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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 73 records · Page 4Linked to original sources

A plasma inhibitor of platelet aggregation in patients with Lassa fever.

Previous studies have shown that haemorrhage in Lassa fever is associated with abnormal in vitro platelet aggregation and a high mortality. In Sierra Leone we studied platelet aggregation in healthy local subjects, patients with laboratory-confirmed Lassa fever and febrile patients in whom Lassa virus infection was excluded. There were no significant differences in the mean platelet counts of these groups. Patients with fulminant Lassa virus infection showed a gross depression of in-vitro platelet responsiveness to 1 and 5 microM ADP and 4 micrograms/ml collagen compared to other groups (P = 0.0004-0.0008 when compared to healthy controls, P = 0.002-0.0008 when compared to mild Lassa fever patients). When plasma samples from five of these patients were mixed 1:1 with control platelet-rich plasma, a marked inhibition of ADP-induced aggregation was observed. No inhibitory activity was detected in plasma obtained from healthy subjects or febrile control patients. The presence of inhibitor was strongly associated with the occurrence of haemorrhage (P = 0.03), depression of platelet aggregation (P = 0.004) and severity of Lassa fever (P = 0.007).

Adenosine Diphosphate

A comparison of head-down tilt with low-dose infusion of atrial natriuretic peptide in man.

1. Procedures that increase atrial pressure, such as head-down tilt, result in an increase in plasma atrial natriuretic peptide (ANP) and a natriuresis, but a direct cause-and-effect relationship between these two responses has not been established. This study was undertaken to compare the effects of head-down tilt with exogenous ANP on renal function. 2. Eight normal sodium-replete volunteers underwent a 3 h placebo infusion, a 3 h ANP infusion at 1.2 pmol kg-1 min-1 and a 3 h period of head-down tilt. Each procedure was performed on a separate day, in random order. 3. ANP and head-down tilt produced similar increases in sodium excretion (65 +/- 24 and 68 +/- 16%, respectively). ANP did not increase urine flow significantly more than placebo. Head-down tilt increased urine flow significantly more than placebo and ANP. 4. Plasma ANP rose from 8.1 +/- 1.0 to 11.4 +/- 2.5 pg ml-1 during head-down tilt and from 6.5 +/- 1.4 to 32.3 +/- 10.7 pg ml-1 with ANP infusion. 5. ANP infusion had no significant effects on systemic haemodynamics whilst head-down tilt increased cardiac output and reduced heart rate and an index of systemic vascular resistance. 6. ANP infusion, whilst achieving a natriuretic response similar to that of tilt, was associated with a 3-fold higher mean plasma ANP level. Although plasma ANP rose during both ANP infusion and tilt, there was a lack of correlation between natriuretic response and plasma ANP. 7. The results are not compatible with a direct cause-and-effect relationship between plasma ANP and sodium excretion during head-down tilt.

Atrial Natriuretic Factor

Immune complexes and rheumatoid factors in canine arthritides.

Thirty two domestic dogs with naturally occurring polyarthritis were investigated to determine the contribution of autoimmunity in the pathological mechanisms. Comparisons were made with canine infective arthritis (12 dogs), osteoarthritis (32), and osteoarthritis secondary to rupture of the cranial cruciate ligament (19). Rheumatoid factors, immune complexes, and complement fixation (C1q binding) were measured in sera and synovial fluids. Compared with normal dogs (32), dogs with rheumatoid arthritis (RA) had increased serum and synovial fluid immune complexes and rheumatoid factors. Increases were generally also seen in dogs with other arthropathies, however. Rheumatoid factors were higher in sera than in synovial fluids. Rheumatoid factors correlated with immune complex levels and complexed rheumatoid factor only in the group of dogs with RA. Both rheumatoid factors and immune complexes may contribute to the pathogenesis of canine RA but are considered to arise as a result of non-specific inflammatory mechanisms in the non-rheumatoid groups.

Animals

Electrocardiographic abnormalities in patients with Lassa fever.

Electrocardiograms from 32 patients with acute Lassa fever were abnormal in over 70% of cases. The changes noted included non-specific ST-segment and T-wave abnormalities, ST-segment elevation, generalized low-voltage complexes, and changes reflecting electrolyte disturbance. None of the abnormalities correlated with clinical severity of infection, serum transaminase levels, or eventual outcome. ECG changes are common in Lassa fever, but usually unassociated with clinical manifestations of myocarditis.

Adolescent

Prospective evaluation of clinical assessment, exercise testing and signal-averaged electrocardiogram in predicting outcome after acute myocardial infarction.

The relative value of exercise testing, late potentials and simple clinical assessment in predicting ischemic and arrhythmic events during follow-up after acute myocardial infarction (AMI) was investigated prospectively in a population of 176 consecutive patients surviving to 7 days after AMI. During 15 +/- 9 (range 3 to 24) months of follow-up, there were 23 ischemic events (2 fatal reinfarctions, 6 nonfatal reinfarctions and 16 patients who underwent coronary artery bypass grafting, 1 after reinfarction) and 11 arrhythmic events (7 symptomatic ventricular tachycardias and 4 sudden cardiac deaths). Stepwise multiple regression analysis showed that out of 11 variables, including exercise testing, late potentials and clinical data, exercise testing was the only independent variable predicting the occurrence of ischemic events (p less than 0.05 not including coronary artery bypass grafting and p less than 0.002 including it). Arrhythmic events were predicted, in order of importance, by Killip class (p less than 0.05), late potentials (p less than 0.005), previous AMI (p less than 0.009), occurrence of in-hospital complications (p less than 0.005) and non-Q-wave AMI (p less than 0.02). The presence of late potentials provided independent prognostic information from the Killip class and the result of exercise testing in predicting both arrhythmic and ischemic events. Exercise testing, late potentials and clinical assessment provide complementary prognostic information in postinfarction patients.

