bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation into possible causes of interference in serum testosterone measurement in women
Authors: Heald A H , Butterworth A , Kane J W , Borzomato J , Taylor N F , Layton T , Kilpatrick E S , Rudenski A 
Published: April 2006

Background: Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women. Methods: Women who had a blood sample referred to Hope Hospital Clinical Biochemistry laboratory for measurement of serum testosterone concentration over a six-month period were studied. Clinical and treatment data were recorded. A difference (direct-minus-extracted testosterone) of less than 1.0 nmol/L was used to define a group with low interference. A difference of 2.5 nmol/L or more was used to define a group with significant interference. Results: The distribution of interference in 1271 serum samples from female patients was unimodal. There were no group differences in clinical presentation or treatment. The median degree of interference was 1.4 nmol/L. In 42 female patients with varying degrees of interference, identified on routine assay, regression analysis showed strong association between dehydroepiandrosterone sulphate (DHEA-S) and interference (direct-minus-extracted testosterone) ( r = 0.77, P<0.001). Conclusions: Given that DHEA-S is present in very variable amounts in blood, it is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.
The LH/FSH ratio has little use in diagnosing polycystic ovarian syndrome
Authors: Cho Li Wei , Jayagopal Vijay , Kilpatrick Eric S , Holding Stephen , Atkin Stephen L 
Published: April 2006

Background: The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending against its use. This study aimed to compare the variability of the LH/FSH ratio in PCOS with that of normal menstruating women over a full cycle in order to establish the diagnostic utility, or otherwise, of the test. Methods: Twelve women with PCOS and 11 matched controls had blood collected at four-day intervals on 10 consecutive occasions over a complete menstrual cycle. Results: The median LH/FSH ratio for individual subjects did not differ significantly between the PCOS and the non-affected group (1.6 versus 1.2, P=0.14). Only 7.6% of samples from PCOS patients had an LH/FSH ratio above three, compared with 15.6% of samples from normal subjects. Conclusion: This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS.
Medication Safety: Occurrence and Impact of Unanticipated Variation in Intravenous Methotrexate Dosing
Authors: Parshuram Christopher S , Dupuis L Lee , To Teresa , Weitzman Sheila S , Koren Gideon , Laupacis Andreas 
Published: April 2006

Background: Studies using direct measurement suggest that the doses of up to 65% of drug infusions are outside industry standards. These preparation-associated errors occur despite routine safety procedures. As of April 5, 2006, the clinical impact of these errors had not been evaluated. Objective: To measure the occurrence and associated clinical outcomes of variations in intravenous methotrexate dosing. Methods: A prospective observational study was performed on 47 methotrexate infusions of 800 mg/m2 that were administered to 19 children with acute lymphoblastic leukemia. Serum methotrexate concentrations were measured at the end of the infusions, which were administered over 24 hours. The total methotrexate dose was determined by direct measurement of the concentration and the volume of each infusion. Results: Dosing errors greater than or equal to 10% occurred in 11 (23%) infusions and ranged from –61% to 55% of the ideal dose. Repeated measures regression analysis found the measured total methotrexate dose was not significantly associated with the serum methotrexate concentration (p = 0.58) or with clinical toxicities. The methotrexate dose administered over the last hours of infusion (p = 0.006) and the serum creatinine level at diagnosis (p = 0.05) were the most significant predictors of the methotrexate concentration. High methotrexate concentrations were significantly associated with increased hepatic aminotransferase levels; however, the degree of elevation was of limited clinical relevance. Conclusions: While unexpected errors in drug dosing are more common than is suggested by other methods, the clinical impact observed in this model of methotrexate infusion was not demonstrably greater than medication errors described by other methods. Subsequent studies in this model of dosing error will require larger sample sizes, and other drugs should be evaluated.
Patient Safety and Quality Improvement Act of 2005
Authors: Fassett William E 
Published: April 2006

