bluuebunny/crossref_metadata_2025 huggingface dataset:
The usefulness of quantitative orbital magnetic resonance imaging in Graves' ophthalmopathy
Authors: Prummel Mark F. , Gerding Martin N. , Zonneveld Frans W. , Wiersinga Wilmar M.
Published: March 2003

BACKGROUND

Two‐thirds of patients with Graves' ophthalmopathy (GO) respond to immunosuppressive treatment (prednisone or orbital irradiation), but one‐third do not respond. Responders are likely to be in the active, oedematous stage of the eye disease, nonresponders in the inactive fibrotic stage. Clinical distinction between the two stages can be difficult. Quantitative magnetic resonance imaging (MRI) might be helpful in this respect, as T2 relaxation times are longer in oedematous than in fibrotic tissues.

STUDY DESIGN

Prospective study on quantitative orbital MRI in healthy subjects and patients with moderately severe GO, evaluating T2 relaxation time of extraocular muscles (EOM): (a) in patients vs. controls, and (b) in patients, as a predictor of outcome to orbital irradiation.

SUBJECTS and MEASUREMENTS

Nine healthy volunteers and 64 consecutive patients with moderately severe untreated GO, who were euthyroid for ≥2 months and qualified for orbital irradiation. T2 relaxation times were measured at the site of the largest diameter in all eight EOM of each subject. Baseline T2 values in patients were related to outcome of radiotherapy, as assessed by an independent observer 6 months later according to predefined criteria.

RESULTS

T2 relaxation times of the eight EOM were longer in GO patients than in controls: median [range] 126 [52–250]vs. 88 [50–126] msec; P = 0·003. Per subject the single eye muscle with the longest T2 time was selected to represent active inflammation (excluding the lateral muscles for technical reasons). Again patients were different from controls: 160 [68–250]vs. 103 [86–115] msec, P < 0·001. In the group of 34 responders to subsequent radiotherapy, these T2 times tended to be longer than in the 30 nonresponding patients: 168 [108–250]vs. 138 [68–216] msec, P = 0·07. Using a cut‐off value of 130 msec (derived from a receiver‐operator‐characteristics curve) a positive predictive value of 64% and a negative predictive value of 92% for the outcome of radiotherapy was calculated.

CONCLUSION

Quantitative orbital magnetic resonance imaging was found to be less accurate in predicting succesful outcome of radiotherapy than expected. It seems more useful in detecting the fibrotic end‐stage than the active stage of Graves' ophthalmopathy. It is therefore of limited use in the decision whether or not to apply immunosuppression in patients with moderately severe Graves' ophthalmopathy.
Effects of the selective oestrogen receptor modulator—raloxifene—on calcium and PTH secretory dynamics in women with osteoporosis
Authors: Oleksik A. , Duong T. , Popp‐Snijders C. , Pliester N. , Asma G. , Lips P.
Published: March 2003

OBJECTIVES A possible mechanism for the maintenance of bone mass by oestrogens and the selective oestrogen receptor modulator (SERM)—raloxifene—is an interaction with calciotropic hormones. We studied the effects of raloxifene on calcium‐PTH homeostasis.

PATIENTS AND MEASUREMENTS Calcium and EDTA infusions were performed in 32 post‐menopausal women with osteoporosis (BMD T score < − 2·5). This cross‐sectional study was performed in the third year of the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, a double‐blind, placebo‐controlled study. After an overnight fast, calcium glubionate (5 mg/kg BW*h), and after 2·5 h of test‐free interval, Na3EDTA (40 mg/kg BW*h) were given intravenously. The duration of infusions was based on individual plasma total calcium before the calcium infusion (t = 0), the target calcium (2·60 and 1·95 mmol/l, respectively), and desired mean calcium change (0·010 mmol/L*min). Blood samples were taken at 0 and every 5 minutes of both infusions. Plasma PTH levels were fitted into an inversed sigmoidal relation with plasma calcium. The effect of raloxifene on calcium‐PTH homeostasis was tested in linear regression models adjusted for age and BMI. Nine patients used placebo, 13 raloxifene 60 mg/day and 10 raloxifene 120 mg/day.

RESULTS Raloxifene use was associated with lower plasma albumin (40·7 ± 1·8 vs. 38·0 ± 2·0 and 38·5 ± 2·3 g/l, for placebo, raloxifene 60 mg/day and raloxifene 120 mg/day, respectively, P = 0·01), lower plasma total calcium at t = 0 (2·28 vs. 2·24 and 2·21; ± 0·07 mmol/L; P = 0·03), lower plasma total calcium at 50% of maximal PTH secretion (PTH set‐point: 2·23 ± 0·06 vs. 2·18 ± 0·07 and 2·16 ± 0·08 mmol/l, P = 0·06), and lower plasma non‐suppressible PTH (0·84 ± 0·19 vs. 0·75 ± 0·10 and 0·73 ± 0·05 pmol/l, P = 0·02). After correction for plasma albumin, the differences for plasma calcium at t = 0 and at PTH set‐point were no longer significant. In contrast, the difference in PTH suppression during calcium load was not explained either by differences in plasma albumin or calcium.

CONCLUSION Raloxifene did not have any detectable effect on the PTH set‐point. An effect on non‐suppressible PTH secretion cannot be excluded.
Bone metabolism and body composition in Japanese patients with active acromegaly
Authors: Kaji Hiroshi , Sugimoto Toshitsugu , Nakaoka Daiki , Okimura Yasuhiko , Kaji Hidesuke , Abe Hiromi , Chihara Kazuo
Published: March 2003

OBJECTIVE Skeletal involvement is a common clinical feature in acromegalic patients. Although several recent reports are available concerning bone mineral density (BMD) in acromegaly, the controversy still exists as to whether BMD of acromegalic patients is increased or not. The present study was performed to examine biochemical bone metabolic indices and BMD as well as body composition in 26 Japanese patients with active acromegaly and 26 control subjects matched for age, sex, race and height in a cross‐sectional study.

