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Biomedical subjects

R Wright

Publications and source records attributed to R Wright.

At least 145 records · Page 8Linked to original sources

An investigation into the validity of the present classification of inflammatory bowel disease.

To assess the validity of the present subdivision of patients with inflammatory bowel disease into those with Crohn's disease of the small bowel or of the colon and those with ulcerative colitis, 252 patients with inflammatory bowel disease have been studied by questionnaire and case note review. One hundred and seventy-two variables concerning the nature and frequency of symptoms in remission and relapse, the incidence of complications and results of investigation have been analysed by computer. As expected, there were many highly significant variables between patients with ulcerative colitis and those with Crohn's disease of the small bowel. The latter showed evidence of a more severe disease course with more complications. There were similar, although less marked, differences between patients with Crohn's disease of the colon and those with Crohn's disease of the small bowel. There were very few differences in disease course between patients with Crohn's disease of the colon and those with ulcerative colitis. The results suggest that while separate classification of patients with Crohn's disease of the small bowel is justified on clinical grounds, the present separation of patients with disease confined to the colon into groups labelled ulcerative colitis or Crohn's disease of the colon is not. Alternative methods of classification should therefore be investigated.

Colitis, Ulcerative↗

Ultrasound survey of gallstones and other hepatobiliary disorders in patients with Crohn's disease.

Abdominal ultrasound was performed in conjunction with liver function tests in 38 patients with small bowel Crohn's disease and a similar number of age- and sex-matched healthy controls. Five (13%) patients had had previous cholecystectomies for cholelithiasis, and eight (21%) were found to have gallstones on ultrasound. Thus, a total of 34% of patients as compared with 8% of controls had gallstones (P less than 0.01). Compared with 8% of controls, 53% of patients had evidence of at least one biochemical or ultrasonic hepatobiliary abnormality (P less than 0.001). A bright liver echo pattern may be indicative of portal triaditis. The high prevalence of gallstones in Crohn's disease should be considered in any patient who continues to complain of abdominal pain despite otherwise appearing to be in remission.

Adult↗

Sex differences in the metabolism of ethanol and acetaldehyde in normal subjects.

Blood ethanol and acetaldehyde concentrations were compared in normal young male and female subjects after intravenous infusion of 0.5 g of ethanol/kg body weight. After the infusion was completed, females had significantly higher mean concentrations of blood ethanol than males, but a significantly lower apparent volume of distribution (Vd) of ethanol (0.56 +/- 0.06 1/kg vs 0.68 +/- 0.17 1/kg, P less than 0.05). There were no differences in ethanol elimination rate (EER) (females 1.78 +/- 0.3 mmol h-1kg-1; males 1.87 +/- 0.41 mmol h-1kg-1). The mean value of the areas under the acetaldehyde/time curves (AUC) were significantly greater for males (88.5 +/- 26.4 mumol/1. h) than for females (58.6 +/- 31.5 mumol/1. h, P less than 0.05). Since the ethanol elimination rate was similar in both sexes, the observed differences in AUC for acetaldehyde may reflect the sex differences in metabolism of this substrate by the liver.

Acetaldehyde↗

Genetics of adeno-associated virus: isolation and preliminary characterization of adeno-associated virus type 2 mutants.

