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Biomedical subjects

L Griffith

Publications and source records attributed to L Griffith.

At least 55 records · Page 3Linked to original sources

Fatal occupational accidents in Ontario, 1986-1989.

We examined 470 fatal occupational accidents in Ontario, 1986-1989, that met eligibility criteria. Homicides and most accidents on public roads were excluded. Information was obtained from coroners' files and records of the provincial Ministry of Labour. Levels of alcohol likely to produce impairment were found in six subjects (2% of the two-thirds of fatalities tested). Cannabis was detected in 3.9% of cases (17% of those tested), but other illegal drugs were not found. Recommendations of coroner's juries showed that organizational factors were considered relevant on many occasions, although language and literacy were rarely mentioned. The incidence rate rose steadily with age. Other data items were examined, although, because of missing information and/or lack of denominator data for many of them, the conclusions that can be drawn are limited. Among these tentative findings was that more fatal accidents occurred in the first half of the shift than in the second half.

Accidents, Occupational↗

Interviewer versus self-administered questionnaires in developing a disease-specific, health-related quality of life instrument for asthma.

We wished to determine the extent to which respondents provided the same answers to a health-related quality of life (HRQL) questionnaire in self- and interviewer-administered forms. One hundred and fifty patients with asthma who were symptomatic or required treatment at least once a week, and had airway hyperresponsiveness to methacholine aerosol (PC20 < 8.0 mg/ml) participated. Patients completed a 152-item HRQL questionnaire in both interviewer and self-administered forms, separated by a 2-week interval, the order determined by random allocation. The percentage of items endorsed by the self-administered approach was significantly higher than that of the interviewer-administered approach overall (46.9 vs 35.8%) (p < 0.0001). The difference was consistent across all six domains; the absolute difference in the proportion of items endorsed varied from 8.9 to 12.3%. The intraclass correlations for the proportion of subjects endorsing an item was 0.84. Self- and interviewer-administered questionnaires yield very similar results in discriminating between subjects, but the self-administered version shows systematically greater HRQL impairment.

Adult↗

Measuring quality of life in the frail elderly.

This study was carried out to develop and test the Geriatric Quality of Life Questionnaire (GQLQ), a health-related qualify of life (HRQL) questionnaire designed for the frail elderly. One hundred patients were asked to identify areas of their daily lives affected by their health. The GQLQ, developed on the basis of the results, the Rand Physical and Emotional Function Questionnaires, and the Barthel Index, were administered serially to a group of 76 patients participating in a randomized trial of a Geriatric Day Hospital. Participants in all phases of the study were over 65 years of age, living in their own home but with sufficient functional status impairment to compromise their ability to live independently. The GQLQ includes 25 questions focusing on activities of daily living (ADL), symptoms, and emotional function. In the ADL and Symptom domains respondents define personal problem areas. The responsiveness coefficients of the GQLQ ADL and Symptom domains (0.26 and 0.30 respectively) were similar to those of the Rand Physical Function instrument and the Barthel Index (0.29 and 0.20). The responsiveness coefficient of the GQLQ Emotional Function domain (0.50) was similar to that of the Rand Emotional Function instrument (0.63). Correlations between the GQLQ ADL domain and the Barthel Index (0.41), and between GQLQ and the Rand Physical Function instrument (0.30), were similar to the correlation between the Barthel Index and Rand Physical Function (0.40). While the GQLQ captures important areas of health-related quality of life impairment for the frail elderly, we failed to show any advantages in either responsiveness or validity to existing, simpler measures. New, specific instruments should be tested in head-to-head comparisons with existing measures, particularly generic instruments, before dissemination.

Activities of Daily Living↗

A prospective study to identify the risk factors associated with acute reactions to platelet and red cell transfusions.

It is generally assumed that febrile nonhemolytic transfusion reactions are an immunologically mediated reaction involving the recipient's plasma and the white cells in the donor unit. This has led to the use of white cell reduction and pretransfusion medication, to try to minimize these reactions. To better understand febrile transfusion reactions, a prospective study was performed in which all patients receiving platelet and red cell transfusions in a tertiary-care medical center were interviewed before and after transfusion to obtain information about the typical presentation of the syndrome. It was found that transfusion reactions were much more frequently associated with platelet transfusion (30.8%) than with red cell transfusion (6.8%, p < 0.0005). The routine use of antipyretics prevented most episodes of fever but did not prevent the occurrence of other symptoms such as chills, cold, and discomfort. The application of logistic regression analysis revealed that the dominant factor determining the risk of a reaction was not white cell contamination, but the age of the component (p < 0.005). The significant relationship between reaction and the increasing age of the component suggests that cytokines released in the component during storage may be responsible for many reactions to blood components.

