department because of a suprahyoid stab wound that extends from one side of the neck to the other. His tongue deviates to the right when protruded; there is no loss of sensory modality on the tongue. Resection of the tumor is scheduled, and the physician also plans to obtain samples of the draining nodes. To find these nodes, a radiotracer is injected adjacent to the tumor and images are obtained. The first draining sentinel node in this patient is most likely found at which of the following locations? This patient most likely has an abnormality of which of the following fetal structures? A 70-year-old man has a 90% blockage at the origin of the inferior mesenteric artery. Which of the following arteries is the most likely additional source of blood to the descending colon? A 30-year-old man comes to the emergency department 1 hour after injuring his left knee in a volleyball game. He says he twisted his left leg when he fell to the floor after he and a teammate accidentally collided. When the patient sits on the edge of the examination table, the left knee can be displaced anteriorly at an abnormal degree. A 70-year-old man is brought to the emergency department because of a 1-week history of increasingly severe left-sided lower abdominal pain and passing gas in his urine. A 60-year-old man has tenderness in the region distally between the tendons of the extensor pollicis longus and extensor pollicis brevis (anatomical snuffbox) after falling on the palm of his right hand. A 20-year-old man is brought to the emergency department 1 hour after he was involved in a motorcycle collision. On auscultation, a harsh continuous murmur is heard at the left of the sternum between the first two ribs. Arterial blood oxygen content is slightly higher in the right hand than in the left hand. A 50-year-old woman is brought to the emergency department because of severe upper abdominal pain for 24 hours. Physical examination shows jaundice and tenderness of the right upper quadrant of the abdomen. Serum studies show a bilirubin concentration of 5 mg/dL, alkaline phosphatase activity of 450 U/L, and lipase activity of 400 U/L (N=14­280). A 6-year-old boy is brought to the physician by his parents for a follow-up examination because of a heart murmur that has been present since birth. A grade 3/6 pansystolic murmur is heard maximally at the lower left to mid left sternal border. He undergoes cardiac catheterization and is found to have a higher than expected oxygen level in the right ventricle. A 32-year-old woman, gravida 2, para 2, develops fever and left lower abdominal pain 3 days after delivery of a full-term male newborn. During a study of bladder function, a healthy 20-year-old man drinks 1 L of water and delays urination for 30 minutes after feeling the urge to urinate. B A C C C B A E E C 23 Histology Systems General Principles of Foundational Science Biochemistry and molecular biology Biology of cells (excludes signal transduction) Apoptosis Cell cycle and cell cycle regulation Mechanisms of dysregulation Cell/tissue structure, regulation, and function Biology of tissue response to disease Pharmacodynamic and pharmacokinetic processes Immune System Blood & Lymphoreticular System Nervous System & Special Senses Skin & Subcutaneous Tissue Musculoskeletal System Cardiovascular System Respiratory System Gastrointestinal System Renal & Urinary System Pregnancy, Childbirth, & the Puerperium Female Reproductive System & Breast Male Reproductive System Endocrine System 30%­35% 1%­5% 1%­5% 5%­10% 1%­5% 1%­5% 1%­5% 1%­5% 5%­10% 5%­10% 1%­5% 1%­5% 1%­5% 5%­10% 24 1. Which of the following changes is most likely to occur in the endometrium after 1 year of treatment? Which of the following muscle cell components helps spread the depolarization of the muscle cell membranes throughout the interior of muscle cells? Tissue remodeling begins at this site with degradation of collagen in the extracellular matrix by which of the following proteins? A 22-year-old man is brought to the emergency department in respiratory distress 15 minutes after he was stung on the arm by a wasp. His pulse is 100/min, respirations are 30/min, and blood pressure is 100/60 mm Hg. He is informed that he will require treatment with intramuscular vitamin B12 (cyanocobalamin) for the rest of his life. This therapy is necessary because this patient lacks which of the following types of cells? Beginning with protein synthesis in membrane-bound ribosomes, hepatocytes secrete proteins into the circulation via which of the following mechanisms? Which of the following is required to transport fatty acids across the inner mitochondrial membrane? An experiment is conducted in which the mitochondrial content of various tissues is studied. It is found that the mitochondrial content is directly proportional to the amount of energy one cell is required to generate and expend. The mitochondrial content is most likely greatest in which of the following types of cells? A 45-year-old man without a history of bleeding or excessive bruising dies suddenly due to rupture of an aortic dissection. A 42-year-old woman comes to the physician for a follow-up examination after two separate Pap smears have shown dysplastic epithelial cells. The viral E6 protein binds to the cellular p53 tumor suppressor gene, causing it to be degraded. Which of the following best describes the mechanism by which the E6 protein causes cervical cancer? Which of the following is the correct sequence of events in the initiation of contraction of a skeletal muscle fiber? Conformational Change in Troponin-Tropomyosin Complex 2 5 5 2 3 Release of Ca2+ from Sarcoplasmic Reticulum 3 4 2 5 4 (A) (B) (C) (D) (E) 14. Depolarization of Sarcolemma 1 2 3 4 5 Propagation into Transverse Tubules 4 3 4 3 1 Acetylcholine Binding to Receptors 5 1 1 1 2 A 90-year-old woman is brought to the emergency department 30 minutes after she fell while climbing the steps into her house. Increased activity of which of the following cell types is the most likely cause of the decrease in bone mass in this patient? A 50-year-old man comes to the physician because of a cough productive of large quantities of mucus for 6 months. A 65-year-old man with severe atherosclerotic coronary artery disease comes to the emergency department because of a 12-hour history of chest pain. During an experimental study, an investigator finds that the regulation of cell cycle and programmed cell death may be initiated