bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between estimated glomerular filtration rate and thyroid function: an observational study
Authors: Woodward Anne , McCann Steven , Al-Jubouri Mohammad 
Published: August 2008

Background Estimated glomerular filtration rate (eGFR) is now routinely reported by most National Health Service laboratories. There are many limitations when interpreting eGFR: thyroid dysfunction is not widely recognized as being one of these. Methods We extracted from the pathology computer system results of all patients with hypothyroidism and hyperthyroidism who also had serum creatinine measured. We also extracted creatinine data on euthyroid patients. eGFR was calculated using the simplified Modification of Diet in Renal Disease Study equation. Results The median eGFRs of the hypothyroid, euthyroid and hyperthyroid patients were 64, 77 and 107 mL/min/1.73 m2, respectively; all groups were significantly different from each other ( P < 0.001). Conclusion Thyroid dysfunction is associated with significant alterations in eGFR and actual GFR.
Platelet contamination causes large variation as well as overestimation of mitochondrial DNA content of peripheral blood mononuclear cells
Authors: Urata Michiyo , Koga-Wada Yui , Kayamori Yuzo , Kang Dongchon 
Published: August 2008

Background Alterations in the copy number of mitochondrial DNA (mtDNA) play a role in the pathogenesis of mitochondrial diseases and other many common diseases. Recently, the copy number of leukocyte mtDNA has been considered to serve as a biomarker to monitor or chase such diseases. Therefore, reproducible mtDNA measurement is required. Methods Peripheral blood mononuclear cells were prepared by a density-based method. The mtDNA/cell was measured by quantitative realtime polymerase chain reaction. Results The degree of platelet contamination varied to a large extent among preparations. The mtDNA copy numbers per mononuclear cell were 269 ± 51 and 146 ± 14 in the samples before and after the platelet depletion, respectively. Conclusion A density-based mononuclear cell preparation causes heavy platelet contamination. The platelet depletion from a sample is particularly important for comparing the mtDNA contents between different dates or between different patients.
Use of routine clinical laboratory data to define reference intervals
Authors: Shine Brian 
Published: August 2008

Background Reference intervals are used to distinguish between healthy and diseased state. Ideally, they are defined using specimens only from ‘healthy’ individuals, but this is often difficult or impossible. In order to use routine clinical laboratory data, outliers must be removed before the underlying distribution and changes related to age and sex can be modelled. This paper illustrates the process for plasma alkaline phosphatase (ALP). ALP levels are high in infancy and childhood, peak in adolescence, are stable from the early 20s and rise after the fourth decade. Three types of normalizing transformations (Logarithmic, Box-Cox and Cole's LMS) are compared. Methods Single ALP results from 75,328 individuals aged 0–80 years were binned by sex and age. The normalizing transformations were applied to each bin, outliers were removed and the normalizing transformations were reapplied to the remaining data. The normality of the transformed data was assessed by normal score plots and the Kolmogorov-Smirnov test. Fractional polynomials were used to model the underlying parameters of the transformations and the derived parametric reference intervals (mean ± 1.96 standard deviations), separately for each sex as a whole and partitioned into two or three age ranges, with overlapping to give smooth transitions. Results All transformations yielded acceptably normal data, but the LMS method gave the closest approximation to normal. Outlier rates were similar for each method. The derived reference ranges were similar for all the three methods. Splitting the data-set into several segments resulted in a better fit with the peak seen in adolescence. Conclusion Routine clinical laboratory specimens can be used to derive reference intervals.
Selenium status in patients with aspirin-induced asthma
Authors: Hassan Afaf M 
Published: August 2008

