PubMed · 7914984
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D A Sack. 1994-08-27. Cholera control.. https://doi.org/10.1016/s0140-6736(94)92003-6
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OBJECTIVE: To determine 1) whether patients with coccidioidal meningitis who had achieved remission with oral azole therapy were cured and 2) when oral azole therapy could be discontinued in these patients. DESIGN: Data were gathered on patients with coccidioidal meningitis who had successfully responded to azole therapy in previous clinical trials. SETTING: Referral centers, including university, county, and veterans' hospitals and clinics. PATIENTS: 18 patients in whom azole therapy for meningitis had been discontinued, usually because of a presumption of cure. MAIN OUTCOME MEASURES: Clinical and cerebrospinal fluid relapse. RESULTS: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with disseminated disease after discontinuation of therapy, for a total of 1 nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and late (range, 0.5 to 30 months) after therapy was discontinued. The characteristics of patients who did not have relapse, including the particular azole used, the duration of therapy, the reason therapy was discontinued, and the cerebrospinal fluid indices before discontinuation, were similar to the characteristics of patients who had relapse. Relapse had serious consequences in some patients; 3 patients died. CONCLUSION: Our data suggest 1) that disease is only suppressed in patients with meningitis who achieve remission while receiving azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative is lifelong treatment with azoles; this appears to be acceptable, because toxicity is uncommon with triazole therapy, even long-term triazole therapy.
We have been investigating the mechanisms by which exogenous protein Ags activate CD8+ T cells. Previously, we have shown that OVA primed CTL precursors in vivo if administered as an emulsion with an adjuvant such as CFA. Such CTLs inhibit development of Ab responses when adoptively transferred into syngeneic mice. Thus, CD8+ CTL are immunosuppressive. These studies were initiated to determine whether CD8+ suppressor T cells were cytolytic T cells. Oral administration of protein Ags is a well-established method for inducing tolerance in humoral and delayed hypersensitivity responses which is associated with development of CD8+ suppressor T cells. OVA was chosen as a model Ag because it has been used extensively in oral tolerance studies, and target cells expressing the OVA gene are well characterized. Our data show that multiple, intragastric doses of native OVA inhibited priming of CD8+ CTL precursors and also inhibited CD4+ T cells and Ab responses. Oral OVA inhibited CTL priming in mice immunized with OVA-loaded EL4 cells, OVA-expressing transfectants, or OVA in CFA. The observed tolerance is specific to the orally administered Ag. Although oral OVA did not prime CTL precursors, it did activate spleen cells that transferred unresponsiveness to naive syngeneic mice. Suppression was mediated by CD4-CD8+ T cells. These CD8+ suppressor T cells were phenotypically distinguished from CTL by reactivity with a mAb that recognizes activated suppressor T cells.
BACKGROUND: The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction. METHODS: We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine, anti-inflammatory agents, and antidepressants. Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine (active placebo) in doses up to 1 mg twice daily over three-week titration, six-week evaluation, and two-week washout phases. Pain intensity, pain relief, and drug liking were rated weekly and psychological features, functional status, and cognition were assessed at baseline and at the end of each evaluation phase. FINDINGS: After dose titration in the 46 patients who completed the study, the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On visual analogue scales, the morphine group showed a reduction in pain intensity relative to placebo in period I (p = 0.01) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline (p = 0.02). No other significant differences were detected. INTERPRETATION: In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement.