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Biomedical subjects

A Kelley

Publications and source records attributed to A Kelley.

16 recordsLinked to original sources

A prospective assessment of mortality in chronic spinal cord injury.

STUDY DESIGN: Prospective mortality study. OBJECTIVE: To assess the relationship between comorbid medical conditions and other health-related factors to mortality in chronic spinal cord injury (SCI). SETTING: Boston, MA, USA. METHODS: Between 1994 and 2000, 361 males >/=1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33-74.4 months) through 12/31/2000 using the National Death Index. RESULTS: At entry, mean (+/-SD) age was 50.6+/-15.0 years (range 23-87) and years since injury was 17.5+/-12.8 years (range 1.0-56.5). Mortality was elevated (observed/expected deaths=37/25.1; SMR=1.47; 95% CI=1.04-2.03) compared to US rates. Risk factors for death were diabetes (RR=2.62; 95% CI=1.19-5.77), heart disease (RR=3.66; 95% CI=1.77-7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390-459) in 40%, and of the respiratory system in 24% (ICD-9 460-519). CONCLUSIONS: These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI.

Adult↗

Breathlessness and exercise in spinal cord injury.

After spinal cord injury (SCI), breathlessness during daily activities is common. In 308 individuals with SCI, the authors measured pulmonary function and administered a survey regarding health status, participation in wheelchair athletics, and breathlessness during different activities. The following questions were included: A. Are you troubled by shortness of breath when hurrying on the level or going up a slight hill?; B. Do you have to go slower than people of your own age on the level because of breathlessness?; C. Do you ever have to stop for breath when going at your own pace on the level?; and D. Do you ever have to stop for breath after going about 100 yards on the level? The analysis was restricted to 183 subjects with neurologically motor complete or incomplete SCI who, to get around, used hand-propelled wheelchairs more than 50% of the time. Of these, 56 (31%) reported breathlessness during some types of activities. Subjects with neurologically motor complete cervical or high thoracic SCI (T-6 and above) were more likely to report breathlessness than others (39% compared with 25%, p = .039). Among wheelchair athletes, the prevalence of breathlessness was 8/49 (16%) versus 48/134 (36%) for non-athletes (p = .011). Adjusting for smoking, neurological level, and history of obstructive lung disease, non-athletes were 2.3 times more likely to report breathlessness than athletes were (p = .049 to .075, depending on regression model). This relationship persisted when adjusted for percent predicted forced expiratory volume (FEV1) and maximal expiratory and inspiratory pressures. Therefore in SCI, wheelchair athletes are less likely to report breathlessness than non-athletes, but the mechanism does not appear to be improvement in respiratory muscle performance or pulmonary function.

Activities of Daily Living↗

Specific changes in food intake elicited by blockade or activation of glutamate receptors in the nucleus accumbens shell.

Blockade of non-N-methyl-D-aspartic acid (NMDA) ionotropic glutamate receptors in the nucleus accumbens shell (AcbSh) with 6,7-dinitroquinoxaline-2,3-dione (DNQX) elicits intense feeding in satiated rats. In order to determine whether or not this feeding is part of a general behavioral activation, we observed the effect of intra-AcbSh DNQX injections on intake of solid food, liquid food, and water, and on gnawing behavior. In addition, we investigated the possibility that activation of a subset of these receptors with (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) could suppress feeding. DNQX significantly increased intake of solid and liquid food, but did not significantly affect water intake or gnawing behavior. Furthermore, injections of AMPA into the AcbSh suppressed deprivation-induced feeding and intake of a palatable 5% sucrose solution without affecting water intake in water-deprived rats. Taken together, these data suggest that DNQX is acting on a system specifically involved with the regulation of food intake.

Animals↗

Induction of tyrosine hydroxylase by forskolin: modulation with age.

