bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a novel semi-automated HPLC procedure for whole blood cyclosporin A confirms equivalence to adjusted monoclonal values from Abbott TDx
Authors: Roberts Norman B. , Dutton John , Higgins Gerald , Allars Lesley 
Published: February 2005

AbstractThe problem in the measurement of cyclosporin (CyA) is that the widely used immuno-based assays suffer from interference by metabolites present in unpredictable excess. To resolve this, the consensus view has been to develop more specific and robust procedures for the measurement of CyA alone in order to give values similar to those obtained by HPLC. We developed an alternative strategy based on Abbott poly- and monoclonal assays to derive an adjusted monoclonal value as an equivalent measurement to HPLC. We have now evaluated a recently developed semi-automated HPLC procedure and used it to test the validity of the adjusted monoclonal value. The automated HPLC procedure with online clean-up was optimised for the separation of CyA and internal standard CyD. The assay was simple to use, precise and gave good recovery of cyclosporin from whole blood. Comparisons with the more specific immunoassays Abbott AxSym and EMIT showed close agreement, whereas Abbott monoclonal values indicated up to 20% positive bias. In contrast, the adjusted monoclonal values gave good agreement with HPLC. Data obtained from HPLC linked to tandem mass spectrometry (MS) indicated closer agreement with Abbott monoclonal values than expected, suggesting some positive bias with MS. The benefit of using an adjusted monoclonal value is that a result equivalent to HPLC is obtained, as well as an indication of the concentration of metabolites from the Abbott polyclonal measurement.
Evaluation of the Bio-Rad VARIANT™ II HbA 2/HbA 1C Dual Program for measurement of hemoglobin concentrations and detection of variants
Authors: Riou Jean , Godart Christian , Mathis Mireille , Hurtrel Didier , Wajcman Henri , Préhu Claude , Bardakdjian Josiane 
Published: February 2005

AbstractIn this work data obtained on the VARIANT™ II hemoglobin analyzer using the Dual Kit elution system were compared to those obtained with the β-Thalassemia Short Program. Since many laboratories still use an earlier model of the hemoglobin analyzer, the Variant™ 1, these data were also compared to those obtained with the latter instrument. Our study is divided into two parts. The first is an evaluation of the precision of the VARIANT™ II for determining the levels of hemoglobin (Hb)A
Interferences in coagulation tests – evaluation of the 570-nm method on the Dade Behring BCS analyser
Authors: Junker Ralf , Käse Margit , Schulte Helmut , Bäumer Ruth , Langer Claus , Nowak-Göttl Ulrike 
Published: February 2005

AbstractThe Dade Behring BCS is a coagulation analyser with optical reaction detection (standard 405nm). The present study was conducted to evaluate measurement at 570nm for analyses in interfering plasma samples. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer in normal (n=50), lipaemic (n=60), icteric (n=113), and haemolytic (n=58) samples were measured at 405 and 570nm. As they are unaffected by the optical properties of the sample, the mechanical STAcompact analyser (Roche Diagnostics) and an ELISA technique were defined as the “comparison” methods. The percentage of valid PT results using the 570-nm method varied from 54% (lipaemic samples) to 97% (haemolytic samples). Valid aPTT measurements were found in 67% (lipaemic samples) up to 93% (icteric samples) of samples. Fibrinogen measurement revealed valid results in 58% (lipaemic samples) to 100% (haemolytic samples) of samples. The number of valid D-dimer results varied from 28% (lipaemic material) up to 100% (haemolytic material). Significant inter-method differences were found: aPTT in lipaemic (BCS 405 vs. 570nm) and icteric samples (STAcompact vs. BCS 405 and 570nm); fibrinogen in lipaemic (BCS 405 vs. 570nm), icteric (BCS 405 vs. 570nm; STAcompact vs. BCS 570nm) and haemolytic samples (STAcompact vs. BCS 405 and 570nm). Differences between the BCS 570-nm and the STAcompact methods were in most cases low and less pronounced than between the BCS 570- and 405-nm methods, making the BCS 570-nm method an alternative to measurement at 405nm. Limitations have to be taken into account regarding lipaemic plasma.
Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism
Authors: Rodrigues Carina , Jorge Paula , Soares José Pires , Santos Isaura , Salomão Regina , Madeira Manuela , Osorió Rui Vaz , Santos Rosário 
Published: February 2005

