The Journal of clinical investigation
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The role of the renin-angiotensin-aldosterone system in the development of congestive failure has been assessed in the conscious dog by use of the nonapeptide converting enzyme inhibitor. Constriction of the pulmonary artery or thoracic inferior vena cava was maintained for 2 wk while daily measurements were made of plasma renin activity, plasma aldosterone, plasma volume, hematocrit, serum sodium and potassium concentrations, sodium and water balance, body weight, and arterial, caval, and atrial pressures. The initial response to constriction was a reduction in blood pressure, a rise in plasma renin activity, plasma aldosterone, and water intake, and nearly complete sodium retention. ⋯ Chronic infusion of the inhibitor in dogs with thoracic inferior vena caval constriction prevented the restoration of blood pressure and suppressed the rise in plasma aldosterone; sodium retention and volume expansion were less than in control experiments. Thus the renin-angiotensin-aldosterone system plays an essential role in the maintenance of blood pressure during the genesis of congestive failure. Initially, the restoration of blood pressure is dependent upon circulating angiotensin II; in the later stages, blood pressure is dependent upon the increase in plasma volume.
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Histamine release from peripheral blood leukocytes challenged with anti-human IgE was studied in patients with chronic urticaria and nonatopic controls. 19 of 23 controls, but only 6 of 20 patients, released over 20% of the total available leukocyte histamine. The response to anti-IgE concentrations of 1.66, 0.33, 0.066, and 0.013 mug antibody N/ml was significantly lower in patients than in controls. Serum IgE levels were significantly higher in the patients but total histamine content of about 10(7) leukocytes was not. ⋯ Ionophore stimulation of aliquots of the same leukocytes used for anti-IgE challenge demonstrated that the urticaria patients' basophils were capable of releasing normal amounts of histamine. Leukocyte cyclic AMP levels in the two groups were not significantly different either in base-line levels or in responsiveness to stimulation with isoproterenol. These data indicate that chronic urticaria patients have a (acquired?) defect in leukocyte histamine release that occurs after the anti-IgE-IgE interaction, but before the actual (second-stage) release process, and that is comparable to the phenomenon of desensitization.
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Clinical Trial Controlled Clinical Trial
Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis. II. Effect on the incidence of pneumonia in seriously ill patients.
All 744 patients admitted to a Respiratory-Surgical Intensive Care Unit (RSICU) were included in a prospective study of the effects of a polymyxin (2.5 mg/kg body wt/day in six divided doses) or a placebo aerosol sprayed into the posterior pharynx and tracheal tube (if present), during 11 alternating 2-mo treatment cycles. The incidence of upper airway colonization in the RSICU with Pseudomonas aeruginosa was 1.6% during the polymyxin treatment cycles (total 374 patients) and 9.7% during the placebo cycles (370 patients) (X2 equals 23.2, P less than 0.01). 3 patients in the RSICU acquired Pseudomonas pneumonia, as defined by independent "blinded" assessors, during the polymyxin cycles while 17 acquired a Pseudomonas pneumonia during the placebo cycles (X2 equals 10.2, P less than 0.01). The overall mortality was similar in both placebo and polymyxin-treated groups (12.2 vs. 12.0%). Systemic antibiotic usage was similar in the different cycles; 49% of patients in the placebo and 53% in the polymyxin-treated groups received systemic antibiotics while in the RSICU.
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Comparative Study
Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia.
We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/min), epinephrine (6 mug/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (plus or minus SE) fasting plasma glucose level of 217 plus or minus 17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steady-state levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. ⋯ Finally, the mean (plus or minus SE) steady-state plasma glucose level of 104 plus or minus 17 mg/100 ml observed during the same basic infusion in five patients with fasting hyperglycemia (mean plus or minus SE, 142 plus or minus 12 mg/100 ml) secondary to chronic pancreatitis suggested that neither chronic hyperglycemia nor hypoinsulinemia per se necessarily lead to insulin resistance. These results demonstrate that marked insulin resistance exists in adult onset diabetics with fasting hyperglycemia. Since previous studies have documented the presence of insulin resistance in patients with chemical diabetes, the possibility exists that insulin resistance may be characteristic of adult onset diabetes mellitus.
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Propylthiouracil (PTU) inhibits peripheral deiodination of thyroxine (T4) and triiodothyronine (T3) and decreases the metabolic effectiveness of T4 in animals. To assess the effect of PTU on extrathyroidal conversion of T4 to T3 in man, 15 studies were performed in athyreotic patients treated with 100 or 200 mug of L-T4 daily for 1 mo before the addition of PTU, 250 mg every 6 h for 8 days. serum T3, T4, and thyrotropin (TSH) were measured daily by radioimmunoassay; serum TSH response to 500-mug thyrotropin-releasing hormone (TRH) was measured before and on the last day of giving PTU. On the 100-mug LT4 dose, serum T3 fell from 120 plus or minus 5 (SE) to 83 plus or minus 6 ng/dl (P less than 0.005) with return to 113 plus or minus 5 ng/dl after stopping PTU; serum T4 (4.5 plus or minus 0.3 mug/dl) did not change. ⋯ Expressed as percent of base-line TSH concentration, TSH rose from 140 plus or minus 52 to 280 plus or minus 44% (control vs. PTU) at 15 min, 265 plus or minus 72 to 367 plus or minus 63% at 30 min, 223 plus or minus 54 to 313 plus or minus 54% at 45 min, 187 plus or minus 45 to 287 plus or minus 51% at 60 min, and 145 plus or minus 22 to 210 plus or minus 28% at 120 min after TRH. The data suggest that PTU blocks extrathyroidal conversion of T4 to T3, thus increasing pituitary TSH secretion and augmenting the TSH response to TRH.