bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking‐type anti‐TSH receptor antibodies and relation to responsiveness to antithyroid drug therapy and remission in Graves’ disease
Authors: Tada Hisato , Mizuta Ikuko , Takano Toru , Tatsumi Ke‐ita , Izumi Yukiko , Hidaka Yoh , Amino Nobuyuki 
Published: June 2003

Summaryobjective Antithyroid drugs are effective in some patients with Graves’ disease but not in others. The factors responsible for this difference are still unknown. We examined the relationship between the nature of anti‐TSH receptor (TSH‐R) antibodies and responsiveness to drugs in Graves’ disease.patients Twenty‐eight untreated patients with Graves’ disease were treated with thiamazole and followed for up to 13 years.measurement Antithyroid microsomal antibodies (MCHAs) and antithyroglobulin antibodies (TGHAs) were measured by the passive haemagglutination method. Anti‐TSH‐R antibodies were measured by a radioreceptor assay (TBII), and thyroid‐stimulating antibodies (TSAbs) and TSH‐stimulation blocking antibodies (TSBAbs) were measured by bioassays using FRTL‐5 cells. Blocking antibodies were also measured by the conversion assay. In order to confirm the usefulness of the conversion assay, in vitro experiments using mixtures of TSAb serum and TSBAb serum were performed.results In in vitro conversion experiments, the conversion assay sensitively detected coexisting blocking antibodies. TSBAb was found in seven patients and a positive conversion ratio was found in four patients, and, of these, three patients had both antibodies. Finally, eight patients (28·6%) had blocking antibodies and 25 of 28 patients (89·3%) had stimulating antibodies. These patients with blocking antibodies (Group A) responded well initially to antithyroid drugs and showed earlier normalization of the serum T4 level (3·0 ± 1·2 weeks) than patients without blocking antibodies (Group B, 10·7 ± 8·5, P < 0·001). Unexpectedly, remission of Graves’ thyrotoxicosis was earlier in Group B (5·1 ± 4·4 years) than in Group A (8·0 ± 4·3 years, P < 0·05). Other parameters, including serum T4, goitre size, ophthalmopathy, TBII, TSAb, TGHA and MCHA, were not different between the two groups.conclusions Graves’ patients with coexisting blocking antibodies initially respond well to thiamazole but are relatively slow to achieve remission. Measurement of blocking antibodies may be useful for selection of treatment options in Graves’ disease.
Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus
Authors: Dane‐Stewart C. A. , Watts G. F. , Barrett P. H. R. , Stuckey B. G. A. , Mamo J. C. L. , Martins I. J. , Redgrave T. G. 
Published: June 2003

Summaryobjectives The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B‐48 and apoC‐III concentrations in postmenopausal women with and without type 2 DM.patients Twenty‐four postmenopausal women without DM and 14 postmenopausal women with diet‐controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state.methods The fractional catabolic rate (FCR) of an intravenously injected chylomicron remnant‐like emulsion was determined from the appearance of 13CO2 in the breath using isotope‐ratio mass spectrometry and multicompartmental modelling. apoB‐48, a marker of particle number of intestinal lipoproteins, was determined immunoelectrophoretically. apoC‐III was measured by immunoturbidimetric assay.results Compared with the nondiabetic women, the women with DM had significantly higher plasma apoB‐48 concentration (16·40 ± 1·18 mg/l vs. 13·0 ± 0·9 mg/l; mean ± standard error mean; P = 0·021), higher plasma apoC‐III concentration (204·24 ± 15·18 mg/l vs. 170·74 ± 10·75 mg/l; P = 0·042) and lower FCR of the chylomicron remnant‐like emulsion (0·06 ± 0·05 pools/h vs. 0·12 ± 0·02 pools/h; P < 0·001). In the diabetic patients, the FCR of the emulsion was correlated significantly with plasma apoB‐48 levels (r = −0·641, P = 0·007) but not with apoC‐III levels.conclusions In postmenopausal women, diabetes mellitus appears to decrease the catabolism of chylomicron remnants and result in an accumulation of these particles in plasma. This may chiefly be due to decreased clearance by hepatic receptors related to an effect of insulin resistance. Impairment in the catabolism of chylomicron remnants may contribute to increased risk of atherosclerosis in postmenopausal women with type 2 diabetes mellitus.
Primary medical therapy for acromegaly
Authors: Sheppard Michael C. 
Published: June 2003

