In 31 canine heart-lung preparations the direct cardiac effects of dopamine were compared to those of norepinephrine and orciprenaline. All three agents increased heart rate by 50-60% to a maximum of 240-250 beats/min. The inotropic effects of the three drugs were not significantly different. Even with the highest doses cardiac arrhythmias were rarely observed. To achieve maximal chronotropic and inotropic effects, dopamine required four times higher doses than norepinephrine and orciprenaline. All three drugs increased right ventricular dP/dt max by about twice as much as left ventricular dP/dt max. Peak systolic pressure (P max) in the right ventricle was increased 4-5 times more than P max in the left ventricle while mean aortic pressure was elevated by 12-16 mm Hg and mean pulmonary pressure by 6-14 mm Hg. The positive inotropic effect of all three sympathomimetics and of CaCl2 was substantially more pronounced on the right than on the left ventricle.
Background: The occurrence of antidrug antibodies is common in children treated with recombinant human growth hormone (rhGH). However, their clinical significance is unclear. Objective: This study aimed to examine the clinical significance of anti-GH antibodies by analyzing the phenotype of patients who tested positive in relation to the quantity of anti-GH antibodies. Method: In this laboratory-based retrospective study encompassing a time span of 6 years, all positive samples were identified, and senders were contacted. Anti-GH antibodies were measured using a radioprecipitation assay; positive samples underwent a confirmatory assay. Results: Out of a total of 104 samples from 66 patients, positive test results were found in 28 samples from 13 patients. Clinical data were available from all but one. The group with positive test results comprised 6 patients with a normal response to GH provocative tests (group A) and 6 with an insufficient response or with isolated GH deficiency (IGHD) type 1A (group B). Diagnoses in group A were neurosecretory dysfunction, bioinactive GH syndrome and constitutional delay of growth and puberty. Diagnoses in group B were IGHD type 1A, septo-optic dysplasia, and cerebral midline defect with multiple pituitary hormone deficiency. Insufficient growth response to rhGH was absent except in one sibling pair with IGHD type 1A and a patient with cerebral midline defect. These patients had the highest concentrations of anti-GH antibodies. Conclusions: The biological significance of anti-GH antibodies seems to be limited to patients with high concentrations of anti-GH antibodies. For all other patients, we recommend a careful “wait and see” strategy and monitoring antibody titers.
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