Oxybutynin

Adonlce Khoury, PharmD, BCPS

Clinical Assistant Professor
College of Pharmacy
University of Florida
U F Health Shands Hospital
Clinical Pharmacy Specialist
Gainesville, Florida

A recent concept is that ischemic myocardial tissue can be nonfunctioning (hibernating) but revitalized by surgical or medical therapy directed at ischemic heart disease medications ending in zole buy generic oxybutynin 2.5 mg online. In basic terms treatment herniated disc cheap oxybutynin line, afterload is the load that the pump has to work against treatment molluscum contagiosum buy cheap oxybutynin 5mg line, which is usually clinically estimated by the mean arterial pressure medicine z pack oxybutynin 2.5 mg low cost. The Frank-Starling law of the heart states that as the ven also the wall tension and intrathoracic pressure that the tricular volume increases and stretches the myocardial muscle myocardium must work against medications prescribed for pain are termed discount oxybutynin online amex. Together symptoms of colon cancer cheap 5mg oxybutynin fast delivery, these 3 vari fibers, the stroke volume increases, up to its maximum capacity. If stroke volume cannot be main tained, then heart rate must increase to maintain cardiac which elevates left-atrial pressure and pulmonary venous output. Initially, this response will suffice, but pro Based on autonomic input, the heart will respond to the longed activation results in loss of myocytes and maladap same preload with different stroke volumes, depending on tive changes in the surviving myocytes and the extracel inherent characteristics of the heart. The stressed myocardium undergoes remodeling and dilation in response to the insult. Remodeling also results in additional cardiac decompensation from complications, including mitral re gurgitation from valvular annulus stretching, and cardiac arrhythmias from atrial remodeling. Patients presen tation can greatly differ, depending on the chronicity of the disease. For instance, most patients experience dyspnea when pulmonary-artery occlusion pressure exceeds 25 mm Hg. This series of Frank-Starling curves demonstrates that at any given preload (end-diastolic volume), increases in contractility capillaries are recruited and increase capacitance to deal with the added volume. At this point, by action of pressure gradients, fluid will form in the interlobular septae and the perihilar region. As noted above, chronic heart failure is associated with increased venous capacitance and lymphatic drainage of the lung. As a result, crackles are often absent, even in the setting of elevated pulmonary capillary pressure. Con tinued sodium retention preferentially results in peripheral edema and, ultimately, in the development of pleural ef fusions. The long-term response to elevated pulmonary venous pressure includes interstitial fibrosis with thicken ing of the alveolar membrane. Evaluation of the Patient With Congestive Heart Failure patients with dyspnea, a chest radiograph is a useful first test for differentiating patients with heart failure from pa the approach to the patient with suspected heart failure tients with primary pulmonary disease (Fig. Radio includes a history and physical examination, chest radio graphic findings suggestive of heart failure include car graph, and a series of diagnostic tests to assess both the diomegaly (cardiac-to-thoracic ratio above 50%), acuity and severity. History alone is insufficient to make cephalization of blood vessels, increased interstitial mark the diagnosis of heart failure, but often provides clues to ings, and pleural effusions. Patients with previous evi failure can be related to either the reduction of cardiac dence of heart disease, diabetes mellitus, hypertension, or output (fatigue, weakness) or to excess fluid retention (dys documented coronary-artery disease are at increased risk pnea, orthopnea, and cardiac wheezing). Fluid retention also ments of cardiac contractility, there were no laboratory results in peripheral edema and occasionally in increasing tests to assist in the diagnosis of heart failure. Absence of dyspnea triuretic peptide is one of a family of neurohormones that on exertion essentially rules out heart failure due to left is produced by the ventricles in response to increased pres ventricular dysfunction. It works to counteract the effect of crackles and wheezing) is predominant in acute or sub the renin-angiotensin system by providing vasodilation, acute disease. A 45), which correlates with elevated pulmonary-artery oc cut-off value of 100 pg/mL diagnoses heart failure with clusion pressure 80% of the time. Pleural effusion blockers protect the heart from the harmful effects of Tachycardia (120 beats/min) norepinephrine and epinephrine. Intolerance to blockers is uncommon and is usually due to bradycardia or dizziness. Diuretics are essential in the relief of dyspnea and signs Therapy for Congestive Heart Failure of sodium and water retention (peripheral edema or pleural effusion). They are best used in the minimum dose needed Understanding the pathophysiology of heart failure al to maintain the dry weight in patients with symptomatic lows one to achieve the goals of treatment, which are to heart failure. Much litera ventricular synchronization, in the hope of improving car ture and research has been published on medical manage diac output. The basic theories include termination of the brillators reduce the risk of death in patients who have renin-angiotensin system to prevent the long-term compli moderate-to-severe symptomatic heart failure and a re cations of the cascade. Treatment often focuses on a com duced ejection fraction despite maximum medical thera bination of afterload-reduction with angiotensin-convert py. Although clinical trials have shown signifi they experience in performing certain activities (Table cantly lower mortality with multiple interventions, the over 2). A recent randomized controlled trial by apneic event, exacerbating the underlying cardiac dysfunc Mansfield et al45 attempted to show clinical benefit from tion. This allows randomizing patients to treat pulmonary edema, which leads to initial hyperventilation. Hanly et al, in a one-night study, decreased compliance, increased airway-closing pressure, discovered that nocturnal oxygen improved oxygenation increased work of breathing, and greater oxygen consump and sleep architecture and decreased sleep-disordered tion. The patients Acute pulmonary edema with respiratory distress is a were predominantly older, white, and male, and had isch common presentation to the hospital. Consistent with pulmonary edema is that positive pressure may limit the previous trials, early analysis showed an improvement in decrease in functional residual capacity, improve respira the occurrence of central apnea, increases in mean oxygen tory mechanics and oxygenation, and decrease left-ven