SummaryThere is now considerable evidence that the clinical outcome in patients with acromegaly can be improved very substantially by means of better surgical expertise and effective medical therapies used in a flexible and innovative manner. Medical therapy alone in patients who have not undergone surgery or radiotherapy (primary medical therapy) offers the prospect of near normalisation of GH/IGF‐I levels together with substantial tumour shrinkage in a significant number of patients.
A 3‐year prospective study to assess uterine growth in girls with Turner's syndrome by pelvic ultrasound
Authors: McDonnell Ciara M. , Coleman Lee , Zacharin Margaret R. 
Published: June 2003

Summaryobjective Adult women with Turner's syndrome who have used the donor ovum IVF programme are reported to have reduced pregnancy outcome with an increased risk for first trimester spontaneous abortion. This is considered to be related to a small uterine size and reduced endometrial thickness. This study examines whether adequate oestrogen replacement during the early adolescent years will result in normal adult uterine dimensions, with consequent reduction in these pregnancy risks.design A prospective evaluation of uterine dimensions by pelvic ultrasound examination over 3 years, in a group of 18 girls commencing pubertal induction with oestrogen or entering puberty spontaneously.patients Girls with Turner's syndrome attending the outpatient clinc at the Royal Children's Hospital and due to start oestrogen treatment were invited to participate in the study.measurements Data were collected for clinical parameters of age, pubertal staging, menarche, oestrogen dose and karyotype. Ultrasonographic measurements of uterine length, sagittal and transverse width, endometrial cavity and identification of ovaries were also included.results The mean age at commencement of the study was 14·6 years, mean age at final evaluation was 17·1 years. Karyotype was 45XO in 6/18, mosaic in 12/18. Spontaneous pubertal onset occurred in 5/18. One of these later required the addition of oestrogen treatment. Pubertal induction with oestrogen was used in 13/18 girls. A total of 15/18 girls have either achieved spontaneous menarche or are using adult doses of oestrogen and progestogen with regular withdrawal bleeds. All 18 girls have achieved a uterine length of 5·8–8·6 cm (mean 7·04 cm) within the normal adult range (5–8 cm). Mean uterine volume was 30·23 cm3.conclusion The study suggests that adequate oestrogen replacement in early to mid adolescence mimicking spontaneous timing of puberty results in normal uterine growth and adult uterine dimensions. Further follow‐up of uterine growth in these girls is warranted.
Feasibility of a randomized trial on adjuvant radio‐iodine therapy in differentiated thyroid cancer
Authors: Dragoiescu C. , Hoekstra O. S. , Kuik D. J. , Lips P. , Plaizier M. A. B. D. , Rodrigus P. T. R. , Huijsmans D. A. K. C. J. M. , Ribot J. G. , Kuijpens J. , Coebergh J. W. W. , Teule G. J. J. 
Published: June 2003

Summarybackground Justification for adjuvant radio‐iodine (I‐131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high‐dosage adjuvant schedules. Randomized trials on the latter application are considered impossible due to anticipated formidable sample sizes required in a disease with an overall excellent prognosis like DTC.objective To develop and validate a model that could stratify for risk of recurrence, rather than survival, as is usually done in prognostic indices, and secondly, to use this model to estimate the sample size required for a randomized trial.design, patients and results From databases of three large Dutch centres, we identified 342 consecutive patients without known residual DTC after (near‐) total thyroidectomy. Using Cox proportional hazards analysis, a model was validated that clearly distinguished risk categories of recurrence using commonly available baseline variables. The model included age, N stage at presentation and T stage in papillary carcinoma. According to this stratification, a subset of patients at substantial risk for relapse (30–40%) was identified. They could be eligible for a trial assessing the impact of high‐dose adjuvant I‐131 on recurrence rates. Assuming a clinically relevant effect of 30% reduction of relapses, 290 patients would have to be entered in either arm (α 0·05, power 80%).conclusion We conclude that even though a randomized trial on this issue will be difficult to design and conduct, sample size is not the main problem.
Re‐assessment of growth hormone secretion in young adult patients with childhood‐onset growth hormone deficiency
Authors: Donaubauer Juliane , Kiess Wieland , Kratzsch Jürgen , Nowak Tanja , Steinkamp Heinz , Willgerodt Helmut , Keller Eberhard , Group Study 
Published: June 2003

