Biomedical subjects
Publications and source records attributed to K J Simpson.
A description of the hardware and software used to create movement patterns that differ spatially and temporally is explained. These tasks are presented to participants using a virtual pattern generator.
The clinical history and examination is essential in the evaluation of patients with liver disease. This chapter details important points in the clinical history and examination allowing the physician to identify likely causes of liver damage and their investigation. The evaluation should allow the physician to differentiate acute and chronic liver diseases, and in the latter case separate those with obstructive or chronic parenchymal liver disease. It should also allow identification of important complications such as encephalopathy, ascites and portal hypertension. Identification of these main features or complications of liver disease by the clinical evaluation leads to a logical plan of investigation and prompt diagnosis and management of the liver disease.
Oral isosorbide-5-mononitrate (Is-5-Mn) was given in doses of 10 and 40 mg acutely and chronically (twice daily for four weeks), allowing a nitrate free interval to 25 patients with cirrhosis. Both 10 mg and 40 mg Is-5-Mn reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance. This was achieved by a reduction in the wedged hepatic venous pressure. The effect on mean azygos blood flow was variable with no significant mean change seen acutely or after chronic use with either dose. The variability was dependent not on the dose used but on the initial azygos flow; the flow in patients with initially low values increased and those with high azygos flows decreased after nitrate challenge. The development of the porto-collateral flow seems an important parameter in predicting haemodynamic response to Is-5-Mn.
Explore the source record for details and available documents.
OBJECTIVES: Transjugular intrahepatic portosystemic stent-shunts (TIPSS) have been shown to reduce portal hypertension consistently and have recently been reported to arrest active variceal hemorrhage. This retrospective and nonrandomized study compares the results of TIPSS with esophageal transection (ET) and devascularization in patients with uncontrolled variceal hemorrhage admitted to a single center with an interest in variceal bleeding. PATIENTS AND METHODS: Two hundred and sixty cirrhotic patients have been referred with variceal bleeding over the past 7 yr. In 41 patients (15.8%), hemorrhage was uncontrolled despite two treatments with sclerotherapy. Thirty-eight patients were eligible for analysis. Nineteen were considered for ET and 19 for TIPSS. Patients in the two groups were well matched for age, sex, etiology of liver disease, and its severity and complications. They have been followed for 13 patient years (TIPSS-7, longest 20 months; ET-6, longest 23 months). Data for survival and rebleeding were analyzed by the Kaplan-Meier method on an intention-to-treat basis. RESULTS: Seven of the 19 were considered unfit for surgery, and 12 underwent esophageal transection and devascularization. TIPSS was undertaken successfully in 17 patients, the Palmaz stent being used in 4 and the Wallstent in 13. Successful TIPSS reduced the mean portal pressure gradient from 22.2 (SE 1.2) to 9.7 (SE 0.7) mm Hg (p < 0.001). Mortality within 30 days of the initial bleed was 42% in the TIPSS group compared with 79% in the ET group (p < 0.05). Rebleeding occurred in 15.6% patients with TIPSS, compared with 26.2% in the ET group. Encephalopathy in the two groups of patients was not significantly different (TIPSS 25% and ET 22%). TIPSS was followed by active infection in 20% compared with 36% after ET. CONCLUSIONS: This study shows that the overall mortality in this group of patients is high whatever the type of treatment used. TIPSS can be performed successfully on these patients who are often not suitable for surgery. Mortality rates were significantly lower in patients treated by TIPSS. Compared with ET, TIPSS should be regarded as the preferred mode of treatment for uncontrolled variceal hemorrhage in patients with cirrhosis.
OBJECTIVE: To test the hypothesis that elevated serum levels of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), (s)E-selectin, (s)P-selectin and soluble interleukin-2 receptor (sIL-2R) occur in patients with biochemically inactive autoimmune hepatitis (AICH) compared with controls. Such a finding would suggest continued immune activation, which in the long-term would contribute to the development of cirrhosis in such patients. METHODS: sICAM-1, sVCAM-1, sE-selectin, sP-selectin and sIL-2R were measured in serum from 50 patients with AICH, divided into two groups according to whether their serum alanine aminotransferase (ALT) levels were normal (below 40 IU/l) or increased (above 40 IU/l). Fourteen healthy subjects served as controls. Eight patients were followed after the induction of remission with increased immunosuppressive therapy. RESULTS: Elevated levels of sICAM-1, sVCAM-1 and sE-selectin were found in patients with AICH compared with controls, independent of their ALT concentration. Only sICAM-1 was significantly elevated in the patients with active disease compared with patients with inactive disease. sIL-2R concentrations were significantly higher in patients with active disease (ALT above 40 IU/l) compared with controls. sP-selectin concentrations were similar in controls and patients with AICH. In patients with clinical and biochemical relapse, increased steroid therapy was followed by a significant reduction in sICAM-1, sVCAM-1 and sIL-2R. The response of sE-selectin was more variable. sICAM-1 remained elevated in five of the eight patients treated with increased steroid therapy despite normalization of their transaminase levels, sIL-2R, sE-selectin and sVCAM-1 levels. In 52% of patients with biochemically inactive AICH (ALT below 40 IU/l), sICAM-1 was above the control range. CONCLUSIONS: These data suggest that patients with AICH have ongoing immune activation despite biochemically inactive disease. This may result in low grade hepatic inflammation and may explain the progression to cirrhosis in patients with AICH despite immunosuppressive therapy.
