Hypothyroidism in polycystic ovarian syndrome: a comparative study of clinical characteristics, metabolic and hormonal parameters in euthyroid and hypothyroid polycystic ovarian syndrome women

Background: This study was conducted to examine influence of hypothyroidism on pathophysiology and features of PCOS with respect to clinical characteristics of polycystic ovarian syndrome (PCOS), hormonal and metabolic profile.Methods: 102 euthyroid PCOS and 18 hypothyroid PCOS women were included in this cross-sectional study after considering inclusion and exclusion criteria. The study subjects were assessed for various signs and symptoms like recent weight gain, obesity, abnormal hair growth, hirsutism, hair loss, acne, acanthosis nigricans and infertility. Various hormonal and metabolic parameters were evaluated viz. Luteinizing hormone, Follicle stimulating hormone, LH:FSH ratio, testosterone, prolactin, dehydroepiandrosterone, fasting insulin and fasting blood glucose. BMI and HOMA values were calculated.Results: Association of hirsutism, excessive hair growth, hair loss, acanthosis nigricans, acne, infertility was not significant between the two groups. Majority of patients in both the groups were overweight/obese. BMI and number of patients complaining weight gain was significantly more in hypothyroid PCOS women. While no statistical difference in LH, FSH, LH:FSH ratio, prolactin, and testosterone levels was found, serum DHEA level was significantly less in hypothyroid PCOS group. No statistical difference in fasting blood glucose and insulin levels was found between the two groups. Though both the groups show insulin resistance, HOMA values were significantly more in hypothyroid PCOS women.Conclusions: Presence of hypothyroidism significantly increased severity of insulin resistance as well as obesity in PCOS. This could have adverse metabolic consequences in them. Concurrent occurrence of both these disorder could also possibly affect other features of the PCOS viz. hair loss and infertility

Delay Of Insulin Addition To Oral Combination Therapy Despite Inadequate Glycemic Control: Delay of Insulin Therapy

BACKGROUND: Patients and providers may be reluctant to escalate to insulin therapy despite inadequate glycemic control. OBJECTIVES: To determine the proportion of patients attaining and maintaining glycemic targets after initiating sulfonylurea and metformin oral combination therapy (SU/MET); to assess insulin initiation among patients failing SU/MET; and to estimate the glycemic burden incurred, stratified by whether HbA(1c) goal was attained and maintained. DESIGN: Longitudinal observational cohort study. SUBJECTS: Type 2 diabetes patients, 3,891, who newly initiated SU/MET between 1 January 1996 and 31 December 2000. MEASUREMENTS: Subjects were followed until insulin was added, health plan disenrolment, or until 31 December 2005. We calculated the number of months subjects continued SU/MET therapy alone, in total, and during periods of inadequate glycemic control; the A1C reached during those time periods; and total glycemic burden, defined as the estimated cumulative monthly difference between measured A1C and 8%. RESULTS: During a mean follow-up of 54.6 ± 28.6 months, 41.9% of the subjects added insulin, and 11.8% received maximal doses of both oral agents. Over half of SU/MET patients attained but failed to maintain A1C of 8%, yet continued SU/MET therapy for an average of nearly 3 years, sustaining glycemic burden equivalent to nearly 32 months of A1C levels of 9%. Another 18% of patients never attained the 8% goal with SU/MET, yet continued that therapy for an average of 30 months, reaching mean A1C levels of 10%. CONCLUSIONS: Despite inadequate glycemic control, a minority of patients added insulin or maximized oral agent doses, thus, incurring substantial glycemic burden on SU/MET. Additional studies are needed to examine the benefits of rapid titration to maximum doses and earlier initiation of insulin therapy

A comparative analysis of toluidine blue with frozen section in oral squamous cell carcinoma

