bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contiguous gene syndrome due to deletion of the first three exons of the Kallmann gene and complete deletion of the steroid sulphatase gene
Authors: Maya‐Núñez Guadalupe , Cuevas‐Covarrubias Sergio , Carlos Zenteno Juan , Ulloa‐Aguirre Alfredo , Kofman‐Alfaro Susana , Pablo Méndez Juan 
Published: March 2003

OBJECTIVELarge terminal or interstitial deletions of the 22.3 region on the short arm of the X chromosome cause contiguous gene syndromes. Kallmann syndrome (hypogonadotrophic hypogonadism with anosmia or hyposmia) associated with X‐linked ichthyosis, due to a contiguous gene syndrome, is an uncommon finding. Genetic defects have been demonstrated in the Xp22.3 region, explaining the presence of one or both entities in affected individuals. In this report we describe the molecular findings of a patient with Kallmann syndrome and X‐linked ichthyosis.PATIENTA 20‐year‐old subject with hypogonadism, anosmia and generalized ichthyosis was studied endocrinologically, biochemically and molecularly.MEASUREMENTSLevels of LH, FSH, GH, testosterone, oestradiol and cortisol were determined basally and after specific stimulation tests. Enzymatic activity of steroid sulphatase was measured in leucocytes. Polymerase chain reaction of the 14 exons of the Kallmann gene and of the 5′ and 3′ extremes of the steroid sulphatase gene was performed in genomic DNA.RESULTSA partial deletion from exon 1 to exon 3 of the Kallmann gene, as well as a complete deletion of the steroid sulphatase gene were observed.CONCLUSIONSA patient bearing a contiguous gene syndrome with partial deletion of the Kallmann syndrome gene and complete deletion of the steroid sulphatase gene is described. This is the first time a mutation in the conserved cysteine‐rich N‐terminal region which corresponds to the whey acidic protein motif of the Kallmann gene has been characterized, thus demonstrating the importance of this specific region for the function of the gene.
Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle
Authors: Massafra Cosimo , De Felice Claudio , Gioia Dino , Buonocore Giuseppe 
Published: March 2003

OBJECTIVEAntioxidant enzymes are an important part of the defence mechanisms against free radical damage. Little is known, however, about the relationship between sex steroid hormones and cellular antioxidant systems. We have investigated the effect of physiological sex steroid changes on the erythrocyte antioxidant glutathione peroxidase (GSH‐Px) activity during the menstrual cycle in a population of healthy normomenorrhoic women.DESIGNProspective, controlled.PATIENTSTen normally cycling women (age range: 19–28 years; mean: 23.3 years) were recruited for alternate‐day blood sampling from the first day of one menstrual bleed until the first day of the subsequent menstrual phase.MEASUREMENTSPlasma was analysed for LH, FSH, oestradiol (E2) and progesterone (P4) concentrations. Erythrocyte GSH‐Px activity was evaluated on the same days in all subjects. Pyruvate‐kinase (PK) activity, as an index of red blood cell population age, was also determined.RESULTSAll the women examined had a normal ovulatory cycle, as indicated by the hormone plasma pattern. Cycle length was standardized on the basis of the preovulatory E2 peak. Significant cycle phase‐related changes in GSH‐Px (P < 0.03) were observed, with higher GSH‐Px activity levels being found from the later follicular to early luteal phase as compared to early follicular phase (χ2 = 8.53, P < 0.001 and χ2 = 5.54, P < 0.002, respectively). A significant positive correlation was observed between mean E2 and GSH‐Px cycle‐related changes (r = 0.78, P = 0.001). Conversely, no significant cycle phase‐dependent variations were detected in PK.CONCLUSIONSThe findings support the hypothesis that physiological ovarian E2 production during the menstrual cycle may play an important role in regulating erythrocyte glutathione peroxidase activity.
Expression of an orphan nuclear receptor DAX‐1 in human pituitary adenomas
Authors: Ikuyama Shoichiro , Mu Yi‐Ming , Ohe Kenji , Nakagaki Hiroyuki , Fukushima Takeo , Takayanagi Ryoichi , Nawata Hajime 
Published: March 2003

