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Biomedical subjects

C J Edmonds

Publications and source records attributed to C J Edmonds.

At least 37 records · Page 2Linked to original sources
PubMed1986

The long-term hazards of the treatment of thyroid cancer with radioiodine.

Two-hundred and fifty-eight patients treated with high-activity 131I for thyroid cancer and on prolonged follow-up have been reviewed to determine long-term hazards and their relation to the radiation dose received. The expectation of life of those dying from causes other than cancer was slightly reduced in the female patients. A small, significant excess of deaths from cancer of the bladder and from leukaemia was found which, assuming that these were due to radiation, gave inferred risk-rates respectively of 0.4 and 4.9 deaths per 10(4) PYG (patient-year-grays) to the bladder wall and red marrow. Of 31 younger patients (eight male, 23 female), four of the marriages have been infertile. The fertile marriages produced a total of 44 live births. Considerable gonad irradiation (estimated 0.8-2.7 Gy) was compatible with apparently normal fertility. Despite the high level of irradiation of the salivary glands, no malignancies and only one adenoma was found. Impaired pulmonary function occurred in only one of the patients who had diffuse bilateral metastases. In this patient, tumour in the lung was persistent throughout, so that radiation was probably not alone responsible.

Abdominal Neoplasms↗
PubMed1986

In-vivo studies of a human-thyrotrophin preparation.

The effects on thyroid function of a new preparation of human thyrotrophin (hTSH) were studied in four subjects whose endogenous production of TSH had been suppressed by administration of thyroxine (T4). The hTSH, prepared from human cadaveric pituitary glands and highly purified using a monoclonal antibody technique, was given as an intravenous bolus of 2 i.u. hTSH. Serum TSH levels rose rapidly to a maximum of about 150 mu./l and then declined exponentially with a half-life of 100 min. After injection, the hTSH distributed rapidly in a volume averaging about 13 litres which corresponded approximately to the expected extracellular fluid volume of the subjects. Serum free tri-iodothyronine and free T4 rose significantly, reaching a maximum between 4 and 8 h after injection of hTSH; serum thyroglobulin was not altered significantly. The rise of thyroid pertechnetate uptake, a measure of the thyroid iodide uptake, occurred later, being only slightly increased at 8 h after administration of hTSH and reaching a maximum at 24 h.

Adult↗
PubMed1985

Thyrotrophin receptors, tumour radioiodine concentration and thyroglobulin secretion in differentiated thyroid cancers.

Tumour radioiodine concentration has been compared with serum thyroglobulin (Tg) and, in a few cases, with tumour complement of thyrotrophin receptors in patients with differentiated thyroid carcinoma. All tumours examined possessed TSH receptors. In most the complement was similar to that of normal thyroid tissue although all but one of the tumours had no detectable 131I concentration in vivo even with excess TSH stimulation. Elevated serum Tg (patient taking T4 in suppressive dose) was generally associated with tumours which had 131I concentrating function when stimulated by excess TSH. Some patients, however, had high serum Tg concentration but only low or indetectable tumour 131I uptake. We conclude that (a) measurement of tumour TSH receptor complement is unlikely to be useful in clinical management as tumours which do not significantly concentrate 131I in vivo may have a normal TSH receptor complement and (b) the capacity to secrete Tg is usually associated with 131I concentration but quantitatively the relationship varies considerably between tumours.

Adult↗
PubMed1985

Total body potassium and water, and exchangeable sodium, in muscular dystrophy.

Total body potassium (40K method) and total body water and exchangeable sodium (both by isotope dilution) were determined in 26 boys, aged 5-17 years, with muscular dystrophy. Total body potassium values were compared with measurements in a large series of normal boys on the basis of height. Total body potassium was reduced even in the youngest patients and was only slightly higher in the older boys, despite their considerably greater height. Exchangeable sodium increased with increasing height in a way similar to that of normal boys. Total body water was also reduced but increased with growth, although to a lesser extent than expected for normal boys. The total body water measurements indicated that many of the affected boys were very obese, despite an apparently normal body weight. An intravenous bolus of 22Na distributed at a similar rate in boys with muscular dystrophy to that in normal males. In relation to the predicted values, total body potassium and 24 h urinary creatinine excretion of the affected boys both declined at a rate of 4% per year.

