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Biomedical subjects

J F Dillon

Publications and source records attributed to J F Dillon.

At least 19 recordsLinked to original sources
PubMed1998

Contractile response of isolated human hepatic arteries to alpha-adrenoceptor agonists is not impaired in patients with cirrhosis.

1. Impaired vasoconstriction in animals with cirrhosis is maintained in isolated vessels in vitro, indicating an intrinsic alteration in function or structure of the cells in the vascular wall. This may be due to receptor down-regulation, a defect in post-receptor signal transduction or overproduction of vasodilator compounds. This investigation examined the role of these mechanisms in modulating alpha-adrenoceptor-mediated contraction in hepatic arteries from patients with advanced cirrhosis. 2. Hepatic arteries were obtained from subjects with and without cirrhosis for functional investigation in vitro. Endothelial cell function was assessed using endothelium-dependent (acetylcholine) and independent (3'-morpholinosydnonimine) vasodilators. alpha-Adrenoceptor-mediated contraction was assessed by constructing cumulative concentration-response curves to the alpha1-selective agonist phenylephrine, the non-selective adrenoceptor agonist noradrenaline and the receptor-independent vasoconstrictor potassium chloride. 3. None of the vessels used in this study had an intact endothelium but endothelium-independent relaxation was not different in arteries from subject with (79.5+/-10.16%; n=23) and without (84.45+/-18%; n=20) cirrhosis. Phenylephrine, noradrenaline and potassium chloride produced contractions that were of similar size (P>0.05) in arteries from subjects with (10.10+/-0.97 g, 8.85+/-1.03 g and 8.56+/-0.65 g respectively) and without (10.42+/-1.23 g, 9.58+/-1.39 g and 8. 62+/-0.98 g respectively) cirrhosis. The sensitivities (pD2) of the responses to these agonists were also similar (P<0.05) in arteries from patients with cirrhosis (5.45+/-0.10, 5.60+/-0.12 and 1.57+/-0. 03 respectively) and those from non-cirrhotic donors (5.58+/-0.11, 5. 67+/-0.11 and 1.54+/-0.05 respectively).4. Contraction of the denuded hepatic artery was unaffected by cirrhosis indicating that vascular abnormalities in this condition in man are not due to an intrinsic alteration of smooth muscle cell function in hepatic conduit arteries.

Adrenergic alpha-Agonists↗
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

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

Platelet function in cirrhosis and the role of humoral factors.

BACKGROUND: Haemorrhagic complications are common in patients with cirrhosis of the liver and contribute to the morbidity and mortality seen in this condition. Several pathological processes are involved in these complications, including a delay and overall reduction in platelet aggregation. OBJECTIVE: To determine whether impaired aggregation in cirrhosis is the result of an intrinsic abnormality in platelet function or is induced by a factor present in the blood of cirrhotic patients. SETTING: Liver unit patients in a teaching hospital. DESIGN: Blood was taken from 11 patients with cirrhosis (Child's B or C) and 11 healthy controls. Crossover experiments were carried out, suspending platelet pellets from patients in platelet-poor plasma from controls, and vice versa. Aggregation of both samples and also of platelet-rich plasma from patients and controls was measured. RESULTS: Aggregation after 1 min was impaired significantly in patient, compared with control, platelets following incubation in either patient (P = 0.0012), or control (P = 0.0242), plasma. Correspondingly, maximum aggregation of patient platelets was also reduced significantly (P = 0.0036) after incubation in patient plasma. Aggregation after 1 min, and maximum aggregation, of control platelets was increased significantly (P = 0.034 and 0.013, respectively) following incubation in patient plasma. Furthermore, there was a trend (non-significant) towards reduced aggregation of patient platelets incubated in control plasma. CONCLUSION: These results confirm both an intrinsic platelet defect causing impaired aggregation and a circulating factor in the plasma of patients with cirrhosis which may compensate for this functional defect.

Female↗
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↗
PubMed1997

Biochemical analysis of the stress protein response in human oesophageal epithelium.