OBJECTIVESAn orphan nuclear receptor, DAX‐1, is known to be involved in the development and differentiation of anterior pituitary cells. The present study aimed to examine 1) whether DAX‐1 is expressed in human pituitary adenomas, and 2) if it is expressed, what types of adenoma express the factor.MATERIALS AND METHODSAdenoma tissues examined included 18 clinically non‐functioning adenomas, 14 GH‐secreting adenomas and 7 PRL‐secreting adenomas. The expression of the following genes were tested by reverse transcription‐polymerase chain reaction (RT‐PCR): DAX‐1, Adrenal‐4‐binding protein/steroidogenic factor‐1 (Ad4BP/SF‐1), Pit‐1, LHβ, FSHβ, gonadotrophin‐releasing hormone receptor (GnRH‐R), GH, PRL, and TSHβ, as well as β‐actin as a control.RESULTSEleven clinically non‐functioning adenomas expressed DAX‐1, 10 of which also expressed Ad4BP/SF‐1. Nine out of the 11 DAX‐1‐expressing adenomas also expressed LHβ, FSHβ and GnRH‐R as well, indicating that these adenomas possessed gonadotrophic properties. Nine clinically non‐functioning adenomas expressed Pit‐1 as well as GH, PRL and/or TSHβ, thus having somatomammotrophic or thyrotrophic properties, 3 of which overlapped with the above DAX‐1‐expressing adenomas. One non‐functioning adenoma expressed Ad4BP/SF1 and FSHβ but not DAX‐1, and another one expressed DAX‐1 and Ad4BP/SF‐1 with PRL. On the other hand, all GH‐secreting and PRL‐secreting adenomas expressed Pit‐1 and GH and/or PRL, but neither DAX‐1 nor Ad4BP/SF‐1.CONCLUSIONSThe results shown here indicate that DAX‐1 is expressed in the majority of human pituitary adenomas of gonadotrophic origin in parallel with Adrenal‐4‐binding protein/steroidogenic factor‐1.
Lack of associations between serum leptin, a polymorphism in the gene for the β3‐adrenergic receptor and glucose tolerance in the Dutch population.
Authors: Janssen J. A. M. J. L. , Koper J. W. , Stolk R. P. , Englaro P. , Uitterlinden A. G. , Huang Q. , Van Leeuwen J. P. T. M. , Blum W. F. , Attanasio A. M. F. , Pols H. A. P. , Grobbee D. E. , De Jong F. H. , Lamberts S. W. J. 
Published: March 2003

BACKGROUNDThe associations between leptin levels and the prevalence of a polymorphism in the β3‐adrenergic receptor were studied in a cross‐sectional analysis of 600 participants in a population‐based study, which were stratified for glucose tolerance by an oral glucose tolerance test.METHODSIn a random sample of 600 participants in the Rotterdam study, aged 55–75 years at baseline (309 men, 291 women) the relationships were studied between the presence of Trp64 Arg mutation in the β3‐adrenergic receptor gene and fasting leptin, glucose and insulin (fasting and after an oral glucose load), and other components of the insulin resistance syndrome.RESULTSMean age of the study population was 66.9 years (SD 5.7). Fasting serum leptin levels overall in men and women were 6.1 μg/l (SE 0.2) and 21.7 μg/l (0.9), respectively, (P < 0.001). These differences were independent of age, body mass index and waist to hip ratio.We identified 73/600 persons who were heterozygotes for the Trp64 Arg polymorphism (allelic frequency 6.1%), but failed to find an association between the presence of this polymorphism and leptin or any measured parameter indicative for obesity, impaired glucose tolerance or type 2 diabetes mellitus.CONCLUSIONHeterozygosity for the Trp64Arg polymorphism of the β3‐adrenergic receptor gene is not accompanied by obesity, impaired glucose tolerance and type 2 diabetes mellitus in the general elderly Dutch population, and is also not associated with changes in circulating leptin levels.
Prevalences of Gsα, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population
Authors: Park  , Koh  , Kim  , Park  , Gong  , Hong  , Ahn  
Published: March 2003

