Improving prognosis in hepatorenal syndrome.
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Hepatorenal Syndrome↗
Biomedical subjects
P A McCormick
Publications and source records attributed to P A McCormick.
COX 2 inhibitor and fulminant hepatic failure.
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Cyclooxygenase Inhibitors↗
A practical guide to the management of oesophageal varices.
Bleeding oesophageal varices are a frequent and sometimes fatal complication of portal hypertension. Prompt resuscitation and arrest of haemorrhage are the immediate short term priorities. Vasoactive therapy to reduce portal pressure is administered on presentation. Early endoscopy is necessary to make a definitive diagnosis and initiate appropriate therapy; usually emergency sclerotherapy or banding. After the acute bleeding episode, follow-up therapy is instituted either to obliterate the varices by sclerotherapy or banding, or to chronically lower portal pressure and hence reduce the risk of bleeding pharmacologically; a combination of both strategies may be also used. Active surveillance of those at risk of developing varices is advocated. Long term beta-blocker therapy has been demonstrated to be effective in both the primary prevention of variceal haemorrhage and the prevention of rebleeding in those who have already bled. Despite a multitude of therapeutic regimes and ongoing clinical trials, mortality from this condition remains disappointingly high.
Esophageal and Gastric Varices↗
Portal hypertension increases vasoconstrictor responsiveness of rat aorta.
We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague-Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71+/-0.12 g) and noradrenaline (1.00+/-0.17 g) but not phenylephrine (0.86+/-0.10 g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45+/-0.04 g, 0.57+/-0.07 g, 0.71+/-0.05 g respectively). In aortas from Sprague-Dawley rats, the maximum response to KCl (1. 21+/-0.21 g) and phenylephrine (1.54+/-0.30 g) but not noradrenaline (0.93+/-0.09 g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59+/-0.09 g, 0.76+/-0.11 g, 1.04+/-0.10 g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [3H]prazosin to alpha1-adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague-Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.
Animals↗
Effects of the selective cyclooxygenase-2 inhibitor nimesulide on vascular contractions in endothelium-denuded rat aorta.
We have examined the effects of the selective cyclooxygenase-2 inhibitor nimesulide and the non-selective cyclooxygenase inhibitor indomethacin on vascular responsiveness of endothelium-denuded rat aorta. Isometric contractions were obtained to the alpha-adrenoceptor agonists phenylephrine (full agonist) and clonidine (partial agonist relative to phenylephrine) and to endothelin-1 and KCl. Maximum contractile responses to the partial agonist clonidine were significantly reduced by nimesulide (10 microM) and by indomethacin (10 microM) to 60.8 +/- 8.5% (n = 8) and 69.0 +/- 9.6% (n = 12) of control, respectively, as compared with the effects of vehicle (99.0 +/- 5.8%; n = 17). The inhibitors had lesser effects against contractions to phenylephrine: nimesulide had no significant effect, whereas indomethacin caused a small but significant reduction in the maximum contraction to phenylephrine to 90.3 +/- 5.0% (n = 12) of control (vehicle: 108.0 +/- 5.2%, n = 15 nimesulide: 111.8 +/- 5.9%, n = 5). Neither nimesulide nor indomethacin had any effect on contractions to endothelin-1 or KCl. These actions differed from the effects of the Ca2+ entry blocker nifedipine, which significantly reduced contractions to clonidine and KCl to a similar extent. The maximum contraction to clonidine was also significantly reduced by the thromboxane receptor antagonist SQ 29548 (1 microM) to 83.4 +/- 6.4% of control (n = 7) (vehicle 115.5 +/- 7.5%, n = 7). It is concluded that the cyclooxygenase inhibitors nimesulide or indomethacin reduce vascular responsiveness to alpha-adrenoceptor agonists in endothelium-denuded rat aorta, presumably by preventing the formation of vasoconstrictor prostaglandins in aortic smooth muscle by cyclooxygenase-2. This reduced vascular responsiveness was most clearly seen with the partial agonist clonidine.
Animals↗
Clinical vs haemodynamic response to drugs in portal hypertension.
