Biomedical subjects

B Crotty

Publications and source records attributed to B Crotty.

26 records · Page 2Linked to original sources

PubMed1992

Salicylates used in inflammatory bowel disease and colchicine impair interferon-gamma induced HLA-DR expression.

Colonic epithelial cells express HLA-DR in inflammatory bowel disease. The effect of drugs used in the treatment of inflammatory bowel disease and colchicine on interferon-gamma (IFN-gamma) induced DR expression has been investigated. HT-29 cells were cultured in 25 cm2 flasks. At 48 hours interferon-gamma (0, 50, or 100 U/ml) +/- drug were added. At 120 hours the cells were stained for HLA-DR and analysed by flow cytometry. 10(-2) M 5ASA reduced DR expression induced by 50 U/ml interferon-gamma from 62 (12)% of cells (mean SD) to 29 (20)% (p less than 0.005). Corresponding figures for 10(-2) M N-acetyl 5ASA were 68 (16)% to 39 (17)% (p less than 0.05); for 10(-2) M 4ASA, 61 (4)% to 57 (4)% (p = 0.6); for 10(-2) M N-acetyl 4ASA, 60 (12)% to 35 (13)% (p less than 0.05); for 10(-2) M olsalazine, 72 (9)% to 3 (1)% (p less than 0.001); for 10(-3) M olsalazine, 72 (9)% to 16 (10)% (p less than 0.001); for 10(-6) M colchicine, 62 (13)% to 5 (3)% (p less than 0.001); and for 10(-7) M colchicine, 62 (13)% to 10 (3)%. Similar results were obtained when DR was induced by 100 U/ml of interferon-gamma except with 10(-2) M 4ASA which reduced expression from 77 (4)% to 68 (3)% (p less than 0.05). Sulphapyridine, prednisolone, indomethacin and cyclosporin A had no effect. Concurrent staining with propidium iodide showed that these results were unchanged when viable cells alone were analysed. Prior incubation of cells with drug, followed by washing, had no effect on interferon-gamma induced DR expression. 5ASA, N-acetyl 5ASA, 4ASA, N-acetyl 4ASA, olsalazine and colchicine reduce interferon-gamma induced HLA-DR expression. In inflammatory bowel disease these compounds may impair antigen presentation by the colonic epithelium.

Aminosalicylic Acid↗

PubMed1992

Inhibition of binding of interferon-gamma to its receptor by salicylates used in inflammatory bowel disease.

5-Aminosalicylic acid (5ASA), 4ASA, their N-acetylated metabolites N-acetyl-5ASA and N-acetyl-4ASA, olsalazine, and colchicine impair interferon-gamma (IFN gamma) induced HLA-DR expression on a colonic cell line, HT-29. The mechanism of this effect is now reported. HT-29 cells were cultured with 50 U/ml IFN gamma with or without drug, and northern blot analysis was performed using a probe for the beta chain of the DR molecule. IFN gamma led to a noticeable increase in HLA-DR mRNA which was attenuated by the drugs. Analysis of the specific binding of increasing concentrations of 125I-IFN gamma by non-linear regression showed a Kd of 1.35 x 10(-10) M and 2.3 x 10(5) binding sites per HT-29 cell. Binding of 125I-IFN gamma was reduced by incubation with increasing concentrations of unlabelled IFN gamma but not with IFN alpha. Incubation with therapeutic concentrations of drugs led to the following reductions in binding: 10 mM 5ASA, 20% (p < 0.001); 10 mM N-acetyl-5ASA, 24% (p < 0.01); 10 mM 4ASA, 21% (p < 0.005); 10 mM N-acetyl-4ASA, 29% (p < 0.001); and 1 mM olsalazine, 29% (p < 0.001). Colchicine (10(-7) M) and 10(-5) M prednisolone had no effect. Incubation with higher concentrations of the drugs revealed a dose-response effect on binding with complete inhibition by 100 mM 4ASA and 10 mM olsalazine, and lesser degrees of inhibition by 100 mM 5ASA, N-acetyl-5ASA, and N-acetyl-4ASA. At concentrations found in the rectal lumen, the salicylates used in inflammatory bowel disease impair the binding of IFN gamma to its receptor on colonic epithelial cells.

Aminosalicylic Acid↗

PubMed1992

Epithelial cells bearing class II molecules stimulate allogeneic human colonic intraepithelial lymphocytes.