OBJECTIVEIn thyroid tumours, ras, Gsα, p53 mutations and ret/PTC rearrangement have been reported with variable prevalences in different geographical regions. We studied the prevalence of these mutations and rearrangement in thyroid tumours in a Korean population. As MDM2 and Bcl‐1 protein expressions have been suggested to be associated with p53 protein, we also studied possible relationships among them.PATIENTS AND DESIGNEleven cases of adenomatous goitre, eight cases of follicular adenoma, five cases of follicular carcinoma and 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT–PCR, SSCP and/or direct sequencing, after subcloning if necessary, were used, and immunohistochemical stainings were performed for p53, MDM2 and Bcl‐2 proteins in cases of papillary carcinoma.RESULTSWe could not find any rearrangement for ret/PTC‐1, ‐2, ‐3 and mutation of Gsα. For the ras oncogene, K and H‐ras mutations were not found, but N‐ras mutations, point mutation of CAA to CGA in codon 61, were detected in one follicular adenoma (12.5%, 1/8) and one follicular carcinoma (33%, 1/3). p53 mutations were detected in only one case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA → GAA). In 30 cases of papillary carcinoma without p53 mutation, the prevalences of positive immunohistochemical staining were 13.3% for p53 protein, 53.3% for MDM2 protein and 56.7% for Bcl‐2 protein. While over‐expression of p53 protein was not significantly related to that of MDM2 and Bcl‐2 proteins, over‐expression of MDM2 and Bcl‐2 in papillary carcinoma were associated.CONCLUSIONret/PTC rearrangement, Gsα, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms from a Korean population, which may reflect genetic and environmental differences from patients in countries with high prevalences. P53 protein over‐expression was noted in 13.3% of papillary carcinoma cases without p53 mutation and was not significantly related to MDM2 and Bcl‐2 expression.
Outpatient assessment of residual growth hormone secretion in treated acromegaly with overnight urinary growth hormone excretion, random serum growth hormone and insulin like growth factor‐1
Authors: Parfitt Vernon J. , Flanagan Daniel , Wood Peter , Leatherdale Brian A. 
Published: March 2003

OBJECTIVETo assess the outpatient investigations, overnight urinary growth hormone (uGH) excretion, random serum GH and insulin like growth factor 1 (IGF‐1), and GH indices from the oral glucose tolerance test (OGTT) (fasting, nadir and mean GH), as measures of mean GH secretion in treated acromegaly, in comparison with a GH day series, which served as a gold standard.DESIGNProspective cross‐sectional study, with patients admitted to a metabolic ward for the following investigations: random GH, IGF‐1, 6 point GH day series (day 1), 9 h timed overnight uGH excretion, OGTT with GH response (day 2). Agreements between the mean GH during the day series and the other outcome measures, and the diagnostic performance of the latter, for the presence or absence of active acromegaly (mean GH during day series  5 or < 5 mU/l, respectively) were determined.PATIENTS26 patients with treated acromegaly (11 with inactive acromegaly off drug therapy).MEASUREMENTSSerum GH and uGH were measured by immunoradiometric assays and IGF‐1 by radioimmunoassay.RESULTSAgreements with the mean GH during the day series were perfect for the nadir GH during the OGTT with a 2 mU/l cutoff (Cohen's kappa (κ) = 1, P < 0.00001), almost perfect for the fasting and mean GH throughout the OGTT (both κ = 0.92, P < 0.0001) and random GH (κ = 0.85, P < 0.0001), and substantial for the nadir GH with a 5 mU/l cutoff (κ = 0.77, P < 0.0001), IGF‐1 (κ = 0.62, P < 0.001) and overnight uGH excretion (κ = 0.61, P = 0.002). Nadir GH with a 2 mU/l cutoff was completely accurate for diagnosing the presence or absence of active acromegaly (positive and negative predictive values (% ± standard error percentage) 100 ± 8% and 100 ± 10%). None of the outpatient tests used alone was an adequate diagnostic test (positive and negative predictive values: overnight uGH excretion − 86 ± 10% and 75 ± 13%; random GH −100 ± 11% and 85 ± 11%; IGF‐1 − 92 ± 10% and 71 ± 13%) and so combinations of tests were assessed. The best was overnight uGH excretion plus random GH (positive and negative predictive values 88 ± 9% and 100 ± 12%). Using all three outpatient investigations, the positive predictive value of three raised results was 100 ± 13%.CONCLUSIONSIn treated acromegaly, residual GH secretion can be reliably assessed with the OGTT, using standard diagnostic criteria. It can also be assessed on an outpatient basis with overnight uGH excretion and random GH, as direct measures, and IGF‐1. If these are all normal, active acromegaly is excluded. Three raised results denote active acromegaly, and one or two raised results would need further investigation with a GH day series.
Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing's disease
Authors: Tabarin Antoine , Laurent François , Catargi Bogdan , Olivier‐Puel Fréderique , Lescene Robin , Berge Jerôme , San Galli François , Drouillard Jacques , Roger Patrick , Guerin Jean 
Published: March 2003

