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Biomedical subjects

David A Smith

Publications and source records attributed to David A Smith.

14 recordsLinked to original sources
PubMed2006

Kinetics of force recovery following length changes in active skinned single fibres from rabbit psoas muscle: analysis and modelling of the late recovery phase.

Redevelopment of isometric force following shortening of skeletal muscle is thought to result from a redistribution of cross-bridge states. We varied the initial force and cross-bridge distribution by applying various length-change protocols to active skinned single fibres from rabbit psoas muscle, and observed the effect on the slowest phase of recovery ('late recovery') that follows transient changes. In response to step releases that reduced force to near zero ( approximately 8 nm (half sarcomere)(-1)) or prolonged shortening at high velocity, late recovery was well described by two exponentials of approximately equal amplitude and rate constants of approximately 2 s(-1) and approximately 9 s(-1) at 5 degrees C. When a large restretch was applied at the end of rapid shortening, recovery was accelerated by (1) the introduction of a slow falling component that truncated the rise in force, and (2) a relative increase in the contribution of the fast exponential component. The rate of the slow fall was similar to that observed after a small isometric step stretch, with a rate of 0.4-0.8 s(-1), and its effects could be reversed by reducing force to near zero immediately after the stretch. Force at the start of late recovery was varied in a series of shortening steps or ramps in order to probe the effect of cross-bridge strain on force redevelopment. The rate constants of the two components fell by 40-50% as initial force was raised to 75-80% of steady isometric force. As initial force increased, the relative contribution of the fast component decreased, and this was associated with a length constant of about 2 nm. The results are consistent with a two-state strain-dependent cross-bridge model. In the model there is a continuous distribution of recovery rate constants, but two-exponential fits show that the fast component results from cross-bridges initially at moderate positive strain and the slow component from cross-bridges at high positive strain.

Animals↗
PubMed2006

Is there a conflicted surrogate syndrome affecting quality of care in nursing homes?

Is there a point at which family complaints about care cease to be constructive and become excessive and counterproductive? Do excessive complaint behaviors represent a "conflicted surrogate syndrome" that is indicative of psychopathology in the family member or family system? Can this psychopathology result in avoidance behavior by the nursing staff sufficient to result in poor care? While many family/resident complaints are valid and should be viewed as constructive there are occasions when excessive complaints by the family of a nursing facility resident are a result of psychiatric illness or psychological problems in the family member(s) or are evidence of an abnormality in the family system. This series of brief case reports is offered to create discussion of what might be termed a "conflicted surrogate syndrome" that may result in avoidance behavior by staff and consequent poor care.

Aged↗
PubMed2004

NSAIDs increase survival in the Sandhoff disease mouse: synergy with N-butyldeoxynojirimycin.

The GM2 gangliosidoses are caused by incomplete catabolism of GM2 ganglioside in the lysosome, leading to progressive storage and a neurodegenerative clinical course. An inflammatory response (microglial activation, macrophage infiltration, oxidative damage) has been found to be a consequence of GM2 storage in the brain, although it remains unclear whether this contributes to pathogenesis or disease progression. In this study, we treated Sandhoff disease mice with nonsteroidal antiinflammatory drugs (indomethacin, aspirin, and ibuprofen) and antioxidants (L-ascorbic acid and alpha-tocopherol acetate). The treated mice lived significantly longer than untreated littermates (12-23%, p <0.0001) and showed a slower rate of disease progression (p <0.001). When aspirin treatment was combined with substrate reduction therapy, synergy resulted (11%, p <0.05) with a maximum improvement of 73% in survival (p <0.00001). This study demonstrates that inflammation contributes to disease progression and identifies antiinflammatory and antioxidant therapies as a potential adjunctive approach to slow the clinical course of this and related disorders.

1-Deoxynojirimycin↗
PubMed2004

Mechanokinetics of rapid tension recovery in muscle: the Myosin working stroke is followed by a slower release of phosphate.

Crystallographic and biochemical evidence suggests that the myosin working stroke that generates force in muscle is accompanied by the release of inorganic phosphate (Pi), but the order and relative speed of these transitions is not firmly established. To address this problem, the theory of A. F. Huxley and R. M. Simmons for the length-step response is averaged over elastic strains imposed by filament structure and extended to include a Pi-release transition. Models of this kind are applied to existing tension-recovery data from length steps at different phosphate concentrations, and from phosphate jumps upon release of caged phosphate. This body of data is simulated by the model in which the force-generating event is followed by Pi release. A version in which the Pi-release transition is slow provides a better fit than a version with rapid Pi release and a slow transition preceding force generation. If Pi is released before force generation, the predicted rate of slow recovery increases with the size of the step, which is not observed. Some implications for theories of muscle contraction are discussed.