Adipose Tissue↗
PubMed1984

Amiloride sensitive and insensitive sodium pathways and the cellular sodium transport pool of colonic epithelium in rats.

Methods for measurement of the epithelial Na transport pool (Nat) using epithelial scrapings and for analysing the transepithelial ionic fluxes of rat distal colon in vivo into transcellular and paracellular components have been used to study the amiloride sensitive (a.s.) and amiloride insensitive (a.i.) transcellular pathways in relation to variations of Nat. In the Na-replete normal rats, substitution of SO4 for Cl in the lumen approximately halved the Na transported by a.i. pathways and reduced Nat by about 60%, but in the Na-depleted rats, substitution of SO4 did not affect either the Na transported by a.s. pathways or Nat. The value of Nat for normal rats, with 150 mM-NaCl in the lumen, was 6-7 nmol Na mg-1 dry weight (corresponding to about 2-3 mmol kg-1 cell water) and fell by about 60% when lumen Na concentration was reduced to 50 mM. Its turnover half-time was 0.6 min. Nat was about threefold greater in the Na-depleted than in the normal rats but became undetectable when amiloride was in the lumen. Amiloride did not affect Nat in normal rats. We conclude that the increased Na absorption in Na depletion depended on substitution of a.s. for a.i. apical membrane pathways allowing increased Na entry into the epithelial cells so expanding Nat and stimulating the basolateral Na pumps.

Amiloride↗
PubMed1984

Receptors for thyroid-stimulating hormone in normal and pathological human thyroid tissues.

The receptors for TSH have been studied in human thyroid tissue to assess their density and binding characteristics in various disease states. A single set of similar independent receptors appeared to be present in both healthy and pathological thyroid tissue. Their binding affinity for bovine TSH averaged 1.1 X 10(10) l/mol in healthy tissue and, with the exception of papillary carcinoma which showed some reduction, was not significantly altered in the various disease states studied. No receptors with low binding affinity were found. The number of receptors was significantly greater in toxic diffuse goitre and in hyperfunctioning follicular adenoma (but these tissues came from patients given antithyroid drugs and often iodine preoperatively), and was reduced in Hashimoto's thyroiditis. In well-differentiated thyroid carcinoma, the number of receptors was similar to or greater than in normal tissue, but in undifferentiated and medullary carcinoma, and in lymphoma of the thyroid, receptors were completely absent. Tracer-binding data obtained with human TSH were uniformly lower than the corresponding data obtained with bovine TSH, but showed an analogous pattern of differences amongst the various normal and pathological tissues.

Humans↗
PubMed1984

Absorption and secretion of fluid and electrolytes by the rectum.

Although the amounts of ions and water absorbed and secreted by the rectum are small compared to those of other parts of the colon, rectal epithelium is capable of generating and maintaining considerable ionic gradients. Absorption of Na+ and Cl- and secretion of K+ and HCO-3 leads to relatively low concentrations of the former and high concentrations of the latter within the lumen. Detailed examination of the transport processes indicates that the epithelial mechanisms can be interpreted in terms of ionic movements through transcellular and paracellular pathways. These results show that the epithelium is relatively tight and largely amiloride-sensitive. Active Na+ absorption and apparent active K+ and HCO-3 secretion occur. The secretion of HCO-3 is related to Cl- and organic anion absorption. Mineralocorticoids increase the transepithelial potential difference (p.d.) as well as stimulating Na+ absorption and K+ secretion. Rectal epithelium may, with various physiological or pathological stimuli, become overtly secretory of a predominantly NaCl containing fluid but it remains uncertain whether some secretion is normally present although masked by absorption.

Animals↗
PubMed1982

Anion transport in the colon.

