bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiated thyroid cancer: a retrospective analysis of 832 cases from Greece
Authors: Tzavara  , Vlassopoulou  , Alevizaki  , Koukoulis  , Tzanela  , Koumoussi  , Sotsiou  , Thalassinos  
Published: March 2003

OBJECTIVETo analyse the initial manifestations, pathological findings, therapy, outcome and prognostic factors in patients with papillary and follicular carcinoma.PATIENTS832 patients with well differentiated thyroid carcinoma managed in our department during a period of 30 years (1965–1995). Follow‐up data were available for 609 patients for a mean of 5.5 years (range 1–38 years), the remainder having been lost to follow‐up.RESULTSThe patients were 677 (81%) with papillary and 155 with follicular carcinoma. They were predominantly female (75%), presenting mainly with a single nodule (53%), while at the time of diagnosis 72% had intrathyroidal carcinomas (class I), 17% had nodal metastases (class II), 7% soft tissue invasion (class III) and 4% distant metastases (class IV). Fifty‐five percent of the patients had a complete thyroidectomy (36% had a near total or total thyroidectomy and 19% near total or total thyroidectomy plus block dissection), 2.6% received external radiotherapy and 94% had radioactive iodine as part of the treatment of the original disease. Kaplan‐Meier survival analysis was used to calculate both cancer related mortality and disease free survival in the patients followed‐up. Although mortality (21 cancer‐related deaths) was slightly higher for follicular than papillary carcinoma (10% vs. 5% and 16% vs. 10% in 10‐and 15‐year survival, respectively) the difference was not statistically significant. Extent of disease at diagnosis, male sex, tumour size and age > 60 years affected probability of cancer death. Cox's proportional hazard regression analysis for disease free survival showed that adverse independent prognostic factors were, for papillary carcinoma, male sex, class II or higher, tumour size > 1 cm and age > 60 years, while for follicular, class III or higher, size > 4 cm and age > 40 years.CONCLUSIONSWe conclude that there is a higher prevalence of follicular carcinoma in our country probably due to a moderate degree of iodine deficiency still existing in Greece. Age and extent of disease at diagnosis were important prognostic factors affecting morbidity and mortality, whereas sex, tumour features and histological type were of minor importance. All these prognostic factors and their relative importance should be taken in consideration in the management of this disease.
Serum leptin levels in healthy ageing men: are decreased serum testosterone and increased adiposity in elderly men the consequence of leptin deficiency?
Authors: Van den Saffele Jan K. , Goemaere Stefan , De Bacquer Dirk , Kaufman Jean Marc 
Published: March 2003

OBJECTIVEThe limited information on serum leptin levels in elderly men suggests the occurrence of an age‐related decrease, with disruption of the relationship between fat mass and leptin levels. A relative leptin deficiency might thus be implicated in the increase of fat mass and decrease of serum testosterone levels in elderly men. Therefore, we have reevaluated the age‐related changes in serum leptin levels and their relationship with adiposity and androgen levels in a large group of community dwelling men.SUBJECTS AND MEASUREMENTSSerum leptin and androgen levels were measured in 271 healthy, ambulatory elderly men (median age 74 years), as well as in 61 middle‐aged (median 43 years) and 40 young (median 25.5 years) controls. Adiposity was assessed by anthropometrical measurements (body mass index; BMI) and by estimation of fat mass by the bio‐impedance method.RESULTSSerum leptin levels, whether or not adjusted for BMI, were found to increase with age, the values tending to level off after the age of 45 years, and were strongly correlated to BMI (r = 0.77) and fat mass assessed by the bio‐impedance method (r = 0.81). Linear regression analysis showed a similar slope for the relationship between BMI and serum leptin in the three age groups. Multiple linear regression analysis indicated BMI, age and serum insulin, but not serum testosterone, as significant independent correlates of serum leptin. Serum (free) testosterone levels were negatively correlated with age and serum leptin, also after partialization for BMI: rank correlation coefficients vs. age and serum leptin, respectively, were − 0.20 (P < 0.001) and − 0.16 (P < 0.01) for total testosterone and − 0.60 (P < 0.001) and − 0.23 (P < 0.001) for free testosterone. Dehydroepiandrosterone sulphate (DHEAS) and leptin levels emerged as significant independent correlates in a multiple linear regression model for total serum testosterone; BMI and serum insulin became highly significant correlates in the same model when leptin was omitted from the independent variables.CONCLUSIONAgeing in men is accompanied by a rise of serum leptin levels with a maintained strong association between serum leptin and adiposity in elderly men. Testosterone does not appear to be a major determinant of serum leptin in healthy men, while leptin does emerge as a negative correlate of serum testosterone. Increased fat mass and decreased testosterone production in elderly men cannot be attributed to a relative leptin deficiency.
Effects of short‐term hormone replacement on serum leptin levels in postmenopausal women
Authors: Lavoie Helene B. , Taylor Ann E. , Sharpless Julie L. , Anderson Ellen J. , Strauss Carrie C. , Hall Janet E. 
Published: March 2003

