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Biomedical subjects

A Chaudhary

Publications and source records attributed to A Chaudhary.

At least 19 recordsLinked to original sources

Current role of portosystemic shunt surgery in the management of hepatic venous outflow obstruction.

BACKGROUND: Hepatic venous outflow obstruction (HVOO) is a rare disorder that occurs predominantly due to a hypercoagulable state. The syndrome may result from hepatic vein obstruction, inferior vena cava obstruction or a combination of both and manifests with post-sinusoidal portal hypertension. The presentation may be fulminant with poor prognosis or as either acute, subacute or chronic forms with relatively better prognosis. Portosystemic shunt surgery (PSS) has thus far been the mainstay of treatment for HVOO. However, over the last decade, transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation have emerged as viable options. This review aims to evaluate the available treatment options and the current relevance of PSS for the management of HVOO. METHODS: A literature review on investigations and treatment was performed using Medline and additional library searches. RESULTS: Portosystemic shunts form the mainstay of treatment for patients with subacute presentation (preserved liver function) with medically intractable ascites or recurrent variceal hemorrhage. Excellent results with 5-year survival of more than 90% have been reported from specialized centers. The main limitation for PSS is the reported perioperative mortality of 10-20% and a declining technical expertise for such surgery. Liver transplantation with disease-specific 5-year survival between 50 and 95% is presently the treatment of choice for patients with fulminant presentation, end-stage liver disease (ESLD), unshuntable anatomy or decompensation after PSS. TIPS may be preferable for sick patients with acute presentation with isolated hepatic vein thrombosis or as a temporizing measure for those with ESLD awaiting transplantation. The drawback of TIPS is late shunt dysfunction that occurs in more than 50% of patients at 1 year. CONCLUSIONS: Due to rarity of the disorder there is a lack of trials comparing the different treatment modalities. Hence, the current treatment recommendations are based on retrospective studies. In a select group of HVOO patients (subacute presentation with preserved liver function), PSS remains the treatment of choice with excellent long-term results.

Budd-Chiari Syndrome↗

Dynamics of organic carbon and microbial biomass in alluvial soil with tillage and amendments in rice-wheat systems.

Rice-wheat cropping systems of the Indo-Gangetic plains (IGP) occupying 12 million ha of productive land are important for the food security of South Asia. There are, however, concerns that yield and factor productivity trends in these systems are declining/stagnating in recent years. Decrease in soil organic carbon is often suggested as a reason for such trends. A field experiment was conducted to study the soil organic carbon (SOC) and soil microbial biomass carbon (MBC) dynamics in the rice-wheat systems. Use of organic amendments and puddling of soil before rice transplanting increased SOC and MBC contents. Microbial biomass carbon showed a seasonal pattern. It was low initially, reached its peak during the flowering stages in both rice and wheat and declined thereafter. Microbial biomass carbon was linearly related to SOC in both rice and wheat indicating that SOC could be used as a proxy for MBC.

Biomass↗

Disseminated Cryptococcus neoformans in a cirrhotic patient.

Disseminated cryptococcal infection often occurs in the setting of an immuncompromised patient. We report a case of disseminated Cryptococcus neoformans in a cirrhotic patient, referred for Orthotopic Liver Transplantation evaluation due to acute hepatic decompensation.

Cryptococcosis↗

Comparison of magnetic resonance cholangiography and percutaneous transhepatic cholangiography in the evaluation of bile duct strictures after cholecystectomy.

