Overdose with this drug in children causes features of both opioid and atropine intoxication and may be fatal arthritis in dogs stem cell treatment buy celecoxib 200mg with amex. It antagonizes peristalsis arthritis pain constant buy celecoxib 100 mg, possibly by antagonizing acetylcholine release in the intramural nerve plexus of the gut arthritis thumb surgery order celecoxib 100mg otc, although non-cholinergic effects may also be involved arthritis vinegar treatment purchase celecoxib 200 mg without prescription. The dose is 4 mg initially incipient arthritis definition purchase 200 mg celecoxib visa, followed by 2 mg after each loose stool up to a total dose of 16 mg/day arthritis no pain purchase 100mg celecoxib mastercard. Adverse effects are unusual arthritis care diet and exercise buy 100mg celecoxib free shipping, but include dry mouth arthritis in back thoracic order 100mg celecoxib free shipping, dizziness, skin rashes and gastric disturbances. Case history A 70-year-old woman who was previously very active but whose mobility has recently been limited by osteoarthritis of the knees and hips sees her general practitioner because of a recent change in bowel habit from once daily to once every three days. Her current medication includes regular co-codamol for her osteoarthritis, oxybutynin for urinary frequency, aluminium hydroxide prn for dyspepsia, and bendroflumethiazide and verapamil for hypertension. Following bowel evacuation with a phosphate enema, proctoscopy and colonoscopy are reported as normal. Bulk-forming drugs, such as ispaghula, methylcellulose and sterculia are useful in controlling faecal consistency in ileostomy and colostomy, and in controlling diarrhoea associated with diverticular disease. In non-pathogenic diarrhoea or viral gastroenteritis, antibiotics and antidiarrhoeal drugs are best avoided. Initial therapy should be with oral rehydration this is a syndrome of acute watery diarrhoea lasting for one to three days and associated with vomiting, abdominal cramps and other non-specific symptoms, resulting from infection by one of a number of enteropathogens, the most common being enterotoxigenic Escherichia coli. Early treatment of diarrhoea with ciprofloxacin will control the great majority of cases and this, together with oral replacement of salts and water, is the currently preferred approach. The pancreas has a large functional reserve and malabsorption does not usually occur until enzyme output is reduced to 10% or less of normal. This type of malabsorption is usually treated by replacement therapy with pancreatic extracts (usually of porcine origin). Unfortunately, less than 10% of the lipase activity and 25% of the tryptic activity is recoverable from the duodenum regardless of the dose schedule. H2-antagonists decrease both acidity and volume of secretion and retard the inactivation of exogenous pancreatic enzymes. Supplements of pancreatin are given to compensate for reduced or absent exocrine secretion in cystic fibrosis, pancreatectomy, total gastrectomy and chronic pancreatitis. Pancreatin is inactivated by gastric acid and therefore preparations are best taken with or immediately before or after food. Gastric acid secretion can be reduced by giving an H2-blocker about one hour beforehand, or antacids may be given concurrently to reduce acidity. Pancreatin is inactivated by heat and, if mixed with liquids or food, excessive heat should be avoided. The dose is adjusted according to size, number and consistency of stools such that the patient thrives. Pancreatin can irritate the perioral skin and buccal mucosa if it is retained in the mouth and excessive doses can cause perianal irritation. The most frequent side effects are gastrointestinal ones including nausea, vomiting and abdominal discomfort. Hyperuricaemia and hyperuricuria have been associated with very high doses of the drug. Withdrawal of the antibacterial drug and the introduction of oral metronidazole or vancomycin should be instituted. Although the symptoms are mostly colonic, patients with the syndrome have abnormal motility throughout the gut and this may be precipitated by dietary items, such as alcohol or wheat flour. The important management principles are first to exclude a serious cause for the symptoms and then to determine whether exclusion of certain foods or alcohol would be worthwhile. An increase in dietary fibre over the course of several weeks may also reduce the symptoms. Psychological factors may be important precipitants and counselling may be helpful. The oral use of better absorbed anticholinergics, such as atropine, is limited by their side effects. In general, however, they should be avoided for such a chronic and benign condition because of their serious adverse effects (see Chapters 19 and 20). The mechanism which produces these changes is not established, but it is known that in hepatic coma and pre-coma, the blood ammonia concentration increases. In many patients, the time-course of encephalopathy parallels the rise in blood ammonia concentrations. The liver is the only organ that extracts ammonia from the blood and converts it to urea. Bacterial degradation products of nitrogenous material within the gut enter the systemic circulation because of a failure of first-pass hepatic extraction (due to hepatocellular damage), or due to bypass of the hepatocytes by collateral circulation or intrahepatic shunting. Another source is urea, which undergoes enterohepatic circulation and yields approximately 3. Ammonia diffuses into the blood across the large intestine epithelium, where it is trapped by becoming ionized due to the lower pH of blood compared to colonic contents. Ammonia is not the only toxin involved, as perhaps 20% of patients with encephalopathy have normal blood ammonia concentrations, and methionine can provoke encephalopathy without causing a significant rise in blood ammonia concentration. Furthermore, ammonia toxicity affects the cortex but not the brainstem, which is also involved in encephalopathy. In addition, these determine the availability of tryptophan to the brain and hence have an effect on 5-hydroxytryptamine synthesis. Intravenous administration of acetylcysteine is used prophylactically in some centres to enhance glutathione synthesis and thereby reduce oxidant (free radical) stresses by scavenging these reactive entities. This disaccharide is not a normal dietary constituent and humans do not possess a lactulase enzyme, so lactulose is neither digested nor absorbed but reaches the colon unchanged, where the bacterial flora breaks it down to form lactate, acetate and other acid products. Side effects include vomiting, anorexia, abdominal pain, diarrhoea, headache and dizziness. Newer vasoactive drugs, such as terlipressin, appear to have a better therapeutic index and fewer side effects, although terlipressin has a short half-life and needs to be administered frequently or as an infusion. A number of trials have demonstrated efficacy of noncardioselective beta-adrenergic antagonists (propranolol, nadolol) in reducing the incidence of gastro-intestinal bleeding in patients with portal hypertension, especially in combination with endoscopic sclerotherapy. Chronic viral hepatitis is diagnosed when there is evidence of continuing hepatic damage and infection for at least six months after initial viral infection. While up to 90% of patients with acute hepatitis B clear the virus spontaneously, up to 60% of those with hepatitis C virus do not do so. Pegylated interferon alfa-2a (peginterferon alfa-2a) may be preferred to interferon alfa. Pegylation (polyethylene glycolconjugation) prolongs the interferon half-life in the blood, allowing subcutaneous once weekly dosing. In chronic hepatitis C, the combination of peginterferon alfa and ribavarin (see Chapter 45) is recommended. Two-thirds of patients with varices die as a result and of these, one-third die of the first bleed, one-third rebleed within six weeks and only one-third survive for one year. Sclerotherapy and surgical shunt procedures are the mainstay of treatment, and drug therapy must be judged against these gloomy survival figures. Drugs currently used for the management of acute variceal haemorrhage include octreotide (the long-acting analogue of somatostatin), vasopressin and terlipressin (a derivative of vasopressin). Terlipressin and octreotide are used to reduce portal pressure urgently, to control bleeding before more definitive treatment, such as sclerotherapy or variceal banding. Betablockers and vasodilators, such as nitrates, are used for long-term therapy to reduce portal pressure. Metabolic pathways may become saturated at high concentrations and drug or metabolites may accumulate, leading to toxicity. Although hepatotoxicity is traditionally divided into dose-dependent and dose-independent hepatotoxicity, the relationship is not always clear-cut. For example, even with predictable hepatotoxins, there is considerable interindividual variation in susceptibility to hepatic damage. This can sometimes be attributed to genetic polymorphism or to environmental stimuli affecting hepatic microsomal enzymes, or to previous liver disease. Particular drugs tend to produce distinctive patterns of liver injury, but this is not invariable (see also Chapter 12). If they are considered to be drug related, but further treatment