bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-κB ligand levels in women with established osteoporosis treated with teriparatide
Authors: Anastasilakis Athanasios D , Goulis Dimirtios G , Polyzos Stergios A , Gerou Spiridon , Pavlidou Vasiliki , Koukoulis George , Avramidis Avraam 
Published: February 2008

ObjectiveThe mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone (PTH) administration are not fully elucidated. The aim of this prospective study was to evaluate the acute effect (up to 1 month) of teriparatide (TPTD; human recombinant PTH 1–34) on serum levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) in women with established osteoporosis.DesignTwenty-three postmenopausal Caucasian women with established osteoporosis (mean age 66.7±1.6 years) received daily injections of 20 μg TPTD for 12 months.MethodsSerum samples for total calcium (Ca), phosphate, alkaline phosphatase, N-terminal propeptide of type I collagen, intact PTH (iPTH), OPG, and RANKL were obtained at baseline, 1 h, 1 day, and 1 month after initiation of therapy. Lumbar spine bone mineral density (BMD) was measured before and 12 months after TPTD treatment.ResultsSerum total Ca increased and iPTH gradually decreased with TPTD treatment. Serum OPG levels remained unchanged, while RANKL increased gradually during the study (P<0.001). There was no correlation between OPG or RANKL and BMD changes or iPTH levels.ConclusionsTPTD therapy in women with postmenopausal osteoporosis results in acute increase in serum RANKL levels but does not affect serum OPG. These changes may reflect an increase in the number of active osteoblasts with therapy and might be responsible for the acceleration of bone turnover rate that characterizes TPTD.
Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR
Authors: Taboada Giselle F , Luque Raul M , Neto Leonardo Vieira , Machado Evelyn de O , Sbaffi Bruna C , Domingues Romeu C , Marcondes Jorge B , Chimelli Leila M C , Fontes Rosita , Niemeyer Paulo , de Carvalho Denise P , Kineman Rhonda D , Gadelha Mônica R 
Published: February 2008

ObjectiveTo determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment.Design and methodsQuantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging).ResultsSSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046–5555), 2098 (194–23 954), 97 (0–460), 14 (0–29 480), and 0 (0–652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=−0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7–10) vs 0.3 (0.1–7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% – area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12).ConclusionsSomatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.
Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study
Authors: Pedersen Inge Bülow , Laurberg Peter , Knudsen Nils , Jørgensen Torben , Perrild Hans , Ovesen Lars , Rasmussen Lone Banke 
Published: February 2008

BackgroundAutoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid antibodies is limited.AimTo evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab.Material and methodsIn a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected.ResultsData were analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPO-Ab status) and both antibodies together. The association between smoking and thyroid autoantibodies was stronger for Tg-Ab than for TPO-Ab. There was no association between smoking and TPO-Ab measured alone or between smoking and TPO-Ab when Tg-Ab was included in the model as an explanatory variable.ConclusionSmoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies.
Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene
Authors: Foppiani L , Forzano F , Ceccherini I , Bruno W , Ghiorzo P , Caroli F , Quilici P , Bandelloni R , Arlandini A , Sartini G , Cabria M , Del Monte P 
Published: February 2008

IntroductionCalcitonin measurement is advised in the diagnosis of thyroid nodules, as it is an accurate marker of medullary thyroid carcinoma (MTC). C-cell hyperplasia (CCH)-induced hypercalcitoninemia cannot be distinguished from that induced by MTC, unless surgery is performed.CaseWe report the clinical and biological features of a patient with a family history of cancer, including melanoma and pancreatic cancer, who had previously undergone surgery for melanoma. He presented the unusual association of papillary thyroid carcinoma (PTC), normocalcemic hyperparathyroidism, and hypercalcitoninemia with a pathological response to pentagastrin, which was histologically deemed secondary to CCH. Multiple endocrine neoplasia (MEN) 2A was diagnosed. RET gene analysis showed a p.V804M missense mutation in exon 14, a low- but variably penetrant defect found in both sporadic and MEN2A-associated MTC/CCH, and a p.G691S polymorphism in exon 11. Furthermore, the germline P48T mutation was found in the CDKN2A gene exon 1, which is known to be associated with melanoma and pancreatic cancer. The patient showed the uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A; this finding, deemed to be a mere coincidence, did not modify the phenotype expected by each single mutation. CCH associated with V804M RET mutation is a precancerous condition and surgery is recommended. In order to exclude MTC, surgery is advised in patients with a pathological calcitonin response to pentagastrin, in the absence of thyroid autoimmunity. CCH-induced hypercalcitoninemia can be associated with thyroid cancers other than MTC (e.g., PTC). Family history is important in scheduling specific genetic screening in high-risk patients and their relatives.
The association between serum parathyroid hormone and bone mineral density, and the impact of smoking: the Tromsø Study
Authors: Sneve Monica , Emaus Nina , Joakimsen Ragnar Martin , Jorde Rolf 
Published: February 2008

