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Biomedical subjects

J S Goodwin

Publications and source records attributed to J S Goodwin.

230 records · Page 13Linked to original sources

Effect of indomethacin in vivo on humoral and cellular immunity in humans.

We studied the effect of indomethacin on intradermal skin testing and antibody responses in humans. Since we and others have shown that prostaglandins are suppressor cell mediators, it was probable that in vivo inhibition of prostaglandin synthesis might enhance the humoral and/or cellular immune response. Administration of indomethacin (Indocin) in a dosage of 100 mg/day to 15 normal men and women resulted in a significantly increased antibody titer to A-Victoria (P less than 0.025) as compared with age- and sex-matched controls. There was no difference in titer to A-New Jersey. Since 90% of the subjects had antibody titers to A-Victoria before inoculation, whereas none had detectable titers to A-New Jersey, we interpret this data as suggesting that indomethacin enhances the secondary but not the primary humoral immune response. Indomethacin administration did not alter the intradermal skin test responses.

Adult↗

Age-dependent variations in polymorphonuclear leukocyte chemiluminescence.

Polymorphonuclear leukocytes from 46 adults (age 18 to 35), 19 adults (age 70 to 91), 10 children (age 1 to 3), and 22 neonates (cord blood samples) were tested for their chemiluminescence response to opsonized zymosan. Results indicated that both cord blood leukocytes and those from individuals over 70 were significantly lower (P less than 0.05) in their chemiluminescence response. Furthermore, when the latter group was divided into two subsets, one containing subjects over 80 years of age and the other containing subjects between 70 and 80 years of age, those over 80 showed a chemiluminescence response significantly lower (P less than 0.05) than those between 70 and 80. The kinetics of the chemiluminescence response was similar with all samples except the neonatal cells, where the response appeared to peak and subside more slowly. These data demonstrate that polymorphonuclear leukocyte chemiluminescence is depressed in the very young and the very old.

Adolescent↗

Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with mitogen dose and preincubation.

In this study we further characterize the properties of the prostaglandin-producing suppressor cell. Overnight preincubation of peripheral blood mononuclear cells results in an increased response of the cells to phytohemagglutinin or Concanavalin A compared to the response of fresh cells. This increase in mitogen response with preincubation was similar in magnitude to the increase in mitogen response of fresh cells after the addition of indomethacin. The two manipulations were not additive; that is, after preincubation, indomethacin caused much less enhancement of mitogen stimulation of peripheral blood mononuclear cells (100 +/- 12% increase before preincubation vs. 12 +/- 6% after preincubation; mean+/-SEM, P < 0.001). Preincubated cells also lose sensitivity to inhibition by exogenous prostaglandin E(2). It requires the addition of 100- to > 1,000-fold more exogenous PGE(2) to produce comparable inhibition of phytohemagglutinin-stimulated preincubated cells than is required for inhibition of phytohemagglutinin-stimulated fresh cells. The enhancing effect of indomethacin increases with decreasing doses of phytohemagglutinin. Indomethacin causes a 1,059+/-134% increase in [(3)H]thymidine incorporation at the lowest dose of phytohemagglutinin (0.2 mug/ml), and a 4+/-3% increase at the highest dose (20 mug/ml). This increase in response to indomethacin with a lower dose of phytohemagglutinin is due to increased sensitivity to inhibition by PGE(2) at lower mitogen doses. The prostaglandin-producing suppressor cell assay and the short-lived suppressor cell assay measure over-lapping phenomena. The increased suppressive effect of the prostaglandin-producing suppressor at suboptimal mitogen dose must be taken into account in the interpretation of any study where the response to a range of mitogen doses is studied.

Adult↗

Partial reversal of the cellular immune defect in common variable immunodeficiency with indomethacin.

We administered indomethacin (25 mg q.i.d.) to two patients with common variable immunodeficiency and measured the effect on their depressed cellular immune responses. The in vitro response of both patients' lymphocytes to phytohemagglutinin increased during indomethacin administration. Both patients were anergic to skin testing before treatment and responded to two of four skin tests during treatment with indomethacin. Thus indomethacin administration in vivo appears to enhance the cellular immune respone, paralleling its previously described effects in vitro.

Adolescent↗

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.

Cyclooxygenase Inhibitors↗

Prostaglandin-producing suppressor cells in Hodgkin's disease.

We examined the role of a prostaglandin-producing suppressor cell in the hyporesponsiveness to phytohemagglutinin seen in Hodgkin's disease. Addition of indomethacin to phytohemagglutinin cultures of lymphocytes from six patients with Hodgkin's disease resulted in an increase of 182 +/- 60 per cent in 3H-thymidine incorporation versus a 44 +/- 18% increase in 29 controls (mean +/- S.D., P less than 0.001). Without indomethacin the mean response of the lymphocytes in Hodgkin's disease was 48% of that of control. With indomethacin it was 94% of the control value. Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P less than 0.02). Removal of glass-adherent cells markedly decreased the enhancement seen with indomethacin; it reduced prostaglandin E2 production by more than 80% and eliminated the differences in response to phytohemagglutinin between Hodgkin-disease and normal lymphocytes. Thus, a glass-adherent, prostaglandin-producing suppressor cell is responsible for the hyporesponsiveness to phytohemagglutinin seen with Hodgkin-disease lymphocytes.

Adult↗

Applying management principles to the occupational health unit.