HLA-DR+ gut epithelial cells may present antigen to intraepithelial lymphocytes (IEL). This study aimed to isolate an IEL population from the human colon to activate CD3 + IEL by a human colonic epithelial cell line (HT-29), bearing different concentrations of class II antigen (HLA-DR). IEL were isolated by a mechanical method from six patients with ulcerative colitis (UC) and from 14 control patients. IEL were cocultured with HT-29 which had been induced to express class II molecules by gamma-interferon (IFN-gamma) in a dose dependent manner. The phenotype and the subsequent expression of activation markers by the IEL were determined to two colour flow cytometry. The IEL population had a CD4/CD8 ratio similar to that seen in tissue sections. In the mixed cell culture, the degree of IEL activation showed a positive correlation with the degree of HLA-DR expression by the HT29 cells and the IEL secreted a IFN-gamma like factor that in turn stimulated the HT-29. Thus, depending on their expression of HLA molecules, colonic epithelial cells are able to activate CD3+CD8+IEL.

Adult↗

PubMed1991

Epidural fentanyl effect on cardiac output and hepatic blood flow.

Epidural opioids provide high quality analgesia with no clinically apparent effect on the circulation or on specific organ blood flow. Little investigative data is available to support these impressions of circulatory stability. Ten patients presenting for thoracotomy were studied at rest preoperatively to determine if epidural fentanyl had any effect on the systemic circulation or hepatic blood flow. Intravascular pressure measurements, cardiac output estimation using the dye-dilution technique and estimation of altered hepatic blood flow by measuring the clearance of indocyanine green were performed. No significant changes in heart rate, perfusion pressure, cardiac output or hepatic blood flow were detected following the administration of fentanyl 50 micrograms into the epidural space.

Analgesia, Epidural↗

PubMed1989

Hepatic extraction of morphine is impaired in cirrhosis.

Using hepatic vein catheterization this study has provided the first direct measurement of morphine hepatic extraction in 8 controls and 8 cirrhotics. The extraction ratio was 0.52 in the control group and was reduced by 25% in the cirrhotics. This reduction is due to impaired enzyme capacity rather than reduced blood flow. The effect of cirrhosis is less than that reported in similar studies of high clearance oxidized drugs and this lends support to the concept that glucuronidation may be relatively spared in cirrhosis. A discrepancy between the systemic clearance and the hepatic clearance provides indirect support for extra-hepatic metabolism of morphine.

Adult↗

PubMed1986

Dominantly inherited cardioskeletal myopathy with lysosomal glycogen storage and normal acid maltase levels.

A family is presented in which 7 members over 3 generations were affected by cardioskeletal myopathy. A vacuolar myopathy with excessive free and intralysosomal glycogen storage in skeletal and cardiac striated muscle was identified in biopsy studies. Post-mortem studies in several patients revealed changes of a congestive cardiomyopathy with myocardial fibrosis. Acid maltase, phosphorylase, debrancher and lysosomal enzyme screens, and glycolytic enzyme levels in skeletal muscle, were normal in 1 case. This is the third report of non-acid maltase deficient lysosomal glycogen storage disease and adds to previous reports with the presentation of detailed family studies, examined of ante- and post-mortem cardiac histology and reports of detailed glycolytic and lysosomal enzyme analysis. This syndrome is unusual among glycogenoses in having a dominant inheritance pattern.

Adult↗

PubMedDate not supplied

Gastrointestinal bleeding from hepatocellular carcinoma invading the stomach.

Bleeding from hepatocellular carcinoma (HCC) invading the gastrointestinal tract is very uncommon. We report the case of a 61 year old man who had a large bleed from HCC invading the fundus of the stomach. Diagnosis was eventually made at laparotomy and he is still alive 7 months after local resection.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

The management of acutely bleeding varices by injection sclerotherapy.

Acutely bleeding varices present a therapeutic dilemma because of the limited efficacy and high complication rates of conventional treatments. Over a period of 26 months, 56 episodes of acutely bleeding varices were treated with injection sclerotherapy as the initial management. Immediate control of haemorrhage was achieved in 91% of patients and control of bleeding during the hospital admission in 84%. Balloon tamponade and surgery were reserved for those patients in whom bleeding was not controlled by sclerotherapy; in 66% of patients the bleeding was controlled by sclerotherapy alone. Of the 56 episodes, 75% survived their admission to hospital. Acute injection sclerotherapy is as least as effective as conventional therapies in the control of bleeding with a low incidence of complications. The technique can be used in all patients irrespective of the severity of their liver disease and, when bleeding is controlled, allows the physician the choice of all the available prophylactic therapies.

Acute Disease↗