Summaryobjective Patients with childhood‐onset GH deficiency (coGHD) need retesting in late adolescence or young adulthood to verify whether they need to continue GH treatment. For this purpose the Growth Hormone Research Society (GRS) recommends the insulin tolerance test (ITT), or as an alternative the arginine + growth hormone releasing hormone test (ARG + GHRH test) as a diagnostic tool in adolescents and adults. However, there are no standardized cut‐off levels based on normal GH secretion for determining GHD vs. GH sufficiency in young adults for the ITT, the ARG + GHRH test or the pyridostigmine + GHRH (PD + GHRH) test, a further new GH stimulation test.patients and measurements We studied 43 patients (28 with organic coGHD, 15 with idiopathic coGHD; 30 males, 13 females; aged 20·4 years, range 16·2–25·4; body mass index 23·5, range 16·3–35·8) using the ARG [0·5 g/kg intravenously (i.v.)] + GHRH (1 µg/kg i.v.) test, the PD (120 mg orally) + GHRH (1 µg/kg i.v.) test and the ITT (0·1 IU/kg i.v.) and compared these data with the results of 40 healthy age‐ and weight‐matched volunteers.results The GH response in patients was significantly lower than in healthy controls: ARG + GHRH test, 0·8 µg/l (interquartile range 0·3–2·6) vs. 51·8 µg/l (32·6–71·2) in controls (P < 0·0001); PD + GHRH test, 0·9 µg/l (0·3–1·9) vs. 40·4 µg/l (27·1–54·4) in controls (P < 0·0001); ITT, 0.1 µg/l (0·0–0·8) vs. 20·3 µg/l (14·7–31·7) in controls (P < 0·0001). In the ARG + GHRH test we found a diagnostic sensitivity of 100% and a specificity of 97·5% for a cut‐off range from 15·1 to 20·3 µg/l, in the PD + GHRH test a sensitivity of 100% and a specificity of 97% (cut‐off range 9·1–13·1 µg/l) and in the ITT a sensitivity and specificity of 100% each within a cut‐off range from 2·7 to 8·8 µg/l.conclusion There were no marked differences in sensitivity and specificity in young adults among ARG + GHRH test, PD + GHRH test and the ITT in assessing GH secretion. Because of the lack of side‐effects, the ARG + GHRH test is the recommended method for re‐evaluation of coGHD in young adults when pituitary GHD is suspected. Furthermore, in adult patient groups where organic pituitary coGHD is common, the ITT may be completely replaced by the ARG + GHRH test. Because of the predominance of hypothalamic GHD in childhood, the ITT is commonly performed for the re‐evaluation of patients with childhood‐onset GHD because of its mechanism of GH stimulation. The present results confirm the high discriminatory capability of the ITT in young adults.
Clinical presentation and outcome of pituitary adenomas in teenagers
Authors: Cannavò S. , Venturino M. , Curtò L. , De Menis E. , D’Arrigo C. , Tita P. , Billeci D. , Trimarchi F. 
Published: June 2003

