ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02329.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02330.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE Because the exact mechanism of action of carbimazole is uncertain, nuclear magnetic resonance (NMR) spectroscopy was used to investigate cellular changes in erythrocytes from Graves' patients following a course of carbimazole therapy.DESIGN NMR spectroscopy was carried out using intact erythrocytes obtained from Graves' patients prior to and at 2 and 12 months after carbimazole treatment. The data were correlated with thyroid hormone and antibody levels. PATIENTS Twenty patients (four males; 16 females) with newly diagnosed and previously untreated Graves' disease were enrolled into the study. Assessments were made prior to the commencement of therapy and after 2 and 12 months on treatment. Of the 20 patients assessed at 0 and 2 months only 12 completed the study.MEASUREMENTS The oxidation‐reduction balance of erythrocyte glutathione was measured directly using1H spin echo NMR spectroscopy of intact cells. Thyroid hormone and antibody levels were measured using reported methods.RESULTS At 2 and 12 months a significant (P<0.01) oxidation of the erythrocyte glutathione was observed. Of the four thyroid related markers (T3, T4, TRAb and TSH) assessed in this study both T3(P<0.001) and TRAb (P<0.001) were observed to correlate with the NMR observed changes in glutathione. However, in‐vitro experiments indicated that carbimazole does not affect red cell glutathione directly.CONCLUSIONS A model is presented which uses the hydrated iodium cation (I+), the natural product of T4conversion to T3, as a chemical oxidant which can produce the observed clinical alteration in intracellular glutathione in ex‐vivo erythrocytes. It is suggested that a major factor in the action of carbimazole in Graves' disease may be to stimulate the function of the deiodinase en

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02331.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE We studied the relationship between endurance training, aerobic capacity, and T3 metabolism in healthy euthyroid men.DESIGN T3 kinetic studies performed on two groups of subjects differentiated on the basis of physical activity status and aerobic capacity.SUBJECTS Five endurance‐trained athletes and five sedentary controls (mean±SDVo2max = 48.2 ± 7.1 vs 23.2±4.5 ml/kg/min, respectively) matched for age, body surface area, lean body mass, and baseline thyroid function.MEASUREMENTS Kinetic analysis performed using serial serum T3 levels measured following oral T3 administration. Metabolic clearance rate, total volume of distribution, disposal rate, and total body pool calculated using non‐compartmental analysis.RESULTS When normalized for lean body mass, all kinetic parameters were 25–38% greater in the athletic group compared to controls (P<0.05). Total volume of distribution, disposal rate, and total body pool were positively correlated with aerobic capacity (r=+0.69 to +0.79;P<0.05). Metabolic clearance rate was positively correlated to a non‐significant degree.CONCLUSIONS These results confirm the findings of prior studies that thyroid hormone metabolism is altered by physical conditioning. In addition, we demonstrated a positive correlation between aerobic capacity and several parameters of T3 kinetics. Differences in absolute lean body mass cannot explain these findings; rather it appears that there is something qualitatively different in the way endurance‐trained tissue processes thyroid hormone, compared to untrained tissue. The study was not designed to elucidate these differences at the cellular level; however, it does support a link between muscle physiology and T3 activity and may suggest a physiological role for thyroid hormone in physical

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02332.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVES There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women.PATIENTS The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls.MEASUREMENTS Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured.RESULTS While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients.DISCUSSION None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02333.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE We investigated possible changes in the pituitary‐thyroid axis after radioactive iodine (RAI) treatment of multinodular non‐toxic goitre.DESIGN Consecutive patients with multinodular non‐toxic goitre, who remained euthyroid after radioactive iodine (RAI) treatment.PATIENTS Twenty‐three women with multinodular nontoxic goitre were followed after treatment with RAI.MEASUREMENTS Free T4 index (FT4I), FT3I, free T4, SHBG (Immunoradiometric assay), and a third‐generation TSH assay (chemiluminetric assay) TSH were measured. RESULTS Three weeks after RAI treatment TSH had decreased and SHBG Increased (P<0.05). Only 2/18 patients actually had suppressed TSH values, while 12/18 had values in between euthyroid and toxic levels. Trend analysis from 1.5 to 24 months after RAI treatment demonstrated a progressive increase in TSH (P<0.01) and gradual decrease in SHBG (P<0.02). No changes in FT4I, FT3I, or free T4 were found.CONCLUSION A third‐generation TSH assay gave detailed information about changes in thyroid status when TSH was below normal values. FT4I, FT3I, and free T4 seem to be less sensitive parameters than TSH and SHBG for recording subtle changes in thyroid status after RAI treatment of nodular non‐toxic goitre. We demonstrated that changes in the pituitary‐thyroid axis continue for a long time after RAI treatment of multinodular non‐toxic goitre. These patients should be followed up in order to detect possible la

