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Biomedical subjects

D A Smith

Publications and source records attributed to D A Smith.

At least 199 records · Page 11Linked to original sources

HIV associated risk factors: a survey of a troubled adolescent population.

The incidence of Acquired Immunodeficiency Syndrome (AIDS) in young adults and the typical incubation period for AIDS suggest that exposure to this disease often occurs in adolescence, a period of life during which risk taking behavior is particularly common. The population of adolescents with mental or behavioral problems and substance abuse problems at the South Dakota Human Services Center were studied by questionnaire and by human immunodeficiency virus (HIV) screening to assess the current prevalence of seropositivity and the potential for HIV transmission in these troubled youths. Sexual behavior, number of partners, prior incarceration, history of sexual abuse, drug and alcohol use, and knowledge about HIV transmission were examined. While no cases of HIV seropositivity were discovered, the authors are disturbed by the prevalence of known and suspected correlate behaviors and historical traits for HIV infection in this population. Implications for intervention and education are discussed.

Acquired Immunodeficiency Syndrome↗

Constant incidence rates of needle-stick injury paradoxically suggest modest preventive effect of sharps disposal system.

Does placement of impenetrable sharps disposal systems in hospitals reduce needle-stick injury? To study this question, annual health questionnaires were distributed on a quarterly basis to all 8000 employees in an academic medical center in a large eastern US metropolitan city asking each employee whether he or she had experienced a needle-stick injury since the last questionnaire. Questionnaires from active floor nurses were separated and hand tallied in 1987, 1989, and 1990, the latter 2 years being after impenetrable sharps disposal systems had been placed at nursing stations and in individual patients rooms. Total needle sticks in staff nurses reported during the 3 years (20.5%, 23.2%, 21.8%, not significant) did not decrease in the last 2 years. Simultaneously, hospital purchases of needle-containing devices increased 13.5%. Thus a constant reported needle-stick incidence rate may paradoxically represent a modest preventive effect of a hospital sharps-disposal system.

Equipment Safety↗

Liquid-liquid extraction and high-performance liquid chromatography for the determination of a novel antidysrhythmic agent (UK-68,798) in human urine.

A routine method for the determination of a novel class III antidysrhythmic agent, 1-(4-methanesulphonamidophenoxy)-2-[N-(4-methanesulponamidophen ethyl)- N-methylamino]ethane, in human urine has been developed. The method involves solvent extraction followed by high-performance liquid chromatography on an unmodified silica column with ultraviolet detection. Despite a low recovery of drug through the three-stage extraction procedure a reliable assay with high precision (coefficient of variation less than 6%) and a limit of determination of 2.5 ng/ml was achieved. The method has been applied to the analysis of samples following single oral and intravenous doses of 1-12.5 micrograms/kg of the drug to human volunteers.

Anti-Arrhythmia Agents↗

Quantitative model for Schädler's isometric oscillations in insect flight and cardiac muscle.

Schädler and colleagues (1969, 1971) and Steiger (1977a) have found that tetanized insect fibrillar and cardiac muscles exhibit damped isometric oscillations in tension following a quick stretch. This behaviour cannot be explained by the conventional sliding filament model at full activation, or by including stretch activation in the obvious way. However, it is predicted by a sliding filament model which allows these muscles to be further activated by an increase in thin-filament tension even at high calcium levels (above 10(-5) M), providing the strength gamma of strain-activation coupling exceeds a critical value. Calculations from a comprehensive model of the actin-myosin contraction cycle suggest that this can be achieved if the phosphate release and head rotation steps are both regulated by calcium and thin-filament tension. The model also predicts a delayed tension rise following a quick release for subcritical values of gamma. Current knowledge of sarcomere structure and regulation of contractility in striated muscle indicates that this strain-activation mechanism alone cannot account for all stretch-activation phenomena, although many can be predicted if the regulatory filament is allowed to carry passive tension.

Actinin↗

Four aspects of creep phenomena in striated muscle.