OBJECTIVESThe ability of MRI to detect pituitary ACTH‐secreting adenomas in patients with Cushing's disease is limited. Owing to different dynamics of contrast enhancement between adenomas and normal pituitary tissue, it has been suggested that obtaining images within seconds after gadolinium (Gad) injection using dynamic procedures increases the sensitivity of MRI in the detection of pituitary microadenomas. The objective of this study was to compare the ability of conventional magnetic resonance imaging (CMRI) and dynamic MRI (DMRI) to detect ACTH‐secreting pituitary adenomas.DESIGNTwenty‐six consecutive patients with ACTH–dependent Cushing's syndrome and 10 normal subjects were investigated. According to the results of inferior petrosal sinus sampling, 21 patients had Cushing's disease and five had ectopic ACTH syndrome. Patients with Cushing's disease were operated regardless of the results of imaging studies. All underwent identical MRI and DMRI procedures using a 1.0 T magnet. Image sampling time during DMRI was 19 sec. Scans were randomly mixed and analysed blind, retrospectively and independently by two experienced radiologists. The clarity of the images was assessed by the analysis of agreement among radiologists. MRI findings were compared to surgical and histopathological findings.RESULTSSurgical exploration identified three macrodenomas and 14 microadenomas. One microadenoma was found at pathological examination after subtotal hypophysectomy and no tumour was found in three cases. According to the combined opinion of radiologists, the three macroadenomas were identified equally well with CMRI and DMRI. Eight ACTH‐secreting microadenomas were detected with CMRI and 11 with DMRI. The three microadenomas detected with DMRI only were visualized within 60 sec following Gad injection. No false positives occurred with CMRI. Three false positives were obtained with DMRI: one in a patient with ectopic ACTH syndrome while a silent microprolactinoma and normal tissue were found at the site of the radiological abnormality in two patients with Cushing's disease. In our study, the sensitivity of DMRI is greater than that of CMRI (0.67 vs. 0.52) but is associated with a loss in specificity (0.80 vs. 1.00). False positives may result from the increased sensitivity of DMRI which detects incidental pituitary lesions, technical artefacts or lowest clarity of images, as suggested by a lower observer agreement of DMRI (Kappa statistic 0.66 vs. 0.83). Overall, the two MR procedures had equivalent diagnostic power (0.72).CONCLUSIONSIn our hands, dynamic procedures did not improve the usefulness of MRI in Cushing's syndrome.
Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication
Authors: Peace  , Orme  , Padayatty  , Godfrey  , Belchetz  
Published: March 2003

OBJECTIVEThis study was carried out to examine the neuropsychological status of patients treated for pituitary tumour by transfrontal surgery, transsphenoidal surgery or medical treatment only, with or without radiotherapy.DESIGN AND MEASUREMENTSThree groups of 23 patients who had been treated for pituitary tumour were compared with 23 healthy controls on a range of neuropsychological measures. The surgical patients were also subdivided into two groups and compared. The neuropsychological measures were standardized psychological tests designed to assess aspects of attention, memory and executive function.PATIENTSThe patients were those who had been treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) and medication only (n = 23). The groups did not differ with respect to age, education or premorbid ability level as assessed by the National Adult Reading Test. All participants were free of known sources of cognitive impairment other than pituitary tumour.RESULTSComparison of the four groups revealed that nearly half of the transfrontal, one‐third of the transsphenoidal and one‐quarter of the non‐surgical group had three or more neuropsychological tests scores below the 10th percentile compared to less than 5% of the controls. Impairments in memory and executive function were found in both surgical groups. The non‐surgical patients appeared to have problems only on tasks requiring high levels of cognitive processing. Differences were found between the two surgical groups with respect to the severity of the cognitive impairment, the transfrontal patients having more severe impairment than the transsphenoidal. No significant negative effects on cognitive functioning were associated with radiotherapy; however, transfrontal surgery patients who had not been treated with radiotherapy were found to be more impaired than other patients. This was thought to be related to radical surgery.CONCLUSIONSMany patients with treated pituitary tumour suffer significant cognitive impairment. The severity and nature of impairment differs between treatment groups, although the cause of this could not be addressed by this study. Recommendations are made for future research and clinical practice.
Bone mineral density in women with cytotoxic‐induced ovarian failure
Authors: Howell  , Berger  , Adams  , Shalet  
Published: March 2003

