bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Mullerian Hormone and Inhibin B in the Definition of Ovarian Aging and the Menopause Transition
Authors: Sowers Mary Fran R. , Eyvazzadeh Aimee D. , McConnell Daniel , Yosef Matheos , Jannausch Mary L. , Zhang Daowen , Harlow Sioban , Randolph John F. 
Published: July 2008

Context/Objective: The objective of the study was to determine whether anti-Mullerian hormone (AMH) and inhibin B are viable endocrine biomarkers for framing the menopause transition from initiation to the final menstrual period (FMP).
Design: We assayed AMH, inhibin B, and FSH in 300 archival follicular phase specimens from 50 women with six consecutive annual visits commencing in 1993 when all women were in the pre- and perimenopausal menopause stages. Subsequently each woman had a documented FMP. The assay results were fitted as individual-woman profiles and then related to time to FMP and age at FMP as outcomes.
Results: Based on annual values from six time points prior to the FMP, logAMH longitudinal profiles declined and were highly associated with a time point 5 yr prior to FMP [including both observed and values below detection (P &lt; 0.0001 and P = 0.0001, respectively)]. Baseline AMH profiles were also associated with age at FMP (P = 0.035). Models of declining loginhibin B profiles (including both observed and values below detection) were associated with time to FMP (P &lt; 0.0001 and P = 0.0003, respectively). There was no significant association of loginhibin B profiles with age at FMP.
Conclusions: AMH, an endocrine marker that reflects the transition of resting primordial follicles to growing follicles, declined to a time point 5 yr prior to the FMP; this may represent a critical biological juncture in the menopause transition. Low and nondetectable levels inhibin B levels also were observed 4–5 yr prior to the FMP but were less predictive of time to FMP or age at FMP.
Twenty-Four Hour Continuous Ghrelin Infusion Augments Physiologically Pulsatile, Nycthemeral, and Entropic (Feedback-Regulated) Modes of Growth Hormone Secretion
Authors: Veldhuis Johannes D. , Reynolds George Ann , Iranmanesh Ali , Bowers Cyril Y. 
Published: July 2008

Background: Ghrelin is a 28-amino acid acylated peptide that potentiates GHRH stimulation and opposes somatostatin inhibition acutely. Whether prolonged ghrelin administration can sustain physiological patterns of GH secretion remains unknown.
Hypothesis: Continuous delivery of ghrelin will amplify physiological patterns of GH secretion over 24 h.
Subjects: Men and women ages 29–69 yr, body mass indices 23–52 kg/m2, were included in the study.
Location: The study was performed at an academic medical center.
Methods: Twenty-four hour continuous sc infusion of saline vs. ghrelin (1 μg/kg·h) with frequent sampling was examined. Deconvolution and entropy analyses were performed.
Outcomes: IGF-I concentrations were determined. Basal, pulsatile, nycthemeral, and entropic measures of GH secretion were calculated.
Results: Ghrelin infusion compared with saline infusion for 24 h elevated (median) acylated ghrelin, GH, and IGF-I concentrations by 8.1-fold (P &lt; 0.001),11-fold (P &lt; 0.001), and 1.4-fold (P = 0.002). GH secretory-burst mass and frequency increased by 6.6-fold (P = 0.004) and 1.7-fold (P &lt; 0.001), respectively, resulting in a 12-fold increase in pulsatile GH secretion (P &lt; 0.001). Interpulse variability decreased significantly (P = 0.046), whereas GH secretory-burst shape and half-life did not change. The amplitude of the nycthemeral GH rhythm increased by 3.4-fold (P &lt; 0.001), and GH patterns became more irregular (higher approximate entropy P &lt; 0.001). Combining GHRH with ghrelin was not an additive in driving GH secretion.
Conclusions: Continuous ghrelin infusion for 24 h elevates acylated ghrelin, GH and IGF-I concentrations, and stimulates pulsatile, nycthemeral, and entropic modes of GH secretion. The consistency of outcomes in a heterogeneous cohort of adults suggests potentially broad utility of this physiological secretagogue in hyposomatotropic states.
Instruments Assessing Capacity to Manage Medications
Authors: Farris Karen B , Phillips Beth Bryles 
Published: July 2008