This paper presents the occupational health unit as a subsystem competing with other subsystems in the organization for limited resources. By applying management principles the nurse can design a program to show management its results in dollar terms. This will enable the health unit to compete more favorably with the other subsystems for limited resources. An example of how this approach can be applied to the problem of absenteeism is presented.

Humans↗

Factors influencing unawareness of hypertension among older Mexican Americans.

BACKGROUND: The objective of the study was to identify factors associated with unawareness of hypertension among Mexican Americans age 65 years and older. METHODS: This was a population-based survey of 3,050 older Mexican Americans conducted in five Southwestern states in 1993-1994. An in-home interview included sociodemographics, review of medications, and blood pressure measurements. RESULTS: Sixty percent of all subjects were hypertensive, and 37% of these were unaware of their diagnosis. Unaware hypertensive had significantly higher mean blood pressures than did aware hypertensives (145.7/ 86.2 mm Hg vs 142.4/83.1 mm Hg). While 77% of aware hypertensives were treated, only 10% of unaware hypertensives were treated. In multivariate analyses, factors associated with unawareness included male gender (OR = 1.8), being married (OR = 1.6), having Medicaid (OR = 1.6), having made fewer than two visits to a doctor in the past year (OR = 2.8), having a history of heart disease (OR = 0.57) or stroke (OR = 0.37), and having poor self-reported health (OR = 0.43). CONCLUSION: Despite 3 decades of hypertension detection and education programs, unawareness of hypertension remains high among older Mexican Americans. There is a continued need for community-based education programs for hypertensives who are unaware of their diagnosis, and also there is need for programs to increase access to primary care physicians.

Aged↗

Hydralazine causes nonspecific binding of antibodies to human lymphocytes in vitro.

In vitro incubation of human lymphocytes or a continuous human Jurkat T cell line with hydralazine (1-hydrazinophthalazine), a widely used antihypertensive agent, produced a nonspecific binding of various antibodies to the cells. This phenomenon was found to produce increases in staining of mitogen-stimulated and mitogen-unstimulated human lymphocytes and Jurkat cells with a variety of antibodies recognizing T and B cell antigens. The increase in nonspecific binding was greatest at 10(-2) M hydralazine, but was seen with concentrations as low 10(-7) M, which is comparable to the serum concentrations of patients prescribed hydralazine. The binding of antibodies is not connected with significant decreases in the cell viability. This property of hydralazine may cause misinterpretation of certain immunological tests employing the antibodies.

Adult↗

Measuring frailty in the hospitalized elderly: concept of functional homeostasis.

Functional homeostasis is the ability of an individual to withstand illness without loss of function. We investigate whether the level of functional homeostasis predicts adverse outcomes in the 6 months posthospital discharge in older men and women. A prospective cohort study was conducted in an acute care geriatric inpatient unit of a university hospital. Subjects included a consecutive series of patients admitted to the unit. The Functional Independence Measure (FIM) instrument was used to assess patients at four time points: preillness, hospital admission, hospital discharge, and 6 months postdischarge. Of the 122 subjects available for analysis, 64 (52%) experienced a decline in functional level from preillness to hospital discharge and were defined as having poor functional homeostasis, whereas 58 (48%) experienced no change or an increase in functional status and were defined as having good functional homeostasis. Those with poor functional homeostasis had a higher 6-month readmission rate to the hospital (59.4 v 39.7%; P=0.03) and a higher rate of any adverse outcome (78.1 v 50%; P=0.001) than those with good functional homeostasis. In logistic regressive analyses, functional homeostasis remained a significant and powerful predictor of adverse outcomes independent of actual level of function at discharge, age, gender, living status, and other factors that might influence outcomes. Change in functional status associated with an acute illness is an independent predictor of adverse outcomes and, in this study, a better predictor than actual level of function at discharge. Functional homeostasis is one approach to the quantification of the important but elusive concept of frailty in the elderly.

Activities of Daily Living↗

The association between emotional well-being and the incidence of stroke in older adults.

OBJECTIVE: Individuals with high levels of depressive symptoms have an increased risk of many illnesses, including stroke. Measures of depressive symptoms include questions about the presence of negative affect, such as sadness, as well as the absence of positive affect, such as happiness and optimism. We assessed whether positive or negative affect, or both, predicted risk of stroke. METHODS: Data were from a 6-year prospective cohort study of a population-based sample of 2478 older whites and blacks from five counties in North Carolina who reported no history of stroke at the baseline interview. Baseline, in-person interviews were conducted to gather information on sociodemographic, psychosocial, and health-related characteristics of subjects. Thereafter interviews were conducted annually for 6 years. RESULTS: Increasing scores on the modified version of the Center for Epidemiological Studies Depression Scale (CES-D) were significantly associated with stroke incidence for the overall sample (relative risk [RR] = 1.04 for each one-point increase, 95% confidence interval [CI] = 1.01-1.09) over the 6-year follow-up period after adjusting for sociodemographic characteristics, blood pressure, body mass index, smoking status, and selected chronic diseases. Positive affect score demonstrated a strong inverse association with stroke incidence (RR = 0.74, 95% CI = 0.62-0.88). CONCLUSIONS: Increasing scores on the modified CES-D are related to an increased risk of stroke, whereas high levels of positive affect seem to protect against stroke in older adults.

Affect↗