bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyrotropin Stimulates the Generation of Inositol 1,4,5-Trisphosphate in Human Thyroid Cells
Authors: Van Sande Jacqueline , Dequanter Didier , Lothaire Philippe , Massart Claude , Dumont Jacques E. , Erneux Christophe 
Published: February 2006

AbstractContext: Dual activation by TSH of the phospholipase C and cAMP cascades has been reported in human thyroid cells. In contrast, Singh et al. reported convincing data in FRTL-5 thyrocytes arguing against such an effect in this model. Their data in FRTL-5 cells indicated no increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to TSH. Therefore, the authors questioned results previously obtained on human cells by cruder methodology.Objective: We investigated the formation of inositol phosphates by HPLC techniques in human thyroid slices to separate the inositol phosphate isomers.Results: Ins(1,4,5)P3, inositol 1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate were increased after TSH stimulation. The effect of TSH in human thyroid cells was reproduced by recombinant TSH and prevented by antibodies blocking the TSH receptor. Thyroid-stimulating antibodies at concentrations eliciting a cAMP response equivalent to TSH failed to stimulate inositol phosphate generation.Conclusions: TSH, but not thyroid-stimulating antibodies, activates both cAMP and the phospholipase C cascade in human thyroid as now demonstrated by an increase in Ins(1,4,5)P3 and its inositol phosphate metabolites. Therefore, this effect cannot be extrapolated to the FRTL-5 cell line. The apparent discrepancy may be due to a difference between species (human vs. rat) or to the loss of the fresh tissue properties in a cell line. The dual effect of TSH in human cells, through cAMP on secretion of thyroid hormones and through the diacylglycerol, Ins(1,4,5)P3 Ca2+ pathway on thyroid hormone synthesis, implies the possible separation of these effects in thyroid disease.
Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults
Authors: Teichman Sam L. , Neale Ann , Lawrence Betty , Gagnon Catherine , Castaigne Jean-Paul , Frohman Lawrence A. 
Published: February 2006

Abstract
Context: Therapeutic use of GHRH to enhance GH secretion is limited by its short duration of action.
Objective: The objective of this study was to examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC-1295, a long-acting GHRH analog.
Design: The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 d.
Setting: The study was performed at two investigational sites.
Participants: Healthy subjects, ages 21–61 yr, were studied.
Interventions: CJC-1295 or placebo was administered sc in one of four ascending single doses in the first study and in two or three weekly or biweekly doses in the second study.
Main Outcome Measures: The main outcome measures were peak concentrations and area under the curve of GH and IGF-I; standard pharmacokinetic parameters were used for CJC-1295.
Results: After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 d or more and in mean plasma IGF-I concentrations by 1.5- to 3-fold for 9–11 d. The estimated half-life of CJC-1295 was 5.8–8.1 d. After multiple CJC-1295 doses, mean IGF-I levels remained above baseline for up to 28 d. No serious adverse reactions were reported.
Conclusions: Subcutaneous administration of CJC-1295 resulted in sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30 or 60 μg/kg. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC-1295 as a therapeutic agent.
Effect of Active Acromegaly and Its Treatment on Parathyroid Circadian Rhythmicity and Parathyroid Target-Organ Sensitivity
Authors: White H. D. , Ahmad A. M. , Durham B. H. , Chandran S. , Patwala A. , Fraser W. D. , Vora J. P. 
Published: February 2006

