Potentially lethal failure of the vapor exclusion system.
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Adult↗
Biomedical subjects
A C Brown
Publications and source records attributed to A C Brown.
Microenvironmental toxicity of azidothymidine: partial sparing with hemin.
Azidothymidine (AZT) is a useful drug in management of AIDS. Nevertheless, its hematologic toxicity such as anemia and neutropenia present further complications to an already compromised hematopoietic state in patients. We studied the effects of AZT on human and murine bone marrow (BM) colony growth as determined by assays of CFU-E, BFU-E, CFU-GM, and fibroblastoid stromal (CFU-Fb) colonies. Cultures were grown in methylcellulose with growth factors and scored after three- to 14-day incubation. In general, murine marrow cultures were more sensitive to AZT as compared with human marrow. Furthermore, interindividual variation in toxicity to AZT was observed between marrow samples; 1 mumol/L AZT inhibited murine CFU-E, BFU-E, and CFU-GM by 98% to 100%, whereas human marrow was inhibited by 52%, 87%, and 65%, respectively. Lower concentrations of AZT (0.1 mumol/L) inhibited murine erythroid colony growth by 85% to 90%, whereas human growth was inhibited by only 39% to 52%. Myeloid colony inhibition was similar for human and murine systems. CFU-Fb growth was markedly suppressed (75%) by 1 mumol/L AZT. Hemin, at a concentration of 10 mumol/L, overcame some of the inhibitory effects of 1 to 0.1 mumol/L AZT without hindering antiviral activity. Inhibition of human CFU-E growth was completely overcome with hemin, whereas CFU-GM growth was recovered to 66% to 74% of control. A similar but less pronounced effect was observed for BFU-E. Furthermore, hemin does not decrease AZT's effects of HIV antigen content in vitro. We conclude that anemia and neutropenia, occurring as a result of AZT, may not be as pronounced in the presence of hemin. Furthermore, CFU-Fb was significantly reduced in the presence of low concentrations of AZT. This may indicate a major target site for BM toxicity since the stromal microenvironment may be responsible for maintaining short- and long-term hematopoiesis.
Animals↗
Heme metabolism and in vitro erythropoiesis in anemia associated with hypochromic microcytosis.
Heme metabolism and in vitro erythropoietic growth (CFU-E, BFU-E) were examined in bone marrow cells taken from two siblings with apparent familial hypochromic microcytic anemia. Bone marrow cells from both patients grew adequate numbers of CFU-E and BFU-E colonies in culture in the presence of erythropoietin. In addition, small numbers of endogenous CFU-E were seen in 7-day cultures. Assays on bone marrow cells taken from both patients revealed that baseline delta-aminolevulinic synthase activity was considerably reduced, but increased six to seven fold (to normal levels) when patients' cells were exposed to pyridoxal phosphate (PLP). In both cases, ferrochelatase and delta-aminolevulinic acid dehydratase activities were normal. Bone marrow heme oxygenase showed no significant differences in activities between normals and patients values in the absence or presence of PLP. In contrast, heme synthesis by patients' bone marrow was less than that of normals. This study demonstrates that bone marrow cells from patients with this rare disorder have some disturbances in heme metabolism, whereas erythropoiesis appeared to be normal when cultured with adequate nutrients in vitro.
5-Aminolevulinate Synthetase↗
The significance of free radicals and free radical scavengers in L1210 leukemia.
L1210 leukemia is a murine leukemia which is associated with anemia and marked neutrophilia. In order to determine the significance of free radicals (FR) in this disorder, we determined the presence and localization of free radical scavengers (FRS) and scavenger-like systems in L1210 leukemia cells obtained in vivo and from in vitro cultures. FR are metabolized or detoxified by certain FRS such as glutathione (GSH and GSSG), superoxide dismutase (SOD) and enzymes such as epoxide hydrolase (EH). In all cases specific fractions of L1210 cells, bone marrow and liver were examined for FR/FRS levels. Reduced (GSH) and oxidized (GSSG) glutathione were measured fluorometerically using o-opthalaldehyde (OPT). SOD was determined colorimetrically utilizing pyrogallol by substrate autolysis inhibition, and EH was determined by utilizing [3H] styrene oxide as a substrate. Ratios of GSH/GSSG in fractions prepared from in vivo and in vitro L1210 cells showed a predominance of GSH-reductase with the highest activity in mitochondria (ratio = 15 vs. 10). Normal liver showed a similar pattern whereas, leukemic liver showed altered GSH/GSSG ratios in mitochrondria and microsomes. Leukemic bone marrow showed a predominance of GSH-reductase in all fractions. EH activity was highest in microsomal fractions obtained from L1210 cells grown in vitro and found to become increased in both the mitrochondrial (100%) and microsomal (200%) fractions when cells were exposed to retinoic acid (RA) in culture. SOD activity in the cytosolic (21.2 U SOD/mg) and mitochondrial (12 U SOD/mg) fractions whereas, leukemic liver showed a significant decrease in activity in all fractions compared to normals. SOD was determined in fractions taken from L1210 cells in vivo and in vitro. Results demonstrated detectable but reduced SOD activity in the L1210 cell fractions as contrasted with liver activity. Results from these studies indicate that certain FRS systems are functional in L1210 leukemic animals. Furthermore, variations in the ratios or levels may be of significance in the leukemic and hematological states.
