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J Clin Oncol 6:1856–1862; Classen J buy famvir 250mg online new antiviral drugs, Souchon R generic famvir 250mg with amex antiviral in pregnancy, Hehr T et al (2002) Radiotherapy for early stages testicular seminoma: patterns of care study in Germany order famvir with mastercard antiviral herpes medication. However cheap 250 mg famvir mastercard hiv infection rate in india, the effect of fractionated radiation on fertility is substantial, as detailed in Table 20. J Natl Cancer Inst Monogr 34:12–17 636 Ugur Selek Follow-Up After completion of definitive treatment, long-term follow-up to detect sec- ond primary tumors, recurrences, or late side effects is recommended (Table 20. Chapter 20 Testicular Cancer 637 Acute adverse effects during radiation therapy for seminoma are usually mild, and may include nausea/vomiting, diarrhea, fatigue, and transient de- cline in blood count. Mehta , Nitika Thawani 3 and Subhakar Mutyala Key Points ? Endometrial cancer is the most common gynecologic malignancy and the 4th most common cancer in women in the United States. Stage, depth of invasion, lymphovascular space involvement, and lymph node in- volvement are the most important prognostic factors. It is the 4th most common cancer in women, and ranks 8th among causes of cancer death. Endometrial carcinoma arises from hyperplasia of the endometrial lining, resulting from exposure to unopposed estrogens. Mehta, Nikita Thawani and Subhakar Mutyala Pathology the majority of uterine epithelial tumors are adenocarcinomas of endome- trioid subtype. In postmeno- pausal patients, vaginal bleeding is unexpected and may range from spotting to heavy blood loss. Pre- or perimenopausal patients may present with men- orrhagia and/or metrorrhagia. Although uncommon, a routine Pap smear for cervical cancer screening may detect abnormal endometrial cells. Mehta, Nikita Thawani and Subhakar Mutyala Diagnosis the diagnosis of endometrial cancer depends on the clinical presentation, history and physical examination, including a thorough gynecologic exami- nation, imaging studies, and laboratory tests ure 21. Endometrial Cancer Suspected by clinical presentation Complete History and Physical Examination Endometrial +/- Trans-vaginal biopsy ultrasound - Non-diagnostic + Dilatation and curettage Pre-operative Observe +/- hysteroscopy assessment - + Figure 21. Mehta, Nikita Thawani and Subhakar Mutyala Prognostic Factors Survival is strongly influenced by the stage at diagnosis (Table 21. Traditionally done through a vertical midline incision, a laparoscopic technique has recently been used. Pathologic data has shown that certain high-risk pathologic features predict higher rates of local recurrence. Systemic therapy is typically used in locore- gionally advanced, recurrent, or metastatic disease (Table 21. Treatment of Early-Stage Endometrial Cancer Surgical resection is the initial management of choice. The pathologic speci- men is then examined for the risk factors listed in “Prognostic Factors” along with patient-related factors to determine a patient’s risk of locoregional re- currence. The patient may be offered adjuvant therapy based on a significant risk of recurrence (Table 21. The general trend shows a local control benefit, but this does not translate into a survival difference. Of note, there are inherent differences between the studies with respect to lymph node surgical staging and treatment with vaginal brachytherapy that make concrete conclusions difficult to make. Mehta, Nikita Thawani and Subhakar Mutyala As seen in the preceding tables and algorithm, there is a mixed recommen- dation of treatment options for the intermediate risk group of patients. This occurs due to the various disease- and patient-related factors that help make a risk assessment. Grade 2/3 histology Age <50 Lymphovascular invasion Outer 1/3 myometrial invasion Age 50-70 Age >70 3 risk factors 2 risk factors Only 1 needed needed risk factor needed Figure 21. The details of vaginal brachytherapy technique and dose fractionation are discussed below. Chapter 21 Endometrial Cancer 653 Locoregionally Advanced Endometrial Cancer Adjuvant Radiation Therapy Patients with locoregionally advanced endometrial cancer as determined by surgical pathology are recommended to