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Biomedical subjects

P C Hayes

Publications and source records attributed to P C Hayes.

At least 19 recordsLinked to original sources
PubMed1998

Haemodynamic parameters predicting variceal haemorrhage and survival in alcoholic cirrhosis.

The relationship between the various haemodynamic abnormalities observed in cirrhosis and their prognostic value remains unclear. We report haemodynamic measurements on 96 patients with alcoholic cirrhosis (mean Childs-Pugh Score, CPS, 9.0 +/- 0.2, mean age 55.6 +/- 1.0 years) and assess their value in predicting variceal bleeding and death during a mean follow-up of 19.3 +/- 1.5 months. Baseline CPS correlated with hepatic venous pressure gradient (HVPG) (p = 0.001), azygos blood flow (p < 0.05), cardiac index (p < 0.05), and inversely with mean arterial pressure (p < 0.01) and systemic vascular resistance index (p < 0.05). Renal blood flow was not related to any haemodynamic parameter or CPS. Thirty-eight patients died during follow-up, and 16 had a variceal bleed. Death (p = 0.001) and variceal bleeding (p < 0.05) were more likely in patients with HVPG > 16 mmHg than in those with HVPG < 16 mmHg, and variceal bleeding was more likely in patients with HVPG > 12 mmHg (vs. HVPG < 12 mmHg, p < 0.05). HVPG also predicted death and variceal haemorrhage on univariate and multivariate analyses. No other haemodynamic parameter predicted death or bleeding. In alcoholic cirrhosis, severity of liver disease is related to HVPG, collateral blood flow and degree of systemic circulatory abnormalities. HVPG is a useful predictor of survival and variceal bleeding in these patients.

Adult↗
PubMed1998

Direct measurement of post-prandial portal haemodynamics in cirrhotic patients with a transjugular intrahepatic portosystemic stent-shunt.

OBJECTIVE: Portal haemodynamics vary in response to eating and other stimuli, but any increase in portal venous pressure (PVP) in cirrhotic patients may be a risk factor for variceal bleeding. We directly assessed post-prandial splanchnic haemodynamics in cirrhotic patients with a transjugular intrahepatic portosystemic stent-shunt (TIPSS) in situ. METHODS: A thermodilution catheter was inserted via the patent TIPSS into the portal vein in 12 cirrhotic patients. PVP,portal venous flow (PVF) (thermodilution method), portal vascular resistance (PVR), porto-atrial pressure gradient (PPG), heart rate, mean arterial pressure (MAP) and right atrial pressure (RAP) were measured. A 505 kcal meal was given and all haemodynamic measurements were repeated at 15 min intervals for 60 min. RESULTS: Following the meal, there was a significant rise in PVP from 11.2 +/- 1.5 to 14.0 +/- 1.9 mmHg at 15 min, and 14.0 +/- 1.8 mmHg at 30 min (P < 0.001); in PPG from 9.5 +/- 1.4 to 12.7 +/- 2.2 mmHg at 15 min and 12.7 +/- 2.1 mmHg at 30 min (P < 0.005); and in PVF from 1110.2 +/- 141.1 to 1543.2 +/- 227.6 ml/min at 30 min (P < 0.01). PVR feil from 0.08 +/- 0.01 to 0.05 +/- 0.01 RU at 30 min (P < 0.05). Heart rate increased from 77 +/- 4.1 to 80.5 +/- 5.4 bpm at 15 min (p < 0.05), but MAP and RAP remained unchanged. CONCLUSION: In cirrhotic patients with TIPSS, significant changes in portal haemodynamics occur at 15-30 min following a meal, with minimal effect on systemic haemodynamics. This model offers a new technique to directly assess the causes for and possible treatments of post-prandial splanchnic hyperaemia in cirrhosis.

Blood Pressure↗
PubMed1998

Acute effect of propranolol and isosorbide-5-mononitrate administration on renal blood flow in cirrhotic patients.