Background Platelets are involved in the pathogenesis of aspirin-induced asthma (AIA). AIA patients suffer from an active disease despite avoidance of aspirin, and it has been suggested that administration of aspirin to these patients increases the generation of immediate oxygen products of arachidonic acid, 12-hydroperoxyeicosatetraenoic acid (12-HPETE), in their platelets. 12-HPETE further activates the 5-lipoxygenase of leukotriene B4-producing inflammatory macrophages precipitating an acute asthmatic attack. Glutathione peroxidase (GPX) has the antioxidant capacity to reduce 12-HPETE, and thus modulate the arachidonic acid metabolic cascade. There is evidence that selenium (Se) nutrition can influence asthma but Se status in AIA patients has not received much attention. Methods We measured Se concentrations and GPX activities in platelets and plasma from 13 patients with AIA. Age- and sex-matched healthy individuals served as the control group. Results Patients with AIA had significantly higher median platelet Se concentration (102 ng/mg platelet protein) when compared with controls (49 ng/mg platelet protein, P = 0.003). Plasma Se concentrations in patients with AIA and controls were not significantly different ( P = 0.59). Median platelet GPX activity was significantly higher in patients with AIA (102.7 mU/mg platelet protein) than in controls (66 mU/mg protein) ( P = 0.05). The patient and control groups when combined showed weak, but significant correlation between platelet Se concentration and platelet GPX activity ( r = 0.44; P = 0.03). Conclusion It is proposed that the higher platelet Se concentration observed in AIA patients contributed to the higher platelet GPX activity seen in these patients. Such an enhanced antioxidant defence system might represent an adaptive response to protect against increasing free radical production by inflammatory cells in AIA and help decelerate ongoing respiratory hypersensitivity.
Audit of acute hypoglycaemia in children: re-audit of procedures for diagnosis
Authors: Lang Timothy F , Cardy David , Carson Dennis , Loughrey Clodagh M , Hanna Elinor 
Published: August 2008

Background A protocol exists for the collection of samples to investigate unexplained hypoglycaemia, termed the ‘hypopack’. These packs are kept in Accident and Emergency departments and neonatal special care baby units throughout Northern Ireland and most wards of the Regional Children's Hospital. A retrospective audit of 107 hypopacks received between July 2001 and December 2003 highlighted a number of problems: samples collected when the patient was receiving dextrose, incomplete clinical history provided, insufficient and haemolysed samples received and poor filing of reports in charts. These were addressed by re-designing the request form, updating the protocol and introducing a summative report. The new protocol was introduced in April 2006. Methods The aim of this study is to assess whether the revised protocol improved utility of the hypopack. A retrospective re-audit of 100 hypopacks received between April 2006 and May 2007 was performed. Results Forty-nine percent of patients were hypoglycaemic (<2.6 mmol/L) compared with 35% in the original audit. In both audits, 33% of laboratory reports were missing from patients' charts. One case of medium-chain acyl-CoA dehydrogenase deficiency, three cases of hyperinsulinism and two endocrine-related cases were identified. Conclusions The new hypopack protocol has increased the number of appropriately performed investigations. Provision of information concerning dextrose infusion has assisted the interpretation of the hypopack results.
Potential Aluminum Exposure from Parenteral Nutrition in Patients with Acute Kidney Injury
Authors: Brown Rex O , Morgan Laurie M , Bhattacharya Syamal K , Johnson Patti L , Minard Gayle , Dickerson Roland N 
Published: August 2008

Background: Patients' exposure to and potential toxicity from aluminum in parenteral nutrition (PN) formulations is an important concern of healthcare providers. Objective: To determine the potential for aluminum toxicity caused by PN in hospitalized adults who have risk factors of both acute kidney injury and PN. Methods: Adults who required PN and had a serum creatinine (SCr) level at least 1.5 times greater than the admission SCr on the first day of PN were studied in a retrospective fashion. Protein was administered based on whether hemodialysis was being used (0 6-1 g/kg/day without hemodialysis; 1.2-1.5 g/kg/day with hemodialysis). Aluminum exposure was determined for each patient by multiplying the volume of each PN component by its concentration of aluminum Unpaired f-tests, Fisher's exact test, and analysis of variance were used for statistical analysis. Data are presented as mean ± SD. Results: Thirty-six patients (aged 50.4 ± 20.4 y; weight 90.2 ± 32.8 kg) were studied. Initial serum urea nitrogen and SCr were 47 ± 23 and 3.3 ± 1.4 mg/dL. respectively. Twelve patients received hemodialysis. The mean aluminum exposure was 3.8 ± 2 μg/kg/day in the 36 patients, Of these, 29 had safe calculated aluminum exposure (<5 μg/kg/day) and 7 had high calculated aluminum exposure (>5 μg/kg/day), Patients with safe aluminum exposure had significantly higher SCr levels than did those with high aluminum exposure (3.5 ± 1.5 vs 2.2 ± 0.7 mg/dL; p < 0.04). Patients with high aluminum exposure received significantly more aluminum from calcium gluconate compared with those who had safe aluminum exposure (357 ± 182 vs 250 ± 56 μg/day; p < 0.02). Limitations of the study include its retrospective design, which resulted in calculated versus direct measurement of aluminum. Conclusions: Using our calculations, we believe that most patients with acute kidney injury who require PN do not receive excessive exposure to aluminum from the PN formulation, despite having 2 risk factors (acute kidney injury, PN) for aluminum toxicity,
Duloxetine-Associated Tachycardia
Authors: Stevens Debra L 
Published: August 2008

