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Biomedical subjects

D M McCarthy

Publications and source records attributed to D M McCarthy.

At least 73 records · Page 4Linked to original sources

Nonsteroidal antiinflammatory drug-induced ulcers: management by traditional therapies.

Endoscopic distinction between ulcers and erosions is difficult. Consequently, existing literature, which must be taken at face value, may be misleading. Nevertheless, from published studies most gastric and duodenal ulcers associated with nonsteroidal antiinflammatory drugs appear to heal on antacids or H2-antagonists. Sucralfate appears useful for duodenal but not gastric ulcers. Continuing nonsteroidal antiinflammatory drugs does not prevent or delay healing of duodenal or small gastric ulcers; their effects on large gastric ulcers remain uncertain. Thus far, only full doses of H2-antagonists, or their combinations with antacids, have been shown to heal ulcers and prevent recurrences. Ulcer recurrences and complications have occurred in small numbers of patients on maintenance doses of H2-antagonists. Available antiulcer drugs (antacids, H2-antagonists, sucralfate) reduce severe acute injury when taken before or with nonsteroidal antiinflammatory drugs. They also reduce ulcerlike symptoms due to nonsteroidal antiinflammatory drugs. Inexplicably, chronic prophylaxis with H2-antagonists for 4 wk or more appears ineffective in preventing gastric ulcers, although duodenal injury is reduced. As the efficacy of available prophylactic therapy (H2-antagonists, sucralfate, and antacids) has not been established, routine use in all cases seems unjustified at present.

Acute Disease↗

Direct hemodynamic effect of insulin in the isolated perfused kidney.

The hemodynamic effect of insulin was examined in isolated perfused kidneys. Experiments were designed to study the effect of the hormone on basal hemodynamics and in the presence of angiotensin II (ANG II). Physiological insulin concentrations caused both renal vasodilation and increased glomerular filtration rate (GFR) during basal perfusion periods and attenuated the vasoconstrictor action of ANG II while limiting the ANG II-induced reduction of GFR. Insulin also increased fractional sodium reabsorption and diminished the natriuretic effect of ANG II. The addition of insulin to perfusions in which ANG II was infused from the start caused renal vasodilation, although supraphysiological concentrations were required. Kidneys perfused with hyperoncotic albumin to prevent filtration similarly demonstrated a vasodilatory effect of insulin that did not require glomerular filtration. Inhibition of prostaglandin (PG) synthesis with indomethacin prevented the vasodilatory effects of insulin. These data support the hypothesis that insulin causes renal vasodilation by a PG-dependent process.

Angiotensin II↗

Mixed lymphocyte cultures using automated blood cell counters.

We compared the standard mixed lymphocyte culture technique with a new technique based on cell count and size distribution in a series of histocompatibility tests on 24 patients and 39 potential donors for bone marrow transplantation. We found that suspensions in which lymphocytes were undergoing transformation could be distinguished from those in which they were not after a 10-day incubation period by measuring the leucocyte count and size distribution in a Coulter S+ IV automated counter. The leucocyte count was higher and the size distribution was wider in suspensions where the lymphocytes were transforming. The correlation between relative response indices calculated using tritiated thymidine uptake or total nuclear mass was close (r = 0.7; p less than 0.001) although there were major differences in the response as assessed by each of the two techniques in some individual cases. We feel this method is suitable to screen large numbers of unrelated donors.

Anemia, Aplastic↗

Genetic transformation in Lactobacillus sp. strain 100-33 of the capacity to colonize the nonsecreting gastric epithelium in mice.

