Clinico-pathological correlations of fatty acid synthase expression in retinoblastoma: an Indian cohort study

Retinoblastoma (RB), the most common intra-ocular malignancy in children under 5 years of age, has an estimated incidence of about 2000 a year in India, where most cases are in advanced stage at the time of diagnosis. Newer therapeutic approaches would reduce the morbidity of chemotherapy in children with RB. Fatty Acid Synthase (FASN), a lipogenic multi-enzyme complex, is minimally expressed in normal human tissues and over expressed in many cancers, making it an attractive target for cancer therapy. We analyzed RB tissues for FASN protein expression by immunohistochemistry, western blot, and ELISA, and FASN mRNA expression by RT-PCR. FASN expression was correlated with the clinico-pathological characteristics of the tumors. FASN immunostaining was positive in all the 44 RB tissues analyzed (100%). However, FASN expression was heterogeneous within the tumor samples. Tumors with invasion of choroid, optic nerve, orbit and/or retinal pigment epithelium showed significantly higher FASN immunoreactivity than the tumors without invasion (P < 0.05), supported by western analysis (P < 0.05). FASN expression was significantly high in poorly differentiated retinoblastomas (P < 0.05). FASN protein and FASN mRNA estimated by ELISA and RT-PCR respectively showed multi-fold expression over the non-neoplastic muller glial cells that varied quantitatively between tumor tissues. FASN mRNA over-expression was substantially lower than the corresponding FASN protein expression values. The present study reports (i) markedly high expression of FASN protein in poorly differentiated and in invasive retinoblastomas, and (ii) multi-fold over-expression of FASN mRNA and protein in RB tissues, although at varying levels, indicating FASN to be a potential therapeutic target in retinoblastoma management.     

Cardiac myxoma in Iceland: a case series with an estimation of population incidence

Cardiac myxoma (CM) is the most common primary benign tumor of the heart, but the true age-standardized incidence rate (ASR) has remained unknown. We therefore used nationwide registries in Iceland to study CM and establish its incidence rate. This was a retrospective study involving all patients diagnosed with CM in Iceland between 1986 and 2010. Cases were identified through three different registries, and hospital charts and histology results reviewed. An ASR was estimated based on a world standard population (w). Nine cases of CM (six women) were identified with a mean age of 62.8 years (range: 37-85), giving an ASR of 0.11 (95% CI: 0.05-0.22) per 100,000. The mean tumor size was 4.4 cm (range: 1.5-8.0) with all the tumors located in the left atrium. Dyspnea (n = 6) and ischemic stroke (n = 2) were the most common symptoms. All patients underwent complete resection of the tumor and there were no postoperative deaths or CM-related deaths at follow-up (mean 85 months). The ASR of CM in Iceland was 0.11 per 100,000. To our knowledge, this is the first study to determine the incidence of CM in an entire population. In Iceland, the presenting symptoms and mode of detection of CM are similar to those in other series.     

Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Senhance robot-assisted adrenalectomy: a case series

We present a case series of 12 consecutive robot-assisted adrenalectomies performed from May 2019 to March 2020 by a single surgeon experienced in laparoscopy using the novel Senhance robotic system. Eleven patients had primary aldosteronism due to an adrenal adenoma, diagnosed by means of endocrinological and radiological evaluation, and 1 had a benign adrenal cyst. The robotic adrenalectomy technique is described in detail. The mean procedure time was 165.1 minutes, with robotic docking time of 11.6 minutes and console time of 98.6 minutes. The mean estimated blood loss was 47 mL, and hospital stay duration was 4.5 days. There was 1 Clavien Dindo IIIB complication and 1 patient underwent conversion to laparoscopy. All patients with adenoma had complete biochemical remission after surgery. In conclusion, the Senhance robotic system is a safe and feasible platform for benign adrenal surgery in high-volume centers.

Laparoscopic adrenalectomy is the gold standard treatment of benign adrenal tumors because of the minimally invasive approach benefits. Although robot-assisted surgery was developed to enhance these benefits, adrenalectomy has not become a widespread robot-assisted procedure, probably due to a relatively low incidence of adrenal pathology. Published reports include a small number of patients, thus limiting conclusions regarding safety and feasibility of the procedure (1). The Da Vinci Surgical System was the only robotic platform in worldwide clinical use for two decades, practically becoming a synonym for robot-assisted surgery, but nowadays novel robotic platforms are emerging. The Senhance Surgical System, introduced into clinical use in 2013, is the first new platform that has proven to be safe and feasible in various surgical, gynecological, and urological procedures (2-6). This is the first detailed case-series of 12 consecutive robot-assisted adrenalectomies performed by using the new Senhance Surgical System reporting technical and clinical aspects of the procedure.     