is indicated, it is reasonable to continue the drug with regular monitoring of liver enzymes if a better alternative therapy is not available. Obesity is a major risk factor for cardiovascular disease, stroke and type 2 diabetes mellitus. It is preventable, since obese patients are fat because they eat too many calories for their energy needs. Naturally, a calorie-controlled diet and adequate but sensible amounts of exercise are the essentials of treatment. Unfortunately, the results of treating patients at weight-reduction clinics are disappointing and only a few individuals achieve permanent weight loss. There has accordingly been a great deal of interest in the possibility of altering appetite pharmacologically in order to help the patient to reduce his or her calorie intake. Unfortunately, the causes of obesity are only currently being more comprehensively studied. If the patient is being treated for a disease associated with hepatic dysfunction, particularly with multiple drugs, identification of the responsible agent is particularly difficult. Elderly are at particular risk Tolbutamide Telithromycin Isoniazid Cholestatic jaundice Hepatocellular damage Hepatitis Mild and self-limiting in 20% and severe hepatitis in 0. Possibly more common in rapid acetylators Pyrazinamide Methyldopa Hepatitis Hepatitis Similar to isoniazid, but more clearly related to dose About 5% of cases have subclinical, raised transaminases; clinical hepatitis is rare Phenytoin Hypersensitivity reaction Resembles infectious mononucleosis; pharmacogenetic predisposition; cross-reaction with carbamazepine Isoniazid Chronic active hepatitis Associated with prolonged treatment, usually regresses when drug is discontinued Nitrofurantoin Dantrolene Halothane Ketoconazole } Hepatitis/hepatic necrosis See Chapter 24 and metabolic control pathways, as well as its exact effects on body weight and energy expenditure. In the future, modulation of leptin activity may provide a target for treating obesity. One hypothesis is that lean people do not become obese when they overeat because their tissues preferentially liberate heat (particularly from brown fat). Therefore, research into drugs for the treatment of obesity has concentrated on finding substances that inhibit appetite. Learned behaviour is probably important in determining the frequency of eating and whether food is taken between major meals. Stretch receptors in the stomach are stimulated by distention, but the main factors that terminate eating are humoral. Bombesin and somatostatin are two candidates for humoral satiety factors released by the stomach. Amphetamines and related drugs suppress appetite but are toxic and have considerable abuse potential. The site of action of amphetamines appears to be in the hypothalamus, where they increase noradrenaline and dopamine concentrations by causing transmitter release and blocking re-uptake. Cardiovascular effects are frequently observed with amphetamines, a doserelated increase in heart rate and blood pressure being the most common effect. Contraindications include major psychiatric illness, ischaemic heart disease, dysrrythmias, hyperthyroidism and pregnancy. Side effects include dry mouth, nausea, abnormal taste, constipation, myalgia, palpitations, alopecia, seizures and bleeding disorders. Adverse effects include nausea, vomiting, diarrhoea, mood changes, anxiety, impaired memory, dizziness and sleep disorders. Orlistat, is an inhibitor of gastro-intestinal lipases, reduces fat absorption and is licensed for use to treat obesity in combination with a weight management programme, including a mildly hypocaloric diet. Although there is less absorption of the fat-soluble vitamins (vitamins A, D, E and K) and of -carotene, this does not appear to cause pathological vitamin deficiency, and vitamin supplementation is not routinely indicated. A high-fibre diet may help weight loss, provided that total caloric intake is reduced, and is desirable for other reasons as well. Thyroxine has been used to increase the basal metabolic rate and reduce weight in euthyroid obese patients. Weight gain occurs during treatment with various other drugs, including atypical neuroleptics. They are nutrients that are essential for normal cellular function, but are required in much smaller quantities than the aliments (carbohydrates, fats and proteins). Vitamins are essential cofactors to or components of enzymes that are integral in intermediary metabolism and many other biochemical processes. Vitamin B12 and folate are discussed in Chapter 49, vitamin D in Chapter 39, and vitamin K in Chapter 30. The vitamin B complex includes vitamins B1 (thiamine), B6 (pyridoxine), B12, folate, plus B2 (riboflavin), B3 (nicotinic acid). Vitamin deficiency usually results from either inadequate dietary intake, increased demand. The concept that various vitamin supplements might decrease the incidence of a variety of diseases, including cancer and atheroma, has been under investigation. Several large prospective placebo-controlled intervention trials have investigated these hypotheses, but to date evidence of clear clinical benefit is lacking. In general vitamins should only be prescribed for the prevention or treatment of vitamin deficiency. Retinol (vitamin A1) is a primary alcohol and is present in the tissues of animals and marine fishes; 3-dehydroretinol (vitamin A2) is present in freshwater fish; retinoic acid shares some but not all of the actions of retinol. Its deficiency retards growth and development, and causes night blindness, keratomalacia, dry eyes and keratinization of the skin. Dietary sources of vitamin A include eggs, fish liver oil, liver, milk and vegetables. Thiamine deficiency leads to the various manifestations of beriberi, including peripheral neuropathy and cardiac failure. Increased carbohydrate utilization requires increased intake because thiamine is consumed during carbohydrate metabolism. It is therefore useful to express thiamine needs in relation to the calorie intake. The body possesses little ability to store thiamine and with absolutely deficient intake, beriberi develops within weeks. Acute thiamine deficiency may be precipitated by a carbohydrate load in patients who have a marginally deficient diet. This is especially important in alcoholics and thiamine replacement should precede intravenous dextrose in alcoholic patients with a depressed conscious level. Failure to do this has historically been associated with worsening encephalopathy and permanent sequelae. Cofactor in cholesterol synthesis Cofactor in mucopolysaccharide synthesis Normal soft tissue growth Figure 35. Regular dietary or parenteral supplementation of vitamin A may be necessary in patients with steatorrhoea. Adverse effects Long-term ingestion of more than double the recommended daily intake of vitamin A can lead to toxicity and chronic hypervitaminosis A. Use Thiamine is used in the treatment of beriberi and other states of thiamine deficiency, or in their prevention. Once the deficiency state has been corrected, the oral route is preferred, unless gastrointestinal disease interferes with ingestion or absorption of the vitamin. Pharmacokinetics Gastro-intestinal absorption of retinol via a saturable active transport mechanism is very efficient, but is impaired in patients with steatorrhoea. Retinol is partly conjugated to a glucuronide and undergoes enterohepatic circulation. Clinical evidence of vitamin A deficiency usually appears only months after reduced intake, when hepatic stores have been depleted. Adverse effects Anaphylactoid reactions following parenteral thiamine dosing have been reported, so parenteral administration should be restricted to situations where it is essential. Pharmacokinetics Absorption of thiamine following intramuscular injection is rapid and complete. Thiamine is also well absorbed through the mucosa of the upper part of the small intestine by both active and passive mechanisms, and surplus intake is excreted unchanged in the urine. Contraindications Excess vitamin A during pregnancy causes birth defects (closely related compounds are involved in controlling morphogenesis in the fetus). Therefore pregnant women should not take vitamin A supplements, and should also avoid liver in their diet. Deficiency of niacin causes pellagra, that can manifest clinically as a syndrome complex which includes dementia, dermatitis and diarrhoea. Pyridoxine is also used to treat certain uncommon inborn errors of metabolism, including primary hyperoxaluria. Large doses are sometimes used to treat premenstrual syndrome, and there is a lobby of enthusiasts for this, despite a paucity of evidence. Adverse effects There have been reports of ataxia and sensory neuropathy following administration of large doses (2 g/day) of pyridoxine for more than two months.