Algorithms↗
PubMed2003

Placental infection with Chlamydia pneumoniae and intrauterine growth restriction.

BACKGROUND: The concept that low birth weight infants are more predisposed to coronary artery disease (CAD) in adulthood has been studied extensively. Although many infectious agents have been associated with intrauterine growth restriction (IUGR), Chlamydia pneumoniae an organism implicated in CAD has not been investigated. It was our aim to assess whether C. pneumoniae DNA is present in placental tissue and whether its detection is associated with IUGR. METHODS: Fifty-nine pregnant women were studied: 32 women had an uncomplicated pregnancy with no antenatal or post-natal evidence of IUGR. Twenty-seven women had pregnancies with ultrasonographically demonstrated IUGR, defined as foetal abdominal circumference measuring less than 2 S.D.s from the mean for gestational age. At the time of delivery, maternal blood and placental tissue samples were obtained. Placental samples were taken from four sites centrally and peripherally on the maternal and foetal side of the placentas and tested by nested polymerase chain reaction for C. pneumoniae DNA. IgG antibodies to C. pneumoniae were measured using microimmunfluorescence. RESULTS: C. pneumoniae DNA was detected in 44% of the placental tissue but there was no difference in the prevalence of bacterial DNA between the control and the low birth weight group (P=0.58). Additionally C. pneumoniae seropositivity did not differ between the index and control groups (78 vs. 70%, P=0.44). CONCLUSIONS: C. pneumoniae is present in placental tissue. Its presence however does not correlate with IUGR. Similarly, maternal C. pneumoniae seropositivity is not related to low birth weight. Thus C. pneumoniae infection is unlikely to play a role in the pathogenesis of IUGR.

Adult↗
PubMed2003

Neopterin levels in patients with coronary artery disease are independent of Chlamydia pneumoniae seropositivity.

BACKGROUND: Chronic infection with Chlamydia pneumoniae (Cpn) has been associated with atherosclerotic cardiovascular disease in sero-epidemiological, pathological and animal-model studies. Inflammation and immune activation has been proposed as the pathophysiological link between chronic infection and atherosclerosis. The aim of this study was to assess whether Cpn seropositivity is associated with serum neopterin concentrations, a marker of macrophage activation, in patients with stable and unstable angina pectoris. METHODS: We examined 100 patients with angiographically documented coronary artery disease: 60 patients had chronic stable angina and 40 had Braunwald class III unstable angina. Neopterin concentrations were measured with a commercially available immunoassay. Cpn titres were measured with a microimmunofluorescence (MIF) assay. RESULTS: Neopterin concentrations were significantly higher in patients with unstable angina compared to those with chronic stable angina (6.30 [4.85-8.80] nmol/L vs 4.95 [3.35-7.05] nmol/L, P =.004), even after adjustment for variables that were significantly different between the 2 groups on univariate analysis. In contrast, the prevalence of positive Cpn serology did not differ significantly between the 2 angina patient groups (65% v 58%, P =.50). Neopterin levels were similar between Cpn-negative and Cpn-positive patients (P =.40) in both stable and unstable angina groups. CONCLUSIONS: Patients with unstable angina had higher neopterin concentrations than patients with chronic stable angina, probably reflecting the higher degree of immune activation in acute coronary syndromes. Neopterin levels, however, were independent of Cpn serostatus when combining both stable and unstable angina patients. Thus, immune activation in patients with acute coronary syndromes appears to be unrelated to Cpn seropositivity.

Analysis of Variance↗
PubMed2002

Indexing systematic rater agreement with a latent-class model.

A latent-class model of rater agreement is presented for which 1 of the model parameters can be interpreted as the proportion of systematic agreement. The latent classes of the model emerge from the factorial combination of the "true" category in which a target belongs and the ease with which raters are able to classify targets into the true category. Several constrained cases of the model are described, and the relations to other well-known agreement models and kappa-type summary coefficients are explained. The differential quality of the rating categories can be assessed on the basis of the model fit. The model is illustrated using data from diagnoses of psychiatric disorders and classifications of individuals in a persuasive communication study.

Humans↗