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Biomedical subjects

N S Brown

Publications and source records attributed to N S Brown.

At least 37 records · Page 2Linked to original sources
PubMed1991

Safe, stable, whole blood samples for quality assessment of glucose measurement by non-laboratory staff.

A whole blood control material has been used to assess the analytical performance of non-laboratory staff who use glucose meters in clinical areas. It is prepared from sterile horse blood which is readily available from a commercial source. There are no known infection or disease transmission risks to users. When the material is stabilized by the addition of sodium fluoride less than 3% loss of glucose over 48 h is observed from an initial value of 10 mmol/L. However, we prefer to stipulate that the glucose is measured on the day of receipt. The material has been used successfully with Reflolux IIM meters and B-M sticks (Boehringer Mannheim, UK) for over a year in our hospital.

Animals↗
PubMed1990

Klüver-Bucy syndrome and psychiatric illness.

A 52-year-old woman, whose initial psychiatric presentation at the age of 15 was with a disorder resembling schizophrenia, developed symptoms of Klüver-Bucy syndrome, and is now thought to suffer from an organic psychotic disorder. Klüver-Bucy syndrome must be distinguished from symptoms of schizophrenia or affective disorder; its presence suggests an organic process.

Affective Symptoms↗
PubMed1989

A comparison of the effects of tetraplatin and cisplatin on renal function and gentamicin pharmacology in rats.

Tetraplatin (tetrachloro[d,l-trans]1,2-diaminocyclohexane platinum IV (TTP)) is a new platinum analogue active against L1210 murine leukemia that is resistant to cisplatin (diamminedichloroplatinum II (DDP)). Since nephrotoxicity is a significant problem with DDP therapy, we compared the effects of equitherapeutic doses of TTP and DDP on renal structure and function in rats. We also studied the effects of the 2 platinum compounds on the distribution and excretion of gentamicin (GENT), an antibiotic that is excreted solely by the kidneys. Rats treated intravenously with 2.85 mg/kg of DDP on days 1, 5 and 9 had significantly different plasma urea nitrogen (BUN) levels and creatinine clearance rates on day 16 than those given the same doses of TTP. The renal function of TTP-treated rats did not differ from that of controls or rats given only GENT. Twenty-four hours after a single GENT dose (given on day 15), DDP-treated rats had higher GENT concentrations in the plasma, liver and spleen than rats given GENT alone. TTP-treated rats had higher GENT levels only in the spleen. DDP-treated rats retained a higher percentage of the injected platinum in the renal cortex than those treated with TTP. Light microscopic examination of renal tissue showed necrotic cells and dilated tubules in the proximal tubules of DDP-treated rats while the kidneys of TTP-treated rats were largely indistinguishable from those of controls. Thus, our results indicate that the distribution of platinum in the kidneys differs between rats treated with TTP and those treated with DDP. This may partly explain the considerably lower nephrotoxicity of TTP.

Animals↗
PubMed1989

Metabolism and disposition of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide Hcl (LY 195448) in rodents.

The disposition and metabolism of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide HCl, or LY 195448 (LY), were studied in rodents 1 hr following a single iv injection of 14C-LY at 30 mg/m2 (10 mg/kg mice and 5 mg/kg rats), In all tissues and carcases, recovery of 14C was nearly complete. The majority of radioactivity was recovered from intestine (40%) whereas liver and urine accounted for 10% each, kidney for 3-5%, and plasma for 1-3% of total administered radioactivity. Analyzing by HPLC and TLC, para-hydroxy-LY (para-OH-LY) in addition to unchanged drug, was found in all tissues. Meta-OH-LY was detected only in urine, intestine and kidney. These metabolites were found to be conjugated with either glucuronide or sulfate moieties. Peaks coeluting with authentic para-OH-meta-methoxy-LY and di-OH-LY were also observed.

Animals↗
PubMed1985

Radioimmunoassay for etoposide and teniposide.

A radioimmunoassay for VP-16 or VM-26 was developed by using tritiated ligand and antisera produced from rabbits immunized with succinyl-VP-16 bovine serum albumin conjugates. Separate determinations of VP-16 and its hydroxy acid, a metabolite which cross-reacted with the VP-16 antisera, could be accomplished by extracting samples with chloroform in which the metabolite was insoluble. The assay was reproducible and sensitive. Extracted standard curves were linear from 0.025 to 5 micrograms for VP-16 and 0.1 to 10 micrograms for the hydroxy acid per 0.5 ml assay mixture. Fifty percent inhibition of binding was achieved at 0.066 and 0.55 microgram for VP-16 or VM-26 and the metabolite, respectively. Preliminary disposition studies in mice and dog, and human urinary excretion support the application of the assay in pharmacologic studies.

