Search PubMed⌕ Search

Biomedical subjects

J P West

Publications and source records attributed to J P West.

At least 19 recordsLinked to original sources
PubMed1999

Immunomodulatory effects of morphine withdrawal in the rat are time dependent and reversible by clonidine.

RATIONALE: It is well established that opioids can modulate the immune status following both acute and chronic administration and that tolerance develops to some of these immunomodulatory effects. Few studies, however, have investigated opioid withdrawal-induced immunomodulation and the mechanism by which that process may be mediated. OBJECTIVES: The present study examines the immunomodulatory properties of morphine withdrawal alone and in the presence of the alpha(2)-adrenergic agonist, clonidine. METHODS: Rats drank a morphine solution for 20 days; withdrawal was induced on day 21 by replacing the morphine solution with plain tap water. Measurements of withdrawal-induced weight change and immunomodulation were obtained at several time points after withdrawal induction. Immune status was assessed by determining concanavalin A (Con-A), toxic shock syndrome toxin (TSST-1), and lipopolysaccharide (LPS)-stimulated splenocyte proliferation, splenic ConA-stimulated interferon (IFN)-gamma production, and splenic natural-killer (NK) cell activity. In a separate series of experiments, systemic injections of clonidine (0.001-0.01 mg/kg) were administered during a 12-h withdrawal episode and all measures of immune status were reassessed. RESULTS: Weight change was time dependent, with peak decreases in weight occurring 24 h following withdrawal induction. Rats also exhibited a time-dependent suppression of immune status in all assays except LPS-stimulated proliferation; immunomodulation was most evident 12 h following withdrawal induction. Clonidine dose dependently prevented withdrawal-induced suppression of Con-A and TSST-1-stimulated splenocyte proliferation, Con-A-stimulated splenocyte IFN-gamma production, and splenic NK cell activity. CONCLUSIONS: These findings demonstrate that opioid withdrawal significantly suppresses a subset of immune parameters and that these effects can be prevented by clonidine.

Animals↗
PubMed1999

A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus.

OBJECTIVE: To determine if dehydroepiandrosterone (DHEA) is beneficial in severe systemic lupus erythematosus (SLE). METHODS: A double-blinded, placebo-controlled, randomized clinical trial in 21 patients with severe and active SLE, manifestated primarily by nephritis, serositis or hematological abnormalities. In addition to conventional treatment with corticosteroids +/- immunosuppressives, patients received DHEA 200 mg/d vs. placebo for 6 months, followed by a 6-month open label period. The primary outcome was a prospectively defined responder analysis, based on a quantitatively specified improvement of the principal severe lupus manifestation at 6 months. RESULTS: Nineteen patients were available for evaluation at 6 months. Baseline imbalance between the groups was noted, with the DHEA group having greater disease activity at baseline (P<0.05 by physician's global assessment). Eleven patients were responders: 7/9 patients on DHEA vs. 4/10 patients on placebo (P<0.10). Of the secondary outcomes, mean improvement in SLE disease activity index (SLE-DAI) score was greater in the DHEA group (-10.3+/-3.1 vs. -3.9+/-1.4. P<0.07). Bone mineral density at the lumbo-sacral spine showed significant reduction in the placebo group, but was maintained in the DHEA group. CONCLUSION: DHEA therapy, when added to conventional treatment for severe SLE, may at most have a small added benefit with respect to lupus outcomes, but baseline imbalances in the study population limit the generalizability of the results. DHEA appears to have a protective effect with respect to corticosteroid-induced osteopenia in such patients.

Adrenal Cortex Hormones↗
PubMed1999

Tacrolimus (FK506) in the treatment of severe, refractory rheumatoid arthritis: initial experience in 12 patients.

OBJECTIVE: To determine if tacrolimus (FK506) has potential as a therapeutic agent in patients with severe and/or refractory rheumatoid arthritis (RA). METHODS: Twelve patients with RA who had severe and active disease and had failed an average of 5.3 disease modifying antirheumatic drugs (DMARD) were treated with tacrolimus 2-6 mg/day in an open label study. Patients were assessed monthly with respect to RA outcomes and drug related toxicities. RESULTS: Of the 12 patients, 7 were able to complete 6 months of treatment. In these 7 patients, significant improvements were seen in tender joint count (from 26.4 +/- 4.2 to 11.7 +/- 3.2; p = 0.007), swollen joint count (from 17.7 +/- 2.5 to 4.1 +/- 1.3; p = 0.001), and other RA outcomes. All 7 patients achieved the 20% response criteria of the American College of Rheumatology (ACR), and 5 of 7 patients met the ACR 50% response criteria. The other 5 patients withdrew in the first 3 months of treatment due to gastrointestinal symptoms (3), chest pain (1), and neuropathic pain (1). Serum creatinine levels were unchanged in all patients, and hypertension was not seen. CONCLUSION: Tacrolimus was tolerated by only 7 of 12 patients, but in 5 of these 7 patients with severe and refractory disease, the clinical responses were very good.