Lactobacillus isolates able to colonize the surfaces of the nonsecreting epithelia in the stomachs of monoassociated ex-germfree mice were derived from Lactobacillus acidophilus 100-33. Strain 100-33 was originally isolated from pig feces and is unable to colonize the murine gastric epithelium. In experiments involving attempts genetically to transform the capacity to colonize the epithelium, cells of strain 100-33 were treated with muralytic enzymes and mixed with polyethylene glycol and genomic or plasmid DNA extracted from Lactobacillus fermentum RI. Strain RI was originally isolated from a conventional mouse and has the capacity to colonize the nonsecreting gastric epithelium. The mixtures containing cells, polyethylene glycol, and DNA were plated on a regeneration medium. After overnight incubation, the cells were washed from the plates and introduced by gastric gavage into germfree mice. Only mice that received regenerated 100-33 cells previously mixed with genomic DNA from strain RI had layers of gram-positive bacteria on the keratinized epithelia of their stomachs. Six isolates cultured from the washed gastric tissues of these animals were characterized. When a culture of each or a pool of cultures of the six were orally administered to germfree mice, layers of gram-positive bacterial cells were visible on the keratinized gastric epithelia of the animals within 1 to 3 weeks. Cells of all six, but not of strain 100-33, reacted with antibody made in rabbits to L. fermentum RI cells, as determined by an enzyme-linked immunosorbent assay. Nevertheless, all six had fermentation profiles identical to that of strain 100-33.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Primary polycythaemia, essential thrombocythaemia and myelofibrosis--three facets of a single disease process?

Primary polycythaemia (PP), idiopathic myelofibrosis (MF), essential thrombocythaemia (ET) and chronic granulocytic or myeloid leukaemia (CGL) are clonal disorders of the pluripotent haemopoietic stem cells. We have studied granulocyte, megakaryocyte and erythroid progenitors from the peripheral blood of 7 patients with PP, 9 with ET, 19 with MF and 6 with CGL in order to characterise similarities and differences at the committed progenitor cell level. Spontaneous megakaryocytic and erythrocytic growth was characteristic of MF, PP and ET but was not seen in CGL. Circulating erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitors were markedly increased in MF and CGL, less raised in ET and closest to normal in PP. Erythropoietin-independent erythroid bursts (EIBFU-E) grew from the blood of patients with MF, PP and ET but spontaneous growth of megakaryocytes occurred in only MF and ET. These results suggest a progression of increasing abnormality from PP, where EIBFU-E occurred with relatively normal numbers of circulating progenitors, to ET where both EIBFU-E and megakaryocyte precursors regularly occur with elevated numbers of progenitors, to MF where spontaneous BFU-E, CFU-Mk and CFU-GM occur at high levels.

Colony-Forming Units Assay↗

Bone marrow transplantation for adults and children with poor risk acute lymphoblastic leukaemia in first complete remission.

Thirty-two patients with poor risk acute lymphoblastic leukaemia in first complete remission received bone marrow transplants (BMT) from fully matched family donors. Their ages ranged from 7 to 41 (median 23) years. Nine patients were aged 16 years or less. Patients were selected for BMT because they had risk factors for relapse with standard treatment approaches. In particular the children who were selected for BMT had presenting blast counts of greater than or equal to 90 x 10(9)/l or null immunophenotypes. The overall disease-free survival was 50% with a relapse risk of 31% at 9 years. Patients aged less than 16 years had a much lower risk of both graft-related disease and relapse than did older patients (disease-free survival 89% for those aged 7-16, 48% for those aged 17-26, 24% for those aged 26-41). We conclude that selection of BMT for young patients with poor risk features is entirely justified but that the prognosis for older patients is poor even after BMT.

Adolescent↗

The effect of 1,25-dihydroxyvitamin D3 on the relationship between growth and differentiation in HL-60 cells.

Cells of the human promyelocytic leukaemia line HL-60 may be induced to differentiate along the monocytic lineage by the seco-steroid hormone 1,25-dihydroxyvitamin D3. We used fluorescence-activated cell sorting to show that, in addition to inducing differentiation, the hormone caused HL-60 cells to accumulate in G1/G0 phases of the cell cycle. We also labelled differentiating cells with both a monocyte-specific antibody and a DNA stain simultaneously. Analysis of these cell populations showed that, although cells acquired the differentiated phenotype irrespective of their position in the cell cycle, they eventually became arrested in G1/G0 as a consequence of differentiation. The normal relationship between differentiation and growth which is lost on malignant transformation is therefore restored by treatment of HL-60 cells with 1,25-dihydroxyvitamin D3.

Calcitriol↗

Mitochondrial DNA in Candida pintolopesii, a yeast indigenous to the surface of the secreting epithelium of the murine stomach.