Abstract
Context: Patients with active acromegaly have increased bone turnover and skeletal abnormalities. Biochemical cure of acromegaly may represent a functional GH-deficient state and result in cortical bone loss. Reduced PTH target-organ sensitivity occurs in adult GH deficiency and may underlie the associated development of osteoporosis.
Objective: We examined the effect of active and treated acromegaly on PTH concentration and target-organ sensitivity.
Patients: Ten active acromegalic subjects (GH nadir &gt; 0.3 μg/liter after 75-g oral glucose load and IGF-I above age-related reference range) and 10 matched controls participated in the study.
Design: Half-hourly blood and 3-h urine samples were collected on patients and controls for 24 h. Samples were analyzed for PTH, calcium (Ca), nephrogenous cAMP (NcAMP, a marker of PTH renal activity), β C-telopeptide (bone resorption marker), and procollagen type-I amino-terminal propeptide (bone formation marker). Serum calcium was adjusted for albumin (ACa). Eight acromegalic subjects who achieved biochemical cure (GH nadir &lt; 0.3 μg/liter after 75-g oral glucose load and IGF-I within reference range) after standard surgical and/or medical treatment reattended and the protocol repeated.
Results: Active acromegalic subjects had higher 24-h mean PTH, NcAMP, ACa, urine Ca, β C-telopeptide, and procollagen type I amino-terminal propeptide (P &lt; 0.05), compared with controls. Twenty-four-hour mean PTH increased (P &lt; 0.001) in the acromegalic subjects after treatment, whereas NcAMP and ACa decreased (P &lt; 0.05).
Conclusion: Increased bone turnover associated with active acromegaly may result from increased PTH concentration and action. Biochemical cure of acromegaly results in reduced PTH target-organ sensitivity indicated by increased PTH with decreased NcAMP and ACa concentrations. PTH target-organ sensitivity does not appear to return to normal after successful treatment of acromegaly in the short term and may reflect functional GH deficiency.
Fibroblast Growth Factor 23 Is Increased in Calcium Nephrolithiasis with Hypophosphatemia and Renal Phosphate Leak
Authors: Rendina Domenico , Mossetti Giuseppe , De Filippo Gianpaolo , Cioffi Michele , Strazzullo Pasquale 
Published: February 2006

Abstract
Context: Nephrolithiasis affects about 10% of the population in industrialized countries, with calcium salts composing more than 80% of renal stones. A significant percentage of patients with calcium nephrolithiasis and normal parathyroid function show hypophosphatemia and reduced renal phosphate reabsorption (i.e. a renal phosphate leak).
Objectives: The objective of the study was to compare serum levels of fibroblast growth factor 23 (FGF23), a regulator of phosphate homeostasis, in 110 recurrent stone formers with or without renal phosphate leak, six patients affected by X-linked hypophosphatemic rickets, five patients affected by oncogenic osteomalacia, and 60 unrelated healthy controls.
Design: This was a prospective interventional study.
Methods: Renal phosphate leak was identified based on the occurrence of idiopathic hypophosphatemia [serum phosphate concentration &lt; 2.50 mg/dl (&lt;0.80 mmol/liter)] and reduced renal threshold phosphate concentration [&lt;2.2 mg/liter (&lt;0.70 mmol/liter)].
Results: In 22 stone formers with renal phosphate leak, serum FGF23 concentration was significantly higher as compared with 88 stone formers without renal phosphate leak and with controls [83.3 (65.6–101.1) vs. 32.1 (26.8–37.4) and 24.5 (19.8–29.1) reference units (RU)/ml, respectively]. Stone formers with renal phosphate leak showed lower FGF23, compared with patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets [572.3 (235.9–908.7) RU/ml]. Among stone formers and controls, serum FGF23 concentration displayed a strong inverse association with serum phosphate (r = −0.784, P = 0.009) and the rate of tubular phosphate reabsorption (r = −0.791, P = 0.008).
Conclusions: In our study population, renal phosphate leak affected 20% of stone formers and was strongly associated with increased serum FGF23 concentration.
Prolonged (48-Hour) Modest Hyperinsulinemia Decreases Nocturnal Heart Rate Variability and Attenuates the Nocturnal Decrease in Blood Pressure in Lean, Normotensive Humans
Authors: Petrova Maja , Townsend Raymond , Teff Karen L. 
Published: February 2006