Objective: To report a case of symptomatic tachycardia that was successfully treated with propranolol in a patient receiving duloxetine. Case Summary: A 26-year-old man presented with episodes of fatigue, tachycardia, diaphoresis, and chest pain approximately 2 months after the initiation of duloxetine 20 mg/day for dysthymic disorder. Cardiac workup including echocardiogram, exercise treadmill testing, and Holter monitoring was negative, except for tachycardia (heart rate 110-120 beats/min). Duloxetine was withheld, and the patient's heart rate returned to normal in less than a week. Duloxetine was restarted at the same dosage, and tachycardia returned within 2 days. Propranolol was added to the treatment regimen to lower the heart rate. Because of therapeutic failure of other antidepressants, duloxetine was continued because of its beneficial effects on mood. Discussion: One published case report describing tachycardia in association with duloxetine in 2 heart failure patients was found in a MEDLINE search (1966-July 2008). Increased blood pressure and heart rate have been reported in duloxetine trials. The proposed mechanism for duloxetine-induced tachycardia is its effects on norepinephrine, which impact the cardiovascular system. Use of the Naranjo probability scale indicated duloxetine as a probable cause of this patient's tachycardia. Conclusions: Clinicians should be aware of the possibility of clinically significant tachycardia in patients receiving duloxetine, even in low doses.
Assessing the Reporting and Scientific Quality of Meta-Analyses of Randomized Controlled Trials of Treatments for Anxiety Disorders
Authors: Bereza Basil G , Machado Márcio , Einarson Thomas R 
Published: August 2008

Background: Mela-analyses of randomized controlled trials (RCTs) constitute the highest level of evidence, but their usefulness depends on their quality. Objective: To assess tho reporting and scientific quality of meta-analyses of RCTs on treatments for anxiety disorders. Methods: Criteria for peer-reviewed, full-text retrieval included meta-analyses of RCTs of drugs versus active ingredient placebo, standard care, or psychotherapy. Sample populations were required to meet Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases and Related Health Problems diagnostic criteria for anxiety disorders. Two reviewers independently searched EMBASE, EBM Reviews. Ovid MEDLINE, Ovid HealthSTAR, and International Pharmaceutical Abstracts from inception to August 2007. Search terms Included meta-analysis, randomized controlled trials, anxiety, anxiolytic, anti-depressant/antidepressant, and pharmacotherapy, without language restrictions. References and reviews were searched manually. Quality was assessed independently by 2 raters, using the Quality of Reporting of Meta-anatyses (QUOROM) and the Overview Quality Assessment Questionnaire (OQAQ). The QUOROM was used to assess the reporting quality of the study, using an 18-item checklist, and the scientific quality was assessed with the OQAQ's 10-item checklist, Kendall's - measured Interrater reliability with statistical significance at p less than or equal to 0.01. Means and standard deviations described the overall quality. A time series analysis was performed. Results: A total of 136 titles and abstracts were reviewed; 48 were retrieved, including 6 from the manual search. Thirty-two were excluded (not pooled analyses, inappropriate condition/treatment, duplications), leaving 16 studies published between 1995 and 2007. Agreement was high: t = 0.801 (p < 0.01) for QUOROM and 0.834 (p < 0.01) for OQAQ. QUOROM quality scored 61% ± 19%. Overall, the results sections of the studies scored lowest, while the introduction and discussion sections scored highest. The overall scientific qualify was 58% ± 28%. Most studies appropriately linked results to priman/ objectives but did not report how bias was avoided or how study validity was assessed. Quality Increased nonsignificantly over time. Conclusions: Reporting/scientific quality was considered less than fair-to-good. Stakeholders should strive for higher scientific quality of meta-analyses.
Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity
Authors: Johansson Lovisa E , Lindblad Ulf , Larsson Charlotte A , Råstam Lennart , Ridderstråle Martin 
Published: August 2008