Four aspects of the slow creep of tension and sarcomere lengths observed during fixed-end tetani are studied with computer simulations, using the instantaneous steady-state (adiabatic) approximation. (1) Most aspects of fixed-end creep phenomena can be simulated in the presence of the passive forces which correctly produce initially shortened end sarcomeres. However, the very large maximum tensions observed with fibres of low resting force for sarcomere lengths greater than 3.0 microns cannot be simulated within the adiabatic approximation. (2) Random variations in the passive tension-length curve between different sarcomeres can predict the reported incidence of contracting sarcomeres in the middle of the fibre, while avoiding significant tension creep when a central segment is length-clamped. They can also reverse the velocity of these sarcomeres during creep in fibres with high resting tension, as observed by Altringham and Bottinelli (1985). At sarcomere lengths of greater than or equal to 3.4 microns we find that spatial variations in passive tension strength also contribute to tension creep. (3) Crossbridge fluctuations in active tension have been estimated from the sliding-filament model, and do not contribute significantly to tension creep. (4) The need for inter-sarcomere stiffness or other mechanisms to produce an additional slow rise in tension at long times, and to smooth the sarcomere length distribution, is assessed.

Animals↗

A method for the harvest, culture, and characterization of human adult atrial myocardial cells: correlation with age of donor.

Myocardial cell culture methods are now well established for animal and fetal human tissue. We present here a method for harvesting and culturing adult human atrial myocardiocytes. Cells are obtained from fresh atrial tissue normally discarded after being removed to cannulate the right atrium during open heart surgery. The atrial tissue is minced and then digested using collagenase. The single cell suspension is initially cultured in serum-containing growth medium, then transferred to defined medium, selective for myocardial cell growth. The cells are characterized by immunoperoxidase stains and transmission electron microscopy. The cultured cells stain positive for myoglobin, whereas control cultured fibroblasts and endothelial cells do not. Electron microscopy shows the presence of numerous myofibrils, Z-bodies, pleomorphic mitochondria, and secretory granules. The chronological age of the donor was an important factor in culturing the adult tissue, the younger tissue correlated with a higher success rate. This method provides a means for in vitro study of human adult myocardial cells and provides guidelines for appropriate atrial tissue to use.

Aging↗

Theory of asynchronous oscillations in loaded insect flight muscle.

A quantitative theory of the oscillatory behavior of loaded insect flight muscle is presented and is derived from the sliding filament model by calculating its nonlinear response to length changes out to third order. Oscillations may occur when the resonant frequency of the muscle and its load lie within the range of the negative second loop of the Nyquist plot for linear a.c. stiffness. They also require the total d.c. stiffness to exceed a threshold value, which may explain why these oscillations are not normally observed in other muscles. The tension-length loops and waveforms, the oscillatory power output, and their variation with load damping are in good agreement with observations. The rise in ATPase hydrolysis rate with oscillatory power is predicted, but the effect is sensitive to details of the sliding filament model. The model also shows a slow growth of oscillations after Ca2+ activation. The even slower rate of decay after deactivation is attributed to cooperative binding in the absence of calcium. Also, the tension responses to large imposed a.c. length changes agree with experiment and show figure-of-eight loops at higher frequencies. Stretch activation effects will require a modification of the theory but are not essential because these oscillations arise from the instability indicated by the negative second loop of the Nyquist plot, which is universal to all striated muscle.

Animals↗

Measurement of the class III antidysrhythmic drug, UK-68,798, in plasma by radioimmunoassay.

A sensitive radioimmunoassay (RIA) for the specific determination of 1-(4-methanesulphonamidophenoxy)-2-[N-(4-methanesulphonamido -phenethyl)-N- methylamino]ethane (UK-68,798), a novel class III antidysrhythmic agent, in human plasma is described. Specific antisera were raised in sheep using desmesyl-UK-68,798-succinate-ovalbumin conjugate as the antigenic hapten carrier protein. The antisera produced exhibited high specificity for UK-68,798 compared with known metabolites from animals, other antidysrhythmic agents and co-administered drugs. Good correlation was found in a comparison of the RIA method with a high-performance liquid chromatography (HPLC) method (r = 0.997) and a 10-fold lower limit of determination was observed for the RIA method compared with the HPLC method (0.05 and 0.5 ng ml-1, respectively). The RIA method was applied to the analysis of UK-68,798 in plasma obtained from human volunteers receiving the compound.

Animals↗

Couples coping with a myocardial infarction: a contextual perspective on wives' distress.

Conventional models of stress and coping are highly individualistic and give little attention to circumstances and involvement with others. A more contextual perspective on wives of patients who had suffered myocardial infarctions was adopted in this study. Wives' distress was related to the character of the infarction, but initial contact with medical personnel and marital quality each had independent contributions. Other analyses related wives' distress to their and the patients' coping. Wives' protective buffering of patients had a positive relationship with their own distress, even though Smith & Coyne (1988) have shown it contributes to patients' self-efficacy. Results suggest the need to acknowledge the limitations on adaptation imposed by health and the health care system. Also, initial conditions set a trajectory for later adaptation and there may be tradeoffs between preserving one's own well-being and contributing to a partner's efficacy.