BACKGROUND/AIMS: The combination of non-selective beta-blockers and nitrates is an effective therapy for the prevention of rebleeding from oesophageal varices. However, a significant number of patients fail to respond and have further haemorrhage. It has been suggested that measurement of the hepatic venous pressure gradient response to long-term drug therapy may allow early selection of non-responders. We aimed to test this hypothesis in 63 patients with cirrhosis and variceal bleeding treated with propranolol+/-isosorbide mononitrate. METHODS: Hepatic venous pressure gradient was measured before and during treatment. Response was defined as a reduction of 20% or more in hepatic venous pressure gradient, or a fall in hepatic venous pressure gradient to 12 mmHg or less. RESULTS: Forty-four patients were evaluable: 28 responders and 16 non-responders. Hepatic venous pressure gradient fell significantly in the responder group (17.5+/-0.5 mmHg vs 12.2+/-0.5 mmHg; p<0.01) but not in the non-responders (18.0+/-1.0 vs 17.9+/-1.2 mmHg; p=n.s.). Overall, there was no difference in rebleeding rates between the two groups: responders 43%, non-responders 25%. However, rebleeding was uncommon in compliant patients with alcoholic cirrhosis, in whom the hepatic venous pressure gradient fell to less than 12 mmHg (9%). CONCLUSIONS: In this study a fall in hepatic venous pressure gradient of 20% was not a reliable predictor of clinical response. A threshold value of 12 mmHg was useful, but applied to relatively few patients.
Adrenergic beta-Antagonists↗
Splitting versus sharing focal attention: comment on Castiello and Umiltà (1992).
A popular metaphor for visual attention is that of a spotlight that enhances perceptual processing within its beam. Many studies on the orienting of visual attention have addressed whether the beam is a unified structure or whether it can be split between noncontiguous locations in space. Although most of the evidence favors the unified model, U. Castiello and C. Umiltà (1992) claimed recently to have results that could most easily be accounted for by a model of visual attention in which resources can be allocated flexibly to independent locations in space. It is argued that Castiello and Umiltà used only indirect empirical evidence to support their position and that their results are not inconsistent with the unified model. Two studies are reported in which important aspects of Castiello and Umiltà's experiments were maintained and a probe procedure was implemented to assess directly if attention was split between 2 spatial locations or if a unified focus of attention was expanded to incorporate the 2 locations. The results clearly supported the latter position.
Attention↗
Cardiovascular actions of nitric oxide synthase inhibition in the portal hypertensive rat.
We have investigated the actions of the nitric oxide synthase inhibitor L-NMMA in the portal hypertensive Wistar rat in vivo. Resting blood pressure in the anaesthetised portal hypertensive rat was 107.8+/-11.0 / 79.2+/-11.7 mmHg (n = 12), which was significantly lower than in sham-operated animals (143.0+/-3.8 / 114.0+/-4.0 mmHg, n = 19; P < 0.01). Cardiac output was significantly higher in portal hypertensive (30.2+/-1.0 ml min(-1) per 100 g, n = 12) than sham-operated animals (23.7+/-2.2 ml min(-1) per 100 g, n = 13; P < 0.01). Intravenous injection of L-NMMA (10 mg kg(-1)) significantly increased systemic blood pressure in both portal hypertensive and sham-operated animals to 123.0+/-15.0 / 93.4+/-14.0 mmHg and 162.1+/-5.7 / 131.6+/-6.0 mmHg, respectively. The magnitude of the changes were similar in both groups. This increase in blood pressure was accompanied by a decrease in cardiac output to 88.5+/-2.8% and 91.5+/-2.4% of control in portal hypertensive and sham-operated animals, respectively (no significant difference). L-NMMA (10 mg kg(-1)) had similar effects on small mesenteric arterial conductance in both portal hypertensive and sham operated animals, reducing conductance to 84.4+/-3.6% (n = 6) and 82.7+/-1.2% (n = 4) of control, respectively. It is concluded that L-NMMA has similar effects in vivo in portal hypertensive as compared with sham-operated rats. Hence, an enhancement of endothelium-derived nitric oxide is not involved in the hyperdynamic state following portal hypertension in the rat.