MEASUREMENTS BMD of the lumbar spine and femoral neck, as well as body composition, was measured by dual‐energy X‐ray absorptiometry. Mid‐radial BMD was measured by single‐photon absorptiometry. We also determined serum levels of IGF‐I, IGFBP‐3 and osteocalcin (OC) as well as urinary levels of deoxy‐pyridinoline (D‐Pyr) and CrossLaps.

RESULTS Percent lean body mass was increased and percent fat mass was decreased in the acromegalic patients compared to control subjects. Serum levels of OC, as well as urinary levels of D‐Pyr and CrossLaps, were significantly higher in acromegalic patients compared to control subjects (9·8 ± 1·2 vs. 5·7 ± 0·77 for OC; 11·8 ± 1·66 vs. 5·0 ± 0·49 for D‐Pyr; 437·6 ± 68·4 vs. 156·5 ± 39·6 for CrossLaps). Z scores of BMD at mid‐radius as well as lumbar spine and femoral neck were significantly higher in acromegalic patients compared to control subjects (1·086 ± 0·311 vs.−0·060 ± 0·274 for mid‐radius; 1·022 ± 0·280 vs. 0·319 ± 0·165 for lumbar spine; 1·292 ± 0·347 vs. 0·232 ± 0·264 for femoral neck).

CONCLUSIONS The present study revealed that a decrease in percent fat mass and an increase in percent lean body mass were observed in Japanese patients with active acromegaly. Bone mineral density at all sites and bone metabolic markers were also increased in acromegaly. The present findings provide additional evidence that the GH/IGF‐I axis might play an important role in the maintenance of bone mass as well as the regulation of body composition in Japanese adults.
Hyperthyroidism is associated with lengthening of ventricular repolarization
Authors: Colzani R. M. , Emdin M. , Conforti F. , Passino C. , Scarlattini M. , Iervasi G.
Published: March 2003

OBJECTIVELengthened ventricular repolarization, as assessed by the QT interval on electrocardiogram (ECG), can predispose to an increased risk of cardiac dysrhythmias; no data are available on QT corrected for heart rate (QTc) in hyperthyroidismin vivo.

DESIGNQT and RR intervals from 24 h ambulatory ECG Holter recording were measured in patients with hyperthyroidism and again following pharmacological achievement of stable euthyroidism for at least 2 months.

PATIENTSWe enrolled a total of 16 hyperthyroid patients with Graves' disease, six males and 10 females (mean age 47 ± 4 years, mean ± SEM); 13 healthy age‐ and sex‐matched subjects were utilized as a control group.

MEASUREMENTSThe QT analysis was carried out by a computerized algorithm (QTc was corrected by the heart rate by Bazett's formula). Serum total T4, total T3, free T4, free T3 and TSH concentrations were measured by a fully automated immunoenzymometric assay; plasma norepinephrine by automatized high‐pressure liquid chromatography, potassium and chloride by a potentiometric method, magnesium and calcium by a colourimetric method.

RESULTSThe 24‐h average QTc in the hyperthyroid patients was significantly prolonged compared to controls (458 ± 7vs.431 ± 6 ms,P = 0·01) and it returned to normal after treatment of thyrotoxicosis (432 ± 6 ms,P < 0·05vs.time H, NSvs.controls). QTc positively correlated with FT3 (r = 0·63,P < 0·001) and with FT4 (r = 0·481,P < 0·02). Conversely, QTc did not correlate with plasma basal norepinephrine levels, nor with electrolytes.

CONCLUSIONSHyperthyroidism is associated with prolonged QTc that normalizes once the patient becomes euthyroid. The strong positive correlation between FT3 and QTc supports the hypothesis of an important role of thyroid hormone on modulation of QTc lengthening.
The nature of human chorionic gonadotrophin glycoforms in gestational thyrotoxicosis
Authors: Talbot J. A. , Lambert A. , Anobile C. J. , McLoughlin J. D. , Price A. , Weetman A. P. , Robertson W. R.
Published: March 2003

OBJECTIVE We examined the charge heterogeneity and carbohydrate complexity of hCG in healthy pregnant Asian subjects and Asian women with gestational thyrotoxicosis to assess whether particular glycoforms of hCG are associated with the thyrotoxicosis of pregnancy.

DESIGN Blood was taken at 8–16 weeks of gestation from five pregnant Asian women with clinical symptoms of gestational thyrotoxicosis and biochemical indicators of hyperthyroidism and from six age‐matched healthy pregnant women. hCG charge heterogeneity and carbohydrate complexity were assessed by fast protein liquid chromatography chromatofocusing and concanavalin A affinity chromatography, respectively. The degree of terminal sialylation of the different glycoforms was measured by ricin affinity chromatography, which detects exposed galactose residues following desialylation.

RESULTS Free T3, free T4 and hCG levels were elevated and TSH suppressed in the thyrotoxic subjects compared to controls (P < 0·007). Overall, the glycoform distribution of the hCG in the blood from the control and thyrotoxic groups was similar, with a median pI of 4·34 (median and range: 3·78–4·68) and pI 4·23 (3·98–4·38). Free T4 (P < 0·028) and free T3 (P < 0·03) levels were positively correlated to both the absolute hCG concentration and the percentage of hCG forms between pI 3·36–4·0. The distribution of simple (73–88·6%), intermediate (9·7–26·4%) and complex (0·1–7·3%) branching oligosaccharide forms was similar in both groups, as was the percent hCG which bound to ricin (< 3·2%).

CONCLUSION We conclude that excessive thyroid stimulation in the thyrotoxic patients is associated both with the absolute concentration of hCG and the relative proportion of acidic glycoforms between pI 3·36 and 4·0.
Mothers with congenital adrenal hyperplasia and their children: outcome of pregnancy, birth and childhood
Authors: Krone Nils , Wachter Isolde , Stefanidou Marianna , Roscher Adelbert A. , Schwarz Hans Peter
Published: March 2003

OBJECTIVES Fertility rates in women with congenital adrenal hyperplasia (CAH) are reported to be poor, but few data are available. We assessed rates and course of pregnancy, mode of delivery and long‐term outcome of offspring from women with CAH.

DESIGN A large cohort of women with CAH due to 21‐hydroxylase deficiency had initially been diagnosed and followed at one centre. Those women who had given birth were contacted. Information was gathered from hospital records, direct patient contact, structured questionnaire and the Documentation of Pregnancy and Preventive Care Booklets.

RESULTS Between 1978 and 1998, 18 women with CAH (one salt wasting, 12 simple virilizing, five nonclassical) had given birth to 31 children (18 females, 13 males). Delivery was by Caesarean section in 16 out of the 31 children. None of the female newborns was masculinized. Twenty‐nine children were born at term, five children were small for gestational age (SGA). Postnatal development was basically normal in all children; 18 are now older than 10 years, seven are between 5 and 10 years old, six are less than 5 years old.

CONCLUSIONS Fertility is reduced in females with CAH, especially those with the severe or salt wasting phenotype. In those women with CAH who do conceive, course and outcome of pregnancy is mostly uneventful, although the rate of SGA offspring may be increased. Psychomotor and somatic long‐term development of the children was within normal limits.
Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa
Authors: Støving R. K. , Andersen M. , Flyvbjerg A. , Frystyk J. , Hangaard J. , Vinten J. , Koldkjær O. G. , Hagen C.
Published: March 2003

objective In animals, somatostatin (SRIH) and growth hormone (GH)‐releasing hormone (GHRH) increase feeding via a common neural mechanism. Furthermore, SRIH counteracts the suppressive action of corticotrophin‐releasing hormone (CRH) on food intake. Hypothetically, SRIH could be involved in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH.

design To study the influence of hypothalamic somatostatinergic inhibition on the exaggerated somatotroph responsiveness to GHRH in patients with severe AN, two GHRH stimulation tests were performed in random order following pretreatment with placebo or PD 2 mg/kg body weight in 13 patients and in 10 age‐matched healthy controls. The test procedure was repeated in the patients after weight gain.

results In controls, PD potentiated the GHRH‐stimulated GH rise but this effect was absent in AN patients. The relative potentiating effect of PD was inversely correlated to cortisol excretion levels and positively correlated to leptin serum levels. After weight gain the relative PD effect increased twofold.

conclusion The pyridostigmine–GHRH responsive pattern points indirectly to greater SRIH withdrawal and greater GHRH release in anorexia nervosa. Moreover, hypothalamic SRIH activity seems to be inversely related to cortisol levels, indirectly supporting the hypothesis that SRIH and CRH neuronal activity are inversely related in anorexia nervosa. Leptin, which is believed to act on hypothalamic feeding mechanisms, seems to be positively related to SRIH activity. Finally, the present data demonstrate that the potentiating effect of pyridostigmine in anorexia nervosa is related to body mass index and increases upon weight gain, suggesting that the low somatostatinergic tone is not primary but is related to the weight loss.
Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation
Authors: Chung J.‐K. , Park Y. J. , Kim T. Y. , So Y. , Kim S.‐K. , Park D. J. , Lee D. S. , Lee M. C. , Cho B. Y.
Published: March 2003

objective This study was designed to investigate whether an elevated serum antithyroglobulin antibody (TgAb) reflects cancer recurrence in thyroglobulin (Tg)‐undetectable patients with differentiated thyroid carcinoma (DTC) after thyroid ablation.

design We measured serum TgAb level and evaluated the disease status in 226 DTC patients who had undergone remnant ablation and showed an undetectable Tg result as assessed by immunoradiometric assay.

measurements Radioligand assay of TgAb was performed. Recurrence was assessed by 131I scan, 18F‐fluorodeoxyglucose positron emission tomography, sonography, computed tomography, or by surgical operation.

results Fifty‐one patients (22·6%) of the Tg‐undetectable patients showed positive TgAb, and 25 (49·0%) of these were confirmed with recurrence. The recurrence rate of TgAb‐positive patients was higher than that of TgAb‐negative patients (3·4%; P < 0·0001). During follow‐up, 73·1% of the disease‐free patients showed spontaneously decreased TgAb levels. A total of 71·4% of patients with recurrent cancer, who showed responses to surgical operation or radio‐iodine treatment, also showed a decreased TgAb level.

conclusions Persistently elevated TgAb levels appear to serve as a useful marker for recurrent or persistent DTC in patients with undetectable serum Tg results. Thus, the routine measurement of TgAb in such patient populations may be indicated.
Spontaneous growth hormone secretory characteristics in children with partial growth hormone insensitivity
Authors: Bjarnason Ragnar , Banerjee Kausik , Rose Steven J. , Rosberg Sten , Metherell Louise , Clark Adrian J. L. , Albertsson‐Wikland Kerstin , Savage Martin O.
Published: March 2003

objective To investigate the characteristics of spontaneous GH secretion in four male children with short stature due to partial GH insensitivity. Their molecular defect consists of inclusion of a mutant intronic pseudoexon in the region of the GH receptor involved in homodimerization.

subjects The subjects were two pairs of brothers who were first cousins, aged 10·4–14·2 years, heights −3·3 to −5·6 SDS, from a consanguineous Pakistani family. Basal serum IGF‐I levels were extremely low (20–29 mg/l; NR > 50), with absent or minimal response to human recombinant GH (hGH) stimulation. Serum IGFBP‐3 SDS levels were also low (−2·9 to −8·9). GH binding protein (GHBP) levels were normal (28·1–51·7%).

methods Spontaneous GH secretion was studied by intermittent (20 min) venous sampling from 2000 to 0800 h. The secretion profiles were analysed using the Pulsar programme and compared to data from a reference population of 76 prepubertal Swedish children [median age 10·7 years, median height −1·1 SDS (−2·0 to 1·4)] according to Swedish growth standards.

results Median (range) Pulsar‐derived values in the four patients and controls were, respectively: GHmax (mU/l) 276·6 (178·7–325·8) and 27·2 (13·1–94·9), mean GH (mU/l) 64·5 (41·9–77·8) and 5·8 (3·2–20·6), baseline (mU/l) 12·3 (11·7–20·1) and 1·1 (0·2–6·1), AUCb (mU/l × 24 h) 1210 (684–1555) and 112·5 (60·6–316·4), i.e. all parameters of GH secretion in the four patients were markedly elevated compared with the control population.

conclusions Spontaneous GH secretion is elevated in partial GH insensitivity. This investigation could be of diagnostic value in children with short stature.
Transdermal oestradiol replacement therapy enhances platelet constitutive nitric oxide synthase activity in postmenopausal women with type 2 diabetes mellitus
Authors: Martina Valentino , Bruno Guido Albino , Origlia Carla , Gaia Daniela , Trucco Fulvia , Pescarmona Gianpiero
Published: March 2003

objective To determine whether treatment with transdermal oestrogen replacement therapy (TERT) in postmenopausal women with type 2 diabetes mellitus was able to increase the activity of constitutive nitric oxide synthase (cNOS) in platelets.

research design and methods Eighteen postmenopausal women with type 2 diabetes mellitus (group A) were studied in basal conditions (A1) and on the 10th day of the third month of a sequential opposed TERT (A2) evaluating platelet cNOS activity measured by the conversion of radiolabelled l‐arginine to l‐citrulline. As a control group (B) 25 normal postmenopausal women underwent the same treatment (B1 and B2 before and during treatment, respectively).

results Basal values of platelet cNOS activity were superimposable (0·6 ± 0·1 vs. 0·7 ± 0·1 fmol/min/109 plts, NS). During TERT, platelet cNOS activity rose in A and B (0·6 ± 0·1 vs. 1·8 ± 0·1 fmol/min/109 plts, P < 0·05 and 0·7 ± 0·1 vs. 2·4 ± 0·2, P < 0·001, A1 vs. A2 and B1 vs. B2, respectively). However, platelet cNOS activity of A2 did not reach the values of B2 (1·8 ± 0·1 vs. 2·4 ± 0·2 fmol/min/109 plts, P < 0·05; A2 vs. B2, respectively).

conclusions Sequential opposed transdermal oestrogen replacement therapy was able to increase platelet cNOS activity in postmenopausal women with type 2 diabetes mellitus, suggesting that its use might be positive in preventing cardiovascular pathologies.
Underexpression of Gcm2, a master regulatory gene of parathyroid gland development, in adenomas of primary hyperparathyroidism
Authors: Correa Pamela , Åkerström Göran , Westin Gunnar
Published: March 2003

objective Glial cells missing (Gcm) was first identified as a binary switch between neuronal and glial determination in Drosophila. Two homologues of DrosophilaGcm have been identified in mice and humans, namely Gcm1 and Gcm2. Mouse Gcm2 is restricted to parathyroid tissues and Gcm2 was recently identified as a master regulatory gene of parathyroid gland development as Gcm2 knockout mice lack parathyroid glands.

design/patients To identify Gcm2 transcripts in human non‐neural tissues and to examine whether Gcm2 is involved in parathyroid gland tumorigenesis we analysed Gcm2 transcript levels in several non‐neural tissues by reverse transcriptase polymerase chain reaction (RT‐PCR) and performed real‐time quantitative RT‐PCR analysis on five normal glands, 15 parathyroid adenomas of primary hyperparathyroidism (HPT) and nine hyperplastic glands of secondary HPT.

results We found high Gcm2 mRNA expression in human parathyroid glands in comparison with other non‐neural tissues and underexpression in parathyroid adenomas but not in lesions of HPT secondary to uraemia.

conclusion Because adenomas demonstrate lower Gcm2 expression than normal glands we suggest that reduced expression of Gcm2 contributes to parathyroid gland tumorigenesis. We speculate that a proper expression level of the Gcm2 transcription factor could be important for maintaining a fully differentiated state of the parathyroid cell.
Preparation for radioactive iodine administration in differentiated thyroid cancer patients
Authors: Liel Yair
Published: March 2003

objective Because in recent years the practice of TSH suppression has changed, and thyroxine doses have been reduced significantly in the treatment of patients with low‐risk differentiated thyroid cancer, the goal of this study was to determine the time needed to attain a target TSH level (of 30 mIU/l) following levothyroxine withdrawal in patients treated with thyroxine according to current guidelines, in anticipation of radioactive iodine (RAI) administration.

design Observational study.

patients Thirteen consecutive patients with differentiated thyroid cancer on suppressive doses of levothyroxine planned for RAI administration. Five of the patients received cholestyramine in an attempt to facilitate TSH recovery.

measurements Serum TSH, free‐T3 and free‐T4, at 3–4‐day intervals.

results In 13 patients on suppressive doses of thyroxine, on 15 separate occasions, baseline TSH levels were between 0·01 and 0·4 mIU/l. The mean interval required to reach the target TSH concentration of at least 30 mIU/l was 17 days (95% CI 15–19; range 11–28 days). Cholestyramine had no effect on the rate of TSH recovery. Once TSH concentration became detectable, it increased exponentially; and once it reached the upper limit of normal, it rarely took more than 10 days to attain target level.

conclusions Attaining target TSH level before radioactive iodine administration requires a considerably shorter time than is currently recommended. Reducing preparation time might improve patients’ acceptance of the procedure.
Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency
Authors: Pedersen Inge Bülow , Knudsen Nils , Jørgensen Torben , Perrild Hans , Ovesen Lars , Laurberg Peter
Published: March 2003

background and aims Autoimmune thyroiditis is one of the most common autoimmune disorders. Autoantibodies against the thyroid gland, with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common autoantibodies, can often be demonstrated in serum in population surveys. In the present study we evaluated if TPO‐Ab and Tg‐Ab tend to develop in parallel or whether one or the other may be more prevalent in subsets of the population.

methods In a cross‐sectional comparative study, performed in two areas of Denmark with mild and moderate iodine deficiency, 4649 randomly selected subjects in age groups between 18 and 65 years were examined. Blood tests were analysed for TPO‐Ab and Tg‐Ab using assays based on the radioimmunoassay (RIA) technique. The participants answered questionnaires, were clinically examined and had urine samples collected.

results The overall prevalence rate of thyroid autoantibodies (TPO‐Ab and/or Tg‐Ab) was 18·8%. The prevalence rates of TPO‐Ab and Tg‐Ab were similar (13·1 vs. 13·0%). Both antibodies were more frequent in females than in males, and in females the prevalence rates increased with age. In the age group 60–65 years thyroid antibodies were more frequently measured in sera from moderate than from mild iodine‐deficient area (P = 0·02), whereas no differences were seen in younger subjects. In 38·8% of participants with thyroid autoantibodies in serum, both antibodies were present. In sera with both TPO‐Ab and Tg‐Ab present the concentrations of the antibodies were generally higher than in sera with only one type of antibody present.

conclusion The prevalence rates of TPO‐Ab and Tg‐Ab were similar in this large population survey. The results suggest that TPO‐Ab and Tg‐Ab predominantly develop due to a general alteration in the immune system, whereas specific antigenic mechanisms are probably of less importance. However, further studies are needed to clarify the mechanisms involved in the development of thyroid autoantibodies.
Hyperprolactinaemia in hypothyroidism: clinical significance and impact of TSH normalization
Authors: Raber Wolfgang , Gessl Alois , Nowotny Peter , Vierhapper Heinrich
Published: March 2003

objectives Menstrual irregularities in hypothyroidism have been reported to occur less frequently than previously described. We therefore studied the influence of serum PRL in patients with newly diagnosed subclinical and overt hypothyroidism and in hyperprolactinaemic patients treated with T4 to distinguish the impact of hypothyroidism from that of confounding drugs on hyperprolactinaemia and menstrual irregularities.

patients and methods PRL was determined in 1003 consecutive hypothyroid patients (TSH > 4·0 mU/l) at referral, and after TSH normalization in 84 (8%) initially hyperprolactinaemic (female, > 480 mU/l; male, > 432 mU/l) subjects. Medical history (psychotropic drugs and oestrogens) and menstrual patterns were assessed at referral and after 8 ± 5 (mean ± SD) months of T4 therapy. Pituitary magnetic resonance imaging (MRI) was offered to patients with persistently elevated PRL.

results Menstrual disturbancies (oligomenorrhoea/secondary amenorrhoea, O/A) were not more common (P = NS) in hyper‐ than in normoprolactinaemic women (26% and 16%, respectively). We observed no galactorrhoea and no correlation between PRL and TSH or O/A except in pregnant or lactating women (N = 11). Oestrogens or antidepressants (including selective serotonin reuptake inhibitors) did not cause hyperprolactinaemia but antipsychotic drugs did. PRL decreased with T4 therapy (P < 0·01) in patients not using confounding drugs (from 720 ± 288 to 360 ± 192 mU/l) but menstrual irregularities persisted. PRL remained unchanged in patients receiving antipsychotic treatment. PRL was also unchanged in patients with pituitary abnormalities (seven micro‐, one macroadenoma).

conclusions Hyperprolactinaemia was not an important feature in patients with newly diagnosed hypothyroidism. Neuroleptic drugs may cause persisting hyperprolactinaemia after TSH normalization. In addition, menstrual disturbancies do not relate to hyperprolactinaemia in hypothyroidism.
Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with β‐thalassaemia disease
Authors: Mahachoklertwattana Pat , Chuansumrit Ampaiwan , Sirisriro Rojana , Choubtum Lulin , Sriphrapradang Arporn , Rajatanavin Rajata
Published: March 2003

objective Thalassaemia/haemoglobinopathy is a hereditary disease causing increased erythropoiesis and expansion of the bone marrow cavity. As a consequence, there is a reduction in trabecular bone tissue resulting in osteopenia/osteoporosis. The present study was performed to assess bone mineral density (BMD) in children and adolescents with β‐thalassaemia disease and to determine biochemical and hormonal changes that may affect BMD.

methods Forty‐eight children and adolescents with β‐thalassaemia were divided into two groups, transfusion‐dependent (TD) (n = 16) and transfusion‐independent (TI) (n = 32). All patients were treated suboptimally. BMD was determined by dual‐energy X‐ray absorptiometry. Bone maturation was assessed by radiographic bone age (BA). Blood and urine samples were obtained for the determination of biochemical and hormonal profiles, which included PTH, 25‐hydroxyvitamin D (25‐OHD), osteocalcin, bone‐specific alkaline phosphatase, IGF‐1, fT4, TSH and urine deoxypyridinoline.

results Most of the patients were short and underweight, and they had delayed BA with mean Z‐scores of −2·77 in the TD and −2·04 in TI groups. The mean Z‐scores of BMD in the TD vs. TI groups of total body, radius, femoral neck and lumbar spine were −2·09 vs.−1·49, −0·73 vs. −0·54, −1·93 vs.−1·17 and −3·45 vs.−2·43, respectively. Although the means BMD values in the TD group were lower than those in the TI group, they were not significantly different. Mean serum IGF‐1 levels were lower in the TD than the TI groups, 11·6 and 24·9 nmol/l, respectively (P < 0·05). Other biochemical and hormonal profiles did not differ between these two groups.

conclusions Patients with undertransfused severe β‐thalassaemia had more bone marrow expansion, lower serum IGF‐1 levels and more delayed bone age than did patients with untransfused moderately severe β‐thalassaemia. Therefore, the severity of the disease appeared to be a primary factor for low bone mineral density in undertransfused patients in association with bone age delay and low serum IGF‐1.
The regulation of growth in glycogen storage disease type 1
Authors: Mundy Helen R. , Hindmarsh Peter C. , Matthews David R. , Leonard James V. , Lee Philip J.
Published: March 2003

objective To study endocrine and metabolic variables that affect growth in patients with glycogen storage disease type 1 (GSD‐1) receiving standard dietary therapy.

design Observational study.

patients and measurements Thirty‐eight patients with GSD‐1, age range 0·6–32·9 years, were investigated on their usual dietary regimens. Data on height, height velocity in prepubertal children, endocrine and metabolic responses to oral glucose load, 24‐h serum cortisol and GH concentration profiles and serum IGF‐1 concentrations were collected.

results The population studied was shorter than average, with a median height standard deviation score (SDS) of −1·60, but significantly taller than a historical population studied at the same institution that had not received dietary therapy at the time of study. A wide range of height SDS was encountered (−5·28 to 1·21) and a subset still exhibit marked growth failure. Median body mass index (BMI) SDS was 0·72 (range −1·34 to 3·96). Those patients with the greatest BMI SDS had the lowest serum GH concentrations but serum IGF‐1 concentrations were within the normal range. Patients with the poorest growth exhibit low serum insulin concentration responses to glucose load, GH insensitivity and higher mean 24‐h plasma cortisol levels when compared to those patients who were better grown.

conclusion This study shows that overall the growth of this group of patients with glycogen storage disease type 1 has improved compared to that of a historical control group. There remains a subset of this population with poor growth despite therapy. The measured endocrine responses in this subset are similar to those reported for untreated patients. To improve the growth further in these individuals it will be necessary to understand whether this is failure of prescribed therapy or failure to comply with therapy.
Fat distribution in non‐obese girls with and without precocious pubarche: central adiposity related to insulinaemia and androgenaemia from prepuberty to postmenarche
Authors: Ibáñez Lourdes , Ong Ken , De Zegher Francis , Marcos Maria Victoria , Del Rio Luis , Dunger David B.
Published: March 2003

objective Precocious pubarche (PP) in girls is associated with hyperinsulinaemia and dyslipidaemia of prepubertal onset, and with ovarian hyperandrogenism and ovulatory dysfunction in adolescence, particularly if they also had prenatal growth restraint and postnatal growth acceleration. Hyperinsulinaemia may be the pathogenic key factor, possibly amplified by hyperandrogenaemia. While such PP girls do not have increased body mass index (BMI), we hypothesized that body fat mass and fat distribution may differ between PP girls and matched controls, and may relate to insulin and androgen levels.

patients and design Sixty‐seven PP girls (age range 6·0–18·0 years) and 65 control girls matched for age and pubertal stage (5·9–18·0 years) had height, weight, waist and hip circumferences measured, and dual‐energy X‐ray absorptiometry (DXA) assessment of total body fat mass, and fat mass in abdominal and truncal regions. All girls had fasting plasma glucose, serum insulin, lipids, testosterone and SHBG levels measured; PP girls also had a standard 2‐h oral glucose tolerance test (oGTT).

results Despite no differences in BMI, PP girls had significantly larger waist circumference, waist‐to‐hip ratio, total fat mass, percentage fat mass, abdominal fat mass, and truncal fat mass vs. controls in each pubertal stage. Overall, fasting insulin levels, free androgen index (FAI) and blood lipid levels were more closely related to central fat than to total body fat mass. In a multiple regression analysis, truncal fat mass was independently related to both fasting insulin (P = 0·009) and FAI (P < 0·0001). Abdominal fat mass was inversely related to birthweight (r = −0·25, P = 0·001). In PP girls, central fat mass was positively related to insulin levels after oGTT (truncal fat vs. 30 min insulin; r = 0·46, P < 0·0005).

conclusions Precocious pubarche girls had excess total body and central fat mass throughout all pubertal stages, and increased central fat was related to hyperinsulinaemia and hyperandrogenaemia. It remains to be verified whether body composition in PP girls can be normalized by insulin‐sensitization and/or antiandrogen therapy.
The effect of a very low‐calorie diet‐induced weight loss on the severity of obstructive sleep apnoea and autonomic nervous function in obese patients with obstructive sleep apnoea syndrome
Authors: Kansanen Martti , Vanninen Esko , Tuunainen Arja , Pesonen Petri , Tuononen Vuokko , Hartikainen Juha , Mussalo Hanna , Uusitupa Matti
Published: March 2003

