Drug interactions with furosemide.
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Biomedical subjects
Publications and source records attributed to R B Scott.
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The genes responsible for the transmission of sickle cell syndromes from one generation to the next were introduced into the new world during the 17th century. However, this disease was not recorded in the medical literature in the United States until 1910 by Herrick of Chicago. During the next 40 years, many additional cases were reported and a fairly large bibliography developed which dealt essentially with descriptive, clinical and pathological aspects of the disease. New interest in the syndrome occurred in 1949 when Pauling and his associates, employing chemical and electrophoretic techniques, showed that an abnormal hemoglobin was responsible for the sickling phenomenon. In the same year, Neel and Beet, working independently of each other, clarified the inheritance of the disease on the basis of the heterozygous-homozygous hypothesis. In 1958, Ingraham combined the techniques of electrophoresis, chromatography, and trypsin digestion ("fingerprinting") to show that the difference between hemoglobins A, C, and S was in the amino acid sequence of the polypeptide chains which make up the hemoglobin molecule. However, despite these notable advances, interest in the disease remained at a relatively low scientific and health care priority until February 1971, when President Nixon in his message to Congress indicated that greater attention and support for sickle cell disease should be made available at the national level. This paper will review some of the important legislative, political, and organizational initiatives which have had a significant impact on the development and implementation of the current national sickle cell disease program in the United States.
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UNLABELLED: The purpose of this study was to correlate the fasting enterohepatic circulation (EHC) of bile acids with the migrating myoelectric complex. Four dogs were surgically provided with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes implanted from stomach to terminal ileum. Bile was collected in equal-volume, timed aliquots over 6 to 10 h. Aliquots were sampled and either returned to the duodenum for study of the intact EHC, or collected and retained in order to study the time course of the bile acid pool washout. In the washout experiments boluses of radiolabeled taurocholic acid were instilled into the duodenum before and after duodenal phase III of the migrating motor or myoelectric complex (MMC). In another group of experiments the bile acid pool was washed out and during a continuous duodenal infusion of taurocholic acid bile was collected to study the pattern of hepatic secretion. RESULTS: (a) In all experiments, a single broad peak of bile flow and bile acid secretion occurred at 35-55% of the MMC migration time. At this time the MMC had migrated to a point 70-85% of the distance along the small intestine. (b) During bile acid pool washout the peak of bile flow and bile acid secretion occurred with the distal migration of the first MMC and then bile flow and bile acid secretion rates decreased to a minimum and stabilized. (c) In bile acid pool washout experiments the radiolabeled bile acids instilled into the duodenum prior to duodenal phase III were secreted and peaked with peak endogenous bile acid secretion. The secretion of radiolabeled bile acids instilled into the duodenum after duodenal phase III was delayed until the subsequent cycle of the MMC. 88% of the bile acid pool collected over 6 h was secreted during the distal migration of the first MMC (2.4 +/- 0.4 h). (d) After bile acid pool washout and during continuous duodenal infusion of taurocholic acid, hepatic bile flow and bile acid secretion continued to fluctuate with the same pattern observed with the EHC intact. CONCLUSIONS: (a) In the fasting state, the transport of intestinal bile acids to the liver is pulsatile rather than continuous and is determined by the MMC. Maximum hepatic secretion occurs when phase III of the MMC propels the intraluminal bile acid pool to its site of absorption in the distal small bowel. (b) The "housekeeping" action of the MMC is very efficient and clears 88% of the 6-h washout bile acid pool in one pass.
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This paper describes the use of a mobile health unit as a part of a community education, screening, and counseling program. By virtue of its mobility and more flexible hours, this model extends services into the basic urban, suburban, and rural community. Quality control of the diagnostic and counseling activities on the unit is maintained through supervision by the full-time staff of the Howard University Center for Sickle Cell Disease. The program is a part of the University Health Science complex which provides backup consultation and referral sources. The mobile health unit is equipped with a laboratory and waiting, education, and counseling areas; it operates in conjunction with a speakers bureau which conducts a significant portion of the community education. Referrals are made from the unit to a variety of community resources but primarily for additional education and counseling for sickle cell and follow-up services for elevated blood pressure and low and borderline hemoglobin levels.
