Biomedical subjects
D Nash
Publications and source records attributed to D Nash.
Testing for West Nile virus.
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Repeat victims of violence: report of a large concurrent case-control study.
HYPOTHESIS: Repeat victims of violence (violence victim recidivism) is a phenomenon known throughout the nation by those who work in hospital emergency departments. A level I trauma center in Baltimore, Md, conducted this study to investigate the postulated risk factors for repeat victims of violence, ie, unemployment, limited educational attainment, and involvement with illicit drug use or drug dealing. DESIGN: A case-control study identified 200 cases and 224 controls during a 16-month period. Cases were persons admitted with traumatic injury secondary to violent assault who had been previously hospitalized for a similar reason. Controls were a random selection of eligible age- and sex-matched patients admitted for reasons unrelated to violent injury. RESULTS: Prominent risk factors associated with recidivism were African American male, median age 31 years, unemployed, lacking medical insurance, annual income less than $10000, current drug user, past or present drug dealer, and a positive test for psychoactive substances on admission to the hospital. One hundred seventy-two (86%) of the cases felt that disrespect (called "dissing" in the local vernacular) was involved with their injury. CONCLUSIONS: The multiplicity of risk factors and the fact that they are interrelated mandate a comprehensive approach to the difficult problem of violence recidivism. Experiments in hospital-based intervention strategies are needed.
Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.
1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA receptor antagonists, a finding which may be important given the NMDA receptor hypofunction hypothesis for the etiology of schizophrenic symptoms.
The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway.
Steps 6 and 7 of de novo purine synthesis are performed by 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide synthetase (SAICARs), respectively. In vertebrates, a single gene encodes AIRc-SAICARs with domains homologous to Escherichia coli PurE and PurC. We have isolated an AIRc-SAICARs cDNA from Drosophila melanogaster via functional complementation with an E. coli purC purine auxotroph. This cDNA encodes AIRc yet is unable to complement an E. coli purE mutant, suggesting functional differences between Drosophila and E. coli AIRc. In vertebrates, the AIRc-SAICARs gene shares a promoter region with the gene encoding phosphoribosylamidotransferase, which performs the first step in de novo purine synthesis. In Drosophila, the AIRc-SAICARs gene maps to section 11B4-14 of the X chromosome, while the phosphoribosylamidotransferase gene (Prat) maps to chromosome 3; thus, the close linkage of these two genes is not conserved in flies. Three EMS-induced X-linked adenine auxotrophic mutations, ade4(1), ade5(1), and ade5(2), were isolated. Two gamma-radiation-induced (ade5(3) and ade5(4)) and three hybrid dysgenesis-induced (ade5(5), ade5(6), and ade5(8)) alleles were also isolated. Characterization of the auxotrophy and the finding that the hybrid dysgenesis-induced mutations all harbor P transposon sequences within the AIRc-SAICARs gene show that ade5 encodes AIRc-SAICARs.
A new conceptual model of asymmetry in motor performance for bidimensional fast-oscillating movements in selected variants of performance.
Spatial characteristics and lateral differences between two upper extremities were investigated in unilateral graphical tasks involving fast oscillating movements in the vertical plane based on the model of restricted (less than 10 degrees) horizontal abduction adduction in the shoulder joint. The spatial locations of reversal points were used to identify two groups of motor performance: with big angles and gross vertical vectors (stretched accordion group), and small projectile angles with small vertical vectors (compressed accordion group). Both groups appeared in right and left arm performance. The former group had a strong pattern of distribution of big and small projectile angles which reflects a particular variant of execution with a significant difference between angles and intermittent big and small angles (BB). Two other variants of execution relating to specific angular patterns of performance were identified in the compressed accordion group: one (Bs) showed a big difference between big and small angles but without intermittance; the other (ss) had only small differences between magnitudes of angles. The Bs variant of execution was observed only in left-handed performance, whilst ss was typical of both extremities. The performances affiliated to the stretched accordion group with the BB variant of execution mostly operated with reciprocal cooperation between alterations of X and Y vectors for the right arm. Performance related to the same group with the Bs variant of execution used concurrent collaboration involving alteration of these vectors for the left arm. The compressed accordion group which deployed the ss variant of execution mostly displayed concurrent alteration of vectors irrespective of the side of performance. It is suggested that the spatial movement strategies might reflect several different schemes of motor control wherein coupling of oscillators controls vertical and horizontal movements. It is also proposed that specific subunits of the functional system of nervous elements responsible for the expression of spatial derivatives of motor programmes may exist at lower levels of the CNS and might be initiated by the left brain or by the cooperative activity of the left and right hemispheres.
stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster.
Adenine nucleotide translocases (ANT) are required for the exchange of ADP and ATP across the inner mitochondrial membrane. They are essential for life, and most eukaryotes have at least two different Ant genes. Only one gene had been described from Drosophila, and this had not been characterized genetically. We show that mutations in this gene correspond to the previously described loci, sesB and l(1)9Ed. Immediately adjacent to this gene is another encoding a second ANT protein, which has 78% identity to that encoded by sesB/l(1)9Ed. These two genes are transcribed from a common promoter, and their mRNAs are produced by differential splicing. Hutter and Karch suggested that the sesB ANT gene corresponded to Hmr, a gene identified by an allele that rescues otherwise inviable interspecific hybrids between Drosophila melanogaster and its sibling species. This hypothesis is not supported by our study of the ANT genes of D. melanogaster.