Mutation spectrum in BBS genes guided by homozygosity mapping in an Indian cohort

Bardet–Biedl syndrome (BBS), a ciliopathy disorder with pleiotropic effect manifests primarily as retinal degeneration along with renal insufficiency, polydactyly and obesity. In this study, we have performed homozygosity mapping using NspI 250K affymetrix gene chip followed by mutation screening of the candidate genes located in the homozygous blocks. These regions are prioritized based on the block length and candidature of the genes in BBS and other ciliopathies. Gene alterations in known BBS (22) and other ciliopathy genes such as ALMS1 (2) were seen in 24 of 30 families (80%). Mutations in BBS3 gene, inclusive of a novel recurrent mutation (p.I91T) accounted for 18% of the identified variations. Disease associated polymorphisms p.S70N (BBS2), rs1545 and rs1547 (BBS6) were also observed. This is the first study in Indian BBS patients and homozygosity mapping has proved to be an effective tool in prioritizing the candidate genes in consanguineous pedigrees. The study reveals a different mutation profile in the ciliopathy genes in Indian population and implication of novel loci/genes in 20% of the study group.     

Cerebrovascular manifestations in scorpion sting: a case series

Cerebrovascular manifestations are uncommon presentations of scorpion sting in the Indian subcontinent. A prospective study was carried out on 50 patients with scorpion sting referred to the Government General Hospital during the period from April 2004 to March 2005. In all the patients, detailed history, physical examination with a specific neurological examination and routine biochemical testing and fundus examination were done. Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) were done in cases with neurological deficit. All these patients also underwent a complete hematological, rheumatologic and cardiovascular work-up for stroke. Cerebrovascular involvement was noted in four patients (8%). Hemorrhagic stroke was noted in two patients (4%) and thrombotic stroke was noted in two patients (4%). The mean time of presentation of neurological symptoms was 2 days. Stroke has been a common presentation in our series (8%). Contrary to world literature, there have been no reports of cranial nerve palsies or neuromuscular involvement in our series.     

Epidemiology of hemimegalencephaly: a case series and review

Hemimegalencephaly (HME) is a congenital brain malformation characterized by unilateral enlargement of the cerebral hemisphere. Clinically, HME is typically associated with hemiparesis, psychomotor retardation, and intractable seizures usually apparent soon after birth. HME is often an isolated finding, but it has been described as an occasional feature of a large number of syndromes, many of which may not be readily identified at birth. There are a multitude of case series and reports of HME in the English literature; however, there is no comprehensive, unbiased, detailed survey characterizing the proportion of cases of HME that are associated with a syndrome. We performed a retrospective study of all cases of HME seen at our institution from 1990 to 2003. Of the 15 cases of HME identified, 53% (8/15) were non-syndromic and 47% (7/15) of the cases were associated with a known or suspected genetic syndrome. In patients with syndromic HME, many of the syndromic features were not readily discernible at birth or in early infancy. It is, therefore, imperative to continually evaluate any infant with HME for signs and symptoms of these and other syndromes. Knowing the relative differential diagnosis will lead to a more comprehensive evaluation, improvement in expectant management, and appropriate counseling of families before considering radical surgical options such as hemispherectomy.     

Bombay phenotype in two North Indian brothers: a case report

Bombay phenotype is unique in the aspect that the red cells are not agglutinated by antisera A, B and H. However the serum of such individuals contains anti A, B and strongly reactive anti H which agglutinates red cells of 'O' group individuals through a wide thermal range. The blood specimen of a 35 year old male donor who donated blood for the first time was subjected to detailed cell and serum grouping. There was a discrepancy between the results. The possibility of Bombay phenotype was considered and the sample was tested with anti H lectin. Further confirmation of blood group and secretor status was done from a reference laboratory. Family studies showed the same blood group in the elder sibling of the propositus. The present case highlights the significance of correlating cell and serum grouping results. Moreover, this blood group is very rare in North India. Family studies revealed the propositus to possess the B gene which was suppressed in the donor but expressed in the offsprings. The use of anti H in discrepant blood grouping results is recommended.     

Gabapentin treatment of the non-refractory bipolar spectrum: an open case series

OBJECTIVE: To determine if gabapentin is effective in monotherapy or add-on treatment of non-refractory bipolar disorder in open prospective treatment. METHODS: Charts of 21 outpatients meeting DSM-IV criteria for bipolar spectrum disorder (type I, type II, NOS, and cyclothymia) and who were treated with gabapentin were reviewed and clinical response was assessed based on prospective application of the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impression scale (CGI), and the Global Assessment of Functioning scale (GAF). Also, response was rated retrospectively using the Clinical Global Impression scale for Bipolar Disorder (CGI-BP). RESULTS: Eight patients received gabapentin monotherapy and 13 received adjunctive therapy. Similar improvement in depression was noted in the monotherapy group, without induction of mania. Gabapentin was associated with a 43.8% improvement in manic symptoms and a 27.6% improvement in depressive symptoms in the overall sample. In the depressed subsample (n=10), there was a 57.5% improvement in depressive symptoms (P=0.10). Using the CGI-BP, gabapentin was moderately to markedly effective in 43% of patients for overall bipolar illness, 38% for depressive symptoms, and 25% for manic symptoms. Of those in the study, 62% reported side effects, mainly sedation and nausea, with 14% of the total sample discontinuing treatment due to adverse events. CONCLUSIONS: Gabapentin, either alone or as an adjunct, appeared moderately effective in treating depression in this small, uncontrolled, heterogeneous sample of non-refractory bipolar spectrum illness. Coupled with the earlier clinical literature, these data suggest the need for prospective double-blind studies of depressive illness in the bipolar spectrum.     

Evaluation of the role of LRRK2 gene in Parkinson's disease in an East Indian cohort

Leucine rich repeat kinase 2 (LRRK2) gene defects cause Parkinson's disease (PD). Recently, LRRK2 has also been shown by genome wide association (GWA) studies to be a susceptibility gene for the disease. In India mutations in LRRK2 is a rare cause of PD. We, therefore, genotyped 64 SNPs across LRRK2 in 161 control samples and finally studied 6 haplotype tagging SNPs for association-based study on 300 cases and 446 ethnically matched controls to explore the potential role of LRRK2 as a susceptibility gene in PD for East Indians. We did not find any significant allele/ genotype or haplotype associations with PD suggesting that common genetic variants within LRRK2 play limited role in modulating PD among East Indians. In addition, we also screened for the common mutations (viz. p.R1441C, p.R1441G, p.R1441H, p.Y1699C, p.G2019S), and a risk variant common among Asians (p.G2385R) but did not observe any of the above mentioned variants in our cohort. Our study, therefore, strongly suggests that LRRK2 has minimal role as a candidate and susceptibility gene in PD pathogenesis among East Indians.     

Effects of a novel anti-exospore monoclonal antibody on microsporidial development in vitro

The possible role of humoral antibodies in the immune response to microsporidiosis was studied using a novel anti-exospore monoclonal antibody (MAb) P5/H1 which recognised Encephalitozoon cuniculi. The effect of the P5/H1 MAb on microsporidial growth in vitro resulted in a reduction of the numbers of E. cuniculi spores in a Vero E6 cell-line culture. This reduction in the number of infected cells and the decrease of intracellular spores in infected cells was found when MAb P5/H1 was present in cultures, compared to cultures with an irrelevant isotype control MAb. Moreover, the presence of P5/H1 MAb increased the number of phagocytosed spores in macrophage cultures, and increased the activation of macrophages measured by nitrite oxide production. These results suggest a possible partial role of specific humoral antibodies in the protection against E. cuniculi infection.     

Headache attributed to psychiatric disorder: a case series

The association between psychiatric illness and headache is widely recognized. However, cases in which psychiatric disorders are the principal cause of headache are believed to be rare. "Headache attributed to psychiatric disorder" is a new category of secondary headache in the 2004 revision of the International Classification of Headache Disorders. The authors describe six patients in whom a psychiatric disorder is the most plausible cause of headache; most meet the new criteria or candidate criteria for headache attributed to a psychiatric disorder. The revised headache classification system appropriately recognizes headaches attributed to psychiatric disorder as a form of secondary headache.