Animals↗
Effect of bovine somatotropin on metabolism of lactating dairy cows: energy and nitrogen utilization as determined by respiration calorimetry.
Effects of exogenous bovine somatotropin (bST) on energy and nitrogen utilization by high producing dairy cows were examined. Nine cows received bST (51.5 IU/d) or exipient (control) in a single reversal design involving 14-d treatment periods. Energy and nitrogen balances were measured in open-circuit respiration chambers. Yield of 4% solids-corrected milk was increased by 22% with bST treatment. Dry matter intake and the apparent digestibilities of dry matter, energy and nitrogen were not altered by treatment. The only significant component of nitrogen utilization that was altered by bST treatment was an increase in milk nitrogen secretion. Cows were in negative tissue nitrogen balance during the control period (-21 g/d) and tended to become more negative during the bST treatment period (-34 g/d). Heat energy loss and milk energy secretion were increased with bST treatment. Tissue energy balance was -1.1 Mcal/d during the control treatment period and the use of energy reserves with bST treatment decreased tissue energy balance to -9.8 Mcal/d. Changes in heat production with bST treatment were equal to those predicted from the changes in milk and body tissue. Overall, the results demonstrated that bST treatment increased yield of milk and milk components even when cows were in negative nitrogen and energy balance. Effects of bST were predominantly associated with nutrient partitioning, and observed heat loss (associated with maintenance and partial efficiencies of milk synthesis and tissue utilization) did not differ from predicted heat loss.
Animal Feed↗
Effect of bovine somatotropin on metabolism of lactating dairy cows: influence on rates of irreversible loss and oxidation of glucose and nonesterified fatty acids.
Effects of bovine somatotropin (bST) on irreversible loss rate (ILR) and oxidation rate of glucose and nonesterified fatty acids (NEFA) were examined. Nine lactating cows received bST or excipient in a single reversal design using 14-d periods. Kinetic variables were estimated by compartmental analysis of blood metabolite and expired CO2 specific activity values obtained during infusion of [U-14C]glucose or [1-14C]palmitate. With bST treatment, milk energy yield increased by 31% but feed intake was unchanged. Blood glucose concentrations were not affected by treatment or correlated with any glucose kinetic variables. In the control period, glucose ILR was 12.1 mol/d with 66.5% utilized for milk lactose synthesis and 17.4% oxidized to CO2. Treatment with bST increased glucose ILR (+1.5 mol/d) and reduced glucose oxidation (-0.4 mol/d); this accommodated the additional glucose (+1.3 mol/d) required for the increase in lactose secretion. Increases in milk energy yield with bST treatment caused cows to be in a substantial negative net energy balance (-9.8 Mcal/d). No acute lipolytic response occurred with bST treatment, but plasma NEFA were chronically elevated (+104 mumol/L) and NEFA ILR increased (+2.3 mol/d). Increased NEFA turnover was primarily used for increased oxidation to CO2 (+0.5 mol/d) and 41% increase in milk fat (equal to approximately 1.3 mol fatty acids/d). For NEFA, plasma concentrations were correlated with ILR (r = +0.80), oxidation to CO2 (r = +0.74) and net energy balance (r = -0.78). Overall, bST resulted in an exquisite coordination of metabolism to meet nutrient needs for increased synthesis of milk components.
Animals↗
Serologic studies in the diagnosis and management of meningitis due to Sporothrix schenckii.