Making the case for quality: an interview with David Nash. Interview by Gary Rosenthal.
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Adding managed care to the physician education equation.
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The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.
BACKGROUND: The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk. METHODS: Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey. RESULTS: We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12. CONCLUSIONS: There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.
High-resolution, high-pressure NMR studies of proteins.
Advanced high-resolution NMR spectroscopy, including two-dimensional NMR techniques, combined with high pressure capability, represents a powerful new tool in the study of proteins. This contribution is organized in the following way. First, the specialized instrumentation needed for high-pressure NMR experiments is discussed, with specific emphasis on the design features and performance characteristics of a high-sensitivity, high-resolution, variable-temperature NMR probe operating at 500 MHz and at pressures of up to 500 MPa. An overview of several recent studies using 1D and 2D high-resolution, high-pressure NMR spectroscopy to investigate the pressure-induced reversible unfolding and pressure-assisted cold denaturation of lysozyme, ribonuclease A, and ubiquitin is presented. Specifically, the relationship between the residual secondary structure of pressure-assisted, cold-denatured states and the structure of early folding intermediates is discussed.
Coping and parental history of cardiovascular disorders influence blood pressure in women tested during different phases of their menstrual cycles.
An anger-provocation paradigm was used to assess coping and stress reactivity in 20 women with a positive parental history of cardiovascular disorders and 14 women whose parents had no cardiovascular disease. Frequency of seeking social support in the natural environment was assessed, as were systolic and diastolic blood pressures, while the women performed anger-inducing arithmetic and speech-stressor tasks during the premenstrual and postmenstrual phases. Premenstrually, the women with a positive cardiac history sought support less frequently than those with a negative history. No differences were found between the groups postmenstrually. When the women were identified according to the frequency with which they sought social support, those who more often sought support registered lower baseline blood pressure levels than those women who less often sought support during both cycle phases. Extending the stress-buffering effects of social support to include efforts at seeking support is discussed.
Guillain-Barré syndrome incidence based on hospital discharge data.
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Health surveillance using an occupational medical database.
This pilot study sought associations between liver function tests (LFTs) and membership in homogeneous exposure groups (HEGs) at a target plant as pre-clinical indications of possible future occupational health problems. A large company database yielded linear models for each of six LFTs (total bilirubin, alkaline phosphatase, gammaglutamyl transferase, lactate dehydrogenase, aspartate transaminase, and alanine transaminase) in terms of sex, body mass index, age, race (white/non-white), alcohol and cigarette consumption, and production/non-production (P/NP) job, permitting control for these in analyses of LFTs vs HEGs at the plant. These analyses, with HEG substituted for P/NP in the large group model, resulted in loosely "suspect" associations significant at P < 0.10. Collapsed HEG variable (containing "suspects" separately and all other non-significant HEG levels pooled) yielded "confirmed suspects" at P < 0.05 in the analysis of an independent LFT set taken at the plant approximately one year later.
The role of pharmacoeconomic evaluations in disease management.
Disease management is a systematic approach to a health condition or a healthcare intervention that organises preventative, interventional and care approaches throughout the continuum of care and which measures outcomes in terms of populations, not individuals. Disease management's advantage over the current component system is that it stresses prevention over acute treatment of a chronic disease. Patients with better control of their chronic diseases will likely have a decrease in the use of emergency room and inpatient hospitalisation services, thereby improving clinical outcomes of patients. To achieve these goals, disease management uses pharmacoeconomic evaluations and outcomes measures to provide information that helps build formularies and clinical practice guidelines. Several problems exist in integrating pharmacoeconomic studies in disease management models, such as the need for more integrated information systems, standardisation and who should perform these evaluations. Some possible solutions will be addressed in this article. With greater emphasis being placed on controlling costs, the need for pharmacoeconomic evaluations in the design of disease management models will continue to increase in the future.
Cramming for comparisons.
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Bone mass and the risk of breast cancer.
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An epidemic of lung cancer due to chloromethyl ethers. 30 years of observation.
A cohort of 125 chemical workers was established in 1963 to investigate an epidemic of lung cancer caused by industrial exposure to chloromethyl ethers (CME). Ninety-three of the men were exposed to CME, and approximate estimates of exposure were made. Standardized mortality ratios (SMRs) were calculated for lung cancer, based on Philadelphia city rates. Over 30 years of observation, 25 of 67 deaths were due to lung cancer, with a dose-response relationship. SMRs were elevated only among 59 moderately and heavily exposed workers, peaked at 23.1 in the first decade, and then declined to 7.4 and 7.9 in later decades. The mean latency period from onset of exposure to death was 21 to 25 years and was inversely related to cumulative exposure. Three of 12 heavily exposed cases occurred in nonsmokers. Small cell carcinoma accounted for 80% of the moderately and heavily exposed cases.