To avoid this arthritis in dogs alternative treatments celecoxib 100mg low cost, inspect all electrodes thoroughly before surgery and use them only once arthritis pain remedies discount celecoxib 200 mg mastercard. Capacitative coupling also diverts current Since the sheath-within-a-sheath design of the resectoscope resembles a capacitor arthritis dogs medication uk purchase 100 mg celecoxib amex, high-voltage current can jump to the outer sheath without direct contact from the electrode pills for arthritis in dogs purchase 100 mg celecoxib with amex. When Munro17 bench-tested electrosurgical generators and electrodes with and without insulation defects arthritis medication for high blood pressure order celecoxib 100 mg mastercard, he found that capacitative coupling with intact electrodes occurred more frequently with high-voltage coagulation current than with lower-voltage cutting current arthritis in fingers surgery generic celecoxib 200mg on line. One way to avoid these injuries is to activate the electrode intermittently rheumatoid arthritis diet milk celecoxib 200mg overnight delivery, with short bursts arthritis in neck and back of head discount celecoxib 200 mg with visa, rather than rolling back and forth over an area with continuous current. Another strategy is placing a damp sponge in the posterior vagina extending out the introitus; this protects the mucosa and perineal skin-especially in obese patients. Electrosurgical and gaseous complications Most electrosurgical complications involve activation of an electrode at the time of perforation, or current diversion to the outer sheath. Thermal injuries also can be caused by overheating of the return pad or use of a weighted speculum that has not fully cooled after removal from the autoclave. The latter can be avoided by immersing the entire speculum in cool saline for at least 1 to 2 minutes prior to inserting it into the vagina. The blade cools much faster than the weighted ball, so be sure to check both to prevent a perineal or buttock burn. Especially when using vaporization electrodes, avoid prolonged activation of the electrode at high power. To minimize risk of vaporization, use a second dispersive pad connected to the first via a "y" connector to further disperse current and heat at the return pad. Also, limit the use of coagulation current and use a maximum generator setting of 60 to 80 W in the coagulation mode. Take steps to avert gas embolism, but watch closely for signs Initial reports of this potentially fatal complication came mostly from laser ablation procedures, but gas embolism can occur during all diagnostic and operative hysteroscopic procedures, especially the latter. Sources of gas embolism: room air, carbon dioxide, carbon monoxide, and other gaseous products of vaporization or tissue combustion. The surgeon should ask to be immediately alerted to any sudden fall in oxygen saturation, as well as to hypotension, hypercarbia, arrhythmias, tachypnea, or a "mill wheel" murmur. If any of these signs are detected and a gas embolism is suspected, stop the procedure and ventilate the patient with 100% oxygen. Reduce the risk of air embolism by avoiding the Trendelenburg position and leaving the last dilator in the cervix until just before inserting the resectoscope. Also limit repetitive removal and reinsertion of the resectoscope, as often occurs during myoma resection. By vaporizing rather than resecting myomas, it is possible to eliminate the need to continually remove fibroid chips. Complications from distention media Excess absorption of distention media is one of the most frequent complications. Most surgeons use low-viscosity, sodiumfree fluids for operative hysteroscopy, since fluids that contain electrolytes are incompatible with monopolar electrosurgical instruments. If swelling exceeds 5%, the risk of severe neurological damage dramatically increases. This sodium pump protects the brain against cerebral edema, which can cause herniation of the brain stem and death. Although men and postmenopausal women develop dilutional hyponatremia, they are less likely to suffer brain damage because the sodium pump is intact. Vigilant monitoring of fluid intake/output during hysteroscopic surgery is necessary to prevent hyponatremic complications. Avoid the pitfall of erroneously attributing deficits to fluid "in the drapes" by using drapes with a fluid-collection pouch. Manufacturers of hysteroscopic equipment offer highly accurate electronic fluid monitoring systems that measure the weight of the distending fluid infused and collected rather than relying on manual estimation of deficit. The latter method may be inaccurate since the volume of the supply bag can vary by as much as 10%. High intrauterine pressure may be desirable for visualization, but it greatly increases the risk of intravasation. I adjust pressure and flow rates by opening or closing the inflow and outflow valves of the resectoscope until slight amounts of bleeding from resected tissue can be visualized. Use a dilute vasopressin injection to constrict blood vessels and decrease the chance of intravasation. Vaporizing electrodes for myoma resection and ablation seal blood vessels and reduce fluid absorption. Do not wait for the result of the sodium level before treatment, since a 5- to 20-minute delay can be catastrophic. I do not limit the duration of resectoscopic procedures as long as fluid deficits are below 750 mL, as measured by electronic fluid monitor. I also ensure that the operating room staff is well educated in the use of the monitor and able to troubleshoot intraoperatively. If the machine fails during the procedure, reset it with the alarm limit lowered to reflect the deficit recorded before failure. Choosing a distention medium There is no ideal distention medium for monopolar operative hysteroscopy. Several authors have suggested that 5% mannitol is advantageous since it is isosmolar and acts as an osmotic diuretic. The main disadvantage of 5% mannitol is its high cost and limited availability in 3-L bags or 4-L bottles. The use of bipolar devices in normal saline prevents dilutional hyponatremia, but fluid deficits must still be monitored electronically so they do not exceed 2,000 mL. The false sense of security that may occur when normal saline is used for distention may lead to inaction when a large deficit occurs. Be alert for endometrial cancer this malignancy has been diagnosed at the time of endometrial ablation and reported in patients who have undergone prior endometrial ablations or fibroid resections. Thus, endometrial sampling should be part of the workup of abnormal uterine bleeding before the patient is scheduled for operative hysteroscopy. In women at high risk for endometrial cancer, perform office diagnostic hysteroscopy, with directed biopsy of any suspicious areas. When viable endometrial glands are "buried" during ablation, or synechiae develop, preventing the egress of blood, there is a chance that diagnosis of endometrial cancer will be delayed. Patients whose abnormal bleeding recurs after ablation should undergo sampling and office hysteroscopy, just as if they had not undergone a previous ablation. Theoretically, women who undergo endomyometrial resection or vaporization should have a lower incidence of endometrial cancer, since the tissue most susceptible to malignancy is removed. In their comprehensive review of late complications of operative hysteroscopy, Cooper and Brady21 suggest that patients at high risk for endometrial cancer who present with abnormal uterine bleeding not controlled by hormones might be better served by hysterectomy. I do perform ablation and resection in patients with complex hyperplasia without atypia if it has been reversed with progestin and does not recur for at least 6 months without progestin therapy. These patients undergo office hysteroscopy and sampling of the endometrium before operative hysteroscopy is scheduled. C O N T I N U E D Postoperative and late complications these include infection, endometrial cancer, iatrogenic adenomyosis, hematometria, post-ablation tubal ligation syndrome, and pregnancy. Endometritis, parametritis, and pyometra are more common following resection of submucous myomas, with rates as high as 2% reported. Infection is more likely after prolonged procedures, especially when the hysteroscope is repeatedly inserted and removed. It also is more likely if the patient has a history of pelvic inflammatory disease. I generally administer prophylactic antibiotics (1 dose of intravenous ceftizoxime, 1 g, approximately 30 to 60 minutes prior to surgery). According to the first, when the endometrium is incompletely resected, scarring over this tissue causes the viable glands to grow into the myometrium. The other theory suggests that viable endometrial debris is transported into the myometrium by vessels opened at resection. I have found that using the vaporization electrode followed by application of a rollerball over the surface of the cavity most effectively reaches maximal tissue depth and, theoretically, prevents adenomyosis. Since most adenomyosis occurs on the posterior wall, I take a strip from this area for pathologic analysis to determine whether adenomyosis preceded the ablation or developed subsequent to it. Hematometria this can occur following operative hysteroscopy if viable glands are left in the fundal or cornual region and synechiae develop in the lower segment, preventing egress of blood. It also can occur if the upper endocervix is ablated and subsequently scars, causing stenosis. Hematometria can be diagnosed easily by ultrasound and treated with office hysteroscopy using a narrow-diameter, rigid, continuous-flow hysteroscope with an operating channel to pass small instruments. Post-ablation tubal ligation syndrome this is cornual hematometria that develops when viable endometrial cells