Antibodies to thyroid hormone analogues.
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Antibodies↗
Biomedical subjects
R John
Publications and source records attributed to R John.
High-resolution localization of 69 potential human zinc finger protein genes: a number are clustered.
In this study, we describe the identification and partial characterization of 101 potential human zinc finger protein genes (ZnFPs). These sequences were isolated by hybridization of cosmids, obtained from mouse-human cell lines enriched for chromosome 11p, with an oligonucleotide specific for the "link" sequence between contiguous zinc fingers. Sixty-nine of these cosmids were regionally localized to human prometaphase chromosomes by in situ hybridization. The localization of these cosmids suggests that a number of finger protein genes occur in linked clusters. Their assignment to chromosomes 3p, 11p, 19p, 19qter, 20p, and 21q makes them valuable as markers or "candidate" genes for diseases associated with these chromosome regions.
Amino Acid Sequence↗
Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.
OBJECTIVE: The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS: Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS: 23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING: Tertiary referral centre for cardiology. RESULTS: In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS: These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.
Action Potentials↗
Antibody interference in free thyroxine assays.
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Antibodies↗
Endemic goitre in Senegal--thyroid function etiological factors and treatment with oral iodized oil.
Endemic goitre and its response to orally administered iodized oil has been studied in seven villages 25-30 km south of Velingara, Eastern Casamance, Senegal. In 502 adults aged greater than 15 years goitre prevalence was 62% with 18.2% having goitre grade 2 or 3. Mean free T4 (FT4) was 11.9 +/- 3.5 (SD) pmol/l and iodine deficiency was confirmed by noting median urinary I of 0.079 mumol/l (14.9 mumol I/mol creatinine) with elevated free T3 (FT3)/FT4 ratios. Serum selenium concentrations were normal. The response to 480 mg of oral iodized oil assessed at 6 and 12 months was characterized by a 35.8% increase in FT4, a 25% decrease in FT3 and a 50% decrease in TSH (all p less than 0.01) at 12 months associated with a significant decrease in goitre size measured in 70 persons when compared to 65 controls not receiving iodine. Urinary iodine rose from 0.071 mumol/l to 0.189 mumol/l (p less than 0.01) during this time and no adverse effects on thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) were observed. A variation in goitre prevalence between villages was noted which, in such a small geographical area, suggests that etiological factors in addition to iodine deficiency may be important in goitre pathogenesis. Oral iodized oil administration is an effective treatment for iodine deficiency goitre in the short term.
Adolescent↗
Comparison of assay kits for unconjugated estriol shows that expressing results as multiples of the median causes unacceptable variation in calculated risk factors for Down syndrome.
We compared the performance of two methods for assaying unconjugated estriol in serum: the modified Amerlex third-trimester RIA kit, as used in seminal papers on unconjugated estriol in Down syndrome screening, and the new optimized Amerlex-M second-trimester kit. The significant difference between the results of each assay could cause unacceptable changes in the detection rate and false-positive rate of Down syndrome screening programs, especially if previously published values for estriol are used in the risk calculation. It is not possible to define new calculation parameters for every assay kit because new parameters will need to be defined every time kit changes occur, which would require a large collection of samples from Down syndrome pregnancies for standardization. Possible solutions to this problem are discussed.
Down Syndrome↗
The effect of weight correction on risk calculations for Down's syndrome screening.
Recent advances in prenatal screening have led to the possibility that the risk of Down's syndrome associated pregnancy may be assessed by blood tests for maternal serum alphafetoprotein, human chorionic gonadotrophin (and possibly unconjugated oestriol) taken at 15-18 weeks of gestation. In neural tube defect screening correction of maternal serum alphafetoprotein for maternal weight has been recommended, although the precise method for weight correction is still under debate. We report an assessment of weight correction for maternal serum alphafetoprotein and human chorionic gonadotrophin based on 1408 singleton pregnancies and for unconjugated oestriol based on 197 singleton pregnancies. We demonstrate that weight correction of maternal serum alphafetoprotein and human chorionic gonadotrophin is statistically valid but that correction of unconjugated oestriol is not.
Body Weight↗
Interference in thyroid-function tests in postpartum thyroiditis.