BACKGROUND: Propranolol and isosorbide-5-mononitrate (ISMN) are increasingly used in the prophylaxis of variceal haemorrhage in cirrhosis. However, recent studies have suggested that these drugs may compromise renal function, possibly by reducing renal blood flow. AIMS: To assess the acute effects of propranolol and ISMN on renal blood flow and other haemodynamic parameters in cirrhosis. PATIENTS AND METHODS: Twenty six cirrhotic patients were given either 80 mg propranolol, 20 mg ISMN, or a combination of the two drugs. Unilateral renal blood flow (RBF), azygos blood flow (AZBF), hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and heart rate (HR) were recorded prior to and one hour after drug administration. RESULTS: Propranolol caused a reduction in HR (p < 0.005), AZBF (p < 0.01), and HVPG (p = 0.05), but no change in MAP or RBF (454.1 (77.3) versus 413.9 (60.3) ml/min). ISMN reduced MAP (p < 0.005) and HVPG (p < 0.01), but had no effect on HR, AZBF, or RBF (302.5 (49.4) versus 301.7 (58.8) ml/min). Combined treatment reduced MAP (p < 0.005), AZBF (p < 0.05), and HVPG (p = 0.002), but HR and RBF (419.2 (62.6) versus 415.1 (61.1) ml/min) remained unchanged. CONCLUSIONS: Despite the anticipated changes in other haemodynamic parameters, acute propranolol and/or ISMN administration did not reduce RBF. These drugs do not seem to compromise RBF in cirrhosis.

Adult↗
PubMed1998

Clinical significance of intrahepatic hepatitis C virus levels in patients with chronic HCV infection.

BACKGROUND: The clinical significance of a single assessment of circulating hepatitis C virus (HCV) RNA and its relation to the level of intrahepatic HCV RNA remains unclear. AIMS: To investigate the relation between intrahepatic HCV levels and clinicopathological characteristics of chronic HCV infection. PATIENTS: Ninety eight consecutive patients with chronic HCV infection were studied; none had received alpha interferon therapy. Of these, 12 patients were repeatedly negative for HCV RNA in serum by reverse transcriptase polymerase chain reaction (RT-PCR). METHODS: After diagnostic laparoscopy and liver biopsy, semiquantitative analysis of intrahepatic HCV RNA levels was carried out by limiting dilution of HCV cDNA. HCV genotypes were assessed in 96 patients by restriction fragment length polymorphism analysis of HCV cDNA. RESULTS: Ten out of 12 patients who were RT-PCR negative for HCV RNA in serum were RT-PCR positive in liver; however, this group had a significantly lower intrahepatic HCV level and serum aminotransferase level than the remaining 86 patients. Histological severity (cirrhosis: n = 10); histological activity index; HCV genotype (genotype 1: n = 41; genotype 2: n = 12; genotype 3: n = 36; genotype 4: n = 7); mode of infection (intravenous drug abuse: n = 58; post-transfusion: n = 10; haemophiliac: n = 4; sporadic: n = 26) and alcohol abuse did not affect the intrahepatic virus level. There was no correlation between patient age, duration of infection, and intrahepatic HCV level. CONCLUSIONS: Intrahepatic virus levels were not determined by host factors (age of patient, mode or duration of infection) or by virus factors (HCV genotype). Repeatedly negative RT-PCR for HCV RNA in serum does not indicate absence of HCV from the liver.

Adult↗
PubMed1998

Patterns of hepatitis G viraemia and liver disease in haemophiliacs previously exposed to non-virus inactivated coagulation factor concentrates.

Hepatitis G virus (HGV), a novel flavivirus, has been implicated as a cause of posttransfusion hepatitis. We have performed a longitudinal study in a cohort of haemophiliacs (n = 68) who previously received non-virus inactivated coagulation factor concentrates to assess both patterns of HGV viraemia and any associated liver disease. Hepatitis C virus (HCV) RNA was present in 58/68 and co-infection with human immunodeficiency virus (HIV) was present in 15/68. HGV RNA was detected in 17/68 (25%) samples from the mid-1980s. There was no association between either HIV infection (p = 0.74) or co-infection with a particular HCV genotype (p = 0.62). However, there was a relationship between HGV viraemia and the severity of haemophilia (p = 0.0004) with HGV RNA detected in 5/19, 9/16 and 3/32 patients with mild, moderate and severe haemophilia respectively. A longitudinal study was performed in 15/17 haemophiliacs with HGV viraemia using stored serum samples from the 1980s and 1990s. HGV viraemia persisted in 8/15 and cleared in 7/15 over a variable period of time. A Weibull model was constructed to estimate the duration of HGV viraemia in the study group. The 75th and 90th percentiles for the duration of HGV were estimated to be 8.7 years (95%, confidence interval 4.8-15.7) and 23.6 years (95% confidence interval 11.8-47.1) respectively. Laparoscopic liver inspection/biopsy was performed in 25/68. There was no association between severity of liver disease and HGV viraemia (p = 0.43). This study demonstrates considerable variation in patterns of HGV viraemia in haemophiliacs. We found little evidence to implicate HGV as a major cause of chronic liver disease in haemophiliacs.

Adolescent↗
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

Peripheral eosinophil count both before and after liver transplantation predicts acute cellular rejection.

Acute cellular rejection is common after orthotopic liver transplantation and an important cause of graft dysfunction. Eosinophils, potent mediators of tissue damage, have been implicated in the pathogenesis of acute rejection. We studied 55 patients, all of whom had a protocol biopsy 7 days after transplantation and whose peripheral eosinophil count was monitored daily for 11 days after transplantation. Patients were divided clinicopathologically into two groups: group A, without rejection, group B, with rejection. Group B (36% of patients) developed rejection within the 11-day study period. The pretransplant eosinophil count was significantly higher in group B, compared with group A (0.31 +/- 0.08 v 0.10 +/- 0.01 (x10(9)/L), p < .001). After transplantation, the eosinophil count fell to low levels in both groups. By day 3 there was a statistically significant rise in the eosinophil count in group B compared with group A, with a maximum at day 7 [0.51 +/- 0.06 v 0.26 +/- 0.03 (x10(9)/L) p < .001]. After treatment with steroids, the eosinophil count dropped to values similar to those in group A and remained low thereafter in 16 of 20 patients. Four patients had a second episode of rejection; in each of these, eosinophils were raised again and decreased with resolution of the rejection. An eosinophil count threshold of 0.13 (x10(9)/L) before transplantation and 0.33 (x10(9)/L) on day 7 after transplantation predicted the development of rejection (sensitivity 72/70%, specificity 66/63%, negative predictive value 82/79%). We conclude that a raised eosinophil count is associated with acute rejection. The raised eosinophil count before transplantation in group B suggests that these patients are predisposed to acute rejection, and earlier intervention may be indicated.

Adult↗
PubMed1997

In vitro evidence for vascular hyporesponsiveness in clinical and experimental cirrhosis.

The mechanisms responsible for vascular hyporesponsiveness in cirrhosis have been investigated extensively using isolated vessel techniques. Increased vasodilator (nitric oxide) production has been implicated in many studies, but there is also evidence of altered receptor/second messenger function and vascular remodelling. Interpretation is hampered by the use of different vessels from a variety of animal models, whilst the relevance of these studies to the condition in humans remains unclear. Additional, more focused investigations, using both human and animal vessels, are required to ascertain the exact cause of the vascular abnormalities associated with hepatic cirrhosis.

Animals↗
PubMed1997

Graft dysfunction following liver transplantation: role of free radicals.