BACKGROUND: Percutaneous transhepatic cholangiography (PTC) has been the preferred investigation to delineate the anatomy of the biliary tract in a patient with a bile duct stricture after cholecystectomy. Recently magnetic resonance cholangiography (MRC) has been described to evaluate the obstructed biliary tract. This paper reports a comparison of MRC with PTC in evaluating patients with an iatrogenic bile duct stricture. METHODS: This was a prospective study of 26 patients who had surgery for a bile duct stricture after cholecystectomy. Before operation all patients underwent both MRC and PTC, the results of which were compared with the intraoperative findings. RESULTS: Both PTC and MRC were comparable with regard to image quality, detection of intrahepatic bile duct dilatation, assessment of the level of injury and detection of abnormalities such as intraduct calculi, cholangitic liver abscesses and atrophy of liver lobes. MRC provided additional information in four patients, including detection of associated fluid collections (n = 3) and portal hypertension (n = 1). In eight patients more than one puncture had to be performed during PTC to delineate the complete anatomy. CONCLUSION: MRC is an accurate and non-invasive imaging procedure for preoperative evaluation of patients with a bile duct injury after cholecystectomy, and is capable of providing additional information which may not be available with PTC.

Adolescent↗

Portal biliopathy.

In patients with portal hypertension, particularly with extrahepatic portal vein obstruction, portal biliopathy producing biliary ductal and gallbladder wall abnormalities are common. Portal cavernoma formation, choledochal varices and ischemic injury of the bile duct have been implicated as causes of these morphological alterations. While a majority of the patients are asymptomatic, some present with a raised alkaline phosphatase level, abdominal pain, fever and cholangitis. Choledocholithiasis may develop as a complication and manifest as obstructive jaundice with or without cholangitis. Endoscopic sphincterotomy and stone extraction can effectively treat cholangitis when jaundice is associated with common bile duct stone(s). Definitive decompressive shunt surgery is sometimes required when biliary obstruction is recurrent and progressive.

Algorithms↗

How do bile duct injuries sustained during laparoscopic cholecystectomy differ from those during open cholecystectomy?

BACKGROUND AND PURPOSE: Bile duct injuries sustained during laparoscopic cholecystectomy differ from those of open cholecystectomy. The authors conducted a retrospective analysis of their experience with 124 major bile duct injuries to identify these differences. PATIENTS AND METHODS: Biliary injury in 83 patients (67%) was sustained during open cholecystectomy, while in 41 patients (33%), it occurred during laparoscopic cholecystectomy. Intraoperative recognition was possible in 21 patients (25%) in the former group and in 14 patients (34%) in the latter (P < 0.05). RESULTS: The median time of presentation after laparoscopic cholecystectomy was 37 days v 240 days after open cholecystectomy (P < 0.001). Twenty-eight patients presented with external biliary fistulae in both groups. Spontaneous closure of these fistulae occurred in 21 patients (75%) in the open cholecystectomy group and in only 10 patients (36%) in the laparoscopic group (P < 0.01). Bismuth type III or IV injuries were the commonest type in the laparoscopic cholecystectomy group (N = 25; 61%) while Bismuth type I or II were the usual injuries in open cholecystectomy (N = 57; 69%) (P < 0.01). After hepaticojejunostomy, over a mean follow-up period of 3.4 years, stenosis of the hepaticojejunostomy was seen in two patients in both groups. CONCLUSION: Compared with open cholecystectomy, biliary injuries sustained during laparoscopic cholecystectomy are more likely to present earlier, are more often associated with persistent bile leaks, and are usually high injuries. However, the results of surgical repair do not appear to be different in these two groups.

Adolescent↗

Biliary complications of pancreatic necrosis.

BACKGROUND: Involvement of the biliary tract in pancreatic necrosis is rare. The authors are presenting six patients with this unusual complication. METHODS: Retrospective analysis of a case series. RESULTS: The necrotic process involved the bile duct in four patients (bile duct alone in two and bile duct with duodenum in two) and the gall bladder in two patients. It was not possible to make a preoperative diagnosis of biliary tract involvement in any of these patients. The lesions in the biliary tract were caused by the direct erosion by the necrotic tissue in five patients, and in one patient with gangrene of the gall bladder, it was a "remote" complication of the necrotizing process. All patients underwent surgery. Necrosectomy and cholecystectomy were performed in patients with gall bladder lesions, and proximal biliary drainage was the method of choice in patients with erosion of the bile duct. One patient died postoperatively. During follow-up, another patient who had bile-duct involvement developed a stricture in the damaged part of the bile duct and needed hepaticojejunostomy CONCLUSIONS: Necrotizing pancreatitis can involve the biliary tract, both by direct extension and by its secondary effects. Although cholecystectomy is the treatment of choice in the presence of gallbladder involvement, proximal biliary diversion may be indicated in patients with erosion of the bile duct.

Adult↗

Long-Term outcome of mitral balloon valvotomy in pregnant women.

BACKGROUND AND AIM OF THE STUDY: The study aim was to examine the long-term outcome (nine years) of mitral balloon valvotomy in pregnant patients with severe mitral stenosis. METHODS: Twenty-three patients with severe, symptomatic (NYHA class III/IV) mitral stenosis underwent mitral balloon valvotomy using an Inoue balloon technique during the second trimester of their pregnancy; mean follow up in 19 patients was 5.1 +/- 2.8 years (range: 1 to 9 years). RESULTS: The procedure was successful in all patients. Immediately after valvotomy, the Doppler-derived mitral valve area increased from 0.90 +/- 0.18 to 1.97 +/- 0.36 cm2 (p <0.0001), and the transmitral mean gradient decreased from 15.7 +/- 4.7 to 5.5 +/- 1.6 mmHg (p <0.0001). Four patients had mild worsening of mitral regurgitation, and six developed insignificant interatrial communication immediately after valvotomy. There was no other morbidity or mortality. Patients showed a significant improvement in mean NYHA class, from 3.0 +/- 0.1 to 1.0 +/- 0.02 (p <0.001). Twenty-two patients had normal deliveries; one cesarean section in week 36 resulted in stillbirth. No developmental abnormalities were seen in the babies. At long-term follow up of mothers, the mitral valve area was 1.8 +/- 0.52 cm2; restenosis developed in three patients (16%). One baby died at one week from sudden infant death syndrome, and one at eight months, from pneumonia. All other children showed normal growth, development and speech for their age. CONCLUSION: Mitral balloon valvotomy using the Inoue balloon technique can provide satisfactory immediate relief and long-term outcome in pregnant patients with severe mitral stenosis.

Adolescent↗

Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338.

We have previously shown that inhibition of phosphatidylinositol (PI) 3-kinase severely attenuates the activation of extracellular signal-regulated kinase (Erk) following engagement of integrin/fibronectin receptors and that Raf is the critical target of PI 3-kinase regulation [1]. To investigate how PI 3-kinase regulates Raf, we examined sites on Raf1 required for regulation by PI 3-kinase and explored the mechanisms involved in this regulation. Serine 338 (Ser338), which was critical for fibronectin stimulation of Raf1, was phosphorylated in a PI 3-kinase-dependent manner following engagement of fibronectin receptors. In addition, fibronectin activation of a Raf1 mutant containing a phospho-mimic mutation (S338D) was independent of PI 3-kinase. Furthermore, integrin-induced activation of the serine/threonine kinase Pak-1, which has been shown to phosphorylate Raf1 Ser338, was also dependent on PI 3-kinase activity and expression of a kinase-inactive Pak-1 mutant blocked phosphorylation of Raf1 Ser338. These results indicate that PI 3-kinase regulates phosphorylation of Raf1 Ser338 through the serine/threonine kinase Pak. Thus, phosphorylation of Raf1 Ser338 through PI 3-kinase and Pak provides a co-stimulatory signal which together with Ras leads to strong activation of Raf1 kinase activity by integrins.

Animals↗

Function of the central domain of streptokinase in substrate plasminogen docking and processing revealed by site-directed mutagenesis.