The principal anions transported by colonic epithelium are Cl-, HCO3- and organic anions (OA-), particularly acetate, butyrate and pyruvate, these last being formed by microbial degradation of carbohydrate. In the normal absorptive rat colon, Cl- is transported from lumen to plasma both by the transcellular and paracellular pathways. The transcellular route appears to depend on amiloride-insensitive coupling of Na+-Cl- at the mucosal (apical) membrane, the Na+ electrochemical gradient energizing Cl- uptake. Intraluminal [HCO3-] rises as Cl- as absorbed, and a mucosal Cl- -HCO3- exchange carrier has been postulated. In some species (and in distal colon of the rat when sodium-depleted), the putative Na+-Cl- carrier is absent so that Cl- absorption then depends largely on the paracellular electrochemical gradient. Absorption of OA- is independent of the transepithelial p.d., is associated with HCO3- secretion and is considerably reduced by acetazolamide. In the absence of Cl-, OA- supports Na+ absorption but does not depend on it continuing unchanged when the latter is blocked. Colonic epithelium can become secretory and an example of this state is congenital chloridorrhoea in which an elevated transepithelial p.d. is associated with excessive Cl- secretion. Here, it appears that the Na+-Cl- and Cl- -HCO3- carriers are lost and Cl- conductance of the mucosal membrane substantially increased. The transepithelial uphill movements of Cl- or HCO3- in the absorptive and secretory colon appear to depend on coupling to other ionic flows, and there seems to be no need to postulate active transport of these ions.

Aldosterone↗
PubMed1981

Total body potassium in relation to thyroid hormones and hyperthyroidism.

1. Body weight and total body potassium were measured in 23 hyperthyroid patients before and at various stages during treatment and in 19 athyreotic patients who were being treated with high-dose L-thyroxine. 2. In the hyperthyroid patients the total body potassium rose by 23 +/- 2.8% (SEM) within a few weeks of restoring the blood thyroid hormone levels to normal. The body potassium values after treatment were close to that expected in these individuals if they were healthy indicating that a considerable loss of body potassium is usual in hyperthyroidism. 3. The gain of total body potassium in hyperthyroidism averaged 71 +/- 8 mmol for each kg of body weight gained (compared with muscle potassium concentration of about 92 mmol/kg). In contrast, weight loss produced by dietary treatment of obesity caused very little change of body potassium (maximum averaged was 14 +/- 4 mmol/kg wt. loss). 4. Among the patients with hyperthyroidism, the greatest muscular weakness was present in those with the greatest body potassium loss and these patients regained a large amount of potassium relative to weight on recovery. 5. Total body potassium changes were closely related to total plasma tri-iodothyronine concentrations but unrelated to the thyroxine levels.

Adult↗
PubMed1981

Autoantibodies to thyroglobulin cross reacting with iodothyronines.

Serum thyroxine was consistently unmeasurable by radioimmunoassay in an elderly patient with myxoedema after successful treatment with oral thyroxine. Abnormal binding of thyroxine was suspected and shown to be due to the presence in serum of antibodies of the IgG variety. The characteristics of these antibodies with respect to their binding of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and human thyroglobulin (Tg) were systematically studied. Three preparations of Tg, and t4, T3 and rT3 were examined for their ability to compete with 125I-Tg, 125I-T4, 125I-T3 and 125I-rT3 for binding to the antibodies. For each tracer used the order of competitive efficiency was Tg greater than T4 greater than T3 greater than rT3. This provides for the first time direct evidence that iodothyronine reacting antibodies occurring in man are generated against Tg. All three iodothyronines were able to inhibit tracer binding of labelled iodothyronines completely, the order of effectiveness being T4 greater than T3 greater than rT3, suggesting antibodies with one type of binding site and that these were probably raised against a Tg sequence incorporating T4, although there was some evidence for the existence of a minor subpopulation of antibodies with higher specificity for T3. Complete displacement of labelled Tg by cold iodothyronines, however, was not possible. The experimental evidence suggests two classes of Tg antibodies, 70% of which were directed towards the T4 containing region, and 30% directed against other part(s) of the Tg molecule. Despite the presence of such Tg antibodies conventional haemagglutination tests of the patient's serum for Tg antibodies were negative.

