Biomedical subjects
Publications and source records attributed to E Whitehead.
The relationship between serum and saliva paracetamol concentrations was investigated in twenty healthy volunteers. The plasma and saliva drug concentrations showed a significant correlation (r = 0.67). However the agreement between the two methods of measurement was poor with limits of agreement of -15.3 mg l-1 to +15.9 mg l-1 with mean sample values of 19.2 and 19.5 mg l-1 for plasma and saliva, respectively.
In this study we compared low (125 micrograms) and conventional (500 micrograms) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity. Following a two week placebo run-in period, 8 healthy male volunteers received 125 micrograms or 500 micrograms of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2. The 500 micrograms dose of cyclopenthiazide had a greater effect than the 125 micrograms dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II. Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers.
Ropivacaine 0.5%, 0.75% and 1.0% was investigated in an open study of extradural anaesthesia in three groups of 15 patients undergoing urological or orthopaedic surgery. Following a test dose of 3 ml of 1.0% lignocaine with 1:200,000 adrenaline, ropivacaine 20 ml was given in incremental doses over 4 min via a lumbar extradural catheter. The onset time for analgesia was short in all groups: T12 was blocked 4-6 min after the end of the injection of ropivacaine. The maximum segmental level was significantly higher in the 0.75% and the 1.0% groups (T2) than in the 0.5% group (T5). Complete motor block was obtained in seven, four and nine patients in the 0.5%, 0.75% and the 1.0% groups, respectively. Duration of analgesia increased with increasing concentration of ropivacaine: mean duration of analgesia was 203 and 266 min at T10 and 253 and 314 min at L5 for the 0.5 and 1% solutions, respectively. Mean duration of complete motor block was 94 and 192 min for the same solutions. Analgesia was satisfactory for surgery in all patients except for one in the 0.75% group. Hypotension was experienced by three, seven and three patients in the 0.5%, 0.75% and 1.0% groups, respectively. Bradycardia occurred in seven patients and was associated with hypotension in five. Backache was experienced after operation by four patients, and three patients complained of a brief mild headache. No late adverse events were seen.
Malignant melanoma of the larynx is a rare tumour. Only 31 cases of primary laryngeal melanoma have been reported in the literature. Cady et al., (1968) found only four cases in a group of 2,500 cases of laryngeal cancer seen over a 25-year period. A case of primary malignant melanoma of the larynx is presented along with a review of the literature. Problems associated with histological diagnosis are discussed. This patient was regarded as a poor risk for laryngectomy and appears to have control of local disease following application of Carbon dioxide laser.
Testicular function was studied in three groups of patients previously treated for malignant disease, and a control group of adult males. The adult patients in groups one and two underwent unilateral orchidectomy for a testicular tumour but only in group two was this followed by post-operative high-dose irradiation (30 Gy) to the remaining testis. Four of the five boys in group three had a unilateral orchidectomy between the ages of 1 and 4 years and all five received a similar dose of irradiation (27.5-30 Gy) to the scrotum as in group two. The five subjects in group three were studied between the ages of 12 and 34 years. In group one the median basal testosterone level (16.0 nmol/l) was normal and the basal gonadotrophin levels mildly but significantly increased, reflecting a resetting of the pituitary-testicular axis following unilateral orchidectomy. In group two the median basal testosterone level (12.5 nmol/l) was significantly lower and the median basal FSH and LH levels were significantly higher than the respective values in group one, indicating that irradiation to the testis in adult life may damage both the germinal epithelium and the Leydig cells. All five males in group three showed grossly increased FSH and LH levels, with a median basal testosterone level (less than 2.5 nmol/l) significantly lower than groups one and two. None of the five showed a testosterone response to a stimulation test with human chorionic gonadotrophin or underwent puberty spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
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Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)
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Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.
The effects of Hodgkin's disease and quadruple chemotherapy on gonadal function have been investigated in 92 male patients with Hodgkin's disease. Nineteen men were studied before they received chemotherapy. Fifteen of the 19 had a sperm count of 20 million/ml or greater and motility was at least 40% in all 15. In the remaining 74 men, gonadal function was studied after completion of chemotherapy (6 months--8 years). Semen was obtained from 49 men who had received six of more courses of MVPP. Forty-two were azoospermic and five of the remaining seven had a sperm count below 1 million/ml. Decreased libido and sexual activity was common during treatment but in the majority of men these returned to normal after completion of chemotherapy. The median FSH and LH levels and the median increments in serum FSH and LH levels after LHRH administration were significantly elevated compared with an age-matched control group. The mean testosterone level of the patients was significantly lower than in controls suggesting Leydig cell damage but androgen replacement therapy was not indicated in any individual patient. No evidence of hyperprolactinaemia as a result of MVPP therapy was found. These results suggest that sperm storage before chemotherapy represents the main possibility for these patients to have children after completing chemotherapy. Before starting chemotherapy, advice should be given to these patients concerning possible changes in sexual behavior during treatment and the very high incidence of permanent infertility following treatment.
