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Biomedical subjects

S Honig

Publications and source records attributed to S Honig.

At least 19 recordsLinked to original sources

Optimization of endometrial preparation results in a normal endometrial function test (EFT) and good reproductive outcome in donor ovum recipients.

PURPOSE: Numerous studies have investigated potential markers of endometrial receptivity as predictors of successful implantation. Cyclin E and p27 have recently been studied using the endometrial function test (EFT). Our objective is to determine the correlation between the expression of cyclin E and p27 and the adequacy of uterine preparation of recipients using donor oocytes. METHODS: Twenty recipients undergoing preparatory cycles with leuprolide acetate, estrogen, and progesterone. Endometrial biopsies were obtained 10-12 days after progesterone supplementation following the course of estrogen. The tissue was prepared for histological analysis and immunohistochemical staining for cyclin E assessment. The outcome of their subsequent ovum donation cycle was blinded to the reviewer of the EFT. RESULTS: All recipients showed normal luteal transformation. Nineteen (95%) of the recipients had a normal EFT. This is significantly higher than what we demonstrated, previously, in unexplained infertility patients, where only 40% of such patients had a normal EFT. Thirteen recipients with a normal EFT had a clinical pregnancy, while 6 did not become pregnant in their subsequent transfer cycles. The sole patient with an abnormal EFT did not conceive on 2 subsequent cycles. CONCLUSIONS: While a normal EFT does not guarantee a successful pregnancy, an abnormal EFT appears to be associated with pregnancy failure. This may be useful in identifying women who need adjustments to their stimulation protocols prior to progressing to a physically, emotionally, and financially costly cycle.

Adult↗

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.

Humans↗

Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.

Adult↗

Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease.

Previous studies support a role for intestinal epithelial cells (IEC) as antigen-presenting cells in mucosal immune responses. T cells activated by IEC are CD8+, suppressor in function, and dependent upon CD8-associated p56lck activation. A 180-kD glycoprotein (gp180) recognized by mAbs B9 and L12 has been identified and shown to be important in CD8+ T cell activation by IEC. Since IEC derived from patients with inflammatory bowel disease (IBD) are incapable of activating CD8+ T cells, we asked whether this correlated with gp180 expression. While frozen sections of normal bowel revealed bright gp180 staining on all IEC, both inflamed and uninflamed ulcerative colitis (UC) specimens showed patchy staining. In Crohn's disease (CD), staining was faint to absent. Flow cytometry confirmed immunohistochemical data. The staining patterns correlated with the ability of IEC to activate CD8-associated p56lck. Normal IEC induced phosphorylation of p56lck in CD8alpha but not CD4+ transfectants. In contrast, both UC and CD IEC activated CD4 and, to a much lesser extent, CD8-associated p56lck. Thus, gp180 expression by IBD IEC appears to be altered, and correlates with a functional alteration of lck activation. This defect may reflect a more proximal event in the pathogenesis of IBD.

CD8 Antigens↗

Microscopic epididymal sperm aspiration (MESA): a new option for treatment of the obstructive azoospermia associated with cystic fibrosis.

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.

Adult↗

Spinal cord claudication from amyloid deposition.

We describe the clinical course of an 81-year-old woman who was evaluated for worsening symptomatology of spinal cord claudication. Diagnostic studies revealed mild lumbar canal stenosis at L3-4, severe stenosis at L4-5 with a myelogram-CT scan demonstrating a complete block at this level mainly a result of a hypertrophied ligamentum flavum. At surgery, the ligamentum was found to be thickened and to be causing severe compression of the dural tube. Pathologic studies of the excised ligamentum flavum revealed extensive amyloid protein deposition. The amyloid was not further classified with further medical evaluation and followup failing to identify any conditions associated with local or systemic amyloidosis.

Aged↗

Myth breaker.

Explore the source record for details and available documents.

Ill-Housed Persons↗

Clinical trials in acute musculoskeletal injury states. An analysis of methodology.

Therapeutic evaluation of nonsteroidal anti-inflammatory drugs in the treatment of acute musculoskeletal diseases and injuries requires the use of adequate models for clinical trials. The objective of a short-term pain study is to determine whether a new treatment is effective and how it compares with a standard or reference drug for the indication being evaluated. Among the requirements for the pain model study are proper protocols and adequate, homogeneous patient populations. Problems in establishing the model include difficulty in finding adequate numbers of patients, inappropriate sites, patient resistance, and varying conditions of natural recovery. Suggestions are presented for conducting these studies: relying on global pain relief scores, keeping a home diary that is simple and objective, and extending the initial observation period in the office to generate single-dose data in a controlled environment. Sports medicine models are useful in allowing investigators the necessary numbers of patients and providing data that meaningfully address pharmacologic treatment for acute musculoskeletal disorders.

Acute Disease↗

Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study.

