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Biomedical subjects

P Kidd

Publications and source records attributed to P Kidd.

54 records · Page 3Linked to original sources

Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit.

Seventy-two rabbits were separated into groups to receive no drug, subcutaneous verapamil, metoprolol, hydralazine, metoprolol and hydralazine, or oral verapamil in 1 of 3 doses daily for 10 weeks. They also received a high-cholesterol diet and had serum triglyceride, cholesterol, and verapamil levels measured twice during the study. Blood pressure (BP), heart rate and weight were measured every 10 days. Approximately 60% of the rabbits given verapamil had detectable levels of the drug in their serum. This group had significantly less severe atherosclerosis in their aortas at the time they were killed, even though they had significantly higher cholesterol levels than the other groups. This group also did not have different BP than the other groups (except for the subcutaneous verapamil group). Thus, protection from atherosclerosis by verapamil in the cholesterol-fed rabbit is not the result of lowering of BP.

Animals↗

The sarcoplasmic reticulum of an ultrafast lobster muscle: first evidence of a tubular configuration.

The sarcoplasmic reticulum (SR) of the remarkably fast remotor muscle of lobster second antenna was investigated with regard to ultrastructure, calcium uptake and protein composition. The SR of this unique muscle dominates the volume of the cell. We were able to preserve the configuration of the SR in its native state simply by processing the muscle for electron microscopy at 0-4 degree C. For the first time the SR is seen as larger (0.1 micrometer diam.) tubules that crowd the space between myofibrils, Previous observations of this organelle have been reported that showed a rather unsatisfying discontinuous vesicular configuration of the SR. This report indicates that these structures were fixation artifacts. The uptake of calcium measured in a microsomal subfraction in the presence of ATP and oxalate does not differ significantly from similar experiments with vertebrate SR. However, gel electrophoresis of lobster SR demonstrate a single intrinsic Ca-ATPase protein of 100,000 mol, wt. with neither of the typical lower molecular weight proteins found in vertebrate SR.

Animals↗

Verapamil preserves myocardial contractility in the hereditary cardiomyopathy of the Syrian hamster.

We attempted to alter the inherited myocardial damage and loss of contractility of the cardiomyopathic Syrian hamster (strain U-MX7-1) by giving cardiac drugs that altered intracellular calcium and myocardial workload. Thirty-seven 21-day-old cardiomyopathic and thirty-seven 21-day-old normal hamsters were divided into five groups each: verapamil-, propranolol-, digoxin-, hydralazine-, and saline-injected. On their 90th day of life, the hamsters were killed. Of the five cardiomyopathic groups, only verapamil reduced myocardial damage. When both "control" and cardiomyopathic hamsters were treated with saline, digoxin, or propranolol, the cardiomyopathic hamsters had significantly less contractile force, maximal rate of force development, and maximum velocity of unloaded shortening. When both groups were treated with verapamil or hydralazine, there were no significant group differences in the indices of contractility. However, when saline-treated cardiomyopathic hamsters were compared with drug-treated cardiomyopathic hamsters, only verapamil preserved myocardial contractility. There was also a weak correlation between the Vmax and the actin-activated ATPase activity of the cardiomyopathic hamsters (r = 0.63, P less than 0.001). We conclude that verapamil helped protect the myocardium of genetically cardiomyopathic hamsters against structural damage, and helped preserve myocardial contractility.

Actins↗

Structural and functional lability induced by diethyl ether on the sarcoplasmic reticulum membrane.

Structural and functional changes occurring in sarcoplasmic reticulum vesicles following exposure to low concentrations (5--7%, v/v) of diethyl ether in aqueous media, were studied by electron microscopy and by kinetic measurements of Ca2+ transport and ATPase activity. Electron microscopy of thin sectioned and freeze-fractured sarcoplasmic reticulum vesicles provided detailed resolution of Ca-ATPase amphiphilic molecules displaying 'lollipop' portions on the outer surface of the vesicle, and non-polar moieties penetrating the membrane's hydrophobic interior. This asymmetric disposition of ATPase molecules was disrupted in vesicles exposed to ether and then centrifuged and/or resuspended in aqueous media. Such vesicles had a tendency to undergo fragmentation, and the distribution of ATPase molecules was markedly altered. The continuous fuzzy layer of lollipops became discontinuous, and the intramembranous particles became randomly distributed over both the concave and the convex freeze-fracture membrane faces. Functionally, the vesicles lost their ability to accumulate calcium in the presence of ATP, although high rates of ATPase activity were maintained. Vesicles which were simply exposed to ether, without being subjected to centrifugation and/or homogenization, did not appear altered ultrastructurally, and retained their ability to accumulate calcium. In fact, the enzyme turnover and the maximal levels of calcium uptake were increased. It is concluded that diethyl ether interferes with lipid-lipid and protein-lipid interactions in the sarcoplasmic reticulum vesicle membrane, thereby facilitating molecular motions which may be a limiting factor in the transport mechanism. On the other hand, these weakened interactions permit structural denaturation and loss of the ability to maintain a transmembrane Ca2+ gradient when the vesicles are subjected to mechanical perturbations which are harmless in the absence of ether.

Animals↗

Intussusception in an infant with acute lymphoblastic leukemia: a case report and review of the literature.

PURPOSE: An ileocecal intussusception developed in a 7-month-old infant with acute lymphoblastic leukemia (ALL) during induction therapy. Gastrointestinal complications, especially intussusception, are rare in children with ALL. PATIENT AND METHODS: The history of a 7-month-old white boy with ALL in whom an ileocecal intussusception developed 1 week into induction chemotherapy was reviewed. In addition, a literature search was performed to determine the prevalence of this complication in children with acute leukemia. RESULTS: On day 4 of induction chemotherapy for B-lineage ALL, the infant developed abdominal distension with hypoactive bowel sounds. After a barium enema and abdominal computed tomography scan, the symptoms were determined to be caused by an ileocecal intussusception. Chemotherapy was resumed 1 week after immediate surgical intervention (reduction of intussusception and resection of the "leading edge") with an uneventful post-operative recovery. Histopathologic examination of the resected edge revealed an intact mucosa with areas of necrosis in the submucosa. This was associated with a dense lymphoid infiltrate composed of mature lymphocytes and leukemic cells, edema, and focal necrosis. Despite a 1-week delay in chemotherapy, a complete remission was documented at day 32. DISCUSSION: The prevalence of intussusception in children with ALL and its possible etiology are discussed. The pathologic changes, clinical manifestations, and treatment outcome are briefly mentioned.

Antineoplastic Combined Chemotherapy Protocols↗

Recombinant alpha-2 interferon in the treatment of hairy cell leukemia.

We treated 14 patients with hairy cell leukemia, 13 of whom had progressive disease, with recombinant alpha-2 interferon administered sc at 2 X 10(6) units/m2, three times per week. Thirteen patients were evaluable for response. All evaluable patients responded within 6-8 weeks. After a minimal treatment duration of 6 months and a maximal of 12 months, three patients have achieved complete response and ten have achieved partial response. With a median treatment duration of 10 months, the responding patients' hematologic parameters are continuing to improve, and no responding patients have relapsed. This outpatient self-administered regimen is well-tolerated, with mild fever, myalgias, and headache usually resolving within 2 months. Although the optimal regimen and the mechanism of action are unknown, recombinant alpha-2 interferon may be the treatment of choice for patients whose disease progresses after splenectomy or who are not surgical candidates.

Adult↗