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Biomedical subjects

A Macpherson

Publications and source records attributed to A Macpherson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Antibodies to colonic epithelial cells from the serum and colonic mucosal washings in ulcerative colitis.

It has been suggested that antibodies to a colonocyte protein of 40 kD (an intestinal isoform of tropomyosin) are specifically found in the serum and mucosa of patients with ulcerative colitis, which has important pathogenic implications. This study isolated and purified tropomyosin from the colonic mucosa, but no specific binding to this protein has been detected in serum samples or immunoglobulins isolated from mucosal washings of 20 ulcerative colitis (UC) patients by enzyme linked immunosorbent assay (ELISA) compared with 21 controls or 17 Crohn's disease (CD) patients. Samples from a further 12 patients with UC and primary sclerosing cholangitis (it is proposed that cross reactivity against the intestinal tropomyosin isoform accounts for the extraintestinal disease) also did not show binding to tropomyosin, whereas monoclonal antitropomyosin antisera bound both ELISAs and western blots. This study also examined the proteins in the normal colonic biopsy specimens on western blots that are bound by both serum samples and mucosal immunoglobulin preparations from these patients groups; there was no specific IgG or IgA binding to patients with UC or UC/primary sclerosing cholangitis, whereas binding to mitochondrial proteins of 70,000 and 45,000 was seen in samples from 12 primary biliary cirrhosis positive controls. This work does not support the hypothesis that autoimmune activity against the intestinal isoform or tropomyosin is important in the pathogenesis of ulcerative colitis.

Adolescent↗
PubMed1995

Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.

Adult↗
PubMed1995

Spontaneous convulsions in Charles River Wistar rats.

Spontaneous clonic convulsions in the Charles River Wistar rat have been observed at an incidence of 1.5%. Females (2.3%) are more susceptible than males (0.7%). These convulsions are not seen in rats of less than approximately 16 weeks of age. Some animals have exhibited single convulsions whilst others have convulsed on numerous occasions. No histopathological abnormalities of the brain have been recorded for these animals following routine examination.

Aging↗
PubMed1994

Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease-modifying antirheumatic drugs.

OBJECTIVE: To identify the source of intestinal blood loss in rheumatoid arthritis patients being treated with nonsteroidal antiinflammatory drugs (NSAIDs) and assess the response to sulfasalazine and other disease-modifying antirheumatic drugs (DMARDs). METHODS: Intestinal inflammation, blood loss, and gastroduodenal damage, and the response to treatment with DMARDs, were assessed in 46 patients taking NSAIDs. RESULTS: Intestinal inflammation and blood loss correlated significantly with one another (r = 0.43, P < 0.003), but not with the macroscopic or microscopic appearance of the gastroduodenal mucosa. Sulfasalazine reduced both intestinal inflammation and blood loss, whereas the other DMARDs did not. CONCLUSION: The small intestine is the main site of mild chronic blood loss in patients receiving NSAIDs, and this blood loss can be reduced with sulfasalazine treatment.

Aged↗
PubMed1994

The effect of intestinal hypoperfusion on intestinal absorption and permeability during cardiopulmonary bypass.

BACKGROUND/AIMS: Mean arterial pressure is reduced during hypothermic cardiopulmonary bypass. The aim of this study was to assess whether this was associated with intestinal hypoperfusion and whether it affected intestinal absorption and permeability. METHODS: Twenty-six patients undergoing coronary artery bypass grafting underwent an intestinal absorption-permeability test involving ingestion of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. Ingestion took place 2 days before, within 3 hours, and 5 days after hypothermic cardiopulmonary bypass. Hemodynamic parameters and gastric mucosal laser Doppler blood flow were measured perioperatively in eight patients. RESULTS: Hypothermic (28 degrees C), nonpulsatile cardiopulmonary bypass resulted in a 25% reduction in mean blood pressure, 10% reduction in cardiac index, and a 46% reduction in gastric mucosal laser Doppler blood flow. There was 85.4%, 85.5%, and 73.6% reduction (P < 0.01) in active (3-O-methyl-D-glucose) and passive (D-xylose) carrier-mediated transport and passive, nonmediated transcellular (L-rhamnose) transport in the immediate postoperative period, respectively. The differential urine excretion of lactulose/L-rhamnose increased sixfold. All parameters returned to control levels by the fifth postoperative day. CONCLUSIONS: Cardiopulmonary bypass, while maintaining generally acceptable levels of hemodynamic performance, is associated with significant intestinal hypoperfusion and malabsorption of monosaccharides, which may have implications for enteral drug treatment in the immediate postoperative period.

Adult↗
PubMed1993

NSAIDS and gastropathy.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Glucose and citrate reduce the permeability changes caused by indomethacin in humans.

