Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

Evaluation of pregnant women with scarred uterus in a low resource setting

AIM: Management of post cesarean pregnancy continues to be a dilemma. The present study was undertaken to evaluate the outcome of such pregnancies in a resource constrained setting so that an appropriate management protocol can be decided. METHODS: An observational study was conducted in the Department Of Obstetrics And Gynecology, King George's Medical University, Lucknow, India. The outcome of all of the women admitted with pregnancy with a previous cesarean section was noted. RESULTS: A total number of 447 women with a post cesarean pregnancy underwent delivery. These comprised 13.7% of total deliveries over the same period. 124 women (27.7%) had successful vaginal delivery while 323 (72.3%) had a repeat cesarean section. Maternal morbidity and perinatal mortality were both significantly higher in the vaginal delivery group (P = 0.00211 and P = 0.0426, respectively). CONCLUSIONS: Vaginal birth after cesarean (VBAC) is associated with higher maternal morbidity and perinatal mortality. Therefore the decision for VBAC must be taken only after proper consideration and counseling of the couple.     

Influence of sugars on the activity of cellulase system from two basidiomycetes cultures

Influence of some sugars was studied on activity of purified cellulase enzymes produced by two white-rot basidiomycetes cultures in submerged fermentation. Exo- and endo-glucanases were found to be stimulated by glucose, sucrose and xylose, but β-glucosidase was inhibited by all sugars tested except sucrose being neutral. Cellobiose severely inhibited all three cellulase activities at all three concentrations taken in reaction mixture.     

Alterations in free radical scavenger system profile of type I diabetic rat brain

The activities of the enzymes related to glutathione synthesis, degradation, and functions as well as reactive oxygen scavenging enzymes were analyzed in different brain regions, such as cerebral hemisphere, cerebellum, brainstem, thalamus, and hypothalamus after 1 and 3 mo of streptozotocin-induced diabetes in rats. Parallel studies were also made in age-matched control rats and insulin-treated diabetic rats. The content of glutathione (GSH) and its synthesizing enzyme γ-glutamylcystein synthetase and also superoxide dismutase (SOD) and catalase activities (reactive oxygen scavenging enzymes) were significantly decreased from almost all the brain regions studied. However, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), γ-glutamyl transpeptidase (γ-GTP), and glutamine synthetase (GS) activities were increased in the diabetic rat brain. Insulin treatment to the diabetic rats resulted in partial to full recovery in these enzymes activities. The present results emphasize the potentially serious alterations of brain free radical scavenger system in uncontrolled Type I diabetes.     

Synthesis and Neuromuscular Blocking Activity of 16β-Piperidino Epiandrosterone Derivatives

This study reports the synthesis of steroidal quaternary ammonium compounds 11 and 12, with quaternary nitrogen at position 3 and 16 of the steroid nucleus in 5α-epiandrosterone series; along with their neuromuscular blocking activity using chick biventer cervicis muscle preparation. The compound 12 was found to be five times more potent than 11 in reducing twitch response to nerve stimulations, indicating the importance of extended interonium distances and 17-acetoxy function for potent antagonist activity.     

Bilateral congenital coronary ostial obstruction: Exertional syncope in an otherwise healthy 8‐year‐old

Congenital stenosis/atresia of a coronary artery is an exquisitely rare anomaly (Congenit Heart Dis, 2, 2007, 347) with increased risk of sudden death. Bilateral coronary obstruction is even more unusual but has been reported in conjunction with aortic valve disease, syphilis, and Takayasu's arteritis. To the best of our knowledge, obstruction of both coronaries in a pediatric patient has only been reported once (Ann Thorac Surg, 55, 1993, 1564). We present a patient with an intramural, anomalous aortic origin of the right coronary artery from the contralateral sinus (AAORCA) with near atresia of the left main coronary ostium. The diagnosis was made by echocardiogram and confirmed by catheterization and magnetic resonance imaging.     

A case report of an unusual presentation of ocular rhinosporidiosis as a conjunctival cystic mass

Ocular involvement of rhinosporidiosis is seen in about 15% of cases and clinically appears as a freely mobile, granular, pink, fleshy sessile or pedunculated mass. The conjunctiva is the most common site of origin. A 25-year-old male presented with a painless mass in the lower part of the left eye for 6 months which was gradually progressive. Examination revealed a pedunculated mass of 15 mm x 15 mm arising from the lower palpebrae of the left eye retracting the lower lid. It appeared to be vascular with few white spots at the apex. Rest of the ocular examinations was within the normal limit. The presentations of ocular rhinosporidiosis vary. Though the conjunctival origin is very common, it may not have a classic pink fleshy appearance at all times. A vascular/cystic painless conjunctival mass should also be considered as a case of rhinosporidiosis in prone areas.     

Incidence of anticardiolipin antibodies and lupus anticoagulant factor among women experiencing unexplained recurrent abortion and intrauterine fetal death

The aim of this research study was to estimate anticardiolipin (IgG & IgM) antibodies (aCL) and lupus anticoagulant (LA) factor in patients of recurrent unexplained pregnancy loss and intrauterine fetal deaths (IUFD). 82 women were selected for this study by virtue of having more than two consecutive unexplained pregnancy losses in their first trimester and were referred by the department of Obstetrics and Gynecology, King Saud Medical City Hospital, Riyadh, KSA. All patients had gone through a standardized investigation sequence. Lupus anticoagulants and Anticardiolipin antibodies (IgM and IgG) were detected in the serum by the enzyme linked immunosorbent assay method. To check the significance of aCL and LA, two-tailed t-test was done. Non parametric data was calculated either by Chi-Square test or Fischer exact test when relevant. Total 82 females grouped as 52 cases of recurrent (≥ 2) mainly first and second trimester miscarriage and 30 cases of recurrent (≥ 2) late intrauterine fetal death. Lupus anticoagulants was observed in twenty one (21) cases (25.6%) while anticardiolipin antibodies IgM and or IgG positive cases were estimated in forty four (44) cases (53.65%). The prevalence of APS in both studied group was thirty five (35) cases (42.68%). Antiphospholipid antibodies are calculated as the most important reason for recurrent abortion. The patients with unexplained recurrent pregnancy loss must be advised to go for a screening test for all this aPL antibodies.