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Biomedical subjects

J S Goodwin

Publications and source records attributed to J S Goodwin.

At least 91 records · Page 5Linked to original sources
PubMed1991

Spontaneous fractures of the long bones in nursing home patients.

Six long-term nursing home residents who experienced fractures of the long bones in the absence of obvious trauma are described. All patients had been essentially non-weight-bearing for at least 2 years before the episode. Four patients experienced fractures on more than one occasion. There was no evidence of physical abuse in any of these of patients; indeed, evidence against abuse was fairly good. Nonetheless, physical abuse was alleged by the patients' families in four of the cases. Long bone fracture in the absence of trauma in patients after prolonged bed rest has been well described in the radiologic and orthopedic literature, but not previously in geriatrics. It is important that this phenomenon be recognized, lest all unexplained fractures in nursing home patients automatically be taken as evidence of abuse or neglect.

Aged↗
PubMed1991

Are prostaglandins proinflammatory, antiinflammatory, both or neither?

Research on the role of prostaglandins (PG) in inflammation has been divided along 2 lines of inquiry. One supposes that PG are proinflammatory, explaining why nonsteroidal antiinflammatory drugs (NSAID), which prevent conversion of arachidonic acid to stable PG through cyclooxygenase inhibition, exert their antiinflammatory effects. The other supposes that PG are antiinflammatory, explaining the reductions in inflammation produced by these substances in various experimental models of arthritis. A number of proinflammatory actions of PG have been identified, including vasodilatation and hyperalgesia. However, these activities are relatively modest and do not appear to account for the antiinflammatory effects of NSAID; indeed, mechanisms for these effects that do not depend on cyclooxygenase inhibition have been advanced. A number of potential mechanisms for antiinflammatory effects of PGE have been identified, including inhibition of neutrophil activation, O2 release and leukotriene B4 and cytokine production. It is likely that the availability of orally active PGE analogs will permit study leading to an integrated understanding of PG activity and an answer to the question whether such agents will prove useful in the treatment of chronic inflammatory diseases.

Adjuvants, Immunologic↗
PubMed1991

Hearing and cognition in the elderly. New findings and a review of the literature.

The purpose of this study was to determine the relationship between hearing status and cognitive status initially and at 5-year follow-up in a cohort of healthy elderly men and women and to relate the results to published reports on this topic. Volunteers older than 60 years with no major illnesses and taking no long-term prescription medications were examined. Baseline testing of hearing and cognition was performed in 224 subjects; 112 subjects underwent cognitive testing at 5-year follow-up. Hearing was measured by the Speech Perception in Noise test; cognition was measured by two parts of the Wechsler Memory Scale and by the Jacobs Cognitive Screening Test, an oral screening instrument. At baseline there were small correlations between hearing acuity and memory scores, but these disappeared after adjustment for age and gender. Analysis of follow-up memory and cognitive screening test scores in relation to baseline hearing ability showed no correlation between hearing at entry and cognitive function at 5 years. In addition, baseline hearing level did not predict change in memory or cognitive screening test scores during the follow-up period. The power of the study was 90% to detect a correlation of .30 between measures of hearing and cognition. There was no evidence for a major effect of hearing acuity on cognitive function over time in this group of healthy elderly. Review of published studies suggests that hearing ability is related to cognitive status in demented subjects, but there is little to suggest that in the normal elderly, hearing impairment leads to cognitive decline.

Aged↗
PubMed1991

A population-based study of functional status and social support networks of elderly patients newly diagnosed with cancer.

We assessed the functional status and social support networks of 799 men and women aged 65 years or older newly diagnosed with cancer and living in six New Mexico counties. Functional limitations included depending on others for transportation (33%) and mental incompetence or poor recent memory (42%). The percentage of patients with functional limitation increased sharply with increasing age. In a substantial number of patients there was also evidence for poor social support networks; 26.5% of subjects lived alone and 38.9% had no children living in the vicinity. In a multiple logistic regression analysis, the predictors of having a poor social support network included non-Hispanic white ethnicity, advanced age, low income, and being a recent migrant to the area. Subjects with functional limitations were more likely to have poor social support networks than subjects without such limitations. The deleterious combination of impaired functional status and a limited social support network may explain why elderly cancer patients are at increased risk for not receiving appropriate therapy. Given the potential complexities involving the evaluation and appropriate treatment of cancer, care must be taken to adequately assess functional status and support mechanisms of older patients, and to provide adequate support to ensure compliance with treatment.