undergo adjuvant pelvic irradiation. Para-aortic irradiation may be added in cases where pelvic or para-aortic lymph nodes are positive. Mehta, Nikita Thawani and Subhakar Mutyala Treatment of Less Common Histologic Subtypes Certain histologic subtypes, such as carcinosarcoma and serous adenocarci- noma, have a different natural history and course of disease than the more common endometrioid adenocarcinoma subtype. The treatment course for these less common subtypes is less well defined, although some studies are available to guide our treatment decisions (Tables 21. Aides that may be used during the simulation included a Foley catheter, intravagi- nal cuff marker, oral, and/or intravenous contrast. External radiation fields should encompass the vaginal cuff (or the entire uterus in inoperable cases) and regional pelvic lymph nodes. Mehta, Nikita Thawani and Subhakar Mutyala Brachytherapy Intravaginal brachytherapy allows the delivery of a high dose to the vagina while minimizing dose to organs at risk. A vaginal cylinder is the most com- mon applicator used, and the largest diameter feasible is preferable. Int J Radiation Oncology Biol Phys 76:S123–S129 Common acute radiation-induced adverse effects include fatigue, cystitis, loose bowel movements, and diarrhea. Late adverse effects include chronic cystitis, chronic proctitis, intractable diarrhea, small bowel obstruction, and vaginal stenosis and dryness. Mehta, Nikita Thawani and Subhakar Mutyala Follow-Up Patients should follow-up with their surgeon and radiation oncologist at regu- lar intervals (Table 21. The patient may be given a vaginal dilator at the first follow-up visit to help prevent vaginal stenosis. Gafney Key Points ? Cervical cancer is the ffth most common cancer in women and the third lead- ing cause of cancer death in women worldwide. The role of adjuvant chemotherapy following concurrent radiation/chemotherapy remains to be determined. Gaffney Key Points (continued) ? Total treatment course duration of more than 8 weeks is associated with de- creased survival. Epidemiology and Etiology Cervical cancer is the fifth most common cancer in women worldwide. However, the incidence remains high worldwide, with an estimated 471,000 new cases and 300,000 deaths annually. In many medically underserved countries, cer- vical cancer remains the most common cancer and the leading cause of death for women. Tumors of the cervix grow exophytical- ly on the portio or expand into the endocervical region. Spread occurs superiorly along the lower uterine segment, laterally to the parametria and uterosacral ligaments toward the pelvic walls and pelvic lymphatics, posteriorly to the perirectal region, and anteri- orly to the bladder. Despite the proximity of bladder and rectum, mucosal involvement of these organs is uncommon.

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Manic Depression patients have impaired metabolism of Inositol and supplemental Inositol may help to overcome this impaired metabolism discount 250mg famvir antiviral immunity. Incorporation of inositol into the phosphoinositides of lymphoblastoid cell lines established from bipolar manic-depressive patients order generic famvir hiv infection timeline of symptoms. Lymphoblastoid cell lines established from patients suffering from bipolar manic-depressive psychosis or from a control group have been used to study the metabolism of the polyphosphoinositides in these cells 250mg famvir free shipping hiv aids infection rates for south africa. Cells were incubated for up to 6 h in [3H]inositol and the extent of inositol incorporation into the mono- buy generic famvir from india side effects of antiviral meds, di- and triphosphoinositides was measured after extracting the water- and lipid-soluble inositol-containing pools. Although both the uptake of inositol and the ‘free’ intracellular inositol pool sizes were similar in the two cell groups, the incorporation of [3H]inositol into the phosphoinositides of the cells derived from bipolar manic-depressives was significantly less (by around 50-60%) than that which occurred in the control cells. A case of mania apparently secondary to vitamin B12 deficiency appeared without other overt clinical features of pernicious anemia and resolved with B12 replacement. Six months later, the patient was