by the mitochondrion. The interaction of the mitochondrion with the activation of the caspase family of proteases and subsequent apoptosis is most likely mediated by which of the following? He enrolls in a clinical study of a novel chemotherapeutic agent that, as a side effect, blocks kinesin, a component of the cellular microtubular transport system. An alteration in which of the following components of the neuromuscular junction is the most likely cause of the muscle weakness? A pathologist uses monoclonal antibodies against several intermediate filament proteins and finds that a tumor section stains positive for cytokeratin only. A D B C B A C B C B 30 Microbiology Microbiology Module (125 items) Systems General Principles of Foundational Science Biology of tissue response to disease Pharmacodynamic and pharmacokinetic processes Microbial identification and classification Bacterial biology Antibacterial agents Viral biology Antiviral agents Fungal biology Antifungal agents Parasitic biology Antiparasitic agents Prions Immune System Blood & Lymphoreticular System Nervous System & Special Senses Skin & Subcutaneous Tissue Musculoskeletal System Cardiovascular System Respiratory System Gastrointestinal System Renal & Urinary System Pregnancy, Childbirth, & the Puerperium Female Reproductive & Breast Male Reproductive Multisystem Processes & Disorders Immunology Module (25 items) Systems Immune System Development of cells of the adaptive immune response Structure, production, and function Cellular basis of the immune response and immunologic mediators Basis of immunologic diagnostics Disorders associated with immunodeficiency Immunologically mediated disorders Adverse effects of drugs on the immune system Blood & Lymphoreticular System Nervous System & Special Senses Skin & Subcutaneous Tissue Respiratory System Pregnancy, Childbirth, & the Puerperium 31 70%­75% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 1%­5% 75%­80% 5%­10% 1%­5% 1%­5% 1%­5% 1%­5% 1. A 45-year-old woman comes to the physician because of progressive facial swelling and pain during the past week. Physical examination shows ecchymoses over the left orbital and periorbital regions with proptosis. Findings on microscopic examination of material from the lesion include broad, irregularly shaped, nonseptate hyphae with branches at right angles. A 21-year-old woman who is a college student is brought to the emergency department 2 hours after the onset of fever, chills, severe headache, and confusion. Physical examination shows numerous petechial lesions over the upper and lower extremities. Analysis of cerebrospinal fluid shows numerous leukocytes and gram-negative diplococci. A sexually active 37-year-old woman comes to the physician because of a 2-day history of pain in the area of her genitals. Pelvic examination shows shallow, small, extremely tender ulcers with red bases in the vulvar and vaginal regions. Which of the following infectious agents is the most likely cause of these findings? During an experimental study, an investigator develops a new member of the class of non-nucleoside reverse transcriptase inhibitors. The organism agglutinates with antiserum directed against type B surface carbohydrate. The virulence of this organism is related to a bacterial constituent that interferes with which of the following host phagocyte functions? A 33-year-old woman contracts malaria while on a 3-month business trip to a Central American country. Which of the following species of Plasmodium is most likely to have caused the second febrile illness? Three weeks after traveling to California to study desert flowers, a 33-year-old man develops fever, chest pain, and muscle soreness. Two days later, red, tender nodules appear on the shins, and the right ankle is tender and painful. At a banquet, the menu includes fried chicken, home-fried potatoes, peas, chocolate eclairs, and coffee. Within 2 hours, most of the diners become violently ill, with nausea, vomiting, abdominal pain, and diarrhea. Analysis of the contaminated food is most likely to yield large numbers of which of the following organisms? A 35-year-old woman is admitted to the hospital because of fever and dry cough for 3 days. A 69-year-old woman comes to the emergency department because of a 2-day history of increasingly severe fever and back pain; she also has a burning sensation with urination, and there is an aromatic smell to the urine. She has had three urinary tract infections treated with ciprofloxacin during the past year. Enterococcus faecalis Escherichia coli Klebsiella pneumoniae Proteus mirabilis Staphylococcus saprophyticus During an experiment, an investigator gently abrades the skin from the flank of a mouse, creating a 1 Ч 2-cm skin window. A glass coverslip is then placed over the area so that cells attracted to the site attach to the coverslip for assessment. Two hours later, an extravasation of cells from the vasculature is noted on the coverslip. Which of the following complement components is the direct cause of the enhanced vascular permeability and chemoattraction in the abraded skin area in this experiment? He has had persistent left upper quadrant abdominal pain for 3 weeks despite therapy with omeprazole. Which of the following mechanisms of action is most likely involved in this resistance? A 3-year-old girl is brought to the emergency department by her father because of a persistent cough for 2 weeks. An investigator injects an experimental animal with a newly discovered bacterial strain to evaluate T-lymphocyte activation. Which of the following cell-surface molecules on the macrophage is most directly involved in the presentation of the processed peptides? An investigator conducts an experiment on Clostridium perfringens and then sterilizes the culture dishes by autoclaving. This method of sterilization is most appropriate because it ensures that which of the following bacterial structures are inactivated? A 52-year-old woman living in Maryland comes to the physician because of a 1-week history of low-grade fever, fatigue, and a red rash over the skin behind her left knee. Physical examination shows an 8-cm, warm, nontender, erythematous lesion with partial central clearing over the skin of the left popliteal area. An 8-month-old girl is brought to the emergency department because of a 1-day history of rapid breathing. A 45-year-old man comes to the physician because of fever and night sweats for 8 days.

