Synchronous VBM and radiotherapy in the treatment of squamous cell carcinoma of the head and neck†

Since April 1974, 60 patients with squamous cell carcinoma of the head and neck region, of poor prognosis and generally in advanced stages, were treated with the combination of a cytotoxic regimen–VBM (Vincristine, Bleomycin and Methotrexate) and radical radiotherapy. The essential feature of the combination is the administration of pulses of VBM synchronous with a course of fractionated external radiotherapy in order to achieve potentiation of radiotherapy. On average 4-5 pulses of VBM were given during treatment, combined with radiotherapy on a Cobalt unit. The selection, preparation and management of the patients are described. Intense mucositis and intercurrent infection provide the main problems during treatment and close management is essential. Late complications have not been a serious problem. The crude actuarial survival rate at 24 months is 61%. The probability of survival without any recurrence to 24 months following initial treatment is 46%. Local control was achieved by the initial treatment in 43 patients. These results suggest that potentiation of radiotherapy and an increased therapeutic ratio has been obtained by the addition of VBM to radiotherapy and there is a possibility that the occurrence of distant metastases has been reduced or postponed.     

PHARMACOKINETIC PROJECTIONS FOR ISOXICAM AND PIROXICAM IN OLD AND YOUNG SUBJECTS

A single-dose pharmacokinetic study to determine the effectof age on the disposition of isoxicam and piroxicam was carriedout on a group of old and a group of young subjects Althoughthere was no significant difference with either drug in themean elimination half-time between the group of young and thegroup of old subjects, there was considerable individual variation.Steady-state levels were calculated to be three times as highin subjects with slow clearance as in those with more rapidclearance. Three weeks would be required with either drug toachieve steady-state drug levels in those subjects with slowdrug-clearance KEY WORDS: Pharmacokinetics, Nonsteroidal drugs, Elderly     

RELATIONSHIPS BETWEEN THE CIRCADIAN RHYTHMS OF TSH, PROLACTIN AND CORTISOL IN SURGICALLY TREATED MICROPROLACTINOMA PATIENTS

Pharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post-operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (less than 420 mU/l) in all patients by surgery (pre-op: 930-2752 mU/l, post-op: 33-376 mU/l) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the cortisol antibody with 11-deoxycortisol was taken into account during the calculation of results. All subjects showed a normal cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (+/- SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 +/- 0.26, 1.29 +/- 0.48; 0.46 +/- 0.26, 0.23 +/- 0.13 and -49 degrees +/- 9.8 degrees; -62 degrees +/- 2.7 degrees respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

THE MORPHOLOGY AND MORPHOMETRY OF THE NORMAL HUMAN TIBIALIS ANTERIOR MUSCLE

The light microscopic appearance of the human tibialis anterior muscle is described based on conchotome biopsy specimens from seven healthy volunteers and 20 patients who presented with myalgia but who had no evidence of neuromuscular disease. The morphometric characteristics of these normal muscles are documented and the similarities and differences between the appearances of the tibialis anterior and other muscles discussed.     

A clinical trial using danazol for the treatment of premenstrual tension

Summary. Forty women with premenstrual tension received either placebo, 100, 200 or 400 mg danazol daily for 3 months in a pilot study arranged as a double-blind trial. Thirteen patients withdrew by the third month usually because they complained of no improvement. They had significantly higher pretrial symptom scores than those who continued. In patients treated with danazol, symptom scores for breast pain during the second and third months and for irritability, anxiety and lethargy during the third month were significantly ( P <0.05) lower than scores in those given placebo. Most symptoms improved on placebo in the first month but by the third month only three remained improved. In contrast eight symptoms were improved on 200 mg danazol by the third month. By the end of the trial more than 75% of patients who were still taking danazol were essentially free of breast pain, lethargy, anxiety and increased appetite, but results for other common symptoms were no better than with placebo.     

EFFECT OF ORAL ADMINISTRATION OF MELATONIN ON GH RESPONSES TO GRF 1–44 IN NORMAL SUBJECTS

In order to investigate the role of melatonin on the neuroregulation of GH secretion, eight healthy male volunteers each underwent four separate tests in random order separated by at least 1 week. Following oral administration of melatonin (500 mg at -60 min and at -30 min) plasma GH levels were higher than after placebo at 45 min (mean +/- SEM 2.9 +/- 0.8 vs 0.9 +/- 0.4 ng/ml, P less than 0.01) and 60 min (mean +/- SEM 2.9 +/- 0.4 vs 0.8 +/- 0.1 ng/ml, P less than 0.05). Likewise, after prior administration of melatonin, GH responses to GRF 1-44 (1 micrograms/kg i.v. at 0 min) were greater than placebo plus GRF at 15 min (mean +/- SEM 22.4 +/- 6.1 ng/ml vs 11.3 +/- 2.3 ng/ml, P less than 0.05), 45 min (mean +/- SEM 26.2 +/- 5.3 ng/ml vs 13.3 +/- 2.5 ng/ml, P less than 0.01) and 60 min (mean +/- SEM, 24.7 +/- 7.4 ng/ml vs 11.1 +/- 2.5 ng/ml, P less than 0.05). In contrast we did not observe any effect of either 10(-9)M, 10(-7)M melatonin on in-vitro basal GH release and GH responses to 10(-8)M GRF by rat anterior pituitary cells in monolayer culture. These data suggest that melatonin plays a facilitatory role in the neuroregulation of GH secretion, probably by acting at the hypothalamic level.