saturation, improved ejection fraction, and suppression of tricular preload and afterload. However, the primary out improve hypercarbia, with a greater decrease in work of comes (death and cardiac transplantation) did not differ breathing. Furthermore, are probably those presenting to the emergency room and no difference was observed in morbidity measured by qual who have a narrow time-window for intervention. Pang et al performed the first meta-analysis concerning Only one prior study reported a mortality benefit with the the use of positive-pressure airway support. Positive pressure ventilation pressure to the maximum tolerated, and expiratory pres in the management of acute and chronic cardiac failure: a systematic sure to a rise in oxygen saturation (initial settings 10/5 cm review and meta-analysis. Do patients with proved the respiratory rate, dyspnea score, and ratio of suspected heart failure and preserved left ventricular systolic func PaO to fraction of inspired oxygen; however, there was no 2 tion suffer from diastolic heart failure or from misdiagnosis? A significant reduction in hospital mortality or need for in prospective descriptive study. Disorders of the heart: normal and abnormal myo cal therapy, and significantly reduced the intubation rate. Pulmonary factors limiting exercise capacity in pa the airway, inability to clear secretions, high risk for as tients with heart failure. Coronary artery disease cally the most critical factor is setting an end point for the in patients with heart failure and preserved systolic function. Am J determination of the need for invasive ventilation, thereby Cardiol 2002;89(6):719?722. Medical therapy can improve the biolog ical properties of the chronically failing heart: a new era in the Summary treatment of heart failure. J Appl in the differential diagnosis in all adult patients who present Physiol 1964;19:713?724. Pulmonary circulation and nosis is established by a careful history and physical ex regulation of fluid balance. Ultrastructural appearances of pulmonary capillaries at high trans giogram may be required if the diagnosis of pulmonary mural pressures. The limited reliability of physical signs directed toward normalizing the underlying physiologic for estimating hemodynamics in chronic heart failure. Brain natriuretic peptide in the management of heart failure: the versatile neurohormone. Chest hypertension) may halt or slow the progression of the dis 2004;125(2):652?668. B-type natriuretic peptide measurements in diagnosing nary disease, cigarette abuse, or diabetes) is essential in congestive heart failure in the dyspneic emergency department pa optimizing patient outcome and improving quality of life. Sleep-related breathing dis development of heart failure in asymptomatic patients with reduced orders and cardiovascular disease. Cardiac resynchronization in chronic heart fail women with congestive heart failure. Daytime sleepiness, snoring, and obstructive sleep ap tum in: N Engl J Med 2005;352(20):2146. Controlled trial of continuous positive airway pres statement for healthcare professionals from the Cardiovascular Nurs sure in obstructive sleep apnea and heart failure. Arch Intern Med syndrome in patients with chronic heart disease: a critical review of 1995;155(12):1297?1302. Plasma norepinephrine as a guide to prognosis in patients with Sleep 1999;22(5):667?689. Influence of negative intrathoracic pressure on right atrial and systemic venous dynamics. Ventilatory and hemodynamic effects of continuous positive air heart failure and central sleep apnea. Ventilatory and diffusion abnormalities in potential tients with heart failure and obstructive sleep apnea. Lung membrane diffusing capacity, heart failure, and heart Obstructive sleep apnoea in patients with dilated cardiomyopathy: transplantation. Anesth Analg 1997; pressure airway support on mortality and the need for intubation in 84(5):1091?1096. Crit Care Non-invasive pressure support ventilation versus conventional oxy Med 1997;25(4):620?628. Noninvasive ventilation in cardiogenic pulmonary edema: a namic effects of bilevel nasal positive airway pressure ventilation in multicenter randomized trial. Now, after more than three decades of continuous use and modification, many added functions of the catheter have alternatives that are less invasive and occasionally more informative. Pul monary venous pressure plays a crucial role in the evolution and treatment of numerous life threatening problems encountered in the practice of intensive care. Pressure Monitoring System Essential system components required for pressure monitoring include a fluid filled catheter and connecting tubing, a transducer to convert the mechanical energy from the pressure wave into an electrical signal, and a signal processing unit that conditions and amplifies this electrical signal for display. Two primary features of the pressure monitoring system determine its dynamic response prop erties: natural resonant frequency and damping coefficient [1, 2]. Once perturbed, each catheter-transducer system tends to oscillate at a unique (natural resonant) frequency, determined by the elasticity and capacitance of its deformable ele ments. An un-damped system responds well to the low-frequency components of a complex waveform, but it exaggerates the amplitude of components near the resonant value. Modest damping is desirable for optimal fidelity and for suppres sion of unwanted high-frequency vibration (?noise); however, excessive damping 112 J. Once zeroed at the left atrial level, movements of the transducer relative to the patient will influence the recorded value. For the hydraulic monitoring system to display accurate pressures, it is essential that the system be zeroed (balanced) at the phlebostatic axis (mid-axillary line, fourth intercostal space). Body angle is not crucial, so that one can zero the transducer with the orthopneic patient upright or semi-upright. Once the transducer has been zeroed, however, movement of the transducer relative to the heart will cause the recorded pressure to underestimate or overestimate the true value (Fig. Because the pulmonary circuit is a low-pressure vascular bed, small errors in transducer position may be clinically significant. The transducer converts mechanical energy from the fluid-filled tubing into an electrical signal that is then amplified and displayed. Entry into the pulmonary artery is reflected by an abrupt rise in diastolic pressure; a dicrotic notch due to pulmonic valve closure may be apparent. Pulmonary Artery Occlusion Pressure: Measurement, Significance, and Clinical Uses 113 A number of factors may interfere with recognition of characteristic waveforms duringcatheterinsertion. Large swings in intrathoracic pressure may create major problems for waveform interpretation. If the patient is mechani cally ventilated, elimination of large respiratory excursions