Antirheumatic Agents↗
PubMed1998

Differential tolerance to morphine's immunomodulatory effects following continuous administration.

Rats were continuously infused with either morphine or saline via an osmotic minipump for 20 consecutive days. Effects on immune status were assessed on the twentieth day of the chronic administration period following a bolus injection of morphine administered 1 h prior to sacrifice. The morphine injection suppressed measures of splenic natural killer (NK) cell activity, mitogen-stimulated T-cell proliferation, and gamma-interferon (IFN) production in rats that received saline via the minipump. In rats that received chronic morphine via the minipump, the morphine injection also suppressed mitogen-stimulated splenocyte proliferation and gamma-IFN production but did not suppress NK cell activity. These data indicate that chronic morphine administration via osmotic minipumps leads to differential tolerance to the immunomodulatory effects of morphine. These findings support previous results indicating differential tolerance development within the immune system following chronic morphine administration via the drinking water.

Animals↗
PubMed1998

Analysis of comfort care for the terminally ill: the hospice approach.

Much of the published literature on hospice care focuses on a single dimension of this increasingly popular approach to meeting the needs of the terminally ill. By contrast, this article takes a broader view by examining the hospice concept and its implementation through the lens of the nine dimensions of the SEPTEMBER model--focusing in turn on each of the social, economic, political, treatment, ethical, managerial, bereavement, education, and research elements. This broader perspective brings together in kaleidoscopic fashion these diverse but interconnected elements of hospice care. This integrated conceptual model helps administrators and health care professionals to develop a clearer overall picture of the multifaceted challenges involved in delivering palliative care to dying patients.

Aged↗
PubMed1997

Tolerance development to morphine-induced alterations of immune status.

A variety of in vitro immune measures were examined in groups of Lewis rats that chronically consumed either tap water or a 0.2, 0.4, or 0.6 mg/ml morphine drinking solution. Rats received a subcutaneous injection of either saline or 15 mg/kg morphine sulfate 1 h before sacrifice. In the drinking groups, the acute morphine injection significantly suppressed splenic natural killer (NK) cell activity, mitogen-stimulated splenic T- and B-cell proliferation and gamma-interferon (gamma-IFN) production. A single, acute injection of morphine did not suppress NK cell activity in rats that drank the two highest concentrations of morphine, whereas it did suppress the mitogen-stimulated splenic T- and B-cell proliferation and gamma-IFN production. These results suggest that rats that drank morphine for 20 days developed tolerance to morphine's suppressive effect on NK cell activity but not to other measures of immune status. Morphine drinking rats also developed tolerance to morphine's antinociceptive effects and revealed signs of physical dependence when the morphine solution was withdrawn or when naltrexone was administered.

Animals↗
PubMed1977

Mortality and morbidity after esophagogastrectomy for cancer of the esophagus and cardia.

Forty-eight esophagastric resections performed for cancer of the esophagus and cardia resulted in a five-year survival rate of four per cent. An operative mortality rate of 23%, comparable to that reported by others, diminishes the value of esophagogastrectomy even for palliation. Nutritional depletion, commonly found in these patients, contributes significantly to the unacceptably high mortality. A review of the recent literature indicates that the routine use of preoperative hyperalimentation and prophylactic antibiotics can significantly reduce morbidity in these high-risk patients and thereby result in better palliation.

Adenocarcinoma↗
PubMed1976

Comparative analysis of community health planning: transition from CHPs to HSAs.

With the implementation of the National Health Planning and Resources Development Act, comprehensive health planning is moving into a new phase. In search of lessons to guide future planning efforts on the part of the Health Systems Agencies (HSAs) established by the act, this paper reviews organizational and operational characteristics of ten relatively "successful" local comprehensive health planning agencies. Several problems are delineated that HSAs will likely share with their predecessors and strategies for confronting these problems are suggested.

Community Participation↗