The effect of quadruple chemotherapy (mustine, vincristine, procarbazine, and prednisolone) on gonadal function was investigated in 15 males and 2 females treated for Hodgkin's disease during childhood. The 2 females have regular menstrual cycles with evidence of ovulation in one. Twelve of the males have shown normal progression of pubertal development since completing their treatment. Nine out of 10 late pubertal or adult subjects had small testes but only one developed gynaecomastia. All 4 prepubertal subjects had normal basal and peak gonadotrophin responses to luteinising hormone-releasing hormone. Nine of the 12 subjects studied during puberty or adulthood had either an increased basal serum follicle-stimulating hormone (FSH) level or an exaggerated FSH response to luteinising hormone-releasing hormone. Each of the 6 males who provided semen for analysis was azoospermic after an interval of between 2.4 and 8 (mean 5.3) years after completion of treatment. We conclude that severe testicular damage is common after treatment with mustine, vincristine, procarbazine, and prednisolone in childhood. The germinal epithelium is particularly vulnerable and the resultant azoospermia is likely to be irreversible. The Leydig cells are less susceptible to cytotoxic-induced damage. Pubertal development is normal and there is no indication for androgen replacement therapy.
The effects of growth hormone (GH) therapy were studied in 6 children, previously treated for brain tumours which did not directly involve the hypothalamic-pituitary axis, and who had received cranial irradiation between 2.1 and 10 years earlier. All 6 were short with a standing height standard deviation score (SDS) from -1.7 to -3.3. Impaired growth hormone responses to an insulin tolerance test (ITT) were observed in all 6 and to a Bovril stimulation test in 5 children. The remainder of pituitary function was essentially normal. All 6 were prepubertal and 5 had a retarded bone age. During the pre-treatment year the 6 children's growth rates varied fom 2.0 to 5.1 cm. Subsequently all received human GH in a dose of 5 units 3 times weekly for 1 year. The growth rate in each was at least 2 cm greater during the treatment year than the pre-treatment year. Growth during the treatment year ranged from 6.0 to 10.1 cm. In 5 of the 6 the improvement in growth rate could be totally ascribed to the GH therapy. In the sixth there was significant pubertal maturation during the treatment year and only in this subject did the bone age advance at a significantly greater rate than the chronological age.
Pituitary function was assessed in 39 patients with previously untreated hyperprolactinaemia. Primary hypothyroidism, drug-induced hyperprolactinaemia and chronic renal failure were excluded in all patients. All of the 22 patients (group 1), who had either a normal pituitary fossa or a minor radiological change on lateral skull X-ray, had completely normal pituitary function with the exception of 2 who were partially growth hormone-deficient. However, 9 of the 17 patients with macroadenomas (group 2) had a deficit of one or more anterior pituitary hormones. After the lateral skull X-ray 13 patients in group 1 had further neuroradiological investigations. In only one was a minor abnormality noted which had not been observed on the plain film and this was not of practical significance. In centres where hyperprolactinaemic patients with a normal pituitary fossa or a minor radiological change on lateral skull X-ray are treated with bromocriptine, further neuroradiological investigations and dynamic tests of pituitary function are not required.
A gas-liquid chromatographic (GLC) method for determining residues of the inseticide-acaricide Supracide (S-[5-methoxy-2-oxo-1,3,4-thiadiazol-3(2H)-yl)-methyl]O,O-dimethyl phosphorodithioate) and its monoxone metabolite in safflower seed, meal, and oil is presented. Supracide and its monoxone metabolite are separated by partitioning with acetonitrile-sodium sulfate and petroleum ether. The petroleum ether fraction containing the Supracide is extracted with acetonitrile and further cleaned up on Florisil column before determination by GLC, flame photometric detection (FPD). The monoxone metabolite is partitioned from the acetonitrile-sodium sulfate fraction with chloroform and cleaned up on a Florisil column before GLC/FPD. Average Supracide recoveries were 86, 82.5, and 92%, and average Supracide monoxone recoveries were 85.7, 81.5, and 89%, in seed, meal, and oil, respectively. The limit of detection was 0.005 ppm for both compounds on all tissues analyzed.
The ATP-dependent exonuclease V from Micrococcus lysodekticus shows a Michaelian relation between steady-state velocity and the concentration of T7 DNA substrate. The Km (expressed as a mass concentration) does not change when the T7 DNA is broken into smaller fragments by a restriction enzyme. This is interpreted to mean that the predominant process by which the exonuclease-V--DNA complex breaks down is digestion of the entire DNA molecule rather than physical dissociation, in accord with the already known processive nature of degradation by this enzyme. The way that the V and Km towards DNA vary with ATP and ADP concentration suggests that enzyme-DNA complex is predominantly formed by reaction of DNA with an enzyme-ATP complex rather than with bare enzyme.
A method is described for the isolation of heteropolysaccharides from human supragingival calculus. One component was identified as hyaluronic acid, by electrophoretic mobility, testicular hyaluronidase digestion and cetylpyridinium chloride profiles. No sulphated glycosaminoglycans were detected.
The combination trimethoprim-sulfamethoxazole was given in high dosage (four tablets twice daily) for either 2 or 5 days to 20 patients with sinusitis diagnosed on clinical grounds. In 11 the infection was improved or cured. Swabs cultured from 18 patients of the series produced no growth in 8. The organisms most likely to be isolated are Hemophilus influenzae and Diplococcus pneumoniae.