Aged↗
PubMed1981

Amiloride sensitivity of the transepithelial electrical potential and of sodium and potassium transport in rat distal colon in vivo.

1. The effect of amiloride within the gut lumen on the transepithelial electrical potential difference (p.d.) and Na and K transport by the distal colon of adrenalectomized (dexamethasone-maintained), normal, aldosterone-infused and Na-depleted groups of rats was examined. 2. Amiloride had no effect in adrenalectomized rats; in normal rats, only the p.d. was significantly reduced. 3. In the group given a short (2 hr) aldosterone infusion, amiloride reduced the elevated p.d. and K secretion rate to normal levels. There was no change in apparent K permeability of the epithelium. 4. In the Na-depleted group, p.d. and Na absorption were virtually abolished by amiloride but although K secretion was reduced it still remained much above normal levels. Adrenalectomy prevented the effects of Na depletion. 5. P.d. change occurred rapidly when amiloride was added to the perfusate. Increasing the Na concentration in the perfusate reduced the sensitivity to amiloride. Apparent 'Km' values estimated from p.d. changes (luminal Na, 50 mM) were similar for aldosterone-infused (7.6 X 10(-6) M) and Na-depleted (5.4 X 10(-6) M) rats. 6. Aldosterone appears to be essential for the induction of amiloride-sensitive Na paths in the mucosal plasma membrane of rat colonic epithelial cells. Prolonged aldosterone stimulation, as in the Na-depleted rats, increases the amiloride-sensitive Na paths while largely suppressing the amiloride-insensitive Na paths; in addition, the K/Na clearance rate ratio of the epithelium is increased. AMiloride interacts only with one set of Na paths and does not interact directly with K paths.

Adrenalectomy↗
PubMed1981

Comparison of binding of bovine and human thyroid-stimulating hormone to receptor sites on human thyroid membranes.

The binding of 125I-labelled bovine TSH (bTSH) to a wide range of human thyroid membrane preparations was compared with that of 125I-labelled human TSH (hTSH). Much higher binding percentages were obtained with the 125I-labelled bTSH. This was because the receptors had a higher binding affinity for bTSH than for hTSH. No differences in tracer purity, nor differences in optimal conditions for the binding of bTSH or hTSH, nor tracer degradation contributed significantly to the better binding of 125I-labelled bTSH. Good correlation was found between binding percentages for 125I-labelled bTSH and 125I-labelled hTSH over the range of thyroid specimens. Useful information on human TSH receptors is, therefore, obtainable from binding studies with 125I-labelled bTSH. The TSH displacement curves yielded linear Scatchard plots whenever the tracer and displacing hormones were of the same species. The data were, therefore, consistent with a simple binding reaction between TSH and a single set of independent receptor sites.

Animals↗
PubMed1980

Pathways of transepithelial potassium movement in the epithelium of distal colon in man.

1. Methods for studying the kinetics of movement of radioactive tracers across human distal colonic epithelium have been developed for use in vivo and applied to examination of transepithelial transfers of potassium. 2. During absorption of 43K from the lumen, two potassium pools, A and B, in the epithelium were identified, having mean turnover half-times of 16 and 87 min respectively. On average about 50% of the potassium lumen-to-plasma flux and most, if not all, of the potassium plasma-to-lumen flux took place through pool A. The transcellular pathway (equated with pool B) appeared to be of relatively little significance in transepithelial movement of potassium in the human distal colon. 3. Sodium and chloride movements were unaffected when lithium was present in the luminal solution, but the potassium secretion rate was nearly trebled due to increased plasma-to-lumen flux through the fast turnover pool A. 4. The permeability of the epithelium to potassium, as judged by the plasma-to-lumen fluxes, greatly exceeded that to sodium. This appeared to depend on a special highly selective potassium channel which differed from the shunt pathway in possessing definite capacity.

Adult↗