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Biomedical subjects

T E Hilditch

Publications and source records attributed to T E Hilditch.

At least 73 records · Page 4Linked to original sources

Defects in intrathyroid binding of iodine and the perchlorate discharge test.

The kinetics of [123I]iodide uptake were studied when organification of iodine by the thyroid gland was normal and when this binding function was diminished by drugs or disease. Each study was terminated by a sodium perchlorate discharge test (300--600 mg iv) at 60 min or, in some cases, 10--30 min. The results confirmed that binding takes place rapidly in the uninhibited gland with the binding rate constant being at least 0.150 min-1. Discharge from the uninhibited gland is less than 3.5% of the gland uptake when perchlorate is given 60 min after the radioiodide. Subjects with an intrinsic binding defect manifested discharges of 11% of greater of the 60 min uptake and the estimated binding rate constants ranged from 0.003--0.057 min-1. Thyrotoxic subjects receiving 5 mg carbimazole twice daily manifested discharges ranging from 5.4--64.2%, and in those receiving 20 mg twice daily the observed discharges were 67.6--94.6% of the 60 min uptake. The study shows that a correctly performed perchlorate discharge test will detect minimal inhibition of iodine binding. An important factor is the duration of the follow-up period after perchlorate is given. In some of the cases studied discharge was not complete until 60 min after the perchlorate.

Binding Sites↗

Intrathyroidal iodide binding rates and plasma methimazole concentrations in hyperthyroid patients on small doses of carbimazole.

1 The effect of small doses of carbimazole on the binding rate constant of intrathyroidal iodide, plasma methimazole concentrations and circulating thyroid hormone concentrations in five hyperthyroid patients is presented. 2 In all patients there was a marked reduction in iodide binding with carbimazole doses as low as 5 to 10 mg daily. 3 In three patients little further reduction in the observed binding rate occurred with daily doses in excess of 10 mg despite progressive increases in plasma methimazole concentrations. 4 At the end of 4 weeks' treatment with 10 mg carbimazole daily, the reduction in thyroid hormone concentrations and clinical improvement were such as to suggest that this dose may be an effective starting dose in many patients.

Adult↗

Antiprostaglandin synthetase activity of nonsteroidal anti-inflammatory drugs and gastrointestinal micro-bleeding: a comparison of flurbiprofen with benoxaprofen.

By using 51Cr-labelled erythrocytes and 141Ce-labelled microspheres to correct for daily variations in faecal output, gastrointestinal microbleeding was measured in hospital patients with rheumatoid arthritis before and after administration of 2 propionic acid derivatives. These were flurbiprofen and benoxaprofen, respectively a potent and a weak prostaglandin synthetase inhibitor. Increased faecal blood loss occurred consistently with flurbiprofen and not with benoxaprofen. Our results provide indirect evidence for the cytoprotective effect of prostaglandins on the gastrointestinal mucosa in man. The quantitative correlation between faecal occult blood loss as measured by the above techniques and the Haemoccult slide test is also discussed.

Aged↗

Quantitation of thyroidal binding of iodide by compartmental analysis verified by an intravenous perchlorate discharge test.

Compartmental analysis was applied to 123I-iodide uptake data to quantitate iodine binding in the human thyroid gland. The method allowed for arterio/venous differences in plasma tracer level and for an "instantaneous" phase of thyroid uptake. Results were checked by an intravenous perchlorate discharge test. Observations in eleven normal and untreated thyrotoxic subjects confirmed earlier findings that iodine binding takes place rapidly, the binding rate constant being much greater than the exit rate constant. A lower limit of 0.15 min-1 for the binding rate constant in the uninhibited gland was estimated from the observations in one subject who demonstrated a small perchlorate discharge. The method was used in the study of eight subjects with an intrinsic binding defect and of twenty-four thyrotoxic subjects being treated with 5 mg or 20 mg carbimazole, twice daily. Binding rate constants (range 0.003--0.105 min-1) were typically less than the exit rate constants (range 0.027--0.156 min-1), the net clearance of iodide ranging from 1.5 to 67.9% of the unidirectioinal clearance, compared to 72% in the uninhibited gland. The method proved useful in assessing the severity of an intrinsic binding defect and in the investigation of lack of response to antithyroid drug therapy.

Computers↗

Unexpected differences in early thyroidal trapping of iodide and pertechnetate.

Compartmental analysis was applied to simultaneously acquired 132-I-iodide and 99mTc-pertechnetate thyroid uptake data. The method allowed for arterio/venous differences in plasma tracer level and for an 'instantaneous' phase of thyroid uptake. Observations in four thyrotoxic patients, before and during antithyroid drug therapy, revealed greater 'instantaneous' uptake of TcO4-. The results also revealed that 'instantaneous' uptake of both I- and TcO4- may increase over the first six months of drug therapy. These findings could not be explained by the estimates of unidirectional clearance which were greater for I- and varied little during the early stages of drug therapy.

Antithyroid Agents↗

Red cell magnesium as a function of cell age.

The variation in the magnesium content of human red cells as a function of cell age has been measured by atomic absorption spectrophotometry. The cell population was split into different age fractions using discontinuous density gradient centrifugation, since it is known that cell density increases with age. A mathematical model relating predicted cell age to cell density has been developed which allows the quantification of the observed fall-off in magnesium content with cell age. This model suggests that cells lose magnesium monoexponentially with age, the half-life being approximately 100 days. A previously proposed hypothesis that magnesium could enter the cells only at erythropoiesis and then decay monoexponentially predicted a half-life of 22.4 days and is therefore seen to be an oversimplification of magnesium kinetics in the red cell. The relevance of the present findings to pathologic conditions with abnormal red cell magnesium concentrations is discussed.

Erythrocyte Aging↗

Monitoring of airborne contamination during the handling of technetium-99m and radioiodine.

Measurements have been made using an air sampler to measure airborne radioactivity produced during the routine handling of large activities of technetium-99m, iodine-125 and iodine-131. The results indicate that 99Tcm can be safely handled in environments without direct exhaust of the ventilated air but that 125I and 131I should always be handled in a ventilated environment such as a fume cupboard or a down-draught work-station of the total-exhaust type. Monitoring of thyroid uptake proves to be the most reliable means of monitoring airborne contamination by these radionuclides, but burdens and radiation doses for typical procedures are well within the maximum permissible limits of the Code of Practice for the Protection of Persons from Ionizing Radiation arising from Medical and Dental Use.

Air Pollution, Radioactive↗

The significance of bone islands, cystic areas and sclerotic areas in dysbaric osteonecrosis.

Dysbaric osteonecrosis is a major hazard to compressed air workers and an increasing hazard to divers. Symptomless osteonecrosis is best recognised by radiology and it is of fundamental importance that interpretation be reliable and accurate. There is much controversy concerning the significance of bone islands and cystic areas; several authors report bone islands and cystic areas to be up to eight times more frequent in compressed air workers and divers and believe that these represent positive evidence of osteonecrosis. Skeletal radiographs of 100 Royal Navy divers, all of whom were at risk to osteonecrosis were matched for age and rank with 100 controls, none of whom had been exposed to high pressures. The radiographs were interpreted by three radiologists working independently without knowing whether the radiographs were in the diving or control group. It is concluded that bone islands, cystic areas and sclerotic areas, as described in this text, occur with equal frequency in divers as in the normal population and do not represent positive evidence of osteonecrosis. The report includes autopsy studies of the proximal femur and proximal humerus in six diving fatalities. Five bone islands in the proximal humerus and one in the femoral neck were studied in bones removed from five divers. In the sixth case a cyst was seen to develop radiologically in the femoral neck and then reduce in size over 3 years and 10 months. Slab radiographs and histological section in all cases show no evidence of osteonecrosis.

Adult↗

The distribution of blood flow between individual muscles and non-muscular tissues in the hind limb of the young ox (Bos taurus): values at thermoneurality and during exposuer to cold.

1. The radioactive microspheres method was used to measure the distribution of blood flow in the hind leg in conscious young steers exposed to thermoneutral and moderately cold environments. Simultaneous measurement of total leg blood flow allowed calculation of blood flow (ml. 100 g tissue-1 min-1) to individual muscles and the major non-muscular tissues in the leg. 2. In the thermoneutral environment, leg blood flow was distributed approximately according to tissue weight, so that about 65% went to muscle and the remainder to bone, skin, connective tissue and fat; 1-7-11-5% of the injected dose of microspheres was found in the lungs, indicating the presence of functioning arteriovenous anastomoses in the leg. 3. During cold exposure leg blood flow increased two-and-a-half fold and 91% of this increase was due to increased blood flow in muscle. This was accompanied by substantial decreases in both total and capillary blood flow in leg skin in three of the four animals. 4. Values for resting tissue blood flow to the six largest individual leg muscles were compared, as well as that for tissue blood flow to the remaining leg muscle. Blood flow in the three large upper thigh muscles (biceps femoris, semimembranosus and semitendinosus) was about half that in muscles in the rest of the leg. 5. Cold exposure caused a threefold increase in total leg muscle blood flow, but the only individual muscles to respond substantially in all four animals were the vastus lateralis and the rectus femoris. Comparison of results from individual animals suggested a relation between total leg blood flow and the number of muscles (apart from vastus lateralis and rectus femoris) involved in shivering. Leg adipose tissue blood flow also increased significantly in the cold.

Adipose Tissue↗

Studies on the carrier state in X-linked recessive (Duchenne) muscular dystrophy.

Observations in 12 normal women and 12 female carriers of X-linked recessive Duchenne muscular dystrophy (DMD), of whom 4 had symptoms and 8 had none, were compared between all 4 groups and with those in 2 DMD boys, one active and one crippled. Carrier symptoms were readily ascertained by systematic examination. Measurement of both lower legs in all 24 women showed neither calf enlargement nor asymmetry in carriers beyond normal variation. Two DMD carrier daughters were noted of the same DMD carrier mother but by different fathers. Whole body counting showed the biological half-life of previously administered 86Rb to be much reduced in DMD, but no differences were found between normal women and any group of carriers. The test is thus valueless for carrier detection, and reasons are given why it should be so. Simultaneous measurement of total body K+, with subsequent determination by isotope dilution of total body water as 3H2O space and extracellular water as NH4 82Br space, showed increased intracellular water and reduced intracellular K+ concentration in all carriers, as if due to osmotic causes, with actual loss of muscle mass and slight diminution of serum K+ in the 4 symptomatic carriers only. Because of diurnal and other variations, the means and standard deviations for six serum enzymes from six fortnightly assays in all subjects were used to measure precise individual status. Their coefficients of variation were abnormal only in symptomatic carriers and ambulant DMD, easily overtexed by even accustomed exertion. This is shown to support previous propositions on the pathogenesis of DMD and the escape of muscle cell content into the circulation.

Adolescent↗

Energy provision, tissue utilization, and weight loss in prolonged starvation.

Daily weight loss measurements in 76 fasting, obese patients (58 females, 18 males) have shown a characteristic pattern of rapid loss initially (up to day 14) followed by a slower but uniform reduction in weight. There were significant sex differences. Measurements of tissue breakdown showed that the initial rapid weight loss was due to the continuing utilization by the nervous system of glucose derived from lean tissue. This requirement fell noticeably from the second week of starvation. Irreversible fluid elimination also contributed to the initial phase of rapid weight loss. Fat remained the primary source of energy throughout starvation and in established fasting (more than 14 days) contributed 96% of that requirement.

Adipose Tissue↗