Objective: To review literature on instruments available for assessing the physical and cognitive ability to take medications as prescribed, which serve as a way to rule out reasons for nonadherence. Data Sources: A PubMed search (1950–February 2008) was conducted to identity relevant articles. Additional references were obtained from cross-referencing the bibliographies of selected articles. Only journals containing English-language articles were selected for review. Study Selection and Data Extraction: Articles that described a simulated assessment of medication management were obtained, irrespective of whether the assessment also contained data about medication adherence or was focused on older adults. Data Synthesis: Fifteen instruments were identified. Six instruments required 5 minutes or less to administer. 5 required 6–30 minutes, and 4 had no administration time data reported. A possible advantage of 3 of the instruments is that they use a subject's own medications and may therefore provide a more authentic assessment. Only 2 instruments have been tested by subjects other than the drug developers and only one has been used in 2 different populations, thereby affording soma insight into generalizability. These studies have used a variety of other validated surveys/assessments to provide an indication of construct validity, including neuropsychological batteries, caregiver reports, prospective outcomes, instrumental activities of daily living, and levels of care. One instrument determined whether Individuals could tell if refills existed, whom to contact, and resources to obtain medications. Three assessed numeracy literacy. Conclusions: Five instruments that measure medication management capacity should be compared for potential further use, including Beckman's tasks, due to their brevity and assessment of numeracy literacy; the Medication Management Ability Assessment, Drug Regimen Unassisted Grading Scale, and Hopkins Medication Schedule because of the evidence supporting their use; and the Medication Management Instrument for Deficiencies In the Elderly because it includes an assessment of the patient's knowledge of how to obtain more medications. No brief tool is available for the primary care setting to identify individuals with medication management problems or to guide the type and amount of support required to manage medications.
Effects of AGTR1 A1166C Gene Polymorphism in Patients with Heart Failure Treated with Candesartan
Authors: Denus Simon de , Zakrzewski-Jakubiak Marcin , Dubé Marie-Pierre , Bélanger François , Lepage Serge , Leblanc Marie-Hélène , Gossard Denis , Ducharme Anique , Racine Normand , Whittom Lucette , Lavoie Joel , Touyz Rhian M , Turgeon Jacques , White Michel 
Published: July 2008

Background: The benefits of angiotensin II receptor blockers (ARBs) in patients with heart failure who are treated with standard pharmacotherapy, including an angiotensin-converting enzyme (ACE) inhibitor, were demonstrated in 2 large randomized trials. It is currently impossible to determine which patient will benefit from the addition of an ARB. Objective: To explore the impact of selected candidate genes on the hemodynamic, neurohormonal, and antiinflammatory effects of candesartan in patients with heart failure who are already being treated with an ACE inhibitor. Methods: We investigated the impact of 10 candidate genetic polymorphisms on the effects of candesartan in patients with heart failure who are treated with an ACE inhibitor. We evaluated their impact on acute (2 wk) and long-term (24 wk) changes in blood pressure and N-terminal proB-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) during treatment with candesartan. Results: Thirty-one patients were included. Homozygotes of the AGTR1 A1166 allele (n = 13) had a greater decrease in systolic (-9.1 ± 4.7 vs 1.1 ± 3.3 mmHg; p = 0.04 by analysis of variance [ANOVA], adjusting for dose) and diastolic blood pressure (-5.1 ± 1.5 vs 1.9 ± 1.9 mm Hg; p = 0.005 by ANOVA, adjusting for dose) compared with C1166 allele carriers (n = 18) following 2 weeks of treatment. After 6 months of treatment, C1166 carriers experienced a greater decrease in NT-proBNP (-151.4 (-207; -19.8] ng/L vs 147.3 (-61.3; 882.9] ng/L; P = 0.03) and hsCRP (-0.8 [-2.2; -0.03] mg/L) vs 0.2 [-1.8; 5.3] mg/L; p = 0.09) compared with patients carrying the AA1166 genotype. No other significant association was found. Conclusions: The results of this proof-of concept study provide the first evidence that the AGTR1 A1166C polymorphism could influence the response to candesartan in patients with heart failure who are receiving ACE inhibitors. Validation of these exploratory findings in larger populations is required before use of the AGTR1 A1166C genotype can be incorporated into clinical practice.
Efficacy of a Premedication Algorithm for Nonemergent Intubation in a Neonatal Intensive Care Unit
Authors: VanLooy JW , Schumacher Robert E , Bhatt-Mehta Varsha 
Published: July 2008