The aim of this study was to examine the effect of a very low‐calorie diet (VLCD)‐induced weight loss on the severity of obstructive sleep apnoea (OSA), blood pressure and cardiac autonomic regulation in obese patients with obstructive sleep apnoea syndrome (OSAS). A total of 15 overweight patients (14 men and one woman, body weight 114 ± 20 kg, age 52 ± 9 years, range 39–67 years) with OSAS were studied prospectively. They were advised to follow a 2·51–3·35 MJ (600–800 kcal) diet daily for a 3‐month period. In the beginning of the study, the patients underwent nocturnal sleep studies, autonomic function tests and 24‐h electrocardiograph (ECG) recording. In addition, 15 age‐matched, normal‐weight subjects were studied. They underwent the Valsalva test, the deep‐breathing test and assessment of heart rate variability at rest. The sleep studies and autonomic function tests were repeated after the weight loss period. There was a significant reduction in weight (114 ± 20 kg to 105 ± 21 kg, P<0·001), the weight loss being 9·2 ± 4·0 kg (range 2·3–19·5 kg). This was associated with a significant improvement in the oxygen desaturation index (ODI4) during sleep (31 ± 20–19 ±18, P<0·001). Before the weight loss the OSAS patients had significantly higher blood pressure (150 ± 18 vs. 134 ± 20, P<0·05, for systolic blood pressure, 98 ± 10 vs. 85 ± 13, P<0·05, for diastolic blood pressure) and heart rate (67 ± 10 beats min−1 vs. 60 ± 13, P<0·05) at rest than the control group. They had also lower baroreflex sensitivity (4·7 ± 2·8 ms mmHg−1 vs. 10·8 ± 7·1 ms mmHg−1, P<0·01). During the weight reduction, the blood pressure declined significantly, and the baroreflex sensitivity increased by 49%. In conclusion, our experience shows that weight loss with VLCD is an effective treatment for OSAS. Weight loss improved significantly sleep apnoea and had favourable effects on blood pressure and baroreflex sensitivity that may have prognostic implications.
How can the variability in ultrasound measurement of intima‐media thickness be reduced? Studies of interobserver variability in carotid and femoral arteries
Authors: Schmidt  , Wendelhag
Published: March 2003

A critical component in scientific studies of most biological variables is the variation or error in measurements which leads to non‐identical results of repeated measurements from the same subject. The aim of this study was to investigate whether the interobserver error (s) in measurement of intima‐media thickness (IMT) in carotid and femoral arteries could be decreased if the mean value obtained using two ultrasound images from each of the right and left arteries was used in the analyses instead of the mean value obtained using images from only the right artery. In addition, we wished to evaluate two different reading procedures, one based on manual tracing of echo interfaces and the other on automated edge detection. In a methodological study, 50 subjects were examined with ultrasound twice in the same day by two independent laboratory technologists. The ultrasound images were analysed in two ways: using a computerized manual tracing analysing system and an automated analysing system. When both right and left carotid arteries were examined (manual reading), the interobserver error was smaller than that determined for the examination of only the right artery, for IMTmean in both the common carotid artery (P = 0·06) and the carotid artery bulb (P<0·05). The interobserver error was also significantly smaller for double‐sided vs. one‐sided examination with automated reading of IMTmean in the common carotid artery (P<0·01) and in the carotid artery bulb (P<0·01). The coefficient of variation (CV) for measurement in the common carotid artery decreased from 8·6% (one‐sided, manual reading) to 5·3% (double‐sided, automated reading). The interobserver error in measurement of IMT in the common femoral artery did not improve by examination of both right and left arteries. The results from this study show that the interobserver errors in measurement of IMT can be decreased by using ultrasound images from both the right and the left carotid arteries, and that the use of an automated analysing system greatly simplifies the reading of ultrasound images with sustained low variability.
Adaptive responses of human skeletal muscle to vibration exposure
Authors: Bosco  , Colli  , Introini  , Cardinale  , Tsarpela  , Madella  , Tihanyi  , Viru
Published: March 2003

The aim of this study was to investigate the effects of whole‐body vibrations (WBV) on the mechanical behaviour of human skeletal muscle. For this purpose, six female volleyball players at national level were recruited voluntarily. They were tested with maximal dynamic leg press exercise on a slide machine with extra loads of 70, 90, 110 and 130 kg. After the testing, one leg was randomly assigned to the control treatment (C) and the other to the experimental treatment (E) consisting of vibrations. The subjects were then retested at the end of the treatment using the leg press. Results showed remarkable and statistically significant enhancement of the experimental treatment in average velocity (AV), average force (AF) and average power (AP) (P<0·05–0·005). Consequently, the velocity–force and power–force relationship shifted to the right after the treatment. In conclusion, it was affirmed that the enhancement could be caused by neural factors, as athletes were well accustomed to the leg press exercise and the learning effect was minimized.
Wall motion abnormalities in male elite orienteers are aggravated by exercise
Authors: Damm  , Andersson  , Henriksen  , Niklasson  , Jonason  , Ahrén  , Wesslén  , Nyström‐Rosander  , Rolf  , Hedenstierna  , Ringqvist  , Friman
Published: March 2003

During the period 1979–92, 16 (15 men and one woman) sudden unexpected cardiac deaths occurred among young Swedish orienteers. This finding indicated a sharp increase in the death rate of orienteers, and necropsy demonstrated that myocarditis was a common histopathological finding. Therefore, an extensive non‐invasive cardiac investigation was performed. A total of 59 male élite orienteers (mean age 23 years) and 36 cross‐country skiers and middle‐distance runners (mean age 22 years), serving as controls, were examined by both echocardiography at rest and radionuclide ventriculography at rest and during exercise.