Candida pintolopesii 108-1 is an indigenous yeast which colonizes the surface of the secreting gastric mucosa of mice. We have been exploring the aerobic respiratory capacities of this organism in reference to its capacity to colonize the stomach surface, an environment that could contain little oxygen for microbial growth. In this paper, we report mitochondrial DNA and membranes in cells of a strain of this yeast isolated from the gastric epithelium of a mouse and compare the findings with those made by other investigators in studies of Saccharomyces cerevisiae. Putative mitochondrial DNA was isolated from crude lysates of C. pintolopesii and S. cerevisiae as fluorescing bands in CsCl gradients containing 4',6-diamidino-2-phenylindole. The DNA from C. pintolopesii hybridized with a 32P-labeled DNA probe for the 21S rRNA gene encoded by mitochondrial DNA in S. cerevisiae. Postvital cell staining with 4',6-diamidino-2-phenylindole and rhodamine 123 revealed mitochondrial DNA and membranes, respectively, in the cytoplasm of intact C. pintolopesii cells. The staining patterns were generally similar to those reported for S. cerevisiae. Finally, structures similar to those reported to be mitochondria in electron micrographs of S. cerevisiae were seen in preparations of C. pintolopesii cells examined by transmission electron microscopy. These data confirm findings from studies of its respiratory capacity published earlier that a strain of C. pintolopesii isolated directly from its native habitat has functional mitochondria.

Aerobiosis↗

ABH and Lewis antigen and antibody expression after bone marrow transplantation.

We have tested 10 bone marrow transplant donors and recipients for ABH and Lewis antigens and ABH antibodies. Two group A2 recipients stably engrafted with group O marrow produced anti-A1. Small quantities of recipient-type ABH substance were found on the posttransplant erythrocytes in cases where the recipient was a secretor but not in a single nonsecretor recipient. Lewis antigens were always of recipient type. The incidence of graft-versus-host disease and graft rejection were similar in 41 patients who received ABO-mismatched and 61 patients who received ABO-matched grafts.

ABO Blood-Group System↗

Effects of six-month afterload reduction therapy with hydralazine in chronic aortic regurgitation.

Seventeen patients with chronic asymptomatic aortic regurgitation (AR) were studied to determine whether 6 months of hydralazine therapy can reduce the severity of AR or reverse left ventricular (LV) enlargement and hypertrophy. Echocardiography, radionuclide angiography at rest and during exercise, and maximal treadmill exercise with respiratory gas analysis were performed at intake and after a 6-month double-blind treatment period. After dose titration with hydralazine, patients were randomized to their maximal tolerated hydralazine dose or to placebo. At intake, hydralazine and placebo groups were similar. Six patients taking hydralazine and 8 taking placebo completed the study protocol. One patient taking placebo died and 2 patients taking hydralazine withdrew with drug-related adverse effects. The mean titrated dose of hydralazine was 96 +/- 9 mg, but the mean treatment dose was 63 +/- 21 mg administered 3 times daily because of drug intolerance. After 6 months, mean systolic blood pressure with hydralazine therapy decreased from 136 to 125 mm Hg (p less than 0.02), and end-systolic posterior wall thickness increased from 1.58 to 1.70 cm (p less than 0.05), resulting in a significant reduction in M-mode meridional end-systolic stress (from 104 to 80 kdynes/cm2) (p less than 0.05). M-mode fractional shortening increased from 0.28 to 0.31 (p less than 0.05) with hydralazine, but mean LV echocardiographic dimensions were unchanged. LV mass increased from 383 to 434 g (p less than 0.05) with hydralazine primarily because of an increase in end-diastolic wall thickness. In the placebo group, there was no change in any of the hemodynamic or echocardiographic parameters at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Colonoscopy after Golytely preparation in acute rectal bleeding.

Thirty-five consecutive patients with acute hematochezia, negative gastric aspirates, and negative sigmoidoscopy underwent urgent colonoscopy after Golytely purgation. Mucosal visualization was excellent. Colonic bleeding lesions were identified in 24 of 35 patients, and hemorrhage originating proximal to the ileoceal valve was documented in three of these 35 patients. Therapeutic endoscopic electrocautery, employed in 12 of 35 patients, was effective in 11. The peroral preparation was well tolerated, and there were no complications of the preparation or of colonoscopy. The data suggest that urgent colonoscopy following Golytely purgation is a safe, sensitive, and specific diagnostic procedure that provides an opportunity for early nonoperative treatment of acute colonic hemorrhage.

Adolescent↗