Background: Preventing significant oxygen desaturation and hypotension through adequate analgesia and sedation during nonemergent Intubation In neonates is desirable. However, in many neonatal intensive care units, elective intubations occur without adequate premedication. There is significant variation In the choice of premedication agen(s) and doses, and an ideal regimen for use during nonemergent intubation has not been developed. Objective: To evaluate the efficacy of an algorithm developed for analgesia and sedation during nonemergent Intubation in neonates. Methods: Prospectively collected continuous quality Improvement data on a premedication algorithm for nonemergent intubation were analyzed following institutions] review board approval. Midazolam 0.1 mg/kg and fentanyl 2 μg/kg (if the patient was not already receiving morphine for sedation) were administered prior to nonemergent intubation. Heart rate, oxygen saturation, respiration rate, mean arterial pressure, and pain scores were recorded at baseline prior to medication administration, during the procedure, and for 2 hours after the procedure. Data during laryngoscopy and until the time of lube taping were obtained from Ine bedside cardiorespiratory monitor. Additional fentanyl was allowed for more than 3 intubation attempts and rocuronium 0.6 mg/kg was allowed for more than 5 attempts. The physiological changes that occurred over time were compared with baseline. The number of attempts made, time to intubation, and medications used are presented. Results: Ninety evaluable patients were included. Mean ± SD birth weight and postnatal age at treatment were 2040 ± 961 g and 14 ± 17 days, respectively. Heart rate decreased and oxygen saturation Increased significantly (160 vs 154 beats/min, p = 0.01; 96.4% vs 93.8%. p = 0.002, respectively) from baseline to completion of the procedure; however, mean arterial pressure showed no significant difference (44.9 vs 44.7 mm Hg; p = 0.85; n = 68). The number of attempts at Intubation were recorded (or 66 patients; of those, 52 required 3 or fewer attempts for successful Intubation (median, 2).The lime to successful intubation was 7.2 ± 5.6 minutes (recorded in 45 pts.). Average fentanyl and midazolam doses were 1.92 ± 0.53 μg/kg and 0.096 ± 0.026 mg/kg, respectively. No patient received rocuronium. Conclusions: A systematic approach to premedication during nonemergent intubation successfully prevented acute physiological changes.
Indiplon: A Nonbenzodiazepine Sedative–Hypnotic for the Treatment of Insomnia
Authors: Marrs Joel C 
Published: July 2008

Objective: To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of indiplon in the treatment of transient and chronic insomnia in adult and geriatric patients. Data Sources: A literature search was conducted using MEDLINE (1966–May 2006), International Pharmaceutical Abstracts (1970–May 2008), and Cochrane database (2007) (or the key words indiplon or NBI-34060. References cited in the articles were reviewed for additional Information. Abstract data were included only in the absence of significant published data. Study Selection and Data Extraction: English-language literature reporting animal and human clinical studies was reviewed to evaluate data on the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of indiplon. Clinical trials selected for inclusion were limited to those with human subjects, with the accepted Inclusion of pharmacology data in animals. Data Synthesis: Indiplon Is a nonbenzodiazepine sedative-hypnotic that exhibits its sedating activity through its interaction with the γ–aminobutyric acid a receptor complex. Indiplon immediate-release (IR) as well as modified-release (MR) forms have shown improvement compared with placebo in patients with DSM-IV-TR primary insomnia in various areas of subjective and objective sleep measurements. Specifically, Improvements In total sleep time, latency to persistent sleep, latency to sleep onset, wake after sleep onset, and sleep quality have been noted In clinical trials. Trials evaluating both indiplon IR and MR have so far not identified any major serious adverse effects. Conclusions: Limited clinical trial data exist on use of indiplon in a “true” transient insomnia patient population. Based on recent Food and Drug Administration requests, clinical trial data assessing direct comparisons of indiplon IR with other approved nonbenzodiazepine sedative–hypnotics are needed to clearly define the differences among these agents.
Hospital Admissions Associated with Adverse Drug Reactions: A Systematic Review of Prospective Observational Studies
Authors: Kongkaew Chuenjid , Noyce Peter R , Ashcroft Darren M 
Published: July 2008