Abstract
Context: Heart rate variability (HRV), an index of cardiac vagal activity, is decreased in individuals with metabolic disease. The relationship between decreased HRV and metabolic disease is unclear.
Objective: The objective of this study was to determine whether experimentally induced glucose intolerance decreases HRV in a circadian relevant manner in healthy individuals.
Design: This was a within-subject, randomized design study with subjects infused for 48 h with saline (50 ml/h) or 15% glucose (200 mg/m2·min). HRV was evaluated using time domain measurements taken over the 48-h period. Blood pressure and heart rate were monitored, and blood samples were taken.
Setting: This study was performed at the General Clinical Research Center of the Hospital of the University of Pennsylvania.
Patients: Sixteen healthy subjects (eight men and eight women; 18–30 yr old; mean body mass index, 21.7 ± 1.6 kg/m2) were studied.
Results: After glucose infusion, mean plasma glucose was increased by 16.8% (P &lt; 0.0001), and plasma insulin was increased by 99.4% (P &lt; 0.0001) compared with after saline infusion. Significant decreases in homeostasis model assessment indicated a decrease in insulin sensitivity (saline, 0.52 + 0.13; glucose, 0.34 + 0.12; P &lt; 0.0001). The nocturnal root mean square successive difference, an index of cardiac vagal activity, was significantly decreased (P &lt; 0.01), and nocturnal HR (P &lt; 0.001) and blood pressure were significantly elevated (saline, 107.4 ± 2.7; glucose, 112.5 ± 3.3 mm Hg; P &lt; 0.05) compared with the saline control. The change in homeostasis model assessment due to glucose infusion was significantly correlated with the change in root mean square successive difference (r = 0.48; P &lt; 0.01).
Conclusions: Prolonged mild hyperinsulinemia disrupts the circadian rhythm of cardiac autonomic activity. Early changes in the neural control of cardiac activity may provide a potential mechanism mediating the pathophysiological link between impaired glucose tolerance and cardiovascular disease.
Molecular Pathology of Müller’s Muscle in Graves’ Ophthalmopathy
Authors: Shih Mei-Ju , Liao Shu-Lang , Kuo Kuan-Ting , Smith Terry J. , Chuang Lee-Ming 
Published: February 2006

AbstractContext: Upper lid retraction is a common sign in Graves’ ophthalmopathy (GO). Whether Müller’s muscle is involved in upper lid retraction has not been fully elucidated.Objective: The objective of the study was to understand the molecular pathology of Müller’s muscle in GO.Design/Setting/Participants: A method for measurement of histological changes was developed and used to correlate severity and expression of cell-specific genes in GO.Main Outcome Measures: Histological changes, clinical severity of upper lid retraction, and mRNA expression in Müller’s muscle in GO were measured.Results: The degree of fibrosis correlates with severity of upper lid retraction. Macrophage infiltration was increased in fibrotic areas, consistent with higher levels of macrophage-colony stimulating factor mRNA. Levels of peroxisome proliferator-activated receptor-γ mRNA were up-regulated and correlated with fat infiltration. Decreased muscle mass correlated with lower myocardin mRNA expression. The expression of c-kit levels was decreased in diseased muscles, consistent with diminished mast cell numbers.Conclusion: The pathological changes of Müller’s muscle correlate with clinical severity of upper lid retraction in GO. Patterns of gene expression appear to correlate with the histopathological changes in this disease process.
Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa
Authors: Misra Madhusmita , Miller Karen K. , Tsai Patrika , Gallagher Katie , Lin Alvin , Lee Noel , Herzog David B. , Klibanski Anne 
Published: February 2006