BACKGROUND: The oesophageal epithelium is exposed routinely to noxious agents in the environment, including gastric acid, thermal stress, and chemical toxins. These epithelial cells have presumably evolved effective protective mechanisms to withstand tissue damage and repair injured cells. Heat shock protein or stress protein responses play a central role in protecting distinct cell types from different types of injury. AIM: To determine (i) whether biochemical analysis of stress protein responses in pinch biopsy specimens from human oesophageal epithelium is feasible; (ii) whether undue stresses are imposed on cells by the act of sample collection, thus precluding analysis of stress responses; and (iii) if amenable to experimentation, the type of heat shock protein (Hsp) response that operates in the human oesophageal epithelium. METHODS: Tissue from the human oesophagus comprised predominantly of squamous epithelium was acquired within two hours of biopsy and subjected to an in vitro heat shock. Soluble tissue cell lysates derived from untreated or heat shocked samples were examined using denaturing polyacrylamide gel electrophoresis for changes in: (i) the pattern of general protein synthesis by labelling epithelial cells with 35S-methionine and (ii) the levels of soluble Hsp70 protein and related isoforms using immunochemical protein blots. RESULTS: A single pinch biopsy specimen is sufficient to extract and analyse specific sets of polypeptides in the oesophageal epithelium. After ex vivo heat shock, a classic inhibition of general protein synthesis is observed and correlates with the increased synthesis of two major proteins of molecular weight of 60 and 70 kDa. Notably, cells from unheated controls exhibit a "stressed" biochemical state 22 hours after incubation at 37 degrees C, as shown by inhibition of general protein synthesis and increased synthesis of the 70 kDa protein. These data indicate that only freshly acquired specimens are suitable for studying stress responses ex vivo. No evidence was found that the two heat induced polypeptides are previously identified Hsp70 isoforms. In fact, heat shock results in a reduction in the steady state concentrations of Hsp70 protein in the oesophageal epithelium. CONCLUSION: Systematic and highly controlled studies on protein biochemistry are possible on epithelial biopsy specimens from the human oesophagus. These technical innovations have permitted the discovery of a novel heat shock response operating in the oesophageal epithelium. Notably, two polypeptides were synthesised after heat shock that seem to differ from Hsp70 protein. In addition, the striking reduction in steady state concentrations of Hsp70 protein after heat shock suggests that oesophageal epithelium has evolved an atypical biochemical response to thermal stress.

Biopsy↗
PubMed1996

Platelet basal cytosolic calcium: the influence of plasma factors in cirrhosis.

BACKGROUND: Platelet cytosolic calcium is necessary for normal platelet function, and may reflect intracellular signalling in vascular smooth muscle cells. METHODS: The cytosolic calcium of platelets from patients with cirrhosis and control subjects was measured in contact with plasma from either source, using FURA 2AM. RESULTS: The basal cytosolic calcium of patients with cirrhosis was found to be significantly lower than that of control subjects (95.7 +/- 10.0 cf. 128.0 +/- 7.8 nmol/l; p = 0.02). When platelets from control subjects were incubated for 45 min with freshly obtained plasma from patients with cirrhosis, the control platelet cytosolic calcium fell to concentrations similar to those of patient platelets (93.0 +/- 7.8 nmol/l; p < 0.005). Such an effect was not observed if patient serum or plasma that had previously been frozen was used. When patient platelets were incubated with fresh control subject plasma, the platelet cytosolic calcium increased (165.4 +/- 19.9 nmol/l; p = 0.01). CONCLUSION: These results indicate that a plasma-borne factor, sensitive to freezing, is responsible for the abnormalities of platelet calcium signalling noted in cirrhosis.

Blood Physiological Phenomena↗
PubMed1996

Neutrophil activation in chronic liver disease.

OBJECTIVE: To assess the relationship between neutrophil activation and indices of disease severity in patients with chronic liver disease. METHODS: Plasma neutrophil elastase was measured by radioimmunoassay as a marker of neutrophil activation, and disease severity assessed by standard clinical, biochemical, haematological and histological techniques. PATIENTS: Eighty-eight patients with chronic liver disease were studied, Thirty-nine had alcohol-induced liver disease (ALD), 18 autoimmune chronic hepatitis, 13 cryptogenic cirrhosis, seven primary biliary cirrhosis, six primary sclerosing cholangitis, three haemochromatosis and two secondary biliary cirrhosis. Seventy-three patients were cirrhotic and 15 were non-cirrhotic, confirmed by biopsy. RESULTS: Levels of neutrophil elastase were raised in Childs C cirrhotic patients with ALD compared with Childs A or B patients with ALD (P < 0.01), Childs A or B patients with non-ALD (P < 0.01), and Childs C patients with non-ALD (P = 0.02). In patients with ALD, neutrophil elastase correlated with prothrombin time (r = 0.679, P = 0.001), bilirubin (r = 0.587, P < 0.001), Child-Pugh score (r = 0.546, P < 0.001) and inversely with serum albumin (r = -0.511, P < 0.001). In patients with non-ALD, there were no correlations with the measurements of with transaminase levels. CONCLUSION: Neutrophil activation, as measured by plasma neutrophil elastase, is a marker of disease severity in patients with alcohol-induced chronic liver damage, but not in those with other causes of liver disease.

Autoimmune Diseases↗
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↗
PubMed1995

Exercise-induced left ventricular dysfunction in alcoholic and non-alcoholic cirrhosis.

BACKGROUND/AIMS: Autonomic and cardiac dysfunction have been reported in patients with cirrhosis. We studied left ventricular and autonomic function in 20 patients with both alcoholic and non-alcoholic cirrhosis. METHODS: Autonomic function was assessed by a standard battery of cardiovascular reflex tests. Supine exercise radionuclide ventriculography was used to assess the cardiac response to exercise. RESULTS: Exercise capacity was reduced in all patients in association with marked chronotropic incompetence (peak heart rates 120.5 +/- 6 bpm). Unlike normal subjects there was no increase in left ventricular ejection fraction on exercise. Stroke volume increased by 23 +/- 6%, mediated by an increase in end-diastolic.volume of > 20%. Cardiac output was subnormal at maximal exercise, increasing by only 96 +/- 14% and 97 +/- 11% in alcoholic and non-alcoholic groups respectively. The majority (83%) of our patients had autonomic reflex abnormalities. CONCLUSIONS: Patients with cirrhosis of alcohol and non-alcohol related aetiologies have significantly impaired cardiovascular responses to exercise, which are similar to those of a denervated heart. This may have important clinical implications for the ability of these patients to withstand cardiovascular stress.

Autonomic Nervous System↗
PubMed1995

The effect of nitric oxide synthase inhibition on portal pressure and azygos blood flow in patients with cirrhosis.

It has been proposed that the hyperdynamic circulation found in cirrhosis is mediated by nitric oxide released through the induction of nitric oxide synthase. To investigate this the effect of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), was studied upon the portal circulation. After a 30-min infusion of 3 mg/kg of L-NMMA there was a significant fall in heart rate from 83.2 +/- 4.4 to 74.2 +/- 3.9 bpm (p = 0.005), and a significant rise in mean arterial pressure from 91.6 +/- 2.2 to 103.7 +/- 3.2 mmHg, p = 0.004). There was, however, no change in hepatic venous pressure gradient (16.7 +/- 1.5 to 16.1 +/- 1.7 mmHg, p = 0.477) nor in azygos venous blood flow (366 +/- 126 to 368 +/- 145 ml/min, p = 0.683). On subgroups analysis by Child-Pugh grade, significant changes occurred in heart rate and mean arterial pressure only in grade A and B patients (p = 0.0061 and p = 0.0068, respectively). Regional peripheral blood flow was studied using hand thermography. All patients who had an isothermic hands (relatively cold fingers compared to palmar temperature) at the start of the study developed an isothermic pattern after the L-NMMA infusion. This study demonstrates a significant systemic effect of nitric oxide synthase inhibition in patients with cirrhosis but no effect upon the portal or portosystemic collateral circulations at this dose.

Adult↗
PubMed1995

Endoscopy.

Laparoscopy under sedation is a safe and a well tolerated procedure which can be readily performed in the endoscopy suite. In the investigation of patients with chronic liver disease it is more accurate than histology alone in staging the severity of disease and adds valuable prognostic information. In patients with focal liver disease it has a high degree of sensitivity and this is likely to increase with technological advances, such as sonolaparoscopy. We strongly believe that in many countries diagnostic laparoscopy is an under utilized diagnostic tool which deserves wider incorporation into clinical practice and training programmes.

Endoscopy, Gastrointestinal↗
PubMed1995

Middle cerebral artery blood flow velocity in patients with cirrhosis.

BACKGROUND: Brain dysfunction is common in patients with advanced liver disease; it is often manifested as hepatic encephalopathy, but its cause is not clearly understood. METHODOLOGY: Intracranial blood flow velocity parameters, including peak systolic velocity, end diastolic velocity and mean velocity of both middle cerebral arteries were measured by transcranial Doppler ultrasonography in 37 patients with cirrhosis without encephalopathy (16 Child's A, 10 Child's B and 11 Child's C) and 12 normal controls. The cause was alcohol-related in 24 and non-alcohol-related in 13. RESULTS: No significant differences in any of the Doppler parameters were detected in Child's group A when compared with controls. However, a statistically significant decrease in middle cerebral artery blood flow velocity was evident when Child's B and C patients without clinically apparent encephalopathy were compared with controls irrespective of the cause. Our results demonstrate that intracranial blood flow is abnormal in patients with advanced liver disease without clinically apparent encephalopathy.

Analysis of Variance↗
PubMed1995

Regional survey on the management of oesophageal variceal haemorrhage.