Animals↗
Tranexamic acid for severe bleeding gastric antral vascular ectasia in cirrhosis.
BACKGROUND: It is believed that severe portal hypertensive gastropathy probably accounts for most non-variceal bleeding episodes in patients with cirrhosis. Gastric antral vascular ectasia (GAVE) also occurs in these patients. It is not clear whether it is a variant of portal hypertensive gastropathy or a distinct condition. PATIENT: A patient, a 66 year od woman, with cirrhosis initially diagnosed as having portal hypertensive gastropathy and subsequently classified as GAVE is described. She required transfusion with a total of 130 units of packed red cells for gastrointestinal blood loss. RESULTS: The bleeding did not respond to portal decompression with TIPS or beta blockers. Following treatment with oral tranexamic acid she has not required further blood transfusion over a period of 30 months. CONCLUSION: Tranexamic acid may be a useful treatment for refractory bleeding due to gastric antral vascular ectasia in patients with cirrhosis.
Aged↗
A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients.
Aminoglycosides are frequently used to treat sepsis in patients with liver disease. However, it has been suggested that cirrhotic patients are particularly sensitive to aminoglycoside-induced renal dysfunction. We investigated the efficacy and incidence of renal impairment with netilmicin plus mezlocillin compared with ceftazidime in 128 cirrhotic patients who required empirical treatment for sepsis. Renal impairment developed in 8 of 63 (13%) patients receiving netilmicin compared with 2 of 65 (3%) patients receiving ceftazidime (P < .05); it occurred despite regular monitoring of trough netilmicin levels. Renal impairment was present at the time of death in 1 of 13 (8%) patients treated with ceftazidime compared with 5 of 9 (56%) of the netilmicin patients (P < .05). Mortality rates were similar in the two groups (ceftazidime 20%, aminoglycoside 14%; P = NS). Renal dysfunction is significantly more frequent in cirrhotic patients treated with netilmicin but with careful attention to dosage and fluid management the clinical effect is likely to be relatively modest.
Adolescent↗
Transmission of a homogenous hepatitis B virus population of A1896-containing strains leading to mild resolving acute hepatitis and seroconversion to hepatitis B e antigen antibodies in an adult.
The pre-core variant, A1896, which switches off hepatitis B e antigen (HBeAg) production, is common in hepatitis B e antigen antibody (anti-HBe)-positive chronic hepatitis patients. It has been observed in occasional case reports of acute hepatitis. However, transmission in the absence of HBeAg-producing strains, leading to acute nonfulminant hepatitis and clearance in adults, has not been reported. Here, we show that this event can occur, further confirming that A1896 strains are "wild-type" and can lead to all the same outcomes as G1896 strains. This is in keeping with phylogenetic evidence that A1896 is transmitted independently on a large scale in the population and explains anti-HBe- positive persons who have not had an HBeAg-positive phase documented.
DNA Primers↗
Orienting attention without awareness.
Previous research has shown that visual attention can be directed to a spatial location in 2 qualitatively different ways. Attention can be allocated endogenously in response to centrally presented precues, or it can be captured exogenously by a visual stimulus with an abrupt onset. It has been suggested that exogenous orienting of attention is an automatic process, whereas endogenous orienting of attention represents a controlled and strategic process. M.I. Posner and C.R.R. Snyder (1975) suggested that an automatic process occurs without intention, does not interfere with other mental processes, and does not necessarily give rise to awareness, whereas a controlled process will likely interfere with other processes and necessarily requires intention and awareness. Three experiments investigated the role of awareness in orienting visual attention. Endogenous and exogenous components of orienting attention were placed in opposition to each other to assess the automaticity of exogenous orienting by examining the potential for brief stimulus events to capture attention in the absence of subjective awareness. Results show that an exogenous cue presented below a subjective threshold of awareness captured attention automatically and without awareness.
Attention↗
Vascular actions of octreotide in the portal hypertensive rat.