Eight patients have previously been reported to have central nervous system infections caused by Sporothrix schenckii. In those patients the fungus proved quite difficult to culture, delaying correct diagnosis and treatment. We describe seven additional patients with sporotrichosis meningitis, all of whom had antibody to this fungus in cerebrospinal fluid and serum. The antibody in the cerebrospinal fluid was most likely produced locally, as evidenced by its oligoclonality and the relatively high ratio of immunoglobulin to albumin in the cerebrospinal fluid as compared with the serum. Only one of these seven patients, who had active sporotrichosis of the knee joint, had obvious extrameningeal infection. None of 130 patients with meningitis known to be caused by other agents and none of 170 patients with other neurologic disorders had antibody to S. schenckii in their cerebrospinal fluid. We suggest that cerebrospinal fluid should be tested for S. schenckii antibody (in addition to other fungal agents) in any patient with chronic meningitis for which no cause is discovered by the usual diagnostic tests.
Adult↗
Marine pollution and health in South Africa.
Although the RSA does not have a serious marine pollution problem, rapid population growth and increasing industrialization make it imperative to assess the pollution status of coastal waters and to plan for future developments. All pollution on earth ends up in the sea, which consequently contains a mixture of substances, the effects of which on the biota and on human health are poorly understood. Many of these substances are accumulated by marine organisms and become ever more concentrated along the food chain; where man is at the top of the chain, he thus runs the greatest risk of all. Too much raw sewage is allowed to pollute the sea, the provision of sewage treatment plants being largely inadequate for the growing population. Notwithstanding the excellent work done by a number of South African organisations and individuals, and the sound basis of the country's anti-marine pollution legislation, a plea is made for greater co-operation between those whose expertise and/or official position would enable them to contribute to combating the problem.
Seawater↗
Relationship between maldistribution of ventilation and airways obstruction in children with asthma.
This study was designed to explore the relationship between ventilation non-uniformity, as assessed by moment analysis of nitrogen washout, and airways obstruction, as assessed by spirometry, in children with asthma. Moment ratios derived from the multibreath washout curves in asthmatics were significantly higher than those obtained from healthy controls (P less than 0.001). Among patients with asthma, moment ratios showed a high degree of negative correlations with spirometric variables expressed as percent of predicted, i.e., increasing airways obstruction was associated with increasing ventilation non-uniformity. When the subjects were tested on multiple occasions during one test day the results demonstrated a strong quantitative relationship within subjects between spontaneous changes in moment ratios and spirometric variables (P less than 0.001), with the slope of the regressions showing a trend to vary from one patient to another. Chi squared analysis showed that significant changes in FEV1 were paralleled by corresponding significant changes in moment ratios with a sensitivity of approximately 81% and a specificity of 82%. Additionally, changes in FEV1 induced by an inhaled bronchodilator were associated with concomitant changes in moment ratios. We conclude that: (1) the majority of children with asthma have some degree of ventilation non-uniformity which is correlated with their degree of airways obstruction, and (2) spontaneous changes in airways obstruction in such subjects are paralleled by changes in ventilation non-uniformity.
Adolescent↗
Evaluation of an emergency cricothyrotomy instrument.
An emergency cricothyrotomy device was placed in 11 anesthetized dogs in order to assess airway damage and problems in placement, ventilation, and design. Posterior airway perforation without esophageal damage occurred in three animals. Submucosal hematomas or cricoid cartilage injury occurred in seven animals. As placement by an untrained operator was surprisingly difficult, prior operator training with this device is recommended. When properly installed, an excellent emergency airway was achieved. Some minor design shortcomings are noted and suggestions for improvement are made.
Airway Obstruction↗
Testing sealing properties of restorative materials against moist dentin.
The objectives of this investigation were (1) to develop a sensitive laboratory system that simulates the physiological and clinical conditions of a prepared human tooth in order to facilitate the determination of the bonding and sealing efficacies of restorative dental materials and (2) to conduct experiments with two dentin bonding agents, two posterior composite resin restorative materials (hybrid and microfilled), and a glass-ionomer type II filling material. The system functioned well and provided data to indicate that, after margination, the two posterior composite resin restorative materials performed equally and both performed better than the glass-ionomer filling material; none of the materials provided a perfect seal immediately after insertion, although some restorations demonstrated perfect seals from 16 hours to 28 days after placement; the seal of the glass-ionomer material improved after 28 days of storage in buffer solution; each successive step in the respective composite resin procedures improved the seal except in one case for the microfilled resin.
Composite Resins↗
A controlled study of hypotensive anesthesia in head and neck surgery.
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Anesthesia, Conduction↗
Pyramidal tract of the cat: axon size and morphology.