The possible role of the central beta-domain (residues 151-287) of streptokinase (SK) was probed by site-specifically altering two charged residues at a time to alanines in a region (residues 230-290) previously identified by Peptide Walking to play a key role in plasminogen (PG) activation. These mutants were then screened for altered ability to activate equimolar "partner" human PG, or altered interaction with substrate PG resulting in an overall compromised capability for substrate PG processing. Of the eight initial alanine-linker mutants of SK, one mutant, viz. SK(KK256.257AA) (SK-D1), showed a roughly 20-fold reduction in PG activator activity in comparison to wild-type SK expressed in Escherichia coli (nSK). Five other mutants were as active as nSK, with two [SK(RE248.249AA) and SK(EK281.282AA), referred to as SK(C) and SK(H), respectively] showing specific activities approximately one-half and two-thirds, respectively, that of nSK. Unlike SK(C) and SK(H), however, SK(D1) showed an extended initial delay in the kinetics of PG activation. These features were drastically accentuated when the charges on the two Lys residues at positions 256 and 257 of nSK were reversed, to obtain SK(KK256.257EE) [SK(D2)]. This mutant showed a PG activator activity approximately 10-fold less than that of SK(D1). Remarkably, inclusion of small amounts of human plasmin (PN) in the PG activation reactions of SK(D2) resulted in a dramatic, PN dose-dependent rejuvenation of its PG activation capability, indicating that it required pre-existing PN to form a functional activator since it could not effect active site exposure in partner PG on its own, a conclusion further confirmed by its inability to show a "burst" of p-nitrophenol release in the presence of equimolar human PG and p-nitrophenyl guanidino benzoate. The steady-state kinetic parameters for HPG activation of its 1:1 complex with human PN revealed that although it could form a highly functional activator once "supplied" with a mature active site, the Km for PG was increased nearly eightfold in comparison to that of nSK-PN. SK mutants carrying simultaneous two- and three-site charge-cluster alterations, viz., SK(RE24249AA:EK281.282AA) [SK(CH)], SK(EK272.273AA;EK281.282AA) [SK(FH)], and SK(RE248.249AA;EK272.273AA:EK281.282AA+ ++) [SK(CFH)], showed additive/synergistic influence of multiple charge-cluster mutations on HPG activation when compared to the respective "single-site" mutants, with the "triple-site" mutant [SK(CFH)] showing absolutely no detectable HPG activation ability. Nevertheless, like the other constructs, the double- and triple-charge cluster mutants retained a native like affinity for complexation with partner PG. Their overall structure also, as judged by far-ultraviolet circular dichroism, was closely similar to that of nSK. These results provide the first experimental evidence for a direct assistance by the SK beta-domain in the docking and processing of substrate PG by the activator complex, a facet not readily evident probably because of the flexibility of this domain in the recent X-ray crystal structure of the SK-plasmin light chain complex.

Amino Acid Sequence↗

Possible genetic association between interleukin-1alpha gene polymorphism and the severity of chronic polyarthritis.

Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). IL-1alpha gene polymorphism was analysed for the exon V and promoter region in 51 patients with destructive and 47 with non-destructive RA, as well as in 94 controls. The two biallelic polymorphisms in the promoter region and the exon V were 100% linked. The rare IL-1A2 allele carriage rate was 45% in the control population. It was increased in destructive (54.4%) and decreased in non-destructive RA (26.8%, destructive versus non-destructive, p < 0.007). All indices of disease activity and joint destruction were significantly lower in the patients positive for IL-1A1, and higher in those positive for IL-1A2. The present findings suggest that this IL-1alpha gene polymorphism may contribute to the pathogenesis of chronic polyarthritis. The presence of the IL-1A2 allele could constitute a risk factor for the development of destructive arthritis and could be used early in the course of the disease as a prognostic marker.

Alleles↗

Evaluation of prochlorperazine buccal tablets (Bukatel) and metoclopramide oral tablets in the treatment of acute emesis.

