Intussusception in a premature neonate: A rare and often misdiagnosed clinical entity

Intussusception is a very rare cause of intestinal obstruction in neonates. It is of extremely rare occurrence among premature neonates. We present a case of 11-day-old premature neonate who presented with abdominal distension, intolerance to feeds, vomiting, significant bilious aspirate and bleeding per rectum. The initial diagnosis of necrotizing enterocolitis (NEC) led to a delay in the diagnosis. On exploratory laparotomy, it turned out to be a case of ileo-colic intussusception with Meckel''s diverticulum as a lead point. This site of intussusception (ileo-colic) and presence of a lead point among premature neonate is of exceedingly rare occurrence and very few such cases have been reported.In this article, the published work about clinical features and management on intussusceptions in premature neonates has been reviewed. The authors intend to highlight the difficulty in distinguishing the NEC and intussusception. Subtle clinical and radiological features which can help in differentiating the two conditions have been emphasized. This can avoid the delay in diagnosis and management which can prove critical. High index of suspicion with timely intervention is the key for optimizing outcome. A diagnosis of intussusception should always be considered in any preterm infant with suspected NEC.     

Mayer-Rokitansky-Kuster-Hauser syndrome and anal canal stenosis: case report and review of literature

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a characteristic syndrome in which the mullerian structures are absent or rudimentary. It is also associated with anomalies of the genitourinary and skeletal systems. There are very few cases reported regarding its association with anorectal malformations, particularly perineal fistulas. To the best of our knowledge, there have not been any reported cases of anal canal stenosis in patients with MRKH. We describe a very rare association of MRKH with anal canal stenosis and multiple renal calculi. The patient underwent corrective surgery for the anomalies and removal of renal calculi. She has been under regular follow-up for the last few months and is doing well.     

Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells

Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the “non-oncogene” addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded “client” proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4–1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G₂-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.     

ADH1B,ALDH2, GSTM1 and GSTT1 Gene Polymorphic Frequencies among Alcoholics and Controls in the Arcadian Population of Central India

Background: Epidemiological research has highlighted the global burden of primary liver cancer cases due toalcohol consumption, even in a low consumption country like India. Alcohol detoxification is governed by ADH1B,ALDH2, GSTM1 and GSTT1 genes that encode functional enzymes which are coordinated with each other to removehighly toxic metabolites i.e. acetaldehyde as well as reactive oxygen species generated through detoxification processes.Some communities in the population appears to be at greater risk for development of the liver cancer due to geneticpredispositions. Methods: The aim of this study was to screen the arcadian population of central India in order toinvestigate and compare the genotype distribution and allele frequencies of alcohol metabolizing genes (ADH1B,ALDH2, GSTM1 and GSTT1) in both alcoholic (N=121) and control (N=145) healthy subjects. The gene polymorphismanalysis was conducted using PCR and RFLP methods. Results: The allele frequency of ALDH2 *1 was 0.79 and ofALDH2*2 was 0.21 (OR:1.12; CI (95%): 0.74-1.71). The null allele frequency for GSTM1 was 0.28 (OR:0.85; CI(95%): 0.50-1.46) and for GSTT1 was 0.20 (OR:1.93; CI (95%): 1.05-3.55). No gene polymorphism for ADH1B wasnot observed. The total prevalence of polymorphisms was 3.38% for ALDH2, GSTM1 and GSTT1. Conclusion: Theresults of this study suggested that individuals of the Central India population under study are at risk for liver disordersdue to ALDH2, GSTM1 and GSTT1 gene polymorphisms. This results may have significance for prevention of alcoholdependence, alcoholic liver disorders and the likelihood of liver cancer.     

Ganetespib radiosensitization for liver cancer therapy

Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33–1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies.     

Challenges in the first seizure clinic for adult patients with epilepsy

Aims. (1) To delineate the challenges in seizure diagnosis in the first seizure clinic setting for adult patients of a teaching hospital, and (2) quantify the diagnostic accuracy of the referral source and the yield of routine investigations, including blood tests, EEGs, and neuroimaging. Methods. We retrospectively reviewed medical records of patients referred by the emergency department to the adult first seizure clinic and seen by the same epilepsy specialist between June 2007 and June 2011. The diagnostic accuracy in the emergency department was calculated by comparing with the final diagnosis made by an epilepsy specialist. Results. In total, 219 patients were referred to the first seizure clinic. Median age was 45 and 60% of patients were male. From the cohort, 38 (17%) patients presented with seizure mimickers; the most common were reflex syncope (74%) and psychogenic non‐epileptic seizures (16%). From the remaining 181 patients presenting with seizures, only 110 (61%) of these patients were diagnosed with true first seizures, and 71 (39%) patients had evidence of previous seizures. Nineteen (17%) of true first‐ever seizures were provoked. The most frequent cause of provoked seizures was alcohol and illicit drugs (65%). In the emergency department, sensitivity and specificity in seizure diagnosis were 0.74 and 0.32, respectively. In our true first seizure patients, the EEG demonstrated epileptiform discharges in 22 (21%) patients. In the same cohort, computed tomography and magnetic resonance neuroimaging conferred 16% and 20% probability of finding a potentially epileptogenic structural abnormality, respectively. The most common epileptogenic abnormality found on magnetic resonance neuroimaging was cortical infarct. Conclusions. The diagnosis and management of first seizure remains challenging due to the variety of seizure mimickers and low yield of investigations. Our data highlight the potential pitfalls and practical challenges in this process, as well as the need for these patients to be assessed in dedicated first seizure clinics.