Biomedical subjects
D A Price
Publications and source records attributed to D A Price.
The doctor-client relationship.
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Assay of hydroxyprogesterone in saliva.
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Regional children's units.
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Normal growth despite abnormalities of growth hormone secretion in children treated for acute leukemia.
We have studied the relationship between abnormalities of the growth hormone-somatomedin axis and growth in 26 children previously treated for acute lymphatic leukemia. Each child had previously received cranial irradiation, was in complete clinical and hematologic remission, and off all drugs. The mean standing height SDS of the 26 children was significantly less than normal. There was no significant difference between the mean standing height SDS, height velocity SDS, somatomedin activities, and degree of bone age retardation between the 17 children who received the higher dose of cranial irradiation (Group 1) and the nine who had the lower dose of cranial irradiation (Group II). Furthermore, there was no significant reduction in mean height velocity SDS, somatomedin activity, or bone age in either group when compared to normal age-matched controls. The peak GH responses to both insulin hypoglycemia and an arginine test were significantly lowered in Groups I and II when compared to a control group of children. We conclude that only a minority of children, who previously received cranial irradiation for ALL were clinically GH deficient and, therefore, likely to benefit from GH therapy despite the finding that the majority of these children had reduced GH responses to pharmacologic stimuli.
A randomized study of factor VIII or prothrombin complex concentrate infusions in children with haemophilia and antibodies to factor VIII.
In four children with haemophilia A and antibodies to factor VIII, 18 bleeding episodes were randomized for treatment with factor VIII concentrate (30 units/kg) and 18 for treatment with a prothrombin-complex concentrate (prothrombinex) given in a dose of 30 units of factor IX/kg. Treatment with prothrombinex was associated with a better clinical response, a significantly greater shortening of the kaolin partial thromboplastin time and significantly lower incidence of post-infusion increase of levels of factor VIII antibodies. Although treatment with factor VIII concentrate was clinically successful in 15 episodes, treatment failures occurred in three instances leading to parental request for withdrawal from study in two families.
Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides.
We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 mM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (Vmax) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarization refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfusion without LPC, with the exception of a persistent depression in the Vmax of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials indentical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia.
Serum somatomedin activity and cartilage metabolism in acutely fasted, chronically malnourished, and refed rats.
Serum somatomedin activity (SM-act) and cartilage metabolism were compared in acutely fasted, marasmic (M), and marasmic kwashiorkor (MK) rats. SM-act was estimated in the porcine bioassay. In vitro uptake of [35S]sulfate and [3H]methylthymidine in costal cartilage of the experimental animals during an incubation in medium immediately after sacrifice, called endogenous activity, and the effect of incubation in 20% normal human plasma after a preincubation of 22 h in medium only, called plasma responsiveness", were determined. Acutely fasted rats had lowered SM-act and a circulating heat-labile inhibitor. Endogenous activity and responsiveness of cartilage were depressed. MK rats (fed ad libitum a 0.5% casein, isocaloric food) showed a profound depression of growth and cartilage endogenous activity despite only partially reduced SM-act and increased responsiveness. M rats received normal food and were pair-fed with MK rats, consuming approximately 0.08 g/g BW . day. They showed very depressed SM-act and low endogenous activity, and responsiveness was increased, though less than in the MK rats. On refeeding M rats, SM-act and cartilage responsiveness increased, followed by an increase of endogenous activity. Catch-up growth was best related to [3H]methylthymidine incorporation by cartilage (endogenous activity). In conclusion, these two types of experimental chronic malnutrition induce a more diversified pattern than does acute fasting. During malnutrition, cartilage metabolism does not reflect bioassayable SM-act of serum but rather the other effects of the nutritional insult. On refeeding, the expected relationship of SM-act and cartilage metabolism is rapidly restored.
FMRFamide increases the adenylate cyclase activity and cylic AMP level of molluscan heart.
FMRFamide (phenylalanyl-methionyl-arginyl-phenylalanine amide) is a cardioexcitatory peptide recently isolated and identified in molluscan ganglia. Both FMRFamide and 5-hydroxytryptamine (5HT), the cardioexcitatory neurotransmitter in molluscs, were tested on the ventricle of the bivalve Mercenaria mercenaria. Both agents increased myocardial contractility, the intracellular cyclic AMP concentration of intact hearts and the adenylate cyclase activity of a myocardial membrane fraction. FMRFamide was 5--10 times more potent than 5HT. All of the effects of 5HT, and none of those of FMRFamide, were blocked by methysergide, a specific 5HT antagonist.
Structure of a molluscan cardioexcitatory neuropeptide.
A cardioexcitatory substance from ganglia of the clam Macrocallista nimbosa, formerly designated peak C, is the tetrapeptide amide Phe-Met-Arg-Phe-NH2. Its structure was determined by the combined use of Edman dansyl degradation and tryptic digestion. The structure was confirmed by synthesis. This neuropeptide is active at about 10(-8)M when assayed on molluscan muscle.
Purification and characterization of a cardioexcitatory neuropeptide from the central ganglia of a bivalve mollusc.
We have purified a cardioexcitatory substance, previously designated peak C, from ganglia of the Sunray Venus clam, Macrocallista nimbosa. Low concentrations (10(-9)-10(-8) M) of this substance not only excite the isolated clam heart, but also produce tonic contractions of the isolated radula protractor muscle of the whelk, Busycon contrarium. These two muscle preparations have therefore been used as a parallel bioassay for peak C. Peak C is inactivated by proteolytic enzymes, has an isoelectric point greater than pH 10 and has an ultraviolet absorption spectrum similar to that of phenylalanine. On thin layer chromatograms, peak C separates into two components; one of these is probably a partially oxidized form produced during purification. Both components react with ninhydrin and with the Sakaguchi reagent for guanidino groups. The amino acid composition of peak C is Phe2.00Met0.81Arg1.12. N-terminal analysis, one round of Edman-dansyl degradation, and tryptic digesting are consistent with the identification of Macrocallista peak C as a tetrapeptide amide: Phe-Met-Arg-Phe-NH2 (FMRFamide).
The use of non-activated prothrombin concentrate in the management of haemophilia A with factor VIII antibodies.
Three children with haemophilia and antibodies to factor VIII were treated with a non-activated prothrombin concentrate (Prothrombinex) for 12 bleeding episodes. There was clear clinical response and joint aspirations were performed after infusions of phothrombinex in a dose of 30--50 factor IX units/kg body weight and there was no clinical evidence of thrombosis or febrile reactions. There was a significant shortening of the activated partial thromboplastin time (PTT) at one and four hours after the initial infusion with a return to pre-infusion levels 9--24 hours after infusion. The shortening in the PTT was less marked in subsequent infusions. There were no changes in the level of factor VIII procoagulant activity, factor VIII related antigen or factor VIII antibodies after the infusion. In two patients platelet function studies were unaltered by the infusion and in one patient procoagulant levels of factor II, IX and X were no greater than expected from the infusion. We conclude that infusions of non-activated prothrombin concentrates are clinically effective in the treatment of children with haemophilia and factor VIII antibodies but the mechanism of action is unknown.