Objective: To review Public Law (PL) 109-41—the Patient Safety and Quality Improvement Act of 2005 (PSQIA)—and summarize key medication error research that contributed to congressional recognition of the need for this legislation. Data Sources: Relevant publications related to medication error research, patient safety programs, and the legislative history of and commentary on PL 109-41, published in English, were identified by MEDLINE, PREMEDLINE, Thomas (Library of Congress), and Internet search engine–assisted searches using the terms healthcare quality, medication error, patient safety, PL 109-41, and quality improvement. Additional citations were identified from references cited in related publications. Study Selection and Data Extraction: All relevant publications were reviewed. Summarization of the PSQIA was carried out by legal textual analysis. Data Synthesis: PL 109-41 provides privilege and confidentiality for patient safety work product (PSWP) developed for reporting to patient safety organizations (PSOs). It does not establish federal mandatory reporting of significant errors; rather, it relies on existing state reporting systems. The Act does not preempt stronger state protections for PSWP. The Agency for Healthcare Research and Quality is directed to certify PSOs and promote the establishment of a national network of patient safety databases. Whistleblower protection and penalties for unauthorized disclosure of PSWP are among its enforcement mechanisms. Conclusions: The Act protects clinicians who report minor errors to PSOs and protects the information from disclosure, but providers must increasingly embrace a culture of interdisciplinary concern for patient safety if this protection is to have real impact on patient care.
Intermittent Ibandronate Preserves Bone Quality and Bone Strength in the Lumbar Spine After 16 Months of Treatment in the Ovariectomized Cynomolgus Monkey
Authors: Müller Ralph , Hannan Mary , Smith Susan Y , Bauss Frieder 
Published: April 2006

Abstract
The dose-dependent effect of ibandronate treatment on bone mass and architecture was assessed in a large animal study of OVX monkeys using μCT for quantitative bone morphometry and biomechanical testing for measures of bone strength. The study showed that intermittent ibandronate preserved lumbar spine bone quality and strength in these animals after 16 months of treatment.
Introduction: Ibandronate is a bisphosphonate, which is a class of compounds that, in pharmacologically active doses, not only suppresses bone resorption and turnover but also prevents loss of bone mass and strength in the ovariectomized (OVX) rat.
Materials and Methods: We evaluated the effects of ibandronate on bone mass and architecture in the OVX cynomolgus macaque. Sixty-one adult female macaques were divided into five groups (N = 11–15): sham control, OVX control, and OVX low- (10 μg/kg), medium- (30 μg/kg), and high- (150 μg/kg) dose ibandronate. Treatment was administered by intravenous bolus injection every 30 days for 16 months starting at ovariectomy. This dosing schedule is equivalent to a 3-monthly dosing regimen in human subjects over 4 years. Animals were killed at the conclusion of the study, and excised bone specimens of the first lumbar vertebra (L1) were evaluated for quantitative bone densitometry, morphometry, and mechanical properties. Architectural parameters were assessed by μCT including direct 3D bone morphometry. A measure of specimen strength was obtained using destructive compression testing.
Results and Conclusions: A significant loss of bone mass and related changes in bone architecture after ovariectomy resulted in a reduction of whole bone strength as expressed by high correlations between architectural and mechanical properties. In this analysis, BMC was the best single predictor of whole bone strength (r2 = 67%). Nevertheless, including architectural indices in a multiple linear regression analysis increased that prediction to 88%. With respect to the treatment, the medium- and high-dose groups were not significantly different from the sham group for all bone mineral and structural parameters. Additionally, significant differences were seen for all measured parameters between the high-dose group and the OVX group, and for some parameters, between the medium-dose group and the OVX group. Intermittent ibandronate treatment effectively and dose-dependently prevented bone loss, architectural deterioration, and strength reduction in the lumbar spine of OVX monkeys.
Neridronate Prevents Bone Loss in Patients Receiving Androgen Deprivation Therapy for Prostate Cancer
Authors: Morabito Nancy , Gaudio Agostino , Lasco Antonino , Catalano Antonino , Atteritano Marco , Trifiletti Aldo , Anastasi Giuseppina , Melloni Darwin , Frisina Nicola 
Published: April 2006

Abstract
Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation.
Introduction: Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation.
Materials and Methods: Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study.
Results: After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study.
Conclusions: Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.
Association Between Exercise and Pubertal BMD Is Modulated by Estrogen Receptor α Genotype
Authors: Suuriniemi Miia , Mahonen Anitta , Kovanen Vuokko , Alén Markku , Lyytikäinen Arja , Wang Qingju , Kröger Heikki , Cheng Sulin 
Published: April 2006