receiving monthly B12 injections and his mental status remained normal. Human case study demonstrated that mania can occur in conjunction with vitamin B12 deficiency and that vitamin B12 injections reversed this mania. Since this study it has been demonstrated that oral vitamin B12 is as effective as injections for restoring vitamin B12 levels in cases of vitamin B12 deficiency. Preliminary results of a double-blind, crossover comparison of normal vanadium intake with reduced intake in manic and depressed subjects are reported. These results are in keeping with the suggestion that vanadium may be an aetiological factor in manic depressive illness. Tryptophan alleviates Manic Depression and is beneficial when suicidal tendencies exist in Manic Depression patients: Chouinard, G. Tryptophan in affective disorders: Indoleamine changes and differential clinical effects. Tryptophan (9,000 mg per day) potentiates the beneficial effects of Lithium in the treatment of Manic Depression. This double-blind, placebo-controlled study involved manic depression patients (aged 18 – 65 years). All patients had experienced at least one manic or hypomanic episode during the preceding year. The significant difference in relapse rate and response was highly clinically significant. A comment on the above study: “this study may represent the first demonstration of an effective therapy for bipolar disorder. The means via which fish oils benefit manic depression patients may involve their ability to increase serotonin levels in the brain. Fish oil supplement reduces bipolar symptoms and improves outcomes in pilot study. Dietary Reference Intakes for Tjiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Dietary Reference Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Annals of the New York Academy of Sciences 378 (Thiamin: Twenty Years of Progress): 316–326. Intestinal absorption of dietary folates (in Folic acid metabolism in health and disease). The B vitamins are well documented for brain Stimulation and are one of the few documented thinking enhancers. The Russian scientists in the 1950 have shown the profound oxygenation stimulation effects of Pangamic Acid (known as B15). The sports effects were profound and the soviets lead the world in Olympic events for the next decades. Since the wellness of any organ or organism is dependent on how well it uses oxygen, Pangamic acid has an overall tonic or panacea for any condition. Perhaps a combination of other known oxygenators with pollen can provide a synergistic effect for cellular oxygenation. Since the action of the pollen seems to be from the nucleotides and the trace elements in the pollen, providing an extra source of nucleotide might facilitate absorption. B12, folic acid and most importantly, B15 were also added to the formula for their strong oxygenation abilities and their methyl donor action, fortifying both lung and liver action. This addition of the higher B complex (B12, folic acid, B15, and B17) helps stabilization of nerval function as well. Oxygenation and stabilization of blood pH is also dependent on zinc in the form of zinc anhydrase and other zinc dependent enzymes. Since the average American diet is deficient in zinc, a trace amount is added to the formula. Here the microamperage output of the body is measured and after the patient takes a deep breath, the amperage increases in correlation to the oxygen absorbed in the blood stream. Random selection of participants, all twenty to thirty-five years of age, were healthy, nonprofessional athletes. Group 2 was given Cerniltons (Swedish bee pollen sports tab) in two pills, twice a day. Distances were recorded before the supplementation program and again ten days later. Twelve somewhat out-of-shape participants were asked to take either the flower pollen or our own formula, and then initiate an n exercise program of weights and running. After three days participants were asked to rate the muscle pain and strain that they experienced from exercise. Ability to flex Results the results of experiment #1 showed conclusively that the Bee Pollen formula, versus the control and the Flower Pollen, was able to put oxygen into cells. The results of experiment #2 showed an increase of approximately one tenth of a mile in performance of the athletes versus control or Bee Pollen.