Angles may be defined as relative and absolute treatment alternatives for safe communities coversyl 8 mg fast delivery, and both may be used in biomechanical investigations symptoms joint pain fatigue discount 4 mg coversyl mastercard. A relative angle measures the angle between two segments but cannot determine the orientation of the segments in space symptoms 2dpo purchase 4mg coversyl overnight delivery. An absolute angle measures the orientation of a segment in space relative to the right horizontal axis placed at the distal end of the segment medications diabetes buy coversyl 8 mg line. How segment angles are defined must be clearly stated when presenting the results of any biomechanical analysis medications parkinsons disease buy discount coversyl 8mg. The kinematic quantities of angular position medicine you can order online discount 8 mg coversyl with visa, displacement, velocity, and acceleration have the same relationship with each other as their linear analogs. Thus, angular 342 Section iii Mechanical Analysis of Human Motion equation review for Angular Kinematics Purpose relative angle between two segments using the law of cosines absolute angle Given Formula u = arccos(b2 + c2 - a2)/(2 Ч b Ч c) u = arctan ([yproximal ­ ydistal]/ [xproximal ­ xdistal]) u = uinitial + vinitialt u = vit + Ѕat2 u = 1/2at2 u = v2/2 Ч a v = (u2 - u1)/(t2 - t1) v = (vinitial + vfinal)/2 vf = vinitial + at v = at v 1vinitial2 12a(u 2a(u uinitial) Length of segments a and b and distance between end of a and b (length c) endpoints ­ horizontal and vertical components calculate position Starting position relative to origin, constant velocity (zero acceleration), and time calculate position Starting position at origin, constant velocity (zero acceleration), and time calculate position initial velocity, time, constant acceleration initial velocity = zero, time, constant calculate position acceleration calculate final displacement Final angular velocity; constant angular acceleration calculate average velocity Displacement and time calculate average velocity initial and final velocity calculate final velocity initial velocity, constant acceleration, and time Starting velocity = zero, constant calculate final velocity acceleration, and time Velocity at time = zero, constant calculate final velocity acceleration, initial position relative to origin, final position initial velocity = zero, constant calculate final velocity acceleration, initial and final position calculate acceleration Final velocity and displacement calculate average acceleration Velocity and time calculate average acceleration Displacement, time calculate time Displacement, constant acceleration calculate linear distance radius, angular displacement calculate linear velocity (tangential) radius, angular velocity calculate linear acceleration radius, angular acceleration (tangential) centripetal acceleration radius, angular velocity centripetal acceleration radius, tangential linear velocity vf2 = 2au v uinitial) a = vfinal2/2u a = (v2 - v1)/(t2 - t1) a = 2u/t2 t 12u/a s = ru v = rv a = ra ac = v2r ac = v2/r revieW QuestiOns True or False 1. Can she increase the velocity of the ball she hits without further training or using a different bat? If the hammer is 180 cm from the axis of rotation, what is the linear velocity of the hammer at release? Calculate the relative angle at the knee and the absolute angles of the thigh given the following positions in m: hip (2. During the support phase of walking, the absolute angle of the thigh has the following angular velocities: Frame 38 39 40 41 Time (s) 0. The final angular velocity of a golf swing was 400°/s with a constant angular acceleration of 501°/s2. An ice skater rotating around a vertical axis decreases in angular velocity from 450°/s to 378°/s in 9. What percent contribution to the tangential velocity of the ball comes from the rotation of the forearm? Functional variability of the lower extremity during the support phase of running. Effects of shoe type on cardiorespiratory responses and rearfoot control during treadmill running. Biomechanics of wheelchair propulsion as a function of seat position and user-to-chair interface. Electromyographic and kinematic analysis of graded treadmill walking and the implications for knee rehabilitation. Walking, running, and sprinting: A three dimensional analysis of kinematics and kinetics. Correlation between physical activity and the gait characteristics and ankle joint flexibility of the elderly. Kinematics was defined as the description of motion with no regard to the cause of the motion. The motion described was translatory (linear), rotational (angular), or a combination of both linear and rotational (general). The search for understanding the causes of motion date to antiquity, and answers to some of these questions were suggested by such notables as Aristotle and Galileo. The culmination of these explanations was provided by the great scientist Sir Isaac Newton, who ranks among the greatest thinkers in human history for his theories on gravity and motion. In fact, the laws of motion described by Newton in his famous book Principia Mathematica (1687) form the cornerstone of the mechanics of human movement (14). The basis for the understanding of the kinetics of linear motion is the concept of force. A force involves the interaction of two objects and produces a change in the state of motion of an object by pushing or pulling it. The force may produce motion, stop motion, accelerate, or change the direction of the object. In each case, the acceleration of the object changes or is prevented from changing. A force, therefore, may be thought of as any interaction, a push or pull, between