Three women are described from a study of patients with postpartum thyroiditis whose sera gave spuriously increased concentrations of free thyroid hormone because of antibody binding of radiolabeled thyroxin (T4) and triiodothyronine (T3) analogs. All of the women showed increased serum concentrations of thyroid autoantibodies. The antibody binding of radiolabeled analogs and its effect on free T4 and free T3 assays disappeared by 48 weeks postpartum. Postpartum women who develop thyroid autoantibodies have approximately 2% prevalence of increased binding of radiolabeled analogs, which can result in an interference in thyroid hormone assays involving T4 and T3 analogs.
Autoantibodies↗
Problems with the Mallampati sign.
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Humans↗
A long-term follow-up of postpartum thyroiditis.
To investigate the long-term outcome of postpartum thyroiditis (PPT), 43 patients with PPT and 171 control women were evaluated 3.5 (range 2-4) years postpartum. Ten (23%) PPT patients were hypothyroid compared to none of the controls (P less than 0.001). Factors associated with the development of hypothyroidism were high antimicrosomal antibody titre measured at 16 weeks gestation (P less than 0.01), severity of hypothyroid phase of PPT, multiparity, and a previous history of spontaneous abortion. The presence of microsomal antibody but no PPT in one pregnancy did not prevent the occurrence of PPT in the next pregnancy in two patients and a further five patients had PPT in two successive pregnancies. There was no association between HLA haplotype, family history of thyroid disease, smoking or frequency of oral contraception, and the development of long-term hypothyroidism after PPT. It is concluded that permanent hypothyroidism is an important sequel to PPT and patients with PPT should be followed up appropriately.
Adult↗
Rate of cerebral embolic events in relation to antibiotic and anticoagulant therapy in patients with bacterial endocarditis.
To quantitate embolic risk we studied a retrospective series of 61 patients with strictly defined bacterial endocarditis. Eighteen patients had neurological complications attributable to cerebral embolism. Seventeen embolic episodes occurred prior to antibiotic treatment and 8 episodes after its commencement. The rate of embolism per patient-week during a 20-week observation period showed a highly significant almost 4-fold reduction to a low level soon after antibiotics were started. Patients already on anticoagulation for prosthetic valves had the same embolic risk as those not so treated. The evidence suggests that anticoagulation at the time of diagnosis of bacterial endocarditis is not warranted.
Adult↗
Congenital hypothyroidism with spuriously increased FT3 concentrations in infant and mother.
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Adult↗
The clinical spectrum of staphylococcal bacteraemia: a review of 101 Melanesian patients from Papua New Guinea.
The clinical features of 101 Melanesian patients with Staphylococcus aureus bacteraemia observed during two 2-year periods (1977-1979 and 1985-1987) in a university teaching hospital in Papua New Guinea are reviewed. The age of the patients ranged from 12 to 70 years. There were 69 males and 32 females. Diabetes mellitus, found in 15 patients, was the most common predisposing factor. Most of the patients (87%) had community-acquired infection. Soft-tissue infection, pneumonia, arthritis, osteomyelitis, intravenous-site thrombophlebitis, cerebral abscess, endocarditis and cavernous sinus thrombosis were among the clinical entities observed. Soft tissues and lungs were the most common sites of primary and secondary foci of infection, respectively. All but 1 of the 101 blood isolates were resistant to penicillin G and none was resistant to methicillin. The overall case fatality rate was 24%. These data demonstrate that staphylococcal bacteraemia in adult Papua New Guineans is mostly community acquired and has a high mortality. Skin and soft tissues are the major primary foci of infection leading to staphylococcal bacteraemia.
Adolescent↗
Concentrations of free thyroxin and free triiodothyronine in serum of patients with thyroxin- and triiodothyronine-binding autoantibodies.
Between 1982 and 1989 we identified 47 subjects with spuriously increased concentrations of free thyroxin (FT4) or free triiodothyronine (FT3) related to autoantibody interference in analog FT4 and (or) FT3 methods. The incidence of autoantibody interference observed during one year (1988) was 1 in 2460. In the subjects identified, 51% and 11%, respectively, showed an increased binding of radiolabeled T4 or T3 analog alone; 38% had an increased binding of both. Of 36 patients tested, 71% had autoantibodies to thyroglobulin and microsomal fraction of the thyroid, 19% to microsomal fraction alone, and 9.5% to thyroglobulin alone. In eight subjects, spuriously increased FT4 concentrations were reported with the following FT4 methods (in decreasing order of interference): Coat-A-Count, Amerlex-M, Amerlite, Seria, Magic Lite, Amerlex-MAB. In the same eight subjects, Amerlex-M and Seria reported spuriously increased concentrations of FT3.
