Biomedical subjects
Publications and source records attributed to R Jalan.
This report describes the instantaneous changes in cerebral blood flow (CBF), determined by intravascular ultrasound and Doppler, in a patient with cirrhosis undergoing placement of a transjugular intrahepatic stent-shunt for uncontrolled variceal bleeding. Acute changes in CBF were observed during and after portasystemic shunting, which culminated in cerebral edema and cerebral herniation.
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Variceal bleeding is the result of portal hypertension, which is a major complication of liver cirrhosis and carries a high mortality rate. Because of the mortality associated with variceal bleeding, strategies for prevention of the first bleed is important. Risk stratification is important in determining those at risk of bleeding from varices and current data suggest that patients with large varices with red signs, severe underlying liver disease and those who have a hepatic venous pressure gradient of greater than 12 mmHg are at high risk of bleeding. Surveillance for varices in patients with cirrhosis is therefore important. The current review evaluates the role of various treatments in the primary prophylaxis of variceal bleeding. The current first choice treatment is non-selective beta-blockers; which is cheap, easy to administer, and reduces the risk of first variceal haemorrhage significantly. Combination of beta-blockers and nitrates looks promising but needs further evaluation. Endoscopic variceal band ligation compares favourably with non-selective beta-blockers in preventing the first bleeding episode in cirrhotic patients and may be an alternative for patients who cannot tolerate, or have contraindications to beta-blockers. The role of monitoring the hepatic venous pressure gradient in those being treated with pharmacological agents, the role of newer drugs such as non-selective beta-blockers with intrinsic alpha-adrenergic activity and angiotensin receptor blockers require further evaluation.
Increased intracranial pressure in patients with acute liver failure remains a major cause of mortality. Treatment options are limited, and without urgent liver transplantation, mortality rates of up to 90% are common in those who fulfill criteria for poor prognosis. Several studies in animal models of acute liver failure set the stage for the clinical application of moderate hypothermia in humans. Few patients are treated with hypothermia for increased intracranial pressure. However, data indicate that moderate hypothermia is a safe and effective method of treatment for increased intracranial pressure that is unresponsive to other medical therapies, and that this treatment can be used as a successful bridge to liver transplantation. Recent data also suggest that increases in intracranial pressure can be prevented during the dissection and reperfusion phases of liver transplantation for acute liver failure if patients are kept hypothermic during the surgical procedure. This article focuses on the use of moderate hypothermia for the treatment of increased intracranial pressure in patients with acute liver failure.
BACKGROUND AND AIMS: Alterations in gluconeogenesis in the diseased liver can be assessed non-invasively using magnetic resonance spectroscopy by measuring changes in phosphomonoester resonance which contains information regarding several metabolites, including the phosphorylated intermediates of the gluconeogenic pathway. METHODS: 31P magnetic resonance spectroscopy was used to determine changes in phosphomonoesters following bolus infusions of 2.8 mmol/kg L-alanine in five patients with functionally compensated cirrhosis and in five patients with functionally decompensated cirrhosis. RESULTS: Compared with six healthy volunteers, baseline phosphomonoester values were elevated by 35% (p<0.05) in the compensated cirrhosis group and by 57% (p<0.01) in the decompensated cirrhosis group. Following alanine infusion, phosphomonoesters in healthy volunteers increased by 46% from baseline values (p<0.01), in patients with compensated cirrhosis by 27% (p<0.02) but those with decompensated cirrhosis showed no increase from baseline. There was a reduction in the percentage of inorganic phosphate signal in all subjects. CONCLUSIONS: By analysing changes in phosphomonoester and inorganic phosphate resonances it is possible to discern clear metabolic differences between healthy volunteers and patients with cirrhosis of varying severity using magnetic resonance spectroscopy. Those patients with functionally decompensated cirrhosis have higher percentage baseline phosphomonoester values but the absence of phosphomonoester elevation following L-alanine infusion suggests that they are unable to mount a significant metabolic response with a progluconeogenic stimulus.
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BACKGROUND & AIMS: The renin-angiotensin and sympathetic nervous systems are activated in cirrhosis. This study aimed to establish the role of angiotensin II (ANG II) in the regulation of basal and sympathetically stimulated vascular tone in preascitic cirrhotic patients and patients with diuretic-refractory ascites compared with age- and sex-matched healthy controls. METHODS: Forearm blood flow (FBF) responses to lower body negative pressure (LBNP) and to subsystemic, intrabrachial infusions of losartan, an angiotensin II type 1 (AT(1)) receptor antagonist, norepinephrine, and ANG II were measured using venous occlusion plethysmography. RESULTS: In all groups, ANG II and norepinephrine caused dose-dependent reductions in FBF (P < 0.001); responses to norepinephrine were similar across the 3 groups but those to ANG II were less in both cirrhotic groups than in controls (P < 0.01). Losartan caused a dose-dependent increase in FBF only in patients with refractory ascites (P < 0.01). LBNP caused less reduction in FBF in refractory ascites patients than in both preascitic patients and controls (P < 0.01). CONCLUSIONS: Despite hyporesponsiveness to exogenous ANG II in both early and advanced cirrhosis, endogenous ANG II contributes to the maintenance of basal vascular tone only in advanced cirrhosis. These findings suggest a role of ANG II in the pathogenesis of ascites. Attenuated LBNP responses occurred only in advanced cirrhosis, without apparent interaction with endogenous ANG II.