Fifty-nine patients with acute gouty arthritis entered into a 7-day multicenter, double blind trial of ketoprofen versus indomethacin. Patients were randomly assigned to receive 100 mg of ketoprofen (n = 29 patients) or 50 mg of indomethacin (n = 30 patients) 3 times a day. More than 90% of the patients in each group reported pain relief within the 1st day of treatment. By Day 5, 7 patients in the ketoprofen group and 6 in the indomethacin group discontinued treatment because of complete or substantial pain relief. At the end of the study, most patients in both groups were rated as having marked improvement both by the investigators and by self-assessment. Three patients in each group withdrew prematurely because of drug related gastrointestinal disorders. Ketoprofen compared favorably for efficacy and safety with indomethacin in the treatment of gouty arthritis.

Administration, Oral↗

Postsurgical pain: zomepirac sodium, propoxyphene/-acetaminophen combination, and placebo.

Zomepirac sodium, a new, nonnarcotic analgesic agent, was compared with the combination of propoxyphene/acetaminophen in a placebo-controlled, double-blind, single-dose study in 196 hospitalized postsurgical patients with pain severe enough to require a prescription analgesic. Patients received 100 mg zomepirac sodium, 50 mg zomepirac sodium, 100 mg propoxyphene napsylate with 650 mg acetaminophen, or placebo. Total pain relief during the 6-hour observation period showed that 100 mg zomepirac sodium was significantly more effective than the propoxyphene combination. All active drugs were superior to placebo. Percentages of patients requiring remedication before the end of the study were: 77 per cent for placebo, 48 per cent for propoxyphene/acetaminophen, 43 per cent for 50 mg zomepirac sodium, and 29 per cent for 100 mg zomepirac sodium. The numbers of patients reporting side effects were not significantly different among the treatment groups. These results confirm those of other single-dose pain studies which showed 100 mg zomepirac sodium significantly more efficacious than the propoxyphene/acetaminophen combination.

Acetaminophen↗

Lack of a direct metabolic effect of fructose, 1,6-diphosphate in ischemic myocardium.

Fructose 1,6-diphosphate (FdP) reportedly protects ischemic myocardium. To determine whether this is a direct action on the heart, we used a canine model in which two coronary arteries were perfused at identical but reduced rates. Into one artery we infused FdP (total doses of 400 mg or 1.8 g) while the other received 0.9% NaCl. After 1 h, biopsies were taken from a normal region and the two ischemic regions and were analyzed for ATP, phosphocreatine (PC), and lactate content. In the 0.9% NaCl-treated ischemic tissue, ATP and PC fell to half the nonischemic levels. The FdP-treated tissue exhibited high-energy phosphate levels similar to the 0.9% NaCl-treated tissue with no significant differences between the two ischemic areas. Lactate levels in both ischemic areas were elevated threefold above nonischemic levels. Contractility studies showed that infusion of FdP directly into the coronary artery depressed contractility in both nonischemic and ischemic conditions. Our data show that, if FdP does have a protective action in ischemia, it is not through a direct action on the heart.

Adenosine Triphosphate↗

Creatine kinase MB isoenzyme in dermatomyositis: a noncardiac source.

Three patients with polymyositis had elevated serum levels of creatine kinase MB isoenzyme. The presence of this isoenzyme is used extensively to diagnose myocardial infarction, but the isoenzyme is also found in sera of patients with primary muscular and neuromuscular disorders. We studied cardiac function in two of our patients with electrocardiograms, technetium stannous pyrophosphate scanning, and technetium 99m-labeled erythrocyte gated blood pool imaging and in the third patient by postmortem examination. There was no evidence of myocardial involvement to account for the high serum levels of isoenzyme. Creatine kinase MB in the sera of patients with polymyositis does not necessarily indicate myocardial necrosis.

Adult↗

The mechanism of action of soluble lymphocyte mediators. VI. Effect of migration inhibitory factor (MIF) on macrophage microtubules.

The effect of migration inhibitory factor (MIF) on macrophage microtubules was examined by functional, biochemical and morphological methods. It was found that: (1) the microtubule-stabilizing agent deuterium oxide (D2O) inhibits spontaneous macrophage migration from capillaries and enhances the migration blocking effect of MIF; (2) MIF does not modify the amount of total tubulin in macrophages, as determined by an 3H-colchicine binding assay, but increases significantly the proportion of tubulin present in polymeric form; (3) macrophages exposed to MIF and examined by immunofluorescence with specific antitubulin antibody demonstrate a striking increase in the percentage of cells with a well-organized microtubular network, characterized by a high density of thick fibrils and prominent paranuclear microtubule organizing centers. It is concluded that MIF inhibits cellular motility by inducing the formation of numerous microtubules, probably by enhancing tubulin polymerization.

Animals↗