We constructed insertion and deletion mutants with mutations within the adeno-associated virus (AAV) sequences of the infectious recombinant plasmid pSM620. Studies of these mutants revealed at least three AAV phenotypes. Mutants with mutations between 11 and 42 map units were partially or completely defective for rescue and replication of the AAV sequences from the recombinant plasmids (rep mutants). The mutants could be complemented by mutants with replication-positive phenotypes. The protein(s) that is affected in rep mutants has not been identified, but the existence of the rep mutants proves that at least one AAV-coded protein is required for viral DNA replication. Also, the fact that one of the rep mutant mutations maps within the AAV intron suggests that the intron sequences code for part of a functional AAV protein. Mutants with mutations between 63 and 91 map units synthesized normal amounts of AAV duplex DNA but could not generate single-stranded virion DNA (cap mutants). The cap phenotype could be complemented by rep mutants and is probably due to a defect in the major AAV capsid protein, VP3. This suggests that a preformed capsid or precursor is required for the accumulation of single-stranded AAV progeny DNA. Mutants with mutations between 48 and 55 map units synthesized normal amounts of AAV single-stranded and duplex DNA but produced substantially lower yields of infectious virus particles than wild-type AAV (lip mutants). The lip phenotype is probably due to a defect in the minor capsid protein, VPI, and suggests the existence of an additional (as yet undiscovered) AAV mRNA. Evidence is also presented for recombination between mutant AAV genomes during lytic growth.

Cell Line↗

Gastric mucosal lymphocyte subpopulations in pernicious anemia and in normal stomach.

Gastric mucosal lymphocyte subpopulations were determined by an indirect immunoperoxidase method applied to cryostat sections of gastric biopsies obtained from 12 patients with pernicious anemia (PA group) and from 12 patients whose stomachs were endoscopically and histologically normal (comparison group). T-Cell populations were identified by means of monoclonal antibodies directed against all T cells (UCHT1), T suppressor cells (anti-Leu-2a), and T helper cells (anti-Leu-3a). Non-T cell numbers were estimated indirectly. Concentrations of all T cells, T suppressor cells, T helper cells, and non-T cells were all significantly greater in the PA than in the comparison group. The most striking difference was in non-T cell numbers, which showed an approximately sixfold increase in the PA group. Mean T/non-T cell ratios in PA and comparison groups were significantly different (0.49 and 1.50, respectively). T suppressor/T helper cell ratios were similar in the two groups. There were highly significant positive correlations between numbers of non-T and T helper cells, and non-T and T suppressor cells in PA, but not in comparison groups. If, as seems likely, the majority of non-T cells in these gastritic stomachs were in fact cells of B lineage, these results would be consistent with the hypothesis that gastric mucosal damage in pernicious anemia is mediated primarily by a humoral mechanism, which may involve cytotoxic autoantibodies.

Adult↗

Hormone and metabolite profiles in alcoholic liver disease.

Circulating hormone and metabolite profiles have been studied in ten patients with alcoholic cirrhosis, five patients with alcoholic hepatitis and/or fatty liver, and nine normal controls over a 12-h period of meals and activity. Blood glucose was elevated throughout the day in both cirrhotic and non-cirrhotic alcoholics (mean 12-h glucose; controls 5.38 +/- 0.16 (SEM) mmol/l; cirrhotics 6.98 +/- 0.30 mmol/l, P less than 0.001; non-cirrhotics 7.18 +/- 0.26 mmol/l, P less than 0.001). Non-cirrhotic alcoholics had an exaggerated insulin response to meals, whereas cirrhotic patients had hyperinsulinaemia throughout the day (mean 12-h insulin; controls 16.3 +/- 2.3 mU/l; cirrhotics 35.8 +/- 6.6 mU/l, P less than 0.02). Growth hormone levels were elevated only in patients with cirrhosis (mean 12-h growth hormone, 7.06 +/- 1.35 v. 0.85 +/- 0.17 micrograms/l, P less than 0.001). Serum cortisol was persistently elevated in cirrhotics but only in the evening in non-cirrhotic alcoholics. Lactate and pyruvate responses to meals were exaggerated in non-cirrhotic patients whereas in cirrhotics, levels were persistently raised. Blood glycerol was elevated in all alcoholic patients whereas ketone body levels were normal. Hypertriglyceridaemia was observed only in non-cirrhotic patients. No relationship between the endocrine and metabolic state was observed in either cirrhotic or non-cirrhotic patients.

Adult↗

Different aetiology of chronic active hepatitis in U.K. and Iraq.