A micromethod was developed to assay the hepatic activity and subcellular distribution of phosphatidate phosphohydrolase (PAH, EC 3.1.3.4), an important regulatory enzyme in triacylglycerol synthesis, in human needle biopsy specimens. In normal liver PAH is predominantly cytosolic in distribution, but on treatment with oleic acid it shifts to the membranous compartments of the cell, its physiologically active site. The hepatic specific activity of PAH was similar in controls and patients with fatty liver but significantly more of the enzyme was associated with the membranous compartments in patients with severe alcoholic fatty liver. These observations may explain the enhanced rates of triacylglycerol synthesis observed in these patients and may be implicated in the pathogenesis of alcoholic fatty liver.
The activity and subcellular distribution, before and after translocation with oleic acid, of hepatic phosphatidate phosphohydrolase (PAH: E.C.3.1.3.4) was measured following acute and chronic administration of ethanol with either 18% or 4.4% total calories as fat, to male Wistar rats. Acute injection produced a significant increase in PAH activity, without affecting the subcellular distribution or translocation of activity from the cytosol into the membraneous compartments induced by oleic acid. PAH activity, subcellular distribution and the translocation of activity by oleic acid was similar in all groups following chronic liquid feeding. Chronic ethanol feeding was associated with significantly increased plasma corticosterone in the ethanol-fed rats compared with controls, independent of the fat content of the diet. Plasma insulin was similar in chronic alcohol fed rats and controls. This suggests that enhanced PAH activity may contribute to triacylglycerol accumulation following acute alcohol injection, but activity normalises as hepatic lipid accumulation progresses and this effect is not due to attenuation of the hormonal effects of ethanol.
1. Chronic alcohol feeding with a low-fat diet (4.4% total calories) produced a two- to three-fold increase in hepatic triacylglycerol and esterified cholesterol compared with pair-fed low-fat diet controls. Plasma lipids were similar in both groups. 2. Hepatic fatty acid synthesis rates measured in vivo with 3H2O were significantly lower in the alcohol-fed animals than in controls. Activities of hepatic fatty acid synthase (EC 2.3.1.85) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced in the alcohol-fed rats. 3. These results indicate that enhanced hepatic fatty acid synthesis does not occur in rats fed alcohol and a low-fat diet for 4 weeks, and is thus not implicated in the pathogenesis of alcohol-induced fatty liver.
Two unique methodological strategies were used to investigate the influence of retroactive inhibition on recall within a contextual interference paradigm. Three independent blocked groups, blocked without retroactive inhibition (BL-without), blocked with 18 trials of retroactive inhibition (BL-18), and blocked with 36 trials of retroactive inhibition (BL-36), were created that varied in order of presentation of tasks. By testing a single task in retention and creating three independent blocked groups, varying amounts of retroactive inhibition were produced. This isolated the effects of retroactive inhibition on blocked compared to control and random subjects' retention. The Acquisition Group x Retention Trials interaction indicated that random and BL-without subjects had shorter reaction time than BL-18 and BL-36 subjects. Thus, blocked subjects with retroactive inhibition exhibited a retention deficit compared to BL-without subjects. The results support previous contextual interference findings and suggest that retroactive inhibition influences the retention deficits demonstrated by blocked compared to random subjects in typical contextual interference investigations.
We assessed the long-term efficacy of transjugular intrahepatic portasystemic stent-shunt (TIPSS) in 64 patients. Insertion was successful in 56 patients (87.5%). The reasons for its use were: variceal bleeding (49); ascites (6); portal hypertensive gastropathy (6); hypersplenism (2); and embolization of a spontaneous shunt (1). Fourteen patients were Childs A, 20 Childs B and 28 Childs C cirrhotics. Two patients were non-cirrhotic; one with amyloidosis and one with non-cirrhotic portal fibrosis. Patients were followed clinically and radiologically (Doppler ultrasonography and routine portography at 6 months). During 33 patient-years of follow-up, 22 died, 12 during index admission (two were procedure-related) and nine were transplanted. Twenty-five patients are alive, with a mean survival of 7.1 (SD 7) months. Variceal rebleeding occurred in 10 patients (22.7%), one of whom died, and was always associated with shunt insufficiency (shunt thrombosis 2, hepatic vein stenosis (HVS) 1, intimal hyperplasia (IH) 4, dislocated stent 1, inadequate stent 2). Clinical encephalopathy was induced in seven patients (17.1%) following TIPSS. All responded to medical therapy, but two required reduction in shunt size. Ascites improved after TIPSS in 36 patients (87.8%), but reaccumulated in seven (17.5%), associated with shunt dysfunction in five (SBP 2, IH 3, HVS 2). Fatal sepsis occurred in two patients, and 14 other episodes of infection required antibiotics. TIPSS is a useful treatment for variceal bleeding, resistant ascites and portal hypertensive gastropathy. Shunt dysfunction and sepsis occur frequently, and regular surveillance is necessary.