are left in the cornua when the cavity also contains synechiae, causing cyclic bleeding. Since there is no egress from the cervix or tubes, blood gradually builds up, leading to hematosalpinx and pain. This complication is less likely after hydrothermablation, since the free-flowing saline ablates the cornua completely. After more than 50 hydrothermablations performed in patients with prior tubal sterilizations, I have not seen any cases of postablation tubal ligation syndrome. Treatment consists of bilateral salpingectomy or tubal fulguration at the cornual region and repeat ablation or resection of viable endometrial tissue. Post-ablation pregnancy can be very complicated Pregnancy after endometrial ablation occurs at a rate of 0. Counsel patients that this procedure does not prevent pregnancy and that contraception is vital. In a review of 37 post-ablation pregnancies, only 11 of 17 women who chose not to terminate carried the gestation beyond 28 weeks. In addition, there was a high incidence of intrauterine growth restriction, prematurity, and placenta accreta. Complications of global ablation Global ablation technologies were developed to enable gynecologists with limited operative hysteroscopy skills to perform endometrial ablation and to make ablation safer for the patient. These technologies completely eliminate the risk of distentionmedia complications, but widespread use has resulted in other complications that have been reported in the literature to only a limited extent. Do not override safety systems Complications are more frequent when devices are misused or safety systems overridden. Most global procedures are performed blindly, and some doctors fail to perform diagnostic hysteroscopy before and after surgery, which I feel is mandatory with any endometrial ablation. Hydrothermablation is the only global technique that has the advantage of direct observation. In more than 150 procedures done in my office under local anesthesia, the only complications were 2 false passages. Both were promptly identified during diagnostic hysteroscopy, and the surgery was rescheduled 2 to 3 months later. Intrauterine adhesions; hysteroscopic diagnosis, classification, treatment, and reproductive outcome. Perioperative complication rates of primary and repeat hysteroscopic endometrial ablations. The effect of dilute vasopressin solution on intraoperative blood loss during operative hysteroscopy: a randomized controlled trial. Endometrial ablation and hysteroscopic myomectomy by electrosurgical vaporization. Efficacy of preoperative medical treatment in facilitating endometrial resection, myomectomy and metroplasty: literature review. Genital tract electrical burns during hysteroscopic endometrial ablation: report of 13 cases in the United States and Canada. Factors affecting capacitative current diversion with a uterine resectoscope: an in vitro study. Changes in serum electrolytes after transcervical resection of endometrium and submucous fibroids with the use of 1. The serosal sign: the hysteroscopic appearance of the uterine cavity just prior to perforation. Resectoscopic cervical trauma minimized by inserting Laminaria digitata preoperatively. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. Over 130 different disorders have been identified to date, with new disorders continually being recognized [1,2]. The accurate and timely diagnosis of these disorders requires a high index of suspicion and specialized testing. Therefore, consultation with a clinical immunologist who is experienced in the evaluation and management of immunodeficiencies is essential, since early diagnosis and treatment are critical for preventing significant disease-associated morbidity and improving patient outcomes [5-7]. This is an open access article distributed under the terms of the Creative Commons Attribution License creativecommons. Disorders of adaptive immunity maturation lead to T-cell (cellular) immunodeficiency disorders, while defects relating to B-cell development and/or maturation result in B-cell (antibody-deficiency) disorders. Disorders of innate immunity T cells and B cells are the primary cells of the adaptive immune system. B cells mediate antibody production and, therefore, play a major role in antibody-mediated (humoral) immunity. Defects occurring at any stage of T-cell development, differentiation and Innate immune responses represent the first line of defense against potentially invading organisms. Appropriate recognition of threats and induction of the inflammatory cascade are essential steps in the removal of these organisms from the system. Failure of the innate system to identify pathogens delays the induction of the immune response and may worsen outcomes of infection. Phagocytes are primarily responsible for phagocytosis, the process by which cells engulf and eliminate invading pathogens. Complement proteins function to identify and opsonize (coat) foreign antigens, rendering them susceptible to phagocytosis. Therefore, clinical suspicion is important for timely diagnosis of these disorders. However, normal Tcell numbers do not exclude the possibility of T-cell defects, and in patients with clinical presentations consistent with immunodeficiency, further investigations of T-cell function are warranted. Patients with these disorders often present later in childhood with recurrent infections and clinical findings that vary depending on the specific syndrome (see Table 1). They comprise a heterogeneous group of disorders characterized by an increased susceptibility to respiratory tract infections with bacteria, particularly Streptococcus pneumoniae and Haemophilus influenzae. Patients usually present after 6 months of age with recurrent, and often severe, sinopulmonary infections such as otitis media, sinusitis, and pneumonia. Diarrhea, fatigue, autoimmune manifestations (particularly autoimmune cytopenias), and sensorineural hearing loss are also common [6,9]. Patients with humoral deficiency often have reduced or absent serum immunoglobulin levels, but may also show normal or increased serum immunoglobulin levels with abnormal function. More than 20 antibody-deficiency disorders have been defined to date, however, many remain undefined. The disorder is characterized by markedly reduced levels of circulating B-cells and serum IgG, IgA and IgM. Affected males usually present within the first 2 years of life with recurrent sinopulmonary infections and absent lymph nodes and tonsils [5,9]. The disorder affects males and females equally, and usually has a later age of onset than other antibody-deficiency disorders. It is associated with recurrent sinopulmonary infections, autoimmune and granulomatous disease, gastrointestinal complications and an enhanced risk of malignancy. Some patients may also present with bronchiectasis (irreversible widening of portions of the bronchi resulting from damage to the airway wall), which is a common cause of morbidity and mortality in these patients [5]. Milder antibody-deficiency disorders, such as selective IgA deficiency, are associated with variably low serum levels of an immunoglobulin class or subclass and, in some cases, impairments in specific antibody formation. IgA deficiency, for example, is characterized by low or absent levels of serum IgA in the presence of normal levels of IgG and IgM. Innate immunodeficiencies B-cell (antibody-deficiency) disorders are the most common type of immunodeficiencies, accounting for Patients with innate immunodeficiency disorders may present at any age, often with unusual or difficult to McCusker and Warrington Allergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S11. The typical signs and symptoms of phagocyte disorders are severe pyogenic (puss-like) bacterial and fungal infections of the skin, respiratory tract, and internal organs, as well as painful sores around the mouth. Hyper-IgE syndrome is another phagocyte disorder characterized by Staphylococcal infections of the skin, bone, and lungs, bony abnormalities and high IgE levels. Patients with these disorders tend to present with systemic autoimmune disease that resembles lupus erythematosus or with severe or recurrent infections with encapsulated organisms (see Table 1) [3,5,8]. Although 70% reported being hospitalized prior to diagnosis (Figure 1C), nearly half (48%) reported no hospitalization since diagnosis (Figure 1D). Conditions before diagnosis 80 70 25 60 50 20 % % 15 10 40 30 20 10 5 0 Ot i ti s Di ar rh ea Ar th M rit ala is bs or pt io n <1 1 to 5 6 to 11 12 to 17 18 to 39 40 to 64 65+ Si nu sit is Br on ch iti Pn s eu m on ia N=2,651 N=2,807 C. Significant lymphopenia, for example, may be the first indication of T-cell (cellular) immunodeficiency. Serum levels that are clearly below age- appropriate reference values may be indicative of B-cell immunodeficiencies.
It delivers iron to tissues that have transferrin receptors arthritis disability order 200 mg celecoxib with visa, especially erythroblasts in the bone marrow which incorporate the iron into haemoglobin arthritis relief heat or cold order celecoxib 200 mg visa. At the end of their life rheumatoid arthritis in dogs feet generic 100mg celecoxib amex, red cells are broken down in the macrophages of the reticuloendothelial system and the iron is released from haemoglobin rheumatoid arthritis types generic celecoxib 200 mg visa, enters the plasma and provides most of the iron on transferrin arthritis in my dogs back legs cheap celecoxib 200 mg mastercard. Only a small proportion of plasma transferrin iron comes from dietary iron arthritis in her fingers cheap 100 mg celecoxib amex, absorbed through the duodenum and jejunum rheumatoid arthritis diet gluten buy celecoxib 100mg low price. Some iron is stored in the macrophages as ferritin and haemosiderin arthritis pain relief cream reviews buy celecoxib 200 mg online, the amount varying widely according to overall body iron status. It contains up to 20% of its weight as iron and is not visible by light microscopy. This is because the body has a limited ability to absorb iron and excess loss of iron as a result of haemorrhage is frequent. These include lack of iron (iron deficiency) or of iron release from macrophages to serum (anaemia of chronic inflammation or malignancy), failure of protoporphyrin synthesis (sideroblastic anaemia) or of globin synthesis (- or -thalassaemia). Most of the iron in the body is contained in circulating haemoglobin (see Table 3. Iron is transferred from macrophages to plasma transferrin and so to bone marrow erythroblasts. A copper-containing enzyme, caeruloplasmin, catalyses oxidation of the iron to the ferric form for binding to plasma transferrin. Iron is also present in muscle as myoglobin and in most cells of the body in iron-containing enzymes. This tissue iron is less likely to become depleted than haemosiderin, ferritin and haemoglobin in states of iron deficiency, but some reduction of haem-containing enzymes may occur. Amount of iron in average adult Haemoglobin Ferritin and haemosiderin Myoglobin Haem enzymes. Chapter 3 Hypochromic anaemias / 37 When plasma iron is raised and transferrin is saturated the amount of iron transferred to parenchymal cells. Raised hepcidin levels therefore reduce iron absorption and iron release from macrophages. In iron deficiency, increased matriptase activity therefore results in decreased hepcidin synthesis. Iron absorption Organic dietary iron is partly absorbed as haem and partly broken down in the gut to inorganic Table 3. Haem is absorbed through a receptor, yet to be identified, on the apical membrane of the duodenal enterocyte. Inorganic iron absorption is favoured by factors such as acid and reducing agents that keep iron in the gut lumen in the Fe2+ rather than the Fe3+ state (Table 3. Ferroportin at the basolateral surface controls exit of iron from the cell into portal plasma. Low hepcidin levels in iron deficiency allow increased ferroportin levels and so more iron to enter portal plasma. Ferrireductase present at the apical surface converts iron from the Fe3+ to Fe2+ state and another enzyme, hephaestin (ferrioxidase) (which contains copper), converts Fe2+ to Fe3+ at the basal surface prior to binding to transferrin. Iron requirements the amount of iron required each day to compensate for losses from the body and for growth varies with age and sex; it is highest in pregnancy, adolescent and menstruating females (Table 3. Therefore these groups are particularly likely to develop iron deficiency if there is additional iron loss or prolonged reduced intake. Iron deficiency Clinical features When iron deficiency is developing, the reticuloendothelial stores (haemosiderin and ferritin) become completely depleted before anaemia occurs. As the condition develops the patient may show the general symptoms and signs of anaemia (see p. Reticuloendothelial (macrophage) stores are lost completely before anaemia develops. The cause of the epithelial cell changes is not clear but may be related to reduction of iron in iron-containing enzymes. In children, iron deficiency is particularly significant as it can cause irritability, poor cognitive function and a decline in psychomotor development. Causes of iron deficiency In developed countries, chronic blood loss, especially uterine or from the gastrointestinal tract, is the dominant cause (Table 3. Half a litre of whole blood contains approximately 250 mg iron and, despite the increased absorption of food iron at an early stage of iron deficiency, negative iron balance is usual in chronic blood loss. Increased demands during infancy, adolescence, pregnancy, lactation and in menstruating women account for the high risk of iron deficiency anaemia in these particular clinical groups. Newborn infants have a store of iron derived from delayed clamping of the cord and the breakdown of excess red cells. From 3 to 6 months there is a tendency for negative iron balance because of growth. From 6 months, supplemented formula milk and mixed feeding, particularly with iron-fortified foods, prevents iron deficiency. In pregnancy increased iron is needed for an increased maternal red cell mass of approximately 35%, transfer of 300 mg of iron to the fetus and because of blood loss at delivery. Menorrhagia (a loss of 80 mL or more of blood at each cycle) is difficult to assess clinically, although the loss of clots, the use of large numbers of pads or tampons or prolonged periods all suggest excessive loss. It takes about 8 years for a normal adult male to develop iron deficiency anaemia solely as a result of a poor diet or malabsorption resulting in no iron intake at all. In developed countries inadequate intake or malabsorption are only rarely the sole cause of iron deficiency anaemia. Gluten-induced enteropathy, partial or total gastrectomy and atrophic gastritis (often autoimmune and with Helicobacter pylori infection) may, however, predispose to iron deficiency. In developing countries, iron deficiency may occur as a result of a life-long poor diet, consisting mainly of cereals and vegetables. Hookworm may aggravate iron deficiency, as may repeated pregnancies or growth and menorrhagia in young females. Laboratory findings these are summarized and contrasted with those in other hypochromic anaemias in Table 3. Red cell indices and blood film Even before anaemia occurs, the red cell indices fall and they fall progressively as the anaemia becomes more severe. The blood film shows hypochromic microcytic cells with occasional target cells and 42 / Chapter 3 Hypochromic anaemias Table 3. Two populations of red cells are present: one microcytic and hypochromic, the other normocytic and well haemoglobinized. A dimorphic blood film is also seen in patients with iron deficiency anaemia who have received recent iron therapy and produced a population of new haemoglobinized normal-sized red cells. The platelet count is often moderately raised in iron deficiency, particularly when haemorrhage is continuing. Bone marrow iron Bone marrow examination is not essential to assess iron stores except in complicated cases. In iron deficiency anaemia there is a complete absence of iron from stores (macrophages) and from developing erythroblasts. In some laboratories, the transferrin content of serum is measured directly by immunodiffusion, rather than by its ability to bind iron, and is expressed in g/L. In iron deficiency anaemia the serum ferritin is very low while a raised serum ferritin indicates iron overload or excess release of ferritin from damaged tissues or an acute phase response. In men and postmenopausal women, gastrointestinal blood loss is the main cause of iron deficiency and the exact site is sought from the clinical history, physical and rectal examination, by occult blood tests, and by appropriate use of upper and lower gastrointestinal endoscopy and/or radiology. Chapter 3 Hypochromic anaemias / 45 cell antibodies, Helicobacter infection and serum gastrin level may help to diagnose autoimmune gastritis. In difficult cases a camera in a capsule can be swallowed which relays pictures of the gastrointestinal tract electronically. Tests for transglutaminase antibodies and duodenal biopsy to look for gluteninduced enteropathy can be valuable. Hookworm ova are sought in stools of subjects from areas where this infestation occurs. If gastrointestinal blood loss is excluded, loss of iron in the urine as haematuria or haemosiderinuria (resulting from chronic intravascular haemolysis) is considered. Oral iron the best preparation is ferrous sulphate which is cheap, contains 67 mg iron in each 200-mg tablet and is best given on an empty stomach in doses spaced by at least 6 hours. Oral iron therapy should be given for long enough both to correct the anaemia and to replenish body iron stores, which usually means for at least 6 months. Iron fortification of the diet in infants in Africa reduces the incidence of anaemia but increases suceptibility to malaria. Ferric hydroxide-sucrose (Venofer) is administered by slow intravenous injection or infusion, usually 200 mg iron in each infusion. Iron dextran (CosmoFer) can be given as slow intravenous injection or infusion either in small single doses or as a total dose infusion given in one day. Ferric carboxymaltose (Ferinject) is also given by slow intravenous injection or infusion. There may be hypersensitivity or anaphylactoid reactions so parenteral iron is only given when there are high iron requirements as in gastrointestinal bleeding, severe menorrhagia, chronic haemodialysis, with erythropoietin therapy, and when oral iron is ineffective. The haematological response to parenteral iron is no faster than to adequate dosage of oral iron but the