We have compared the clinical, biochemical and immunological features of patients with biopsy-proven chronic active hepatitis from Iraq and from the United Kingdom. Clear-cut differences emerge, which can mostly be attributed to the HBV status, as 91% of patients from Iraq were HBsAg-positive compared to only 6% from the U.K. Most patients from Iraq presented insidiously with established cirrhosis, while those from the U.K. presented more acutely and systemic symptoms were more common. Autoantibodies and associated autoimmune conditions were common in U.K. patients but extremely rare in Iraqis.

Adult↗

The influence of endotoxin in vitro on hepatic macrophage lysosomal enzyme release in different rat models of hepatic injury.

Since bacterial endotoxin is known to be involved in the pathogenesis of hepatic injury, the influence of endotoxin on lysosomal enzyme production by hepatic macrophages has been investigated. Macrophages have been isolated from the livers of normal rats, from the livers of rats given stilboestrol subcutaneously 4 days previously and from the livers of rats given Corynebacterium parvum intravenously 6 days previously. Following isolation and overnight culture, the macrophages have been maintained in in vitro culture for a further 24 h and the production of N-acetyl-beta-glucosaminidase (NAG) has been measured. Histological assessment has shown that in stilboestrol model an approximate doubling of sinusoidal cell numbers occurs and in the C. parvum model a heavy mononuclear cell infiltrate is present, together with granuloma formation. These changes are reflected in the numbers of macrophages isolated from the respective models. Levels of NAG production by resident macrophages from normal livers are low (0.25 +/- 0.05 nmol substrate hydrolysed/microgram cell protein/h) and unchanged following endotoxin exposure (0.25 +/- 0.05 units). Macrophages isolated from the stilboestrol model show levels of NAG production similar to normal (0.34 +/- 0.06 units), but this increases significantly following exposure to endotoxin (0.42 +/- 0.07 units). Macrophages from the C. parvum model demonstrate markedly enhanced production (0.61 +/- 0.09 units), but this does not increase significantly following endotoxin exposure (0.65 +/- 0.09 units). In contrast to macrophages from normal rat livers, macrophages recently recruited in the stilboestrol model demonstrate enhanced lysosomal enzyme production following endotoxin exposure. It is suggested that endotoxin, as well as other mediators of macrophage activation, may promote hepatic damage through this influence on newly recruited macrophages.

Acetylglucosaminidase↗

Dupuytren's contracture, chronic liver disease and IgA immune complexes.

Contrary to previous reports, Dupuytren's contracture was found to be equally common in patients with alcoholic and non-alcoholic biopsy-proven liver disease (25% v 28%). Furthermore, in 69 patients with Dupuytren's contracture referred for surgical correction, there was no significant increase in either history of alcohol abuse or abnormality of liver function compared to a matched control group. Patients with Dupuytren's contracture were found to have increased levels of circulating IgA immune complexes compared to those without (p less than 0.05 for those with liver disease; p less than 0.001 for those awaiting surgical correction). Circulating immunoglobulins and immune complexes of other classes were similar between the groups with and without Dupuytren's contracture. These results suggest that the importance of alcohol has previously been exaggerated but that IgA immune complexes may be involved in the pathogenesis of the condition.

Adult↗

Delay in diagnosis of adult coeliac disease.

The delay in diagnosis of 106 patients with adult coeliac disease, diagnosed between 1976 and 1980, was studied. Overall, delay in diagnosis was 11 +/- 10.6 years, being considerably greater in females (12.8 +/- 7.8 years) than in males (3.5 +/- 9.8 years). Most of this delay occurred prior to hospital referral, although that following referral to hospital clinics was still significant (1.8 +/- 4.8 years). The most common presenting complaints were lassitude (75%) anaemia (65%) and flatulence (50%). Typical gastro-intestinal symptoms were relatively uncommon and mild, but when present led to a more speedy diagnosis. It is concluded that, despite advances in modern diagnostic procedures, little progress has been made in hastening the diagnosis of coeliac disease.

Aged↗