OBJECTIVEPremature ovarian failure is associated with a reduction in bone mineral density. As survival rates following treatment for haematological malignancies improve, chemotherapy‐induced ovarian failure is becoming more common. However, there are few data concerning the impact of this on bone mineral density (BMD). We have therefore measured the BMD in 33 women with ovarian failure following treatment with cytotoxic chemotherapy.PATIENTS AND DESIGNWe studied 33 women who received combination chemotherapy for Hodgkin's disease (n = 27), non‐Hodgkin's lymphoma (n= 4), sarcoma (n = 1) and acute myeloid leukaemia (n= 1). The mean (range) age of the subjects at the time of BMD measurement was 37.5 (24–50) years and the mean (median: range) duration of amenorrhoea was 49 (24: 5–277) months. Eleven women had received hormone replacement therapy (HRT) for a mean (range) duration of 25 (1–62) months. BMD was measured by single photon absorptiometry or single X‐ray absorptiometry, and dual energy X‐ray absorptiometry at the distal and proximal radius, the femoral neck and the lumbar spine, respectively. BMD was expressed as Z‐scores and statistical analysis was performed using the Wilcoxon matched‐pairs signed‐rank test.RESULTSThere was no significant reduction in BMD at the hip, spine or forearm in the cohort as a whole, although there was a trend to reduce bone density at all sites. When patients who had received HRT were excluded from the analysis there were small reductions in mean BMD at all sites, but this was only statistically significant at the proximal forearm (Z‐score = −0.65; P = 0.03). Mean BMD of the HRT‐treated patients was normal at all sites. Only seven patients (21%) had a BMD Z‐score < −2 at any site.CONCLUSIONIt is inappropriate to assume that ovarian failure from different aetiologies has a similar deleterious impact on the skeleton. Untreated premature ovarian failure following cytotoxic chemotherapy results in some reduction in bone mineral density, but this is of a minor degree and is less than that observed in other hypo‐oestrogenic states. The reason for this is unclear but studies of residual hormone production in the cytotoxic‐damaged ovary may provide an answer.
The systemic stress response to thermal injury in children
Authors: Sedowofia Kofi , Barclay Cameron , Quaba Awf , Smith Alberto , Stephen Rhona , Thomson Margaret , Watson Anthony , McIntosh Neil 
Published: March 2003

OBJECTIVEThermal injury is extremely stressful, but data characterizing the endocrine stress response to this injury in children are sparse. The objective of this study was to measure the effects of thermal injury on the levels of stress hormones in children and to assess the temporal changes associated with them.PATIENTSTwenty‐three children, 13 girls and 10 boys aged between 5 months and 12 years 3 months (mean, 2 years 11 months), with burns covering 10–61% of their body surface (mean, 20.5%) were studied during the first 5 days following injury.MEASUREMENTSThe levels of arginine vasopressin, angiotensin II, cortisol, adrenaline, noradrenaline and dopamine were measured in sequential blood samples obtained from thermally injured children on admission and at specified time intervals during the 5 days of the investigation.RESULTSAt admission the concentrations of all the hormones were high, and varied widely between individual patients. The geometric mean and 95% confidence intervals of admission hormone levels were as follows: arginine vasopressin 18.3 (8.3–40.7) pmol/l; angiotensin II 122.0 (56.0–266.2) pmol/l; cortisol 650.6 (473.0–895.0) nmol/l; dopamine 1.0 (0.1–8.0) nmol/l; adrenaline 6.4 (3.2–12.5) nmol/l and noradrenaline 2.3 (1.3–4.3) nmol/l. Although the concentrations of arginine vasopressin and cortisol returned to normal 24 to 36 h after admission, the levels of angiotensin II, adrenaline and dopamine fluctuated and remained higher than normal throughout the study (108 h).CONCLUSIONSThermal injury results in the release of abnormally high levels of stress hormones in children. Although there are similarities between some of the data reported here and those reported in adults, higher levels of adrenaline and lower levels of noradrenaline than reported in adults suggest important differences too. These differences may need to be taken into account in the management of burn‐injured children.