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Biomedical subjects

M Mathur

Publications and source records attributed to M Mathur.

At least 19 recordsLinked to original sources

Role of PSF-TFE3 oncoprotein in the development of papillary renal cell carcinomas.

A subset of papillary renal cell carcinomas (RCC) is characterized by the expression of a TFE3 fusion protein, where the fusion partner can be any of the several proteins identified so far such as PSF (PTB associated splicing factor), NonO, PRCC, CLTC and ASPL. These proteins result from chromosomal translocations involving the TFE3 gene located on the X chromosome. Our present study documents the central role of PSF-TFE3 in oncogenic transformation. We show that the inhibition of PSF-TFE3 expression through siRNA or shRNA leads to impaired growth, proliferation, invasion potential and long-term survival of UOK-145 papillary renal carcinoma-derived cells, which endogenously express PSF-TFE3. The oncogenic potential of PSF-TFE3 became evident by stable expression of PSF-TFE3 in NIH-3T3 mouse fibroblast cells, which leads to the acquisition of anchorage-independent growth as revealed by soft agar assay. In addition, the expression of PSF-TFE3 in normal renal proximal tubular epithelial cells from where such tumors originate leads to dedifferentiation and loss of some key functional proteins, which may reflect an initial step in the multistep process of tumor development. This suggests that the expression of PSF-TFE3 in renal epithelial cells plays an important role in the initiation and maintenance of oncogenic phenotype in papillary RCC.

Animals↗

A prospective double-blind randomised controlled trial of intraoperative pelvic instillation with bupivacaine for management of pain following laparoscopy and dye.

The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the effectiveness of intraperitoneal instillation of bupivacaine following laparoscopy and dye test. Women received either 15 ml of 0.9% saline (n= 42) or 15 ml of 0.5% bupivacaine (n= 43), which was instilled intraperitoneally. Pain and nausea scores were recorded on a visual analogue scale (VAS). Pain perception was no different in the bupivacaine group compared with the control group with median values of VAS at 2 hours (18, 19; P= 0.8), 6 hours (21, 22; P= 0.5), 12 hours (19, 25; P= 0.8), 24 hours (27, 27; P= 0.9) and 48 hours (21, 13; P= 0.26). Women in the bupivacaine group were less nauseated than controls in the immediate postoperative period (with median VAS scores of 0, 8; P value = 0.03 at 2 hours and 0, 7; P= 0.01 at 6 hours).

Anesthetics, Local↗

Simple and economical method for speciation and resistotyping of clinically significant coagulase negative staphylococci.

An attempt was made to speciate 102 clinically significant isolates of coagulase negative staphylococci (CoNS) by a practical scheme adapted from various references. This scheme utilizes slide and tube coagulase test, urease test ornithine decarboxylase, novobiocin susceptibility and aerobic acid from mannose for assigning species group. Inclusion of one or two additional tests in a species group could identify the isolates to species level. Ninety eight (97%) isolates were conveniently identified as S. epidermidis (41%), S. saprophyticus (16.6%), S. haemolyticus (14.7%), S. hominis (14.7%), S. lugdunensis (4.9%), S. schleiferi (1.9%) and S. capitis (1.9%). Only four isolates were not identified to the species level, two of which were probably S. capitis subspecies ureolyticus / S. warneri / S. simulans . Antibiotic susceptibility testing showed maximum resistance to ampicillin (89%) followed by cefotaxime (59%) with no resistance to vancomycin. The increasing recognition of pathogenic potential of CoNS and emergence of drug resistance amongst them denotes the need to adopt simple laboratory procedures to identify and understand the diversity of staphylococci isolated from clinical material.

Bacteriological Techniques↗

HIV-1 seronegativity in a child with proved perinatal HIV infection on HAART.

OBJECTIVES: To report the unexpected absence of HIV-1 antibodies and provirus in the peripheral blood of a 4 year old with previously diagnosed perinatal HIV infection. METHODS: Case study including review of clinic and laboratory records and confirmation of results of HIV-1 enzyme linked immunosorbent assay (ELISA), western blot, and HIV-1 DNA PCR from reference laboratory. RESULTS: This child had high plasma viral load at the initiation of highly active antiretroviral therapy (HAART) at 10 months of age. Following undetectable HIV viraemia continuously for a 3 year period, he had normal CD4 and immunoglobulin levels. When retested at the request of the parent, HIV-1 ELISA, western blot, and HIV DNA PCR were all negative, raising the question of misdiagnosis and the parental misperception of a "cure." A rebound increase in viral load on cessation of therapy led to these diagnostic tests becoming positive again, with better parental acceptance of the diagnosis and treatment plan. CONCLUSIONS: Patients and providers should exercise caution in interpreting negative serological tests in children on HAART.

Antibodies, Viral↗

Septic arthritis due to Arcanobacterium haemolyticum.

Diphtheroids or "coryneform" bacilli are usually considered to be nonpathogenic "normal flora" of human skin and mucous membranes. Because bacterial cultures are frequently contaminated with these organisms the correct diagnosis and treatment may be delayed by the failure to recognize serious infections caused by them. Few confirmed cases of orthopaedic infections due to Arcanobacterium haemolyticum infection have been reported, partly because of inadequate identification of this bacterium. We report a case of septic arthritis due to A. haemolyticum.

Actinomycetaceae↗

Evaluation of the polymerase chain reaction analysis for diagnosis of falciparum malaria in Delhi, India.

Plasmodium falciparum infections are frequently fatal if untreated and hence need to be diagnosed and treated early. Malaria diagnosis, with conventional Giemsa staining as a gold standard, has had several limitations. New rapid and accurate methods are needed for diagnosis. In this study, polymerase chain reaction (PCR) analysis specific for diagnosis of P. falciparum was evaluated. For the study, blood samples were collected from 310 patients suspected of having malaria. PCR analysis for P. falciparum from venous blood and at the same time Giemsa staining of thick and thin blood smears was done. A total of 160 (51.6 %) samples were positive for malarial parasite of which 63 (39.4 %) were positive for P. falciparum by Giemsa staining while 61 (38.1 %) were positive for P. falciparum by PCR analysis. Giemsa staining was time consuming, laborious and may give poor results in cases with low parasitaemia. The PCR analysis for P. falciparum was able to detect 3 cases of low parasitaemia missed initially on Giemsa staining, was 96.8 % sensitive, 100% specific but was very costly, needed a lot of practice and standardization and was time consuming. PCR analysis can be used to supplement the conventional Giemsa staining for reliable diagnosis of falciparum malaria especially in cases with low parasitaemia.

Animals↗

Epidural mass due to aspergillus flavus causing spinal cord compression--a case report and brief update.

Aspergillus infection of the central nervous system (CNS) is an uncommon disease. Most of the reported cases are of sinocranial spread and cases with contiguous spread to spinal cord from lung and other organs are uncommon. A case of pulmonary aspergillosis with extension to thoracic vertebrae forming a paraspinal mass resulting in neurological deficit due to Aspergillus flavus, is reported. The 43 year old patient did not have any obvious predisposing condition. He presented with loss of motor function and succumbed to the infection despite operative intervention and antifungal therapy. A brief update on CNS aspergillosis is presented along with detailed clinical, radiological and laboratory work up of the patient.

Adult↗

Diagnostic role of stool culture & toxin detection in antibiotic associated diarrhoea due to Clostridium difficile in children.

BACKGROUND & OBJECTIVE: Mere diagnosis of Clostridium difficile by culture does not help in the diagnosis of antibiotic associated diarrhoeae (AAD) due to C. difficile. Detection of toxins A and B form the mainstay in the diagnosis of AAD due to C. difficile. This study was undertaken to find out the role of stool culture and toxin detection in the diagnosis of AAD due to C. difficile. As there are very few documented reports from India about AAD due to C. difficile in children in the age group of 5-12 yr, this age group was selected. METHODS: Faecal samples were collected from 250 hospitalized children in the age group of 5-12 yr who developed diarrhoea on receiving antibiotics for different medical problems for more than five days duration. Also faecal samples of 250 age and sex matched controls were collected. Culture for C. difficile was done on cycloserine cefoxitin fructose egg yolk agar (CCFA) and colonies were identified by standard laboratory techniques. ELISA for toxins A and B detection and tissue culture on HeLa cells for toxin B detection were also done. RESULTS: Overall positivity was 18 per cent in this study group compared to the controls (P<0.001). Maximum positive cases were in 5-8 yr age group (84.4%). Severe diarrhoea, liquid stool with mucus and blood, faecal leucocytes >5/high power field, altered flora and presence of Gram-positive bacilli with oval subterminal spores on Gram stain were sensitive predictors for diagnosis of AAD due to C. difficile. Amongst positive cases, 68.9 per cent responded to discontinuation of antibiotics and 31.1 per cent to metronidazole therapy. INTERPRETATION & CONCLUSION: C. difficile was an important pathogen responsible for antibiotic associated diarrhoea (AAD) in children of 5-12 yr age group. Conservative use of antibiotics would be beneficial to decrease the incidence of AAD.

Anti-Bacterial Agents↗

Alterations in expression of retinoid receptor beta and p53 in oral submucous fibrosis.

