Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress

We have previously shown that acute erythropoietic (Ep) stress by hemolysis or hypobaric hypoxia causes elevations of HbF in the baboon. The magnitude of these elevations is genetically determined, ranging from 3% to 60% (low, intermediate, and high responders). These genetic differences in HbF levels among animals are mainly due to differences in the number of HbF-containing cells ("F-cells"). The present study was undertaken to study the influence of prolongation and of the severity of Ep stress on HbF levels and the number of F-cells. The packed cell volume (PCV) of the blood of 4 animals, approximately 3 yr old, was maintained at 20% by daily phlebotomies, and the animals were exposed to varying degrees of hypobaric hypoxia for up to 40 days. In these experiments, the number of F-cells increased rapidly and reached individually constant levels ranging from 60% to 80%, when the PCV reached 20%, and no further increase was observed regardless of the subsequent degree of hypoxia. On the other hand, HbF levels, and with it the values for HbF per F-cell, increased proportionally to the severity of the Ep stress and could be maintained at a constant level dependent on the degree of the hypoxia, e.g., at 19,000 feet HbF levels of one animal remained 20%-25% throughout the duration of the exposure of 14 days. These data are indicative of separate control of F-cell numbers and of the levels of HbF per F-cell. It appears that with the increase of Ep stress, those Ep stem cells that have retained the HbF program are mobilized into maturation. A model, attempting to explain this phenomenon is presented.     

In vivo assessment of the inotropic and toxic effects of oxidized ouabain

Summary Oxidized ouabain, a product of the oxidative cleavage of the rhamnose ring in ouabain has been found to have a higher inotropic toxic ratio in cultured cardiac myocytes.The purpose of our study was to evaluate the efficacy and toxicity of oxidized ouabain in comparison with ouabain in intact animals. Drugs were infused to healthy cats; the positive inotropic effect, and the time-course of development of arrhythmia were followed and recorded until death. Oxidized ouabain was associated with a higher increase in arterial blood pressure, a mean increase of 41±19% as compared with 21±8% in the ouabain group (p<0.10). There were no significant differences in maximal increases of dP/dt or dP/dt/P (65±29%, 28±10% for oxidized ouabain and 49±16%, 27±11% for ouabain, respectively). The mean doses causing persistent arrhythmia (toxic dose) were 93±23 g/kg of oxidized ouabain vs 39±14 g/kg of ouabain. Lethal arrhythmias were produced by 215±46 g/kg of oxidized ouabain and 62±16 g/kg of ouabain. The radio of toxic to lethal doses was 0.62±0.11 for ouabain vs 0.45±0.09 for oxidized ouabain (p<0.05), but the inotropic to toxic dose ratios were not different.We conclude that oxidized ouabain acts similarly to the known cardiac glycosides in doses which produce inotropic effects in cats, has a lower potency as compared to ouabain, and appears to have a more benign course of intoxication.     

Clonidine for patients with rapid atrial fibrillation.

OBJECTIVE: To determine whether clonidine can slow ventricular rate in patients with rapid atrial fibrillation. DESIGN: Randomized, controlled trial, with a 4-hour follow-up period. SETTING: Emergency room of a university hospital. PATIENTS: A consecutive sample of 18 hemodynamically stable patients who were evaluated or treated for rapid atrial fibrillation. Exclusion criteria included acute or terminal illness; current use of antiarrhythmic agents, calcium-channel blockers, or beta-blockers; excessive hypertension; pulmonary, valvular, or pericardial disease; and electrolyte imbalance. INTERVENTIONS: Patients were randomly assigned to receive either "no treatment" (control group) or clonidine, 0.075 mg orally, at baseline and after 2 hours if heart rate did not decrease by at least 20%. MEASUREMENTS: Blood pressure was measured by the same nurse in the same arm for 4 consecutive hours, and a full 12-lead electrocardiographic evaluation was done. MAIN RESULTS: Heart rate decreased to below 100 beats/min in eight of nine patients receiving clonidine compared with two of nine patients in the control group. The difference in the mean decreases in heart rate was 38 beats/min (95% CI, 20 to 56 beats/min). Six patients who were treated with clonidine and one patient in the control group reverted to normal sinus rhythm. Systolic blood pressure decreased slightly in both groups, without significant differences. Clinical follow-up was uneventful. CONCLUSION: Low-dose clonidine was an easy, efficient, and effective treatment for patients with rapid atrial fibrillation who were hemodynamically stable.     

Extensive Gastric Heterotopia of the Small Intestine Resulting in Massive Gastrointestinal Bleeding, Bowel Perforation, and Death: Report of a Case and Review of the Literature

Gastric heterotopia of the small intestine is a rare occurrence outside of Meckel's diverticulum and intestinal duplication. The vast majority of cases of gastric heterotopia occur as polypoid or tumorous lesions in the duodenum. These lesions have been associated with clinical symptoms including diarrhea, obstruction, dyspepsia, ulceration, and gastrointestinal bleeding. We present a case of gastric heterotopia that is unique because the lesions occurred as multiple, carpet-like, nonpolypoid areas throughout a large portion of the small intestine. A review of the literature is included. Received March 10, 1999; accepted June 28, 1999.