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02334.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE, PATIENTS AND DESIGN X‐linked hypophos‐phataemic rickets (HYP) is the most common inherited form of rickets and the gene causing this disorder has been localized to Xp22.3‐p21.3 by linkage studies of affected families of Northern European origin. In addition, the locus order Xpter‐(DXS207‐DXS43, DXS197)‐HYP‐DXS41‐Xcen has been established and the flanking markers are useful for the presymptomatic diagnosis of HYP. However, a recent study indicates locus heterogeneity and this may hinder the use of the flanking markers for presymptomatic diagnosis in additional families and in particular those from different populations. We have therefore investigated one Saudi‐Arabian family (13 affected and six unaffected members) with hypophosphataemic rickets for linkage to these and other X‐linked markers. A total of 17 cloned human X chromosome sequences identifying restriction fragment length polymorphisms were used to localize the mutant gene causing this disorder in the Saudi Arabian family.RESULTS Nine (four from Xp and five from Xq) of the 17 X‐linked DNA probes proved informative and linkage was established between HYP and the DSX41 locus, peak LOD score = 4.22 (recombination fraction, ±= 0.00). A positive peak LOD score of 2.32 (. = 0.05) was also obtained between HYP and the DXS207 locus. Thus, the HYP gene in this Saudl Arabian family is linked to two of the four flanking markers which demonstrated linkage in families of Northern European origin.CONCLUSION We conclude that the X‐linked hypophosphataemic rickets gene in a Saudl Arabian family is located in the Xp22.3–p21.3, a region where this gene has previously been mapped by linkage studies of families of Northern European origin. Our studies have not demonstrated locus heterogeneity, so the flanking markers for HYP previously established in the families of Northern‐European origin will be useful in the genetic counselling and presymptomatic diagnosis of this disorder

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02335.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE The objective of the present study was to elucidate the parathyroid responsiveness by measurements of blood Ionized calcium and serum intact parathyrold hormone (PTH) concentrations, before and during trisodium citrate induced hypocalcaemia.PATIENTS AND CONTROLS Sixteen patients with primary hyperparathyroidism and 32 healthy volunteers.DESIGN Blood ionized calcium concentration was lowered by about 0.20 mmol/l and maintained at this level for 2 hours by blood ionized calcium controlled trisodium citrate infusion.MEASUREMENTS Serum PTH(1–84) was measured by an Immunoradiometric assay.RESULTS In patients and controls, baseline measurements of blood Ionized calcium were 1.39±0.07 vs 1.24±0.04 mmol/l (mean.SD) (P<0.001) and of serum PTH (1–84) 9.7.5.4 vs 3.2 1.1pmol/l (P<0.001). During a trisodium citrate clamp, serum PTH(1–84) rose to a maximal concentration after 5–10 minutes in both groups, the patients to 2–10 times baseline, whereas controls rose to 4–7 times baseline values. In both groups the peak of serum PTH(1–84) declined to a steady state concentration around 2–4 times baseline.CONCLUSIONS in conclusion, adenoma cells seem to react in almost the same way as normal parathyroid cells. They respond to initiation of hypocalcaemia by the release of preformed PTH(1–84), and continue to secrete increased amounts of PTH(1–84) during the maintenance of relative hypocalcaemia. The increased baseline concentrations of blood ionized calcium and serum PTH(1–84) and the serum PTH(1–84) response during blood ionized calcium lowering all suggest a shift upwards

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02336.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE We Investigated the effect of an oplate (morphine) and an opiate antagonist (naloxone) on the maternal secretion of oxytocin in the first stage of labour.DESIGN Patients were randomized to receive either morphine 5 mg (n= 9), naloxone 1.2 mg (n= 10) or sterile water (n= 9) which was injected intravenously.PATIENTS Healthy women in the first stage of labour between 3 and 6 cm dilated with no prior analgesia or oxytocin administration were recruited for the study.MEASUREMENTS Peripheral maternal oxytocin levels were measured by radloimmunoassay for 15 minutes before and 15 minutes after administration of the assigned substance. Sampling was at 2.5 minute intervals.RESULTS Significant reduction in the mean oxytocin concentration was found in the patients who received morphine (— 2.62 pmol/l/sample) but no change was found in the naloxone group (+ 0.57 pmol/l/sample) when compared with controls (+ 0.64 pmol/l/sample).CONCLUSION Maternal oxytocin secretion is inhibited by exogenous opiates in the first stage of labour while an effect of opiate antagonism was not demonstrate

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02337.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

OBJECTIVE We observed the effects on bone metabolism of the addition of different doses of oral norethisterone during treatment with the GnRH agonist nafarelin (Synarel, Syntex).PATIENTS Ninety‐four women with a subjective complaint of heavy menstrual blood loss or objective evidence of endometriosis received intra‐nasal nafarelin 400 μg daily for 6 months and also received, in a randomized, double blind manner, either 0.7 mg (n= 24), 1.4 mg (n= 23) or 2.45 mg (n= 23) of oral norethisterone or placebo (n= 24) daily. Follow‐up was continued for a further 6 months after treatment.RESULTS Thirty‐one patients (33%) left the study prematurely and three patients were non‐compliant with the study drug. By 6 months significant increases in urinary calcium/creatinine ratio were seen, compared to baseline, in the nafarelin and placebo (P=0.001,n= 14), 0.7 mg (P=0.04,n= 13) and 1.4 mg norethisterone groups (P=0.009,n= 17) but not in the nafarelin or 2.45 mg norethisterone groups (P= 0.72,n= 16). Densltometry of the spine, however, showed decreases at 6 months in all groups: 6.14% (P=0.0004,n= 11), 5.46%n= 0.0006,n= 13), 3.93% (P=0.008,n= 14) and 4.04% (P= 0.004,n= 16) for the groups receiving nafarelin and placebo, nafarelin and norethisterone 0.7, 1.4 and 2.45 mg respectively. Six months after stopping nafarelin, with or without norethisterone, bone mass was not different from baseline.CONCLUSION The concomitant daily use of up to 2.45 mg of norethisterone does not eliminate the bone deminerallzation seen during GnRH agonist therapy with nafarelin in premenopa

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02338.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY