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Biomedical subjects

V Malhotra

Publications and source records attributed to V Malhotra.

At least 55 records · Page 3Linked to original sources

Transurethral resection of the prostate.

Transuretheral resection of prostate (TURP) is a common operation in most hospitals. The patients are elderly and usually have concomitant diseases such as diabetes, hypertension, cardiac and respiratory ailments that increase their perioperative risk. Perioperative morbidity and mortality approaches 20% and 1% respectively. Regional anesthesia, notably spinal anesthesia, offers many advantages over general anesthesia for TURP with some evidence of lower morbidity even though similar mortality rates and overall outcomes are reported for both groups. Procedure-specific complications include TURP syndrome, bladder perforation, primary fibrinolysis, bacteremia, and septicemia. All are associated with significant morbidity and mortality but amenable to early and aggressive therapeutic intervention.

Anesthesia↗

Is the technically limited echocardiographic study an endangered species? endocardial border definition with native tissue harmonic imaging and Optison contrast: a review of 200 cases.

OBJECTIVE: Our goal was to determine whether contrast adds diagnostic value to both fundamental and native tissue harmonic imaging (NTHI) for endocardial border definition. METHODS: Two hundred consecutive patients who underwent stress echocardiography imaging were studied in either fundamental (n = 52) or NTHI mode (n = 148) with an Acuson Sequoia echocardiographic system. Contrast agent (Optison) was administered (0.5 to 1 mL) for enhancement of endocardial borders. Two- and 4-chamber views were analyzed before and after administration of contrast at peak stress for grading of 5 endocardial border segments. Scores from 0 to 5 were assigned to each study for all the images both before and after contrast (0 = 0 segments completely visualized; 5 = 5 segments completely visualized). RESULTS: The use of Optison contrast significantly enhanced border definition when imaging was performed in either fundamental or NTHI mode. Addition of contrast resulted in better endocardial border definition in fundamental mode (4.1 + or - 1.0 versus 2.3 + or - 1.3, P <.001). However, in NTHI mode, the presence of contrast resulted in enhanced definition of endocardial border compared with its absence (4.8 + or - 0.5 versus 3.3 + or - 1.1, P <.001). The combination of NTHI and contrast resulted in more visualization of endocardium when compared with the combination of fundamental imaging and contrast (4.8 + or - 0.5 versus 4.1 + or - 1.0, P <.001). In addition, interobserver agreement for border detection increased from 83% in fundamental mode without contrast to 95% with the use of NTHI with Optison (P <.001). CONCLUSION: As defined in 200 cases, the combination of NTHI with Optison contrast results in nearly complete and consistent endocardial border definition.

Albumins↗

Hemangiopericytoma in a child: a case report.

Hemangiopericytoma (HPC) is a rare vascular tumour seen infrequently in the paediatric age group. It has an incidence of about 10% in children. The difficulty in assessing the malignant potential of this tumour may cause confusion to the clinician in deciding the proper line of management.

Adolescent↗

Gbetagamma-mediated regulation of Golgi organization is through the direct activation of protein kinase D.

We have shown previously that the betagamma subunits of the heterotrimeric G proteins regulate the organization of the pericentriolarly localized Golgi stacks. In this report, evidence is presented that the downstream target of Gbetagamma is protein kinase D (PKD), an isoform of protein kinase C. PKD, unlike other members of this class of serine/threonine kinases, contains a pleckstrin homology (PH) domain. Our results demonstrate that Gbetagamma directly activates PKD by interacting with its PH domain. Inhibition of PKD activity through the use of pharmacological agents, synthetic peptide substrates, and, more specifically, the PH domain of PKD prevents Gbetagamma-mediated Golgi breakdown. Our findings suggest a possible mechanism by which the direct interaction of Gbetagamma with PKD regulates the dynamics of Golgi membranes and protein secretion.

Animals↗

Hepatic fibrogenesis using chronic arsenic ingestion: studies in a murine model.

Chronic oral arsenic (As) ingestion has been alleged to cause hepatic fibrosis, non-cirrhotic portal fibrosis and cirrhosis of the liver. The present study was aimed to investigate if hepatic fibrogenesis and non-cirrhotic portal fibrosis (NCPF) is caused by arsenic. A significant increase in the hepatic protein and collagen was seen compared with controls; hepatic 4-hydroxyproline levels, indicative of fibrogenesis, were increased 4-14 folds with different dosages of arsenic compared to the controls. Hepatocellular necrosis and inflammation were negligible to mild in all the groups. None of the animals developed significant splenomegaly or features of non-cirrhotic portal hypertension. The results suggest that (i) prolonged oral arsenic ingestion in mice leads to significant hepatic fibrogenesis and collagen synthesis with minimal hepato-cellular injury; (ii) arsenic ingestion alone is unlikely to cause non-cirrhotic portal fibrosis or cirrhosis of liver. This murine model of arsenic feeding could be used for the evaluation of new antifibrotic agents for the liver.

Animals↗

Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis.