ObjectiveTo explore the relation between serum parathyroid hormone (PTH) and bone mineral density (BMD), adjusted for lifestyle factors including smoking.DesignCross-sectional study.MethodsThe Tromsø Study is a population-based study performed for the fifth time in 2001. Serum PTH was measured and the subjects filled in a questionnaire covering lifestyle factors. BMD at the hip, distal and ultradistal forearm was measured.ResultsComplete datasets were available in 1442 men and 1368 women. Age, body mass index and serum PTH were strong predictors of BMD level at the hip in both genders. No significant relation was seen between serum PTH and BMD at the distal or ultradistal forearm. When smokers and non-smokers were analysed separately, the relation between PTH and BMD at the hip was significant in current non-smokers only. In males, current non-smokers had significantly higher BMD at all three measurement sites compared with current smokers. Male former smokers had values in between current and never smokers. There was a significant and negative relation between number of years smoked and BMD at the hip. In male former smokers, there was an increase in BMD with increasing years since smoking cessation.ConclusionSerum PTH is negatively associated with BMD at the hip, and the relation seems to be masked, or diminished, by smoking. Smoking reduces BMD at the hip, distal and ultradistal forearm in males, and the effect appears to be mainly time and not dose dependent.
Impaired quality of life of patients with acromegaly: control of GH/IGF-I excess improves psychological subscale appearance
Authors: Matta Maria P , Couture Elisabeth , Cazals Laurent , Vezzosi Delphine , Bennet Antoine , Caron Philippe 
Published: February 2008

IntroductionAcromegaly, a chronic disease caused by GH/IGF-I excess, has a major impact on quality of life (QoL).ObjectiveTo evaluate QoL of acromegalic patients in relation to control status of the disease.Design and methodsSingle center observational study including 93 patients with acromegaly recruited to complete QoL questionnaire (AcroQol). QoL was evaluated at least 3 months after surgery and/or medical treatment. Patients were divided into two groups: controlled (I) and uncontrolled (II) according to the latest consensus acromegaly ‘control’ criteria and further subdivided into four subgroups according to the previous pituitary adenoma surgery (Ib and IIb) or without surgery (Ia and IIa).ResultsMean GH (0.81±0.47 ng/ml) and IGF-I (195±71 ng/ml) values in group I were significantly lower than in group II (GH, 7.01±12.05 ng/ml and IGF-I, 513±316 ng/ml; P<0.001). There was no difference in total AcroQol score, physical, or psychological scales between groups I and II. However, when adjusted to age and disease duration since diagnosis, patients of group I (63±20%) showed an improved psychological subscale appearance than those of group II (58±17%; P=0.035). In group II, IGF-I level was lower after surgery (IIa=588±353, IIb=410±225 ng/ml; P<0.038), and psychological subscale appearance was significantly better in subgroup IIb (64.9±18.1%) than in subgroup IIa who had medical treatment (53.9±14.3%; P=0.009).ConclusionQoL is severely impaired in acromegalic patients. Control of GH/IGF-I excess by surgery or medical treatment seems to have a positive impact on psychological subscale appearance.
Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker
Authors: Wang Gang , Lai Fernand Mac-Moune , Lai Ka-Bik , Chow Kai-Ming , Kwan Bonnie Ching-Ha , Li Philip Kam-Tao , Szeto Cheuk-Chun 
Published: February 2008

BackgroundPodocyte injury and its subsequent loss in urine play an important role in the pathogenesis of diabetic nephropathy; blockade of the renin–angiotensin system may ameliorate the damage.MethodsIn a non-randomized setting, we studied 71 patients with diabetic nephropathy on a stable dose of angiotensin-converting enzyme inhibitor (ACEI). In 37 patients, angiotensin receptor blocker (ARB) was added (the combination group); ACEI alone was continued in the other 34 (the control group). The mRNA expressions of nephrin, podocin, and synaptopodin in urinary sediment were measured at 0 and 12 weeks.ResultsBaseline glomerular filtration rate (GFR) correlated with the urinary expression of nephrin (r=0.320, P=0.007), podocin (r=0.336, P=0.004), and synaptopodin (r=0.350, P=0.003). After adjusting for the baseline expression, the combination group had a significantly lower urinary synaptopodin expression (7.49 (95% confidence interval CI, 0.62–115.29) vs 14.83 (95% CI, 1.03–241.43), P=0.026) than the control group after 12 weeks of treatment. The percentage change in urinary podocin expression over 12 weeks of treatment had a modest correlation with the rate of GFR decline in 1 year (r=−0.243, P=0.041).ConclusionIn patients with diabetic nephropathy, urinary mRNA expression of podocyte markers correlated with baseline renal function. Urinary expression of synaptopodin was lower after 12 weeks of ACEI and ARB combination therapy. Our result suggests that serial measurement of urinary podocyte markers may have a value for the monitoring of therapeutic response.
Metabolic evidence for impaired 17α-hydroxylase activity in a kindred bearing the E305G mutation for isolate 17,20-lyase activity
Authors: Tiosano Dov , Knopf Carlos , Koren Ilana , Levanon Nurit , Hartmann Michaela F , Hochberg Ze'ev , Wudy Stefan A 
Published: February 2008