OBJECTIVELeptin is a hormone which is secreted by adipocytes and appears to influence the reproductive axis. Previous studies have demonstrated higher leptin levels in relation to body fat mass in women compared to men, higher levels in normally cycling compared to postmenopausal women, and a decrease in leptin levels with increased age. The purpose of this study was to determine whether oestrogen replacement with or without progesterone increases serum leptin levels in postmenopausal women, independently of changes in body fat, and to determine if ageing affects leptin levels at baseline or in response to hormone replacement.PATIENTSTwenty‐one healthy postmenopausal women on no hormone replacement were studied at baseline, after 1 month of oestrogen (E2: estraderm 50 μg/day) and after a further month of oestrogen and 7 days of progesterone (P: progesterone 100 mg per vagina bid) designed to achieve physiological hormone levels. Subjects included 11 younger (45–55 years) and 10 older (70–80 years) postmenopausal women.RESULTSThe relationship between leptin and the absolute fat mass (% body fat × weight [kg]) at baseline was not different between the younger and older postmenopausal women. The adequacy of physiological hormone replacement was confirmed in all subjects. Despite the absence of an effect of hormone replacement on weight, body mass index (BMI), % and absolute fat mass (bioimpedance) or waist‐hip ratio, there was an increase in serum leptin levels with hormone replacement (15.4 ± 1.7, 17.6 ± 1.7, and 18.1 ± 1.6 μg/l; mean ± SEM at baseline, with E2, and with E2 + P, respectively; P < 0.001 vs. baseline) for the group as a whole. An increase in leptin with hormonal treatment was seen in both the younger (15.1 ± 2.1, 18.1 ± 2.4, and 18.5 ± 1.9 μg/l; P < 0.01) and the older (15.7 ± 2.8, 17.0 ± 2.5, 17.7 ± 2.8 μg/l; P = 0.06) postmenopausal women.CONCLUSIONS(1) Short‐term physiological oestrogen replacement increases serum leptin levels in postmenopausal women independently of changes in fat mass; and (2) physiological progesterone replacement does not influence leptin levels in postmenopausal women.
Association of CTLA4 gene A–G polymorphism with type 1 diabetes in Chinese children
Authors: Lee Yann‐Jinn , Huang Fu‐Yuan , Lo Fu‐Sung , Wang Wei‐Chu , Hsu Chyong‐Hsin , Kao Hsin‐An , Yang Tzu‐Yao , Chang Jan‐Gowth 
Published: March 2003

OBJECTIVEThe CTLA4 (cytotoxic T lymphocyte associated antigen‐4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. Thus it is a strong candidate gene for T cell‐mediated autoimmune disease. There is polymorphism at position 49 in exon 1 of the CTLA4 gene, providing a A–G exchange. This polymorphism is reportedly associated with type 1 diabetes in Caucasians but not in a small data set of Chinese. We wished to test this polymorphism in a larger and more homogeneous data set of Chinese children with type 1 diabetes and normal adult controls.DESIGNA population‐based case‐control study of a CTLA4 gene 49 A–G polymorphism was performed to look for an association with type 1 diabetes in Chinese children.PATIENTSWe analysed this polymorphism in 253 unrelated children (128 boys) with type 1 diabetes (age at diagnosis 7.1 ± 3.7 years) and 91 randomly selected normal adults. All individuals were Han Chinese.RESULTSThe genotype and gene frequencies of children with type 1 diabetes differed significantly from those of adult controls (P = 0.0091 and P = 0.0051, respectively). Genotype CTLA4 49 G/G and G allele conferred a risk of type 1 diabetes (RR = 2.13, 95% CI = 1.31–3.46, P = 0.0022; RR = 1.68, 95% CI = 1.17–2.43, P = 0.0051, respectively).CONCLUSIONSThis study demonstrates that CTLA4 49 A–G polymorphism is associated with type 1 diabetes in Han Chinese children. The CTLA4 49 G allele confers an increased risk of type 1 diabetes.
Identification of missense mutations in the SRD5A2 gene from patients with steroid 5α‐reductase 2 deficiency
Authors: Vilchis  , Méndez  , Canto  , Lieberman  , Chávez  
Published: March 2003