We have developed an assay using permeabilized cells to monitor fragmentation of the Golgi complex that occurs during mitosis. Golgi stacks, in permeabilized interphase normal rat kidney (NRK) cells, upon incubation with mitotic extracts undergo extensive fragmentation, and the fragmented Golgi membranes are dispersed throughout the cytoplasm. We find that the continued presence of p34cdc2, the mitosis initiation kinase, is not necessary for Golgi fragmentation. Instead, fragmentation depends on cytosolic mitogen-activated protein kinase kinase 1 (MEK1 or MAPKK1). However, the known cytoplasmic substrates for MEK1, ERK1, and ERK2 are not required for this process. Interestingly, we find a Golgi-associated ERK, which we propose as the likely target for MEK1 in Golgi fragmentation.

Animals↗

Ultrasound-guided fine-needle aspiration cytology diagnosis of gallbladder lesions: a study of 82 cases.

Carcinoma of the gallbladder (GB) is among the five most common forms of cancers and tops the list of gastrointestinal malignancies in females of the Delhi region. Lack of specific signs and symptoms prevents early detection of GB carcinoma. However, in recent years ultrasonographically (US)-guided fine-needle aspiration (FNA) cytology has been found to be a reliable procedure for its diagnosis. The present study was carried out during a period of 5 yr (1986-1990) in 64 female and 18 male patients to find out the diagnostic utility of US-guided FNA cytology in gallbladder lesions. Ultrasonography in these 82 cases revealed a mass in the gallbladder/GB area in 74 (90.2%), a mass in the GB/pancreas in 1 (1.2%), gallstones in 32 (39.0%), and miscellaneous gallbladder lesions in 4 (4.9%). The other findings included space-occupying lesions in liver in 18 (22.0%), portal lymphadenopathy in 12 (14.6%), and infiltration in other organs in 7 (8.5%). The initial cytodiagnosis was malignancy in 48 cases, inflammatory in 12, and inadequate in 22. Following review of the smears by one of the investigators (D.K.D.), the number of malignant cases remained 48 (58.5%). There were 10 (12.2%) inflammatory and 24 (29.3%) inadequate cases. Adenocarcinoma was the most common malignancy (83.3%), followed by squamous-cell and adenosquamous carcinoma (12.5%) and small round cell tumors (4.2%). The 10 inflammatory lesions showed slight (+) to excessive (+3) neutrophilic infiltration and included one case each of xanthogranulomatous cholecystitis and a necrotizing granulomatous lesion likely to be of tuberculous etiology.

Adenocarcinoma↗

Dysembryoplastic neuroepithelial tumour.

We report here a classic case of dysembryoplastic neuroepithelial tumour, which was situated in the left frontal lobe of a 13-year-old boy who presented with intractable partial complex seizures since 3 years of age. This tumour entity was first described in 1988, and has been incorporated in the 2nd edition (1993) of the WHO histological typing of CNS tumours. Fewer than 100 cases have been reported from all over the world. To our knowledge, this is the first report of this tumour from India. It is important to recognise this entity since surgery is the only means of cure and radio- or chemotherapy is unwarranted.

Adolescent↗

The organisation of the Golgi apparatus.

The past year has seen considerable progress in understanding the mechanism of COPI (coatomer protein I) vesicle docking and SNARE (soluble NSF attachment protein receptor) mediated fusion, the mechanism of cisternal growth and stacking and the regulation of Golgi architecture. The route taken by cargo proteins through the Golgi apparatus is still a matter of some dispute.

Animals↗

Low-dose recombinant interferon therapy in anti-HBe-positive chronic hepatitis B in Asian Indians.

Approximately 15% of Indian patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant-related CLD in Asian Indians. Eighteen patients (mean age 38.2 +/- 12 years, M:F: 17:1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antige (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti-HBe positive, HBV-DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV-DNA (both by dot-blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV-DNA by dot-blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 +/- 12 vs 55 +/- 29 IU/L, P < 0.01) and the histological activity index (15 +/- 1.4 vs 12 +/- 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 +/- 0.4 g/dL vs 3.8 +/- 0.4 g/dL, P = 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV-DNA positive at the end of follow up. This study concluded that: 1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant-related chronic liver disease in Asian Indians. 2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate. 3. Prolonged low-dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.

Adult↗

Helicobacter pylori infection in recurrent abdominal pain.

