New approach to polycystic ovary syndrome and other forms of anovulatory infertility

Anovulation can be classified in the clinic on the basis of serum hormone assays. Low gonadotropins along with low estrogen concentrations are suggestive of a central origin of the disease, whereas low estrogen levels along with elevated gonadotropins indicate a primary defect at the ovarian level. Most anovulatory patients (approximately 80%) present with serum FSH and estradiol levels within the normal range (World Health Organization class II). Polycystic ovary syndrome (PCOS) is a common but poorly defined heterogeneous clinical entity. Historically, characteristic ovarian abnormalities represented a hallmark of the syndrome. Because several etiological factors may lead to a similar end point (i.e., polycystic ovaries), the development of a clinically applicable classification of the syndrome has proven difficult. Clinical, morphological, biochemical, endocrine, and, more recently, molecular studies have identified an array of underlying abnormalities and added to the confusion concerning the pathophysiology of the disease. Despite the vast literature regarding the etiology and classification of PCOS, no consensus has been reached regarding the validity of criteria used to diagnose the syndrome. For instance, the significance of elevated serum luteinizing hormone (LH) concentrations, insulin resistance or polycystic-appearing ovaries assessed by ultrasound for PCOS diagnosis remains uncertain. In contrast, hyperandrogenism and chronic anovulation generally are believed to be mandatory diagnostic features. Patients with PCOS might visit a dermatologist for hirsutism, a generalist, or internist for complaints related to obesity or a gynecologist for irregular or absent bleeding. However, most patients seek the care of a gynecologist because of cycle abnormalities (oligomenorrhea) and infertility. In PCOS, serum FSH and estradiol (E2) levels are usually found to be within the (broad) normal ranges, whereas LH may either be normal or elevated. Because PCOS with normal or high LH does not seem to represent different clinical entities, it seems justifiable to consider this syndrome as a subgroup of WHO-II patients, although estrogen levels may be tonically elevated in these patients. This review will focus on characteristics of the heterogeneous group of WHO-II patients in an attempt to identify factors involved in the etiology and possible ovulation induction outcome of PCOS. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to outline the current classification of anovulatory infertility and to explain the characteristics and features used for classification.     

Improving recipient vessel exposure during microvascular breast reconstruction

Microvascular tissue transfer has become the gold standard for breast reconstruction. The primary drawback to these procedures is the technical expertise required for microsurgical anastomosis. This problem is compounded by the difficulties in the exposure of recipient vessels deep within the axilla. Previous techniques used for exposure of these vessels are difficult to setup, provide less than optimal exposure, and have been associated with brachial plexus injuries. The authors retrospectively review their experience using the pediatric OMNI retractor for exposure of recipient vessels during microvascular breast reconstruction. Patient demographics, flap choice, recipient vessels, the incidence of neuropraxia/brachial plexopathy, and microvascular complications were analyzed. Patients in whom more traditional methods of vessel exposure were used (ie, Gelpi retractors, arm positioning, fish hooks; 517 reconstructions in 392 patients) were compared with patients in whom vessel exposure was performed using the pediatric OMNI retractor (699 reconstructions in 571 patients). No differences were noted in comorbid conditions or the incidence of microvascular complications. However, the use of the pediatric OMNI was associated with a significant reduction in operative time in unilateral reconstructions (6:23 +/- 0.05 h vs 7:48 +/- 0.05 h; P <0.01) and decreased incidence of brachial plexus injury (0.17% vs 3.3%; P <0.01). The authors think the decreased neuropraxia rate is the result of better exposure afforded by the pediatric OMNI retractor, which improves exposure and eliminates the need for excessive arm abduction or awkward positioning during the dissection and anastomosis of axillary recipient vessels.     

End-to-side neurorrhaphy: an experimental study in rabbits

The concept of end-to-side nerve repair was recently introduced; however, most authors have reported conflicting results with this technique. This study was conducted to assess the effectiveness of end-to-side nerve repair in both fresh and predegenerated specimens by histological evaluation in an animal study in rabbits. Thirty male rabbits were divided into three groups. In group 1 (n = 14), the peroneal nerve was divided and sutured end-to-side to the tibial nerve via an epineurial window. In group 2 (n = 13), the peroneal nerve was divided and sutured end-to-side to the tibial nerve after a 1-week "predegeneration period." In group 3 (n = 3), which was considered the control group, the peroneal nerve was divided and sutured to the adjacent soft tissues. After 3 months, specimens were harvested for histological evaluation. Nerve fiber count, in normal peroneal nerves, averaged 532/cross section. In groups 1 and 2, average nerve fiber count in implanted peroneal nerves was 6.24 and 7.00/cross section, respectively. No significant statistical difference was observed between fresh and "predegenerated" groups (P = 0.90). These data suggest that collateral sprouting of donor nerves is possible after end-to-side neurorrhaphy through an epineurial window, but the number of nerve fibers in recipient nerves is too low to result in any functional recovery in the target organ.     

The Common 677C>T Gene Polymorphism of Methylenetetrahydrofolate Reductase Gene is not Associated with Breast Cancer Risk

Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and plays a role in DNA biosynthesis, methylation, and repair in actively dividing cells. A common 677C>T polymorphism in the gene for MTHFR, leading to a thermolabile enzyme with decreased activity, has been associated with reduced plasma folate levels and elevated homocysteine levels and could be a risk factor for breast cancer. In the present case-control study, MTHFR genotype was determined in 500 women with clinically verified breast cancer and 500 female age-matched healthy control subjects. The homozygous TT genotype was found in 13.0% patients and 13.1% controls (P = n.s.). The odds ratio of TT homozygotes for breast cancer was 0.99 (95% confidence interval 0.68–1.43). The MTHFR genotype was furthermore not associated with tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. In a subgroup of 116 premenopausal patients, no increased frequency of the homozygous 677T genotype was found (13.8%). Therefore, we conclude that the MTHFR 677C>T polymorphism is not associated with individual susceptibility to breast cancer.     