Summaryobjective Pituitary adenomas rarely occur in childhood and adolescence, but their mass effect and endocrine abnormalities can compromise both quality and length of life. In this study we evaluated the symptoms at onset and the long‐term consequences induced in teenagers by functioning or nonfunctioning pituitary adenomas.design and patients Clinical, biochemical and neuroradiological data of 44 young patients (12 males and 32 females, aged 16·3 ± 1·9 years at diagnosis) with pituitary adenomas were evaluated retrospectively at baseline and after therapy. Patients underwent surgery, radiotherapy and/or medical treatment depending on clinical history and endocrine secretion of the tumour. Follow‐up ranged from 8 to 252 months (median 55 months).measurements Baseline and dynamic pituitary function were evaluated in all cases at diagnosis and after treatments. Magnetic resonance imaging (MRI) or computed tomography (CT) scan were performed before therapy and during follow‐up. Hormone levels were measured using commercial radioimmunologic or immunoradiometric methods.results Pituitary macroadenomas (group 1) or microadenomas (group 2) were found in 61% and 39% of cases, respectively. Overall, 68% were PRL‐secreting, 7% GH‐secreting, 5% ACTH‐secreting and 20% nonfunctioning. The most frequent symptoms at onset were oligoamenorrhoea (62%) and galactorrhoea (59%) in the girls, and headache (58%) in the boys. Pubertal development was delayed in 12/27 (44%) cases with macroadenoma. Growth failure was observed in 4/44 (9%) patients (3 in group 1 and 1 in group 2). At diagnosis, hypopituitarism was detected in 10/27 (37%) patients with macroadenoma. Surgery alone cured 4/18 (22%) and 4/9 (44%) patients in group 1 and group 2, respectively. Adjuvant therapies (second surgery and/or radiotherapy and/or medical treatment) cured the disease in 2/13 (15%) patients with macroadenoma and allowed a persistent normalization in other 4/13 (31%) and 2/4 (50%) cases in group 1 and group 2, respectively. Medical treatment alone cured 2/9 (22%) patients with PRL‐secreting macroadenoma and normalized PRL levels in another six (66%) with macroprolactinoma and in 2/7 (28%) patients with microprolactinoma.conclusion Delay of growth was rarely observed in teenagers with pituitary adenomas. At the onset of the disease, many girls complained of oligoamenorrhoea and galactorrhoea, while headache and delay of pubertal development were the symptoms more frequently referred by boys. Surgery alone was effective in a minority of patients and adjuvant therapies were helpful to obtain the remission of the disease in many cases. In patients with PRL‐secreting pituitary adenoma, medical treatment, both as first choice or as adjuvant therapy, normalizes serum PRL levels in 14/27 (52%) cases.
Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer
Authors: Lin Shih Y. , Wang Ya Y. , Sheu Wayne H.‐H. 
Published: June 2003

Summaryobjective Vascular endothelial growth factor (VEGF), a potent angiogenic peptide, and matrix metalloproteinase 9 (MMP‐9), a proteolytic enzyme, are found to be abundantly expressed in several types of cancer and correlate with tumour progression. In this study, we investigated the relationship between preoperative plasma VEGF, MMP‐9 levels and disease stages in papillary thyroid cancer.design Plasma samples were consecutively collected from 30 patients with papillary thyroid cancer preoperatively (seven males and 23 females with a mean age of 45 ± 16 years) and control plasmas obtained from 30 patients with benign goitre (seven males and 23 females with a mean age of 44 ± 18 years) and 23 healthy persons (four males and 19 females with a mean age 44 ± 15 years). Plasma VEGF and MMP‐9 concentrations were determined by enzyme‐linked immunosorbent assay. Cancer progression was staged by the TNM classification of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC).results In thyroid cancer patients, the plasma VEGF and MMP‐9 values were higher than those in controls (51·8 ± 11·5 ng/l vs. 27·0 ± 0·8 ng/l; 72·3 ± 23·3 µg/l vs. 22·1 ± 3·0 µg/l, respectively; P < 0·05), and those in benign goitre (51·8 ± 11·5 ng/l vs. 39·7 ± 8·8 ng/l; 72·3 ± 23·3 µg/l vs. 23·0 ± 2·2 µg/l, respectively; P < 0·05). But, there was no difference of plasma VEGF and MMP‐9 between patients with goitre and normal subjects. A comparison of VEGF and MMP‐9 levels in patients at each cancer stage and in patients with benign nodule found that plasma VEGF and MMP‐9 values in TNM stages III and IV, but not stage I or II, were significantly elevated (P < 0·05). When cancer patients were grouped according to clinopathological features, the plasma VEGF and MMP‐9 concentrations were both significantly elevated in patients with large tumour size (P < 0·01), lymph node involvement (P < 0·01), extrathyroidal invasion (P < 0·05), distant metastasis (P < 0·05) or advanced stages (P < 0·01).conclusion Our study demonstrated that circulating VEGF and MMP‐9 levels correlated with progression of papillary thyroid cancer, suggesting plasma VEGF and MMP‐9 may serve as preoperative adjuvant markers for assessing disease activity in papillary thyroid cancer. However, they should not be used as a diagnostic tool for differentiating malignant from benign thyroid disorders.
Cortisol and the metabolic syndrome in South Asians
Authors: Ward Alexandra M. V. , Fall Caroline H. D. , Stein Claudia E. , Kumaran K. , Veena S. R. , Wood Peter J. , Syddall Holly E. , Phillips David I. W. 
Published: June 2003