Activities of Daily Living↗
PubMed1990

Determinants of cancer stage. A population-based study of elderly New Mexicans.

To assess the role of delay and other factors in determining stage of cancer at diagnosis, the authors interviewed a population-based sample of 800 elderly persons with newly diagnosed cancer at selected sites. Lengthening delay interval was associated with a declining proportion of local stage cases for breast cancer but not other sites. Of the other determinants of stage examined, older age, having a family physician, receiving medical checkups, having greater knowledge of cancer, and having no functional loss were most strongly predictive of local stage. For breast cancer, performance of breast self-examination also predicted local stage.

Activities of Daily Living↗
PubMed1990

Decreased specific antibody synthesis in old adults: decreased potency of antigen-specific B cells with aging.

The rise in rates of infection in adults over the age of 60 is accompanied by a decreased ability of older adults to make specific immune responses after immunization with a variety of specific antigens (Ag). This investigation delineates age-related changes in Ag-specific humoral immunity, comparing adults over age 60 to young adults aged 18-40, using tetanus toxoid (TT) as an immunologic probe. A culture system which does not require TT booster immunizations of study subjects was used to induce in vitro specific antibody responses. The amount of anti-TT antibody (Ab) produced in serum and in culture was measured by a TT-specific enzyme-linked immunosorbent assay (ELISA). The numbers of anti-TT Ab-secreting B cells were measured by a TT-specific ELISA-plaque assay. The TT-specific responses of old subjects were significantly less than that seen for young control subjects in the following measures: (1) serum anti-TT Ab titers (mean +/- S.E. log 2 titer = 3.3 +/- 1.1 vs. 9.5 +/- 1.4, P less than 0.01); (2) anti-TT Ab produced by peripheral blood lymphocytes (PBL) in cultures stimulated with TT (6 +/- 2.1 ng/ml vs. 22 +/- 8.4 ng/ml, P less than 0.01); (3) numbers of anti-TT Ab secreting B cells per million cells cultured (6.7 +/- 3.4 vs. 26.6 +/- 7.6, P less than 0.001) and (4) mean ng Ab secreted per anti-TT Ab-secreting B cell (0.6 +/- 0.4 ng vs. 12.7 +/- 7.8 ng, P less than 0.01). This study shows that both decreased numbers of Ag-specific immune B cells and decreased potency on a per cell basis contribute to the impaired immune responses to immunizations in older adults.

Adolescent↗
PubMed1990

Control of human T cell proliferation by platelet-activating factor.

Platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), is a membrane phospholipid with immunomodulatory functions. We studied the influence of PAF on mitogen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC), purified T cells and T cell subsets. High concentrations of PAF suppressed the proliferation of all cell populations studied (44% mean inhibition with 5 microM PAF and 78% inhibition with 10 microM PAF). In contrast, the deacetylated metabolite of PAF, lyso-PAF, had no effect on proliferation at micromolar concentrations. Lower, and presumably physiologically relevant, concentrations of PAF (10(-14) to 10(-8) M) stimulated a small increase in the proliferation of unfractionated T cells. When T cells were fractionated into CD4+ and CD8+ subsets, a difference in sensitivity to PAF was observed. PAF stimulated a modest, yet statistically significant, increase in the proliferation of CD4+ T cells at concentrations ranging from 10(-14) to 10(-10) M, while either having no effect or inhibiting the proliferation of CD8+ cells across the entire concentration range. Addition of indomethacin to the cultures further enhanced CD4+ proliferation, possible due to the blockade of PAF-induced PGE2 production by monocytes. The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation. These findings suggest that while high concentrations of PAF suppress T cell proliferation, low concentrations selectively stimulate proliferation of the CD4+ subset, an effect which is partially counteracted by PAF-induced monocyte PGE2 production.