Wall motion abnormalities were found in eight orienteers using echocardiography. The purpose of this study was to examine whether the group of orienteers with wall motion abnormalities found using echocardiography had a smaller increase in ejection fraction from rest to exercise using radionuclide ventriculography than the rest of the orienteers and the controls, indicating an aggravation of the wall motion abnormalities during exercise. There were no significant differences in the ejection fraction at rest between the groups. In the orienteers with wall motion abnormalities (group 1), 62% (five out of eight) had less than a 0·05 unit increase in left ventricular ejection fraction compared with 27% (14 out of 51) of the remaining orienteers (group 2) and 19% (7 out of 36) of the controls (group 3). A comparison of athletes in group 1 with those in groups 2 and 3 combined revealed a statistically significant difference (P < 0·05). The divergent response in left ventricular ejection fraction during exercise suggests an aggravation of the wall motion abnormalities with exercise. Both the echocardiographic and the radionuclide ventriculographic findings indicate that the orienteers in group 1 had concealed left ventricular damage.
Middle cerebral artery blood velocity during exercise in patients with atrial fibrillation
Authors: Ide  , Gulløv  , Pott  , Lieshout J. J. Van , Koefoed  , Petersen  , Secher
Published: March 2003

Atrial fibrillation limits the ability to increase cardiac output during exercise and may, in turn, affect the exercise‐associated elevation in cerebral perfusion. In nine patients with atrial fibrillation (AF) and in five age‐matched healthy subjects, middle cerebral artery blood velocity (MCA Vmean) was measured during incremental exercise using the transcranial Doppler. The AF patient group exhibited a lower aerobic capacity than the control group [peak work rate: 106 W (71–153 W; median and range) vs. 129 W (118–159 W) and maximal oxygen uptake: 1·4 l min–1 (1·0–1·9 l min–1) vs. 1·7 l min–1 (1·4–2·2 l min–1); P =  0·05]. At rest, MCA Vmean was not significantly different between the two groups [43 cm s–1 (39–56 cm s–1) vs. 52 cm s–1 (40–68 cm s–1)]. During intense cycling, the increase in MCA Vmean was to 51 cm s–1 (40–78 cm s–1) (9%) in the AF group and lower than in the healthy subjects [to 62 cm s–1 (50–81 cm s–1) 23%; P<0·05], which corresponded with the smaller than expected increase in cardiac output [156% (130–169%) vs. 180%]. Thus, there was a correlation between the increase in MCA Vmean and the ability to increase cardiac output (r2 = 0·55, P<0·01). We suggest that, during exercise with a large muscle mass, atrial fibrillation affects the ability to elevate cerebral perfusion, and this results from an impaired ability to increase cardiac output.
Efficient lung scintigraphy
Authors: Tägil  , Evander  , Wollmer  , Palmer  , Jonson
Published: March 2003

Lung scintigraphy is a first‐choice method to diagnose lung embolism. The clinical routine in most centres is a perfusion study complemented with a ventilation study when judged necessary. We describe a routine with ventilation scintigraphy preceding perfusion scintigraphy, which is completed within one hour. Furthermore, the data acquired allow the determination of lung clearance of the tracer 99mTc‐DTPA (diethylene triamine penta‐acetate) used for the ventilation scintigraphy. An aerosol generator charged once a day with 99mTc‐DTPA solution is used for all inhalations during the day. Inhalation is monitored with a counter and interrupted when the count rate corresponds to about 20 MBq. The ventilation imaging starts and ends with posterior projections. This allows calculation of lung clearance of 99mTc‐DTPA. Perfusion scintigraphy is performed in a standard fashion with 100 MBq of 99mTc‐MAA (macro‐aggregated albumin). The ventilation study was considered to give some diagnostic information in the majority of the patients. The clearance determination allows detection of inflammatory lung disease. The background activity caused by the ventilation study comprised only 13% of the activity in the perfusion scintigraphy and did not significantly interfere with interpretation of the perfusion scan. The cost for the investigation is low because of the rational system for aerosol administration and the short time for a complete study.
Osteocalcin metabolism in the pulmonary circulation
Authors: Aliberti  , Pulignano  , Proietta  , Tritapepe  , Cigognetti  , Menichetti  , Russo  , De Michele  , Corvisieri  , Minisola
Published: March 2003

The aim of this study was to evaluate the role of the pulmonary vessel endothelium in the removal of circulating osteocalcin, by measuring the osteocalcin levels in serum from pulmonary and radial artery blood from 39 patients undergoing aorto‐coronary bypass. Because of the discrepancies between methods of measurement, two methods were used. Significant differences were observed in group A (n = 18), tested with heterologous radioimmunoassay (2·85 ± 0·67 μg l−1 in the pulmonary versus 2·69 ± 0·67 μg l−1 in the radial artery serum, P<0·001) and in group B (n = 21), tested with a two‐site immunoradiometric assay (5·22 ± 1·46 versus 4·93 ± 1·36 μg l−1, P<0·01). The percentage differences were –5·54 ± 4·76% (P<0·001) in group A and –4·99 ± 8·13% (P<0·01) in group B; the comparison between the percentage differences was not significant. These different osteocalcin concentrations between the two vascular compartments were considered a marker of osteocalcin degradation. Therefore, the study seems to demonstrate that, as well as kidney, liver and bone, the lung is a relevant site of osteocalcin catabolism. The proteolytic activity of pulmonary vessel endothelium seems to involve about 5% of the circulating peptide.
Effect of Qi‐training on blood pressure, heart rate and respiration rate
Authors: Lee Myeong Soo , Kim Byung Gi , Huh Hwa Jeong , Ryu Hoon , Lee Ho‐Sub , Chung Hun‐Taeg
Published: March 2003

To examine the physiological effects of Korean traditional Qi‐training, we investigated the changes in blood pressure, heart and respiratory rates before, during and after ChunDoSunBup (CDSB) Qi‐training. Twelve normal healthy CDSB Qi‐trainees (19–37 years old; trained for 1·3 ± 0·2 years; 9 men and 3 women) volunteered to participate in this study. Heart rate, respiratory rate, systolic blood pressure and rate–pressure product were significantly decreased during Qi‐training. From these results, we suggest that CDSB Qi‐training has physiological effects that indicate stabilization of cardiovascular system.