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The second part of the artery gives off a series of branches to the right atrium (21 purchase famvir overnight antiviral tea. The largest of these branches runs along the lower border of the heart and is called the right marginal branch buy 250mg famvir with visa hiv infection timeline symptoms. The third part of the artery also gives off atrial and ventricular branches to the right atrium and to the diaphragmatic wall of the right ventricle generic 250mg famvir with mastercard hiv early symptoms yeast infection. The posterior interventricular branch of the right coronary artery gives off branches to the diaphragmatic wall of the right ventricle; and some to the left ventricle purchase famvir 250mg online antivirus windows free. Some branches run upwards and forwards into the posterior one-third of the interventricular septum. The anterior interventricular branch gives off several large branches to the anterior wall of the left ventricle (21. One of these is specially prominent and runs downwards and to the left between the anterior interventricular and circumfex arteries. Sometimes the diagonal branch arises directly from the trunk of the left coronary artery. The anterior interventricular branch also gives off a few small branches to the right ventricle. The anterior interventricular branch also sends several branches downwards into the interventricular septum. Some branches to the septum arise from the terminal part of the artery after it has entered the posterior interventricular groove. The circumflex branch gives off several branches to the wall of the left ventricle. The circumfex artery also gives some branches to the diaphragmatic surface of the left ventricle. Almost the whole of the left atrium is supplied by branches of the circumfex artery. Instead of ending in the atrioventricular groove, the circumfex branch may continue into the posterior inter- ventricular groove replacing the posterior interventricular branch of the right coronary (21. From the foregoing descriptions of the distribution of the right and left coronary arteries, it is seen that the right atrium and ventricle are supplied mainly by the right coronary artery, and the left atrium and ventricle by the left coronary artery. However, small parts of each ventricle, and of the left atrium are supplied by the artery of the opposite side. The anterior two-thirds of the interventricular septum is supplied by the left coronary artery, and its posterior one-third by the right coronary artery. Some small branches given by the anterior interventricular branch to the right atrium are not drawn for sake of clarity 21. The left coronary artery and its branches are seen in A, and the right coronary artery in B. In this case the posterior interventricular branch is derived from the left coronary artery (instead of the more common derivation from the right coronary). Such a condition is referred to as left dominance 430 Part 3 ¦ Thorax CliniCal Correlation Coronary Angiography 1. The coronary arteries and their branches can be visualised by coronary angiography and sites of narrowing determined (21. In this connection, it is necessary for the student to know that the nomenclature used in clinical texts for some branches of the coronary arteries are different from those in textbooks of anatomy as follows: a. The anterior interventricular branch of the left coronary artery is described as the anterior descending branch. The posterior interventricular branch of the right coronary artery is described as the posterior descending branch. The right marginal branch of the right coronary artery is named the acute marginal branch. The left marginal branch of the left coronary artery (which may be multiple) is referred to as the obtuse marginal branch. They are meant for distribution of blood to the head and neck and to the upper limbs. They reach the head and neck by passing through the superior mediastinum of the thorax. All these arteries arise from the summit of the arch of the aorta that lies at the level of the middle of the manubrium sterni (or the disc between the third and fourth thoracic vertebrae). From here, it runs upwards and backwards and as it does so it winds round the trachea to reach its right side. It ends behind the right sternoclavicular joint by dividing into the right common carotid and right subclavian arteries. The left common carotid artery arises from the arch a little to the left of the brachiocephalic artery. The left subclavian artery arises from the arch of the aorta a little to the left of and behind the left common carotid artery, the origin lying to the left of the trachea. The artery runs almost vertically along the left side of the trachea to enter the neck at the level of the left sternoclavicular joint, where it lies behind the common carotid artery. Apart from several small branches to the oesophagus, the pericardium, the diaphragm (phrenic branches) and to lymph nodes in the posterior mediastinum (mediastinal branches) it gives off the bronchial, posterior intercostal and subcostal arteries. The posterior intercostal and subcostal arteries have already been described (Chapter 18). These arteries supply the bronchi, the connective tissue of the lung and related lymph nodes. It may arise from the upper left bronchial artery or from the third right posterior intercostal artery. Other Arteries in the Thorax the internal thoracic artery, and the superior intercostal artery arise in the neck and descend into the thoracic wall. Veins that Drain the Heart These are the coronary sinus and its tributaries; and some small veins. Large Veins Present in the M ediastinum These are the superior vena cava, the right and left brachiocephalic veins, the inferior vena cava, and the pulmonary veins. Most of the veins draining the heart wall end in a wide vein, about two centimeters long, called the coronary sinus (21. The great cardiac vein is seen mainly on the sternocostal aspect of the heart (21. It ascends in the anterior interventricular groove (parallel to the anterior interventricular branch of the left coronary artery). Veins not normally seen from the front are not normally seen from the back are drawn as if the drawn as if the walls of the chambers of the heart were walls were transparent transparent 2. At the upper end of the groove the vein turns to the left in the coronary sulcus (alongside the circumfex branch of the left coronary artery), winds round the left margin of the heart and ends in the left extremity of the coronary sinus.

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However discount 250mg famvir visa antiviral infection, treatment information and the risks and benefits for a meaningful deliberation and agreement on of each generic famvir 250mg mastercard hiv infection without ejaculation. Underlying patient needs authorization from a physician to this approach are two key assumptions purchase famvir with a mastercard hiv infection and stroke. The second is that the physician should not ing an agreement that both can live with buy cheap famvir 250 mg online antiviral lip balm. As have an investment in the decision-making pro- noted above, if agreement cannot be reached the cess or the decision made. In other words, patient process may terminate at this point unless one sovereignty reigns in this approach, with the phy- party can be persuaded to adopt the other’s pre- sician providing technical input only, in the form ferred option. The different approaches described above are In a shared approach both patient and physi- ‘ideal types’ in the sense that the role depictions cian deliberate about treatment options in an for physician and patient in each model are defined interactive process where it is assumed that both as invariant, predictable and distinct from one parties have a legitimate investment in the treat- another. This emphasis on behaviour of physicians and patients in each interaction ensures patient input, but also makes model are rarely so clear-cut. There are various the process potentially more cumbersome and ‘in-between’ approaches to treatment decision time-consuming than the other approaches. In a making which do not conform precisely to one of shared process both parties need to be willing to the ideal types but rather lie somewhere in- engage with each other, exchanging both infor- between and may be characterized as shades of mation and treatment preferences. For example, starting with the paternalistic can legitimately give a treatment recommenda- model, the more that each stage moves from a phy- tion to patients and try to persuade them to sician-dominated encounter to one where the accept the recommendation. However, physicians patient’s input is recognized, nourished and val- using this approach would also have to listen to ued, the more the model evolves into a shared patients and try to understand why they might approach. If no agreement can be treatment decision-making processes are likely to reached, several possibilities can occur. The phy- reflect some form of in-between approach rather sician would need to decide whether to endorse than a pure type. The patient would need to decide should be noted that we have described only the whether to stay with this physician or to seek most simple type of interaction, that between one advice elsewhere. Nonetheless, the framework provides the paternalistic and informed models, the deci- an analytic tool for articulating the different sion maker is one person; in the first case it is the stages in treatment decision making, identifying physician and in the second, the patient. However, the defining characteristics of the paternalistic, neither party is totally autonomous because each informed and shared approaches to undertaking faces constraints in implementing the decision. Since then, a citation making context to which our model could be analysis undertaken by Makoul & Clayman in applied. Our goal was to assess the degree of con- 2006 suggests widespread dissemination of and gruence in the meaning of shared decision making references to this model in the international treat- as defined in our conceptual model and as per- ment decision-making literature. In the questionnaire we included four stantial uncertainty, where there is often no right clinical treatment decision-making examples or or wrong answer, and where treatments vary in scenarios in which the roles of the patient and their impact on the patient’s physical and psycho- the physician were systematically varied. Information about the risks and benefits of After looking at your medical records and examining each choice is given and discussed with you. The you the doctor presents a treatment that he/she doctor asks you to decide on a treatment and states thinks is best for you. Example 4 Example 2 After looking at your medical records and examining After looking at your medical records and examining you the doctor presents you with treatment you the doctor presents you with the treatment choices. Information about the risks and benefits of of each choice is given and discussed with you. You ask questions and obtain all the information you ask questions and obtain all the information you want from the doctor. The doctor recommends a your preferences for treatment given your lifestyle treatment that you accept. In example 2, information was shared oncologists the extent to which they practised between patient and physician but the physician shared decision making with their patients, their alone made the treatment decision (what we comfort level with this approach and perceived call some sharing). More provided information to the patient but the latter physicians from each specialty (89% of surgeons was the sole decision maker (what we call an and 87% of oncologists) reported high comfort informed approach). In example 4, the patient levels with example 4 (the pure shared approach) and physician both participated in all phases of than with any other of the examples presented. None of the examples had making was like example 4 than any other example any labels attached so physicians were unaware presented (69% of surgeons and 56% of oncolo- that we had deliberately constructed each scenario gists). Interestingly, reported comfort levels with to represent a particular type of decision-making example 4 were 20% higher for surgeons and 31% approach. Few physicians lack of time, patient anxiety, patient lack of infor- (less than 5%) described example 1, the paternalis- mation or misinformation, and patient unwilling- tic scenario, as shared. The latter barrier to reflect a two way sharing of information but a could be attributed to many factors, for example single decision maker (physician) was identified patient lack of interest and/or limitations in per- as a shared approach by approximately 28% and sonal capacity, which in turn may be influenced 34% of surgeons and oncologists respectively. Example 4, illus- Many of the above factors and others (including trating a pure shared approach as defined in our physician factors) have also been identified in model, was identified as shared by 94% of other studies as barriers to implementing a shared surgeons and 87% of oncologists. More- physicians in other clinical areas such as general over, despite attempts like ours and those of practice and diabetes to further refine our model others (Deber 1994, Edwards & Elwyn 2001)to and modify certain aspects of it to fit the respective clarify the meaning of shared decision making, decision-making contexts of different clinical areas there are still different perspectives on what it (Montori et al 2006, Murray et al 2006). In the same study referred to above (Charles There has been increasing interest and activity in et al 2004), we also asked Ontario surgeons and the development, use and evaluation of decision Treatment decision making in the medical encounter: the case of shared decision making 305 aids as instruments or tools to assist patients to par- little like putting the cart before the horse. No mat- ticipate in the treatment decision-making process ter how rigorous the methodological steps are with their physicians (Whelan et al 2002). Whereas in developing a decision aid, the resultant tool some studies (Whelan et al 2002, 2003, 2004) have will still be flawed if not guided initially by a clear shown that such tools improve patients’ knowl- statement about the goals of the instrument and a edge and comfort with decision making, others conceptual foundation of hypotheses and assump- have not (Goel et al 2001). The term decision aid is tions about the mechanisms to incorporate in the a general term applied to a broad array of different tool that are intended to produce the desired tools. Unless these analytical processes are made patients by providing them with evidence-based clear, it is difficult for others to judge the thinking information about relevant treatment options and behind the development process or the extent to their risks and benefits, to structure the decision- which such tools will resonate with physicians making process in what the designers hope will and patients. Finally, it is sometimes the case in this be a useful and logical way, and to encourage field of research that what we can measure drives patients to think about their treatment preferences what we should measure. Some of the more com- One of the more recent developments in the mon formats include decision boards, interactive design of decision aids is the attempt to structure videos, pen and paper exercises, and coaching into these tools exercises intended to help patients exercises to help patients interact with their clarify their values (O’Connor et al 1999). There are edy this situation an international collaboration of many variations on this exercise. The goal is to help scholars in different countries has been assembled patients assess whether the treatment decision to develop critical appraisal criteria (primarily they are leaning towards is consistent with the methodological) for evaluating such aids, but this priorities they have identified in the exercise. This movement is still in its infancy (O’Connor et al type of exercise assumes that undertaking a prefer- 2005). Other issues include, for example, the degree it is often not clear what the designers of such exer- of fit of different aids with a variety of clinical and cises mean by the concept of values and their vari- cultural contexts. Second, the alleged need for to commonly assume that a single type of aid will such exercises assumes that patients on their own fit multiple contexts without the need for modifica- do not know and cannot articulate their own tion (a kind of ‘one size fits all’ mentality), but in values related to the desirability or undesirability reality this is unlikely to be the case. In addition, of various treatments and need help to identify the theoretical underpinnings and assumptions and weigh these. It is further assumed that all underlying the development of such interventions patients use a similar (universalistic) method to often vary, may not be made explicit, or may be weigh the benefits and risks of various treatments, absent completely as a foundation on which an assumption that may or may not be true. These include: To do so would require that we first know what the the definition, types and levels of patient values patient’s true values are so that we could use them to be considered when attempting to help patients as a ‘gold standard’ by which to judge which clarify their preferences for different treatment approach resulted in a treatment decision most decisions; the definition and influence of culture congruent with these values. But if we knew what on patients’ preferences for decision-making pro- the patient’s true values were in the first place, cesses and outcomes (Charles et al 2006); the fact we would not need any explicit exercise to help that measurement activities often drive goal- the patient define them. Finally, the exercise of setting activities for decision aids rather than the helping patients clarify their values may act inad- other way round; and the lack of precision in the vertently as an intervention, changing patients’ stated rationale for and meaning of various goals values through the exercise itself. Thus, while suggested for decision aids, and for mechanisms laudable in intent, many current values clarifica- through which they are intended to have an tion exercises are fraught with difficulties and impact.

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Endometriosis 273 specific for endometriosis and are also associated with women with endometriosis order famvir 250mg free shipping hiv infection due to blood transfusion, none of them has been proved other gynecological and non-gynecological disorders to be useful for predicting the presence of the disease order famvir on line amex timeline for hiv infection. Anti-endometrial Abs have cohort studies and seven case-control studies including been widely demonstrated to be increased in women with women with infertility or chronic pelvic pain (6) famvir 250mg mastercard stages of hiv infection symptoms. The exact antigen remains unknown; sensitivity was only 28%; if the sensitivity was increased to therefore generic famvir 250 mg visa antiviral gel for herpes, no simple antigen-antibody assay is currently 50%, the specificity decreased to 72%. When the analysis available (8) and the measurement of these Abs is not used was limited to women with advanced endometriosis, the in clinical practice. For a cardiolipin, ethanolamine, and beta-2-glycoprotein 1 have specificity of 89%, the sensitivity was 47%; an increase of increased levels in women with endometriosis but up to now the sensitivity to 60% resulted in a decrease of the specifi- there is no evidence that these Abs can be used in a clinical city to 81%. Serum protein-containing glycotopes such as sialy- lated T antigen might induce Abs response in patients with There are a limited number of reports on the significance endometriosis. Aberrant immunological mechanisms includ- secreted from the endometrium and endometriotic ing the production of auto-Abs may be involved in the implants; its serum levels may be slightly increased in pathogenesis of endometriosis-related infertility. Infertile women with endometriosis however the measurement of patients with endometriosis have increased prevalence of this molecule does not allow to discriminate patients with auto-Abs against laminin-1, which is a multifunctional gly- endometriosis from controls. Thyroid autoimmunity has also been documented in triosis but up to now it has not been largely investigated. Angiogenin, which may promote the establish- marker will yield sufficient sensitivity and specificity to be ment of new blood supply for the lesions, has increased used in clinical practice. However, in recent years, proteo- serum levels in women with endometriosis during the folli- mic technology has been applied to the research of new cular phase of the menstrual cycle and has recently been markers of endometriosis with promising results (12). It is contro- Contraceptives (to be reassessed) versial whether histology should be obtained if peritoneal Oral contraceptives disease alone is present; visual inspection is usually adequate Contraceptive patch but histological confirmation of at least one lesion is ideal. In Contraceptive ring Progestogens cases of ovarian endometrioma and in deeply infiltrating dis- Derivative of progesterone ease, histology should be obtained to identify endometriosis Medroxyprogesterone acetate and to exclude rare instances of malignancy (13). It is possible Megestrol acetate to suspect the presence of endometriosis on the basis of symp- Dydrogesterone toms reported by the patients and findings at gynecological Derivative of 19-nortestosterone Norethindrone examination, but limited information can be obtained on the Norgestrel extent of lesions. Therefore, preoperative imaging is required Lynestrenol for determining the location and severity of disease. Recently, multislice- conceive although they may have an anti-ovulatory effect computed tomography combined with colon distension by when taken at mid-cycle. Several studies proved that water enteroclysis has been proved to have high accuracy in suppression of ovarian function for 6 months reduces determining the presence of bowel endometriotic nodules with endometriosis-associated pain (13). Minimal lesions are more difficult to of the potential effects on the ectopic lesions and on the diagnose during clinical consultation, and they are usually immune system (4, 17, 18). Therapy Both gonadotropin-releasing hormone analogs and dana- zol have been used in the treatment of endometriosis; Medical therapy aims primarily to eradicate painful however, they may cause several adverse effects. In the symptoms; there is no evidence that currently available last 20 years, our understanding of the pathogenesis of medical therapies can enhance fecundity and reduce the endometriosis at the molecular and cellular levels has extent of endometriosis. Differences in character- and they may improve our ability to eliminate endome- istics among 1,000 women with endometriosis based on triotic lesions when present or more likely to prevent extent of disease. Fertil Steril 2002; ciated