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Biomedical subjects

R Jalan

Publications and source records attributed to R Jalan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Peripheral vascular tone in patients with cirrhosis: role of the renin-angiotensin and sympathetic nervous systems.

OBJECTIVE: The aims of the study were to establish the roles of angiotensin II and of the cardiopulmonary baroreceptor reflex in the regulation of peripheral vascular tone in patients with cirrhosis. METHODS: Forearm blood flow responses to subsystemic, locally active intrabrachial infusions were measured in patients with Child's Grade C cirrhosis and matched controls using bilateral venous occlusion plethysmography. Responses were determined to the angiotensin II type I receptor antagonist, losartan, noradrenaline, angiotensin II and the nitric oxide synthase inhibitor, L-NG-monomethyl arginine. RESULTS: Losartan at 30 and 90 micrograms/min caused no significant change in blood flow in controls, but caused 23 +/- 6% and 27 +/- 5% increases in patients respectively (p < 0.001). Lower body negative pressure caused a mean bilateral reduction in forearm blood flow of 20 +/- 4% in controls (p < 0.001) but only tended to reduce flow (9 +/- 5%; p = 0.06) in patients (p < 0.001; controls vs. patients). Noradrenaline, angiotensin II and L-NG-monomethyl arginine caused significant vasoconstriction (p < 0.001) in both patients and controls although angiotensin II caused significantly less vasoconstriction in patients (p = 0.01). CONCLUSIONS: We conclude that angiotensin II makes an important contribution to basal peripheral vascular tone in patients with cirrhosis in the face of reduced vascular responses to its local administration. In addition, the vasoconstrictor response to cardiopulmonary baroreceptor unloading is attenuated despite normal vascular responses to noradrenaline. These responses are consistent with chronic activation of the renin-angiotensin and sympathetic nervous systems in patients with advanced cirrhosis.

Analysis of Variance↗
PubMed1998

Prediction of cirrhosis in patients with chronic hepatitis C infection by artificial neural network analysis of virus and clinical factors.

The diagnosis of cirrhosis in patients with hepatitis C virus (HCV) infection is currently made using a liver biopsy. In this study we have trained and validated artificial neural networks (ANN) with routine clinical host and viral parameters to predict the presence or absence of cirrhosis in patients with chronic HCV infection and assessed and interpreted the role of the different inputs on the ANN classification. Fifteen routine clinical and virological factors were collated from 112 patients who were HCV RNA positive by reverse transcriptase-polymerase chain reaction (RT-PCR). Standard and Ward-type feed-forward fully-connected ANN analyses were carried out both by training the networks with data from 82 patients and subsequently testing with data from 30 patients plus performing leave-one-out tests for the whole patient data set. The ANN results were also compared with those from multiple logistic regression. The performance of both ANN methods was superior compared with the logistic regression. The best performance was obtained with the Ward-type ANNs resulting in a sensitivity of 92% and a specificity of 98.9% together with a predictive value of a positive test of 95% and a predictive value of a negative test of 97% in the leave-one-out test. Hence, further validation of the ANN analysis is likely to provide a non-invasive test for diagnosing cirrhosis in HCV-infected patients.

Adult↗
PubMed1997

Hepatic encephalopathy and ascites.

The first abnormality leading to sodium and water retention in cirrhosis is the renal tubular defect that is related to deteriorating liver function and hyperaldosteronism. With progression of liver disease and portal hypertension, renal blood flow declines because of the hepatorenal reflex, and is then maintained by the vasoactive hormonal systems. With increasing peripheral vasodilatation, intrarenal factors for maintenance of renal perfusion cause intense cortical vasoconstriction. The systemic vasoactive factors are predominantly compensatory; any attempts to counteract their action risk circulatory collapse. Future studies should be directed at intrarenal factors. The ideal drug for the treatment of portal hypertension would reduce portal pressure, increase renal blood flow, and produce insignificant changes in arterial pressure.

Ascites↗
PubMed1997

Influence of cyclic guanosine monophosphate changes on hemodynamics after reperfusion in liver transplantation.