Objective: Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme.Subjects and methods: The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1–17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns.Results: Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected.Conclusion: The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.
Serum cytokine levels in GH-deficient children during substitutive GH therapy
Authors: Pagani Sara , Meazza Cristina , Travaglino Paola , De Benedetti Fabrizio , Tinelli Carmine , Bozzola Mauro 
Published: February 2005

Objective: The aim of the present study was to investigate the effect of exogenously administered human GH (hGH) on serum levels of interleukin (IL)-4, IL-6, IL-12 and tumour necrosis factor (TNF)-α in GH-deficient (GHD) children.Design and methods: We evaluated 13 short prepubertal GHD children, aged between 2 and 13 years, and 13 age-matched healthy subjects as controls. Circulating cytokine values were evaluated in basal conditions in all children, and 6 and 24 h following the 1st hGH injection (0.23 mg/kg per week), and then after 3 months of hGH treatment in GHD patients. Serum levels of IL-4, IL-6, IL-12 and TNF-α were measured by commercially available ELISAs.Results: No significant differences were found between controls and GHD children in basal values of serum IL-4, IL-6, IL-12 and TNF-α (P> 0.05 by Mann–Whitney U test). Analysis of cytokine levels during hGH treatment showed significant changes over time in TNF-α and IL-6 levels (P= 0.0014 andP= 0.00 024 respectively), with the more pronounced effect observed at 6 h following the first administration of hGH (i.e. increase in IL-6 (Wilcoxon matched pairs test,P= 0.0015) and TNF-α levels (P= 0.0015)). No significant changes over time were observed in IL-4 and IL-12 serum levels.Conclusions: In vivorelease of the pro-inflammatory cytokines IL-6 and TNF-α can be affected by hGH treatment in GHD children, suggesting a direct effect of GH on the immune function.
Thyroid and adrenal axis in major depression: a controlled study in outpatients
Authors: Brouwer Jantien P , Appelhof Bente C , Hoogendijk Witte J G , Huyser Jochanan , Endert Erik , Zuketto Cassandra , Schene Aart H , Tijssen Jan G P , Van Dyck Richard , Wiersinga Wilmar M , Fliers Eric 
Published: February 2005

Objective: Major depressive disorder has been associated with changes in the hypothalamus–pituitary–thyroid (HPT) axis and with hypercortisolism. However, the changes reported have been at variance, probably related to in- or outpatient status, the use of antidepressant medication and the heterogeneity of depression. We therefore conducted a controlled study in unipolar depressed outpatients who had been free of antidepressants for at least 3 months.
Design: We assessed endocrine parameters in 113 depressed outpatients and in 113 sex- and age-matched controls.
Methods: Patients were included if they had a major depression according to a Structural Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM), fourth edition (SCID-IV) and if they had a 17-item Hamilton rating scale for depression (HRSD) score of ≥16. Endocrine parameters contained serum concentrations of TSH, (free) thyroxine, tri-iodothyronine, cortisol, thyroid peroxidase (TPO) antibody titre and 24-h urinary excretion of cortisol.
Results: The serum concentration of TSH was slightly higher in depressed patients as compared with controls (P < 0.001), independent of the presence of subclinical hypothyroidism and/or TPO antibodies (n = 28). All other HPT axis parameters were similar in both groups. The 24-h urinary cortisol excretion was similar in patients and controls. In atypical depression, serum cortisol was lower than in non-atypical depression (P = 0.01). Patients with neither melancholic depression nor severe depression (HRSD ≥23) had altered endocrine parameters. Finally, serum TSH values could not be related to cortisol values.
Conclusion: When compared with matched control subjects, outpatients with major depression had slightly higher serum TSH, while urinary cortisol levels were similar. Furthermore, we observed lower serum cortisol in atypical depression than in non-atypical depression.
Effect of recombinant human GH on circulating granulocyte colony-stimulating factor and neutrophils in patients with adult GH deficiency
Authors: Sohmiya Motoi , Kanazawa Ippei , Kato Yuzuru 
Published: February 2005