Adolescent↗

Testicular dysfunction with amiodarone use.

Amiodarone, an antiarrhythmic drug approved for use in patients who survive cardiac arrest, has been associated with infiltration of or inflammatory changes in various tissues. To date thyroid dysfunction has been the only endocrine disturbance noted. In an initial group of seven amiodarone-treated men undergoing evaluation for sexual dysfunction, an elevation in serum gonadotropin concentration was detected, suggesting testicular dysfunction. Because of this finding, gonadal function was prospectively evaluated in 44 men (18 who had been treated with amiodarone for greater than 1 year and 26 survivors of cardiac arrest who had been treated with antiarrhythmic drugs other than amiodarone). Amiodarone-treated men had higher serum follicle-stimulating hormone (41.8 +/- 22.8 vs. 14.4 +/- 10.4 mIU/ml, p less than 0.001) and luteinizing hormone (34.8 +/- 26.4 vs. 10.1 +/- 5.2 mIU/ml, p less than 0.001) concentrations compared with control subjects. Although serum total and free testosterone levels were comparable between the two patient groups, these levels were inversely correlated (r = -0.53, p less than 0.05; r = -0.62, p less than 0.01, respectively) with cumulative amiodarone dose. Hyperresponsiveness to the administration of gonadotropin-releasing hormone was noted in the 10 amiodarone-treated men evaluated by this diagnostic test. Sexual dysfunction was common in both groups (70% of control subjects and 82% of amiodarone-treated subjects), although atrophic testes were more commonly observed in amiodarone-treated men (p less than 0.05). Because of the elevated serum gonadotropin level, it is concluded that testicular dysfunction may result from prolonged amiodarone treatment.

Adult↗

Platelet activation by immobilized monoclonal antibody: evidence for a CD9 proximal signal.

Anti-CD9 monoclonal antibodies (MoAbs) are reported to activate human platelets through stimulation of the Fc gamma II receptor. We show here that nonstimulatory F(ab')2 fragments of the anti-CD9 MoAb 50H.19 induce dense-granule release and dose-dependent platelet aggregation when attached to polystyrene latex beads. Cross-linking F(ab')2 fragments of MoAb 50H.19 by F(ab')2 fragments of goat anti-mouse IgG does not result in platelet aggregation unless the second antibody is bound to latex beads, indicating that immobilization, and not cross-linking of the stimulus, is critical to the initiation of the CD9 signal. In contrast, F(ab')2 fragments of the second antibody readily induce the aggregation of platelets treated with the anti-Fc gamma II receptor MoAb IV.3. Immobilization of MoAb per se is insufficient to induce an activation signal because intact and F(ab')2 fragments of nonstimulatory MoAb directed to glycoprotein Ib and HLA class I do not become stimulatory when attached to beads. CD9-induced activation requires cytoskeletal rearrangement because it is inhibited by cytochalasin B. Aggregation is blocked by inhibitors of the thromboxane pathway, indicating that CD9 activates phospholipase C indirectly through prior activation of phospholipase A2.

Adenosine Diphosphate↗

Retinal pigment epithelium response and the use of the EOG and Arden Ratio in depression.

Supersensitivity to light in depression has been observed with both neuroendocrine and ophthalmological assessment methods. The biological defect underlying this abnormality may be localized in either the photoreceptors, the retinal pigmented epithelium, or some interaction of the two. The present study assessed responses of the retinal pigmented epithelium (RPE). All subjects underwent thorough ophthalmological and mood assessments. The electrooculogram (EOG) was used to measure standing potentials of the RPE in response to light and dark in 20 normal controls and 20 unmedicated depressed patients. Both groups were matched for age, sex, time of day for the procedure, and prior lighting history. Reproducibility of the EOG measure on two independent occasions for 13 control subjects had an intrasubject reliability coefficient of 0.70. The mean +/- SD Arden Ratio (light peak/dark trough) of the control group (2.13 +/- 0.42) compared to the depressed group (2.28 +/- 0.72) showed no statistical difference. There was, however, a significant difference between groups in response to darkness; depressed patients had a lower standing potential in the dark compared to controls, suggesting supersensitivity to light. No difference between groups was detected in standing potentials at baseline or in response to light. Supersensitivity to light in depression may be related to abnormal function of the RPE, but the inherent reliability of the EOG precludes the use of this instrument in pursuing this hypothesis.

Adult↗

Neuroendocrine effects of caffeine in normal subjects.