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A proteinaceous nuclear substructure (nuclear protein matrix or nuclear pore complex-lamina) has been described in a number of cells and may be a universal feature of cell nuclei. We have investigated the nuclear protein matrix (NPM) in the rabbit blood granulocyte and its precursor cells to determine (A) whether the NPM composition is similar to other cells that have been studied and (B) to determine whether the dramatic morphological changes that the granulocyte nucleus undergoes during cell maturation are related to changes in the composition or structure of the NPM. NPM preparations from rabbit granulocytes were similar but not identical to those found in HeLa cells or rat liver nuclei. The NPM structure of more mature cells retained more DNA during the isolation procedures than did immature cell NPMs, and the DNA was less accessible to DNAse in the mature cell nuclei. Scanning and transmission electron microscopy revealed a continuous outer covering of the NPM preparation and a lattice-like internal structure. Recognizable nuclear form persisted although the preparations represented less than 20% of the original nuclear protein. NPM preparations from mature cells were similar in overall dimensions and internal structure to NPM from immature cells, suggesting reexpansion during isolation of a previously compacted NPM structure in segmented neutrophils. NPM proteins are synthesized primarily in early stages of cell development. The NPM appears to play a major, but passive, structural role in the nuclear changes observed during maturation of granulocytes.
Alterations in nuclear proteins during maturation may be responsible for gene activation and repression. Study of these proteins requires: (1) a system for separating cells into varying degrees of maturity, and (2) a procedure for separating the nuclear proteins. The former was accomplished using Ficoll/Hypaque density gradients to separate rabbit granulocyte precursors. Erythrocytes and their precursors were removed by hypotonic lysis. Histones were extracted from purified nuclei with sulfuric acid, and analyzed on polyacrylamide gels containing urea. Residual non-histone proteins were separated by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. Quantitation of nuclear proteins during development shows no change in the histones, but a significant increase in the non-histone proteins. Therefore, the ratio of non-histone to histones increases progressively during maturation. Histone electrophoresis revealed no significant qualitative or quantitative changes in their five major classes during development. By contrast, electrophoretic analysis of the non-histone proteins revealed distinct changes which include a striking decrease in low molecular weight protein during maturation, and also certain changes in other peptide bands. These changes may reflect alterations in nuclear structure, a changing complement of the nuclear proteins involved in genetic regulation, or a combination of both.
A case is presented for light scatter as a potentially important discrimination parameter for electronic sorting of hemopoietic stem cells. Examples are presented of application of light scatter to sorting of primitive hemopoietic cells from bone marrow, thymus, and fetal yolk sac, using simple empirical approaches and a cell sorter equipped with a standard fixed-angle detector. Cells sorted in this way were ultrastructurally indistinguishable from stem cells observed in whole tissue sections or unfractionated suspensions and remained viable under culture conditions. Cells were further sorted into proliferative and nonproliferative stages whose morphologies were those expected for primitive and mature cells, respectively. Light scatter was a more specific marker for primitive thymocytes than binding of peanut agglutinin. Cells sorted from fetal yolk sac suspensions were ultrastructurally similar to candidate pluripotential stem cells of bone marrow. Therefore, where sorting rather than positive identification is the primary objective of flow analysis and histochemical correlations can be established after sorting, viable stem cells can be sorted from the simple hemopoietic tissues in high and verifiable purity. Sorting of pure stem cells from marrow will require an additional parameter for which an additional angle of light scatter may suffice.
Cholelithasis was diagnosed in 40 of 100 consecutive patients with sickle cell anemia treated in the emergency room. Incidence apparently was not related to sex or degree of reticulocytosis, but did increase with age and perhaps was greater in patients with lower percentage of hemoglobin F and more complications of their hemoglobinopathy. Cholelithiasis was not unusual in children less than 11 years old. No major surgical complications were noted during 29 elective cholecystectomies, but urgent cholecystectomy, performed for real or suspected acute cholecystitis in seven patients, resulted in multiple major postoperative problems. With the low morbidity of elective procedures, as well as simplification of subsequent abdominal pain crisis management, elective cholecystectomy in patients with stable sickle cell conditions is recommended. Surgery during sickle cell crises or acute cholecystitis, with the attendant increased morbidity, should be avoided.
Screening for sickle cell hemoglobin can detect carriers, who can benefit from education and genetic counseling, and can bring about early diagnosis, supportive care, and management for patients with established disease. However, such screening programs should be designed and supervised properly by health professionals to avoid methodological pitfalls and other unfortunate circumstances that have occurred in the past.
We have obtained cells in various stages of granulocytic development by a combination of isopycnic separation and electronic cell sorting. Not only were immature cells (blast cells, promyelocytes and myelocytes) separated from mature cells (bands and polys), but the immature cells were separated into proliferating (S + G2 + M) and resting (Go/G1) compartments of the cell cycle. This permits the study of the morphological and biochemical changes associated with development apart from those changes associated with proliferation.
A commerical cell sorter was used to obtain preparations of cells in various stages of granulocyte development from rabbit marrows stimulated by inflammatory response. Marrow cells were fractionated on density gradients of Ficoll/Hypaque and each fraction sorted using light scatter. Trial and error selection of appropriate gradient fractions and light scatter windows allowed sorting of early (blast cells, promyelocytes), intermediate (myelocytes, metamyelocytes) and late stage (band cells, polys) granulocytes with enhanced purity.
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