with improvements not only in pain symptoms but 78(4): 733–9. Laboratory testing for endome- women with endometriosis, and this technique decreases triosis. An Laparotomy should be reserved for patients with advanced association of IgG anti-laminin-1 autoantibodies with endo- stage disease in whom laparoscopy is judged to be not metriosis in infertile patients. Pregnancy loss and endometriosis: Pathogenic role of anti- There is no solid evidence that the development of endo- laminin-1 autoantibodies. Hum unclear whether lifestyle (regular exercise, cigarette smok- Reprod 2005; 20(10): 2698–704. Future perspectives in the medical treatment of endome- macrophages in endometriosis: Correlation between the triosis. Some of these patterns are related with global autoimmune regulation whereas others may be related with inflammatory autoimmunity against ovarian antigens. This syndrome (amenorrhea, hot flushes, genital autoantibodies are detected in patients with Addison’s dis- atrophy, infertility) was first described by Atria in 1950. In the first one, there is a bodies, which are also present in just 15–20% of patients complete absence of ovarian follicles, and it is characteristic with Addison’s disease but without amenorrhea. Autoantibodies against other endocrine systems: Auto- are the target of autoimmune attack. Antireceptor antibodies: Antireceptor antibodies are pellucida binding, and recognition of porcine oocytes targeted against membrane hormone receptor. These appears to be highly non-specific because it occurs in sera antibodies may act mimicking the physiologic hormo- from 60% of healthy fertile women and even occurs in nal action or blocking the hormone function depending 40% of male serum samples. Some investigators zona pellucida autoantibodies may be more in the order have described the presence of antibodies directed of 2. However, such antibodies have also been detected in patients with iatrogenic ovarian failure (4). In experimental animal models, immune conditions varies somewhat between different these antibodies have been able to inhibit the follicular development (15). These patients with normal represent secondary effects of a more global endocrine number of ovarian follicles present gonadotrophin resis- autoimmune dysfunction. Autoimmune Ovarian Failure 279 and it has been suggested that estrogen may modulate the interfering with zona pellucida antigens, thereby disrup- T-cell activation arguing that T-cell activation observed in ting ovulation and/or fertilization (4). Furthermore, hormonal repla- include those methods that target zona pellucida; thus, cement therapy may decrease the number of activated immunization with heterologous zona pellucida antigens T cells (16). The T-killer cells are also diminished in number results in autoimmune oophoritis characterized by follicle and function as monocytes are (16). An inflammatory oophoritis such as that observed following immunization with ovarian homogenate, however, does not occur (18). These patients have normal menstrual cycle, spontaneously develop autoimmune oophoritis along with but they used to have bad results in in vitro fertilization autoimmune disorders of the thyroid, gut, parotid gland, cycles with high rates of canceled cycles. They determined a number of autoantibodies includ- lating autoantibodies against oocytes, zona pellucid proteins, ing antiovary, antiendometrium, antihypofysis, antiadrenal, and steroid-producing cells appear within 4 weeks and antimicrosomal, anticardiolipin, antihistone, antinuclear, reach their highest titers within 7–9 weeks. The inflammation and other; they also determined different type of T cells subsides after 14 weeks, and the ovaries become atrophic. They also included two control This type of experimental oophoritis in mice is similar to groups. The authors concluded that subclinical ovarian failure is not an Conclusion autoimmune alteration. Its etio- pathogenic factors remain unclear in most cases but include chromosomal, genetic, enzymatic, toxic, infectious, and Experimental Animal Models iatrogenic causes. Serum ovarian present a greater incidence of type I diabetes and myasthe- antibodies appear after 28 days and may passively transfer nia gravis than general population. Kamada M, Daitoh T, Mori K, Maeda N, Hirano K, Irahara M, failure and ovarian autoimmunity. A novel autoantigen in patients with premature ovarian fail- J Clin Endocrinol Metab 1991; 73: 360–7. Silva, Eduardo Ferreira Borba, Marcello Cocuzza, Jozelio Freire de Carvalho and Elo?sa Bonfa Abstract Testicular autoimmune disease may be primary or secondary. The former is characterized by an isolated infertility and autoantibodies directed to sperm, basement membrane, or seminiferous tubules without evidence of a systemic autoimmune disease.

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