Background: We previously reported that short-term continuous subcutaneous infusion (CSI) of recombinant human growth hormone (rhGH) increased plasma erythropoietin levels and hemoglobin concentrations in patients with adult GH deficiency. In the present study, we investigated the effect of rhGH on plasma granulocyte colony-stimulating factor (G-CSF) levels and neutrophil counts in patients with adult GH deficiency.Methods: rhGH was administrated for 1 year in six patients with adult GH deficiency (age range, 24–69 years; mean ±s.e.m., 51.7 ± 5.8 years; two males and four females) by means of CSI at a rate of 0.25 U/kg per week. Blood samples were obtained in the morning after overnight fasting every month before and after the start of rhGH administration. Plasma GH, insulin-like growth factor I (IGF-I) and G-CSF levels, and neutrophil counts, were measured.Results: Mean ( ±s.e.m.) plasma GH levels increased from 0.26 ± 0.14 to 2.28 ± 0.20 μg/l 1 month after the start of rhGH administration. An increase of the plasma GH levels was accompanied by an increase in the plasma IGF-I levels from 64.7 ± 8.5 to 293.3 ± 80.6 μg/l. Plasma G-CSF levels increased at 2, 3, 8, 9 and 10 months after the start of rhGH administration compared with 28.6 ± 11.0 ng/l at time 0. The neutrophil counts increased at 2, 3, 7, 8, 9, 11 and 12 months after the start of rhGH administration compared with 2822 ± 377 neutrophils/μl at time 0.Conclusion: rhGH administration increased plasma G-CSF levels and neutrophil counts. GH and/or IGF-I might stimulate neutrophil production and/or release via G-CSF.
The selective prostaglandin EP4 agonist, APS-999 Na, induces follicular growth and maturation in the rat ovary
Authors: El-Nefiawy Nagwa , Abdel-Hakim Khaled , Kanayama Naohiro 
Published: February 2005

Objective: It is known that prostaglandin E2 (PGE2) plays a crucial role in the ovulation process. PGE2 mediates its actions through four subtypes of receptors designated EP1–EP4. However, the nature of the ovulation-promoting effect of PGE2 is not well understood. We have carried out thisin vivoresearch utilizing a new selective EP4 receptor agonist (EP4A; APS-999 Na) to investigate its role in folliculogenesis aiming at more understanding of the biological mechanism of action of PGE2.Design and methods: Immature, 22 day old Wistar rats were used. Animals were injected once either with placebo, 20 IU pregnant mare serum gonadotrophin (PMSG), or EP4A (10, 20 or 50 μg). In other experiments, EP4A was injected in PMSG stimulated rats. Ovarian follicle growth and development was assessed through total count and size measurement of ovulatory follicles in whole ovaries of the investigated groups. Utilizing immunohistochemistry, the spatial localization of the EP4 receptor in immature rat ovary and IL-8 pattern of expression after EP4A injection was also investigated.Results: Our study showed that injection of EP4A resulted in increased follicle growth and development compared with the control, in a time- and dose-dependent manner. The highest values for follicle count and size were observed 12 and 24 h after EP4A injection. EP4A induced follicle growth with morphological characteristics similar to that induced by the standard PMSG. Most dense immune staining for EP4 receptor was noticed in proliferating granulosa cells of the secondary follicles while those of the primordial and primary follicles were not stained. EP4A injection induced the expression of IL-8 in the follicles.Conclusions: Our study revealed that: (i) the localization of EP4 receptor in the ovary implies a role in follicle growth, (ii) PGE2 induced ovarian follicle growth and development is mediated at least in part through the EP4 receptor, (iii) the action of EP4A is mediated through IL-8 up regulation and (iv) the new EP4A could be a promising reagent for various systems used to induce follicle maturation in clinical or agricultural fields. This knowledge may provide useful targets for manipulation of infertility.
The ‘bio-assay’ quality of life might be a better marker of disease activity in acromegalic patients than serum total IGF-I concentrations
Authors: Bonapart Ingrid E , van Domburg Ron , ten Have Saskia M T H , de Herder Wouter W , Erdman Ruud A M , Janssen Joop A M J L , van der Lely Aart Jan 
Published: February 2005