BACKGROUND/AIMS: Following orthotopic liver transplantation primary graft non-function occurs in about 10% of patients, and survival depends on early retransplantation. The aetiology has yet to be defined, but reperfusion injury as a result of free radical production has been considered as a possible mechanism. In this study we looked for evidence of free radical generation intraoperatively and assessed the relationship between free radical production and graft function. METHODS/RESULTS: Twenty-one patients (M:F 10:11, mean age; 53 +/- 3.8 years) who underwent liver transplantation for end-stage liver disease were studied. Free radical activity increased significantly following reperfusion, as shown by: (i) the diene conjugated method, where the percentage molar ratio increased from a baseline of 10.87 +/- 0.78% to 24.42 +/- 7.8% (p < 0.01), and (ii) by electron paramagnetic resonance, where a more than a twofold rise in radical concentration was detected (p < 0.05). The increase in free radical activity detected by the diene conjugated method was significantly higher in patients with poor outcome as compared with those who had uneventful recovery (p < 0.01). CONCLUSION: Free radical activity is increased following reperfusion of liver graft during transplantation, and the magnitude of the rise is related to the severity of graft dysfunction.

Biomarkers↗
PubMed1997

The correction of autonomic dysfunction in cirrhosis by captopril.

BACKGROUND/AIMS: Vagal dysfunction is reported in about 70% of patients with cirrhosis, irrespective of aetiology, as detected by cardiovascular reflex tests. We have previously shown that RR-variability on 24-h ECG is a more sensitive marker of vagal dysfunction in cirrhosis. Angiotensin II inhibits vagal function in animals, and it is elevated in cirrhosis and may be the cause of the vagal dysfunction. Our aim was to observe the effect of captopril on vagal dysfunction in cirrhosis. METHODS: Eight patients with cirrhosis (biopsy proven, male two, female six, mean age 54.25) had 24-h ECG RR-variability performed. They then received captopril 25 mg t.d.s. for 48 h. The 24-h ECG was repeated on therapy. RESULTS: Mean blood pressure remained unchanged: baseline 89.8 +/- 4.8 mmHg (mean +/- sem) versus 91.8 +/- 5.9 mmHg, p = not significant. Median baseline RR-variability was 791 (range 18-5344) counts/24 h and increased in all but one patient, with captopril, to 1548 (56-4824) p = 0.008. Three increased into the normal range. CONCLUSION: The vagal dysfunction of cirrhosis is caused by neuromodulation by angiotensin II and is not due to a neuropathy.

Adult↗
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

Pharmacokinetics of N-acetylcysteine are altered in patients with chronic liver disease.

BACKGROUND: The threshold plasma paracetamol concentration at which N-acetylcysteine (NAC) treatment is recommended to treat paracetamol poisoning in a patient with induced liver enzymes (for example, with chronic liver disease or taking anticonvulsant drugs) is 50% lower than in a patient without induced liver enzymes. More patients with chronic liver disease might therefore be expected to be exposed to NAC treatment than previously. In addition, there is increasing use of NAC in patients with chronic liver disease for multiorgan failure or hepatorenal syndrome. Little is known of NAC's pharmacokinetic properties in patients with cirrhosis. AIM: The aim was to determine if the pharmacokinetics of NAC are altered by chronic liver disease. SUBJECTS AND METHODS: NAC was given intravenously in a dose of 600 mg over 3 min to nine patients with biopsy-proven cirrhosis (Child's grade; 1 A, 4 B, 4 C: aetiology: 7 alcohol-related, 1 primary biliary cirrhosis, 1 secondary biliary stenosis) and six healthy matched controls. Venous blood was taken at 20, 40, 60 and 90 min then at 2, 3, 4, 6, 8 and 10 h after NAC administration. Serum NAC was estimated by HPLC. The data were normalized to a standard body weight of 70 kg. RESULTS: The area under the serum concentration-time curve was increased (152.34 mg/L.h +/- 50.38 s.d.) in cirrhotics compared with normal controls (93.86 mg/L.h +/- 9.60 s.d.) (P < 0.05). The clearance of NAC was reduced in patients with chronic liver disease (4.52 L/h +/- 1.87 s.d.) compared with controls (6.47 L/h +/- 0.78: P < 0.01). CONCLUSIONS: Increased vigilance for untoward anaphylactoid reactions is necessary in cirrhotics as they may have higher plasma NAC concentrations. Further studies to determine the optimum dosage regimen in such patients are required.

Acetylcysteine↗