Orthotopic liver transplantation (OLT) is often associated with hemodynamic instability upon reperfusion, recognized as postreperfusion syndrome. Changes in vascular tone due to humoral factors released upon reperfusion of the graft have been suggested as a possible mechanism. In this study, we looked at the perioperative changes in cyclic guanosine monophosphate (cGMP), a mediator of vascular smooth muscle relaxation, and investigated its relationship with hemodynamic parameters. cGMP was measured in the plasma of 14 patients undergoing OLT by radioimmunoassay serially at the preanhepatic and anhepatic phases, and after reperfusion at 30, 60, and 120 min. Hemodynamic data recorded were systemic and pulmonary arterial pressures, cardiac output, and pulmonary and systemic vascular resistance. cGMP decreased markedly after reperfusion from a baseline level of 5.33+/-0.7 ng/ml to 1.63+/-0.5 ng/ml (P<0.01). Pulmonary arterial pressure increased from 17+/-1.21 mmHg to 23.5+/-1.9 mmHg (P<0.05), and pulmonary vascular resistance increased from 62.8 +/-12.9 dynes/sec/cm5 to 135+/-42.7 dynes/sec/cm5 (P<0.01). Changes in cardiac output and systemic vascular resistance were not significant. The changes in cGMP correlated with pulmonary arterial pressure (r=0.74, P=0.005) and pulmonary vascular resistance (r=0.7, P=0.01). These data confirm the occurrence of hemodynamic changes during OLT, and provide evidence to suggest that the reduction in cGMP after reperfusion may mediate the vascular changes.

Blood Pressure↗
PubMed1997

A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices.

The aim of this study was to compare transjugular intrahepatic portosystemic stent-shunt (TIPSS) with variceal band ligation (VBL) in the secondary prophylaxis of esophageal variceal hemorrhage in patients with cirrhosis. Fifty-eight patients with cirrhosis who presented with the first episode of esophageal variceal hemorrhage were randomized to TIPSS (31) or VBL (27), 24 hours after control of bleeding. Shunt function was assessed after 1 month and then at 6 monthly intervals thereafter. VBL was performed weekly until variceal eradication, and then at 3 months, 6 months, and yearly thereafter. Mean follow-up in the TIPSS group was 15.7 (+/-10.2) months; in the VBL group, it was 16.8 (+/-10.9) months. Results for rebleeding and mortality were analyzed on an intention-to-treat basis and using the Kaplan-Meier method. The frequency and the severity of variceal rebleeding was significantly lower in the TIPSS group (9.8%), compared with the VBL group (51.9%) (P < .0006). Although mortality rates were not significantly different, 8 of the patients who rebled in the VBL group required TIPSS therapy for uncontrolled bleeding. No significant differences were found in the frequency of other complications such as encephalopathy and sepsis. Patients in the VBL group required significantly greater time in the intensive care unit during the period of this study (<0.03). The total direct cost of treatment incurred was pound sterling 1,373 ($2,200) per patient, the cost being less in the patients treated with TIPSS compared with VBL. The results of this study show that TIPSS is superior to VBL for the secondary prophylaxis of variceal hemorrhage in patients with cirrhosis.

Adolescent↗
PubMed1997

Elevation of intracranial pressure following transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage.

Increased intracranial pressure and cerebral oedema in patients with chronic liver disease is rare and is more typical of acute liver failure. Transjugular intrahepatic portosystemic stent-shunt is being increasingly used in the management of uncontrolled variceal haemorrhage in patients with cirrhosis. In our institution, a total of 160 patients has undergone transjugular intrahepatic porto-systemic stent-shunt for variceal haemorrhage; 56 of these procedures were emergencies for uncontrolled variceal haemorrhage. Four of these 56 patients developed features of acute liver failure, with marked deterioration in liver function tests and elevated intracranial pressure. This unusual but important complication of transjugular intrahepatic portosystemic stent-shunt has not been reported in the literature previously, and may have important consequences both for clinical practice and in the provision of further clues to understanding the pathogenesis of increased intracranial pressure in patients with liver diseases.

Adult↗
PubMed1997

A comparison between gastric and oesophageal variceal haemorrhage treated with transjugular intrahepatic portosystemic stent shunt (TIPSS).