Objective: To determine the prevalence of hospital admissions associated with ADRs and examine differences in prevalence rates between population groups and methods of ADR detection. Data Sources: Studies were identified through electronic searches of Cumulative Index to Nursing and Allied Hearth Literature. EMBASE, and MEDLINE to August 2007. There were no language restrictions. Study Selection and Data Extraction: A systematic review was conducted of prospective observational studies that used the World Health Organization ADR definition. Subgroup analysis examined the influence of patient age groups and methods of ADR detection on reported ADR admission rates. All statistical analyses were performed using STATA v 9.0. Data Synthesis: Twenty-five studies were identified including 106, 586 patients who were hospitalized; 2143 of these patients had experienced ADRs. The prevalence rates of ADRs ranged from 0.16% to 15.7%, with an overall median of 5.3% (interquartile range [IQR] 2.7–9.0%). Median ADR prevalence rates varied between age groups: for children, the ADR admission rate was 4.1% (IQR 0.16–5.3%), while the corresponding rates for adults and elderly patients were 6.3% (IQR 3.9–9.0%) and 10.7% (IQR 9.6–13.3%), respectively. ADR rates also varied depending on the methods of ADR detection employed in the different studies. Studies that employed multiple ADR detection methods, such as medical record review and patient interview, reported higher ADR admission rates compared with studies that used medical record review alone. Antiinfective drugs were most often associated with ADR admissions in children; cardiovascular drugs were most often associated with ADR admissions in adults and elderly patients. Conclusions: Approximately 5.3% of hospital admissions were associated with ADRs. Higher rates were found in elderly patients who are likely to be receiving multiple medications for long-term illnesses. The methods used to detect ADRs are also likely to explain much of the variation in the reported ADR prevalence rates between different studies.
Overexpression of Bone Sialoprotein Leads to an Uncoupling of Bone Formation and Bone Resorption in Mice
Authors: Valverde Paloma , Zhang Jin , Fix Amanda , Zhu Ji , Ma Wenli , Tu Qisheng , Chen Jake 
Published: July 2008

Abstract
The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the cytomegalovirus (CMV) promoter. CMV-BSP transgenic (TG) mice and wildtype mice were weighed, and their length, BMD, and trabecular bone volume were measured. Serum levels of RANKL, osteocalcin, osteoprotegerin (OPG), TRACP5b, and PTH were determined. Bone histomorphometry, von Kossa staining, RT-PCR analysis, Western blot, MTS assay, in vitro mineralization assay, and TRACP staining were also performed to delineate phenotypes of this transgenic mouse line. Compared with wildtype mice, adult TG mice exhibit mild dwarfism, lower values of BMD, and lower trabecular bone volume. TG mice serum contained increased calcium levels and decreased PTH levels, whereas the levels of phosphorus and magnesium were within normal limits. TG mice serum also exhibited lower levels of osteoblast differentiation markers and higher levels of markers, indicating osteoclastic activity and bone resorption. H&E staining, TRACP staining, and bone histomorphometry showed that adult TG bones were thinner and the number of giant osteoclasts in TG mice was higher, whereas there were no significant alterations in osteoblast numbers between TG mice and WT mice. Furthermore, the vertical length of the hypertrophic zone in TG mice was slightly enlarged. Moreover, ex vivo experiments indicated that overexpression of BSP decreased osteoblast population and increased osteoclastic activity. Partly because of its effects in enhancing osteoclastic activity and decreasing osteoblast population, BSP overexpression leads to an uncoupling of bone formation and resorption, which in turn results in osteopenia and mild dwarfism in mice. These findings are expected to help the development of therapies to metabolic bone diseases characterized by high serum level of BSP.
Vitamin D Metabolites and Calcium Absorption in Severe Vitamin D Deficiency
Authors: Need Allan G , O'Loughlin Peter D , Morris Howard A , Coates Penelope S , Horowitz Michael , Nordin BE Christopher 
Published: July 2008