The dizziness associated with vertiginous disorders is often accompanied with nausea and/or vomiting. Antiemetic effect of prochlorperazine (PCZ) is diminished by its low bioavailability owing to a significant gastric and hepatic first pass effect. This effect could be further diminished by likelihood of regurgitation of nauseating patients further limiting the therapeutic effect of oral PCZ. A buccal preparation achieves higher plasma concentrations through direct systemic absorption. In this study buccal prochlorperazine (Bukatel) was compared for its efficacy and tolerability with commonly used metoclopramide. Bukatel was well tolerated and well rated by both patients and investigators with no adverse effects on buccal mucosa and causing less drowsiness and sedation. Results indicate that Bukatel is safe and effective for the treatment of nausea and/or vomiting in patients suffering from vertiginous disorders and could be safely and strongly recommended as an alternative to less bioavailable and indiscriminately used oral metoclopramide tablets.

Administration, Buccal↗

Double blind, randomised, parallel, prospective, comparative, clinical evaluation of a combination of antispasmodic analgesic Diclofenac + Pitofenone + Fenpiverinium (Manyana vs Analgin + Pitofenone + Fenpiverinium (Baralgan) in biliary, ureteric and intestinal colic.

In this double blind, prospective study, the relative efficacy of Diclofenac + Pitofenone + Fenpiverinium (Manyana) and Analgin + Pitofenone + Fenpiverinium (Baralgan) in 200 patients of biliary, ureteric and intestinal colic was evaluated. Patients were given these coded drugs thrice daily for five days starting from day 0 to day 5. The results of the present clinical evaluation demonstrated that Manyana appeared to be superior to Baralgan in biliary and ureteric colic while it was therapeutically equivalent to Baralgan in reducing the pain intensity in intestinal colic. Both the medications were tolerated well and there were no side-effects reported.

Adolescent↗

Probing the phosphoinositide binding site of the clathrin assembly protein AP-2 with photoaffinity labels.

The relative binding specificities of the subunitsof bovine assembly protein AP-2 for the phosphatidylinositol polyphosphates (PtdInsPn) and inositol polyphosphates (InsPn) were determined by photoaffinitylabeling. Three types of benzophenone-containing photoprobes were employed: (i) the water-solubleP-1- or P-2-tethered p-benzoyldihydrocinnamoyl-InsPn (BZDC-InsPn) analogs, (ii) P-1-linked phosphotriester PtdInsPn analogs that sampled the interface between the water and lipid phases, and (iii) sn-1-O-acyl-linked PtdInsPn analogs that interacted with proteins penetrating the bilayer. The InsPn and PtdInsPn probes bind with highest selectivity and affinity to the two alpha subunit isoforms, with certain probes and conditions resulting in strong labeling of the 50-kDa mu subunit. Three main conclusions were reached: (i) head group recognition predominated over acyl chain recognition, (ii) the PtdInsPn binding site of alpha-AP-2 prefers more highly phosphorylated species, and (iii) the protein-acyl chain interactions showed high capacity but low selectivity.

Adaptor Proteins, Vesicular Transport↗

Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phosphoinositide effector protein for regulated exocytosis.

The calcium-dependent activator protein for secretion (CAPS) is a novel neural/endocrine-specific cytosolic and peripheral membrane protein required for the Ca2+-regulated exocytosis of secretory vesicles. CAPS acts at a stage in exocytosis that follows ATP-dependent priming, which involves the essential synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In the present studies, CAPS is shown to bind liposomes that contain acidic phospholipids and binding was markedly enhanced by inclusion of PtdIns(4,5)P2 but not other phosphoinositides in the absence of Ca2+. PtdIns(4,5)P2, but not other phosphoinositides including PtdIns(3, 4)P2 and PtdIns(3,4,5)P3, altered the susceptibility of CAPS to proteolysis by trypsin and proteinase K, suggesting that phosphoinositide binding promoted a conformational change. Photoaffinity labeling studies with a photoactivatable benzoylcinnimidyl acyl chain derivative of PtdIns(4,5)P2 confirmed the phosphoinositide-binding properties of CAPS and suggested a hydrophobic aspect of the interaction. CAPS, as one of very few characterized proteins with a binding specificity for 4-, 5-phosphorylated inositides over 3-phosphorylated inositides, may function in regulated exocytosis as an effector of PtdIns(4,5)P2.

Animals↗