BACKGROUND AND AIMS: To test the contribution of portal pressure gradient (PPG) and neurohumoral factors to sodium handling in cirrhotic patients without ascites, by comparing preascitic cirrhotic patients with patients with transjugular intrahepatic portosystemic stent shunt (TIPSS) and previous ascites. PATIENTS: Ten patients with TIPSS and 10 preascitic cirrhotic patients. METHODS: Changes in glomerular filtration, renal plasma flow, urinary sodium excretion (U(Na)V), and neurohumoral factors were measured before and for two hours after infusion of one litre of 0. 9% saline over one hour. RESULTS: Glomerular filtration rate and renal plasma flow were significantly higher in patients with TIPSS compared with preascitic cirrhotic patients. Following saline infusion both parameters increased significantly; this increase was significantly greater in patients with TIPSS. U(Na)V increased significantly in both groups following saline infusion. The increase in U(Na)V was significantly greater in the TIPSS group. Plasma renin activity and angiotensin II decreased significantly in both groups. Basal U(Na)V was independently correlated with angiotensin II concentration and PPG and the change in U(Na)V correlated with the PPG. CONCLUSIONS: Results suggest that patients with advanced liver disease and low portal pressure handle sodium as well as patients with compensated liver disease and high portal pressure. These results are consistent with the notion that in addition to peripheral vasodilatation and severity of liver disease, the severity of portal hypertension contributes to the abnormalities of sodium retention in cirrhosis.
BACKGROUND/AIMS: To measure cerebral benzodiazepine receptor binding using (11)C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy. METHODS: Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of (11)C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances. RESULTS: The mean volume of distribution of (11)C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls. CONCLUSIONS: The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.
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Antiphospholipid syndrome can have various clinical presentations, two of the most common being arterial and venous thrombosis. It is, however, unusual for them to occur in combination. We report here a case of combined hepatic artery and segmental portal venous occlusion in a 32-year-old patient who was shown to have a lupus anticoagulant. There have been no previous reports of thrombosis occurring simultaneously in the coeliac axis and the portal vein. Computerised tomography, Doppler ultrasound scanning and selective visceral angiography were used to demonstrate the anatomical lesions. The patient was treated medically with unfractionated heparin leading to a favourable clinical outcome. The diagnosis and management of this case is discussed with reference to the current literature on visceral thrombosis and antiphospholipid antibody syndrome.
BACKGROUND: Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure. METHODS: We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling. FINDINGS: The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed. INTERPRETATION: Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.
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BACKGROUND/AIMS: Primary graft dysfunction is difficult to predict. We have previously shown that indocyanine green clearance measured at 24 h following orthotopic liver transplantation predicts graft survival and outcome. We prospectively evaluated the use of indocyanine green clearance (with a cut-off value of 200 ml/min) as a marker of graft function following orthotopic liver transplantation and investigated its relationship with the markers of reperfusion injury during orthotopic liver transplantation. METHODS: In all patients indocyanine green clearance was measured at 24 h. Repeated blood samples were taken before, during the anhepatic and reperfusion phase and up to 12 h following orthotopic liver transplantation to measure the levels of neutrophil elastase and reactive oxygen intermediates. All patients studied had normal hepatic arterial pulse on Doppler-ultrasound post orthotopic liver transplantation. RESULTS: All patients with indocyanine green clearance >200 ml/min recovered following orthotopic liver transplantation and remained well up to 3 months of follow up. Four patients had an indocyanine green clearance <200 ml/min; three were re-transplanted for graft failure within 3 days of the transplant, while one survived after prolonged intensive support and hospitalization. Indocyanine green clearance significantly correlated with reactive oxygen intermediates production and neutrophil elastase during orthotopic liver transplantation (r=-0.61, p<0.002 and r=-0.66, p<0.0009, respectively). Indocyanine green clearance was also significantly correlated with alanine aminotransferase and prothrombin time at 24 h post-transplantation (r=-0.35, p<0.02 and r=-0.4, p<0.0077, respectively). CONCLUSION: Indocyanine green reflects the degree of reperfusion injury and is a good early marker of primary graft function. Indocyanine green clearance over 200 ml/min is associated with favorable outcome.