Adult↗
PubMed1990

Changes in surgical treatments: the example of hysterectomy versus conization for cervical carcinoma in situ.

From 1969 through 1985, 4584 women in the state of New Mexico were diagnosed with carcinoma in situ of the cervix. Of these women, 65.5% underwent hysterectomy while 31.1% had a conservative therapy (primarily conization). Over the 17-year period, there was a steady increase in the percentage of women receiving conservative therapies, from 11.8% in 1969 to 50.3% in 1985. Younger women, unmarried women and American Indian women were more likely to receive conservative therapy. This marked shift in therapeutic approach occurred during a time of apparent controversy as to the optimal treatment for cervical carcinoma in situ, and illustrates a rapid change in surgical practice in the absence of any controlled trials comparing the two major treatment modalities.

Adolescent↗
PubMed1990

Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60.

Previous studies have suggested an association between depressed cell-mediated immunity and increased mortality in elderly persons. However, the effects of age and existing disease on this association have not been adequately addressed. We studied the association between cell-mediated immunity and subsequent morbidity and mortality in 273 initially healthy persons 60 years of age and older. In 1979, two tests of cell-mediated immunity were conducted--mitogen stimulation with phytohaemagglutinin, and delayed hypersensitivity skin testing. The study group was followed annually for development of pneumonia, cancer, and death. Anergy was associated with all-cause mortality (hazard ratio of 2.16; 95% confidence interval [1.10,4.28]). When the results were adjusted for age, the resulting hazard ratio was 1.89;[0.94,3.79]. A relationship was also suggested between anergy and cancer mortality although this association was not statistically significant. Response to phytohaemagglutinin was a poorer predictor of mortality than was response to delayed hypersensitivity skin testing. The results show that anergy may be a good indicator of subsequent all-cause mortality, and perhaps cancer mortality, in elderly who lack other indicators of poor health.

Aged↗
PubMed1990

Alcohol intake in the healthy elderly. Changes with age in a cross-sectional and longitudinal study.

Several cross-sectional studies have shown a decline in alcohol intake with increasing age. Longitudinal studies have failed to confirm this trend, which suggests that cohort effects may account for the reported decline. To address this, both cross-sectional and longitudinal analyses of alcohol use in 270 healthy elderly persons over a seven-year period (1980-1987) were performed. Alcohol consumption was assessed by three-day diet records. One hundred sixty-five subjects (61.1%) remained in the study until 1987; 143 (53%) completed diet records for every year. Longitudinal analysis showed a statistically significant decline in the percent of subjects consuming any alcohol over time (slope = -2% per year; 95% confidence interval -2.8, -1.1%). A cross-sectional analysis of the 1980 data revealed a similar decline in percent drinkers with increasing age (slope = -2.7% per year; 95% confidence interval -4.4, -1.1%). Mean alcohol intake for those who continued to drink did not change over time except among heavy drinkers (consumption of greater than 30 g per day in 1980), who did show a significant decline in mean alcohol intake (P = .02). Thus, in our population the decline in percent of drinkers with age found by a cross-sectional analysis was confirmed in longitudinal analyses, suggesting that this represents a true age-related decline rather than a cohort effect.

Age Factors↗
PubMed1989

Lipoxygenase inhibitors enhance the proliferation of human B cells.

The addition of drugs which inhibit the lipoxygenase pathways of arachidonic acid metabolism to 5 day cultures of mitogen-stimulated human B cells enhanced the proliferative response more than 10-fold. Several chemically dissimilar lipoxygenase inhibitors increased proliferation in this system, whereas the specific cyclooxygenase inhibitor indomethacin had no effect. A lipoxygenase inhibitor could be added as late as 48 to 72 h after the initiation of culture and still cause a significant increase in B cell proliferation. These drugs increased the proliferation of both peripheral blood B cells and tonsillar B cells activated by Staphylococcus aureus Cowan I or anti-Ig M antibodies, in combination with a crude T cell supernate, a commercial B cell growth factor preparation, or recombinant lymphotoxin. A similar effect was observed in tonsillar B cells purified by counterflow centrifugal elutriation to remove esterase positive accessory cells, suggesting this is a direct effect on the B cell. Lipoxygenase blockade also caused a greater than twofold increase in polyclonal Ig production. The enhanced proliferation caused by lipoxygenase blockade could not be reversed by adding back exogenous leukotrienes or hydroxyeicosatetraenoic acids to the cultures. Furthermore, B cells prelabeled with [3H]arachidonic acid did not produce radiolabeled lipoxygenase metabolites of arachidonic acid under the same culture conditions in which the addition of lipoxygenase inhibitors had a profound effect on proliferation. Thus, lipoxygenase inhibitors markedly stimulate B cell proliferation under a variety of experimental conditions, although the mechanism responsible for this action has not yet been elucidated.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Impaired T-cell activation in patients with systemic lupus erythematosus.