BACKGROUND AND OBJECTIVEMutations of the steroid 5α‐reductase type 2 (SRD5A2) gene in karyotypic males result in a spectrum of external genitalia phenotypes ranging from complete female to nearly complete male. Here we performed genomic DNA analyses from individuals bearing the enzyme deficiency in order to detect the molecular abnormalities.PATIENTSFour unrelated 46,XY patients of Mexican origin with ambiguous external genitalia were studied. A fertile, phenotypically normal male was also included.MEASUREMENTSCoding sequence abnormalities of the SRD5A2 gene were assessed by exon‐specific polymerase chain reaction, single‐stranded conformational polymorphism and sequencing analysis.RESULTSFive different missense mutations (two of them novel mutations) were identified. Three subjects presented homozygous single base mutations. These were located at exon 2 (G115D), exon 4 (P212R) and exon 5 (R246Q), and such changes have been described previously. The fourth patient was a compound heterozygote who presented two mutations located in exons 1 and 2. We found a hitherto unreported G → A transition at the second nucleotide of codon 85 in exon 1 (GGC → GAC), substituting glycine for aspartic acid (G85D). This patient also presented an identical alteration at codon 115 of exon 2, which was carried by his father (G115D). Finally, in another subject who was included originally as a control, we found a C → A transversion (yet undescribed) at codon 245 in exon 5 (S245Y).CONCLUSIONSFour different single base mutations that cause amino acid substitutions were detected in the steroid 5α‐reductase type 2 gene of affected individuals. One patient and a normal control had two previously undescribed mutations. Although in the latter individual we cannot exclude the possibility that the base change is a genetic polymorphism, the molecular screening of 100 chromosomes suggests strongly that the change at codon 245 does represent a heterozygous mutation. Further studies, including the recreation of the mutations, will help to reveal the biochemical consequences resulting from these changes.
Reversible hypogonadotrophic hypogonadism in sexually infantile male thalassaemic patients with transfusional iron overload
Authors: Chatterjee R. , Katz M. 
Published: March 2003

OBJECTIVETo determine the severity and reversibility of the lesion in the hypothalamic–pituitary (H‐P) axis of male transfusion‐dependant thalassaemic patients with failed puberty (FP).DESIGN AND SUBJECTSThe hypothalamic–pituitary axes of 20 male thalassaemic patients (study group) were compared with two male subjects with idiopathic hypogonadotrophic hypogonadism (IHH) and five prepubertal healthy siblings (control group). GnRH‐gonadotrophin insufficiency was characterized by nocturnal 12 h ultradian gonadotrophin profiles followed by a 100 μg GnRH bolus test (GBT) 4–6 times at 6 monthly intervals. Thalassaemic and IHH patients were then subjected to pulsatile subcutaneous GnRH infusions every 120 minutes for 3 months. Ultradian gonadotrophin profiles and GBT were repeated after 6 weeks of GnRH infusion and again at 3 months following infusion.MEASUREMENTSFSH and LH were measured by radio‐immunoassay. Ferritin was assayed by an immunoradiometric method.RESULTSPatients with IHH who were apulsatile prior to infusion, developed normal gonadotrophin pulses with marked increment in their gonadotrophin responses to the GBT after 3 months of GnRH infusion. In contrast, the thalassaemic patients with apulsatile failed puberty (AFP) remained apulsatile (nonresponders) and had no increment in their gonadotrophin responses to the GBT after GnRH infusion. All patients with pulsatile failed puberty (PFP) had abnormal gonadotrophin pulses prior to GnRH infusion. Their pulse defects were either totally or partially corrected (responders) following infusion. The serum ferritin levels (9500 ± 500 μg/l vs. 5966.67 ± 1139 μg/l; P < 0.01) and percentage of organ dysfunction (87% vs. 17%; P < 0.01) were higher in the nonresponders than the responders.CONCLUSIONSThis study shows that thalassaemic patients with severe organ damage and iron overload are likely to be apulsatile with irreversible damage to their hypothalamo–pituitary axis, while those with less severe iron overload are likely to have potentially reversible hypogonadotrophic hypogonadism (HH). Our results also suggest that gonadotrophin pulse parameters, rather than the gonadotrophin response to a GnRH bolus following prolonged pulsatile GnRH infusion, may be more useful in discriminating reversible from irreversible hypogonadotrophic hypogonadism.
Impaired β‐cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients
Authors: Kasayama Soji , Otsuki Michio , Takagi Miki , Saito Hiroshi , Sumitani Satoru , Kouhara Haruhiko , Koga Masafumi , Saitoh Youichi , Ohnishi Takanori , Arita Norio 
Published: March 2003

OBJECTIVEAbnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and β‐cell function in acromegalic patients.DESIGNTwenty‐four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and β‐cell function, we used correct homeostasis model assessment (HOMA) model, a computer‐solved model. We also investigated the effects of surgical success on both parameters.RESULTSHOMA insulin sensitivity (HOMA‐%S) in the acromegalic patients was 74 ± 51 (SD)%, significantly lower than that in 24 healthy controls (144 ± 49%). HOMA‐%S in 12 normal glucose tolerance (NGT) patients was 54 ± 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 ± 60%). By contrast, HOMA β‐cell function (HOMA‐%β) in the NGT acromegalic patients was 163 ± 67%, significantly higher than the IGT/DM acromegalic patients (89 ± 34%) and the healthy controls (72 ± 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA‐%S significantly increased to control ranges (from 76 ± 26 to 159 ± 61%) within 2 weeks after the surgical success.CONCLUSIONSWe conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of β‐cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.
CYP21 analysis and phenotype/genotype relationship in the screened population of the Italian Emilia–Romagna region
Authors: Balsamo  , Cacciari Emanuele , Baldazzi Lilia , Tartaglia Lucia , Cassio Alessandra , Mantovani Vilma , Piazzi Sandro , Cicognani Alessandro , Pirazzoli Piero , Mainetti Benedetta , Zappulla Franco 
Published: March 2003

OBJECTIVESWe have genotyped the patients with congenital adrenal hyperplasia due to 21‐hydroxylase deficiency identified from March 1980 to December 1997 through a combined program of neonatal screening and case survey in the Emilia–Romagna Region (Italy). We have also analysed retrospectively the possible advantages of genotypical neonatal classification.DESIGNA ‘phase A’ of screening and clinical monitoring (March 1980–September 1983 and March 1991–December 1997) and a ‘phase B’ of clinical monitoring only (October 1983–February 1991) were taken into account.PATIENTSA total of 61 patients (20 salt wasting, nine simple virilizing and 32 nonclassical forms) were genotyped, HLA typed and hormonally tested to understand better the genotype/phenotype relationship and the epidemiology and geographical distribution of associated mutations. The fully genotyped patients were classified into four mutation groups according to the degree of enzymatic activity (‘null’ and ‘A’ to ‘C’).RESULTThe most frequent genotype alterations were deletion (24.1% classical, 3.3% nonclassical forms), large gene conversion (9.2% classical, 1.7% nonclassical forms), In2 splice (27.7% classical, 15.0% nonclassical forms), I172N (5.5% classical, 10.0% nonclassical forms), V281L (3.7% classical, 43.3% nonclassical forms), P453S (5.0% nonclassical forms). A significant difference (χ2 = 5.101; P < 0.025) in the distribution of classical genotypes was found in Romagna (south‐east; incidence 1 : 7437 newborns) compared to Emilia (north‐west; incidence 1 : 25 090 newborns). Two putative new mutations were found in our population. Little discrepancy was found between genotype and phenotype.CONCLUSIONSThe high frequency of genotypes ‘null’ or ‘A’ in the ‘phase A’vs. ‘phase B’ of our study confirms the usefulness of neonatal screening in preventing the death of male patients with salt wasting forms. The substantial similarity in the mutational spectrum of classical forms found in our study, based on the detection of all the classical patients of a specific area, leads us to believe that the distribution of mutations is due to the inherent characteristics of the gene locus, and that regional effects play a minor role. Prompt neonatal genotyping can be of valuable diagnostic assistance in neonatal screening for the confirmation of the diagnosis in newborns with moderately elevated 17 hydroxyprogesterone levels.
Thyroid function in wholly breast‐feeding infants whose mothers take high doses of propylthiouracil
Authors: Momotani Naoko , Yamashita Ryoko , Makino Fuminori , Noh Jaeduk Yoshimura , Ishikawa Naofumi , Ito Koichi , Ito Kunihiko 
Published: March 2003