Objectives: To investigate the quality of life (QoL) in acromegalic patients in relation to biochemical parameters.
Design and methods: Single-center, open label study in 14 acromegalic patients (eight woman and six men, age 33–77 years), with normal serum IGF-I levels during long-term treatment with monthly injections of 20 mg of long-acting octreotide. We investigated which biochemical parameter might reflect optimal QoL, using the SF-36 questionnaire.
Results: We observed that six patients had a low QoL score at baseline in the same range as observed in cancer patients. The other eight patients had a normal QoL. GH, IGF-I nor free IGF-I could discriminate these two subgroups at baseline. After skipping one monthly injection, all six subjects with the low QoL escaped in their free IGF-I concentrations. Also total IGF-I concentrations escaped in four of these six. In the subjects with normal QoL, free IGF-I levels remained normal in all, while total IGF-I levels only escaped in one.
Conclusions: This study tells us that the currently used biochemical criteria for disease control in acromegaly might be sufficient in assessing long-term mortality and morbidity, but they are insufficient in addressing the most important parameter from the patient’s perspective – QoL.
Effects of metformin and ethinyl estradiol–cyproterone acetate on lipid levels in obese and non-obese women with polycystic ovary syndrome
Authors: Rautio K , Tapanainen J S , Ruokonen A , Morin-Papunen L C 
Published: February 2005

Objective: Women with polycystic ovary syndrome (PCOS) exhibit risk factors for cardiovascular diseases such as abdominal obesity, insulin resistance and dyslipidemia. Insulin sensitizers, especially metformin, have been shown to improve these metabolic disturbances, but there are only a few studies on their effects on serum lipids in polycystic ovary syndrome.Methods: Thirty-five women with PCOS (18 obese and 17 non-obese) were randomized to 6-month treatments with metformin or ethinyl estradiol–cyproterone acetate oral contraceptive pills.Results: In the whole-study population (non-obese and obese women) serum levels of high-density lipoprotein cholesterol increased from 1.4±0.2 to 1.6±0.1 mmol/l (means ±s.e. throughout) at 3 and 6 months (P< 0.001), the total cholesterol:high-density lipoprotein cholesterol ratio decreased significantly from 3.8±0.3 to 3.3±0.2 at 6 months (P< 0.001) and a similar trend was observed in serum triglyceride levels during metformin treatment. In the oral contraceptive group, serum levels of total cholesterol increased from 4.9±0.3 to 5.4±0.3 mmol/l (P< 0.05), high-density lipoprotein cholesterol increased from 1.2±0.1 to 1.5±0.1 mmol/l (P< 0.001), the total cholesterol:high-density lipoprotein cholesterol ratio decreased from 4.6±0.4 to 3.7±0.2 (P< 0.001) and triglycerides increased from 1.3±0.1 to 1.9±0.2 mmol/l at 6 months of treatment (P< 0.001). Serum low-density lipoprotein cholesterol levels remained unchanged during both treatments. Milder but similar changes in the subgroups of obese and non-obese women were observed during both treatments. Moreover, in the whole-study population both systolic (P= 0.02) and diastolic (P= 0.05) blood pressures decreased over the 6 months of metformin treatment.Conclusion: In women with PCOS, metformin treatment had beneficial effects on lipid profile and blood pressure, and therefore it could be useful in the prevention of cardiovascular complications in these women.
Chronic glucocorticoid treatment alters spontaneous pulsatile parathyroid hormone secretory dynamics in human subjects
Authors: Bonadonna Stefania , Burattin Anna , Nuzzo Monica , Bugari Giovanna , Rosei Enrico Agabiti , Valle Domenico , Iori Nicoletta , Bilezikian John P , Veldhuis Johannes D , Giustina Andrea 
Published: February 2005

Objective: Spontaneous parathyroid hormone (PTH) secretory dynamics include tonic and pulsatile components. It is not known how glucocorticoids might alter these secretory dynamics.
Design: The aim of our study was to evaluate spontaneous fluctuations in serum PTH levels in six adult male patients (aged 31–64 years) receiving chronic (>6 months) therapy with glucocorticoids (daily dosage >7.5 mg of prednisone or dose equivalent of other corticosteroid) as compared with a control group of 10 age- and sex-matched normal subjects.
Methods: Peripheral venous blood sampling was performed every 3 min for 6 h from 0900 to 1500 h. Plasma PTH release profiles were subjected to deconvolution analysis, a method that resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, that in turn provides an integrated measure of the serial regularity or orderliness of the release process.
Results: In the glucocorticoid-treated group, the PTH tonic secretory rate was reduced (4.3±0.74 vs 8.8±1.4 pg/ml per min in controls, P = 0.017). There was, however, an increase in the fractional pulsatile PTH secretion (42±8.2 vs 18.3±3.9 pg/ml per min, P = 0.006) in glucocorticoid-treated vs normal subjects. Mean overall PTH concentration, as well as mean integrated area, was similar among normal and glucocorticoid-treated subjects.
Conclusions: These results demonstrate, for the first time, that chronic glucocorticoid treatment induces a redistribution of spontaneous PTH secretory dynamics by reducing the amount released in tonic fashion and increasing the amount released as pulses.
Relationship between serum adiponectin concentration, pulse wave velocity and nonalcoholic fatty liver disease
Authors: Kim S G , Kim H Y , Seo J A , Lee K W , Oh J H , Kim N H , Choi K M , Baik S H , Choi D S 
Published: February 2005

Objectives: We aimed to investigate the relationship between nonalcoholic fatty liver disease (NAFLD), serum adiponectin concentration and brachial-ankle pulse wave velocity (baPWV) as a risk marker for atherosclerosis.
Methods: A total of 213 nonalcoholic subjects (67 males, 146 females) participated in this study. Division of subjects into the NAFLD group or the normal group was based on the existence of fatty liver detected by sonography.
Results: Serum adiponectin levels in the NAFLD group were significantly lower than those in the normal group. After adjusting for age, body-mass index (BMI) and the homeostasis model of assessment (HOMA), there was a significant negative correlation between NAFLD and serum adiponectin level only in females (r = −0.22, P = 0.008). Multiple logistic regression analysis showed a tendency of inverse correlation between NAFLD and serum adiponectin level in females (P = 0.055). After adjustment for age, BMI and HOMA value, serum adiponectin levels were inversely correlated with serum alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels (r = −0.199 (P = 0.004) and r = −0.282 (P < 0.001)). On the other hand, baPWV in the NAFLD group was also significantly higher than that in the normal group in females (P = 0.005). Individual levels of serum ALT, aspatate aminotransferase (AST), alkaline phosphatase (ALP) and GGT were positively correlated with baPWV after adjusting for age, sex, BMI, HOMA and systolic blood pressure (P < 0.05).
Conclusion: Serum adiponectin level and baPWV were significantly associated with NAFLD and various liver enzymes, especially in females.
Is there a gender difference in the associations of birthweight and adult hypothalamic–pituitary–adrenal axis activity?
Authors: Reynolds Rebecca M , Walker Brian R , Syddall Holly E , Andrew Ruth , Wood Peter J , Phillips David I W 
Published: February 2005

Objective: Increased hypothalamic–pituitary–adrenal (HPA) axis activity in men of low birthweight may be an important link between early life and the adult metabolic syndrome. In animal models females are more sensitive than males to HPA axis programming, but whether gender influences susceptibility in humans is unknown.
Design: Birth cohort study.
Methods: We studied 106 women aged 67–78 years, from Hertfordshire, UK, in whom birthweight was recorded. Negative feedback sensitivity was assessed by an overnight low-dose (0.25 mg) dexa-methasone suppression test, and adrenal sensitivity by a low-dose (1 μg) ACTH1 – 24 stimulation test. Cortisol and its metabolites were analysed in a 24 h urine collection. Data were compared with previously published identical measurements in 205 men aged 66–77 years from the same cohort.
Results: In women, plasma cortisol levels after dexamethasone were lower (P < 0.0001) and peak cortisol following ACTH1 – 24 were higher (P < 0.0001) than in men, suggesting a more responsive HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH1 – 24 (P = 0.05 for trend) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from that in men; a 1 lb decrease in birthweight was associated with an incremental rise in cortisol of 12.6 nmol/l (95% confidence interval (CI) 1.4, 23.8) in men, P = 0.03, and 14.8 nmol/l (95% CI −0.4, 29.9) in women, P = 0.05 (P = 0.82 for birthweight × gender interaction). In a combined analysis of men and women adjusted for gender (n = 302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) greater incremental rise in plasma cortisol, P = 0.003.
Conclusions: Associations between lower birthweight and increased HPA axis activity are similar in men and women, supporting the hypothesis that HPA axis activation is an important mechanism underlying programming of adult disease.