ContextThe CYP17A1 gene encodes many enzymatic reactions including 17α-hydroxylase and 17,20-lyase activities. Mutations that selectively ablate the 17,20-lyase activity, causing isolated 17,20-lyase deficiency, are exceedingly rare and may belong to the rarest of all disorders of steroidogenesis. We have previously reported an E305G mutation in the active site of CYP17A1 that apparently causes isolated 17,20-lyase deficiency. Expression studies suggested intact 17α-hydroxylase activity which was at odds with subnormal tetracosactrin stimulated cortisol in the patients.ObjectivesTo investigate the in vivo activity of the adrenal enzymes, we used the metabolomics approach with urinary steroid profiling by gas chromatography–mass spectrometry.PatientsOf the 11 subjects investigated, 6 patients in the kindred were found to be homozygous, 4 members were asymptomatic heterozygous, and 1 was homozygous for the wild-type allele.ResultsIn the homozygous patients for E305G, both serum and urinary steroids showed a severe lack of androgens (C19-steroids) pointing to the absence of 17,20-lyase activities. Furthermore, precursor/product ratios of urinary steroid metabolites characterizing 17α-hydroxylase activity showed variable decreases in 17α-hydroxylase activities.ConclusionsThe results confirm the complete absence of 17,20-lyase activity in vivo, as in the in vitro expression studies. On the other hand, in vivo 17α-hydroxylase activity was partially impaired. Thus, the in vivo metabolic data seem to be more sensitive than the expression study and suggests that this mutation also impairs 17α-hydroxylase activity.
GH responses to two consecutive bouts of neuromuscular electrical stimulation in healthy adults
Authors: Sartorio A , Jubeau M , Agosti F , De Col A , Marazzi N , Lafortuna C L , Maffiuletti N A 
Published: February 2008

BackgroundIt is well established that repeated GHRH administration or repeated voluntary exercise bouts are associated with a complete blunting of GH responsiveness when the administration of the second stimulus follows the first one after a 2-h interval.AimTo evaluate GH responses to neuromuscular electrical stimulation (NMES) in healthy adults.MethodsSix volunteers (mean age±s.d. 31.7±5.5 years) were studied before and after two consecutive bouts of NMES exercise (a series of 20 contractions at the maximum of individual tolerance, frequency: 75 Hz, pulse duration: 400 μs, on–off ratio: 6.25–20 s) administered at a 2-h interval.ResultsBaseline GH levels (mean: 0.3±0.2 ng/ml) significantly increased after the first NMES (peak: 4.2±3.7 ng/ml), with a complete normalization after 120 min (0.3±0.3 ng/ml). The administration of the second bout of NMES of comparable characteristics also resulted in a significant GH increase (peak: 5.2±3.2 ng/ml), which was comparable with that observed after the previous one. GH net incremental area under the curve after the first and second bouts of NMES were not significantly different (155.1±148.5 and 176.9±123.3 ng/ml per h, P=0.785).ConclusionsUnlike repeated pharmacological stimuli and voluntary exercise bouts, subsequent sessions of NMES administered at a 2-h interval appear to circumvent feedback mechanisms and to re-induce the GH responses, thus indicating a possible different underlying mechanism elicited by different GH-releasing stimuli.
Pretreatment with Albuterol versus Montelukast for Exercise‐Induced Bronchospasm in Children
Authors: Raissy Hengameh H. , Harkins Michelle , Kelly Franceska , Kelly H. William 
Published: February 2008