ObjectiveThe insulin responsive adiponutrin or patatin-like phospholipase 3 (PNPLA3, previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity, and to investigate their effect on insulin resistance and β-cell function.Methodsrs738409 (Met148Ile) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay in a Swedish population-based sample (n=1811). Oral glucose tolerance test (OGTT) with data from three time points (0, 30, and 120 min) were available from individuals under the age of 50 years (n=973).ResultsBoth variant alleles were associated with decreased prevalence of obesity (P<0.05); odds ratio 0.75 (0.61–0.93) per carried Ile-allele for rs738409 and 0.80 (0.64–1.00) per carried G-allele for rs2072907. For obesity as a quantitative trait, there was no association in the whole population, but in obese subjects body mass index (BMI; P=0.023) and waist (P=0.0098) were higher in carriers of the Ile-allele. The Ile-carriers also displayed decreased insulin secretion in response to OGTT (30 min insulin; P=0.007, insulinogenic index; P=0.0051) with no significant differences in fasting plasma glucose (P=0.31), β-cell function (disposition index; P=0.17) or homeostasis model of assessment insulin resistance (HOMA-IR; P=0.063). The correlation between BMI and HOMA-IR differed (Met/X versus Ile/Ile, P=0.028), Met-allele carriers were seemingly more insulin resistant at a lower BMI. The rs2072907 variant shows similar results for insulin secretion. The significance of this finding remained after adjusting for age, gender, and level of self-reported leisure-time physical activity.ConclusionWe confirm the association between PNPLA3 and obesity. In addition, the rs738409 variant was associated with insulin secretion. There seems to be a differential effect of the Ile-allele depending on the degree of obesity, possibly as a consequence of insulin resistance.
Discrepancies in Identification of Major Bleeding Events in Patients Taking Warfarin
Authors: Seto Anna C. , Kenyon Kenneth , Wittkowsky Ann K. 
Published: August 2008

Study Objective. To assess the level of agreement between one subjective definition of major bleeding (criteria A) and two objective definitions: the International Society on Thrombosis and Haemostasis ([ISTH] criteria B) and the Italian Study of Complications of Anticoagulant Therapy ([ISCOAT] criteria C).Design. Retrospective cohort study.Setting. Four anticoagulation clinics at a university‐affiliated medical center.Patients. One hundred twenty patients aged 21–96 years who were taking long‐term warfarin therapy and experienced a nonminor bleeding event between July 1, 2001, and June 30, 2006.Measurements and Main Results. Bleeding events were evaluated using three definitions of major bleeding: criteria A—event was fatal or required hospitalization; criteria B—event was fatal, was symptomatic in a critical area or organ, caused a decrease in hemoglobin level of 2 g/dl or more, and/or led to transfusion of 2 or more units of whole blood or red blood cells; and criteria C—event met criteria B definition (but less inclusively identifies critical areas or organs) and/or necessitated surgical or angiographic intervention. One hundred thirty‐eight bleeding events in the 120 patients met at least one of the definitions of major bleeding and thus were included in the analysis. Level of agreement among the definitions was determined by the κ statistic. The level of agreement between criteria B and C was excellent; no discrepancies were found; however, the level of agreement between criteria A and criteria B or C was poor, with a κ statistic value of −0.134 (95% confidence interval −0.196 to −0.071). Use of criteria A resulted in underreporting of 31 major bleeding events by excluding events that were managed on an outpatient basis.Conclusion. The discrepant event rates determined by using three different definitions of major bleeding underscore the need for implementation of a standardized objective definition. Use of a standardized definition in clinical trials to accurately predict and compare patient outcomes and in clinical practice as a marker for patient safety will increase quality of care and decrease total costs of care in patients treated with warfarin. We suggest implementation of the ISTH criteria in clinical practice as a method to standardize the reporting of major bleeding events.
Continuous versus Intermittent Infusion of Prophylactic Cefoxitin After Colorectal Surgery: A Pilot Study
Authors: Suffoletta Terri J. , Jennings Heath R. , Oh Jennifer J. , Stephens Dana , Poe Kevin L. 
Published: August 2008