OBJECTIVE: Knowledge of the molecular pathogenesis of oral submucous fibrosis (OSF), a potentially malignant condition with high risk of transition to oral cancer, is meagre. Alterations in the expression of retinoic acid receptor beta (RARbeta) and tumor suppressor gene, p53 are early events in oral tumorigenesis. The aim of this study was to investigate the alterations in the expression of RARbeta and p53 in OSF lesions and determine their association with disease pathogenesis. METHODS: The expression of RARbeta and p53 proteins was analyzed by immunohistochemistry in 50 cases of OSF and 30 histologically normal oral tissues. RESULTS: No detectable RARbeta expression was observed in 35 of 50 (70%) OSF cases. p53 protein accumulation was observed in 24 of 50 (48%) OSF cases analyzed. Thirty-six percent OSF lesions showed loss of RARbeta and p53 overexpression. Interestingly, 41 of 50 (82%) of OSF lesions showed altered expression of at least one of these two proteins. CONCLUSION: Altered expression of either RARbeta or p53 in majority of OSF lesions suggests their association with disease pathogenesis and warrants follow-up to determine whether OSF lesions harboring concomitant alterations in RARbeta and p53 are at a high risk of transition to malignancy.

Adolescent↗

Selective transmission of multidrug resistant HIV to a newborn related to poor maternal adherence.

OBJECTIVES: To report perinatal transmission of multidrug resistant (MDR) HIV related to variable maternal adherence antenatally. METHODS: Case study including review of clinic records, adherence information, laboratory data, and HIV genotyping results in mother and infant. RESULTS: Poor maternal adherence to clinic visits and antiretroviral therapy contributed to detectable viraemia antenatally. When tested for the first time at age 6 months, the infant was found to have virus with resistance to multiple drugs. In this case, prophylaxis with zidovudine (AZT) failed to prevent the transmission of the MDR strain. CONCLUSIONS: Perinatal transmission of MDR HIV can occur despite standard peripartum prophylaxis with AZT. Perinatal prophylaxis should be tailored to the mother's treatment history and resistance profile. Paediatric HIV specialists should be prepared to deal with a small, but slowly increasing number of babies with a "nightmare" multidrug resistant virus with limited treatment options.

Adult↗

Evaluation of the direct acridine orange staining method and Q.B.C. test for diagnosis of malaria in Delhi, India.

Conventional Giemsa stained peripheral blood smear examination for demonstration of malarial parasites remains the gold standard for diagnosis of malaria in developing endemic countries. However this technique is time consuming, requires training and may give poor results in cases with low parasitaemia. To overcome these problems and improve diagnostic accuracy two newer tests have been studied and compared with standard Giemsa staining. These are the wet mount fluorescence microscopy of Acridine Orange stained thin blood films (A.O.) and the Quantitative Buffy Coat technique (Q.B.C) for diagnosis of malaria. A.O. staining was found to be 97.5% sensitive and 100% specific for detection of all stages and species of malarial parasite. The Q.B.C assay was found to be 100% sensitive and 97.5% specific for diagnosis of malaria. A.O. staining was very fast and the species identification was easy once the staining was optimised. The Q.B.C. test required considerable amount of practice, costly equipment, however it was fast and in our study was found to be highly sensitive.

Acridine Orange↗

A clinicopathological study of acute necrotising jejunoileitis.

We describe a variety of acute necrotizing enteritis that is endemic to the Indian subcontinent. During the period 1992-1998, 18 cases of acute jejunoileitis (AJI) were managed. Only those in whom the diagnosis was confirmed at laparotomy have been included in this study. The most common symptoms were abdominal pain (100%), fever (77%), and blood in the stool (100%). A stricture following conservative treatment was present in 1 case. The mean age at presentation was 6.5 years (range 6 months-12 years); the male:female ratio was 1.2:1. All cases were seen during May-October. Routine investigations and X-ray films were nonspecific. Stool cultures did not show any clostridia, shigella, or salmonella. The jejunum was involved most commonly; 28% of patients did not require a bowel resection. Only 1 child presented with shock; the mortality was less than 5%. Short-bowel syndrome resulted in 1 patient due to extensive disease. The histopathologic features that were characteristic of the disease were patchy transmural mucosal necrosis extending centrifugally with submucosal edema, interstitial hemorrhage, type III hypersensitivity reaction, and extensive neovascularization. This type of AJI seen in South/Southeast Asia does not seem to be due a to bacterial infective etiology; immune mediation is suggested. The milder forms can be confused with dysentery. Mild forms of the disease can be managed conservatively, but carry the risk of developing strictures. This disease should be suspected in cases of prolonged dysentery during the summer and autumn months.

Acute Disease↗

Alterations in p53 and pRb pathways and their prognostic significance in oesophageal cancer.

