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Biomedical subjects

R B Scott

Publications and source records attributed to R B Scott.

At least 145 records · Page 8Linked to original sources

Reflections on the current status of the national sickle cell disease program in the United States.

Some clouds of concern now appear on the horizon for the national sickle cell disease program. There is flagging general attention by the black population and a dilution of interest in and visibility of the sickle cell problem brought about by political maneuvering to bring the program under the legislative umbrella of many other genetic diseases (which occur predominantly in Caucasians). In addition, the federal program has recently phased-out six comprehensive sickle cell centers and imposed budgetary cutbacks in the remaining centers. The victims of this disease, the black population in general, and the researchers and investigators who seek ways to bring this disease under control need reassurance from the current national administration that the sickle cell program will not be permitted to die a slow death from financial attrition, attenuation of interest, and skillful neglect leading to the phasing-out of another "minority project." The national sickle cell program, in the relatively short span of six years, has made significant and notable progress not only in research endeavor but also in improved patient care and community-wide education. In this context, certainly, the positive aspects of the national sickle cell disease program continue to far outweigh any negative ones.(1)

Anemia, Sickle Cell↗

Genetic diversity in hemoglobins. Disease and nondisease.

Recent mass screening programs for sickle cell trait have been the first large-scale efforts to detect potentially deleterious genes and to provide genetic counseling to healthy carriers. In these programs, the expected prevalence of sickle hemoglobin and hemoglobin C has been found, and other mutant hemoglobin genes have also been uncovered. Many of these are not associated with disease, but simply reflect normal genetic diversity. A paradox of this finding is illustrated when, in counseling, many persons demonstrate difficulty in understanding that though they have an abnormal hemoglobin gene, they themselves are not ill or abnormal. The problem's solution lies in educating both health professionals and the public so that the normal existence of considerable genetic diversity is recognized. Since every person may carry mutant genes, whether potentially deleterious or innocuous, our definition of normal must be revised.

Genes↗

Characterization of marrow granulocyte development: enzyme-specific activity profiles in response to inflammatory reactions.

Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose-6-phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals.

Acid Phosphatase↗

Separation of rabbit marrow precursor cells by combined isopycnic sedimentation and electronic cell sorting.

Separation of developing cells into fractions of differing stages of maturity is critical to effective biochemical study of the process of cellular differentiation. Density gradient techniques utilizing rate-zonal or isopycnic separations have permitted partial separations based on cell mass or cell density. In this study the separation of various rabbit marrow cells was improved by high-speed flow analysis and sorting in a Coulter Two-Parameter Cell Sorter. After preliminary isopycnic separation of marrow cells in Ficoll-Hypaque, cells were sorted into lymphoid and myeloid elements, utilizing light-scatter (LS) profiles to determine sorting. Characteristic LS patterns were present for erythrocytes, lymphocytes, devitalized cells, and granulocytes. When erythrocytes and their precursors were removed by hypotonic lysis, the remaining granulocytes could be sorted to give samples with much greater purity with respect to developmental stage than was possible with density gradients alone. Thus the combination of techniques represents a significant improvement in the ability to study the mechanisms of normal or altered cellular maturation.

Animals↗

Hemolytic potential of methocarbamol.

Methocarbamol, a compound related to mephenesin, has in vitro hemolytic potential. A study was performed to determine whether any hemolysis was detectable after intravenous injection. Methocarbamol and its vehicle (50% polyethylene glycol-300) was compared with vehicle alone and with normal saline controls in high- and low-dose regimens in normal volunteers. Significant increases in plasma hemoglobin were detected 30 min after intravenous injection of methocarbamol or its vehicle alone. Maximum initial plasma hemoglobin levels were approximately 10 mg/dl with vehicle alone, but only 4 mg/dl with the methocarbamol added. Serum haptoglobin levels fell after both high-dose methocarbamol and vehicle during the 3-day period of treatment. Hemolysis, though detectable, did not exceed levels found under physiologic circumstances such as exercise, and represents only a small fraction of the normal daily hemolysis of aged erythrocytes.

Adult↗

A filtration model for study of leukocyte transit in the microcirculation.

In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes.

Adult↗

Five-year retrospective study of hospitalization and treatment of patients with sickle cell anemia.

Examination of computerized hospital records of 463 admissions of 255 patients with sickle cell anemia was made. Patients ranged in age from infancy to 65, with a mean age of 17-7 years. Only 119 of the 255 patients were male, but 54% of the admissions were for males. Most patients were admitted to pediatrics and internal medicine services. Fluids and blood derivatives were given in over 60% of cases and anti-infection drugs in 40%. Mean hospital stay was 14.75 days, twice the mean for other patients. Thirty-six percent of the patients were admitted more than once. Mortality was 1.3% for the 463 admissions. Blue Cross or Medicaid accounted for payment in 51% of admissions. This information can be helpful to health planners providing comprehensive services for sickle cell patients.

Adolescent↗

Hypoplastic acute myelogenous leukaemia.

The clinical course, diagnosis and management of nine cases of hypoplastic acute myelogenous leukaemia are described. Such cases may follow a slowly progressive course and should not receive anti-leukaemic chemotherapy unless the disease is advancing rapidly or unless some specific complication develops. If chemotherapy has to be given, usually because of severe and recurrent infections, then prompt and prolonged remission of disease may occur.

Adult↗

Studies of leukocyte exudates in cyanate-treated animals.

Cyanate (NCO), which impedes sickling by increasing the oxygen affinity of sickle haemoglobin, may react with many proteins in the body and potentially interfere with many functional systems. Leukocyte glycogen was studies because elevated liver glycogen has been noted after high dose NCO treatment in rats. Leukocyte function was also studied in peritoneal exudates. In animals given NCO alone, blood leukocyte glycogen was 2.8 plus or minus 0.3 (SE) mg per 10+9 WBC while control values were 3.3 plus or minus 0.6, a difference not statistically significant. In casein-induced peritoneal exudates, more WBC were recovered from NCO-treated animals (265 x 10+6 WBC vs. 214 x 10+6 WBC; P = 0.0009). Glycogen in blood leukocytes of casein-stimulated animals was not significantly different from NCO-treated animals. Leukocyte glycogen in peritoneal exudates was markedly increased over blood leukocyte glycogen in both controls (19.4 plus or minus 0.6 vs. 2.7 plus or minus 0.3 mg per 10+9/WBC; P less than 0.0001) and NCO-treated animals (17.5 plus or minus 0.7 vs. 3.6 plus or minus 0.5 mg per 10+9 WBC; P less than 0.001), although levels in exudates from control and NCO-treated animals did not significantly differ from each other. 14-C-glucose incorporation into glycogen was significantly increased (P = 0.020) in exudate leukocytes of NCO-treated animals. Initial phagocytic rates were equal in exudate leukocytes of control and NCO-treated animals. Although NCO treatment has demonstrable effects on ome aspects of leukocyte glycogen metabolism, exudation of leukocytes and phagocytic function are not impaired.

Animals↗