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Biomedical subjects

A Chaudhary

Publications and source records attributed to A Chaudhary.

At least 19 recordsLinked to original sources
PubMed2002

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Specific interaction of Golgi coatomer protein alpha-COP with phosphatidylinositol 3,4,5-trisphosphate.

The phosphoinositide binding selectivity of Golgi coatomer COPI polypeptides was examined using photoaffinity analogs of the soluble inositol polyphosphates Ins(1,4,5)P3, Ins(1,3,4,5)P4, and InsP6, and of the polyphosphoinositides PtdIns(3,4,5)P3, PtdIns(4,5)P2, and PtdIns(3,4)P2. Highly selective Ins(1,3,4,5)P4-displaceable photocovalent modification of the alpha-COP subunit was observed with a p-benzoyldihydrocinnamide (BZDC)-containing probe, [3H]BZDC-Ins(1,3,4,5)P4. A more highly phosphorylated probe, [3H]BZDC-InsP6 probe labeled six of the seven subunits, with only beta, beta', delta, and epsilon-COP showing competitive displacement by excess InsP6. Importantly, [3H]BZDC-triester-PtdIns(3,4,5)P3, the lipid with the same phosphorylation pattern as Ins(1,3,4,5)P4, showed specific, PtdIns(3,4,5)P3-displaceable labeling of only alpha-COP. Labeling by the PtdIns(4,5)P2 and PtdIns(3,4)P2 photoaffinity probes was less intense and showed no discrimination based on PtdInsPn ligand. Thus, both the D-3 and D-5 phosphates are critical for the alpha-COP-PtdIns(3,4,5)P3 interaction, suggesting an important role for this polyphosphoinositide in vesicular trafficking.

Affinity Labels↗
PubMed1998

Probing the phosphoinositide 4,5-bisphosphate binding site of human profilin I.

BACKGROUND: Profilin is a widely and highly expressed 14 kDa protein that binds actin monomers, poly(L-proline) and polyphosphoinositol lipids. It participates in regulating actin-filament dynamics that are essential for many types of cell motility. We sought to investigate the site of interaction of profilin with phosphoinositides. RESULTS: Human profilin I was covalently modified using three tritium-labeled 4-benzoyldihydrocinnamoyl (BZDC)-containing photoaffinity analogs of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). The P-1-tethered D-myoinositol 1,4,5-trisphosphate (Ins(1,4,5)P3) modified profilin I efficiently and specifically; the covalent labeling could be displaced by co-incubation with an excess of PtdIns(4,5)P2 but not with Ins(1,4,5)P3. The acyl-modified PtdIns(4,5)P2 analog showed little protein labeling even at very low concentrations, whereas the head-group-modified PtdIns(4,5)P2 phosphotriester-labeled monomeric and oligomeric profilin. Mass spectroscopic analyses of CNBr digests of [3H]BZDC-Ins(1,4,5)P3-modified recombinant profilin suggested that modification was in the amino-terminal helical CNBr fragment. Edman degradation confirmed Ala1 of profilin I (residue 4 of the recombinant protein) was modified. Molecular models show a minimum energy conformation in which the hydrophobic region of the ligand contacts the amino-terminal helix whereas the 4,5-bisphosphate interacts with Arg135 and Arg136 of the carboxy-terminal helix. CONCLUSIONS: The PtdIns(4,5)P2-binding site of profilin I includes a bisphosphate interaction with a base-rich motif in the carboxy-terminal helix and contact between the lipid moiety of PtdIns(4,5)P2 and a hydrophobic region of the aminoterminal helix of profilin. This is the first direct evidence for a site of interaction of the lipid moiety of a phosphoinositide bisphosphate analog with profilin.

Binding Sites↗
PubMed1998

Bile duct obstruction due to portal biliopathy in extrahepatic portal hypertension: surgical management.

BACKGROUND: Varices can develop in and around the bile duct in the presence of portal hypertension, especially when it is caused by extrahepatic portal vein thrombosis. The term 'portal biliopathy' is used to describe changes in the bile duct due to these varices, which may cause bile duct obstruction. This paper reviews experience of the surgical management of patients with symptomatic portal biliopathy. METHODS: Nine patients with extrahepatic portal vein obstruction with symptomatic portal biliopathy. were reviewed retrospectively. RESULTS: Eight patients presented with jaundice, two had abdominal pain and one had recurrent cholangitis. Endoscopic retrograde cholangiography revealed abnormality of the bile duct wall, with stricture in eight patients and bile duct calculi in two. Portasystemic shunting relieved jaundice in five of seven patients, and in two a second-stage hepaticojejunostomy was required. CONCLUSION: Symptomatic biliary obstruction in patients with extrahepatic portal hypertension may be relieved by a portasystemic shunt. Rarely biliary bypass may be required and is rendered safer by previous portasystemic shunting to decompress the pericholedochal varices. A direct approach to the biliary tract without a preliminary shunt may be hazardous and is frequently unnecessary.

Adolescent↗