Morphometric analysis of cortical bone upon the exposure to sustained delivery of anabolic promoting agents using adult male rats as a model.

Several investigations have documented that the use of anabolic agents could promote osteogenesis and enhance bone ingrowth in traumatized bone. Previously, anabolic steroids have been shown to increase the mineralization of bone. However, their clinical use has been limited because of the unwanted virilizing activity. The previous studies used systemic administration of anabolic steroids, which subjects other tissues within the body to high concentrations of hormones. In addition, different anabolic/androgenic steroids have varying affinities to different cell types within tissues. The specific objectives of this study were (i) to histopathologically evaluate the structural changes associated with sustained delivery of testosterone (T), dihydrotestosterone (DHT), and androstendione (AED) using adult male rats as a model, and (ii) to morphometrically evaluate the cortical areas and length upon the exposure of the aforementioned hormones for 90 days. A total of 23 adult rats were randomly divided into five groups (group I = control, group II = sham, group III = AED, Group IV = T and group V = DHT treated). At the end of the treatments the animals were euthanized and the x-rays, blood, and bones were analyzed using standard laboratory protocols. Data obtained from this investigation revealed the following: (A) all treated femurs appeared healthy with no traumatic responses observed in comparison to control animals, (B) measurements of the inner perimeter of the bone on the endosteal side showed significant reduction in the androgen treated animals. This suggesting that the androgens caused increases in the cortical bone. The differences seen in the amount of reduction was in the following ease: T > DHT > AED. C) quantitative measurements of the cortical length showed slight increases in the cortical lengths in the androgen treated rats in comparison to the control.

Adverse reactions to thalidomide in patients infected with human immunodeficiency virus.

Thalidomide is emerging as a useful agent in the management of several complications of disease due to human immunodeficiency virus (HIV). We conducted three prospective studies of 56 HIV-infected patients who were treated with thalidomide for 14-21 days; 24 (43%) of these patients discontinued therapy owing to adverse reactions. Cutaneous and/or febrile reactions were the most frequent toxicities, arising in 20 (36%) of the patients. These reactions occurred after a mean interval (+/-SD) of 10 +/- 3 days and were associated with significantly lower CD4 T lymphocyte counts in reactors than in nonreactors (median count, 52.5/mm3 vs. 242 cells/mm3, respectively; P = .009). Four of four rechallenged patients experienced accelerated hypersensitivity; hypotension occurred in one case. Although sedation was an almost universal side effect among the patients, it was moderate or severe in only seven (13%); constipation was moderate or severe in five (9%) of the patients. Severe neuropathic symptoms and mood changes were each noted in two (4%) of the 56 patients. We conclude that the increasing use of thalidomide to treat HIV-infected patients must be accompanied by recognition of the drug's increased potential for toxicity in this population.

Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis.

BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha (TNF alpha), is essential for host immunity, but overproduction of this cytokine may have serious pathologic consequences. Excess TNF alpha produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (alpha-N-phthalimidoglutarimide) has recently been shown to suppress TNF alpha production by human monocytes in vitro and to reduce serum TNF alpha in leprosy patients. We have therefore conducted a two-part placebo-controlled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNF alpha levels, and weight. MATERIALS AND METHODS: 30 male patients with active tuberculosis, either human immunodeficiency virus type 1 positive (HIV-1+) or HIV-1-, received thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were evaluated. RESULTS: Thalidomide treatment was well tolerated, without serious adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differential cell counts. TNF alpha production was significantly reduced during thalidomide treatment while interferon-gamma (IFN gamma) production was enhanced. Daily administration of thalidomide resulted in a significant enhancement of weight gain. CONCLUSIONS: The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production both in vivo and in vitro and is associated with an accelerated weight gain during the study period.

Cytokine gene activation and modified responsiveness to interleukin-2 in the blood of tuberculosis patients.

Selected parameters of cellular immunity relating to cytokine gene activation and responsiveness to interleukin-2 (IL-2) were analyzed in 27 patients with active pulmonary tuberculosis and no human immunodeficiency virus type 1 infection. Cytokine mRNAs were not expressed by peripheral blood mononuclear cells (PBMC) of normal controls. In PBMC of tuberculosis patients, messages for IL-1, IL-8, and tumor necrosis factor-alpha were uniformly expressed, whereas PBMC of only 5 of 18 patients expressed IL-6. PBMC of 7 patients (all of those with systemic symptoms) expressed interferon-gamma mRNA and none expressed IL-2 mRNA. Most patients' cells demonstrated IL-4 mRNA. Limiting dilution analysis of IL-2-responsive cells in PBMC revealed that tuberculosis patients had 10-fold fewer IL-2-responsive cells than did controls.

Instructions and group versus individual reinforcement in modifying disruptive group behavior.

Head Start children were matched into two groups on the basis of rates of disruptive behavior during rest periods. Attempts were made to modify their behavior using either individual or group token reinforcement procedures. While the reinforcement procedures reduced inappropriate behavior somewhat, the addition of instructions to the reinforcement reduced the inappropriate behavior to near zero for both groups. Instructions alone, however, were ineffective in controlling behavior. Type of reinforcement (group or individual) did not produce differential effects. While experimental control over the target behavior was demonstrated, there was little carryover from the experimental room to the regular classroom. Even when treatment was introduced into the regular class, follow-up results showed that with time the target behavior approximated pretreatment levels. The results suggest that (a) the combination of instructions and reinforcement is much more effective than either one of these alone, (b) behavior change is specific to the environmental contingencies, and (c) the group reinforcement technique, which is much more easily implemented, was at least as effective as individual reinforcement in the present study.