Study Objective. To compare 30‐day postoperative surgical site infections (SSIs) and rates of antibiotic discontinuation within 24 hours after surgery in patients receiving continuous‐infusion versus intermittent‐infusion cefoxitin for postoperative antibiotic prophylaxis.Design. Retrospective, cohort‐matched pilot study.Setting. Tertiary‐care medical center.Patients. One hundred sixteen adults undergoing colorectal surgery between August 1, 2004, and February 28, 2007.Intervention. Cefoxitin prophylaxis was administered as a continuous infusion in 58 patients and as an intermittent infusion in 58 patients (controls). The controls received weight‐based doses of cefoxitin (1 g if 80 kg or 2 g if > 80 kg) every 8 hours for three doses, starting 3 hours after surgery and completed within 24 hours. The continuous‐infusion group were given weight‐based doses of cefoxitin (3 g if 80 kg, 6 g if > 80 kg), started immediately after surgery and infused over 20 hours.Measurements and Main Results. Patients and controls were matched according to colorectal procedure and risk index category. They were stratified by medium risk (50 patients) and low risk (66 patients) for the end point of 30‐day postoperative SSI. For the 25 medium‐risk patients who received the continuous infusion, a 50% relative reduction in the 30‐day postoperative SSI rate was observed with continuous versus intermittent infusion (4% vs 8%, p=0.55). For the 66 low‐risk patients, 30‐day postoperative SSI rates were equal (3%) with both intermittent and continuous infusions. Risk stratification was not performed for the proportion of patients who discontinued antibiotic prophylaxis within 24 hours after surgery. All patients receiving the continuous infusion met this end point compared with 47 (83.9%) of the 56 controls (p=0.0015) included in the analysis.Conclusion. Compared with intermittent infusion, continuous infusion of cefoxitin for postoperative prophylaxis resulted in a nonsignificant reduction in 30‐day postoperative SSI rates in medium‐risk patients undergoing colorectal surgery. Continuous infusion also resulted in reliable discontinuation of postoperative prophylaxis within 24 hours.
Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice
Authors: Fujii Nobuharu , Ho Richard C. , Manabe Yasuko , Jessen Niels , Toyoda Taro , Holland William L. , Summers Scott A. , Hirshman Michael F. , Goodyear Laurie J. 
Published: August 2008

OBJECTIVE—We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance.
RESEARCH DESIGN AND METHODS—Muscle-specific transgenic mice expressing an inactive form of the AMPK α2 catalytic subunit (α2i TG) and their wild-type littermates were fed either a high-fat (60% kcal fat) or a control (10% kcal fat) diet for 30 weeks.
RESULTS—Compared with wild-type mice, glucose tolerance in α2i TG mice was slightly impaired on the control diet and significantly impaired on the high-fat diet. To determine whether the whole-body glucose intolerance was associated with impaired insulin sensitivity in skeletal muscle, glucose transport in response to submaximal insulin (450 μU/ml) was measured in isolated soleus muscles. On the control diet, insulin-stimulated glucose transport was reduced by ∼50% in α2i TG mice compared with wild-type mice. High-fat feeding partially decreased insulin-stimulated glucose transport in wild-type mice, while high-fat feeding resulted in a full blunting of insulin-stimulated glucose transport in the α2i TG mice. High-fat feeding in α2i TG mice was accompanied by decreased expression of insulin signaling proteins in gastrocnemius muscle.
CONCLUSIONS—The lack of skeletal muscle AMPK α2 activity exacerbates the development of glucose intolerance and insulin resistance caused by high-fat feeding and supports the thesis that AMPK α2 is an important target for the prevention/amelioration of skeletal muscle insulin resistance through lifestyle (exercise) and pharmacologic (e.g., metformin) treatments.