stores are replenished faster. Intravenous iron has also been found to increase functional capacity and quality of life in some patients with congestive heart failure, even in the absence of anaemia (see p. The pathogenesis of this anaemia appears to be related to decreased release of iron from macrophages to plasma because of raised serum hepcidin levels, reduced red cell lifespan and an inadequate Anaemia of chronic disorders One of the most common anaemias occurs in patients with a variety of chronic inflammatory and malignant diseases (Table 3. The anaemia is corrected by successful treatment of the underlying disease and does not respond to iron therapy. In many conditions this anaemia is complicated by anaemia resulting from other causes. Sideroblastic anaemia this is a refractory anaemia defined by the presence of many pathological ring sideroblasts in the bone marrow. These are abnormal erythroblasts containing numerous iron granules arranged in a ring or collar around the nucleus instead of the few randomly distributed iron granules seen when normal erythroblasts are stained for iron. Sideroblastic anaemia is diagnosed when 15% or more of marrow erythroblasts are ring sideroblasts. In the hereditary forms the anaemia is usually characterized by a markedly hypochromic and microcytic blood picture. This condition is discussed together with the other types of myelodysplasia in Chapter 16. In some patients, particularly with the hereditary type, there is a response to pyridoxine therapy. In many severe cases, however, repeated blood transfusions are the only method of maintaining a satisfactory haemoglobin concentration and transfusional iron overload requiring iron chelation therapy becomes a major problem. Ring sideroblast formation (<15% of erythroblasts) may also occur in the bone marrow in: other malignant diseases of the marrow. Lead poisoning Lead inhibits both haem and globin synthesis at a number of points. The anaemia may be hypochromic or predominantly haemolytic, and the bone marrow may show ring sideroblasts. The clinical history is particularly important as the source of the haemorrhage leading to iron deficiency or the presence of a chronic disease may be revealed. The country of origin and the family history may suggest a possible diagnosis of thalassaemia or other genetic defect of haemoglobin. Physical examination may also be helpful in determining a site of haemorrhage, features of a chronic inflammatory or malignant disease, koilonychia or, in some haemoglobinopathies, an enlarged spleen or bony deformities. Conversely, in iron deficiency anaemia the indices fall progressively with the degree of anaemia and when anaemia is mild the indices are normal or only just reduced below normal. Iron deficiency or the anaemia of chronic disorders may also occur in these subjects. In some -thalassaemia patients, however, occasional red cells show deposits of Hb H (4) in reticulocyte preparations (Chapter 7). Bone marrow examination is essential if a diagnosis of sideroblastic anaemia is suspected but is not usually needed in diagnosis of the other hypochromic anaemias. Chapter 3 Hypochromic anaemias / 49 Iron is present in the body in haemoglobin, myoglobin, haemosiderin and ferritin, and in iron-containing enzymes. Transferrin is the main transport protein in blood and hepcidin the main regulator of iron absorption and iron release from macrophages. Iron metabolism is regulated according to iron status by intracellular iron regulatory proteins and by control of hepcidin synthesis. The serum ferritin, serum iron and saturation of the iron binding capacity are reduced. In Western countries, it is usually caused by haemorrhage from the gastrointestinal or the female genital tract. It is treated by oral or parenteral iron and by treating, as far as possible, the underlying cause. Other frequent causes of a hypochromic, microcytic anaemia are the anaemia of chronic disorders, which occurs in patients with chronic inflammatory or malignant diseases, and - or -thalassaemia. Less frequent causes include sideroblastic anaemia (some cases) and lead poisoning. Sideroblastic anaemias are characterised by frequent ring sideroblasts in the marrow. Chapter 4 Iron overload / 51 There is no physiological mechanism for eliminating excess iron from the body and so iron absorption is normally carefully regulated to avoid accumulation. Iron overload (haemosiderosis) occurs in disorders associated with excessive absorption or may result from repeated blood transfusions in patients with severe chronic anaemias. Excessive iron deposition in tissues can cause serious damage to organs (haemochromatosis), particularly the heart, liver and endocrine organs. The serum ferritin is the most widely used test and this and the percentage saturation of transferrin (iron-binding capacity) are useful screening tests for iron overload and for monitoring its treatment. Liver biopsy with staining for iron and chemical analysis of iron content is useful for assessing both parenchymal iron (hepatic cells) and reticuloendothelial iron in Kupffer cells. Assessment of iron status the tests that can be performed to assess iron overload are listed in Table 4. Increased iron absorption Hereditary (primary) haemochromatosis Ineffective erythropoiesis. This allele has a prevalence of approximately 1 in 300 within the white North European population. A second mutation resulting in a histidine to aspartic acid substitution H63D is found with the C282Y mutation in approximately 5% of patients but homozygotes for the H63D mutation do not have the disease. Low serum hepcidin levels lead to high levels of ferroportin on the basolateral surface of the duodenal enterocyte and so lead to increased iron absorption and increased release of iron from macrophages. Chapter 4 Iron overload / 53 the consequent iron overload damages parenchymal cells and patients may present in adult life with hepatic disease, endocrine disturbances such as diabetes mellitus or impotence, melanin skin pigmentation. Diagnosis is suspected by increased serum iron, increased serum transferrin saturation and ferritin. There are differences of opinion whether patients without evidence of organ dysfunction from iron overload should be treated but most do venesect if the serum ferritin is raised, whatever the organ status. Rarer forms of genetic haemochromatosis are caused by mutations in the genes for hemojuvelin, transferrin receptor 2 and hepcidin (Table 4. They often present as severe iron overload with cardiomyopathy in children, adolescents or young adults. However, ferroportin mutations usually cause reticuloendothelial but not parenchymal cell iron overload but may rarely cause parenchymal overload, depending on the site of the mutation in ferroportin gene. Mutations of the ferritin light chain gene cause a raised monoclonal serum ferritin with cataracts resulting from ferritin deposition in the eye but no tissue iron overload. African iron overload this occurs in sub-Saharan African through a combination of increased iron absorption because of a genetic defect, possibly in the ferroportin gene, and a dietary increased iron overload caused by consumption of beverages of high iron content because of the use of iron cooking pots. Transfusional iron overload this develops in patients with refractory anaemias, most frequently thalassaemia major, who are sustained by blood transfusions. To make matters worse, iron absorption from food is increased in -thalassaemia major and many other anaemias secondary to ineffective erythropoiesis due to inappropriately low serum hepcidin levels. Skin pigmentation as a result of excess melanin and haemosiderin gives a slate grey appearance at an early stage of iron overload. In the absence of intensive iron chelation, death occurs in the second or third decade in thalassaemia major, usually from congestive heart failure or cardiac arrhythmias. It can detect increased cardiac iron before sensitive tests detect impaired cardiac function.