1. We have investigated the actions of the somatostatin analogue octreotide in the portal hypertensive Wistar rat in vivo and in rat small mesenteric artery and aorta in vitro. 2. In small mesenteric artery, octreotide (0.1-0.3 microM) failed to produce any direct contraction, nor did it affect contractions to noradrenaline (NA, 10 microM) or endothelium-dependent relaxations to acetylcholine. 3. In rat aorta, octreotide (0.3 microM) and somatostatin (1 microM) failed to affect contractions to NA (1 microM), or concentration-contractile response curves to NA. 4. In rat vas deferens, octreotide and somatostatin significantly reduced contractile responses to electrical stimulation with pD2 values (-log IC50) of 8.19 +/- 0.10 (n = 4) and 8.16 +/- 0.26 (n = 4), respectively. Hence, the lack of effect of these agents in aorta or mesenteric artery was not due to lack of efficacy or inappropriate choice of concentration. 5. In the anaesthetized portal hypertensive rat, intravenous injection of octreotide (1-100 microg kg[-1]) did not significantly affect systemic blood pressure, nor did it affect mesenteric vascular conductance as measured by laser doppler flow probes. However, octreotide (100 microg kg[-1]) significantly reduced vascular conductance to 74.2 +/- 7.7% of control (n = 6) in porto-systemic shunt vessels as measured by laser doppler flow probes. 6. Phenylephrine (1 microg kg[-1]) significantly raised blood pressure and significantly decreased vascular conductance in both mesenteric (66.6 +/- 3.7% of control) and porto-systemic shunt vessels (58.7 +/- 10.0% of control). 7. It was concluded that octreotide has selective effects on porto-systemic shunt vessles in vivo in the portal hypertensive rat.
Animals↗
TIPS (transjugular intrahepatic portasystemic shunt) for the surgeon.
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Catheterization↗
Noncirrhotic hepatoma presenting with paraneoplastic neurologic manifestations: two cases.
Hepatocellular carcinoma usually occurs in patients with cirrhosis and is rarely associated with paraneoplastic neurologic disorders. We describe two young patients with hepatomas occurring in noncirrhotic livers, both of whom presented with neurologic symptoms. A 19-yr-old man who presented with coma and a 23-yr-old woman with a 3-month history of progressive hemiparesis, dysarthria, and altered affect were each found, at autopsy, to have hepatocellular carcinoma occurring in a noncirrhotic liver. Neuropathologic examinations revealed widespread multifocal necrotizing leukoencephalopathy in the man and occlusive noninflammatory cerebral vasculopathy with widespread cortical and subcortical infarcts in the woman. It is unlikely that the neuropathologic findings in these patients are explicable on the basis of antibody-mediated tissue injury.
Adult↗
On knowing which way to trace: direction errors during visual curve tracing.
McCormick and Jolicoeur's (1991; 1994) zoom lens model of visual curve tracing proposes that curve tracing involves tracking a curve with a variable size local operator. Unspecified in their model is how the executive function guiding the processing field of this operator initially knows which direction to trace. An experiment was conducted to determine whether observers occasionally curve trace in the wrong direction. A typical curve tracing task involving the determination of whether two dots occur on the same line in a display consisting of two dots and two intertwining lines was used. Lengthening the curve segment at the beginning of a to-be-traced curve resulted in a slowing of response times only to dot locations close to the end of the to-be-traced line. Apparently, observers calculate curve tracing direction based on the spatial location of the second (i.e., target) dot, which can result in erroneously tracing in the wrong direction at dot locations farther along the line.
Humans↗
Why portal hypertensive varices bleed and bleed: a hypothesis.
Continued bleeding or early rebleeding is associated with a poor prognosis in patients with variceal haemorrhage. It is not clear why bleeding stops in some patients and continues or restarts in others. It is suggested that secondary haemodynamic changes in the splanchnic circulation after a bleed may contribute to the risk of further bleeding. These changes include the effects of hypotension on portocollateral resistance, the effects of blood in the gut on splanchnic blood flow, and the effects of blood volume expansion on portal venous pressure during resuscitation. These factors, working in concert, cause a secondary rise in portal venous pressure, which may precipitate further bleeding. Treatment aimed at preventing these secondary haemodynamic changes may be beneficial. It is probable that somatostatin and octreotide could act in this way, which may explain their therapeutic efficacy.
Animals↗