two objects that can cause an object to accelerate either positively or negatively. For example, a push on the ground generated by a forceful knee and hip extension may be sufficient to cause the body to accelerate upward and leave the ground-that is, jump. It is also necessary to state the direction of a force because the direction of a force may influence its effect, for example, on whether the force is pushing or pulling. Vectors, as described in Chapter 8, are usually represented by arrows, with the length of the arrow indicating the magnitude of the force and the arrowhead pointing in the direction in which the 348 Section iii Mechanical Analysis of Human Motion Forces have two other equally important characteristics, the point of application and the line of action. The point of application of a force is the specific point at which the force is applied to an object. This is very important because the point of application most often determines whether the resulting motion is linear or angular or both. In many instances, a force is represented by a point of application at a specific point, although there may be many points of application. In many cases, the muscle is not attached to a single point on the bone but is attached to many points, such as in the case of the fan-shaped deltoid muscle. In solving mechanical problems, however, it is considered to be attached to a single point. Other points of application are the contact point between the foot and the ground for activities such as jumping, walking, and running; hand contact with the ball for a baseball throw; and the contact point between the racquet and the ball in tennis. The line of action of a force is a straight line of infinite length in the direction in which the force is acting. A force can be assumed to produce the same acceleration of the object if it acts anywhere along this line of action. Thus, if the force coming up from the ground in the last jump phase of a triple jumper has a line of action directed to 18° with respect to the horizontal, the jumper accelerates forward and upward in that direction. The orientation of the line of action is usually given with respect to an x, y coordinate system. The orientation of the line of action to this system is given as an angular position and is referred to as the angle of application. The four characteristics of a force-magnitude, direction, point of application, and line of action-are illustrated in Figure 10-1A for a muscular force and in Figure 10-1B for a high-jump takeoff. As presented in the discussion of kinematic vectors in Chapter 8, a single force vector may be resolved into perpendicular components, or several forces can be resolved into one vector. That is, a single force vector can be calculated or composed to represent the net effect of all of the forces in the system. Similarly, given the resultant force, the resultant force can be resolved into its horizontal and vertical components. Several types of force systems must be defined to compose or resolve systems of multiple forces. Any system of forces acting in a single plane is referred to as coplanar, and if they act at a single point, they are called concurrent. Any set of concurrent coplanar forces may be substituted by a single force, or the resultant, producing the same effect as the multiple forces. The force vectors a, b, and c all act in the same direction and can be replaced by a single force, d, which is the sum of a, b, and c. Thus: d a b c 5N 7N 22 N 10 N the force vector d would have the same effect as the other three force vectors. In Figure 10-2B, however, two of the force vectors, a and b, are acting in one direction, but the vector c is acting in the opposite direction. When the force vectors are not collinear but are coplanar, they may still be composed to determine the resultant force. Graphically, this can be done in exactly the same manner as described in Chapter 8 in the section on adding vectors. The force vectors a and b are not collinear, but they may be composed or added to determine their net effect. With the arrow of vector a placed at the tail of vector b, the resultant composed vector c is the distance between the tail of a and the arrow of b. First presented in Chapter 8, this involves first breaking each vector down into its components using resolution. After they are resolved into vertical and horizontal components, the orthogonal components for each vector are added, and the resultant vector is composed. To illustrate, the four vectors shown in Figure 10-2D will be assigned values of length 10 and u = 45° for vector A, length 6 and u = 0° for vector B, length 5 and u = 30° for vector C, and length 7 and u = 270° for vector D. Mass is a scalar and is the measure of the amount of matter that constitutes an object and is expressed in kilograms. The greater the mass of an object, the greater its inertia and thus the greater the difficulty in moving it or changing its current motion. Newton suggested that an object at rest- an object with zero velocity-would remain at rest. Additionally, an object moving at a constant velocity would continue to do so in a straight line. If it is noted that constant velocity results in zero acceleration just as zero velocity does, then it can be understood how this law holds for both cases. Therefore, the inertia of these objects would compel them to maintain their status at a constant velocity. Overcoming the inertia of such objects requires a net external force greater than the inertia of the object. If an object is subjected to an external force that can overcome the inertia, the object will be accelerated. To get an object moving, the external force must positively accelerate