The binge eating and compensatory behaviors both occur rheumatoid arthritis quality of life questionnaire pdf 100mg celecoxib free shipping, on average joints in dogs legs buy celecoxib 200mg line, at least once a week for 3 months D juvenile rheumatoid arthritis medication treatment effective 100mg celecoxib. The disturbance does not occur exclusively during episodes of anorexia nervosa Table 5 arthritis in the feet and knees purchase celecoxib 200 mg otc. The binge eating episodes are associated with three (or more) of the following: 1 arthritis knee ligaments celecoxib 100mg low price. The binge eating is not associated with the recurrent use of inappropriate compensatory behavior arthritis in young horses neck buy 100 mg celecoxib with visa. Bulimia nervosa (of low frequency and/or limited duration): All of the criteria for bulimia nervosa are met arthritis in back l4 l5 purchase celecoxib 200 mg with mastercard, except that the binge eating and inappropriate compensatory behaviors occur arthritis pain after chemo purchase 100mg celecoxib amex, on average, less than once a week and/or for less than 3 months. Binge eating disorder (of low frequency and/or limited duration): All of the criteria for binge eating disorder are met, except the binge eating occurs, on average, less than once a week and/or for less than 3 months. Night eating syndrome: Recurrent episodes of night eating, as manifested by eating after awakening from sleep or by excessive food consumption after the evening meal. Anorexia nervosa primarily affects adolescent girls and young women and is characterized by distorted body image with a pathological fear of becoming fat that leads to excessive dieting and severe weight loss. Criterion A focuses on behavior like restricting calorie intake and no longer includes the word "refusal" in terms of weight maintenance, since that implies intention on the part of the patient and can be difficult to assess. Bulimia nervosa is characterized by frequent episodes of binge eating followed by behaviors such as selfinduced vomiting, abuse of laxatives, diuretics or other medications, fasting, or excessive exercise to avoid weight gain. Binge eating disorder is defined as recurring episodes of eating significantly more food in a short period of time than most people would eat under similar circumstances, with episodes marked by feelings of lack of control. The person may have feelings of guilt, embarrassment, or disgust, and may binge eat alone to hide the behavior. This disorder is associated with marked distress and occurs, on average, at least once a week over three months. While overeating is a challenge for many, recurrent binge eating is much less common, far more severe and is associated with significant physical and psychological problems. In contrast, the prevalence in team sports is about 15% in elite female athletes, while corresponding values in technical sports are about 17%. In addition, there are factors specific to the athletic community, such as dieting to enhance performance, personality factors (such as perfectionism, obsessiveness), pressure to lose weight, frequent weight cycling, early start of sportspecific training, overtraining, recurrent and nonhealing injuries, unfortunate coaching behavior, and regulations in some sports. Injured athletes often experience undesired weight gain, combined with the negative effects that injuries may cause. However, it is reasonable to expect that the health consequences reported among nonathletes will also apply to athletes. Most complications of anorexia nervosa, such as depletion of muscle glycogen stores, loss of muscle mass and bone mass, and anemia, occur as a direct or indirect result of starvation. These conditions are associated with fragility fractures and stress fractures, even in the young population. Severe complications such as collapse of the femoral head and hip fracture have been reported even among athletes. The consequences of bulimia nervosa have not been studied as extensively as anorexia nervosa, possibly due to more normal ranging body weight values and because it is a more difficult problem to diagnose. While multiple neuroendocrine abnormalities may be present, they tend to be less pronounced than with anorexia nervosa. The loss of fluids and electrolytes during purging can result in serious medical problems such as acidbase abnormalities, cardiac rhythm disturbances, and dehydration. The variety of medical problems related to bulimia nervosa includes tooth decay, parotid enlargement, carpopedal spasm, stomach rupture, metabolic alkalosis, hypercarotenemia, hypokalemia, and pancreatitis. Menstrual dysfunction and impaired bone health are also present in this group, but the incidence is highly variable and seems to increase with the presence of previous anorexia nervosa. The weight gain related to binge eating will likely lead to the same medical problems in athletes as in nonathletes, especially in those athletes participating in the more technical, less endurance type sports. Furthermore, the risk of overuse injuries and other muscle skeletal problems is likely higher than in nonbinging athletes. In the sports medicine field, the relationship between energy availability, menstrual function, and bone health is referred to as the female athlete triad (the Triad). Each clinical condition of the Triad comprises the pathologic end of a spectrum of interrelated subclinical conditions between health and disease. Typically function by suppressing appetite and may cause a slight increase in metabolic rate. May induce rapid heart rate, anxiety, nervousness, inability to sleep, and dehydration. Weight loss is primarily water and any weight lost is regained once use is discontinued. Dehydration and electrolyte imbalances, constipation, cathartic colon, and steatorrhea are common. Weight loss is primarily water and any weight lost is quickly regained once use is discontinued. Gastrointestinal problems, including esophagitis, esophageal perforation, and esophageal ulcers may occur. Effect on performance Poor exercise performance due to general weakness, reduced ability to cope with pressure, decreased muscle force, and increased susceptibility for diseases and injuries. May be addictive and the athlete can develop resistance, thus requiring larger and larger doses to produce the same effect. Saunas Excessive exercise Weight loss is primarily water and any weight lost is quickly regained once fluids are replaced. In recent years, studies have found the Triad in elite athletes representing both leanness and nonleanness sports, in female college athletes and highschool athletes, as well as in women who are not competing in sports. A study of the entire population of female elite athletes in Norway demonstrated that 4. Therefore, we recommend that health personnel working with female athletes look closely for evidence of Triad disorders. It should also be noted that an additional component of Triad disorders, endothelial dysfunction, has recently been introduced in the literature. Endothelial dysfunction is an important factor in the pathogenesis of cardiovascular disease, which needs further examination in future studies on athletes. This is especially true in females and particularly in sports where leanness or a low body weight is considered important for optimal performance. Delayed menarche, bone growth retardation, reduced height, weight, and body fat have been reported in gymnasts. Performance consequences It goes without saying that health should be more important than performance for the athlete and their respective team. For them, a focus on performancerelated consequences may provide more incentive to improve than a focus on the health consequences in terms of being willing to cooperate in a treatment program. It has been shown that cortisol maintains plasma glucose concentration by breaking down skeletal muscle into amino acids for gluconeogenesis in the liver. Stimuli such as starvation or intense training leading to reduced plasma glucose concentration may therefore result in atrophy, leading to decreased muscle strength and power and an increased injury risk. Endurance performance is likely to be impaired if the liver and muscle glycogen levels are lower or if the athlete is dehydrated or anemic. Further, acute dehydration can lead to loss of motor skills and coordination, while a reduced blood volume may impair thermoregulatory capacity during exercise, which can lead to impaired performance. In addition to causing energy and nutrient deficiencies, purging poses some unique problems regarding athletic performance, including most notably dehydration and severe electrolyte imbalances. Electrolyte imbalances may slow nerve conduction velocity and muscle contraction leading to increased reaction times and reduced recovery rates. Electrolyte abnormalities over time may also lead to a loss of muscle mass followed by decreased strength and power. Other consequences related to fluid and electrolyte imbalances not coincident with peak performance are fatigue, lightheadedness, insomnia, and reduced ability to concentrate (Table 5. For athletes, the stress of constantly obsessing about food, denying hunger, agonizing over body weight, and fearing increased body weight can be mentally exhausting. Special considerations One challenge for health personnel, coaches, and athletes is that some who severely restrict their energy intake for short periods and lose weight do experience an initial, albeit transient, improvement in performance. One explanation may be due to the initial physiological and psychological consequences of starvation where the athlete may feel lighter due to weight loss and thus experience a psychological boost, particularly when competing in sports in which being lighter can correlate with improved performance. Most athletes will only divulge their symptoms when asked directly by their coach, teammates, or sport physician and allied health personnel. These instruments have been validated in the general population, but are not well enough tested for sensitivity or validity with athletes. Even though selfreport questionnaires are valuable and easy to use, it is recommended that they are complemented with other informationgathering tools, such as indepth personal interviews. Are there any types of food you try to avoid or do you have any "forbidden" foods Possibly question the athlete about purging methods (preferably referring to the past) Questions about weight What have your highest and lowest body weight been during the last year What is the longest period of time you have experienced lack of menstrual bleeding Questions about training and injuries Please