with sedation (or temporary paralysis) may aid in delineation of the tracing and will enhance reli ability of the measurements obtained [5]. Overdamping occurs when air bubbles, clots, fibrin, or tubing kinks diminish transmission of the pulsatile pres sure waveform to the transducer, resulting in a decrease in systolic pressure and an increase in diastolic pressure. Because of the length and small gauge of the catheter, very high pressures are generated near the transducer when the flush device is opened. An appropriately damped system will show a rapid fall in pressure with a modest overshoot and prompt return to a crisp pulmonary artery tracing upon sudden closure of the flush device. In contrast, an overdamped system will demonstrate a gradual return to the baseline pressure, without an overshoot. Pulmonary Artery Pressure the pulmonary artery waveform has a systolic pressure wave and a diastolic trough. A dicrotic notch due to closure of the pulmonic valve may be seen on the terminal portion of the systolic pressure wave, and the pressure at the dicrotic notch closely approximates mean pulmonary artery pressure [6]. Like the right atrial V wave, the pulmonary artery systolic wave typically coincides with the electrical T wave (Fig. The pulmonary artery diastolic pressure is recorded as the pressure just before the beginning of the systolic pressure wave. Pulmonary artery pressure is determined by the volume of blood ejected into the pulmonary artery during systole, the resistance within the pulmonary vascular bed, and the downstream (left atrial) pressure. The normal pulmonary vascular network is a low-resistance circuit with enormous reserve, sothatlargeincreasesincardiacoutputdonotcause pressure torise significantly. However, in the setting of increased vascular resistance, the degree to which pulmonary artery pressure increases will be influenced by the cardiac output. Pulmonary hypertension may result from the combination of a modest increase in vascular resistance and a major increase in cardiac output due to sepsis, cirrhosis, agitation, fever or other factors. The latter may be particularly relevant when assessing the response to vasodilators that affect both the pulmonary and systemic vascular Pulmonary Artery Occlusion Pressure: Measurement, Significance, and Clinical Uses 115 beds.

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Each dilution is then mixed with an equal volume of substrate plasma that is known to contain normal levels of all factors lb 95 medications cheap oxybutynin 2.5mg visa, except the factor that is being assayed treatment 8mm kidney stone buy oxybutynin overnight delivery. The results are plotted on a log/log graph (polynomial curve) with percent factor on the abscissa and the time in seconds on the ordinate symptoms 4dp5dt purchase oxybutynin 2.5 mg. The test results of the above dilutions will form a straight line that forms the basis for a standard curve at the connected points which can then be used to determine the activity of that coagulation factor in patient samples treatment eating disorders buy cheap oxybutynin on line. To analyze a factor activity level on an unknown sample medications before surgery buy discount oxybutynin 2.5mg on line, 1:5 (100% activity) and 1:10 (50% activity) dilutions are prepared and mixed with substrate plasma treatment 3 degree heart block purchase oxybutynin 5mg otc. The percent activity is read from the abscissa of the graph by finding where the clotting time obtained for the unknown sample intercepts the standard curve. All of this now is in fact programed into our analyzers, and graph paper can no longer be found in our laboratory. Isolated deficiency of Factor V activity may be inherited (incidence 1/1,000,000) or rarely acquired in patients suffering from amyloidosis. Cases of congenital factor V deficiency associated with the production of a dysfunctional molecule have also been reported. Inhibitors directed against factor V can be seen in patients exposed to fibrin glue prepared with bovine thrombin. Note: Factor V deficiency is not synonymous with Factor V Leiden (see hypercoagulable state discussion). Acquired factor X deficiency is most commonly seen in conjunction with vitamin K deficiency or therapy with vitamin K antagonists. Factors affecting test results (false positives and negatives) (Factor Assays Studies): Factor activity results can be influenced by the type of coagulometer or the reagents used to perform the test. Dilution errors can adversely affect the obtained factor activity results as well. The presence of the Lupus Anticoagulant has been associated with falsely decreased results. Diagnosis of deficiency states or inhibitors affecting factors in the intrinsic pathway of the coagulation cascade. Analysis is performed by making serial dilutions (1:5 to 1:320 dilutions of calibration reference plasma or factor assay reference plasma in buffer (both with known assay values for the factor of interest). Each dilution is mixed with an equal volume of substrate plasma that is known to contain normal levels of all factors except the factor of interest. The results are plotted on a log/log graph (polynomial curve) with the percent dilution on the abscissa and the time in seconds on the ordinate. The connected points from the above dilutions form a straight line that is the basis for a standard curve. This standard curve is then used to measure the factor activity of patient samples with unknown factor content. To analyze the factor activity level on an unknown sample, 1:5 (100% activity) and 1:10 (50% activity) dilutions are prepared and mixed with immunoabsorbed, factor deficient (<1%) plasma. The percent factor activity of the patient sample is read from the abscissa of the standard curve graph by finding where the time obtained on the unknown intercepts the standard curve. Hemophilia A is inherited in an X-linked recessive manner and occurs in approximately 1 in every 10,000 live male births. These autoantibodies are associated with autoimmune disorders, malignancies, medications and the peripartum period. Like hemophilia A, hemophilia B is inherited in an X-linked recessive fashion but its incidence is about 10-fold less common occurring in 1 out of every 50-100,000 male births. These antibodies are associated with anaphylactic reactions among hemophilia B patients when receiving factor replacement. The presence of the Lupus Anticoagulant has been associated with falsely decreased results. The urea stability test is sensitive to levels of 1-5%, while the acetic acid method is sensitive to below 10%. There are other assays available but only the Berichrom is approved in the United States. Of note there are reports of the thromboelastogram being abnormal, with reduced maximum amplitude and strength and increased clot cyis at 30 minutes. By comparing the difference in factor activity of the patient incubation