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Biomedical subjects

R Hayes

Publications and source records attributed to R Hayes.

At least 127 records · Page 7Linked to original sources

Porcine heparin increases postoperative bleeding in cardiopulmonary bypass patients.

One hundred thirteen patients undergoing cardiopulmonary bypass were randomly assigned to receive either bovine or porcine heparin. Heparin was infused at 4.5 mg/kg during bypass and administered at the lesser of 70 units/kg or 5000 units/dose at 12-hour intervals postoperatively. Platelet counts decreased to 45% of preoperative levels during the first 3 days postoperatively (porcine, 44 +/- 13%, n = 50; bovine, 46 +/- 15%), but returned to preoperative levels by the seventh postoperative day. The average blood loss in the porcine heparin group significantly exceeded that of the bovine heparin group (porcine, 1350.7 +/- 727.8 ml; bovine, 1059.6 +/- 381.0 ml; p less than .01). Consequently, the platelet transfusion requirement was greater in the porcine heparin group (porcine, 1.7 +/- 3.9 units; bovine, 0.5 +/- 1.7 units; p less than .05); however, blood and blood component (with the exception of platelets) administration was not significantly different between the two groups. The four patients taking anticoagulants or antiinflammatory agents in the porcine group required a mean of 8.5 units of red blood cells (RBC) plus supplemental platelets. The seven such patients in the bovine group received a mean of 3.0 units of RBC and no platelets. Thus, the use of porcine heparin resulted in a generalized increase in postoperative bleeding with increased management problems in patients undergoing cardiopulmonary bypass.

Animals↗

Measuring malnutrition in famines: are weight-for-height and arm circumference interchangeable?

Data from two surveys in Sudan have been used to examine whether weight-for-height (WFH) and mid-upper arm circumference (MUAC) can be used interchangeably at a population level to define the proportion of children aged one to four years that are malnourished, whether they identify the same individual children as malnourished, and whether the relationship between WFH and MUAC varies with age. A MUAC cut-off of 13.0 cm consistently defined approximately the same proportion of children malnourished as 80% WFH in all seven groups of children examined, even though the proportion of children with less than 80% WFH varied between 8.6% and 30.7%. However, sensitivity/specificity analysis showed that many of the children identified as malnourished by the two indices were not the same individuals. Both the MUAC cut-off defining the same proportion malnourished as 80% WFH, and the sensitivity/specificity values, varied substantially with age. Studies of other populations have revealed both different MUAC cut-offs defining the same proportion of children malnourished as 80% WFH, and different sensitivities and specificities of MUAC relative to WFH. We do not recommend the direct comparison of data from surveys using WFH and those using MUAC.

Age Factors↗

Effect of noncompetitive blockade of N-methyl-D-aspartate receptors on the neurochemical sequelae of experimental brain injury.

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-D-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.

Adenosine Triphosphate↗

Phase IB study of low-dose intraperitoneal recombinant interleukin-2 in patients with refractory advanced ovarian cancer: rationale and preliminary report.

The biological activity of recombinant Interleukin-2 (rIL-2) administered intraperitoneally (ip) has not been determined and may differ significantly from the maximum tolerated dose (MTD). In this trial, the pharmacokinetics, toxicity, and biologic activity of a single ip dose were studied initially followed a week later by a 5-day ip rIL-2 given for 2 weeks every 28 days. Planned dose escalation was from 2 x 10(3) to 2 x 10(7) U given in 2 liters of D5W. Drug was obtained from the NCI and was administered through an ip port. Four patients received 1 U/ml and four patients received 10 U/ml. Preliminary data demonstrate an increase in the peritoneal fluid mononuclear cell count. Mononuclear cell phenotyping tested in the first eight patients showed a modest increase in Leu 2a+, Leu 15- cells, corresponding to CTL. A similar increase in Leu 19+ cells was also demonstrated (NK cells). Soluble IL-2 receptor was elevated in peritoneal fluid. Cytotoxicity against K562 and Daudi cell lines was not observed at the first two dose levels. Toxicity of treatment was minimal and related to abdominal distention. No objective responses were seen but in one patient we documented a reduction in serum CA-125 levels. The observed biologic response and lack of toxicity is promising and justifies further exploration of this immune-modulating approach.

Antigens, Differentiation↗

Effects of the N-methyl-D-aspartate receptor blocker MK-801 on neurologic function after experimental brain injury.

