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Biomedical subjects

D E Roach

Publications and source records attributed to D E Roach.

10 recordsLinked to original sources

Decrease in density of INa is in the common final pathway to heart block in murine hearts overexpressing calcineurin.

Overexpression of calcineurin in transgenic mouse heart results in massive cardiac hypertrophy followed by sudden death. Sudden deaths are caused by abrupt transitions from sinus rhythm to heart block (asystole) in calcineurin-overexpressing (CN) mice. Preliminary studies showed decreased maximum change in potential over time (dV/dt(max)) of phase 0 of the action potential. Accordingly, the hypothesis was tested that decreased activity of the sodium channel contributes to heart block. Profound decreases in activity of sodium currents (I(Na)) paralleled the changes in action potential characteristics. Progressive age-dependent decreases were observed such that at 42-50 days of life little sodium channel function existed. However, this was not paralleled by decreased protein expression as assessed by immunocytochemistry or by Western blot. Since calcineurin can interact with the ryanodine receptor, we assessed whether chronic in vitro treatment with BAPTA-AM, thapsigargin, and ryanodine could rescue the decrease of I(Na). All of these treatments rescued I(Na) to levels indistinguishable from wild type. The nonspecific PKC inhibitor bisindolylmaleimide I also rescued the decrease of I(Na). To assess whether decreased sodium channel activity contributes to sudden death in vivo, the response to encainide (20 mg/kg) was assessed: 6 of 10 young CN mice died because of asystole, whereas 0 of 10 wild-type mice died (P < 0.01). Moreover, encainide produced exaggerated prolongation of the QRS width in sinus beats before the heart block. Catecholamine tone appears necessary to support life in older CN mice because propranolol (1 mg/kg) triggered asystolic death in five of six CN mice. We conclude that decrease in sodium channel activity is in the common final pathway to asystole in CN mice.

Action Potentials↗

Information scaling properties of heart rate variability.

Many chaos detection methods have proven inherently ambiguous in that they yield similar results for chaotic signals and correlated noise. The purpose of this work was to determine whether human resting heart period sequences have global properties characteristic of chaotic systems. We investigated the inherent global organization of heart period sequences by quantifying how the information content of the embedded sequences varied as a function of scale. We compared the information scaling characteristics of 60-min heart period sequences obtained from 10 healthy resting volunteers with those obtained from numerous periodic and chaotic control sequences. The information scaling properties of the heart period sequences were significantly different from those obtained for the controls, particularly at the coarsest scales (P = 0.0003 vs. low-dimensional periodic controls; P = 0.0005 vs. low-dimensional chaotic controls; P = 0.0003 vs. low-dimensional periodic and chaotic controls). We also showed that nondeterministic components, such as large tachycardic (or bradycardic) events or aperiodic fluctuations, can lead to scaling characteristics similar to those observed for the resting heart period sequences. This, in addition to previous evidence from spectral, nonlinear predictability and lexical studies, favors an events-based approach to understanding heart rate variability.

Adult↗

A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.

Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization.

Adult↗

Six-year clinical and immunologic follow-up of workers exposed to trimellitic anhydride.

We report a 6-year study from 1979 through 1985 of workers exposed to trimellitic anhydride (TMA) in three groups of volunteers. Twenty-nine percent of workers (5/17) originally studied had immunologically induced respiratory disease. Subsequent to this evaluation, increased environmental control of TMA exposure was instituted. Since that time, there have been decreasing clinical symptoms and decreasing levels of antibody against TMA conjugated to human serum albumin. These long-term studies originally used radioimmunoassays, but enzyme-linked immunoassays against TMA-conjugated proteins are now demonstrated to be equally appropriate and are more cost-effective. With appropriate clinical and immunologic studies, immunologic airway reactions to TMA may be identified and then prevented by environmental control to decrease inhalation exposure to TMA. This is likely applicable to certain other chemical antigens that immunize by inhalation.

Air Pollutants, Occupational↗

The relationship of airborne trimellitic anhydride concentrations to trimellitic anhydride--induced symptoms and immune responses.