A questionnaire was sent to 116 consultant gastroenterologists in Scotland and North-East England to assess their management of oesophageal variceal haemorrhage. Most respondents (58%) dealt with < 10 variceal bleeds per year. Sclerotherapy, tamponade, vasoconstrictor therapy and oesophageal transection were available to 87.5-97.5% clinicians, compared with trans-jugular intrahepatic porto-systemic shunts (TIPSS) (39.5%) and band ligation (27%). To arrest bleeding, sclerotherapy, tamponade, octreotide/somatostatin and vasopressin/glypressin were used by 75.5%, 44.5%, 37% and 32% respectively (many used > 1 treatment) and if bleeding continued, transection, TIPSS and shunt surgery were considered by 44.5%, 27% and 6%. Sclerotherapy was used for primary and secondary prophylaxis by 11% and 75.5%, and beta-blockers by 17.5% and 49.5% respectively. A wide variation in the management of variceal haemorrhage therefore exists. Most clinicians do not attempt to prevent primary variceal bleeds, with only a minority using beta-blockers but a significant number using sclerotherapy in this situation.

England↗
PubMed1995

Laparoscopy and histology in the diagnosis of chronic liver disease.

We compared laparoscopy with histology in identifying fatty change, fibrosis, the degree of inflammatory activity, cirrhosis and the cause of liver disease. Laparoscopic liver biopsy was performed in 145 consecutive patients. The laparoscopist and the histologist were provided with similar clinical and biochemical information. Both scored the appearances on respective examinations for the degree of fatty change, fibrosis and activity, presence or absence of cirrhosis; and provided a provisional diagnosis. The final diagnosis was determined by clinicopathological conference and clinical follow-up. Laparoscopy was successfully performed in 142 patients (97.9%). Compared with histology, the sensitivity and specificity of laparoscopy for identifying fatty change were 96.4% and 100%, 100% and 95% for fibrosis and 94% and 95% for inflammatory activity, respectively. For cirrhosis, laparoscopy was 100% sensitive and 97.1% specific. Histology missed 10 cases of cirrhosis (6.1%). Histology did, however, provide additional information in 9 patients (6.3%) which contributed to the final diagnosis. Overall, histology is required in addition to laparoscopy in cases where the aetiology is unclear. The sensitivity and specificity in identifying fatty change, fibrosis, activity and cirrhosis are similar for laparoscopy and histology. The combination of information gained on laparoscopy with histology provides the diagnosis in most patients. Laparoscopy may replace the need for liver biopsy in patients in whom the aetiological diagnosis is not in question and the biopsy is being performed to stage the disease. We used it as an integral part of the work-up of a patient with liver disease.

Adolescent↗
PubMed1994

Hand skin temperature changes in patients with chronic liver disease.

Previous studies have shown that changes in the peripheral circulation occur in patients with liver disease. We have investigated the temperature of the hands of 26 patients and 13 controls using a liquid crystal contact thermography system. Significant differences in resting hand temperature and appearance were observed when the patients were categorised according to Child's score. The appearance depended upon the severity of liver disease; Child's A patients have warm hands of normal thermographic appearance; Child's B patients have cold hands with an abnormal thermographic appearance; whilst Child's C patients have warm hands with an abnormal thermographic appearance. After right-hand ice-cold water immersion, right-hand recovery was abnormally slow in Child's B & C groups compared with Child's A patients and controls. In addition, there was left-hand reflex vasoconstriction during the right-hand warm-up period in those with severe liver disease. With regard to autonomic function, no significant difference in right-hand temperature, thermographic appearance or warm-up rate was detected between those with and those without autonomic neuropathy. These results indicate that autonomic nervous system dysfunction is not the predominant cause of these changes.

Autonomic Nervous System↗
PubMed1994

Diagnostic laparoscopy and liver disease: experience of 200 cases.

BACKGROUND: Laparoscopy is an old technique that is frequently used by gastroenterologists in America and Germany. With modern equipment it is now possible to perform this technique under local anaesthesia. AIM: To evaluate the usefulness and safety of laparoscopic liver biopsy. METHODS: Liver biopsy was routinely performed by laparoscopy under local anaesthetic and sedation. A standard 5 mm laparoscope was used and a pneumoperitoneum induced with nitrous oxide. RESULTS: Two hundred consecutive patients were laparoscoped and underwent liver biopsy. In five patients the liver could not be visualised due to adhesions. Two patients had bleeds related to the procedure. Twenty-five patients had malignancy diagnosed by guided biopsy. Eight of these had been missed by ultrasound prior to laparoscopy. Cirrhosis was diagnosed laparoscopically in 72 patients. Histology was unable to confirm this diagnosis in four patients. CONCLUSION: Laparoscopy can be performed safely and comfortably on patients with local anaesthetic and sedation. The visualisation of the liver can add valuable information to liver biopsy.

Biopsy↗