Pharmacologic inhibition of excitatory amino acid (EAA) neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia and improves neurologic outcome after experimental traumatic spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor blocker MK-801 on cardiovascular and neurologic function after experimental fluid-percussion (FP) brain injury in the rat. Animals received either an intravenous bolus of MK-801 (1 mg/kg) or saline (equal volume) 15 min prior to FP brain injury or 15 min following FP brain injury. MK-801 pretreatment significantly improved postinjury cardiovascular variables and attenuated postinjury neurologic dysfunction. Postinjury treatment with MK-801 also significantly improved cardiovascular variables, but had little effect on postinjury neurologic scores. These results suggest that EAA neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive blockade of the NMDA receptor prior to brain injury may reduce EAA-induced damage and limit neurologic dysfunction.

Amino Acids↗

Factors influencing vaccination compliance in peri-urban Gambian children.

The vaccination status of 251 children aged 12-18 months in two peri-urban Gambian communities was determined from their health cards. Two subgroups were identified: children who were fully vaccinated, and those who had received less than half their vaccinations. The social and environmental circumstances of these children were investigated to detect factors which were associated with poor vaccination compliance. Mothers of well vaccinated children were more inclined to bring them for non-curative services. Mothers of poorly vaccinated children had a poorer knowledge of the diseases against which their children should be vaccinated and they also had a more superstitious view of disease causation. Those children who showed poor compliance came from larger families. In the poorly vaccinated group both parents were less well educated and there was a trend towards poorer literacy.

Adult↗

Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants.

A randomised, controlled trial of bovine rotavirus vaccine was undertaken in Gambian infants. Three doses were administered, from the age of ten weeks, concurrently with oral or killed polio vaccine. Prevaccination rotavirus neutralising antibody levels were high. 84/185 infants (45%) showed an increase in neutralising antibody titre after receiving rotavirus vaccine, compared with 20/91 (22%) unvaccinated infants. Clinical rotavirus infection was detected in 24/78 (31%) children in the rotavirus/oral polio group, 34/83 (41%) children in the placebo/oral polio group, and 23/92 (25%) children in the rotavirus/killed polio group, giving an overall vaccine efficacy of 33% (95% CI 4-53%). RIT 4237 did not appear to reduce the severity of clinical infections. Most cases (92%) were caused by rotaviruses with short RNA electropherotypes. Serological responses to rotavirus vaccination appeared unaffected by the concurrent administration of oral polio vaccine. Lower types 1 and 3 polio antibody levels were found in children who received oral polio and rotavirus vaccines but the differences were not statistically significant.

Animals↗

Oxidation of 15-hydroxyeicosatetraenoic acid and other hydroxy fatty acids by lung prostaglandin dehydrogenase.

The oxidation of the 15-hydroxy group of prostaglandins of the A, E, and F series by the NAD+-dependent prostaglandin dehydrogenase (PGDH) has been well documented. In addition to prostaglandins, we have observed that the purified lung PGDH also will oxidize 15-HETE to a novel metabolite that was isolated by reverse-phase HPLC and identified by gas chromatography-mass spectrometry as the 15-keto-5,8,11-cis-13-trans-eicosatetraenoic acid (15-KETE). The Km for 15-HETE was 16 microM, which was 2.5 times lower than the value obtained for PGE1. In addition to 15-HETE, 5,15-diHETE and 8,15-diHETE also were substrates for the lung PGDH with Km values of 138 and 178 microM, respectively. Other hydroxy derivatives of eicosatetraenoic acid that did not have a hydroxy group at carbon atom 15 did not support the PGDH-mediated reduction of NAD+. In addition to the 15-hydroxy derivatives of eicosatetraenoic acid, 12-HHT also was a substrate for the lung enzyme with a Km of 12 microM. These data indicate that omega 6-hydroxy fatty acids, in addition to prostaglandins, are also substrates of the lung NAD+-dependent PGDH and that the enzyme does not require the cyclopentane ring of prostaglandins.

Animals↗

Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa.

Mortality and morbidity from malaria were measured among 3000 children under the age of 7 years in a rural area of The Gambia, West Africa. Using a post-mortem questionnaire technique, malaria was identified as the probable cause of 4% of infant deaths and of 25% of deaths in children aged 1 to 4 years. The malaria mortality rate was 6.3 per 1000 per year in infants and 10.7 per 1000 per year in children aged 1 to 4 years. Morbidity surveys suggested that children under the age of 7 years experienced about one clinical episode of malaria per year. Calculation of attributable fractions showed that malaria may be responsible for about 40% of episodes of fever in children. Although the overall level of parasitaemia showed little seasonal variation, the clinical impact of malaria was highly seasonal; all malaria deaths and a high proportion of febrile episodes were recorded during a limited period at the end of the rainy season.

Age Factors↗

Ethnic differences in the prevalence of splenomegaly and malaria in The Gambia.