Activities of Daily Living↗

Treatment of Diamond-Blackfan anaemia with haematopoietic growth factors, granulocyte-macrophage colony stimulating factor and interleukin 3: sustained remissions following IL-3.

We have treated six transfusion-dependent, steroid-unresponsive, Diamond-Blackfan anaemia (DBA) patients with the recombinant human growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), administered sequentially with an interim rest period. GM-CSF was given at a dose of 500 micrograms/m2/d subcutaneously for 6 weeks. Three patients increased their absolute reticulocyte counts 1.5-35-fold (mean 20.8-fold) and into the normal range, but only one showed a reduction in transfusion requirements. Between 4 and 25 weeks after discontinuation of GM-CSF, these six patients were treated with recombinant human IL-3, at doses of 60 or 125 micrograms/m2/d subcutaneously for 4-6 weeks. Three increased their absolute reticulocyte counts from 2- to 28-fold (mean 10.6-fold) and two required fewer transfusions. One of these two patients has remained transfusion independent for over a year since completion of IL-3 therapy, and the second patient required infrequent transfusions for 9 months and then became transfusion independent for the subsequent 5 months. The sustained clinical remissions seen in two of the six patients after IL-3 therapy is very encouraging and further studies in a larger cohort of DBA patients with IL-3 alone or in combination with GM-CSF or other growth factors should be carried out.

Adolescent↗

OBRA regulations.

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Attitude of Health Personnel↗

Marital interactions.

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Adaptation, Psychological↗

Age-dependent stereoselective increase in the oral clearance of hexobarbitone isomers caused by rifampicin.

1. The disposition of hexobarbitone enantiomers before and after rifampicin treatment (600 mg daily for 14 days) was investigated in six young (29 +/- 3 years old) and six elderly (71 +/- 4 years old) healthy male volunteers. Hexobarbitone was given as a single 500 mg oral dose of the racemate. 2. The mean (+/- s.d.) oral clearance of S-(+) hexobarbitone was 1.9 +/- 0.3 and 1.8 +/- 0.2 ml min-1 kg-1, respectively, in young and elderly subjects and increased approximately six fold following 14 days of rifampicin treatment in both young (to 11.9 +/- 2.2 ml min-1 kg-1) and elderly (to 10.7 +/- 2.8 ml min-1 kg-1) subjects. 3. In contrast, rifampicin treatment produced a larger and a differential increase in the oral clearance of R-(-) hexobarbitone in young and elderly subjects; an 89 fold change in the young (15.6 +/- 16.4 to 1146.7 +/- 1478.0 ml min-1 kg-1) and a 19 fold change (10.3 +/- 3.0 to 199.9 +/- 98.1 ml min-1 kg-1) in the elderly.

Administration, Oral↗

Marital adjustment, parental disagreements about child rearing, and behavior problems in boys: increasing the specificity of the marital assessment.

2 studies were conducted to illustrate how measuring a specific aspect of marriage, namely, child-rearing disagreements, provides a better understanding of the link between marriage and boys' behavior. In Study 1, 200 mothers of 3-year-old boys completed unstandardized measures of marital functioning and child behavior. An index of child-rearing disagreements: (1) correlated with a greater variety of behavior problems than nonchild disagreements, and (2) improved upon the prediction of behavior problems after accounting for nonchild disagreements as well as after accounting for boys' exposure to marital conflict. In Study 2, 87 mothers with 4-6-year-old sons completed the index of child-rearing disagreements used in Study 1 as well as standard measures of marital functioning and child behavior. Child-rearing disagreements: (1) predicted a greater variety of behavior problems than global marital adjustment, and (2) improved upon the prediction of internalizing problems after controlling for global marital adjustment as well as after controlling for boys' exposure to marital conflict.

Adaptation, Psychological↗

Psychiatric side effects of non-psychiatric drugs.

Many drugs prescribed for somatic diseases are capable of causing psychiatric symptoms in patients, especially in the elderly, the demented and probably in those who already suffer from a mental illness. In this study a random sample of drugs listed in the PDR was reviewed. In 65% of the drugs the manufacturer lists potential psychiatric side effects.

Aged↗