the object. On the other hand, to stop the object from moving, the external force must negatively accelerate the object. Because body mass determines inertia, an individual with greater mass has to generate larger external forces to overcome inertia and accelerate. Laws of motion the publication of the Principia Mathematica in 1687 by Sir Isaac Newton (1642 to 1727) astounded the scientific community of the day (14). In this book, he introduced his three laws of motion that we use to explain a number of phenomena. This relationship is expressed as: F = ma this equation can also be used to define the unit of force, the newton. By substituting the units for mass and acceleration in the right-hand side, it can be seen that: F = ma kg-m Newton s2 where kg-m is kilogram-meters. In this equation, the force is the net force acting on the object in question, that is, the sum of all of the forces involved. In adding up all forces acting on an object, it is necessary to take the direction of the forces into account. If the net force produces acceleration, the accelerated object will travel in a straight line along the line of action of the net force. Acceleration was previously defined as the time rate of change of velocity, or dv/dt. When two objects interact, the force exerted by object A on object B is counteracted by a force equal and opposite exerted by object B on object A. The result is that these two forces cannot cancel each other out because they act on and may have a different effect on the objects. For example, a person landing from a jump exerts a force on the earth, and the earth exerts an equal and opposite force on the person. Because the earth is more massive than the individual, the effect on the individual is greater than the effect on the earth. This example illustrates that although the force and the counterforce are equal, they may not necessarily have comparable results. In human movements, an action force is generated on the ground or implement, and the reaction force generally produces the desired movement. As shown in Figure 10-3, the jumper makes contact with the ground and generates a large downward force because of the acceleration of the body combined with forces generated by body segments at contact, and a resulting reaction force upward controls the landing. It is generally represented by the letter p and has units of kilogram-meters per second. To change the momentum of an object, an external force must be applied to the object. The momentum may increase or decrease, but in either case, an external force is required. F types of Forces the forces that exist in nature and affect the way humans move may be classified in a number of ways. The most common classification scheme is to describe forces as contact or noncontact forces (11). These are the forces involved, for example, when a bat hits a baseball or the foot hits the floor. As implied by the name, these are forces that are exerted by objects that are not in direct contact with one another and may actually be separated by a considerable distance. With the law of gravitation, Newton identified gravity as the force that causes objects to fall to the earth, the moon to orbit the earth, and the planets to revolve about the sun. This law states: "The force of gravity is inversely proportional to the square of the distance between attracting objects and proportional to the product of their masses. The constant value G was estimated by Newton and determined accurately by Cavendish in 1798. The gravitational attraction of one object of a relatively small size to another object of similar size is extremely small and therefore can be neglected. In biomechanics, the objects of most concern are the earth, the human body, and projectiles. The attractive force of the earth on an object is called the weight of the object. This is stated as: Gmobject Mearth W Fg r2 the force of gravity causes an object to accelerate toward the earth at a rate of 9.

When the periods were compared symptoms zoloft withdrawal generic 4mg coversyl with visa, there were no statistically significant differences in the severity of these four gastrointestinal symptoms medicine 5e buy coversyl 4 mg free shipping. Conclusion(s): People who identify themselves as severely lactoseintolerant may mistakenly attribute a variety of abdominal symptoms to lactose intolerance medicine online buy coversyl 4 mg visa. When lactose intake is limited to the equivalent of 240 ml of milk or less a day treatment genital warts discount coversyl 4 mg visa, symptoms are likely to be negligible and the use of lactosedigestive aids unnecessary symptoms low blood pressure buy discount coversyl 4 mg on-line. Race/ethnicity: white 89%; East Indian 11% Comorbidities: not reported Cointerventions: not reported medicinebg coversyl 4mg for sale. Inclusion criteria: Subjects who had an increase in hydrogen concentration from baseline of 20 ppm. Methods to measure outcomes: Subjects were to record symptoms after ingestion (time period unclear) Data source: 11 American adults similarly characterized as maldigesters as in Study 1 by breath hydrogen analysis following a 50-g lactose load and by past experience with intolerance symptoms following the consumption of dairy foods Inclusion and exclusion criteria: Same as Study 1. Conclusion(s): Authors conclude that the cause of milk intolerance in up to rd 1/3 African Americans claiming symptoms after ingestion of a moderate amount of milk cannot be due to its lactose content. Quality of the Study Gender: not reported but mostly female (70%) in the eligible population. Race/ethnicity: not reported Comorbidities: not reported Cointerventions: not reported 50 g of lactose dissolved