Significant variations in the prevalence of splenomegaly were found among members of the three main ethnic groups resident in North Bank Division, The Gambia. Among young children splenomegaly and malaria were less prevalent in Mandinkas than in Wollofs or Fulas, suggesting that some genetic or environmental factors protect Mandinka children from this infection. Among older children and adults splenomegaly was found most frequently in Fulas. Six of 22 adults with very large spleens had a high serum IgM level and probably had the hyperreactive malarial splenomegaly (tropical splenomegaly) syndrome. Four of these six subjects were Fulas. This finding, together with the results of a previous study in Nigeria, suggest that Fulas have a predisposition to this condition.

Adolescent↗

Deaths in infancy and early childhood in a well-vaccinated, rural, West African population.

A survey of deaths in children under the age of 7 years was made over a 1-year period in a rural area of The Gambia with few facilities for curative medicine but with a good record of infant immunizations. One hundred and eighty-four deaths were investigated. Only 12% of deaths occurred in a hospital or health centre but an attempt was made to establish a cause of death by interviewing the family of each dead child and by examining any health records that were available. The infant mortality rate was 142 per 1000 live births and the child mortality rate (death in children aged 1-4 years) 43 per 1000 per year. Acute respiratory infections, malaria and chronic diarrhoea with marasmus were the most frequent causes of death after the 1st month of life. Few children died of diseases that could have been prevented by routine immunizations. An effective immunization programme has probably had some effect on deaths in infancy and early childhood but it will be necessary to find ways of preventing deaths from malaria, acute respiratory infections and chronic diarrhoea/marasmus at the primary health care level if infant and childhood mortality are to be reduced further in rural areas of The Gambia.

Age Factors↗

omega-Hydroxylation of 15-hydroxyeicosatetraenoic acid by lung microsomes from pregnant rabbits.

15-Hydroxyeicosatetraenoic acid (15-HETE) was converted by lung microsomes from pregnant rabbits to a polar metabolite that was identified by mass spectrometry as the 15,20-dihydroxyeicosatetraenoic acid. The formation of the 20- or omega-hydroxylated product was NADPH dependent, with a specific activity of 1.87 +/- 0.53 nmol/min/mg of microsomal protein. Other hydroxylated derivatives of eicosatetraenoic acid that possessed hydroxy groups at the 5- and 12-carbon atoms were not metabolized by the lung microsomes. This hydroxylation of 15-HETE was observed in lung microsomes of pregnant rabbits and only minor amounts were formed by nonpregnant rabbits. The specific activity for 15-HETE omega-hydroxylation was similar to the value obtained for prostaglandin E1 (1.48 +/- 0.33 nmol/min/mg). It is known that rabbit lungs possess a cytochrome P-450 that is induced during pregnancy and catalyzes the 20-hydroxylation of prostaglandins. The addition of the antibody to cytochrome P-450 prostaglandin omega-hydroxylase or prostaglandin E1, a substrate of this enzyme, resulted in potent inhibition of 15-HETE omega-hydroxylation, providing strong evidence that a common cytochrome P-450 catalyzes the omega-hydroxylation of both prostaglandins and 15-HETE.

Animals↗

Amino acid sequence of the sex steroid binding protein of human blood plasma.

The amino acid sequence of the sex steroid binding protein (SBP) from human plasma has been determined. The SBP subunit consists of a 373-residue polypeptide chain containing two disulfide bonds and three oligosaccharide chains. The sequence was solved primarily by analysis of peptides derived by cleavage at either lysyl or methionyl residues. In our preparations, approximately half of the protein molecules have the amino-terminal sequence Arg-Pro-Val-Leu-Pro; the other half lack Arg-Pro and begin with the valine. Preparations of Hammond et al. [Hammond, G. L., Robinson, P. A., Sugino, H., Ward, D. N., & Finne, J. (1986) J. Steroid Biochem. 24, 815] have an additional leucine at the amino terminus, making a total of 373 residues in the chain. Oligosaccharide chains are placed at Thr-7 and at Asn residues 351 and 367. The two disulfide bonds connect Cys-164 to Cys-188 and Cys-333 to Cys-361. The reported heterogeneity of preparations of the molecule may result in part from the amino-terminal microheterogeneity, in part from variations in the oligosaccharide moieties, and possibly in part from rearrangements involving cyclic imide formation in two Asn-Gly sequences. Certain hydrophobic segments are suggested as possible components of the steroid-binding sites. The protein shows no homology either with the cDNA-derived sequences of the estrogen and glucocorticoid receptors found by others to be homologous with each other or with any other protein sequence in the 1986 data base.

Amino Acid Sequence↗