Animals↗
PubMed1983

Clonidine is a better test for growth hormone deficiency than insulin hypoglycaemia.

The oral clonidine test was compared with the standard intravenous insulin hypoglycaemia test in 41 children and adolescents with short stature. In those without growth hormone deficiency clonidine provoked a significantly higher mean plasma growth hormone response and gave fewer false subnormal responses (apparent growth hormone deficiency) than insulin. Children with psychosocial deprivation had poorer responses to both tests. In view of these findings and the absence of unacceptable side effects with clonidine it is concluded that the oral administration of this alpha-adrenergic stimulant is a safe and reliable alternative test of growth hormone release.

Adolescent↗
PubMed1982

Does calcitonin cause hypocalcaemia after thyroidectomy?

Plasma calcitonin, parathyroid hormone, total thyroid hormones and calcium were measured in 6 patients before, during and after thyroidectomy for hyperthyroidism. In 4 patients, plasma calcium fell postoperatively by 0.23--0.46 mmol/l, but there was no change in calcitonin or parathyroid hormone levels. In one patient, in whom there was a postoperative fall in plasma calcium of 0.55 mmol/l, thyroid hormones rose to a peak at 1 h and calcitonin to a peak at 12 h after resection. However, the rise in calcitonin occurred 8 h after the initial decrease in plasma calcium. In this patient, parathyroid hormone levels showed a slight rise only. It is concluded that, while thyroid hormones and calcitonin may leak from the damaged thyroid remnant after surgery, it is unlikely that calcitonin is important in the production of postoperative hypocalcaemia. However, impaired parathyroid hormone secretion may be a contributing factor.

Adolescent↗
PubMed1982

Clinical pharmacology of bruceantin by radioimmunoassay.

During the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2 beta) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2 beta on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration X time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

Antineoplastic Agents, Phytogenic↗
PubMed1982

Postoperative glucose tolerance during extradural analgesia.

Thirteen patients undergoing lower abdominal gynaecological surgery were allocated to general anaesthesia (halothane and nitrous oxide) or general anaesthesia plus extradural analgesia (T8-S5). I.v. glucose tolerance tests were performed on the day before surgery and 8 h after skin incision. All patients having extradural analgesia (T8) were pain-free following surgery. Extradural analgesia blocked the hyperglycaemic response to surgery but not the late postoperative cortisol response, although values were significantly less than in the group receiving general anaesthesia alone. Impairment of glucose tolerance and of insulin response to the glucose load in the period after operation were not influenced by extradural analgesia and this may have resulted from insufficient inhibition of the stress-induced release of catecholamines or cortisol, or both, or from blockade of stimulatory efferent sympathetic pathways to pancreatic islets.

Adult↗
PubMed1982

What is the significance of raised plasma TSH levels after thyroid surgery?

Thyroid function was assessed prospectively for five years in 73 patients treated surgically for Graves's disease. No patient developed hypothyroidism after the sixth postoperative month, despite the presence of raised plasma TSH levels in 70 per cent of euthyroid patients at the end of the first year. Indeed, in those with evidence of temporary hypothyroidism (low T4, raised TSh at 3 months but normalisation of T4 at 6 months) plasma TSH continued to fall for up to three years. The majority (6) of patients developing recurrent hyperthyroidism did so within the first year, but in one of three patients who relapsed subsequently, plasma TSH had been elevated at one year. Plasma TSH cannot be used to predict thyroid status following surgery for Graves' disease. Although regular review remains necessary, it should not include measurement of TSH unless this is needed to confirm the validity of a low thyroxine level after the third postoperative month and before starting permanent replacement therapy.

Adult↗
PubMed1982

Effect of ECT on the neuroendocrine response to apomorphine in severely depressed patients.

Animal studies have suggested that the mechanism of the antidepressant action of ECT may be to increase monoaminergic post-synaptic receptor sensitivity. We have tested this hypothesis in 12 drug-free patients suffering from severe depression, 11 of whom had depressive delusions. The responses of growth hormone, prolactin and cortisol to 0.75 mg subcutaneous apomorphine were examined before and after a successful course of ECT. There were no significant differences between hormonal measurements on the two occasions, with the exception that basal plasma cortisol concentrations were significantly lower following ECT and recovery from depressive illness. These results do not support the hypothesis that ECT increases dopaminergic post-synaptic receptor sensitivity.

Adult↗
PubMed1982

Prolactin response to metoclopramide in hyperthyroidism.