in 200 ml of water plus galactosidase (gal) enzyme preparations 1) Lactogest soft gel capsules x 2 (Thompson Medical Inc, New York, New York), 2) Lactogest capsules x 4 3) Lactaid caplets x 2 (Lactaid Inc, Pleasantville, New 50 g of lactose dissolved in 200 ml of water plus two soft gel vitamin E capsules containing 420 rag/capsule of -tocopherol in soybean oil as a Placebo (Pharmacaps Inc, Elizabeth, New Jersey) Symptom scores, expressed as the sum of mean scores rating symptoms from 1 (none) to 5 (worst ever experienced) at baseline and 4 and 8 hours after challenge. Conclusion(s): Symptom scores for bloating, cramping, nausea, pain, diarrhea, and flatus were not significantly different between treatments and the Allocation concealment: adequate (small brown coded envelopes) Blinding: double Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no withdrawals reported Funding: Some industry support D-366 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria outcomes: Subjects kept a similar diary to Study 1, except that symptoms of bloating, abdominal cramps, nausea, abdominal pain, diarrhea and gas were self-scored by subjects at baseline and 4 and 8 hr on a 1-5 scale (none to worst ever experienced). Data source: 9 lactose intolerant Danish children Inclusion criteria: Subjects had to fulfill two of the following: 1) An increase in blood glucose during a lactose tolerance test (2 g of lactose per kilogram of body weight); 2) Diarrhea, borborygmus, and/or flatulence during a lactose tolerance test; 3) Low or no lactase activity in an intestinal biopsy specimen taken at the ligament of Treitz. Ethnicity: 6 subjects immigrants from Korea, Pakistan, or Turkey (plus 3 native Danes) Comorbidities: No subjects had renal or endocrine disorders or hereditary diseases. Conclusion(s): Children had significantly fewer clinical symptoms and signs within 24 hours after consuming lactose-hydrolyzed milk compared to regular milk. Allocation concealment: unclear Blinding: double Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no withdrawals reported Funding: nonindustry D-367 Appendix Table D8. Inclusion criteria: Lactose intolerance based on a lactose tolerance test (not defined), with no known disorders of the gastrointestinal tract. Exclusion criteria: lactose tolerance Methods to measure outcomes: Subjects completed questionnaire concerning the development of symptoms (borbo rygmus and meteorism, colic attacks, flatulence, and/or diarrhea) based on the following: 0=no symptoms; 1=slight; 2=moderate; 3=severe. Race/ethnicity: Latin American 100% Comorbidities: not reported Cointerventions: not reported 250 and 500 mL low-lactose milk (lactose content 1. Conclusion(s): Ingestion of 500 mL low-lactose milk resulted in significantly fewer symptoms compared to regular skim milk. After ingestion of 250 mL low-lactose milk there was a tendency to fewer symptoms but the difference was not statistically significant. Allocation concealment: unclear Blinding: double Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no withdrawals reported D-368 Appendix Table D8. Methods to measure outcomes: On a 24 hour diary sheet, subjects reported abdominal symptoms based on the following. For diarrhea, No diarrhea=formed stools; mild/moderate= 3 liquid/soft stools; severe= 4 liquid/soft stools. Data source: 9 symptomatic American adults from an outpatient clinic and 5 milk tolerant controls. Inclusion criteria: Subjects with a blood sugar <20 mg/100 mL after ingestion of 50 g lactose and had symptoms when challenged with 250 mL of skim milk. Subject Characteristics Treatment-Active, Adherence Evaluations 500 mL low-lactose milk (lactose content 3. TreatmentControl, Adherence Evaluations 500 mL ordinary milk (lactose content 25 g), x 1 dose. Outcome assessment/ Results and Conclusions Number of subjects reporting symptoms after ingestion Conclusion(s): There was a significant reduction in abdominal symptoms after ingestion of lactose-hydrolyzed milk compared to regular milk. Conclusion(s): Lactose-hydrolyzed milk significantly Allocation concealment: unclear Blinding: double Intent-to-treat analyses:100% followup Study withdrawals adequately described: no withdrawals reported D-369 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria Methods to measure outcomes: Subjects rated the occurrence and severity of gastro intestinal symptoms experienced during the 24-hour period after each test meal. Data source: 24 American lactose malabsorbers (determined by breath hydrogen test) and 75 lactose absorbing adolescent volunteers. Methods to measure outcomes: Symptomatology questionnaires were given to subjects each day after the test beverage was consumed. One or more Subject Characteristics Treatment-Active, Adherence Evaluations TreatmentControl, Adherence Evaluations 3) Sweet acidophilus milk x 1 week. Outcome assessment/ Results and Conclusions reduced pain and gas symptoms in the "Milk-intolerant" group compared to regular skim milk. Cointerventions: not reported "Milk-tolerant" (n=5) Mean age (range): 33 (22-48) Gender: women 60%. Race/ethnicity: white 87% (northern European n=65; southernEuropean n=8; Jewish n=14), Asian 10%, black 3%. Allocation concealment: Blinding: double Intent-to-treat analyses: Study withdrawals adequately described: D-370 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria relevant symptoms occurring between one and 24 hours indicated a positive response to the dairy drink for that test day. The 4 symptoms (bloating, flatulence, cramps, diarrhea) indicative of lactose intolerance were rated according: 0=none; 1=mild; 2=moderate; 3=severe Data source: Chilean volunteers from the Santiago penitentiary. Inclusion criteria: Lactose intolerance, determined by blood glucose analysis [<20 mg/ 100 considered deficient lactase activity] and developed symptoms after ingestion of 50 g lactose. Lactose tolerant subjects (n=16) Mean age (range): 27 (18-38) Gender: men 100% Race/ethnicity: Latin American 100%. Comorbidities: not reported Cointerventions: not reported 500 mL low lactose milk (lactose content 0. Results are expressed as the number of times a score was given to each symptom during the experiment. Conclusion(s): Lactose intolerant subjects had more symptoms and more severe symptoms with skim milk. Allocation concealment: unclear Blinding: noted as double, unclear if milks were given out randomly. Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no withdrawals reported D-371 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria present but not interfering with daily activities or <2 liquid bowel movements) = 1, severe (symptoms present and interfering with daily activities or caused great discomfort or >2 liquid bowel movements) = 2. Data Source: 17 American volunteers who reported symptoms after ingesting 25 g lactose but not after placebo. Placebo 250 ml (saccharin, lemon juice water) Regular skim milk 500 ml (25 g lactose). Regular whole milk 500 ml (25 g lactose) Sum of score of bloating, gas, cramps and diarrhea on scale: 0-none, 1=mild, 2= moderate, 3=severe. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup 8 hours Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria containing approxi mately 20 g of lactose. Exclusion criteria: Pregnant or lactating, had prior gastro intestinal surgery, had illness that would interfere with the experiment, or had used antibiotics within the past 30 days. Methods to measure outcomes: Subjects kept a dairy of symptoms and selfrated gas, stomach pain and/or cramps and diarrhea and/or loose stool for each hour from 0 to 8 hours following the test meal. Scores are expressed as the mean of the sum of scores rating symptoms from 0 (none) to 5 (severe) for each hour from baseline to 8 hr after the challenge. Ethnicity: the 6 subjects were immigrants from Indonesia, Japan, Malaysia, and Laos. After an overnight fast the subjects consumed 300 mL of each of five milk products in a Number of subjects who reported specific symptoms. Conclusion(s): the results suggest that a 50% level of lactose reduction in milk may be adequate to relieve the signs and symptoms of milk Allocation concealment: unclear Blinding: single Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no D-373 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria based on the results of a challenge with 300 mL whole milk contain-ing 14 g lactose after an overnight fast based on a peak breath hydrogen excretion >20 ppm. Methods to measure outcomes: At hourly intervals they rated their symptoms (cramps, flatulence, and diarrhea) on a scale of 0, no symptoms; 1, mild; 2, moderate; and 3, severe. Data source: 80 Italian adults, data from 71 subjects: 40 lactose malabsorbers and 30 lactose absorbers. Subjects were defined as lactose malabsorber if maximum increase in blood glucose concentration above fasting level was <20 mg/dL. Methods to measure outcomes: Subject Characteristics Treatment-Active, Adherence Evaluations 300 mL 80% lactose reduced milk (Balance) (lactose content 1 g) 300 mL 95% lactose reduced milk (Digestelact) (lactose content <0. Outcome assessment/ Results and Conclusions intolerance in the majority of healthy adults with lactose malabsorption. Conclusion(s): Lactose malabsorbers had significantly fewer symptoms with skim milk vs. The authors found, contrary to earlier findings, that fat seemed to contribute to milk intolerance in lactose malabsorbers rather than reduce it. Allocation concealment: unclear Blinding: double Intent-to-treat analyses: no, 74 of 80 completed study satisfactorily but data only for 71 (3 refused to drink milk at room temperature) Study withdrawals adequately described: yes D-374 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria Questionnaire was given to subjects to indicate whether they experienced diarrhea, flatulence, bloating, or abdominal pain during the 24 hours after consuming the milk test. Data source: 50 Mexican adults were enrolled, 25 lactose malabsorbers and 25 absorbers. Methods to measure outcomes: Subjects completed symptom questionnaire document presence or absence of 4 gastrointestinal symptoms (abdominal cramps, gas/flatulence, vomiting, and/or diarrhea). Race/ethnicity: Mostly Mexican with various degrees of European and Indian descent. Conclusion(s): Addition of LactAid significantly reduced symptoms of intolerance among the 25 lactose malabsorbers subjects. Allocation concealment: unclear Blinding: double Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no withdrawals reported Funding: industry supplied supplies D-375 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria Total points were then summed for each of the treatment periods. Exclusion criteria: recent history or concurrent use of antibiotics or recent gastrointestinal disease. Data source: 67 American lactose malabsorbing (determined by blood glucose analysis) and 43 lactose absorbing adolescent volunteers. Methods to measure outcomes: Subjects reported abdominal symptoms on a questionnaire containing yes/no or multiple choice questions regarding symptoms over 24 hours after consumption. Comorbidities: not reported Cointerventions: not reported 240 or 480 mL lactose-free chocolate dairy drink. Number of subjects reporting symptoms during 24 hours after consumption 18% of lactose malabsorbers were symptomatic after consuming 240 mL of lactose-free solution versus 28% after consuming 240 mL lactose solution. Allocation concealment: unclear Blinding: double Intent-to-treat analyses:100% followup Study withdrawals adequately described: no withdrawals reported D-376 Appendix Table D8. Methods to measure outcomes: Subjects reported abdominal symptoms on a questionnaire containing yes/no or multiple choice questions regarding symptoms (bloating, flatulence, cramps, or diarrhea) over 24 hoursafter consumption by checking 1=none; 2= mild; 3=moderate; and 4=severe. Data source: 87 American elderly volunteers, in which 23 were lactose malabsorbers (determined by breath hydrogen analysis after ingestion of 25 g lactose) and 64 lactose absorbers. Subject Characteristics Treatment-Active, Adherence Evaluations 240 or 480 mL lactose-free chocolate dairy drink. TreatmentControl, Adherence Evaluations 240 or 480 mL lactose-containing (lactose content 10. Outcome assessment/ Results and Conclusions Number of subjects reporting symptoms during 24 hours after consumption Among lactose malabsorbers, 27% were symptomatic after consuming 240 mL of lactose-free solution versus 9% after consuming 240 mL lactose solution. Conclusion(s): Factors other than lactose malabsorption may be responsible for a significant proportion of mild symptoms of "milk intolerance" in an adolescent population similar to this study. Quality of the Study All subjects (N=87) Age range: (14-19) Gender: not reported Race/ethnicity: black 30%, white 64%; Asian 6%. Gender: women 77% Race/ethnicity: Northern/western European ancestry 76% (35% of the malabsorbers), 240 mL lactose-free chocolate dairy drink. Symptom frequency was not significantly different between beverages in both Allocation concealment: unclear Blinding: double Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no D-377 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria Inclusion criteria: Subjects with no known gastrointestinal disease. Methods to measure outcomes: Subjects were interviewed the following morning after the test and were asked to state the occurrence severity of gas, bloating, cramps, or diarrhea during the previous afternoon. Symptom severity was based as follows: none; mild (noticeable, but not troublesome); moderate (troublesome, but not seriously uncomfortable); severe (uncomfortable, could not carry out normal activities). Data source: 150 Mexican volunteers, in which 97 were lactose malabsorbers (determined by blood glucose analysis [<25 mg/dl considered deficient lactase activity] after ingestion of 50 g lactose). Methods to measure Subject Characteristics Treatment-Active, Adherence Evaluations TreatmentControl, Adherence Evaluations Outcome assessment/ Results and Conclusions malabsorbers and absorbers. Conclusion(s): Authors conclude factors other than lactose malabsorption appeared to be responsible for the symptoms of intolerance reported and most may have been psychosomatic in origin. Mexico Duration of symptom recording: 6 hours All subjects (N=150) Mean age (range): 24 (16-50). Gender: women 41% Race/ethnicity: Mexican 100% 60 of the volunteers had previously participated in lactose mal absorption studies and were also 250 mL lactose-free milk plus 7. Conclusion: Authors concluded that lactose-intolerant subjects are indeed lactose-intolerant and that the frequency of abdominal symptoms that occur in persons with lactose malabsorption increases directly with the lactose content in milk. Allocation concealment: unclear Blinding: double Intent-to-treat analyses: 100% followup Study withdrawals adequately described: no withdrawals reported D-378 Appendix Table D8. Evidence table for blinded lactose intolerance treatment studies: Question 4 (continued) Author, Year, Study Design, Study Sponsorship, Country, Length of Followup Subject Selection, Data Source, Methods to Measure Outcomes, Inclusion/Exclusion Criteria outcomes: Symptoms were rated according: 1+ if mild; 2+ if moderate; 3+ if marked. Symptoms were scored as severe if diarrhea was present or if a cumulative rating of other symptoms (abdominal cramps, bloating, flatulence) was 4+. Data source: 22 lactose malabsorbers and 10 lactose absorber African American volunteers. Malabsorption was based on blood sugar rise of 26 mg/mL following ingestion of 2 lactose load (50 g/ m of body surface) Inclusion criteria: no overt gastrointestinal or metabolic disease, Methods to measure outcomes: Symptoms voluntarily mentioned were recorded.

Additional information:

• Mebeverine

References

• Leung AN, Bull TM, Jaeschke R, Lockwood CJ, Boiselle PM, Hurwitz LM, et al. An Official American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guideline: Evaluation of Suspected Pulmonary Embolism In Pregnancy http://www.thoracic.org/statements/resources/pvd/evaluation-of-suspected-pulmonary-embolism-inpregnancy. pdf 85.
• Lee RE, Yousem SA. The frequency and type of lung involvement in patients with Gaucher's disease. Lab Invest [Abstract] 1988;58:54 18.
• Stein MB, Chartier M, Walker JR. Sleep in nondepressed patients with panic disorder: I. Systematic assessment of subjective sleep quality and sleep disturbance. Sleep 1993;16:724-6.
• Ross JDC, Jensen JS: Mycoplasma genitalium as a sexually transmitted infection: implications for screening, testing and treatment, Sex Transm Infect 82(4):269n271, 2006.
• Plante MK, Marks LS, Anderson R, et al: Phase I/II examination of transurethral ethanol ablation of the prostate for the treatment of symptomatic benign prostatic hyperplasia, J Urol 177(3):1030n1035, discussion 1035, 2007.
• Latifpour J, Fukumoto Y, Weiss RM: Regional differences in the density and subtype specificity of endothelin receptors in rabbit urinary tract, Naunyn Schmiedebergs Arch Pharmacol 352:459, 1995.