In double-blind crossover experiments, we examined the effects of oral caffeine (250 or 500 mg) added to decaffeinated coffee on plasma hormone levels in adults who normally consume one to three cups of coffee a day. In one experiment, 250 mg (about 4 mg/kg) caffeine was given to men; in two other experiments, 500 mg (8 mg/kg) was given to both sexes. Caffeine, 500 mg, elevated plasma levels of beta-endorphin-like immunoreactivity in both men and women but had no significant effect on plasma levels of cortisol, thyroid-stimulating hormone, growth hormone, prolactin, or triiodothyronine in men nor on plasma levels of prolactin or cortisol in women. The 250-mg dose induced no significant changes in plasma levels of any of the hormones measured. We conclude that the threshold for caffeine's endocrine effects is higher than that for its behavioral effects.

Administration, Oral↗

Neuroendocrine effects of caffeine. II. Effects on thyrotropin and corticosterone secretion.

Caffeine injected i.p. to rats decreased serum thyrotropin and markedly increased serum corticosterone with ED50 values of 40 to 50 mg/kg. Adrenalectomy did not affect the response of thyrotropin to caffeine. Theophylline was as potent as caffeine in inhibiting thyrotropin and stimulating corticosterone secretion; theobromine and paraxanthine were less potent, but their own serum concentrations were also lower. One week of once-daily injections of 50 mg/kg of caffeine produced tolerance to its effects on thyrotropin and corticosterone. The lowest caffeine dose to produce tolerance to a 50-mg/kg challenge dose was 25 mg/kg. Adenosine receptor agonists did not affect serum thyrotropin nor did they block the caffeine-induced decrease in serum thyrotropin. Blockade of the hypothermic effect of caffeine did not alter the effect of caffeine on serum thyrotropin. Similarly, the caffeine-induced decrease in serum thyrotropin was additive to the decrease produced by placing rats in a warm environment or to the increase in serum thyrotropin produced by placing them in the cold. Deviating from the stress-like pattern of increased corticosterone and decreased thyrotropin, caffeine did not affect prolactin secretion in ovariectomized rats with or without estrogen pretreatment.

Adrenalectomy↗

Fluconazole therapy for coccidioidomycosis in Japanese macaques.

The South Texas Primate Observatory is the home of more than 200 Japanese snow macaque monkeys and of a small number of vervets. The colony was established to study social behavior in monkey families; consequently, animals range freely over more than 59 acres. During the past 6 years, there have been six documented cases of coccidioidomycosis. In addition, there have been six probable cases and five possible cases. Disease was progressive in all monkeys and was characterized by cough, wasting, and the appearance of draining cutaneous abscesses. Untreated, monkeys usually died within several months. Fourteen monkeys were treated with oral fluconazole; eight improved rapidly, and the others had no response. Four of the monkeys that improved relapsed quickly after fluconazole treatment was interrupted. Two monkeys showed initial improvement, relapsed when fluconazole treatment was interrupted, and again improved when fluconazole treatment was resumed. The present studies suggest that fluconazole may be effective treatment in primates with coccidioidomycosis and that euthanasia is no longer necessary. However, prolonged treatment is necessary, and relapses may occur.

Animals↗

Confidence intervals for cost-effectiveness ratios.

The problem of variability in computed cost-effectiveness ratios (CERs) is usually addressed by performing sensitivity analyses to determine the effects on these ratios of plausible ranges of values of input parameters. However, the sampling variation that exists in these estimated parameters can be utilized to obtain confidence intervals for cost-effectiveness ratios. As cost-effectiveness analysis becomes more widely used, new techniques need to be developed for establishing when a difference in strategies evaluated is meaningful. A first step is to establish the precision of the CER itself. The authors estimate the precision of a CER in the context of a statistical model in which the primary outcome is survival, with cost and effectiveness defined in terms of the underlying survival distribution (S). Effectiveness (alpha) is measured by life expectancy, restricted to a finite time horizon and discounted at a fixed rate r, alpha = integral of e-rtS(t)dt. Cumulative cost (beta) per patient is regarded as resource utilization and incurred randomly over time depending on the survival experience of the patient, beta = integral of e-rtS(t)dC(t), where C(t) is the total potential resources utilized up to time t. Average cost-effectiveness (ACE) of a single strategy is beta/alpha, and when comparing two strategies, the CER is delta beta/delta alpha, the ratio of the incremental cost to the difference in mean survival. Utilizing the sampling distribution of the Kaplan-Meier estimate of S yields standard errors and confidence intervals for ACE and CER. The technique is applied to survival data from 218 previously studied patients to assess 95% confidence intervals for the CER and ACE of the implantable cardioverter defibrillator as compared with electrophysiology-guided therapy.

Confidence Intervals↗