Dysgerminoma presenting at fifty, consequence to undiagnosed Swyer syndrome

Swyer syndrome or XY complete gonadal dysgenesis (CGD) is a rare disorder of sex development (DSD) characterized by presence of dysgenetic gonads in a phenotypically female patient with a male karyotype. Usually Swyer syndrome is diagnosed following appropriate evaluation for amenorrhea in adolescence and prophylactic gonadectomy is done as these patients have high risk of developing malignancy in their dysgenetic gonads.  Here we presented patient who presented later in life with gonadal malignancy which turned out to be a consequence of undiagnosed Swyer syndrome. Her case exemplifies that fact that improper evaluation of primary amenorrhea in adolescence and omission to do prophylactic bilateral gonadectomy led to her presenting with malignancy at this advanced age. Therefore, be aware to not let Swyer syndrome go undiagnosed and mismanaged

Retain womb in retained placenta: hysterotomy for retained bilobed placenta in a preterm angular pregnancy

Angular pregnancy is a unique condition, which may be associated with both foetal and placental abnormalities, as well as preterm labour and retained placenta. Ultrasound is a useful tool in deciding feasibility of manual removal placenta by ruling out adherent placenta. A twenty five years primipara, five hours following preterm vaginal delivery, at 31 weeks of gestation presented with retained placenta. Uterus was well retracted with minimal bleeding, on trans-abdominal ultrasonography placenta accreta was ruled out. After stabilising, she had hysterotomy and placenta was removed which was bilobed. Neonate had cardiac and renal anomaly and succumbed at the end of one month of life. In young women prime priority is to preserve the uterus, by conservative approach as in our case

Ever intriguing ‘Primary Amenorrhea’- an audit

Background: Primary amenorrhea though its incidence is less than 0.1% often is a diagnostic challenge in establishing etiology and causes management dilemma to the gynecologist in the developing countries.Methods: A retrospective audit of all the cases of primary amenorrhea coming to our tertiary care teaching hospital in South India over 6 years, from January 2006 to December 2012.Results: Ninety-eight cases of primary amenorrhea were analyzed and it was found that the causes of primary amenorrhea were structural anomalies in 47.9%, endocrinological abnormality in 31.6%, and genetic factors in 20.5% of the patients. Mullerian anomalies were the most common cause for primary amenorrhea compared to gonadal dysgenesis in our study group; hence surgical correction formed an important mode of treatment following diagnosis.Conclusions: Primary amenorrhea work-up may seem to be complex, nevertheless a well elicited history, carefully conducted physical examination followed by use of imaging modalities and bio assays for endocrine abnormalities, permitted the clinician to narrow the diagnostic possibilities and reach an accurate diagnosis quickly that helped in choosing the appropriate management option. While managing, counselling of the patient and her near relatives was very essential for fruitful outcome. Among the surgical approaches for management, sigmoid vaginoplasty was found to be a promising alternative to MacIndoe’s vaginoplasty in our series.

Isolation, Characterization and Bioactivities of an Extracellular Polysaccharide Produced from Streptomyces sp. MOE6.

A Streptomyces strain was isolated from soil and the sequence of 1471 nucleotides of its 16S rDNA showed 99% identity to Streptomyces sp. HV10. This newly isolated Streptomyces strain produced an extracellular polysaccharide (EPS) composed mainly of glucose and mannose in a ratio of 1:4.1, as was characterized by Fourier transform infrared spectroscopy (FTIR), HPLC and ¹H-NMR. The antioxidant activities of the partially purified MOE6-EPS were determined by measuring the hydroxyl free radical scavenging activity and the scavenging of 2,2-diphenyl-2-picryl-hydrazyl (DPPH) radicals. In addition, the partially purified MOE6-EPS showed high ferrous ion (Fe2+) chelation activity which is another antioxidant activity. Interestingly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays that were colorimetric assays for NAD(P)H-dependent cellular oxidoreductases and a proxy of the number of viable cells, showed that the partially purified MOE6-EPS inhibited the proliferation of the human breast cancer cells (MDA-MB-231). The scratch wound assay showed that MOE6-EPS reduced the migration of mouse breast cancer cells (4T1). This study reports the production of EPS from Streptomyces species with promising antioxidant, metal chelating and mammalian cell inhibitory activities

Genotype-Phenotype Aspects of Type 2 Long QT Syndrome

Objectives The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Background Previous studies were limited by population size in their ability to examine phenotypic effect of location, type, and topology. Methods Study subjects included 858 type 2 LQTS patients with 162 different KCNH2 mutations in 213 proband-identified families. The Cox proportional-hazards survivorship model was used to evaluate independent contributions of clinical and genetic factors to the first cardiac events. Results For patients with missense mutations, the transmembrane pore (S5-loop-S6) and N-terminus regions were a significantly greater risk than the C-terminus region (hazard ratio [HR]: 2.87 and 1.86, respectively), but the transmembrane nonpore (S1-S4) region was not (HR: 1.19). Additionally, the transmembrane pore region was significantly riskier than the N-terminus or transmembrane nonpore regions (HR: 1.54 and 2.42, respectively). However, for nonmissense mutations, these other regions were no longer riskier than the C-terminus (HR: 1.13, 0.77, and 0.46, respectively). Likewise, subjects with nonmissense mutations were at significantly higher risk than were subjects with missense mutations in the C-terminus region (HR: 2.00), but that was not the case in other regions. This mutation location-type interaction was significant (p = 0.008). A significantly higher risk was found in subjects with mutations located in alpha-helical domains than in subjects with mutations in beta-sheet domains or other locations (HR: 1.74 and 1.33, respectively). Time-dependent beta-blocker use was associated with a significant 63% reduction in the risk of first cardiac events (p <0.001). Conclusions The KCNH2 missense mutations located in the transmembrane S5-loop-S6 region are associated with the greatest risk. (J Am Coll Cardiol 2009; 54: 2052-62) (C) 2009 by the American College of Cardiology Foundatio

Targeting MCL-1 and BCL-2 with polatuzumab vedotin and venetoclax overcomes treatment resistance in R/R non-Hodgkin lymphoma: Results from preclinical models and a Phase Ib study

The treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge. Here, we identify the pro-survival BCL-2 protein family member MCL-1 as a resistance factor for the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma (NHL) cell lines and primary NHL samples. Mechanistically, we show that the antibody-drug conjugate polatuzumab vedotin promotes MCL-1 degradation via the ubiquitin/proteasome system. This targeted MCL-1 antagonism, when combined with venetoclax and the anti-CD20 antibodies obinutuzumab or rituximab, results in tumor regressions in preclinical NHL models, which are sustained even off-treatment. In a Phase Ib clinical trial (NCT02611323) of heavily pre-treated patients with relapsed or refractory NHL, 25/33 (76%) patients with follicular lymphoma and 5/17 (29%) patients with diffuse large B-cell lymphoma achieved complete or partial responses with an acceptable safety profile when treated with the recommended Phase II dose of polatuzumab vedotin in combination with venetoclax and an anti-CD20 antibody.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175920/1/ajh26809_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175920/2/ajh26809.pd