BACKGROUND: Transjugular intrahepatic portosystemic stent-shunts (TIPSS) are becoming widely used in the management of oesophageal variceal haemorrhage (OVH). Their place in the treatment of gastric variceal haemorrhage (GVH), a condition with a traditionally poor prognosis, remains unclear. The aims of our study were to compare portal haemodynamics and patient outcome in patients undergoing TIPSS for either GVH or OVH. PATIENTS AND METHODS: 106 consecutive patients undergoing TIPSS at our institution for either GVH (32 patients) or OVH (74 patients) were studied. The groups were similar with regard to patient age, aetiology and severity of liver disease and number of procedures carried out as an emergency (34.4% vs. 36.5%). Episodes of shunt insufficiency, rebleeding, encephalopathy and other clinical sequela were recorded. Mean follow-up was similar in both patient groups (14.2 vs. 12.1 months). RESULTS: Baseline portocaval pressure gradient was lower in patients with GVH compared with those with OVH (13.0+/-0.9 mmHg vs. 19.0+/-0.6 mmHg) (P < 0.001). Rates of variceal rebleeding, encephalopathy and shunt insufficiency during follow-up were similar in both groups and there was no difference in survival. CONCLUSION: Patients with GVH had markedly lower portocaval pressure gradients than those with OVH, but shunt and clinical complications and survival were similar during follow-up. TIPSS appears to be an effective treatment for GVH and should be compared with endoscopic or surgical techniques in controlled trials.

Esophageal and Gastric Varices↗
PubMed1997

Reduction in renal blood flow following acute increase in the portal pressure: evidence for the existence of a hepatorenal reflex in man?

BACKGROUND: To investigate the relation between changes in portal haemodynamics and renal blood flow (RBF) in patients with cirrhosis. PATIENTS/METHODS: Twenty patients with cirrhosis and transjugular intrahepatic portosystemic stent-shunts were divided into two groups which were well matched. At routine portography, either changes in unilateral RBF (group I) or changes in cardiac output (group II) before and after shunt occlusion were studied. Blood was obtained from the renal and systemic circulations for the measurement of neurohumoral factors before and after shunt occlusion in group I patients. RESULTS: After shunt occlusion, there was a progressive reduction in unilateral RBF from a mean (SD) of 289 (32) to 155 (25) (-43.5%) (p < 0.001). These changes correlated significantly with the changes in the portal atrial gradient (p < 0.001). There was no significant change in heart rate, mean arterial pressure and right atrial pressure. No significant changes were found in the concentrations of the various neurohumoral factors measured. There was a less notable but significant reduction in the cardiac output (-10.9%) (p = 0.02) unaccompanied by significant reduction in the pulmonary capillary wedge pressure or mean arterial pressure. CONCLUSIONS: These results suggest the existence of hepatorenal reflex in man which is important in the regulation of RBF, although other mechanisms may also be contributory.

Female↗
PubMed1996

Neutrophil elastase: a determinant of endothelial damage and reperfusion injury after liver transplantation?

Reperfusion injury has been implicated in the development of primary graft dysfunction (PGD) after liver transplantation. Neutrophil migration and activation may be involved in the pathogenesis of this injury. We studied neutrophil activation and its role in the etiology of PGD by measuring neutrophil elastase by radioimmunoassay, in serial blood samples of 19 patients before, during, and for 24 hr after transplantation. In a subgroup of patients, we also measured soluble thrombomodulin at the same time points as a marker of endothelial damage. The pretransplant elastase level was significantly raised (40.13+/-4.84 ng/ml, mean+/-SEM) compared with levels of healthy controls (18.7+/-5.6 ng/ml, P<0.05). A marked increase in elastase activity followed reperfusion, with a peak at 2 hr (370+/-50.5 ng/ml, P<0.01). Thereafter, there was a decline, but elastase remained elevated at 24 hr (186+/-60.94 ng/ml). The mean increase in neutrophil elastase after reperfusion correlated significantly with markers of graft function (P<0.05) and with the mean rise in soluble thrombomodulin (P=0.042), which increased from a pretransplant level of 81.2+/-11.32 to 186+/-50.4 ng/ml, 6 hr after reperfusion (P<0.05). The results of this study indicate that marked neutrophil activation and endothelial cell damage occurs after graft reperfusion during orthotopic liver transplantation, and the degree of activation correlates with markers of graft function, which may suggest a role in the etiology of PGD.

