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Biomedical subjects

J Seth

Publications and source records attributed to J Seth.

17 recordsLinked to original sources

Dietary modulators of lipid metabolism in the Indian diet-heart study (I.D.H.S.).

Of the 621 adults (25 to 65 years of age, 531 males) with either risk factors or with coronary heart disease (CHD) 310 subjects were given a cardiovasoprotective (CVP) diet (group A) and 311 subjects a normal diet (group B) in a randomized, single blind and controlled fashion. Risk factors and incidence of CHD were comparable between the two groups. The intervention group received a significantly higher percentage of calories in relation to complex carbohydrates, vegetable proteins, polyunsaturated fatty acids and high P:S ratio diet as compared to the control group. The control group received higher saturated fat and cholesterol. Compliance was assessed by dietary questionnaire during the follow-up. After 8 weeks of dietary trial, there was a significant decrease in mean serum total cholesterol (8.2 vs 2.1%), low density lipoprotein (LDL) cholesterol (9.8 vs. 2.7%) and triglyceride (11.2 vs 5.8%) in the intervention group compared to baseline levels and changes in control subjects. Body weight and physical activity at the entry to study and during the trial were similar in both groups. The decrease in mean HDL cholesterol were insignificant both in the intervention (4.3%) and control group (5.0%). There were no adverse effects of diet during the 8 weeks of trial. It is possible that a diet with 27.5% energy from total fat including 10.1% energy from monounsaturated fatty acids, P:S ratio 1.38, 120 mg dietary cholesterol, 26.0 g dietary fibre per 1000 kcal would modulate the lipid metabolism resulting in a significant reduction in serum total cholesterol, LDL cholesterol and triglyceride with no reduction in HDL cholesterol. This diet may be capable of reducing CHD incidence and mortality in the long term Indian diet-heart study (IDHS).

Adult

Failure of the TRH test to predict the clinical course of patients in remission after antithyroid drug therapy for Graves' disease.

In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.

Adult

How often should patients be reviewed after treatment with iodine-131 for thyrotoxicosis?

Six to 18 years after treatment with iodine-131 for thyrotoxicosis 69 euthyroid patients with raised serum thyrotrophin (TSH) concentrations (mean 25.0 +/- SE 2.0 mU/l) and 61 with normal concentrations (mean 4.0 +/- 0.2 mU/l) were included in a prospective five-year follow-up study beginning in 1972. During this period 13 patients from the original group with raised serum TSH concentrations became hypothyroid. In contrast it was five years before hypothyroidism developed in a single patient from the group with normal serum TSH concentrations in 1972, although raised concentrations were recorded in 19 of these patients during the study.

Aged

A simple radioimmunoassay for plasma cortisol.

A simple radioimmunoassay (RIA) for plasma cortisol is described which combines the advantages of (i) direct analysis of untreated plasma samples, (ii) use of solid-coupled anti-cortisol antibodies and (iii) use of a gamma-labelled radioligand. The reagents are relatively easily prepared and stable, and the analysis can be completed in 4 h. Inter-assay precision (C.V.) is 8-11%. Critical examination of specificity using high pressure liquid chromatography showed that 23-35% of the immunoassayable material in plasma was not cortisol. RIA results on samples collected under basal conditions were on average 40 nmol/l lower than fluorimetric results, while in insulin hypoglycaemia and synacthen (ACTH) stimulation tests, this difference increased to over 100 nmol/l. The RIA is technically more simple than fluorimetric, competitive-protein-binding, and many RIA methods, and can be used with advantage in the routine investigation of adrenocortical function. However, using the present antiserum, the RIA is not applicable to investigations on patients receiving metyrapone, nor in suspected cases of congenital adrenal hyperplasia.

Animals

Thyroid function after surgical treatment of thyrotoxicosis. A report of 100 cases treated with propranolol before operation.

We assessed thyroid function for 12 months after subtotal thyroidectomy in 100 tyrotoxic patients treated with propranolol alone before and immediately after operation. The operation proved safe, with low morbidity. Suppression of the hypothalamic-pituitary-thyroid axis, present in the majority one month after operation, was evidenced by normal or low levels of serum total tri-iodothyronine and thyroxine, but absent or subnormal serum thyrotropin response to thyrotropin-releasing hormone. Eighty patients were euthyroid at 12 months. Three patterns of thyroid function were observed in this group between the first and 12th months: normal serum total tri-iodothyronine, thyroxine and thyrotropin levels at all stages (20 patients); normal serum total tri-iodothyronine and thyroxine, but raised thyrotropin levels on one or more occasions (40 patients); and temporary hypothyroidism (20 patients). Of the remaining 20 patients, permanent hypothyroidism developed in 14, and six relapsed. Postoperative thyroid function was related to the estimated weight of the thyroid remnant.