Summaryobjective The cardiovascular risk factors which comprise the metabolic syndrome are associated with increased hypothalamic–pituitary–adrenal axis (HPAA) activity in some Caucasian populations. South Asians have high rates of cardiovascular disease and its risk factors. We have investigated the relationships between HPAA activity, adiposity and the metabolic syndrome in a South Asian population.design Cross‐sectional cohort study.participants A total of 509 men and women born at the Holdsworth Memorial Hospital, Mysore, South India between 1934 and 1954 and still living in the area.measurements Fasting 09·00 h cortisol and corticosteroid‐binding globulin. The cohort had previously been investigated for features of the metabolic syndrome.results At 09·00 h, cortisol concentration was strongly associated with systolic and diastolic blood pressure (r = 0·25 and r = 0·24, respectively; P < 0·001), fasting glucose concentration (r = 0·26; P < 0·001), insulin resistance (r = 0·20; P < 0·001) and fasting triglyceride concentration (r = 0·17; P < 0·001). In general, higher cortisol concentrations added to the effect of adiposity in increasing cardiovascular risk factors, but there was evidence of an interaction between cortisol and adiposity in determining fasting glucose concentration (P = 0·045) and insulin resistance (P = 0·006).conclusions Associations between 09·00 h cortisol concentration and cardiovascular risk factors in this South Asian cohort were stronger than those previously shown in Caucasian populations, despite similar mean cortisol concentrations, and were amplified by adiposity. This suggests that increased glucocorticoid action may contribute to ethnic differences in the prevalence of the metabolic syndrome, particularly among men and women with a higher body mass index.
Demonstration of progesterone receptor‐mediated gonadotrophin suppression in the human male
Authors: Brady B.M. , Anderson R.A. , Kinniburgh D. , Baird D.T. 
Published: June 2003

Summaryobjective Synthetic gestogens in combination with testosterone have potential as a male hormonal contraceptive, predominantly acting by augmenting suppression of gonadotrophin secretion. Little is known, however, of the effects of gestogens in the male. Gestogens have affinity for both androgen and progesterone receptors but the relative contribution of action at these two receptors in gonadotrophin suppression remains unclear. In this study the effects of progesterone, with no significant androgen‐receptor affinity are compared to desogestrel, a synthetic gestogen with relatively low affinity for the androgen receptor, on gonadotrophin secretion in normal men.design Subjects received either 50 mg progesterone intramuscularly (i.m.) or 300 µg desogestrel orally daily for 7 days. Frequent blood sampling over 12 h was undertaken before and after drug administration. GnRH [100 µg intravenously (i.v.)] was administered 2 h before the end of the frequent sampling period.subjects Twenty healthy men were randomly allocated to the two treatment groups.results Both progesterone and desogestrel administration resulted in decreases in the concentration of both LH and FSH secretion, as well as testosterone. Analysis of the pulsatile nature of LH secretion indicated that both treatments reduced LH pulse amplitude, and that progesterone reduced LH pulse frequency. Progesterone, but not desogestrel, treatment also reduced the increase in LH secretion in response to GnRH.conclusions The effects of progesterone were at least as marked as those of a maximally effective dose of desogestrel. As progesterone has negligible affinity for the androgen receptor, these results are compatible with the suppressive effects of synthetic 19‐norgestogens on gonadotrophin secretion in the male being mediated via the progesterone receptor, with its androgenicity contributing minimally to gonadotrophin suppression.
Population genetics of the endangered Knysna seahorse, Hippocampus capensis
Authors: Teske P. R. , Cherry M. I. , Matthee C. A. 
Published: June 2003

AbstractThe evolutionary history of the endangered Knysna seahorse, Hippocampus capensis, and the extent of gene flow among its three known populations, were investigated using 138 mitochondrial DNA control region sequences. Similarly high levels of genetic diversity were found in two of the populations (Knysna and Keurbooms Estuaries), whereas diversity in the third population (Swartvlei Estuary) was lower. Although most haplotypes are shared between at least two populations, based on the haplotype frequency distributions the three assemblages constitute distinct management units. The extant population structure of H. capensis suggests that the Knysna seahorse originated in the large Knysna Estuary. The presence of seahorses in the two smaller estuaries is either the result of a vicariance event at the beginning of the present interglacial period, colonization of the estuaries via the sea, or a combination of the two.