OBJECTIVE: To study the relationship between Helicobacter pylori (Hp) infection and recurrent abdominal pain (RAP) and to evaluate various modalities to diagnose Hp infection. DESIGN: Prospective case control study. SETTING: Teaching hospital. METHODS: Children between 3-12 years of age with RAP in whom upper gastrointestinal endoscopic examination was indicated were studied. Endoscopic biopsy specimen were collected from duodenum, antrum and esophagus. Apart from histopathological examination of biopsy material, rapid urease test (RUT) of the antral biopsy specimen and blood examination to estimate specific IgG antibodies to Hp by Indirect Solid Phase Enzyme Immunoassay was performed. The results of Hp IgG antibodies was compared with age matched controls. RESULTS: Thirty one children with RAP were subjected to endoscopic examination and their anti Hp IgG antibodies status compared with 26 controls. Hp colonization was detected in 7 children (23%) with RAP; by RUT in 23% and antral biopsy in 16% of cases. Anti Hp IgG antibodies were also positive in almost equal proportion (19%) of controls (p = 0.757). Endoscopic examination revealed esophagitis in 16% of cases and none had evidence of gastric or duodenal erosion, ulcer or cobblestone appearance of antrum. A significant correlation of Hp was noticed with chronic antral gastritis (p = 0.002), chronic duodenitis (p = 0.02) and age > 10 years (p = 0.02). No significant correlation was noticed between Hp colonization and various socioeconomic risk factors. CONCLUSION: Hp does not seem to be commonly associated with RAP in our patient population as Hp colonization was detected in only 23% of cases which was not significantly higher than the seroprevalence of anti Hp IgG antibodies in the controls. However, a small sample size of our study limits drawing any firm conclusions. Antral gastritis and chronic duodenitis had a significant correlation with Hp colonization. RUT was found to be a reliable diagnostic test to detect Hp.

Abdominal Pain↗

The mechanism of Golgi segregation during mitosis is cell type-specific.

Golgi membranes in Drosophila embryos and tissue culture cells are found as discrete units dispersed in the cytoplasm. We provide evidence that Golgi membranes do not undergo any dramatic change in their organization during the rapid mitotic divisions of the nuclei in the syncitial embryo or during cell division postcellularization. By contrast, in Drosophila tissue culture cells, the Golgi membranes undergo complete fragmentation during mitosis. Our studies show that the mechanism of Golgi partitioning during cell division is cell type-specific.

Animals↗

Role of NAD+ and ADP-ribosylation in the maintenance of the Golgi structure.

We have investigated the role of the ADP- ribosylation induced by brefeldin A (BFA) in the mechanisms controlling the architecture of the Golgi complex. BFA causes the rapid disassembly of this organelle into a network of tubules, prevents the association of coatomer and other proteins to Golgi membranes, and stimulates the ADP-ribosylation of two cytosolic proteins of 38 and 50 kD (GAPDH and BARS-50; De Matteis, M.A., M. DiGirolamo, A. Colanzi, M. Pallas, G. Di Tullio, L.J. McDonald, J. Moss, G. Santini, S. Bannykh, D. Corda, and A. Luini. 1994. Proc. Natl. Acad. Sci. USA. 91:1114-1118; Di Girolamo, M., M.G. Silletta, M.A. De Matteis, A. Braca, A. Colanzi, D. Pawlak, M.M. Rasenick, A. Luini, and D. Corda. 1995. Proc. Natl. Acad. Sci. USA. 92:7065-7069). To study the role of ADP-ribosylation, this reaction was inhibited by depletion of NAD+ (the ADP-ribose donor) or by using selective pharmacological blockers in permeabilized cells. In NAD+-depleted cells and in the presence of dialized cytosol, BFA detached coat proteins from Golgi membranes with normal potency but failed to alter the organelle's structure. Readdition of NAD+ triggered Golgi disassembly by BFA. This effect of NAD+ was mimicked by the use of pre-ADP- ribosylated cytosol. The further addition of extracts enriched in native BARS-50 abolished the ability of ADP-ribosylated cytosol to support the effect of BFA. Pharmacological blockers of the BFA-dependent ADP-ribosylation (Weigert, R., A. Colanzi, A. Mironov, R. Buccione, C. Cericola, M.G. Sciulli, G. Santini, S. Flati, A. Fusella, J. Donaldson, M. DiGirolamo, D. Corda, M.A. De Matteis, and A. Luini. 1997. J. Biol. Chem. 272:14200-14207) prevented Golgi disassembly by BFA in permeabilized cells. These inhibitors became inactive in the presence of pre-ADP-ribosylated cytosol, and their activity was rescued by supplementing the cytosol with a native BARS-50-enriched fraction. These results indicate that ADP-ribosylation plays a role in the Golgi disassembling activity of BFA, and suggest that the ADP-ribosylated substrates are components of the machinery controlling the structure of the Golgi apparatus.

Adenosine Diphosphate Ribose↗

Regulation of Golgi structure through heterotrimeric G proteins.

We have previously shown that ilimaquinone (IQ), a marine sponge metabolite, causes complete vesiculation of the Golgi stacks. By reconstituting the IQ-mediated vesiculation of the Golgi apparatus in permeabilized cells, we now demonstrate that this process does not require ARF and coatomers, which are necessary for the formation of Golgi-derived COPI vesicles. We find that IQ-mediated Golgi vesiculation is inhibited by G alpha(s)-GDP and G alpha(i3)-GDP. Interestingly, adding betagamma subunits in the absence of IQ is sufficient to vesiculate Golgi stacks. Our findings reveal that IQ-mediated Golgi vesiculation occurs through activation of heterotrimeric G proteins and that it is the free betagamma, and not the activated alpha subunit, that triggers Golgi vesiculation.

Animals↗