Nonsteroidal anti-inflammatory drug (NSAID)-induced increased intestinal permeability appears to be a prerequisite for NSAID enteropathy. It has been suggested that early metabolic events leading to the permeability changes may involve inhibition of glycolysis and the tricarboxylic acid cycle, in which case the coadministration of glucose and citrate (the substrates for these metabolic pathways) with indomethacin may afford some protection. The present study, using a combined intestinal absorption-permeability test including 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and [51Cr]ethylene-diaminetetraacetic acid (EDTA) as test probes and the differential urine excretion ratio of [51Cr]-EDTA/L-rhamnose, showed that indomethacin (50 + 75 mg) increased intestinal permeability. A formulation of indomethacin containing 15 mg glucose and 15 mg citrate to each milligram of indomethacin did not increase intestinal permeability significantly above baseline values. When given alone with indomethacin, neither glucose nor citrate (45 mg to each milligram of indomethacin) had any protective effects. Pharmokinetic studies showed that the effects of glucose and citrate cannot be explained on the basis of altered drug absorption. These results suggest a new approach to reducing the small intestinal side effects of NSAIDs.

Adult↗
PubMed1991

Alterations of the LPS determine virulence of Neisseria gonorrhoeae in guinea-pig subcutaneous chambers.

The virulence of lipopolysaccharide (LPS) variants of Neisseria gonorrhoeae strain Gc40 was studied in vivo using the guinea-pig subcutaneous chamber model. Survival of variants D1, D2, D4 and D5 was assessed by viable counts made on chamber fluid at various times after inoculation. Chemotactic effect was measured by counts of white cells in the chambers. Differential cell counts and assessments of the location of the gonococci were made on Giemsa-stained smears of chamber fluid. Sensitivity of the variants to normal guinea-pig serum was determined by in vitro bactericidal assays. D1 and D5 had relatively high Mr LPS which was shed in the medium, were serum resistant, produced intense infections and were mainly extracellular. Large number of damaged white cells were present. D2 and D4, had low Mr LPS which was poorly shed in the medium, were serum sensitive and produced low grade infections. D2 was the least infective and was seen mainly inside neutrophils. Collectively the data indicates that the type of LPS on the gonococcal surface and possibly the amount of shed LPS strongly influence the fate of gonococci in vivo, in an environment in which antibodies, complement and phagocytic cells are freely available. This may be decisive at some stages of the human infection.

Animals↗
PubMed1989

Uterine receptivity in women receiving steroid replacement therapy for premature ovarian failure: ultrastructural and endocrinological parameters.

Endometrial biopsies and plasma oestradiol (E2) and progesterone (P4) levels in 23 patients were evaluated during 26 replacement therapy cycles for premature ovarian failure. Plasma E2 and P4 levels showed wide patient to patient variability, despite each patient being given the same hormone replacement therapy. Biopsies were studied by conventional histological dating and scanning electron microscopy (SEM). Eight morphological features of the surface epithelium that have previously been linked to uterine receptivity for implantation were identified and quantified. No correlation was found between endometrial surface morphology by SEM and circulating E2 and P4 levels. The results of this study do not support the hypothesis that there is an obligatory link between any of the eight morphological features measured in this study and uterine receptivity for implantation. To date, three ongoing pregnancies have been achieved following 18 embryo transfers to a total of 10 of the women in the study group.

Adult↗
PubMed1989

Carcinoma-associated dermatomyositis responding to plasmapheresis.

We report a case of severe carcinoma-associated dermatomyositis which, having shown no response to conventional treatment, improved markedly within 48 h of plasmapheresis. We believe that this is the first time that dermatomyositis associated with an advanced carcinoma has been reported to respond in this way. Dermatomyositis can prove extremely difficult to treat and sometimes fails to respond even to very high doses of steroids and immunosuppressants. There is currently only a single report of the use of plasmapheresis in adult dermatomyositis. We therefore wish to support the findings of Dau and draw attention to the value of this therapeutic option in refractory dermatomyositis.

Adenocarcinoma↗
PubMed1989

The changing gastrointestinal side effect profile of non-steroidal anti-inflammatory drugs. A new approach for the prevention of a new problem.

The most serious side effects of non-steroidal anti-inflammatory drugs (NSAIDs) involve gastroduodenal perforations and massive haemorrhage. It is becoming increasingly clear, however, that it is the small intestine that bears the main brunt of NSAID-related gastrointestinal toxicity. Hence 70% of patients receiving NSAIDs in the long term have evidence of small-intestinal inflammation, and the same patients lose blood and protein as a consequence. Many patients have asymptomatic ileal dysfunction and occasionally may develop unique small-intestinal strictures necesitating surgery. The pathogenesis of the intestinal inflammation is beginning to emerge. There are data to support that an imbalance between prostaglandins and leukotrienes is important in disrupting small-intestinal integrity during drug absorption. Furthermore, a simple mixture of glucose and citrate with indomethacin appears to minimize the damage. Whether this overcomes a metabolic block caused by NSAIDs and replenishes ATP levels or acts by scavenging oxygen free radicals is unknown, but our further understanding of the mechanism may revolutionize our approach to prevention of the gastrointestinal toxicity of NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