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Biomedical subjects

D Hall

Publications and source records attributed to D Hall.

At least 109 records · Page 6Linked to original sources

Elevated concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan Eskimos.

Eskimos living in rural southwestern Alaska depend on fish and marine mammals as major sources of subsistence food. Fatty acid concentrations in 80 Yupik Eskimos living in either a coastal or river village of southwestern Alaska were compared with those of non-Native control subjects. Concentrations of total plasma omega-3 fatty acids, eicosapentaenoic acid (20:5 omega-3), and docosahexaenoic acid (22:6 omega-3) were 4.3, 13, and 6.8 times higher, respectively, in Native participants than in non-Native control subjects. Concentrations of these fatty acids were higher in coastal-village than in river-village participants; concentrations paralleled consumption of marine mammal oil and marine fish. The ratios of eicosapentaenoic to arachidonic acid for adult coastal- and river-village participants were 1.16 and 0.70, respectively, 14 and 9 times those of non-Native adults, respectively. There was no increase in the mean bleeding times of Native participants of either village.

Adolescent↗

Alternating nevirapine and zidovudine treatment of human immunodeficiency virus type 1-infected persons does not prolong nevirapine activity.

The potential use of an alternating treatment strategy with nevirapine and zidovudine in prolonging the antiretroviral effects of nevirapine was evaluated. Ten human immunodeficiency virus type 1 (HIV-1)-infected p24 antigen-positive persons who had not received prior antiretroviral therapy were treated for 9-13 weeks with an alternating regimen of 1 week of nevirapine (200 mg/day) and 3 weeks of zidovudine (600 mg/day). Serum p24 antigen levels declined during the first week of nevirapine treatment (median, 59%); however, subsequent courses of nevirapine were characterized by rising p24 antigen levels, while antigen levels remained stable or declined during zidovudine treatment. Serum beta 2-microglobulin levels and CD4+ cell counts exhibited similar responses. HIV-1 isolates obtained from 2 patients revealed 40- and 1000-fold reductions in nevirapine sensitivity after 8 weeks. These findings demonstrate that alternating treatment with zidovudine and nevirapine does not prolong the effectiveness of nevirapine and does not prevent the development of nevirapine resistance.

Adolescent↗

Zinc improves postischemic recovery of isolated rat hearts through inhibition of oxidative stress.

We studied the cardiac protective qualities of zinc in the postischemic isolated rat heart. Hearts, perfused with Krebs-Henseleit buffer with or without zinc-bis-histidinate, were subjected to 20 min of "no-flow" normothermic global ischemia. Pre- and postischemic treatment with 0, 10, 20, or 30 microM zinc resulted in concentration-dependent enhancement of postischemic function as evidenced by decreased end-diastolic pressure (37 +/- 3, 25 +/- 5, 17 +/- 5, and 8 +/- 2 mmHg, respectively) and increased recovery of developed systolic pressure (41 +/- 6, 59 +/- 17, 76 +/- 18, and 87 +/- 16 mmHg, respectively) and maximum rate of rise in pressure (+dP/dtmax; 823 +/- 141, 1,413 +/- 396, 1,700 +/- 450, and 2,157 +/- 407 mmHg/s, respectively) as well as decreased lactate dehydrogenase efflux from the hearts (peak: 1,002%, 840%, 580%, and 440%, respectively). Only preischemic treatment resulted in an intermediate protective effect, whereas treatment starting at reperfusion worsened postischemic damage. In hearts perfused with zinc throughout the experiment, prolongation of the preischemic treatment interval further enhanced postischemic recovery. With the use of salicylate as a trap for .OH, it was determined that zinc virtually eliminated the early postischemic "burst" of this species normally observed in this preparation. Atomic absorption studies demonstrated that hearts treated with 30 microM zinc contained 27% less copper than control hearts by the end of the reperfusion period. In control hearts, electron microscopy revealed swollen mitochondria with marked loss of inner matrix density, whereas morphology of postischemic zinc-treated hearts was essentially normal. These studies indicate that zinc possesses cardiac cytoprotective qualities and support the concept that this metal can decrease .OH formation by affecting copper reactivity.

Animals↗

Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation.