Abstract
Genetic and environmental factors contribute to bone mass, but the ways they interact remain poorly understood. This study of 245 pre- and early pubertal girls found that the PvuII polymorphism in the ER-α gene modulates the effect of exercise on BMD at loaded bone sites.
Introduction: Impaired achievement of bone mass at puberty is an important risk factor for the development of osteoporosis in later life. Genetic, as well as environmental, factors contribute to bone mass, but the ways they interact with each other remain poorly understood.
Materials and Methods: We investigated the interaction between a PvuII polymorphism at the ER-α gene and physical activity (PA) on the modulation of bone mass and geometry in 245 10- to 13-year-old pre- and early pubertal Finnish girls. Level of PA was assessed using a questionnaire. Bone properties were measured using DXA and pQCT. The analyses were controlled for the effects of Tanner stage and body size index.
Results: Girls with heterozygote ER-α genotype (Pp) and high PA had significantly higher bone mass and BMD, as well as thicker cortex, at loaded bone sites than their low-PA counterparts. No differences were found in bone properties of the distal radius, which is not a weight-bearing bone. Bone properties did not differ in either homozygote groups (PP and pp) regardless of the PA level.
Conclusions: These findings suggest that the PvuII polymorphism in the ER-α gene may modulate the effect of exercise on BMD at loaded bone sites. The heterozygotes may benefit most from the effect of exercise, whereas neither of the homozygote groups received any significant improvement from high PA. Furthermore, high PA may hide the genetic influence on bone. Indeed, it seems that one may compensate one's less favorable Pp genotype by increasing leisure PA at early puberty.
Anti-Hip Fracture Efficacy of Bisphosphonates: A Bayesian Analysis of Clinical Trials
Authors: Nguyen Nguyen D , Eisman John A , Nguyen Tuan V 
Published: April 2006

Abstract
In postmenopausal women, the efficacy of bisphosphonates on hip fracture risk is not clear. This Bayesian meta-analysis quantitatively reviewed data from 12 randomized clinical trials with 18,667 patients and found that bisphosphonate treatment was associated with a reduced risk for hip fracture by 42%.
Introduction: The efficacy of antiresorptive bisphosphonates therapy on reducing hip fracture is not clear, because evidence from randomized clinical trials (RCTs) is inconclusive. This study was undertaken to quantitatively assess the effect of bisphosphonates on hip fracture using literature review and meta-analysis.
Materials and Methods: Bayesian methods of meta-analysis were applied to synthesize data from 12 RCTs available between 1990 and 2004. The trials involved 18,667 postmenopausal women with low BMD or osteoporosis who have been followed or treated for between 1 and 4 years. The medications used were etidronate (two trials) alendronate (six trials), risedronate (three trials), and clodronate (one trial). The primary endpoint was the incidence of hip fracture.
Results: When data from all 12 studies were pooled, treatment with bisphosphonates was associated with a reduced risk for hip fracture by 42% (relative risk {RR}, 0.58; 95% credible interval {CrI}, 0.42-0.80). The absolute rate reduction was 52 hip fractures per 10,000 women (95% CrI, 4–110) for a period of 3-year treatment. The probability that bisphosphonates are better than placebo (in reducing hip fracture risk by at least 30%) was 0.90.
Conclusions: In postmenopausal women with osteoporosis or low BMD, bisphosphonate treatment is associated with reduced risk of hip fracture.
Immune Regulation of 25-Hydroxyvitamin-D3-1α-Hydroxylase in Human Monocytes
Authors: Stoffels Katinka , Overbergh Lut , Giulietti Annapaula , Verlinden Lieve , Bouillon Roger , Mathieu Chantal 
Published: April 2006