With aging, circulating catecholamines are elevated in both humans and animals. This may be related to the increased basal levels of tyrosine hydroxylase messenger RNA (mRNA) levels and tyrosine hydroxylase enzyme activity in the adrenal medulla of senescent compared with younger animals. In addition, tyrosine hydroxylase gene expression in the senescent rat is resistant to further stimulation by cold exposure as compared with younger animals. Collectively, these observations suggest either that tyrosine hydroxylase expression is already maximally stimulated in senescent rats or that tyrosine hydroxylase gene induction pathways are impaired with senescence. To help distinguish between these possibilities, we examined the induction of tyrosine hydroxylase mRNA, tyrosine hydroxylase immunoreactivity and tyrosine hydroxylase enzyme activity in the adrenal medulla following forskolin administration to young and old F-344 rats. Forskolin at doses of 1.8 and 3.5 mg/kg increased tyrosine hydroxylase mRNA levels 2.5-fold in adrenal medulla from young rats but did not increase either tyrosine hydroxylase immunoreactivity or tyrosine hydroxylase enzyme activity 5 h after administration. Prolonged treatment with forskolin (3 doses, 12 h apart) increased tyrosine hydroxylase mRNA levels and tyrosine hydroxylase immunoreactivity and tyrosine hydroxylase enzyme activity. In senescent rats, the baseline level of tyrosine hydroxylase mRNA was more than 2-fold higher compared with young rats. A single injection of the lower dose of forskolin increased tyrosine hydroxylase mRNA levels by the same increment in senescent as compared with young rats. These data indicate that the tyrosine hydroxylase gene in the adrenal medulla from senescent rats is still capable of further stimulation.

Adrenal Medulla↗

First-time suicide attempters, repeat attempters, and previous attempters on an adolescent inpatient psychiatry unit.

OBJECTIVE: To compare clinical characteristics of hospitalized adolescents who (1) have recently made their first suicide attempt, (2) have recently made a second or subsequent attempt, (3) have made previous but no recent attempts, or (4) have never made an attempt. METHOD: Semistructured psychiatric diagnostic interviews were used to determine history of recent and previous suicidal behavior among 225 consecutively admitted adolescents to an inpatient psychiatric facility. Twenty-seven first-time attempters, 32 repeat attempters, and 40 previously suicidal youths were compared with 126 nonsuicidal youths in terms of severity of self-reported depressive symptoms, state anxiety, trait anxiety, state anger, and trait anger. RESULTS: Repeat attempters and previous attempters both reported more depressive symptomatology and trait anxiety than did nonsuicidal youths. In addition, youths with a previous history of suicide attempts, but no recent attempts, evidenced more trait anger than all other groups. First-time suicide attempters reported levels of distress that were intermediate to the other groups. CONCLUSIONS: Repeat attempters and previous attempters in hospital settings both report more distress than do nonsuicidal youths. Interventions should focus not only on resolution of immediate crises, but also on youths' ability to cope with ongoing difficulties that engender depression and chronic anxiety.

Adaptation, Psychological↗

Personality and coping styles in the prediction of dropout from treatment for cocaine abuse.

This study was designed to distinguish between dropouts and completers of residential therapeutic community treatment for cocaine abuse on the basis of the Millon Clinical Multiaxial Inventory II (MCMI-II; Millon, 1987) and Ways of Coping Checklist (WCCL; Folkman, Lazarus, Dunkel-Schetter, DeLongis, & Gruen, 1986) scales, which measure detached, dependent, and independent personality and coping styles. Dropouts were differentiated from completers in two discriminant functions defined, in part, by scores on scales that tap a fiercely independent orientation with manipulative, exploitive, and confrontive interpersonal features. Also contributing to the discriminant functions identified in this study were scores on scales that measure responsiveness to direction from others associated with strong desire for social approval and ability to establish self-control of emotional and behavioral reactions.

Adaptation, Psychological↗

Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance.

