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Biomedical subjects

R Welch

Publications and source records attributed to R Welch.

At least 55 records · Page 3Linked to original sources

Mechanism of Escherichia coli alpha-hemolysin-induced injury to isolated renal tubular cells.

Alpha-hemolysin (AH) is a 110,000-dalton protein secreted extracellularly by certain Escherichia coli. This protein is an acknowledged virulence factor for E coli and recently has been implicated as an important determinant in the pathogenesis of E coli pyelonephritis. Recombinant engineered strains of E coli were used that varied only in their ability to secrete AH extracellularly. The effect of AH on vital dye exclusion, oxygen consumption rate (QO2) adenosine triphosphate (ATP) levels, superoxide (O2-) and hydrogen peroxide (H2O2) production in preparations of isolated rat cortical renal tubular cells (RTCs) was assessed. Approximately 5-10 pg of AH dramatically stimulated QO2 by nearly 150%. This was associated with a marked increase in production of O2- and H2O2, to 13.9 +/- 1.7 and 13.2 +/- 2.1 nM/mg cell protein, respectively (P less than 0.05), as well as a 38% decrease in cellular ATP. These biochemical effects were all seen after a 30-minute exposure to AH and by 120 minutes were associated with 15.7% +/- 1.1% of RTCs that were unable to exclude vital dye. The effect of AH on QO2 and O2- formation was prevented by pretreatment of RTCs with ouabain, which indicates that the effect of AH on oxygen metabolism is linked to Na-K ATPase activity. However, when ouabain-treated RTCs were exposed to AH, ATP remained depressed despite the inhibition of QO2 and O2- production. In contrast, in ouabain-pretreated RTCs, cell membrane integrity was dramatically protected, because only 2.4% +/- 0.4% of RTCs were not unable to exclude vital dye. Thus, the data demonstrate that E coli AH provokes at least two biochemical events that may be injurious to RTC: increased oxygen intermediates (O2- and H2O2 and ATP depletion. These findings with ouabain suggest that the first mechanism of injury may be a more proximate cause of cell death. Moreover, the data suggest that endogenous production of reactive oxygen molecules may be critical modulators of RTC membrane injury.

Adenosine Triphosphate↗

Controlled trial of medical therapy for active upper gastrointestinal bleeding and prevention of rebleeding.

UNLABELLED: This multicentered, placebo-controlled trial evaluated the efficacy of medical therapy to stop bleeding in 285 patients with active upper gastrointestinal bleeding (bleeding phase) and 194 patients who had ceased gastrointestinal bleeding and in whom therapy was instituted to prevent rebleeding during the same hospitalization (prevention phase). Patients in the bleeding phase were given cimetidine (300 mg every six hours) or intravenous placebo. There was no significant overall difference between intravenous cimetidine (71 percent) and placebo (77 percent) in stopping acute upper gastrointestinal bleeding. There was also no significant difference noted between intravenous cimetidine and placebo when specific bleeding lesions were evaluated. Once gastrointestinal bleeding had stopped, recurrence of bleeding while receiving prevention therapy (cimetidine tablets 300 mg one three times a day and at bedtime, or Mylanta II liquid 30 ml every hour, or cimetidine plus hourly antacids, or placebo) was evaluated in 194 of the patients in the bleeding phase. Twenty-four percent (12 of 51 patients) rebled while receiving cimetidine, 13 percent (five of 39 patients) rebled while receiving hourly antacids, 11 percent (six of 54 patients) rebled while receiving cimetidine plus hourly antacids, and 26 percent (13 of 50 patients) rebled while receiving placebo. None of these prevention regimens reached statistical significance (p = 0.13). Evaluation of specific bleeding lesions within this group also failed to show any significant value of prevention therapy. IN CONCLUSION: (1) intravenous cimetidine offers no advantage over placebo in stopping active upper gastrointestinal bleeding; (2) the occurrence of rebleeding during the same hospitalization does not appear to be significantly affected by any of the medical regimens used for prevention. These findings would suggest that the cessation of active bleeding and the prevention of recurrent upper gastrointestinal bleeding during a single hospitalization appear to be unaffected by therapy directed at acid neutralization or reduction.

Adult↗

Gastrointestinal blood loss in patients with chronic renal failure.

In the management of patients with chronic failure one of the persistent medical problems is that of anemia. Since iron deficiency can be an important component of this anemia, this study was designed to evaluate the possible contribution of gastrointestinal blood loss to their anemia. Blood loss was quantitated by 51 chromium labeling red cells in normals and in patients with chronic renal failure both before and during chronic hemodialysis. Four normal volunteers had a gastrointestinal blood loss of 0.83 ml/day, six azotemic patients not yet on hemodialysis had significantly greater gastrointestinal blood loss of 3.15 ml/day (p less than 0.05). Ten patients on chronic regular hemodialysis had a daily gastrointestinal blood loss of 6.27 ml/day which was significantly greater than both the normals (p less than 0.01) and the predialysis azotemic patients (p less than 0.05). Complete gastrointestinal tract evaluation in the chronic dialysis patients revealed several upper gastrointestinal tract mucosal abnormalities although discrete bleeding sites were not identified. In conclusion, azotemic patients both before and after chronic hemodialysis have increased gastrointestinal blood loss. This increased blood loss contributes to the increased iron loss in this patient population.

Adult↗

Generalization gradients following differential intradimensional autoshaping.

Three pigeons were trained on a differential, intradimensional autoshaped discrimination. A 45 degrees line tilt was always paired with food whereas a 15 degrees line tilt was never paired with food. All subjects learned the discrimination within 17 sessions. The pigeons were then given generalization tests in extinction over seven line tilts (0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees and 90 degrees). The subjects yielded generalization gradients with maxima at 45 degrees and minima at 15 degrees. An area shift, but no peak shift, was found for each subject.

Animals↗

Methadone maintenance: an assessment of potential fluctuations in behavior between doses.

Thirty methadone maintenance outpatients were measured 1 and 25 hours after ingestion of methadone on auditory threshold, distance perception, simple and differential reaction time, time perception, attention span, and short-term memory. The results revealed a small but statistically significant difference between the two tests for distance perception. In addition, treatment interacted with preparatory interval on differential reaction time and with sex on attention span.

Adolescent↗

Controlled trials of aluminum hydroxide gels for peptic ulcer.

Relief of duodenal ulcer pain by aluminum hydroxide gel (AG) was compared with that obtained by a dummy gel (DG) in randomized trials. In 44 individual pain episodes, complete relief was obtained by 15-ml doses of AG in 79% and by DG in 45% (P less than 0.05). In 48 identical blind trials replicated at another hospital the difference was not significant. The gels were also tested against ulcer pain induced by intragastric acid instillation (Palmer test) in 35 patients; pain was relieved by AG in 63% and by DG in 62%. Presumed effectiveness in terminating ulcer episodes was studied in 65 patients admitted for pain; 37 received milk and cream hourly and 28 did not. All were treated with 15 ml of AG or DG during waking hours. Median time for complete disappearance of spontaneous pain was 3 days for AG and 7 days for DG, the same in both groups. In all patients the acid instillation test was repeated every few days. For the milk and cream group it became negative after 4 days with AG and after 6 days with DG. In 18 patients with gastric ulcer treated for 4 weeks AG led to greater reductions in size than did DG. A number of these trials indicate AG to be more effective than DG, but sampling and other methodological problems limit the certainty of any conclusions.

Aluminum Hydroxide↗