Abstract
Contrary to frequent claims, vitamin D insufficiency does not generally cause malabsorption of calcium because serum 1,25(OH)2D, which is the major determinant of calcium absorption, is maintained by secondary hyperparathyroidism. Nevertheless, because malabsorption of calcium has been described in osteomalacia, there must be a 25(OH)D level below which the serum 1,25(OH)2D can no longer be sustained, although it has never been defined. This paper seeks to define it. We examined the records of 3661 patients and found 319 with a serum 25(OH)D ≤40 nM, in whom calcium absorption, serum calcium, PTH, bone markers, and vitamin D metabolites had been measured. They were grouped according to their serum 25(OH)D into four categories, 0–10, 11–20, 21–30, and 31–40 nM, and differences between the groups were tested by ANOVA. Correlations between the variables were also examined. Serum calcium, 1,25(OH)2D, and calcium absorption were significantly decreased and serum PTH and alkaline phosphatase (ALP) and urine hydroxyproline were increased in those with 25(OH)D ≤10 nM. Serum ALP and urine hydroxyproline were more strongly related, inversely, to calcium absorption than to the vitamin D metabolites. We conclude that vitamin D deficiency does not reduce serum 1,25(OH)2D, and therefore calcium absorption, until the serum 25(OH)D falls to ∼10 nM. At this level, the substrate concentration seems to be insufficient to maintain the level of the dihydroxy metabolite despite secondary hyperparathyroidism. Further studies are needed to see how these changes correlate with the histological changes of osteomalacia.
Age-Dependent Demise of GNAS-Mutated Skeletal Stem Cells and “Normalization” of Fibrous Dysplasia of Bone
Authors: Kuznetsov Sergei A , Cherman Natasha , Riminucci Mara , Collins Michael T , Robey Pamela Gehron , Bianco Paolo 
Published: July 2008

Abstract
We studied the role of somatic mosaicism in fibrous dysplasia of bone (FD) within the context of skeletal (“mesenchymal”) stem cells by assessing the frequency of mutated colony forming unit-fibroblasts (CFU-Fs) from FD lesions, and in some cases, from unaffected sites, in a series of patients. There was a tight inverse correlation between the percentage mutant CFU-F versus age, suggesting demise of mutant stem cells caused by exuberant apoptosis noted in samples from young patients. In older patients, either partially or completely normal bone/marrow histology was observed. On in vivo transplantation, FD ossicles were generated only by cell strains in which mutant CFU-Fs were identified. Strains that lacked mutant CFU-F (but were mutation positive) failed to regenerate an FD ossicle. These data indicate that GNAS mutations are only pathogenic when in clonogenic skeletal stem cells. From these data, we have evolved the novel concept of “normalization” of FD. As a lesion ages, mutant stem cells fail to self-renew, and their progeny are consumed by apoptosis, whereas residual normal stem cells survive, self-renew, and enable formation of a normal structure. This suggests that activating GNAS mutations disrupt a pathway that is required for skeletal stem cell self-renewal.
Bone Markers Predict Cardiovascular Events in Chronic Kidney Disease
Authors: Fahrleitner-Pammer Astrid , Herberth Johann , Browning Steven R , Obermayer-Pietsch Barbara , Wirnsberger Gerhard , Holzer Herwig , Dobnig Harald , Malluche Hartmut H 
Published: July 2008

Abstract
Recent studies have indicated a link between bone metabolism and cardiovascular events in patients with chronic kidney disease (CKD). CKD is a major health problem worldwide. This study evaluates the role of noninvasive markers of bone metabolism in predicting cardiovascular morbidity (coronary artery disease, peripheral vascular disease, stroke) and mortality in patients with mild to severe forms of CKD. In a prospective cohort study, 627 patients with CKD were screened. To focus on bone metabolism, traditional risk factors for cardiovascular events were excluded, and 135 patients with CKD stages 1–5 were followed for 4 yr. Glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula. PTH (measured by four different assays), vitamin D 25 and 1,25, bone-specific alkaline phosphatase (BSALP), TRACP-5b, osteocalcin, serum collagen cross-link molecules, RANKL, and osteoprotegerin were determined. Predictors of cardiovascular events were evaluated by multivariable logistic regression, Kaplan-Meier survival, and Cox regression analysis. There were a total of 45 cardiovascular events (33%). Event rates were 5.6%, 29.1%, 45.2%, and 45.0% in CKD stages 1–2, 3, 4, and 5, respectively. In logistic regression, cardiovascular events were predicted only by (1) CKD stage (independent of age or sex; p &lt; 0.001); (2) BSALP (p = 0.03); and (3) TRACP-5b (p = 0.04). Markers of bone formation (BSALP) and resorption (TRACP-5b) can serve as predictors of cardiovascular morbidity and mortality in CKD.