Study Objectives. To compare pretreatment with albuterol versus montelukast added to the current asthma regimen for protection against exercise‐induced bronchospasm in children with mild‐to‐moderate asthma, and to determine whether cysteinyl leukotriene (Cys‐LT) concentrations measured in the exhaled breath condensate correlated with response to montelukast.Design. Prospective, randomized, double‐blind, double‐dummy, crossover studySetting. Asthma clinic at a university‐affiliated medical center.Patients. Eleven children aged 7–17 years with physician‐diagnosed mild‐to‐moderate asthma for at least 6 months and with self‐reported exercise‐induced bronchospasm (defined as ≤ 15% decrease in forced expiratory volume in 1 sec [FEV1] at screening and baseline visit).Intervention. Patients were randomly assigned to receive 3–7 days of oral montelukast 5–10 mg/day or 2 puffs of an albuterol metered‐dose inhaler just before an exercise challenge and then were crossed over to the alternate therapy for the last visit.Measurements and Main Results. Serial spirometry was performed before and at 0, 5, 10, 15, 30, 45, and 60 minutes after the exercise challenge at each visit. Measurement of exhaled breath condensate was performed at the screening visit and study visits 1 and 2. The primary outcome was the maximum change in FEV1 after exercise. Secondary outcomes were the area under the curve for FEV1 (expressed as percentage decrease from baseline) during the first 60 minutes (AUC0–60) after exercise and the proportion of patients in whom exercise‐induced bronchospasm was prevented (defined as < 15% decrease in FEV1 after exercise challenge). The mean ± SD maximum decrease in FEV1 was 27.5 ± 7.9% at baseline. Patients receiving montelukast had an 18.3 ± 13.7% decrease in FEV1 compared with 0.7 ± 1.6% in patients receiving albuterol (p=0.002, paired t test). Exercise‐induced bronchospasm was prevented in 100% of the patients receiving albuterol compared with 55% receiving montelukast (p<0.05, McNemar's test). The AUC0–60 was significantly smaller with albuterol compared with montelukast (p<0.001, Wilcoxon signed rank test). No correlations were found between Cys‐LT concentration and the severity of exercise‐induced bronchospasm or the response to montelukast.Conclusion. Pretreatment with albuterol is more effective than montelukast for prevention of exercise‐induced bronchospasm in children with asthma.
In Vitro Activity of Cefepime, Imipenem, Tigecycline, and Gentamicin, Alone and in Combination, Against Extended‐Spectrum β‐Lactamase‐Producing Klebsiella pneumoniae and Escherichia coli
Authors: Cha Raymond 
Published: February 2008

Study Objective. To evaluate the activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended‐spectrum β‐lactamase (ESBL)‐producing Klebsiella pneumoniae and Escherichia coli.Design. In vitro susceptibility and time‐kill analysis.Setting. University‐affiliated research laboratory.Isolates. Ten K. pneumoniae and 10 E. coli clinical strains known to produce ESBL.Measurements and Main Results. Minimum inhibitory concentration (MIC) testing was performed at 5.5 and 7.0 log10 colony‐forming units (cfu)/ml. Time‐kill studies were performed over 24 hours with a high inoculum of 7.0 log10 cfu/ml for cefepime, imipenem, tigecycline, and gentamicin at 1 times MIC. Combination studies were tested for cefepime plus tigecycline, cefepime plus imipenem, imipenem plus tigecycline, and for adjunctive gentamicin with cefepime, imipenem, or tigecycline. At the high inoculum, the MIC ranges for cefepime, imipenem, tigecycline, and gentamicin were 0.25–256 (MIC for 90% of tested strains [MIC90] = 32), 0.125‐2 (MIC90 = 1), 0.25‐16 (MIC90 = 4), and 0.25‐4 mg/L (MIC90 =1), respectively, for all isolates. At the higher inoculum, MICs shifted for cefepime, imipenem, and tigecycline. Change in log10 cfu/ml from baseline to 24 hours for cefepime, imipenem, and tigecycline alone ranged from 4.85‐0.71, 5‐4.22, and 3.5‐1.01, respectively, for all isolates. Bactericidal activity was observed for cefepime alone (10 [50%] of 20 isolates), imipenem alone (20 [100%] of 20), and tigecycline alone (3 [15%] of 20). Combination studies with cefepime plus tigecycline resulted in synergy against 4 (20%) of 20 isolates. Combination studies with gentamicin resulted in synergy against 6 isolates (30%) with cefepime and 4 isolates (20%) with tigecycline. No synergy was observed with imipenem combinations. No antagonism was observed. With the exception of cefepime, correlations were observed between MIC and terminal densities for studied agents.Conclusions. Cefepime exhibited bactericidal activity but was unrelated to susceptibility. Tigecycline exhibited predictable bacteriostatic activity and synergy in combination against a subset of study isolates. Imipenem exhibited predictable bactericidal activity against all isolates. The utility of combination regimens with novel agents requires further exploration.