Background:Surgical excision of the primary tumor with safe margins remains the mainstay of treatment for oral cavity squamous cell carcinoma (OSCC). The standard of care for assessment of intraoperative margins is frozen section histopathology. Unfortunately the facility is not available at most centers in limited resource countries. Toluidine blue, a metachromatic dye, has been well described in clinical identification of malignant and premalignant lesion in the oral cavity. Considering this we decided to explore intraoperative use of toluidine blue staining, in comparison with frozen sections, for the assessment of tumor-free margins. Methods: After obtaining clearance from the in-house ethical review committee, a prospective study was conducted at Aga Khan University Hospital, Karachi, from August 15, 2009 to March 14, 2010. A sample of 56 consenting Patients with biopsy-proven OSCC were included in the study, giving us 280 tumor margins. Margins were analyzed using toluidine blue staining and frozen section histopathology. A receiver operator curve (ROC) was then applied to compare assessment of margin status by toluidine blue and frozen section. Results: Of the 280 examined margins 11 stained positive with toluidine blue, three were positive on frozen section biopsy, and three were positive on final histopathology. Toluidine blue staining had sensitivity and specificity of 100% and 97%, respectively. The diagnostic accuracy of toluidine blue was found to be 97.1% with a positive predictive value (PPV) of 27.2% and a negative predictive value (NPV) of 100%. Conclusions: Toluidine blue can be used as an effective screening modality for the assessment of intraoperative margins in resource limited environments and reducing the number of frozen section biopsies performed. Further by providing real-time clinical information within minutes it can reduce indirect costs such as operating room time. It may also be used as an ad hoc for frozen section biopsies where frozen section facilities are available

A predictive score for retinopathy of prematurity in very low birth weight preterm infants

Aims This study describes the development of a score based on cumulative risk factors for the prediction of severe retinopathy of prematurity (ROP) comparing the performance of the score against the birth weight (BW) and gestational age (GA) in order to predict the onset of ROP.Methods A prospective cohort of preterm infants with BWp1500 g and/or GAp32 weeks was studied. the score was developed based on BW, GA, proportional weight gain from birth to the 6th week of life, use of oxygen in mechanical ventilation, and need for blood transfusions from birth to the 6th week of life. the score was established after linear regression, considering the impact of each variable on the occurrences of any stage and severe ROP. Receiver operating characteristic (ROC) curves were used to determine the best sensitivity and specificity values for the score. All variables were entered into an Excel spreadsheet (Microsoft) for practical use by ophthalmologists during screening sessions.Results the sample included 474 patients. the area under the ROC curve for the score was 0.77 and 0.88 to predict any stage and severe ROP, respectively. These values were significantly higher for the score than for BW (0.71) and GA (0.69) when measured separately.Conclusions ROPScore is an excellent index of neonatal risk factors for ROP, which is easy to record and more accurate than BW and GA to predict any stage ROP or severe ROP in preterm infants. the scoring system is simple enough to be routinely used by ophthalmologists during screening examination for detection of ROP. Eye (2012) 26, 400-406; doi: 10.1038/eye. 2011.334; published online 23 December 2011Hosp Clin Porto Alegre, Dept Ophthalmol, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Dept Ophthalmol, Sch Med, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, Sch Med, São Paulo, BrazilUniv Fed Rio Grande do Sul, Dept Paediat, Newborn Sect, Sch Med, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, Sch Med, São Paulo, BrazilWeb of Scienc

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy

Mutations in SPATA13/ASEF2 cause primary angle closure glaucoma

Current estimates suggest 50% of glaucoma blindness worldwide is caused by primary angle-closure glaucoma (PACG) but the causative gene is not known. We used genetic linkage and whole genome sequencing to identify Spermatogenesis Associated Protein 13, SPATA13 (NM_001166271; NP_001159743, SPATA13 isoform I), also known as ASEF2 (Adenomatous polyposis coli-stimulated guanine nucleotide exchange factor 2), as the causal gene for PACG in a large seven-generation white British family showing variable expression and incomplete penetrance. The 9 bp deletion, c.1432_1440del; p.478_480del was present in all affected individuals with angle-closure disease. We show ubiquitous expression of this transcript in cell lines derived from human tissues and in iris, retina, retinal pigment and ciliary epithelia, cornea and lens. We also identified eight additional mutations in SPATA13 in a cohort of 189 unrelated PACS/PAC/PACG samples. This gene encodes a 1277 residue protein which localises to the nucleus with partial co-localisation with nuclear speckles. In cells undergoing mitosis SPATA13 isoform I becomes part of the kinetochore complex co-localising with two kinetochore markers, polo like kinase 1 (PLK-1) and centrosome-associated protein E (CENP-E). The 9 bp deletion reported in this study increases the RAC1-dependent guanine nucleotide exchange factors (GEF) activity. The increase in GEF activity was also observed in three other variants identified in this study. Taken together, our data suggest that SPATA13 is involved in the regulation of mitosis and the mutations dysregulate GEF activity affecting homeostasis in tissues where it is highly expressed, influencing PACG pathogenesis