Adolescent↗
Growth hormone responses to growth hormone releasing factor in primary degenerative dementia.
The growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL) responses to growth hormone releasing factor (GRF) were investigated in 18 patients suffering from primary degenerative dementia (PDD) and in 20 age- and sex-matched normal elderly controls. There was no significant difference in the growth hormone response to GRF stimulation between patients and controls, and in neither subject group was there a demonstrable TSH or prolactin response to GRF. These findings indicate that the pathophysiology underlying the blunted growth hormone response to pharmacological challenge in PDD must lie at a suprapituitary level.
Aged↗
Effect of nadolol on plasma lipids in hyperthyroidism.
The effect of Nadolol treatment on lipid subfractions in a group of 23 hyperthyroid patients was assessed in a randomised double-blind placebo controlled trial lasting six weeks, carbimazole being given to both groups from weeks 2 to 6. Clinical and biochemical euthyroidism was seen in both groups at 6 weeks; no effect of nadolol on peripheral monodeiodination of T4 to T3 was observed. At time 0 there were significant negative correlations between total cholesterol and free T3 (r = 0.68), and free T4 (r = 0.54). In the Nadolol group there were significant rises between 0 and 6 weeks in total cholesterol (52.6%, P less than 0.01), LDL cholesterol (30.3%, P less than 0.01) and HDL cholesterol (18.2%, P less than 0.05). HDL cholesterol rose significantly in the placebo group (12.4%, P less than 0.05) but there were no significant increases in LDL cholesterol or total cholesterol. The rise in triglyceride during this period in the Nadolol group (64.7%, P less than 0.05) was significantly greater (P less than 0.05) than the rise in the placebo group (8.8%). Nadolol increases triglyceride more than placebo during the early management of hyperthyroidism.
Adult↗
The epicardial electrogram: a quantitative assessment during balloon angioplasty incorporating monophasic action potential recordings.
An electrogram was recorded from the angioplasty catheter guide wire when coronary blood flow was interrupted in 20 patients undergoing percutaneous transluminal coronary angioplasty. Monophasic action potentials were recorded from the right ventricular septum together with the routine electrocardiogram. The patients were studied during angioplasty for lesions in the left anterior descending (12), circumflex (3), and right coronary arteries (6). ST elevation in the electrogram recorded in the left anterior descending and circumflex systems was usually more obvious than that in the electrocardiogram. Signals obtained from the right coronary artery were of very low amplitude and registered only minimal ST changes. The ST elevation developed in the electrogram during insertion of the catheter before inflation of the balloon in 11 of the 15 patients undergoing angioplasty of the left system. In eight of the patients showing pre-inflation ST elevation the ST shift lessened after successive inflations. Monophasic action potential recordings were obtained during 45 balloon inflations in 19 patients. In those patients undergoing angioplasty for lesions of the circumflex coronary artery the monophasic action potential showed no change during balloon inflation. In patients undergoing angioplasty for the right coronary artery the mean normalised duration at 60 seconds' occlusion was 99.6 (1.5)% of control. Of a total of 25 occlusions in the patients undergoing angioplasty for the left anterior descending coronary artery 19 showed shortening of less than 5%, five showed shortening between 5 and 10%, and one showed a shortening of 16.4% in the monophasic action potential. The QT interval was satisfactorily measured in the electrogram during 36 balloon inflations, and in 24 of these it was also measured in the electrocardiogram. QT changes in the electrogram tended to be the opposite of those in the electrocardiogram. When changes in RR interval were minimal (less than 20 ms) during the balloon inflation 14 of 17 electrograms showed QT prolongation but only one of 12 electrocardiograms showed prolongation. Conversely one of 17 electrograms showed shortening compared with eight of 12 electrocardiograms. There was angiographic evidence of the development of collaterals in six of 15 patients undergoing angioplasty of the left system. ST segment elevation in both the electrogram and electrocardiogram was less pronounced in these patients than in those without evidence of the development of collaterals. ST segment changes recorded from the angioplasty guide wire provide a more sensitive index of ischaemia than the surface 12 lead electrocardiogram, and fall in ST segments on balloon deflation is a prognostic index of a good angiographic result in the left anterior descending and circumflex arteries, but not in the right coronary artery.
Action Potentials↗