In this study, peripheral-blood mononuclear cells from patients with chronic hepatitis B and spontaneous or therapy-induced disappearance of HBsAg were examined for HBV DNA. Samples were evaluated by in situ hybridization and polymerase chain reaction both before and after clearance of HBsAg. By in situ hybridization, positive signals were observed in 2 of 13 samples collected after HBsAg loss, in 8 of 15 samples before HBsAg loss and in 0 of 4 control patients without serological markers of active or prior HBV infection. When polymerase chain reaction analyses were performed, HBV DNA was detected in 5 of 12 HBsAg-negative samples and 10 of 15 HBsAg-positive samples from the study group. Testing of mononuclear cells after disappearance of HBsAg revealed that two of eight patients were HBV DNA positive by in situ hybridization and by polymerase chain reaction, whereas two additional patients were positive by polymerase chain reaction alone. Mononuclear cell-associated HBV DNA was detected between 2 and 9 mo after the disappearance of circulating HBsAg by in situ hybridization and as long as 4 yr later by polymerase chain reaction. These data indicate that patients who have undergone HBsAg seroconversion may nonetheless harbor HBV DNA in their peripheral-blood mononuclear cells for prolonged periods.

Adult↗

Low-dose recombinant interleukin-2 and low-dose cyclophosphamide in metastatic breast cancer.

We undertook a preliminary study to examine the response rate of recombinant interleukin-2 (rIL-2) in patients with advanced measurable breast cancer, in a phase II clinical trial. The regimen we utilized was designed to allow outpatient administration. A treatment cycle consisted of low-dose cyclophosphamide (350 mg/m2) given on day -3 followed by the bolus administration of rIL-2 (3.6 x 10(6) Cetus units/m2) on days 1-5, and 8-12. Toxicity was significant but acceptable. One partial remission was seen in 13 evaluable patients. In 2 additional patients clear evidence of an antitumor response was observed. The study was terminated prematurely owing to a shortage of rIL-2. Additional evaluation of rIL-2 in breast cancer appears warranted.

Adult↗

Activation of rat pulmonary lavage cells by intratracheal administration of polyinosinic-polycytidilic acid.

Systemic administration of biologic response modifiers (BRMs) is often limited by serious adverse effects. Local delivery of a BRM may provide a means to avoid systemic side effects while enhancing host defense. To test this hypothesis, the effects of intratracheal administration of the interferon inducer polyinosinic-polycytidilic acid (Poly-I:C) were examined. We demonstrated that intratracheal administration of Poly-I:C in rats results in alterations in pulmonary lavage cell number, population distribution, and function, suggestive of cellular activation. Following intratracheal instillation of 15, 75, or 150 mg of Poly-I:C, we observed a dose-dependent increase in Fc receptor-mediated phagocytosis, a dose-independent tumoricidal activity directed against xenogeneic P815 murine mastocytoma target cells, and a dose-independent decrease in superoxide anion (O2-) generation. With the exception of O2- generation, these functions returned to normal control levels by 7 days after a single dose of Poly-I:C. Thus, localized administration of Poly-I:C enhanced the host defense capability of pulmonary lavage cells, providing a rationale for compartmentalized immunoprophylaxis in the lung.

Analysis of Variance↗

Inhibition of IFN-gamma-induced Ia antigen expression on synovial fibroblasts by IL-1.

Naturally occurring substances capable of the negative regulation of class II molecules on synovial fibroblasts may play an important role in controlling the sustained immune processes ongoing in the rheumatoid joint. We report here that rIL-1 is capable of such a negative regulatory process. The simultaneous addition of rIL-1 and rIFN-gamma to rat synovial fibroblasts resulted in decreased Ia Ag and mRNA expression when compared with synovial fibroblasts treated with IFN-gamma alone. Both rIL-1 alpha and rIL-beta inhibited to a similar degree with the level of inhibition being dependent on both the concentration of IL-1 and IFN-gamma. Other cytokines, including IFN-alpha/beta, IL-2, and TNF, had no antagonistic effect on IFN-gamma-induced Ia expression. Time course experiments showed that IL-1 inhibited when present immediately before addition of IFN-gamma or when added during the first 24 h of IFN-gamma stimulation but not at later time points. Indomethacin failed to reverse the IL-1-mediated inhibition, despite the fact that exogenously added PGE2 also inhibited IFN-gamma-induced Ia expression. IL-1 treatment of synovial cells did not alter the ability of IFN-gamma to bind to the cells. These findings provide evidence for a negative regulatory role for IL-1 on synovial fibroblasts independent of PGE2 production and thus suggest that IL-1 is capable of both pro- and antiinflammatory actions within the rheumatoid joint.

Animals↗