Biomarkers↗
PubMed1996

Transjugular intrahepatic portosystemic stent-shunt (TIPSS) occlusion and the role of biliary venous fistulae.

BACKGROUND/AIM: The aim of this study was to assess the pathology and pathogenic mechanisms involved in the occlusion of transjugular intrahepatic portosystemic stent-shunts. METHODS: Thirty-four patients with transjugular intrahepatic portosystemic stent-shunt who had at least two portographic assessments of shunt function were the subjects of this study. The contents of any shunt demonstrating > 70% stenosis were biopsied before balloon dilatation. Further assessment was made of 10 livers obtained at either post mortem (8) or at liver transplantation (2). Cholangiography was performed in these explanted livers, which were then perfused and fixed with formaldehyde. The shunts were dissected out, sectioned, opened and the contents and the surrounding liver examined macroscopically, histopathologically and immunohistochemically. RESULTS: Fourteen patients with TIPSS developed shunt stenosis. In eight patients the stenosis was greater than 70% and significant re-stenosis occurred in all at repeat portography. Three of these patients who were managed by insertion of new shunts showed no further shunt-related problems, whereas the five who were treated solely by dilatation developed further re-stenosis. Organising thrombus was found in all eight patients and bile was incorporated in the thrombus in four. Biliary epithelium was found in two. Four of the ten explanted livers showed evidence of shunt stenosis, of which three were severe and one was mild (< 70%). The occluding material in patients with severe stenosis was composed of organising thrombus containing bile and a granulomatous inflammatory response. This was associated with a transected bile duct, and the degree of stenosis was related closely to the size of the bile duct transected. The shunts free of bile showed no stenosis. CONCLUSIONS: The results of this study suggest that transection of a major bile duct and bile leak play an important role in the stenosis and occlusion of the intraparenchymal portion of transjugular intrahepatic portosystemic stent-shunt. This has important implications for patient management and stent design.

Biliary Fistula↗
PubMed1996

Review article: pathogenesis and treatment of chronic hepatic encephalopathy.

The various treatment strategies for hepatic encephalopathy are compared in the light of the available body of scientific work on the pathogenesis of the syndrome. Data on animal models of hepatic encephalopathy and in vitro studies on brain slices are discussed. Difficulties in extrapolating the results obtained to the human situation are highlighted, while results of human positron emission tomography and magnetic resonance spectroscopy studies are outlined on the background of the potential weaknesses of these non-invasive techniques.

Animals↗
PubMed1996

Differing actions of the acute administration of propranolol and isosorbide-5-mononitrate on the portal circulation.

BACKGROUND: The aim of this study was to clarify the actions of propranolol and isosorbide-5-mononitrate upon the portal circulation. METHODS: Portal haemodynamics were assessed in 16 patients with transjugular intrahepatic portosystemic stent shunts. A reverse thermodilution catheter was positioned in the portal vein, and portal vein pressure and portal vein flow were measured directly. The effects of propranolol 80 mg and isosorbide-5-mononitrate 20 mg over 1 h were determined independently. RESULTS: This demonstrated that propranolol reduced both portal pressure gradient (7.7 +/- 2.3 to 5.5 +/- 2.1 mmHg, P < 0.01) and portal vein flow (925 +/- 123 to 597 +/- 99 mL/min, P = 0.01) significantly, implying a reduction in splanchnic inflow as its main effect. In contrast, isosorbide-5-mononitrate tended to increase portal vein flow (814 +/- 186 to 911 +/- 211 mL/min; P = 0.06) whilst reducing portal pressure significantly (108 +/- 12 to 92 +/- 10 mmHg P = 0.014). This suggests a fall in intrahepatic resistance and provides no evidence for baroreceptor-mediated reflex splanchnic vasoconstriction. CONCLUSIONS: These drugs act upon different variables contributing to portal hypertension and so they may have a powerful synergistic effect in combination. Direct measurement of portal vein flow is a valuable method for assessing the pharmacological modulation of portal venous inflow.

