In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.
In a randomized, double-blind crossover study, 29 patients with painful diabetic neuropathy received 6 weeks of amitriptyline and 6 weeks of an "active" placebo that mimicked amitriptyline side effects. Amitriptyline was superior to placebo in relieving pain in weeks 3 through 6. Both steady, burning pain and lancinating pains were relieved. Patients able to tolerate higher amitriptyline doses reported greater relief, through the maximum dose of 150 mg nightly. Amitriptyline analgesia was similar in depressed and nondepressed subgroups and was not associated with mood improvement. We conclude that amitriptyline relieves pain in diabetic neuropathy; this effect is independent of mood elevation.
Sixty-four patients were entered into a randomized trial that evaluated intra-arterial (I.A.) versus intravenous (I.V.) 5-fluorodeoxyuridine (FUDR) for colorectal liver metastases. There was a significant improved response rate for I.A. (62%) compared with I.V. (17%) treatment (p less than 0.003). However, the improved response rate for patients in whom I.A. therapy was used did not translate to a significantly improved survival rate. The 2-year actuarial survival rates for the groups for which I.A. and I.V. therapy was used were 22% and 15% respectively, with the survival curves not differing significantly (p = 0.27). These results may have been due to the inclusion of patients with tumor in draining hepatic lymph nodes. The presence of tumor in hepatic lymph nodes was associated with a poorer prognosis. Analysis of a subgroup of patients with negative hepatic lymph nodes suggested an improved actuarial survival rate in patients for whom I.A. versus I.V. therapy was used (p less than 0.03). The toxicity of I.A. FUDR was considerable, and side effects included chemical hepatitis (79%), biliary sclerosis (21%), peptic ulcers (17%), and gastritis/duodenitis (21%). The only major effect of toxicity of I.V. FUDR was severe diarrhea (59%). Regional I.A. FUDR allowed more drug delivery to liver tumors, which resulted in increased tumor responses when compared with use of systemic therapy. However, the small gain in survival seen in a select subgroup of patients with negative hepatic nodes appeared to be offset by the toxicity of I.A. FUDR.
No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.
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