A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk

A common 936 C/T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels. In our case-control study, we investigated the role of this polymorphism for breast cancer risk. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29.4%) than among patients (17.6%; p = 0.000014). The odds ratio for carriers of a 936T-allele for breast cancer was 0.51 (95% confidence interval 0.38-0.70). Additionally, VEGF plasma levels were determined in 21 nonsmoking post-menopausal controls; carriers of a 936T allele had significantly lower levels (median 23 pg/ml; range 6-50 pg/ml) than noncarriers (37; 21-387; p = 0.034). We conclude that carriers of a VEGF 936T-allele are at decreased risk for breast cancer, this, however, requiring further confirmation in a larger study.     

Adult toxicology in critical care: part I: general approach to the intoxicated patient

Intensivists are confronted with poisoned patients on a routine basis, with clinical scenarios ranging from known drug overdose or toxic exposure, illicit drug use, suicide attempt, or accidental exposure. In addition, drug toxicity can also manifest in hospitalized patients from inappropriate dosing and drug interactions. In this review article, we describe the epidemiology of poisoning in the United States, review physical examination findings and laboratory data that may aid the intensivist in recognizing a toxidrome (symptom complex of specific poisoning) or specific poisoning, and describe a rational and systematic approach to the poisoned patient. It is important to recognize that there is a paucity of evidence-based information on the management of poisoned patient. However, the most current recommendations by the American Academy of Clinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists will be reviewed. Specific poisonings will be reviewed in the second section of these review articles.     

Bilateral asynchronous acute epidural hematoma : a case report

Background  

Bilateral extradural hematomas have only rarely been reported in the literature. Even rarer are cases where the hematomas develop sequentially, one after removal of the other. Among 187 cases of operated epidural hematomas during past 4 years in our hospital, we found one case of sequentially developed bilateral epidural hematoma.     

Local and systemic effects of intralaryngeal injection of cidofovir in a canine model

OBJECTIVE: The safety of intralaryngeal injection of cidofovir remains a concern. Our goal was to evaluate local and systemic effects of intralaryngeal injection of cidofovir. STUDY DESIGN: Animal study using a canine model. METHODS: Two groups of three young beagle dogs (6 vocal folds in each group) were used. Subepithelial vocal fold injections were performed in each group biweekly for 6 months with 0, 2.5, 5, 10, 20, and 37.5 mg cidofovir in a 0.5 mL volume. Direct laryngoscopy was performed at each injection interval. Complete blood cell count and renal parameters were measured at baseline and monthly thereafter. Histopathologic examination of the vocal folds was performed after the 6-month injection period in one group of animals and after an additional 6-month observation period in the second group. RESULTS: Endomysial edema with muscle fiber separation and dose-dependent atrophy and scarring of the vocal folds was present. Onset of atrophy and scarring was observed after 3, 7, and 11 injections in the vocal folds injected with 37.5, 20, and 10 mg cidofovir, respectively. After the 6-month observation period, recovery of histologic abnormalities was complete in the low-dose (0, 2.5 mg) vocal folds, near complete in the intermediate-dose (5, 10 mg) vocal folds, and no apparent recovery was seen in the high-dose (20, 37.5 mg) vocal folds. Leukocyte count and renal parameters remained unchanged at up to 4.26 mg/kg body weight of systemic dose of cidofovir. CONCLUSIONS: Intralaryngeal cidofovir leads to dose-dependent scarification of the vocal folds that appears irreversible at higher doses. Lower concentrations of this drug should be used in intralesional intralaryngeal use.     

Risk factors for failure of 5-fluorouracil needling revision for failed conjunctival filtration blebs

PURPOSE: To investigate the risk factors for failure of 5-fluorouracil (5-FU) needling revision, a useful procedure for restoring a failed filtration bleb. DESIGN: Interventional case series.METHODS: Retrospectively conducted study. SETTING: Institutional. STUDY POPULATION: Sixty-four eyes of 64 consecutive glaucoma patients that underwent 5-FU needling revisions for failed filtering bleb following either trabeculectomy or phaco-trabeculectomy with or without adjunctive mitomycin C (MMC). OBSERVATION PROCEDURES: Goldmann applanation tonometry, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. MAIN OUTCOME MEASURES: Successful outcome of the initial 5-FU needling revision, arbitrarily defined as target intraocular pressure (IOP) control with not more than two topical glaucoma medications and no additional 5-FU needling or other surgical procedures, was analyzed by Kaplan-Meier survival analysis, and risk factors for failure of the initial 5-FU needling revision were analyzed by Cox proportional hazards regression analysis. RESULTS: The cumulative success rate of the initial 5-FU needling revision was 45% at 1 year, 33% at 2 years, and 28% at 4 years. Failure of the initial 5-FU revision correlated significantly with preneedling IOP > 30 mm Hg (P =.0003), lack of MMC use during the previous filtration surgery (P =.013), and IOP >10 mm Hg immediately following needling revision (P =.0012) according to Cox's proportional hazards regression analysis.CONCLUSIONS: Pre-needling IOP > 30 mm Hg, lack of MMC use during the previous filtration surgery, and IOP > 10 mm Hg immediately after needling were found to be significant risk factors for failure of the initial 5-FU needling procedure. Therefore, it is important to monitor IOP closely following needling revision in those patients with such risk factors. They are more likely to require additional therapeutic interventions, including repeat needling revisions.