BACKGROUNDPropylthiouracil (PTU) might theoretically be preferred over methimazole (MMI) during breast‐feeding because of its lower milk/serum concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often relapses during the postpartum period, and high doses of PTU are sometimes needed to control maternal hyperthyroidism) during breast‐feeding. However, there are virtually no data on the effects of maternal PTU on thyroid status of infants whose mothers take more than 300 mg PTU daily and who are wholly breast‐feeding.OBJECTIVESTo investigate whether mothers can breast‐feed without adverse effects on infants' thyroid status while taking 300 mg or more daily of PTU .SUBJECTS AND DESIGNEleven infants who were wholly breast‐fed while their mothers took PTU 300–750 mg daily for Graves' hyperthyroidism were included in this study. In one of the 11 infants, the mother also took iodine 6 mg daily for a limited period. Thyroid status in these infants was evaluated.MEASUREMENTSFree T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb) concentrations were examined at least once in the age range 6 days to 9 months. Maternal blood was also examined for FT4 and TBIAb on the same day, or within a week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth were examined, using cord blood, in cases where antithyroid drugs had been continued through delivery.RESULTSThree of the 11 infants had TSH concentrations higher than the normal range for adults. In one of the three infants, the TSH concentration, which was determined 19 weeks after birth, was just above the normal range. In the remaining two infants whose mothers had taken PTU through delivery, TSH concentrations, determined within 7 days after birth, were distinctly high, but they became normal while maternal PTU doses were the same as or higher than those at the initial examination. Maternal PTU doses or FT4 concentrations were not significantly correlated with infants' TSH concentrations.CONCLUSIONMothers can breast‐feed while taking propylthiouracil at doses as high as 750 mg daily without adverse effects on thyroid status in their infants.
Characterization of a novel DNA polymorphism in the human CYP21 gene and application for DNA diagnosis of congenital adrenal hyperplasia
Authors: Lee Yong‐Ho , Park Eun‐Sook , Kang Shin‐Hye , Kim Hogeun , Lee Jin‐Yong , Lee Jin‐Sung 
Published: March 2003

OBJECTIVESCongenital adrenal hyperplasia (CAH) is a common endocrine disorder and CYP21 (21‐OH, EC 1.14.99.10) deficiency is the most common cause of the disease. The presence of a pseudogene and a wide range of mutation types often makes DNA diagnosis difficult. Analysis of mutant alleles from patients with CAH identified a new DNA polymorphism in exon 10. To test the usefulness of this polymorphism, linkage analysis was performed using three RFLP's at both end of the CYP21 gene in patients and controls.DESIGN AND PATIENTSGenomic DNA was extracted from 21 unrelated patients and 39 unaffected individuals. Haplotyping analysis was performed for three RFLPs, MspI and Fnu4HI in intron 2 and a new SmaI RFLP in exon 10. All three polymorphic sites were characterized by DNA sequencing and usefulness of these RFLPs for DNA diagnosis was tested in patients' families.MEASUREMENTCAH patients were diagnosed by clinical symptoms and biochemical tests. Allele frequencies and heterozygosities were studied for three RFLP's in patients and controls using polymerase chain reaction (PCR).RESULTSA new SmaI RFLP showed a sequence difference as G or A at the nucleotide position 2694 in exon 10. Sequences at the MspI and Fnu4HI polymorphic sites were T or C at the nucleotide position 395 and 453, respectively. All of these RFLPs showed biallelic DNA polymorphisms and codominant segregation in family analysis. Heterozygosities were 0.31 for MspI, 0.48 for Fnu4HI and 0.44 for SmaI in normal individuals. There was no linkage disequilibrium for three RFLPs between patients and controls.CONCLUSIONSThe SmaI RFLP can be useful for linkage analysis and DNA diagnosis in conjunction with RFLPs in intron 2 in CAH families because the polymorphic site is within the active gene at the 3′ end. DNA sequencing results revealed that these RFLPs were created by gene conversions as with other mutations in the CYP21 gene.