We have sequenced 45 mutations in mec-7, a beta-tubulin gene required for the production of 15-protofilament microtubules in the nematode Caenorhabditis elegans, and have correlated sequence alterations with mutant phenotypes. The expression patterns of most alleles have also been determined by in situ hybridization and immunocytochemistry. Most (12/16) complete loss-of-function alleles, which are recessive, result from nonsense mutations, insertions, or deletions; three others disrupt a putative GTP-binding domain. Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers. Most (8/9) mild alleles are caused by missense mutations. Two mild alleles appear to increase microtubule stability and lead to the elaboration of ectopic neuronal processes in mec-7-expressing cells. Most (15/23) mutations that cause severe dominant or semidominant phenotypes are clustered into three discrete domains; four others occur in putative GTP-binding regions. Many of these dominant mutations appear to completely disrupt microtubule assembly.

Alleles↗

Screening mammography: the Mount Sinai BreastCheck experience.

Early detection can result in a decrease in the death rate from breast cancer. Screening mammography is the most important modality available to discover early so-called "minimal" cancer. In an effort to make screening mammography more available to the women of north central Connecticut, Mount Sinai Hospital, a community based, university-affiliated hospital initiated a screening program five years ago. During the four-year interval on which we are reporting, we have screened almost 15,000 women using a mobile van. Seventy-seven cancers were discovered in this screened population, with a detection rate of five cancers per 1,000. Our biopsy rate was 1.5% with a positive predictive value of 34%. Sixty-one percent of the tumors discovered were so-called "minimal" cancers and only 12 of the 77 patients had positive lymph nodes.

Adult↗

Hyalin, a sea urchin extraembryonic matrix protein: relationship between calcium binding and hyalin gelation.

The protein hyalin, a major component of the sea urchin extraembryonic hyaline layer, was previously shown to undergo a Ca(2+)-induced self-association into large aggregates (gelation). This reaction represented a major step in assembly of the layer. In the experiments reported here, digestion with trypsin resulted in a rapid dissociation of hyalin into a mixture of peptides which retained the capacity to bind Ca2+. However, unlike intact hyalin, none of these peptides associated into large aggregates (gelation) in the presence of Ca2+, Mg2+, and NaCl. Loss of the ability to undergo gelation was not accompanied by any significant change in the content of acidic plus amide amino acid residues. Decreasing the pH to 5.6 resulted in a loss of 25% of hyalin's Ca(2+)-binding capacity but had no effect on the ability of the protein to undergo gelation. Peptide fragments were only partially effective at inhibiting hyalin gelation. Clearly, not all the Ca(2+)-binding sites were required for hyalin gelation and Ca2+ binding alone was insufficient to drive this reaction. In addition, hyalin appeared to possess two classes of protein-protein interaction domains, one of which was essential for gelation.

Amino Acids↗

Gastroschisis wringer clamp: a safe, simplified method for delayed primary closure.

When primary abdominal wall closure in a newborn with gastroschisis cannot be accomplished safely, placement of a reinforced Silastic silo facilitates delayed primary closure (DPC). In this report we describe our experience with the gastroschisis wringer clamp (GWC). The GWC is an autoclavable, 140-g, aluminum alloy device reminiscent of an old wringer washing machine. It consists of two apposing serrated rollers that pull the Silastic silo through a slotted base plate. This protects the intestine and converts the circular defect into a vertical slit to ease DPC. The GWC is adjusted daily on the awake newborn in the nursery and the magnitude of each adjustment is gauged by the infant's cardiac and pulmonary status. For the past 10 years we have cared for 116 newborns with gastroschisis. The average birth weight was 2,530 g (range, 1,380 to 3,300 g). Eighty-six infants (74.1%) have undergone primary closure. The remaining 30 infants (25.9%) were treated by placement of a Silastic silo and application of the GWC, forming the basis of this report. The DPC operation was performed an average of 6.7 days (range, 3 to 23 days) following the application of the silo. Extubation was usually possible prior to the DPC, with the mean length of mechanical ventilation being 3.8 days. Three patients developed serious complications including two dehiscences of the silo-fascia interface. There were no deaths in this group of 30 patients. The GWC offers many technical advantages and can be easily reversed when the infant's cardiopulmonary status deteriorates. We advocate its adoption as a method of choice in the newborn with gastroschisis who requires DPC.

Abdominal Muscles↗

Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure.

OBJECTIVES: This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure. BACKGROUND: The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin-converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed. METHODS: In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol. RESULTS: Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01). CONCLUSIONS: In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin-independent actions of angiotensin-converting enzyme inhibition.

Adult↗