Adult

Spectrum of thyroid function in patient's remaining in remission after antithyroid drug therapy for thyrotoxicosis.

Thyroid function was assessed in 110 patients who were in remission for a period of 7-6 +/- 0-6 years (mean +/- S.E.) (range 0-25--25 years) after the withdrawal of antithyroid drug therapy for thyrotoxicosis. On the basis of clinical examination and on the results of thyroid-function tests, the following group of patients were identified: (I) euthyroid with normal plasma-total thyroxine (T4) and triiodothyronine (T3) concentrations, but an absent or subnormal response of plasma-thyrotrophin (T.S.H.) to thyrotrophin-releasing hormone (T.R.H.) (16%); (II) euthyroid with normal concentrations of plasma total T4 and T3 and a normal plasma-T.S.H. response to T.R.H. (59%); (III) euthyroid with normal concentrations of circulating thyroid hormones and a normal basal plasma-T.S.H., but an exaggerated plasma-T.S.H. response to T.R.H. (13%); (IV) euthyroid with normal plasma total T4 and T3 concentrations, but a raised basal plasma-T.S.H. concentration and an exaggerated plasma-T.S.H. response to T.R.H. (6%); (V) hypothyroid (6%). Although the need for short-term follow-up to identify those patients treated with antithyroid drugs who will relapse is well recognised, 16% of all patients in remission for longer than 4 years (10-8 +/- 0-7 years) in the present study showed some degree of thyroid failure. Evidence of hypothyroidism was associated with an increased frequency of thyroid microsomal antibodies. If the morbidity of the late development of hypothyroidism is to be avoided, patients who have been treated with antithyroid drugs should have long-term follow-up, as do patients treated surgically or with radioiodine.

Antithyroid Agents

Temporary hypothyroidism after surgical treatment of thyrotoxicosis.

Mild clinical hypothyroidism associated with low levels of serum total thyroxine (T4) and tri-iodothyronine (T3) and raised levels of serum thyroid-stimulating hormone (T.S.H.) has been observed in 14 of 40 patients (35%) in the early months after a subtotal thyroidectomy for thyrotoxicosis under cover of propranolol. In 10 of the patients, however, the hypothyroidism was temporary and at 6 months after operation the thyroid hormone levels were normal and the serum T.S.H. levels had fallen. In 4 of the patients in whom clinical and biochemical evidence of hypothyroidism persisted 6 months postoperatively, long-term T4 replacement therapy was instituted. It is concluded that the diagnosis of permanent hypothyroidism should not be made with confidence before 6 months have elapsed after operation and that the incidence of hypothyroidism following the surgical treatment of thyrotoxicosis may have been overestimated in the past.

Adult

Simple solid-phase radioimmunoassays for total tri-iodothyronine and thyroxine in serum, and their clinical evaluation.

1. Simple solid-phase radioimmunoassay methods for total tri-iodothyronine and thyroxine in serum or plasma are described. By using antibodies that are covalently coupled to microcrystalline cellulose, virtually identical assay procedures can be used for the determination of both hormones. An alkaline sodium glycinate buffer provides better assay conditions than the buffers often recommended for thyroid hormone radioimmunoassay. 2. Assay results are unaffected by moderate sample haemolysis. Plasma samples stored at room temperature for more than nine days often show an apparent increase in concentration of both thyroid hormones. 3. Serum tri-iodothyronine and thyroxine concentrations in healthy euthyroid subjects, and in euthyroid pregnant women are reported. In a series of 100 consecutive patients referred to a thyroid clinic the tri-iodothyronine assay discriminated better than the thyroxine assay between hyperthyroid and euthyroid patients. The thyroxine assay was much better than the tri-iodothyronine assay in discriminating between hypothyroid and euthyroid patients.

Anilino Naphthalenesulfonates

Hypothalamic/pituitary/adrenal function in patients treated with intermittent high-dose prednisolone and cytotoxic chemotherapy.

Hypothalamic/pituitary/adrenal (H.P.A.) function was assessed in ten patients receiving intermittent high-dose prednisolone and cytotoxic chemotherapy for myeloma of lymphoma in order to predict their possible requirement for additional steroid therapy between and at the end of treatment courses. Standard insulin hypoglycaemia tests performed 36 hours after the last dose of prednisolone often demonstrated impairment of corticotrophin (adrenocorticotrophic hormone, A.C.T.H.) and growth-hormone responses, indicating hypothalamic/pituitary suppression; plasma-corticosteroid responses to endogenous A.C.T.H. and tetracosactrin were abnormal in two patients, indicating secondary adrenal suppression. Such hypothalamic/pituitary and adrenal suppression may make these patients susceptible to acute adrenal insufficiency in times of stress. H.P.A. function should be fully assessed on completion of chemotherapy.

Adrenal Cortex Hormones

Propranolol in the treatment of thyrotoxicosis by subtotal thyroidectomy.

Subtotal thyroidectomy was performed in 40 patients with thyrotoxicosis in whom propranolol alone was used as preparation for surgery. Propranolol was given orally in a dose of 40 mg every 6 h for a mean preoperative period of 17 days (range 4-60 days) and continued for seven days after operation. The mean +/- SE blood loss at operation was only 160 +/- 20 ml. The period of follow-up was from three to nine months. Recurrent thyrotoxicosis has not occurred in any patient. Low levels of total serum triiodothyronine (T3) and total serum thyroxine (T4) were observed in the early postoperative weeks in some patients and were associated with symptoms of mild hypothyroidism, but by six months in the presence of a raised serum thyrotropin (TSH) the thyroid hormone levels returned to normal. Permanent hypothyroidism developed in only two patients. Despite normal or low total serum T3 and T4 levels, the TSH response to thyrotropin-releasing hormone (TRH) was absent in all patients one week after operation. At four weeks and at eight weeks, the response was absent or sub-normal in 70% and 20% of the patients respectively, indicating a delay in the recovery of the hypothalamo-pituitary axis previously exposed to high levels of T3 and T4. It is considered that subtotal thyroidectomy for thyrotoxicosis in patients prepared with propranolol is an acceptable procedure which has some advantages over the conventional preparation with carbimazole and potassium iodide, not the least of which are the potential reduction in preparation time, the more flexible timing of operation, and the reduced operative blood loss.

Female

Thyroid function in the long-term follow-up of patients treated with iodine-131 for thyrotoxicosis.

In February, 1972, 58% of patients euthyroid after iodine-131 therapy for thyrotoxicosis between 1954 and 1966 had a raised plasma thyroid-stimulating-hormone (T.S.H.) (greater than 7-4 mU/l) and 42% a normal T.S.H. level. A group of 69 of the euthyroid patients with a raised plasma T.S.H. (25-0 +/- 2-0 mU/l) in 1972 was re-examined annually for three years. There was no apparent change in the mean plasma T.S.H. level between 1972 and 1975 in the patients remaining euthyroid, but overt hypothyroidism developed in 3 patients in 1973, in a further 3 patients in 1974, and in 1 patient in 1975. In contrast, none of a group of 61 patients, euthyroid with a normal plasma T.S.H. (4-0 +/- 0-2 mU/l) in 1972, developed overt hypothyroidism over the next three years, although slightly raised T.S.H. levels were recorded in 3 patients in 1974 and in a further 6 patients in 1975. Both the mean serum T-4 and T-3 in the euthyroid patients with a raised plasma T.S.H. were significantly lower, but still in the respective normal ranges, than those in the euthyroid patients with a normal plasma T.S.H. No significant difference in the fasting serum-cholesterol or triglyceride levels could be demonstrated between the two groups. Since no patient with a normal plasma T.S.H. after iodine-131 treatment for thyrotoxicosis six to eighteen years earlier developed overt hypothyroidism over a three-year period, the follow-up of such patients need not be so frequent as that of similarly treated euthyroid patients with a raised plasma T.S.H. in whom overt hypothyroidism develops at the rate of 2-5% per year.

Cholesterol

Solid-phase radioimmunoassay of thyroxine in untreated serum.

We describe a simple, convenient solid-phase radioimmunoassay of total thyroxine in unextracted serum. Serum samples are added directly to the assay incubation mixture, interference in the antigen/antibody reaction by the thyroxine-binding serum proteins being almost completely eliminated by the addition of 8-anilino 1-naphthalene sulfonic acid and incubation at pH 10.5. Residual interference is compensated for by including thyroxine-free serum in the standards. Use of thyroxine antibodies that are coupled to a solid support permits separation of free and antibody-bound hormone by a single washing step, followed by centrifugation. The method is specific, accurate, and reasonably precise. The results obtained compare well with those for radioimmunoassay of thyroxine in serum freed of protein by gel filtration, and with results of a competitive protein-binding method. The technical simplicity of the procedure should readily permit automation. These features suggest that the technique should be well suited for routine clinical laboratory use.

Anilino Naphthalenesulfonates