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Biomedical subjects

J Feely

Publications and source records attributed to J Feely.

At least 163 records · Page 9Linked to original sources
PubMed1980

Influence of surgery on plasma propranolol levels and protein binding.

The influence of surgery and anesthesia on perioperative plasma propranolol levels was studied in 25 hyperthyroid and five euthyroid patients undergoing thyroidectomy. Propranolol levels fell markedly after surgery as a consequence of poor drug administration in the immediate postoperative period due largely to patients' nausea and inability to swallow. Propranolol was not detectable in the plasma of three hyperthyroid patients 8 hr after surgery. When propranolol was given through a nasogastric tube, propranolol levels were satisfactory throughout. Compared with preoperative levels, in all patients there was a two- to threefold rise in total and free propranolol levels 24 hr after surgery, suggesting decreased hepatic clearance of propranolol. The degree of plasma protein binding of propranolol had also increased on the day after surgery, leading to a 30% reduction in propranolol free fraction. Surgery and anesthesia greatly influence the handling of propranolol in the perioperative period.

Absorption↗
PubMed1980

Propranolol dosage in thyrotoxicosis.

Eighteen thyrotoxic patients receiving chronic treatment with propranolol (160 mg/day) were studied to determine the relationship between plasma propranolol concentration and drug effect. There was a considerable interindividual variability in both the plasma propranolol steady state concentration and the degree of beta-adrenergic blockade. The plasma propranolol steady state concentration correlated significantly with both beta-adrenergic blockage and weight change but not with the degree of subjective improvement. In a group of 40 patients, including 10 severely thyrotoxic patients, who had the dosage of propranolol titrated objectively preoperatively to bring about a greater than 25% reduction in exercise heart rate at the end of a dosage interval, no case of thyroid storm was encountered. Many patients, the younger and severely thyrotoxic in particular, require doses in excess of 160 mg/day to achieve this degree of beta-adrenergic blockade.

Adolescent↗
PubMed1980

Hyperthyroidism in the land of Graves: results of treatment by surgery, radio-iodine and carbimazole in 837 cases.

A review of the outcome of treatment by subtotal thyroidectomy, radio-iodine and carbimazole of 837 patients with hyperthyroidism seen consecutively over the period 1954--78 inclusive is presented. The age and sex distribution, the male to female ratio, the ABO blood group distribution and the prevalence of pernicious anaemia and diabetes mellitus in these patients was also analysed. Life-table data showed that the five-year and ten-year cumulative relapse rates following a two-year course of carbimazole (n = 162) were 56 per cent and 62 per cent; following surgery (n = 266), 6 per cent and 10 per cent and following radio-iodine (n = 43), 3 per cent and 14 per cent. Five-year and ten-year cumulative hypothyroid rates after surgery were 10 per cent and 18 per cent, and after radio-iodine 10 per cent and 30 per cent. Hypothyroidism did not occur after carbimazole therapy. Of 31 patients who took carbimazole for less than two years (mean 11 months, range 6--19 months), 91 per cent had relapsed at five years. Of 79 patients treated for longer than two years (mean 3.8 years, range 2 1/2--14 years), relapse rates at five and eight years were 49 per cent and 62 per cent. Nine patients (3.4 per cent) suffered permanent vocal cord paralysis and five (1.9 per cent) had permanent hypocalcaemia. The male/female ratio was 9.9 to 1, with a peak female prevalence between 25 and 30 years and a peak male prevalence between 40 and 45 years. The ABO blood group distribution among patients did not differ significantly from the distribution in the general population (chi 2 = 13.4, p = 0.2). Forty-seven patients (5.6 per cent) had diabetes mellitus and thyrotoxicosis whilst two patients (0.23 per cent) had diabetes, thyrotoxicosis and pernicious anaemia.

ABO Blood-Group System↗
PubMed1979

Propranolol, triiodothyronine, reverse triiodothyronine and thyroid disease.

Propranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1-2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.

Adolescent↗
PubMed1979

The physiology of thyroid function in pregnancy.

Pregnancy has a variety of effects on maternal thyroid function. Thyroid gland enlargement is common particularly in areas of relative iodine deficiency. The renal clearance of iodine is increased in pregnancy and together with an increased volume of iodine distribution, leads to a low plasma inorganic iodine and thus increases the thyroidal iodine clearance. However, the absolute iodine uptake and hormone production rate remain unchanged. There is an increase in the serum thyroxine (T4)and triiodothyronine (T3) concentration largely due to an increase in thyroid hormone-binding proteins. Free thyroxine and free T3 remain unchanged in pregnancy as does the Free Thyroxine Index, which gives the single most accurate measure of thyroid function. The placenta secretes a number of thyroid stimulators including human chorionic gonadotrophin and possibly chorionic thyrotrophin and molar thyrotrophin whose physiological role is to date poorly understood. The fetal thyroid develops independently, and although fetal T4 CONCENTRATION RISES PROGRESSIVELY To maternal by term, the T3 concentration is markedly reduced owing to preferential formation of inactive reverse T3.

Female↗
PubMedDate not supplied

Simple preparation of the major urinary metabolites of flunitrazepam and nitrazepam.

An alarming increase in the misuse/abuse of nitrobenzodiazepine derivatives, especially flunitrazepam, prompted us to establish reliable analytical protocols for their routine detection. Whilst the parent drugs are readily available from a number of commercial sources, it was found difficult to obtain samples of the corresponding amino metabolites which were required as analytical standards. This lead us to develop the straightforward synthetic protocol described here, to convert the readily available parent drugs, namely flunitrazepam and nitrazepam, to their respective 7-amino derivatives. The method requires minimum laboratory facilities. It involves the reduction of the nitro functionality in the parent drug to an amino group using tin (II) chloride under mild conditions, using ultrasonication at room temperature. The method is simple and should give toxicology laboratories better access to these much needed compounds.

Anti-Anxiety Agents↗
PubMedDate not supplied

Ethnic differences in the frequency distribution of serum cholinesterase activity.

We studied the activity of the enzyme pseudocholinesterase (serum cholinesterase) and its sensitivity to inhibition by dibucaine and fluoride in 400 (200 Iranian and 200 Irish) healthy subjects. The results show Irish subjects have significantly higher serum cholinesterase activity than Iranian subjects (7.82 +/- 0.14 vs 5.22 +/- 0.09 u/ml, mean +/- SEM, p < 0.01). Furthermore, the percent of inhibition of enzyme activity by dibucaine (82.19 +/- 0.68 vs 69.29 +/- 0.68) and fluoride (79.90 +/- 70.13 +/- 0.62) was also significantly higher (p < 0.001) in Irish than in Iranian subjects. One subject (Iranian) with very low pseudocholinesterase activity and a dibucaine number below 20 (atypical) had a history of apnoea following succinylcholine (suxamethonium). These data indicate that the frequency of atypical and heterozygote genes for cholinesterase activity leading to prolonged apnoea is much higher in Iranian than Irish populations. This study emphasises the importance of ethnic pharmacology.

Adult↗
PubMedDate not supplied

Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.

Lipid peroxidation is a free radical process which is implicated in the formation of atherosclerosis. Vitamins C and E are important natural antioxidants which inhibit lipid peroxidation and a high intake of these vitamins, particularly vitamin E, is related to a reduced incidence of ischaemic heart disease. Hypertension is an independent risk factor for atherosclerosis and its relationship to antioxidant status is undetermined. In this study, we investigated free radical activity by measuring plasma malondialdehyde (MDA) using high-performance liquid chromatography (HPLC), vitamin C status measured as plasma ascorbic acid and vitamin E status measured as plasma lipid standardized alpha-tocopherol and erythrocyte alpha-tocopherol. We compared 28 patients with essential hypertension to 31 healthy subjects. Results showed that in comparison with the healthy subjects, the hypertensive patients had significantly higher plasma MDA levels (0.95 +/- 0.28 vs 0.69 +/- 0.21 mumol/l, mean +/- SD, p < 0.001) and significantly lower levels of plasma ascorbic acid (34.83 +/- 12.88 vs 51.76 +/- 13.34 mumol/L, p < 0.01). In addition, erythrocyte alpha-tocopherol concentration, which may reflect vitamin E protection in cell membranes, was significantly lower in hypertensive patients when compared with the normotensive controls (3.87 +/- 0.53 vs 4.82 +/- 1.01 mumol/l, p < 0.001), although plasma alpha-tocopherol levels were similar in the two groups (25.07 +/- 10.45 vs 23.96 +/- 6.07 mumol/l). Our results suggest that hypertensive patients may have increased lipid peroxidation and reduced protection from vitamins C and E. This may contribute to the propensity in such patients to develop atherosclerosis.

Adult↗
PubMedDate not supplied

Underreporting of adverse drug reactions: attitudes of Irish doctors.

Despite the fundamental importance of reporting of suspected adverse drug reactions, less than 10 per cent of serious adverse drug reactions are reported. To further enhance our understanding of doctors' knowledge and attitudes to the current Adverse Drug Reaction (ADR) reporting scheme we surveyed 158 doctors, including some 106 general practitioners and 23 hospital-based doctors. The response rate was 39.5 per cent. The majority had experience of reporting an ADR. Seriousness of the ADR appears to be the most important reason for reporting. Uncertainty that the adverse drug reaction was definitely caused by the medicine, that the adverse drug reaction was too trivial to report or that it was too well known a reaction to report are common reasons for not reporting. Of concern 84 per cent of doctors are unaware of the criteria of the National Drug Regulatory Agency indicating the need for additional education and information in this regard. We also found considerable disagreements in doctors' understanding of the meaning of common, occasional, rare, or very rare as applied to ADRs.

Adverse Drug Reaction Reporting Systems↗