describe your normal training volume (frequency, intensity, duration) Have you altered training methods, volume, or intensity recently (or in the past) Eating habits are characterized by the same restrictive intake of "acceptable" foods each day. A person with bulimia nervosa constantly attempts to postpone calorie consumption then overeats in the afternoon and evening. Therefore, focus should also be placed on younger athletes (high school age) in terms of screening and identification of these problems. Prime opportunities include the preparticipation exam, an annual checkup, or any time an athlete is evaluated for a related problem, such as recurrent injury, stress fracture, amenorrhea, or illness. Careful reflection required whether assessment of body mass and composition may trigger more problems. Biochemical Complete blood count Complete metabolic panel Lipid panel Iron profile Thyroid function. If preparticipation physical, general medical history, including menstrual history/status, bone health, history of stress fracture and other injuries, osteoporosis. Energy intake, total daily energy expenditure, resting metabolic rate, exercise energy expenditure, energy availability, energy density; macronutrients (expressed in gram/kilogram per day) and micronutrients, fluid balance, and hydration, including sweat rate, food restrictions, allergies, intolerance; scary foods; nutrient and fluid timing; carbohydrate availability during intense training; carbohydrate and fiber related to appetite; recovery nutrition; competition preparation and fueling, travel nutrition and appetite issues during travel or intense training. Targetspecific issues such as weightmaking or body image depending on sport; evaluation of training/competition plan in discussion with coach; countries at risk for inadequate food access and food safety concerns; work/school schedules and time for food preparation, eating, recovery; level of athlete and experience. Special considerations Unfortunately, it is often rare for an athlete to admit an eating problem during the first consultation. They may complain that others make suspicious comments about their eating behavior, their weight loss, or related issues. Regardless of which complaints or symptoms are presented during the first consultation, healthcare professionals should search for underlying causes. Questions about food intake, dieting methods, and training should be straightforward and concrete. In addition, coaches and parents can be part of the treatment team if they have a positive relationship with the athlete. Often though, complicating medical factors are present, and therefore, the physician should remain central in the follow up process. Among athletes, there is limited evidence related to the effect of different treatment methods. Training and competition recommendations during treatment For athletes who agree to treatment, eligibility to continue training while symptomatic should be determined on an individual basis by treatment Disordered eating and eating disorders in female athletes 53 Table 5. Group therapy Family therapy Nutritional counselling Pharmacotherapy Source: Reproduced with permission from Sundgot-Borgen (2002). At minimum, the athletes should be cleared medically and psychologically, their training should not be used as a means to diet or control weight, and they should be required to follow a prescribed set of health maintenance criteria. Sometimes negotiation with athletes is important in areas of energy intake and return to training and competition. It is recommended that support staff in other countries also follow these guidelines or use them as a starting point for further developing their management of this complex problem. For athletes willing to follow the recommended treatment and include their coach (if athlete and coach have a good relationship) and also the parents (if appropriate) in the treatment, the compliance and prognosis is generally good. The athlete may return to competition when goal weight or body composition is reached, and they are mentally prepared and really want to compete. For athletes who refuse treatment, both training and competition should be withheld until they agree to participate. Summary and recommendations Sports and physical activity is healthy for females at all ages when carried out appropriately and should be promoted for both health benefits and enjoyment. Female athletes should undergo annual screening in order to make early identification possible. We should not restrict screening to elite athletes, leanness athletes, or older athletes, and there is a value in screening younger athletes. Ideally, these individuals should also be familiar with and have an appreciation for the sport environment. Finally, potential treatment initiatives should be multidisciplinary in origin and be initiated as early as possible. Drinkwater B, Loucks A, Sherman R, SundgotBorgen J, and Thompson R; International Olympic Committee Medical Commission Working Group Women in Sport. Lebrun2,3 1Sport Medicine Center, Department of Orthopedic Surgery, the Hadassah-Hebrew University Medical Center, Jerusalem, Israel of Family Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada 3Glen Sather Clinic, University of Alberta, Edmonton, Alberta, Canada 2Department Bone health in the female athlete this chapter will review what is currently known about bone health in the female athlete, including assessment techniques and various factors that impact bone health-both positively (such as exercise) and negatively (including the Female Athlete Triad) (Figure 6. The skeleton is comprised mainly of two types of bone tissues-dense bone tissue (compact bone), found primarily in the outer part of cylindrical long bones, and spongy bone tissue (trabecular bone) that includes many spaces that give it the appearance of a sponge. As bone ages, the amount of bone is decreased and the structural integrity of trabecular bone is impaired. These definitions were developed for the evaluation and management of postmenopausal women with low bone density and are frequently used as decision points for initiation of treatment. The main disadvantage of this method is that it does not reflect other important factors 56 Bone health 57 Figure 6. However, menstrual dysfunction associated with low energy availability may compromise optimal bone mineral density. Another drawback is it is actually a 2dimensional measurement and therefore can be confounded by vertebral body size, and surrounding soft tissues leading to measurement errors. The main disadvantages to this method are its low availability, high price, and the high radiation doses involved. For these reasons, this assessment technique is sometimes used in initial screening for osteoporosis. The acquisition of bone that occurs during childhood and adolescence accounts for 90% of adult bone mass. This also accounts for other bone health parameters such as bone geometry, bone turn over markers, and risk for osteoporotic fractures. There is an additional rapid decrease in the few years immediately during and after menopause, especially in trabecular bone (Figure 6. Both lean body mass as well 100 90 80 Age (years) 70 60 50 Postmenopausal decade Wrist fracture Vertebral fracture Hip fracture 20 40 60 Age (years) Figure 6. These include dietary fibers, caffeine, alcohol, phosphorus, vitamin K, protein, sodium, and more. Researchers do not agree about the effect of increased consumption of caffeine on bone density. Caffeine seems to have little impact, if any, on calcium and bone density in people who meet the daily calcium intake recommendations. The forces include compression forces from gravity, loads placed upon the bone with activity, and pulling forces at the tendon interface. Mechanical loading in childhood and during adolescence positively affects bone health in adulthood and decreases osteoporotic fractures, probably by increasing peak bone mass, whereas inactivity is associated with lower bone mass. Physical activity needs to be continuous throughout life in order to maintain the peak bone mass achieved and to prevent bone loss at any age. The osteogenic effect of physical activity on bone is especially prominent in highimpact sports such as running, jumping, and ball games. On the other hand, swimming and cycling, which are nonimpact sports (nonweight bearing) do not affect bone density much. The effect of physical activity Bone health 59 on bone mass depends also on the specific sites of impact of the various sport activities and therefore varies between bones. It appears that calcium intake especially during childhood, acts synergistically with physical activity to promote bone health, but physical activity has a larger osteogenic effect compared with calcium intake. Estrogen is osteoprotective, primarily through its action to inhibit bone resorption. Progesterone is thought by some researchers to have a role in stimulating bone formation. In adolescents and young women, the sustained production of estrogen is essential for the maintenance of bone mass. Testosterone stimulates osteoblasts, and through its aromatization to estrogen, may also inhibit osteoclastic activity. Leptin regulates bone formation through both central (hypothalamic) and peripheral (direct) pathways, and leptin deficiency is associated with low bone mass.
