Premature ovarian failure

Premature ovarian failure (POF) causing hypergonadotrophic hypogonadism occurs in 1% of women. In majority of cases the underlying cause is not identified. The known causes include: (a) Genetic aberrations, which could involve the X chromosome or autosomes. A large number of genes have been screened as candidates for causing POF; however, few clear causal mutations have been identified. (b) Autoimmune ovarian damage, as suggested by the observed association of POF with other autoimmune disorders. Anti-ovarian antibodies are reported in POF by several studies, but their specificity and pathogenic role are questionable. (c) Iatrogenic following surgical, radiotherapeutic or chemotherapeutic interventions as in malignancies. (d) Environmental factors like viral infections and toxins for whom no clear mechanism is known. The diagnosis is based on finding of amenorrhoea before age 40 associated with FSH levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work-up. There is no role of ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the only proven means for the latter being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.     

Identification of amino acid residues of anthrax protective antigen involved in binding with lethal factor

Protective antigen (PA) and lethal factor (LF) are the two components of anthrax lethal toxin. PA is responsible for the translocation of LF to the cytosol. The binding of LF to cell surface receptor-bound PA is a prerequisite for the formation of lethal toxin. It has been hypothesized that hydrophobic residues P184, L187, F202, L203, P205, I207, I210, W226, and F236 of domain 1b of PA play an important role in the binding of PA to LF. These residues are normally buried in the 83-kDA version of PA, PA83, as determined by the crystal structure of PA. However, they become exposed due to the conformational change brought about by the cleavage of PA83 to PA63 by a cell surface protease. Mutation of the above-mentioned residues to alanine resulted in mutant proteins that were able to bind to the cell surface receptors and also to be specifically cleaved by the cellular proteases. All the mutant proteins except the F202A, L203A, P205A, and I207A mutants were able to bind to LF and were also toxic to macrophage cells in combination with LF. It was concluded that residues 202, 203, 205, and 207 of PA are essential for the binding of LF to PA.     

An amazing case of working wrist watch in the esophagus

Foreign bodies in the esophagus are commonly seen in otolaryngologic practice. We report the successful removal of a working wrist watch dial lodged for one month in the esophagus of an adult schizophrenic patient, which is a rare incident.     

Marginal and Internal Gap of Metal Copings Fabricated Using Three Types of Resin Patterns with Subtractive and Additive Technology: An In Vitro Comparison

This study analyzes the evidence of the marginal discrepancy and internal adaptation of copings fabricated using three types of resin patterns with subtractive (milling) and additive technology (3D printing), as it is not widely reported. Working casts (n = 15) were scanned and patterns were completed using computer-aided designing (CAD). Resin patterns were fabricated using the designed data and divided into three groups according to the method of fabrication of patterns: subtractive technology–CAD milled polymethyl methacrylate resin (Group-PMMA), additive technology [digital light processing (DLP) technique]–acrylonitrile–butadiene–styrene (ABS) patterns (Group-ABS), and polylactic acid (PLA) patterns (Group-PLA). Resin patterns were casted with Cobalt–Chromium (Co–Cr) alloy (lost wax technique). Internal and marginal gaps of the metal copings were analyzed with the replica technique under optical microscope. The Kruskal–Wallis test was used to compare values among the groups, and post hoc multiple tests confirmed the specific differences within the groups. The median marginal gap was least for CAD milled resin patterns, followed by PLA printed resin patterns and ABS printed resin patterns. There were significant differences between Group-PMMA and Group-PLA and Group-ABS (p = 0.0001). There was no significant difference between Group-PLA and Group-ABS (p = 0.899). The median internal gap was least for metal copings fabricated from Group-PLA, followed by Group-ABS and Group-PMMA. The differences were not statistically significant (p = 0.638) for the internal gap. Full metal Co–Cr copings fabricated from the milled PMMA group had a better marginal fit, followed by the PLA and ABS printed groups. Copings fabricated with the PLA printed group had the best internal fit, though the values were statistically insignificant between the groups.     

Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14–25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.     

Determinants of lymph node resolution in patients of tubercular lymphadenitis treated with anti tuberculous chemotherapy: A hospital based longitudinal study

IntroductionThe variable course of illness in patients of Tubercular lymphadenitis remains a therapeutic challenge to treating physicians in a significant proportion of patients. This study was aimed to explore the possible determinants which could predict the outcome of this subgroup of patients.MethodologyThis was a prospective cohort study where 94 patients of TB lymphadenitis were enrolled who could be followed up till the end of treatment. They were evaluated in the beginning and monitored till the end of treatment keeping into account the clinical behaviour of lymph nodes during the course of Anti tubercular chemotherapy.ResultsOut of 94 patients, 60 had their lymph nodes resolved at the end of prescribed treatment duration wheras 34 were classified as partial responders. Another 26 amongst them had their nodes resolved by an extension of continuation phase by 3–6 months. Presence of bilateral and multiple lymph nodes, necrosis on Fine needle aspiration at initial diagnosis and occurrence of Paradoxical upgrading reaction were associated with the partial resolution of lymph nodes at the end of stipulated ATT duration.ConclusionTreatment duration should be individualized by the treating physicians. Certain parameters mentioned above can be taken as warning signals of patients ending up as partial responders and hence the need of a prolonged extension phase.