Adult

Mechanisms of joint damage in an experimental model of hemophilic arthritis.

Autologous whole blood was injected into the knee joints of rabbits 3 times each week for 12 weeks. The resulting destructive arthritis showed macroscopic and microscopic changes similar to those described in hemophilic arthritis in humans. Immunofluorescence studies indicated that a specific immune response is probably not involved in the pathogenesis of hemophilic arthritis. Detailed histopathologic examinations of knee joints in both the early and the late phase of arthritis revealed an obvious synovial and cartilage iron load, in the absence of inflammatory changes. The implications of these findings in the pathogenesis of destructive cartilage changes are discussed.

Animals

Searching for coding sequences in the mammalian genome: the H-2K region of the mouse MHC is replete with genes expressed in embryos.

We have searched for expressed genes in 170 kb of cosmid cloned DNA from the H-2K region of the mouse MHC. This region is known to contain two genes, H-2K and K2. We identified unique/low copy sequences evenly spaced along the cloned DNA, and used these as probes to search for conserved sequences in Southern blots from a variety of mammalian species. The majority of the unique sequences were found to have homologues and most of these were associated with CpG non-methylated islands. Northern blot analysis and isolation of clones from 5.5 and 10.5-day embryo cDNA libraries showed five additional genes encoded in the H-2K region. Four of these are abundant in embryos; the fifth is exclusively expressed in lymphoid cells. Our data indicate a minimum of seven genes in 170 kb, an unexpectedly high gene density. These results differ from two recent studies where similar lengths of cloned DNA were examined for expressed genes, and only one, or a part of one gene was found. The combined data suggest that the spatial organization of genes in the mammalian genome may not be random.

Animals

Intra-H-2 recombination in t haplotypes shows a hot spot and close linkage of 1tw5 to H-2K.

The embryonic lethal mutation in the tw5 haplotype is known to map near the H-2K region of the mouse major histocompatibility complex. Additional data obtained by classical genetic methods demonstrate that the tw5 lethal gene is effectively inseparable from H-2K. No recombinants were found between H-2K and tw5 in a sample representing over 1200 mice. On a statistical basis tw5 must be less than 250 kb from the H-2K gene. In the course of these mapping studies we obtained a set of 11 intra-H-2 recombinants. We have analyzed these and three others derived from another experiment to define their breakpoints as precisely as possible. Southern blot analysis with molecular probes to the D, S, I, and K regions of the H-2 complex defines seven recombinations between the D and S regions, two between S and I, none within the I region, and five events between I and K. The last category was studied in finer detail by developing unique copy probes to the I-K boundary region. Two of the five events occurred within probably less than 6 kb of each other: these two recombinants define the centromeric limit of the location of the tw5 gene within the H-2K region. The other three I-K recombinants occurred in at least two other nearby locations. Altogether at least three, and probably all five I-K recombinants fall within a 45 kb recombinational hot spot recently identified in Mus musculus castaneus.

Animals

Hemodynamic response to treadmill exercise in normal volunteers: an assessment by Doppler ultrasonic measurement of ascending aortic blood velocity and acceleration.

Accurate assessment of ascending aortic blood velocity indices and reproducibility of a Doppler ultrasonic system during exercise were determined; the Doppler technique was then used to assess the effects of age, sex, and beta blockade on exercise hemodynamics. Doppler-determined velocity correlated well with an invasive electromagnetic system. Reproducibility of Doppler variables during three exercise tests was high (coefficient of variation less than 10%) and did not deteriorate appreciably with exercise. Peak velocity (PV) and maximum acceleration (MA) were inversely related to age, the relationship being more significant during exercise, whereas the systolic velocity integral showed no such relationship either at rest or during exercise. Doppler variables showed no difference between sexes, except at high levels of exercise. Beta blockade markedly attenuated the exercise response as shown by significant decreases in both MA and PV during exercise. The Doppler velocity data presented in this study provide a reference against which previously documented changes in exercising ischemic patients can be better related.

Adult

Research skills and the research environment: a needs assessment of allied health faculty.

Allied health faculty are expected to successfully compete with other academic faculty in the research arena, yet many feel unprepared for this role. Most faculty have been trained as clinicians and, thus, bring to academe few skills in research design and methodology. A national study was conducted to assess the research skills and the research milieu of allied health faculty across eleven disciplines. Data are presented from 2,187 survey responses. Unmet needs included skills in obtaining funding, statistical analysis of the data, and publishing research results. Major barriers to research included the undervaluing of research relative to education and service, the lack of financial and administrative support, the absence of professional resources, and the generally low priority given research. Faculty with earned doctorates perceived their research environments more favorably and had fewer gaps in research skills than did faculty with a bachelor's or master's degree.

Allied Health Personnel

Research productivity profile of allied health faculty.

Many allied health faculty are expected to obtain graduate degrees and engage in scholarly activity to advance knowledge in their professions and fulfill the research mission of their academic institution. A national study of ten allied health disciplines was conducted to assess the level of allied health research productivity and to determine the relationship between the amount of research and faculty characteristics. Research productivity included the number of major paper presentations and research publications, number of times served as project principle investigator, and the time devoted to research per week. Faculty characteristics were the type of employing institution, and the academic degree, rank, and tenure status of the faculty member. Data from 2,187 survey respondents indicated that faculty who are employed by four-year research universities, possess earned doctorates, hold the rank of professor, and are tenured had significantly higher levels of research productivity.

Allied Health Personnel