The pRb (p16-pRb-cyclin D1) and p53 (p53-MDM2-p21) pathways play a critical role in tumorigenesis. To evaluate which of these cell cycle regulatory proteins are related to patients' prognosis, a comprehensive analysis of alterations in these components was carried out in 100 ESCCs (oesophageal squamous cell carcinoma) using immunohistochemistry and correlated with clinicopathological parameters by univariate analysis. Overexpression of p53, MDM2 and cyclin D1 proteins was observed in 73, 42 and 67% of the cases, respectively, while loss of expression of p21, p16 and pRb was observed in 36, 45 and 75% of the cases, respectively. Multiple logistic regression analysis revealed that loss of p16 immunoreactivity was a significant risk factor for tumour stage (pT) (Odds Ratio (OR)=3.3), whereas the loss of pRb was a significant risk factor for nodal metastasis (pN) (OR=8.8). MDM2 overexpression emerged as the most significant risk factor for distant organ metastasis (pM) (OR=4.6). Of the ESCC patients who underwent oesophagectomy, 50 cases were followed-up for a maximum period of 44 months and median of 16 months. Survival analysis revealed that Cyclin D1 overexpression is an adverse prognosticator for disease-free survival, as well as overall survival, and tumour stage (pT) is an adverse prognosticator for disease-free survival. In conclusion, these data support a model of oesophageal cancer pathogenesis in which both the pRb and p53 pathways are inactivated and suggests an in-depth evaluation of the clinical utility of these putative markers is warranted.

Adult↗

Prognostic factors in betel and tobacco related oral cancer.

Paucity of well-defined prognostic molecular markers severely hampers prediction of the clinical course of squamous cell carcinoma (SCC) of oral cavity. The aim of the study was to evaluate the prognostic significance of impairments in the expression of proteins involved in cell cycle regulation and locoregional spread in oral SCC of habitual betel and tobacco chewers. A prospective study was performed in 105 betel and tobacco consumers with oral SCCs during the period 1988-1999, to evaluate the prognostic relevance of impairments in the expression of proteins involved in cell cycle regulation and locoregional spread. Alterations in the expression of p53, pRb, p16, MDM2, p21, and Ets-1 proteins were determined by immunohistochemical analysis in formalin fixed, paraffin embedded tissue sections from oral SCCs. Analysis of multiple molecular biological factors showed overexpression of p53 in 69/105 (66%) cases, MDM2 in 72/105 (69%) cases, p21 in 57/105 (54%) cases and Ets-1 in 64/105 (61%) cases. Loss of pRb was observed in 58/105 (55%) cases and p16 loss was observed in 72/105 (69%) cases. Interestingly, multivariate analysis revealed loss of pRb as the most significant predictor of advanced tumour stage [P=0.001; Odd's Ratio (OR)=3.5] and overexpression of Ets-1 protein was an independent risk factor for lymph node metastasis (OR: 10.1; P<10(-6)). Multiple logistic regression models showed that pRb loss [Hazard's Ratio (HR): 3.93] and p53 overexpression (HR: 2.97) may serve as adverse prognosticators for disease free survival of the patients. The data demonstrate multiple impairments in p53/MDM2/p21/Ets-1 and p16/pRb pathways in betel and tobacco related oral tumourigenesis.

Adult↗

Angiographic and immunologic studies in acute necrotizing jejunoileitis.

Eighteen cases of laparotomy-proven acute necrotizing jejunoileitis were treated during the period 1992-1998. Routine laboratory investigations and bacteriological studies were non-contributory towards establishing an etiological basis for the diagnosis. Superior mesenteric artery digital subtraction angiography, carried out in five patients, demonstrated extensive neovascularization. IgG, IgM and IgA were normal in all eight children in whom it was measured; IgE levels were grossly elevated (mean 900 IU/ml; normal range 0-100 IU/ml). Four cases had evidence of hypersensitivity reactions (type I in one patient and type III in three patients) on histopathological examination of the resected small bowel. In addition, histopathological examination also showed the neovascularization observed on angiography. The evidence suggests an immunologically mediated insult resulting in intense vasculitis, which in turn causes ischemic damage to the bowel wall.

Biopsy↗

Rhinocerebral mucormycosis in a pregnant woman with diabetic ketoacidosis.

Rhinocerebral mucormycosis (RCM) is a rare but often fatal condition characterized by aggressive necrotizing infection originating from nose and spreading to paranasal sinuses, orbit and central nervous system. Although Fungi and spores of mucorales show minimal intrinsic pathogenicity towards normal persons, they can initiate fulminant infections in patients with underlying debilitating conditions. A case of RCM in a pregnant woman with diabetic keto-acidosis successfully treated by supportive care, amphotericin B and surgery is reported.

Adult↗