Abstract
Monocytes express 1α-hydroxylase, the enzyme responsible for final hydroxylation of vitamin D3, in response to IFNγ and CD14/TLR4 activation. Cross-talk between the JAK-STAT, the NF-κB, and the p38 MAPK pathways is necessary, and direct binding of C/EBPβ to its recognition sites in the promoter of the 1α-hydroxylase gene is a prerequisite.
Introduction: The activated form of vitamin D3, 1,25(OH)2D3, known for its action in bone and mineral homeostasis, has important immunomodulatory effects. 1,25(OH)2D3 modulates the immune system through specific nuclear receptors, whereas macrophages produce 1,25(OH)2D3. In monocytes, the expression of 1α-hydroxylase, the enzyme responsible for final hydroxylation of vitamin D3, is regulated by immune stimuli. The aim of this study was to elucidate the intracellular pathways through which interferon (IFN)γ and Toll-like receptor (TLR) modulation regulate expression of 1α-hydroxylase in monocytes/macrophages.
Materials and Methods: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) and stimulated with IFNγ (12.5 U/ml) and/or lipopolysaccharide (LPS; 100 ng/ml) for 48 h. The following inhibitors were used: janus kinase (JAK) inhibitor AG490 (50 μM), NF-κB inhibitor sulfasalazine (0.25 mM), p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 μM). 1α-hydroxylase mRNA expression was monitored by qRT-PCR. Phosphorylation of transcription factors was studied by Western blotting. Transfection of mutated or deletion promoter constructs, cloned in the pGL3-luciferase reporter plasmid, were performed in the RAW264.7 cell line. Cells were stimulated with IFNγ (100 U/ml) and LPS (100 μg/ml), and promoter activity was studied. Binding of signal transducer and activator of transcription (STAT)1α, NF-κB, and C/EBPβ to their respective binding sites in the promoter was analyzed by gel shift assays.
Results: 1α-hydroxylase mRNA expression in monocytes is synergistically induced by IFNγ and CD14/TLR4 ligation and paralleled by 1,25(OH)2D3 production. This induction requires the JAK-STAT, NF-κB, and p38 MAPK pathways. Each of them is essential, because blocking individual pathways is sufficient to block 1α-hydroxylase expression (JAK inhibitor, 60% inhibition, p &lt; 0.01; NF-κB inhibitor, 70% inhibition, p &lt; 0.05; p38 MAPK inhibitor, 95% inhibition, p &lt; 0.005). In addition, we show the involvement of the p38 MAPK pathway in phosphorylation of C/EBPβ. Direct binding of C/EBPβ to its recognition sites in the 1α-hydroxylase promoter is necessary to enable its immune-stimulated upregulation.
Conclusion: IFNγ and CD14/TLR4 binding regulate expression of 1α-hydroxylase in monocytes in a synergistic way. Combined activation of the JAK-STAT, p38 MAPK, and NF-κB pathways is necessary, with C/EBPβ most probably being the essential transcription factor controlling immune-mediated transcription.
Incidence of Primary Hyperparathyroidism in Rochester, Minnesota, 1993–2001: An Update on the Changing Epidemiology of the Disease
Authors: Wermers Robert A , Khosla Sundeep , Atkinson Elizabeth J , Achenbach Sara J , Oberg Ann L , Grant Clive S , Melton L Joseph 
Published: April 2006

Abstract
We updated the incidence of primary hyperparathyroidism in Rochester, Minnesota. The lower rates previously noted persisted, whereas parathyroidectomies at our institution remained high. These data suggest an etiologic factor may be responsible for the peak incidence in the 1970s.
Introduction: Automated serum calcium measurements were associated with a dramatic rise in primary hyperparathyroidism in the early 1970s, but a progressive decline in the incidence thereafter was unexpected and suggested a fundamental change in the epidemiology of the disease. Our objective was to evaluate trends in the incidence of primary hyperparathyroidism since 1992.
Materials and Methods: In this population-based descriptive study, Rochester, MN, residents who met defined diagnostic criteria for primary hyperparathyroidism from January 1993 through December 2001 were identified through the medical record linkage system of the Rochester Epidemiology Project and the Mayo Clinic Laboratory Information System. Changes in incidence were evaluated by Poisson regression.
Results: Altogether, 136 Rochester residents (94 women and 42 men) were newly identified with primary hyperparathyroidism in 1993–2001. Their mean age was 56 years, and 93% had definite disease. The overall age- and sex-adjusted (to 2000 U.S. whites) rate during this period was 21.6 per 100,000 person-years, which was less than the annual rate of 29.1 per 100,000 observed in 1983–1992 and 82.5 per 100,000 in July 1974–1982. Although community incidence declined, the number of parathyroidectomies performed at our institution increased during the same period. Serum calcium was deleted from the automated chemistry panel in June 1996, but most subjects remained asymptomatic at diagnosis (95%) with mild hypercalcemia. The majority of subjects were observed without parathyroid surgery (75%), and there was minimal impact on patient management from the 1990 NIH consensus conference on asymptomatic primary hyperparathyroidism.
Conclusions: The lower incidence of primary hyperparathyroidism noted through 1992 has persisted in our community through 2001, whereas parathyroidectomies at our institution remained high. These data suggest that some underlying etiologic factor, in addition to the introduction of automated serum calcium testing, may have been responsible for the peak incidence in the 1970s.