Explore the source record for details and available documents.
The insertion of a transjugular intrahepatic portasystemic stent shunt (TIPSS) was evaluated in 22 patients with recurrent upper gastrointestinal haemorrhage related to portal hypertension (bleeding from oesophageal varices 10, gastric varices six, portal hypertensive gastropathy six). TIPSS was successfully performed electively in 15 patients and as an emergency in three patients. Twelve patients have had no further admissions with bleeding after TIPSS. Single episodes of bleeding were noted in six patients after TIPSS associated with shunt thrombosis (two), intimal hyperplasia within the shunt (two), and shunt migration (one). Another patient presented with reaccumulated ascites suggesting poor shunt function but died from massive variceal haemorrhage before further assessment could be performed. There was one death related to the procedure. Two patients developed encephalopathy after TIPSS, in one patient this was controlled by the insertion of a smaller diameter stent within the existing TIPSS. Several complications arose in earlier patients that have not recurred after modification of the initial technique. TIPSS can be life saving and is effective in controlling variceal haemorrhage and rebleeding from oesophageal or gastric varices and portal hypertensive gastropathy. Larger and longer term studies are required, however, to define the role of TIPSS in the overall management of such patients.
Transjugular intrahepatic portosystemic stent shunt (TIPSS) is a new percutaneous technique for reducing portal venous pressure. We attempted TIPSS in six patients with recurrent bleeding for oesophageal or gastric varices between July 1991 and January 1992 with success in five. There have been no deaths. One patient re-bled after TIPSS. His portal pressure was found to be elevated persistently indicating an inadequate shunt. Following further dilatation of the shunt, portal pressure fell to a satisfactory level and bleeding has not recurred. No bleeding episodes have occurred in the other patients following successful TIPSS. Our series contributes to the growing body of experience which suggests that TIPSS is a safe and effective treatment for recurrent variceal bleeding.
Explore the source record for details and available documents.
Understanding the morphological, movement, and biomechanical characteristics that influence rearfoot motion during lateral movements is necessary for footwear design and for the determination of injury mechanisms. The purpose of this study was to identify factors related to rearfoot kinematics during a lateral braking movement. Seven highly skilled male tennis players performed 24 trials of side shuffle movements at various speeds. A rear view of the right leg performing a braking step onto a force platform was filmed. The neutral-O landing style was most commonly demonstrated. Average movement velocity, foot velocity at touchdown, and body mass were variables demonstrating weak or nonsignificant correlations with the rearfoot parameters. Although structural inversion was correlated significantly with the maximum rearfoot angle and velocity (r = -0.52 and -0.69), the results were affected by movement speed and sample size. The biomechanical characteristics displayed the greatest influence on the various rearfoot kinematic parameters. The magnitude of the significant (P less than 0.0001) correlations generally decreased in the following order: maximum horizontal and vertical force gradients, corresponding times to the maximum gradient values, maximum horizontal and vertical forces, and the corresponding times to maximum forces. In conclusion, the gradient-associated parameters were the most useful biomechanical parameters for predicting changes in rearfoot kinematics.
Explore the source record for details and available documents.
In experimentally produced alcoholic fatty liver microsomal fatty acid composition was measured using gas chromatography. The results showed an increase in linoleic acid (18:2, n-6) and hexadecaenoic acid (22:6, n-3) and a decrease in arachidonic acid (20:4, n-6) in alcohol-fed rats. Using high performance liquid chromatographic separation of radiolabelled substrate and products, delta 9, delta 6 and delta 5 desaturase enzymes were assayed. The activity of delta 9 and delta 5 desaturase was decreased in alcohol-fed rats and delta 6 desaturase activity was similar in control and alcohol-fed groups. These results indicated there was no causal relationship between desaturase activity and membrane fatty acid changes. Increased amounts of eicosatrienoic acid (20:3, n-9) in rats fed less than 5% fat were observed in both control and alcohol-fed rats. The results indicated that essential fatty acid deficiency was not due to alcohol consumption.