Eighteen workers exposed to trimellitic anhydride (TMA) powder were evaluated in 1979. Twelve of these workers were available for longitudinal study until 1982. Annual clinical evaluations and serum radioimmunoassays for total antibody binding and specific IgE binding to 125I-TM-HSA were performed. In 1979, five workers had antibody against TM-HSA. Of these, three workers were diagnosed with the late respiratory systemic syndrome (LRSS) and one worker with TMA-induced allergic rhinitis. The LRSS workers had significantly elevated total antibody binding of 125I-TM-HSA and the worker with rhinitis had significantly elevated specific IgE binding of 125I-TM-HSA per milliliter of serum. Although TMA handling was intermittent throughout the year, average airborne dust concentrations from 1974 to 1978 at job stations of the two heaviest TMA-exposed occupations, operator and assistant operator, were 2.1 and 0.82 mg/m3, respectively. After local exhaust ventilation had been improved, average airborne dust concentrations of TMA at the two latter job stations fell to levels of 0.03 and 0.01 mg/m3, respectively, in 1982. The decrease in TMA exposure coincided with a gradual fall in total antibody binding of 125I-TM-HSA per milliliter in 1982 and symptomatic improvement in the three individuals with the LRSS. The continuous low-level exposure of the worker with TMA rhinitis was sufficient to elicit a rise in specific IgE against TM-HSA from 1.1 ng of 125I-TM-HSA bound per milliliter in 1979 to 2.12 in 1982.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution↗

Clinical and immunologic correlations in trimellitic anhydride airway syndromes.

Twenty workers exposed to trimellitic anhydride (TMA) powder were evaluated to correlate respiratory symptoms with total antibody activity against trimellityl human serum albumin (TM-HSA). Further, specific IgG, IgA, and IgE against TM-HSA were compared to total specific antibody levels against that antigen. The workers were categorized clinically as having either the late respiratory systemic syndrome (LRSS), immediate rhinitis and asthma, or an irritant reaction. There were no histories compatible with the pulmonary disease--anemia syndrome. Total antibody and IgG antibody activity to TM-HSA correlated well (R8 = 0.75, p less than 0.05). Total antibody activity was found in almost all TMA-exposed workers, it did not discriminate the symptomatic workers from asymptomatic workers as well as did the IgG or total antibody determinations. IgE antibody activity against TM-HSA was elevated in one worker with immediate-type asthma. Previous studies correlated symptoms caused by TMA inhalation with antibody activity. This study indicates that clinical assessment plus total antibody determination or IgG antibody and IgE antibody determination should establish a means of diagnosis of the presence or absence of immunologic respiratory disease caused by TMA powder.

Adult↗

Health status of plant workers exposed to fluorochemicals--a preliminary report.

Higher than normal levels of organic fluorine were found in the blood of workers exposed to fluorochemicals in an industrial environment. No ill health effects attributable to exposure to fluorochemicals were found among these workers. The ambient air in the process operation areas in the plant was found to contain measurable amounts of organic fluorine. Through certain modifications in the process steps and improvements in engineering controls. A substantial reduction in the airborne fluorochemical levels within the plant was achieved.

Air Pollutants, Occupational↗

A cross-sectional survey of 46 employees exposed to trimellitic anhydride.

This is a report of 46 employees exposed to trimellitic anhydride (TMA). The evaluation consisted primarily of periodic serum antibody studies and a questionnaire that identified symptoms compatible with allergic asthma and/or rhinitis, late respiratory systemic syndrome (LRSS), or pulmonary disease anemia (PDA) syndrome. Industrial hygiene data from the plant in 1989 reported exposures that were lower than levels in 1979. Seven employees had positive IgE antibody against trimellityl-human serum albumin (TM-HSA); one had TMA rhinitis, and another possibly had TMA asthma/rhinitis. Fourteen employees had positive IgG antibody against TM-HSA of whom only three had titers high enough to cause disease, and none of them had symptoms compatible with LRSS or PDA. At most, two workers had asthma or rhinitis during the 1990 evaluation. In summary, in this employee population with low level TMA exposure there is a low incidence of immunologically mediated disease due to TMA.

Adult↗