Interleukin-2 (IL-2) production was studied in T lymphocytes from 32 patients with systemic lupus erythematosus (SLE) and 27 healthy volunteers. The IL-2 production by phytohemagglutinin (PHA)-stimulated cells from SLE patients was significantly depressed compared to control values, with a correlation between degree of depression and disease activity. The depressed IL-2 production by SLE T cells are largely reversed by the addition of either phorbol ester (PMA) or partially by a calcium ionophore. SLE T cells had significantly lower peak increases in intracellular free calcium [( Ca2+]i) than controls after stimulation by PHA or by a monoclonal antibody against the CD3 antigen. This abnormality was found even in T cells from patients with mild disease activity or in those whose T cells produced normal amounts of IL-2. Calcium ionophore produced similar increases in [Ca2+]i in SLE patients as in normals. These results suggest that a major component of the defect responsible for decreased IL-2 production by SLE lymphocytes is proximal to protein kinase C activation and may involve impaired signal transduction after activation of the antigen receptor complex.

Adult↗
PubMed1989

Phosphatidyl inositol hydrolysis after CD3 binding in human peripheral blood T cells: inhibition by prostaglandin E2.

Hydrolysis of phosphatidyl inositol-4,5-bisphosphate, leading to generation of inositol phosphates (IPs), occurs after crosslinking CD3 antigens on the surface of murine and human T-cell lines and clones, and is thought to represent a basic mechanism of signal transduction after antigen receptor binding. Previous investigators have had difficulty demonstrating this phenomenon using human peripheral blood T-cells. In this paper we demonstrate significant IP generation after anti-CD3 stimulation of human peripheral blood lymphocytes and T-cells. The amount of IP generation is less and considerably more variable than what is obtained using a T-cell line. Also, exposure to ammonium chloride in the E-rosetting procedure totally inhibits IP generation, perhaps explaining previous unsuccessful attempts. Finally, prostaglandin E2 and other agents that raise cyclic AMP inhibit IP generation by anti-CD3 antibodies in human T-cells and a T-cell line.

Adult↗
PubMed1989

Dibutyryl guanosine cyclic monophosphate causes proliferation of interleukin-2-dependent T-cells in the presence of suboptimal levels of interleukin-2.

The effect of dibutyryl guanosine cyclic monophosphate (db-cGMP) on proliferation of an interleukin-2 (IL-2)-dependent T-cell line was investigated. Dibutyryl cGMP added to HT-2 cell cultures without IL-2 or in the presence of an optimal IL-2 concentration (60 U/ml) had no effect on proliferation. The same amount of db-cGMP (10(-5)M) added to cultures in the presence of suboptimal amounts of IL-2 (3-6 U/ml) produced significant increases in proliferation. In contrast, db-cAMP caused substantial inhibition of HT-2 cells cultured with IL-2. Similar effects were observed using human T-cell blasts produced after 72 h stimulation with phytohemagglutin. These results suggest that cyclic GMP may play a role in the cellular response of IL-2 responsive cells to IL-2.

Animals↗
PubMed1989

Social, psychological and physical factors affecting the nutritional status of elderly subjects: separating cause and effect.

The fact that most of the important changes in nutritional status with age are not secondary to aging per se in no way detracts from their importance. This paper reviews three factors that can affect nutritional status in elderly adults: ethanol intake, cognitive status, and institutionalization. The discussion focuses on the difficulties in obtaining reliable information on the interaction of nutritional status with these factors.

Aged↗