The purpose of this work was to determine the number and morphology of pyramidal tract (PT) axons in the cat, using electron microscopy, modern methods of fixation, and computer-assisted morphometric analysis. Sections taken at the level of the medullary pyramids in three animals were fixed and magnified up to 10,000 X to produce photomicrographs. Morphological data were entered into computer files for analysis by tracing axon perimeters on micrographs mounted on a digitizer tablet. The number of axons per PT averaged 415,000, of which 88% were myelinated and 12% were unmyelinated. 90% of the myelinated axons fell in the diameter range 0.5-4.5 microns. Axons larger than 9 microns diameter accounted for 1% of the total; the largest were 20-23 microns. Myelinated axon mean diameter was 1.98 microns; because of the skewed distribution, with many small axons and a few very large axons, median diameter was 1.60 micron. Size distribution was relatively uniform throughout the PT cross section, with all sizes represented in all regions. However, the more medial regions had a higher proportion of small fibers than the more lateral regions: mean medial diameter was 1.85 micron while mean lateral diameter was 2.09 microns. Myelin sheath thickness averaged 7.9% of fiber diameter for axons up to 11 microns, but was constant at 0.9 micron for larger fibers. Myelinated fibers were distorted from the circular shape in cross section, with a mean circularity index (or form factor) of 0.85, which implies that the fibers could swell about 15% without rupture of the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Spatial summation of pre-pain and pain in human teeth.
The purpose of this work was to investigate the relation between the sensations of pain and 'pre-pain' evoked by stimulation of teeth in human subjects. Electrical pulses of progressively increasing amplitude, generated by a computer-controlled stimulator, were applied to 1 or 2 teeth, and the subjects responded by indicating the nature of the resulting sensation. Pre-pain and pain could be readily and rapidly distinguished by all 11 subjects (response latency about 0.4 sec). Both sensations had stable thresholds with relatively small variance (S.D. 10-15% of threshold value) for a given subject. Subjects characterized the stimuli as indifferent or unpleasant, localized, and brief. By using special stimulation strategies (termed 'optimal trajectories') for exciting 2 teeth simultaneously, spatial summation for pre-pain was demonstrated in most subjects and for pain in almost all subjects. Spatial summation of pre-pain resulted in pain rather than in more intense pre-pain. These results are consistent with both the dual modality (separate afferent fibers for pre-pain and pain) and the single modality hypotheses (single type of afferent fibers) of tooth pulp sensibility, but favor single modality innervation.
Adult↗
Expression of sperm antigens during spermatogenesis and maturation detected with monoclonal antibodies.
The expression of hamster sperm antigens was investigated during spermatogenesis and sperm maturation with the use of monoclonal antibodies generated in culture from mice immunized with hamster cauda epididymal spermatozoa or sperm heads. Antigens were localized by immunofluorescence and immunoperoxidase techniques which were first visualized on isolated spermatids over the developing acrosome. In one case, antibody inhibited fertilization in vitro although localization on testicular or epididymal spermatozoa was minimal compared with the early spermatid. Antibodies also recognized surface antigens first expressed in the epididymis whose localization on the spermatozoon altered during epididymal transit or incubation in capacitating medium. The results were discussed in relation to the expression and function of surface determinants on the haploid germ cell.
Animals↗
Mitochondrial granules: are they reliable markers for heavy metal cations?
Mitochondrial granules have been used as markers for heavy metal cations, but since such granules can also be found in tissues in the absence of such cations, an attempt was made to define conditions under which these different granules might be visualised. The tissue used was the smooth muscle of the central ear artery of the rabbit. In all studies, the presence or absence of mitochondrial granules was determined by several observers, using coded specimens so that the previous treatment of the specimens was not at the time known to the observers. Paired tissues were exposed for 30 or 90 minutes at 20, 30 or 39 degrees C to an incubate containing either 10 mmol/l barium or a control barium-free solution. After fixation in osmium tetroxide, there was no difference between the two groups; in both cases granules appeared more frequently the longer the time and the higher the temperature of incubation. In a further series where glutaraldehyde was the fixative, granules were identified in 23 out of 41 tissues incubated with barium, but in only 1 out of 41 control tissues (P less than 0.001). Electron probe microanalysis showed that granules in osmium-fixed tissues contained osmium as the main element, whereas granules in glutaraldehyde-fixed tissues which had been incubated with barium showed barium as the predominant cation. Thus mitochondrial granules can be reliable markers for heavy metal cations, but only under carefully controlled conditions.
Animals↗
Treatment of alopecia areata.
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Adolescent↗
Prescribing psychotropic drugs in general practice: three year study.
A three year longitudinal study of psychotropic drug prescribing in one inner city general practice showed that there was a greater use of such drugs among women and elderly men and women. Repeat prescriptions without consultation accounted for 44% of prescriptions written. We think that any attempt to reduce the volume of prescriptions for psychotropic drugs should take into account the prescribing habits and attitudes of doctors as well as the problems and needs of patients.
Adolescent↗