The response of PRL to the oral administration of the dopamine receptor-blocking agent metoclopramide and the effect of metoclopramide on the TRH-induced release of PRL and TSH were measured in eight patients with hyperthyroidism and in eight age- and sex-matched euthyroid controls. As expected from the known direct inhibitory influence of thyroid hormones on pituitary TSH secretion, there was no TSH rise in response to metoclopramide in either group. PRL levels, on the other hand, rose significantly after the administration of metoclopramide in both the hyperthyroid and euthyroid subjects (P less than 0.0005 at 60 and 120 min). However, the increase in PRL at 120 min was significantly less in the hyperthyroid subjects than in the euthyroid controls (P less than 0.0025). Furthermore, the administration of metoclopramide failed to reestablish normal responsiveness of either PRL or TSH to TRH in the hyperthyroid subjects. We have previously suggested that thyroid hormones inhibit PRL secretion by stimulating the hypothalamic secretion of dopamine. These results suggest, however, that elevated levels of thyroid hormones also inhibit PRL release directly at the anterior pituitary level.

Administration, Oral↗
PubMed1981

Searching for the infertile man with hyperprolactinemia.

The purpose of this study was to determine whether routine prolactin measurement was of use when investigating men with infertility. Prolactin levels were slightly higher in men with primary infertility, compared with men with secondary infertility and a fertile control group. Although this slight increase was statistically significant, most readings were within the laboratory normal range in all groups, and we did not find any clinically significant cases of hyperprolactinemia. We conclude that routine prolactin estimation is not justified unless there are other indications, e.g., impotence, dialysis, or a history of previous pituitary disease.

Adult↗
PubMed1981

The effect of bromocriptine on insulin secretion and glucose tolerance in patients with acromegaly.

The oral administration of bromocriptine 5 mg 6-hourly to twelve patients with acromegaly for a mean period of 12 (range 3-27) months significantly reduced whole blood glucose, plasma insulin and plasma growth hormone (GH) concentrations during a 50 g oral glucose tolerance test (OGTT). After this period of treatment, bromocriptine was withdrawn for 48 h resulting in a significant rise in whole blood glucose, plasma insulin and plasma GH concentrations during a repeat OGTT. It is concluded that bromocriptine therapy improves glucose tolerance in acromegaly by suppressing GH secretion and consequently GH-mediated antagonism of insulin.

Acromegaly↗
PubMed1981

Sensitive radioimmunoassay for vancomycin.

A radioimmunoassay for vancomycin has been developed which uses rabbit antiserum induced by vancomycin-bovine serum albumin conjugates and vancomycin labeled with 3H or 125I. Using either isotope, the method is simple and reproducible and has a sensitivity of 4 or 0.04 ng/ml, depending on the tracer used. This is 200- to 20,000-fold improvement in sensitivity compared with the most sensitive bioassay. Drug levels in serum or urine samples from patients receiving vancomycin can be determined by this assay procedure without processing. The data obtained with 3H and 125I labels were in good agreement. Patients' plasma vancomycin concentrations determined by radioimmunoassay correlated well with those determined by bioassay when the drug was administered intravenously. However, after oral administration the drug could be detected only by radioimmunoassay. The antiserum was evaluated for cross-reactivity with a wide variety of antibiotics and cancer chemotherapeutic agents, and no significant interference was found.

Animals↗
PubMed1981

Pharmacokinetics of cefoperazone in patients with neoplastic disease.

The pharmacokinetics of cefoperazone, a new semisynthetic cephalosporin, were studied in 34 patients with neoplastic disease. This compound was administered in a variety of doses and schedules without observable toxicity in any patient. The mean peak serum concentration after a 15-min intravenous infusion of 2 g was 264 microgram/ml after the first dose; the serum half-life was 2.1 h. There was no significant change in half-life or serum concentrations after 4 or 7 days of therapy. The mean peak serum concentration after infusion of 1 g over 15 min was 133 microgram/ml, with a mean of 10.7 microgram/ml at 6 h. The serum half-life was 2 h. The mean peak serum concentration after infusion of 1 g over 0.5 h was 101 microgram/ml. When 8 g was subsequently administered daily by a continuous infusion schedule, levels were maintained at 80 microgram/ml. When the dose was increased to 16 g daily, serum concentrations were maintained at an average of 153 microgram/ml. Only 37% of cefoperazone was recovered in the urine in a 12-h period after the initial dose, suggesting the importance of other mechanisms of excretion; however, serum concentrations in one patient with renal insufficiency were significantly higher than serum concentrations in patients with normal renal function.

Adolescent↗