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Biomedical subjects

A N Hunter

Publications and source records attributed to A N Hunter.

5 recordsLinked to original sources

Parathyroid-hormone-related protein in sarcoidosis.

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.

Adult

Alterations in thyroid function after cholecystographic contrast agents.

The radiographic contrast agents commonly used for oral cholecystography have diverse effects on thyroid hormones in man. They may: (i) decrease serum triiodothyronine (T3) and increase reverse T3 in both hyperthyroid and euthyroid subjects, an effect attributable to inhibition of phenolic (outer) ring deiodination of iodothyronines; (ii) acutely increase serum thyroxine (T4) by displacing it from the liver, so inviting an erroneous diagnosis of hyperthyroidism; (iii) precipitate hyperthyroidism in apparently euthyroid subjects who have autonomous thyroid tissue. In comparison with the cholecystographic agents which are taken up by the liver, the renally-excreted contrast agents used for angiography or intravenous urography are much less potent in producing these effects. The paradox of T4 excess with normal T3 may arise after cholecystography, either by an acute T4 increase in a euthyroid subject, or by normalization of T3 in hyperthyroidism, thus creating a diagnostic dilemma. The recent trend towards use of oral cholecystographic agents in the urgent management of hyperthyroidism, because of their effect on serum T3, needs to be regarded with caution in view of the risk that hyperthyroidism may eventually be worsened if synthesis of T4 is not effectively blocked. For this reason, contrast media should probably be used in the treatment of hyperthyroidism only in conjunction with conventional antithyroid drugs. A history of exposure to contrast media should be sought in any acute or unexpected exacerbation of hyperthyroidism, or when T4 excess is found without an increase in T3.

Cholecystography

Thyrotrophin-binding-inhibition assay: comparison of crude and purified membrane preparations.

Two different thyroid membrane preparations (TMP), crude and pure, made from a homogenate of normal human thyroid tissue, were used to test purified serum IgG from 36 patients with Graves' disease, and 10 normal control subjects, in the thyrotrophin-binding-inhibition (TBI) assay. All reagents for the assay were identical, and aliquots of each IgG were tested in both TMP simultaneously, under exactly comparable conditions. Blood was drawn while the patients were hyperthyroid (19), euthyroid (13), or hypothyroid (4); 15 of the patients were untreated and 21 were being treated. The frequency of positive TBI was similar in both TMPs and highest among the 131I-treated patients. Comparison of TBI results in both TMP for each IgG sample revealed wide differences, and 47.1% of the Graves' IgGs were TBI positive in one membrane preparation, while negative in the other. There was no correlation of TBI values between the two TMP, or with clinical status, or the presence of standard thyroid antibodies. The findings indicate that the IgGs of Graves' disease, as now tested in the TBI assay, bind heterogeneous to different fractions of the thyroid membranes.

Binding Sites, Antibody

Atrial fibrillation and arterial embolism in hyperthyroidism.

Atrial fibrillation or flutter was present in 70 of 381 patients with uncontrolled hyperthyroidism; return to stable sinus rhythm occurred in 39 with antithyroid and antiarrhythmic treatment. One third of the patients who reverted did so in the first week of treatment while still hyperthyroid. As expected, reversion was more likely in younger patients, and in those with arrhythmia of recent onset, without evidence of other heart disease. Eight patients with arrhythmia had proven (five) or probable (three) major arterial embolic episodes. Four of these eight patients died. Embolism tended to occur at an early stage, during uncontrolled hyperthyroidism, in patients with both atrial fibrillation and cardiac failure. These findings suggest that prophylactic anticoagulation may be appropriate in this high risk group, although more extensive studies are necessary before effective prevention of embolism can be claimed.

Adolescent

Methods of assessing diabetic control.

Control of diabetes from complete normalisation to less adequate degrees of metabolic regulation needs to be assessed with regard to conditions of evaluation and to severity of the disease. Under optimal conditions the therapeutic events should occur with well-timed regularity. Different assessment criteria are appropriate depending on the severity of the deficiency of endogenous insulin. Plasma and urine glucose and ketone body measurements remain the practical standards for assessing diabetic control. Abnormalities of lipid and protein metabolites serve to augment the scope of the assessment. Triglycerides and haemoglobin AIc are also useful indicators of control. In mild (Type II) diabetes it may be possible to achieve normal plasma glucose measurements two hours after meals. Such aims carry a risk of hypoglycaemia in severe (Type I) diabetes. Normoglycaemia and aglycosuria in severe diabetes are feasible only preprandially in most cases. The use of urine glucose tests requires evaluation of blood-to-urine glucose relationships. Practical and convenient methods for identifying patients with high or low "renal thresholds" are described. Investigational methods for characterising diabetic patients assess the variability of glucose and other variables during therapy, as well as the degree to which normal values are attained. Such assessment methods may gain increasing practical importance as therapeutic approaches to diabetic control which are experimental at present come into practice.

Blood Glucose