Longer Courses Of Therapy Research Articles

Treatment of gynecomastia with tamoxifen: A double-blind crossover study

Benign asymptomatic or painful enlargement of the male breast is a common problem, postulated to be due to an increased estrogen/testosterone ratio or due to increased estrogenic or decreased androgenic stimulation via estrogen or androgen receptor interactions. Treatment at present consists of analgesic medication or surgery. However, treatment directed against the preponderance of estrogenic stimulation would seem to represent a more specific form of therapy. In the present double-blind crossover study, one-month courses of a placebo or the antiestrogen tamoxifen (10 mg given orally bid) were compared in random order. Seven of ten patients experienced a decrease in the size of their gynecomastia due to tamoxifen ( P < 0.005). Overall, the decrease for gynecomastia for the whole group was significant ( P < 0.01). There was no beneficial effect of placebo ( P > 0.1). Additionally, all four patients with painful gynecomastia experienced symptomatic relief. There was no toxicity. The reduction of breast size was partial and may indicate the need for a longer course of therapy. A followup examination was performed in eight out of ten patients nine months to one year after discontinuing placebo and tamoxifen. There were no significant changes from the end of the initial study period except for one tamoxifen responder who developed a recurrence of breast tenderness after six months, and one nonresponder who demonstrated an increase in breast size and a new onset of tenderness after ten months. Therefore, antiestrogenic treatment with tamoxifen may represent a safe and effective mode of treatment for selected cases of cosmetically disturbing or painful gynecomastia.

Long-term follow-up of ambulatory management of osteomyelitis.

Over four years, 50 patients with osteomyelitis (32 classified as acute and 18 as subacute or chronic disease) were treated with oral antibiotics in an ambulatory setting. The profile of clinical and laboratory parameters, including etiologic agents, was similar to previous series. Forty-eight patients initially received parenteral drugs, mean duration 14 days (range 0-36). Oral agents administered at home included cephalosporins, clindamycin, dicloxacillin, penicillin VK, amoxicillin, and sulfa-trimethoprim. Mean duration of total therapy was 53.2 days (range 16-365). In follow-up, ranging from 12 to 60 months (mean 35), relapses occurred in one patient with acute and one with chronic disease. Both responded to oral treatment. No residual infection has resulted, although clinical and radiographic sequelae remain in six more patients initially termed subacute or chronic. Long-term follow-up of patients receiving high-dose oral antibiotic therapy for osteomyelitis due to sensitive organisms confirms the safety and efficacy of this mode of treatment and the feasibility of ambulatory management. The outcome after oral therapy is equivalent to that following parenteral therapy. Patients with subacute or chronic disease have a significantly poorer prognosis despite a milder initial illness and longer course of therapy.

Evaluation of the antitumour activity of the non-steroidal antioestrogen monohydroxytamoxifen in the DMBA -induced rat mammary carcinoma model

The antitumour activity of monohydroxytamoxifen has been compared with tamoxifen in the DMBA-induced rat mammary carcinoma model. In general antioestrogen therapy between 30 and 60 days after DMBA administration was more successful than therapy between 60 and 90 days after DMBA. Although monohydroxy-tamoxifen was a more potent antioestrogen than tamoxifen and equivalent dosage regimens were more effective at reducing cytoplasmic oestrogen receptor concentrations in the ovariectomized rat uterus, tamoxifen appeared to be a more potent antitumour agent. The administration of 4 weekly courses of tamoxifen ( 0.2, 3, 50 or 800 μg daily, 5 times a week) starting 30 days after DMBA produced a dose-related delay in tumour appearance and a decrease in tumour numbers. By contrast, monohydroxytamoxifen ( 0.012, 0.2, 3 or 50 μg daily, 5 times a week) was only weakly active at delaying tumour appearance although tumour numbers were reduced. Most of the tumours that developed in groups previously treated with antioestrogens regressed upon ovariectomy of the host. From studies in ovariectomized rats, tamoxifen was found to have long term effects upon the uterus whereas equivalent doses of monohydroxytamoxifen were only effective for a short period after the cessation of therapy. These data suggest that mammary tumour development is best inhibited in the constant presence of an antioestrogen i.e., biological half-life, as well as potency, is important for antitumour activity. The principle was exemplified by a reduction in the number and sizes of mammary tumours developing during continuous therapy with monohydroxytamoxifen ( 3 or 50 μg daily, 5 times a week) starting 30 days after DMBA. Overall it was clear that antioestrogens do not destroy all the foci of hormone dependent tumour cells and long courses of therapy or the use of other antihormonal methods e.g., ovariectomy, are essential to control tumour growth.

THE EFFICACY OF GANTRISIN AS COMPARED TO KEFLEX IN THE TREATMENT OF URINARY TRACT INFECTIONS IN COLLEGE COEDS

During, the past three years on 354 occasions college coeds with culture proven acute symptomatic urinary tract infections (2 cultures >100,000 col) were treated with either Gantrisin (123) or Keflex (231) in subgroups of 3, 7, 10, 14 or 21 days. A comparison of the recurrence rates for each of the subgroups within the Gantrisin (G) and Keflex (K) groups were not statistically different. For this reason, all subgroups for each of the drugs were combined in order to compare the combined efficacy of each group. Cantrisin (Total Recurrence Rate Post Theraphy 12.79%) appears to be more effective than Keflex (Total Recurrence Rate Post Therapy 35.4%) in the treatment of urinary tract infections in college coeds. In addition, three days of therapy proved to be as effective as longer courses of therapy in these young women.