mixture and a control mixture, the amount of inhibitor present is calculated in Bethesda units. A modification of the Bethesda assay, the Nijmegen modification, dilutes patient plasma in buffered plasma to eliminate the decrease in factor activity that occurs with pH shifts during incubation. The imprecision introduced with unbuffered plasma is relevant particularly for lower titer inhibitors. Inhibitors to specific coagulation factors can be classified as being either autoantibodies or alloantibodies. Immunosuppressive therapy is effective in eradication of these antibodies in 60-70% of patients. In contrast to autoantibodies, alloantibodies develop in patients who lack a particular coagulation factor and generate an alloantibody upon exposure to this factor during treatment with coagulation factor concentrates. The prevalence of inhibitors is much lower among patients with hemophilia B where their occurrence has been estimated to be 2%. Patients with low titer inhibitors can be effectively treated with factor concentrates by doubling or tripling the dose. The advantage of this approach is that factor activity levels can be followed to objectively assess the adequacy of therapy. The ability to measure factor levels can be very useful in situations in which objective confirmation of the adequacy of replacement therapy is important such as during major surgical procedures or treatment for life-threatening bleeds. This assay cannot distinguish between specific factor inhibitors and fibrin degradation products, heparin, or heparin like inhibitors that may also lead to a positive mixing test result. Four major type 2 variants are recognized: type 2A, type 2B, type 2M and type 2N von Willebrand disease. It is an autosomal recessive form in which one abnormal gene is inherited from both parents. Ristocetin Cofactor Assay the Ristocetin Cofactor Assay Measures the Functional Level of von Willebrand Factor in Plasma Indications (Ristocetin Cofactor Assay): 1. The Ristocetin Cofactor Assay is performed by agglutinating a standardized suspension of platelets in the presence of von Willebrand Factor (provided by the patient plasma) using the antibiotic, Ristocetin. Although the platelets play a passive role in such agglutination, there is an absolute requirement that the Ristocetin-dependent receptor be intact. Levels of Ristocetin Cofactor activity are determined by the ability of the test plasma and Ristocetin to induce aggregation in a standardized platelet suspension. Following reconstitution, lyophilized platelets are treated with Ristocetin in the presence of dilutions of normal standardized human plasma with a known amount of Ristocetin Cofactor Activity. A standard curve is prepared, after which patient plasma is then used as a source of Ristocetin Cofactor Activity. The Ristocetin Cofactor Activity of the patient sample is interpolated from the standard curve. This loss of higher molecular weight multimers will be reflected in an abnormal distribution of multimers. Prolonged transport of samples to the laboratory or inadequate sample preparation. In type 1 von Willebrand disease, there is a mild to moderate reduction in the amount of this protein. In extremely rare instances, anti-rabbit antibodies that can lead to aberrant test results in affected individuals. Diagnosis of the hypercoagulable state associated with resistance to activated Protein C caused by the Factor V Leiden gene mutation. The sensitivity and specificity of the assay for activated protein C resistance is unaffected by plasma samples obtained from patients on warfarin. The prescribed assay procedure allows for the analysis of plasma from heparinized patients at heparin levels < 1U/mL plasma (un-fractionated and low molecular weight heparins). Although the 1:4 pre-dilution strongly decreased interference, the assay may give misleading results in patients with high titer inhibitors (lupus anticoagulants). Hence, the presence of this mutation is responsible for the vast majority of cases of activated Protein C resistance. This complex allows the cleavage and release of a fluorescein tag, which can be detected by a fluorescence plate reader. If the mutant factor V sequence is present instead of the wild type sequence then only the mutant probes form a complex and only this sample generates a fluorescence signal. Likewise if both mutant and wild type sequences are present (the heterozygous states), both probes generate a signal. Wild type and mutant controls are included on each run to assist in signal interpretation. Possible results and interpretation (Factor V Leiden): Patients can be negative for the Factor V Leiden mutation, heterozygous or homozygous for the mutation. The presence of Factor V Leiden is a potent risk factor for venous thrombosis, with heterozygotes and homozygotes having a 5-8-fold and 50-fold, respectively, increased risk of thrombosis. There is a substantial variation in the Factor V Leiden gene frequency according to the ethnic background of the individual. There is also an association between this mutation and an increased risk of cerebrovascular disease among young individuals. The risk of thrombosis increases 20-25 times normal when this mutation occurs in conjunction with Factor V mutation. Homocysteine this Test Measures the Concentration Of Homocysteine in A Patient Sample Indications (Homocysteine): 1. Possible results and interpretation (Homocysteine): Homocysteine is a thiol-containing amino acid produced during the metabolism of methionine that can be re methylated back to methionine by methionine synthase (cobalamin and folate are cofactors) or converted to cysteine by cystathionine-beta-synthase (pyridoxine is a cofactor), in a trans-sulfuration step. Homocysteine has numerous effects on various components of hemostasis, but the mechanism by which it promotes thrombosis is not completely clear. Hyperhomocysteinemia has been associated with a 2-3 fold increased risk of venous and arterial thrombosis. Markedly elevated levels of homocysteine (can be several hundred micromol/L or more) can be seen in patients with the autosomal recessive metabolic disorder, homocystinuria. Cause of hyperhomocysteinemia may occur as a result of inherited disorders that alter the enzyme activity in the remethylation and transulfuration pathways or by nutritional deficiencies of cobalamin (vitamin B12), folate or pyridoxine (vitamin B6). However, differences in sample handling can cause significantly different results in homocysteine measurement. The homocysteine in plasma/serum samples is stable for at least several days in room temperature, for several weeks at 4oC and for years at -20 oC. Activated Partial Thromboplastin Time (Described above in the Screening test section) F. Although the presence of these antibodies can prolong phospholipid based coagulation tests in vitro, these antibodies are associated with an increased risk of thrombosis and fetal loss in vivo. If the ratio results are within the established laboratory normal reference ratio range (? Antiphospholipid antibodies have been associated with an increased risk of venous and arterial thrombosis and fetal loss. Serum samples are incubated in microtiter plate wells coated with anticardiolipin. The amount of colored reaction product formed is measured photometrically at 405 nM and directly corresponds to the amount of antibody present in the patient serum sample. Although the correlation between anticardiolipin antibody results and clinical events has varied from study to study, low positive results have generally not been associated with an increased risk of clinical events. Moderately increased antibody levels and particularly high antibody levels have been associated with clinical symptoms. Clinical studies indicate that elevated IgG antibodies levels are most consistently associated with an increased risk of thrombosis while elevated IgM levels have been less consistently associated with clinical sequelae. IgA antibodies do not appear to be associated with an increased risk of thromboembolism in most studies. While anticardiolipin antibodies have been associated with a variety of different illnesses, their presence must be integrated with clinical information for optimal clinical decision-making. The diagnosis of antiphospholipid antibody syndrome requires clinical and laboratory evidence of the disease. Patients with positive test results who are asymptomatic do not fulfill criteria for the antiphospholipid antibody syndrome and thus, should not be treated. Since transient anticardiolipin antibodies can be seen in conjunction with many viral infections, patients should have positive test results confirmed by repeat testing. Washes before and after the addition of the secondary antibody eliminates excess unbound protein and antibody. Free protein S antigen is probably the better than the functional protein S activity assay, which has a larger coefficient of variation and occasional false positives when the factor V Leiden mutation is present. Total protein S Total protein S antigen is measured by various types of immunoassay techniques. These tests generally involve dilution of plasma samples, which favors dissociation of the protein S-C4b-binding protein complexes. Free protein S Original free protein S assays used polyethylene glycol precipitation to remove protein S-C4b binding protein complexes from plasma; free protein S was then measured by immunoassay of the supernatant fractions. Functional assays Functional assay methods are based upon the ability of protein S to serve as a cofactor for the anticoagulant effect of activated protein C. However, some of these assays are not specific for protein S since they are also sensitive to the defect characterized by resistance to activated protein C. As a result, their use can lead to an erroneous diagnosis of functional protein S deficiency in a patient with other causes of activated protein C resistance. Plasma concentration the average plasma concentration of total protein S antigen in normal adults is 23 microg/mL. Levels increase with advancing age and are significantly lower and more variable in females than males.

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Restricting intake of fats medications similar to vyvanse discount oxybutynin 2.5 mg without prescription, especially trans-fats and sugars is also associated with good sperm quality symptoms kidney cancer discount oxybutynin. A Cochrane review of 34 studies has reported that men with poor semen quality showed improvement in sperm parameters following antioxidant therapy symptoms whooping cough order oxybutynin 5 mg otc. However medicine zetia purchase 5mg oxybutynin fast delivery, these numbers are too small to be definitive and further research is needed (Showell et al crohns medications 6mp order 5 mg oxybutynin overnight delivery. Justification No relevant papers on treatment for miscarriage schedule 8 medicines buy oxybutynin cheap, or recurrent pregnancy loss associated with a male factor problem have been found. Association between socio-psycho-behavioral factors and male semen quality: systematic review and meta-analyses. Varicocelectomy does not impact pregnancy outcomes following intracytoplasmic sperm injection procedures. Varicocele management in the era of in vitro fertilization/intracytoplasmic sperm injection. Several of the included randomized controlled trials did not meet current criteria for methodological quality (uncertain/high risk of bias) and potential adverse effects were not adequately described. Treatment with allogeneic cells raises serious safety concerns and in transfusion practice great efforts are made to lymphocyte-deplete blood before used for transfusion. There is a substantial risk of neonatal alloimmune thrombocytopenia and production of red blood cell antibodies, which can result in erythroblastosis fetalis (Christiansen et al. Furthermore, the protocols used in the randomized trials were very heterogeneous with substantial variations between IvIg dosages used and start of treatment before or during pregnancy. Moderate adverse events such as headache and skin rash were significantly more frequent in IvIg treated compared to placebo-treated patients but there was no difference in the incidence of serious adverse events. Both the intervention and placebo group received empiric treatment with low dose aspirin and heparin (Gomaa et al. A very high prednisolone dose (40-50 mg/day was administered for the whole duration of pregnancy. However, the treated patients had a significantly higher risk of preterm birth (62% versus 12%, p<0. Patients could be selected for such trials due to presence of biomarkers suggesting immune activation. There were no significant benefits for any of the anticoagulants in comparison to placebo or no treatment (de Jong et al. There was no benefit of heparin compared to placebo/multivitamins with regard to live birth rate. High folic acid intake may have negative effects especially in elderly people with low B12 vitamin levels and a study also suggested a higher frequency of insulin resistance in children born to mothers taking high dose folic acid (Selhub and Rosenberg, 2016). Therefore, high-dose folic acid supplementation is only recommended for selected groups of women trying to conceive (Yajnik et al. The Cochrane analysis pooled the results from four small trials that had substantive methodologic limitations none of the trials specified the method of concealment of study-group assignments, and only two trials used a placebo for comparison. The main problem with this study is that treatment was initiated at a late stage of first trimester (mean gestational age 6. Women were randomized to twice daily vaginal suppositories containing either 400 mg of micronized progesterone (n=398) or matched placebo (n=428) from a time soon after a positive urinary pregnancy test (up until 6 weeks) up through 12 weeks of gestation. A recent meta-analysis combined 10 trials, including the trials of Kumar and Coomarasamy, to a total of 802 women receiving progesterone and 784 receiving placebo. A recent meta-analysis, including the recent trials showed a benefit of progesterone on miscarriage rate and live birth rate (Saccone et al. However, the meta-analysis is flawed by the quality of the older included studies, and hence, we decided to base the recommendation on the included and recent high quality trials. There is some evidence that oral dydrogesterone initiated when fetal heart action can be confirmed may be effective. Furthermore, as progesterone is important during implantation of the embryo, benefit from supplementation may be realized if progesterone is administered from the luteal phase, rather than after a positive pregnancy test. More trials are needed to evaluate oral progesterone and administration of progesterone from the luteal phase. In recent years, Intralipid has emerged as a treatment for poisoning by local anesthetics and various other drugs. Evidence Clark and colleagues reported that infusions of Intralipid reduced the fetal resorption rate in specific mice matings (Clark, 1994). However, a series of serious adverse effects has been reported after the use of higher doses of intravenous lipid emulsions: acute kidney injury, cardiac arrest, acute lung injury, venous thromboembolism, fat embolism, fat overload syndrome, pancreatitis, allergic reactions and increased susceptibility to infection (Hayes et al. Furthermore, prognostic variables were no equally distributed in the three groups. In an editorial comment the editor-in-chief of Human Reproduction has recently challenged the evidence for using this procedure in any patient before awaiting results from more controlled trials (Evers, 2016). A randomized clinical trial of endometrial perfusion with granulocyte colony-stimulating factor in in vitro fertilization cycles: impact on endometrial thickness and clinical pregnancy rates. Major histocompatibility complex antigens, maternal and paternal immune responses, and chronic habitual abortions in humans. Placebo-controlled trial of active immunization with third party leukocytes in recurrent miscarriage. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data. Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial. Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. Adverse effects of intradermal allogeneic lymphocyte immunotherapy: acute reactions and role of autoimmunity. Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Beneficial or harmful effect of antipaternal human leukocyte antibodies on pregnancy outcome? Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. Effectiveness and potential mechanisms of intralipid in treating unexplained recurrent spontaneous abortion. Controlled trial of treatment of recurrent spontaneous abortion by immunisation with paternal cells. Pasquier E, de Saint Martin L, Bohec C, Chauleur C, Bretelle F, Marhic G, Le Gal G, Debarge V, Lecomte F, Denoual Ziad C et al. Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double blind placebo-controlled trial. Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Granulocyte-colony stimulating factor as treatment option in patients with recurrent miscarriage. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme. Low-Molecular-Weight Heparin for the Treatment of Unexplained Recurrent Miscarriage With Negative Antiphospholipid Antibodies. The effect of intravenous immunoglobulin passive immunotherapy on unexplained recurrent spontaneous abortion: a meta-analysis. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Another older review came to a similar conclusion based on 41 studies (involving 3660 participants) comparing Chinese herbal medicine alone or in combination with conventional medicine, with placebo or conventional medicine (Yang et al. Overall, it is unclear, based on the available studies -all conducted in China and with different compositions of herbs whether Chinese Herbal treatment is effective, and in addition, data on safety are scarcely reported, which may evoke serious concerns. Diet antioxidants A narrative review summarized the basic science and clinical case reports for antioxidants to improve pregnancy outcome by reducing oxidative stress in the placenta based on a literature search (Hovdenak and Haram, 2012). The authors concluded that whilst vitamin C may confer some benefit to pregnancy outcomes, vitamin E could be harmful. Recently, bioresonans therapy and naprotechnology have been suggested as treatment options for pregnancy loss, but there are no data available supporting their use in clinical practice. Justification Based on frequent questions from couples, it was decided to add a recommendation on vitamin supplements. As there is no conclusive evidence supporting the use of vitamin supplements, they are not recommended as treatment. Chinese herbal medicines for unexplained recurrent miscarriage Cochrane Database of Systematic Reviews. Chinese herbal medicine for the treatment of recurrent miscarriage: a systematic review of randomized clinical trials. Every trial included had adequate random sequence generation, good allocation concealment and no selective reporting, and most trials clearly addressed incomplete outcome data. High or unclear risk of bias in most studies (selection, performance, reporting) b. Impact of subclinical hypothyroidism in women with recurrent early pregnancy loss. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation. Chinese herbal medicines for unexplained recurrent miscarriage Cochrane Database of Systematic Reviews. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Pregnancy outcome after preimplantation genetic screening or natural conception in couples with unexplained recurrent miscarriage: a systematic review of the best available evidence. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. A meta-analysis of low molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia. A feasibility trial of screening women with idiopathic recurrent miscarriage for high uterine natural killer cell density and randomizing to prednisolone or placebo when pregnant. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Study the effect of pre-conceptual weight loss on live birth rate using diet, exercise of therapeutic interventions. A call was launched for experts in the field interested in joining the guideline development group. All applications were reviewed and experts were selected based on expertise and geographical location. Based on the defined key words, literature searches were performed by the methodological expert (Dr. If no results were found, the search was extended to randomized controlled trials, and further to cohort studies and case reports, following the hierarchy of the levels of evidence. If necessary, additional searches were performed in order to get the final list of papers. When there was no recent valid systematic review available, we systematically searched for relevant studies, as described above. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes. We used the words we recommend for strong recommendations and we suggest for conditional recommendations. Suggested interpretation of strong and conditional recommendations by patients, clinicians and health care policy makers is as follows: Implications for Strong recommendation Conditional recommendation Patients Most individuals in this situation would the majority of individuals in this situation want the recommended course of action, would want the suggested course of and only a small proportion would not action, but many would not Clinicians Most individuals should receive the Recognize that different choices will be intervention appropriate for individual patients and that Adherence to this recommendation you must help each patient arrive at a according to the guideline could be used as management decision consistent with his a quality criterion or performance indicator or her values and preferences Formal decision aids are not likely to be Decision aids may be useful in helping needed to help individuals make decisions individuals to make decisions consistent consistent with their values and with their values and preferences preferences Policy makers the recommendation can be adopted as Policy making will require substantial policy in most situations debate and involvement of various stakeholders For each recommendation, it is mentioned whether it is strong or conditional and what the quality of the supporting evidence was. In the justification section, more data are provided on the considerations taken into account when formulating the recommendations: balance between desirable and undesirable effects, certainty of the evidence of effects, certainty in how people value the outcome, acceptability and feasibility of the intervention. They are asked to encourage local implementation by, for instance, translations or condensed versions, but they are also offered a website link to the original document. The patient version is a translation of the recommendations in everyday language, with emphasis on questions important to patients. Every care is taken to ensure that this publication is correct in every detail at the time of publication. However, in the event of errors or omissions, corrections will be published in the web version of this document, which is the definitive version at all times. The list of representatives of professional organization, and of individual experts that provided comments to the guideline are summarized below.

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Lp(a) lipoprotein is an independent medicine ads trusted 2.5 mg oxybutynin, discriminating risk factor for premature peripheral atherosclerosis among white men symptoms stomach ulcer order 5mg oxybutynin with visa. Lipoprotein Lp(a) and cerebrovascular disease in the elderly: correlations with the severity of extracranial carotid atherosclerosis assessed by ultrasonography medicine ball chair buy cheap oxybutynin 5 mg. Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery medicine online buy cheap oxybutynin 5mg on line. Elevated Lipoprotein(a) does not promote early atherosclerotic changes of the carotid arteries in young symptoms after flu shot order 5mg oxybutynin free shipping, healthy adults symptoms hypoglycemia buy oxybutynin canada. Conventional and Mendelian randomization analyses suggest no association between lipoprotein(a) and early atherosclerosis: the Young Finns Study. Relationship between lipoprotein(a) concentrations and intima-media thickness: a healthy population study. Lipoprotein (a) levels are not associated with carotid plaques and carotid intima media thickness in statin-treated patients with familial hypercholesterolemia. Lipoprotein(a), Chlamydia pneumoniae, leptin and tissue plasminogen activator as risk markers for valvular aortic stenosis. Effects of serum levels of novel atherosclerotic risk factors on aortic valve calcification. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia. Correlation analysis between serum lipoprotein (a) and the incidence of aortic valve sclerosis. Lipoprotein(a) is a risk factor for aortic and mitral valvular stenosis in peripheral arterial disease. Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Increased plasma levels of lipoprotein(a) and the risk of idiopathic and recurrent venous thromboembolism. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood. Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors a multicentre case-control study. Prothrombotic risk factors in children with spontaneous venous thrombosis and their asymptomatic parents: a family study. Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors. Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease. Renal venous thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. High lipoprotein(a) and low risk of major bleeding in the general population: a Mendelian randomization study. Inverse association between serum lipoprotein(a) and cerebral hemorrhage in the Japanese population. Lipoprotein(a) as a modifier of fibrin clot permeability and susceptibility to lysis. Proteomics of Lipoprotein(a) identifies a protein complement associated with response to wounding. Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Tissue-type plasminogen activator binds to and is inhibited by surface-bound lipoprotein(a) and low-density lipoprotein. Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator. Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients. Lipoprotein(a) in restenosis after percutaneous transluminal coronary angioplasty and coronary artery disease. Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans. Lipoprotein Lp(a) in homozygous familial hypercholesterolemia: density profile, particle heterogeneity and apolipoprotein(a) phenotype. Diverse effect of ethnicity on plasma lipoprotein[a] levels in heterozygote patients with familial hypercholesterolemia. Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations. Relation to the presence of coronary artery disease in familial hypercholesterolemia. Plasma lipoprotein(a) concentration in familial hypercholesterolemic patients without coronary artery disease. Lp(a) levels and atherosclerotic vascular disease in a sample of patients with familial hypercholesterolemia sharing the same gene defect. Familial Hypercholesterolemia in the Danish General Population: Prevalence, Coronary Artery Disease and Cholesterol-lowering medication. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype phenotype relationship, and clinical outcome. The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans. The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Green and red parts correspond to the bottom 80% and top 20% of the entire population distribution of plasma lipoprotein(a) concentrations (see Figure 3). The 4 different statistical parts of a complete Mendelian randomization study design to examine causality from high plasma lipoprotein(a) concentrations to high risk of cardiovascular disease. Comparison of observational studies and Mendelian randomization studies to help understand causality from high plasma lipoprotein(a) concentrations to high risk of cardiovascular disease. Observational associations between high plasma lipoprotein(a) concentrations and risk of cardiovascular disease in the Copenhagen City Heart Study and Copenhagen General Population Study combined (left panel) and in the Emerging Risk Factors Collaboration (right panel). Hazard ratios in 56 the left panel were estimated by Cox proportional hazard regression models and were adjusted for age and sex and corrected for regression dilution bias. Observational and causal, genetic associations between high plasma lipoprotein(a) concentrations and risk of cardiovascular disease in the Copenhagen City Heart Study and Copenhagen General Population Study combined. Hazard ratios for observational analyses of plasma lipoprotein(a) concentrations were estimated by Cox proportional hazard regression models and were adjusted for age and sex. Causal risk ratios for analyses of genetically determined plasma lipoprotein(a) concentrations were estimated by instrumental variable analyses and were adjusted for age and sex. Observational associations between high plasma lipoprotein(a) concentrations and risk of coronary, carotid, and femoral atherosclerotic stenosis in the Copenhagen Ischemic Heart Disease Study, Copenhagen Carotid Stroke Study, and Copenhagen City Heart Study, respectively. Odds ratios were estimated by logistic regression models and were adjusted for age and sex. Observational associations between high plasma lipoprotein(a) concentrations and risk of aortic valve stenosis in the Copenhagen City Heart Study and Copenhagen General Population Study combined. Observational associations between high plasma lipoprotein(a) concentrations and risk of venous thromboembolism in the Copenhagen City Heart Study and Copenhagen General Population Study combined. Hazard ratios were estimated by Cox proportional hazard regression models and were adjusted for age and sex. Observational changes were by linear regression, and causal, genetic estimates were by instrumental variable analyses. Baseline characteristic in individuals from the Copenhagen General Population and the Copenhagen City Heart Study combined. The micronutrient vitamin D is an important steroid hormone that acts on many crucial cellular mechanisms. Current evidence suggests a strong role of vitamin D in promoting genomic and epigenomic changes. Introduction Vitamin D is an important micronutrient that is essential for optimal health throughout life. The main forms of vitamin D in nature are vitamin D3 (cholecalciferol) that is synthesized in the skin of animals and humans in response to sunlight and obtained through diet. Vitamin D must undergo several hydroxylation steps to become an active metabolite. The synthetic pathway involves 25 and 1-alpha-hydroxylation of vitamin D3 and D2, in the liver and kidney, respectively. The biologically active form of vitamin D3 is2 involved in the regulation of numerous cell cycle regulatory mechanisms protecting the vasculature from pathological conditions. Given that vitamin D synthesis is mainly through sunlight, factors such as the skin tone, availability of sunlight, etc. However, the presence of receptors for vitamin D in the vascular wall suggests that this micronutrient might play a role in the pathogenesis of arterial diseases [10]. A number of risk factors are currently known, several of these are known to cause alterations to the genome and epigenome. This results in poor outcome for the patient, with chronic claudication pain, ischemic ulcerations, repeated hospitalizations, revascularizations, limb necrosis and eventual limb loss. Furthermore, the geographical location of the patient population tested varied between the studies, leading to other confounding factors, which could potentially lead to the change in vitamin D levels. An interesting population-based cohort study from northern Sweden, showed seasonal hypovitaminosis in the population [43]. These observations suggest that further studies are required to understand which vitamin D metabolite is optimal in ascertaining vitamin D status [54]. Vitamin D has shown to be potent growth modulator, protector of endothelial function and in? Optimal vitamin D status is crucial for the functioning of the resident cells and thus it plays a major protective e? Both cell types are shown to downregulate the production of atherogenic molecules when exposed to vitamin D [72], suggesting that optimal vitamin D status is crucial for the functioning of these cells. Vdr null mice display a pro-thrombotic state that was associated with a decrease in antithrombin and thrombomodulin [76]. Vitamin D supplementation protected hypercholesterolemic Yucatan microswine against atherosclerosis by controlling cholesterol e? Vitamin D has an important role in the immune system as it has been shown to have immune-modulating anti-in? Administration of calcitriol induces two major immune cells induced in atherosclerotic lesions namely, Tregs and immature dendritic cells via the intestinal immune system, resulting in mutually suppressing pathogenic immune processes that play a pivotal role in the progression of atherosclerosis [86]. Calcitriol has been shown to be anti-atherosclerotic in ApoE-/ mice by attenuating macrophage accumulation, promoting functions of Tregs and dendritic cells [86] and in swine by promoting cholesterol e? However, preclinical studies show that caution must be employed when administering vitamin D supplementation, as lower levels of paricalcitol administration was protective against aortic calci? Majority of the anti-angiogenic information regarding vitamin D is derived from cancer studies and vitamin D was shown to exhibit anti-cancer e? Vitamin D intervention does not improve vascular regeneration in diet-induced obese male mice with peripheral ischemia [113]. The study shows that recovery of hind limb use in diet-induced obese mice following acute ischemic injury was improved in niacin-treated mice compared to vitamin D-treated mice suggesting limited bene? Vitamin D and the Genome Physiologically, vitamin D is sourced from cutaneous radiation by ultraviolet B from the sun and dietary intake [7,114] (Figure 1). Recent advances in molecular techniques has facilitated elucidation of vitamin D genomic e?

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