Blood Pressure↗
PubMed1996

Prospective evaluation of haematological alterations following the transjugular intrahepatic portosystemic stent-shunt (TIPSS).

BACKGROUND: TIPSS is effective in reducing portal hypertension and provides access to the portal system for direct pressure measurements. OBJECTIVE: To assess the incidence and severity of haemolysis and its course following TIPSS, and also to assess changes in spleen size and any relationship to changes in the platelet and white cell count and haemoglobin concentration. DESIGN: A prospective study. MATERIALS AND METHODS: Twenty-three patients undergoing TIPSS with a mean follow-up of 8 months (SE 1.2) were studied. Male-female ratio was 13:10 and the mean age was 53.6 years (SE 1.7). Full blood count, reticulocyte count, serum haptoglobin, urinary haemosiderin, examination of the peripheral blood smear and spleen size (ultrasonography) were measured prior to and 3, 7 and 30 days after TIPSS and 6-monthly thereafter. RESULTS: Seven patients (30.4%) developed haemolysis, which was clinically significant in three (13%). This settled spontaneously within 2 weeks of TIPSS. Portal pressure gradient was reduced from a mean of 21.9 (SE 1.6) to 9.5 (SE 1) mmHg (P < 0.001) and did not change significantly thereafter. Haemoglobin concentration improved significantly from a mean of 89 (SE 16) to 113 (SE 19) g/l (P < 0.05) after TIPSS. Significant changes in spleen size and platelet count occurred, with a reduction in the former from 16.9 (SE 1.1) to 13.7 cm (SE 2.4) (P < 0.01) and an increase in the latter from 85.9 (SE 8.4) to 135.3 x 10(9)/l (SE 16.8) (P < 0.01). No significant correlations were found between the changes in the portal pressure gradient, spleen size and platelet count. There was no significant change in the white cell count. CONCLUSION: Transient significant haemolysis occurs in about 13% of patients following TIPSS. TIPSS is useful for reducing splenomegaly and improving thrombocytopenia and haemoglobin. There is no correlation between the changes in portal pressure gradient, spleen size and platelet count.

Anemia, Hemolytic↗
PubMed1996

Mechanisms of changes in renal handling of sodium following transjugular intrahepatic portal systemic stent-shunt (TIPSS).

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic stent-shunt (TIPSS) reduces the portal pressure gradient and leads to better control of ascites. The aim of this study was to evaluate (1) changes in renal handling of sodium following TIPSS and (2) the mechanism of these changes. DESIGN: Prospective study. SETTING: Tertiary referral centre for liver diseases. METHODS: Eighteen patients with ascites undergoing TIPSS for recurrent variceal haemorrhage (16) (3 or more hospital admissions because of variceal haemorrhage whilst being treated endoscopically) or refractory ascites (2) were studied. Urinary sodium (UNa), creatinine clearance (CrCl), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), Angiotensin II (AII) and lithium clearance (LiCl) were measured before and 3 months after TIPSS when portography was performed and the portal pressure gradient (PPG) also measured. All patients were haemodynamically stable and had received no diuretics for at least 1 week before blood sampling. RESULTS: Improvement in ascites was achieved in all patients in whom TIPSS was inserted successfully (reduction in PPG to < 12 mmHg). PPG was reduced from a mean of 19 (+/-6) to 8.8 (+/-3.4) mmHg (P < 0.001). Urinary sodium and creatinine clearance improved significantly following TIPSS (P < 0.001, P < 0.001, respectively). PRA, All, cGMP and LiCl were abnormal before TIPSS and improved significantly following TIPSS (P < 0.007, P < 0.001, P < 0.001 and P < 0.01, respectively). ANP was not significantly different from normal controls and did not change significantly following TIPSS. Changes in UNa did not correlate with the Pugh score or the change in PPG. CONCLUSION: The results of this study show that TIPSS is associated with significant improvement in UNa, CrCl, PRA, AII, cGMP and LiCl. The change in UNa following TIPSS was independent of the severity of underlying liver disease or the change in PPG.

Adult↗