AbstractBackground: Peptide YY (PYY) is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Anorexia nervosa (AN) is associated with a deliberate reduction in food intake and low bone density, but endocrine modulators of food intake in AN are not known. In addition, known regulators of bone turnover, such as GH, cortisol, and estrogen, explain only a fraction of the variability in bone turnover marker levels.Hypotheses: We hypothesized that PYY may be elevated in AN compared with controls and may contribute to decreased food intake and bone formation.Methods: Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12–18 yr old. We also examined GH, cortisol, ghrelin, and leptin (overnight frequent sampling) and fasting IGF-I, estradiol, total T3, and bone markers. Macronutrient intake and resting energy expenditure (REE) were measured.Results: AN girls had higher PYY levels compared with controls (17.8 ± 10.2 vs. 4.8 ± 4.3 pg/ml; P &lt; 0.0001). Predictors of log PYY were nutritional markers, including body mass index (r = −0.62; P &lt; 0.0001), fat mass (r = −0.55; P = 0.0003), and REE (r = −0.51; P = 0.0006), and hormones, including GH (r = 0.38; P = 0.004) and T3 (r = −0.59; P = 0.0001). Body mass index, fat mass, REE, GH, and T3 explained 68% of the variability of log PYY. Log PYY predicted percentage of calories from fat (r = −0.56; P = 0.0002) and independently predicted osteocalcin (r = −0.45; P = 0.003), bone-specific alkaline phosphatase (r = −0.46; P = 0.003), N-telopeptide/creatinine (r = −0.55; P = 0.0003), and deoxypyridinoline/creatinine (r = −0.52; P = 0.001) on regression modeling.Conclusion: Elevated PYY may contribute to reduced intake and decreased bone turnover in AN.
Acetylsalicylic Acid Improves Lipid-Induced Insulin Resistance in Healthy Men
Authors: Möhlig Matthias , Freudenberg Madlen , Bobbert Thomas , Ristow Michael , Rochlitz Helmut , Weickert Martin O. , Pfeiffer Andreas F. H. , Spranger Joachim 
Published: February 2006

Abstract
Context and Objective: Insulin resistance is a central feature of type 2 diabetes. Salicylates prevent lipid-induced insulin resistance in rodents by interrupting inflammatory pathways. We therefore investigated whether salicylates reduce lipid-induced insulin resistance in humans by affecting inflammatory pathways as reflected by serum adipocytokines.
Participants and Intervention: Ten healthy men were included in a crossover intervention study. Four euglycemic-hyperinsulinemic clamps were performed, one without pretreatment, one with prior 2-h lipid infusion, one after pretreatment with 4 g acetylsalicylic acid (ASA), and one with ASA pretreatment and prior lipid infusion.
Main Outcome Measure: Lipid-induced insulin resistance was quantified by the euglycemic-hyperinsulinemic clamp technique running at least 2 h. Repeated-measures ANOVA on two factors was used for comparison, and results were Bonferroni adjusted for multiple measurements. ASA effects on serum adipocytokines were addressed by comparing the areas under the curves.
Results: Glucose infusion rate (M value) of the control clamp without pretreatment was 6.3 (± 0.6) mg/kg·min. ASA pretreatment did not change glucose infusion rates (P = 0.6). Lipid infusion significantly decreased the M value to 4.1 (± 0.6) mg/kg·min (P = 0.008). After ASA pretreatment and lipid infusion, the M value was 4.8 (± 0.7) mg/kg·min and was significantly improved, compared with the lipid-only clamp (P = 0.036 after Bonferroni’s adjustment). General biomarkers of inflammatory processes (IL-6, C-reactive protein), the insulin-sensitizing mediator adiponectin, and circulating adiponectin oligomers were unchanged by ASA pretreatment.
Conclusions: ASA pretreatment attenuated lipid-induced insulin resistance in healthy humans. This acute insulin-sensitizing effect of ASA was unrelated to changes of circulating inflammatory markers.
Estrogen Metabolites and Systolic Blood Pressure in a Population-Based Sample of Postmenopausal Women
Authors: Masi Christopher M. , Hawkley Louise C. , Berry Jarett D. , Cacioppo John T. 
Published: February 2006

AbstractContext: Lower systolic blood pressure (SBP) and lower rates of coronary heart disease among premenopausal women compared with similarly aged men and postmenopausal women suggest that female sex hormones may confer cardiovascular protection. 2-Hydroxyestradiol, a product of 17β-estradiol oxidative metabolism, inhibits the proliferation of vascular smooth muscle cells in vitro. The other major product of 17β-estradiol oxidative metabolism, 16α-hydroxyestradiol, does not demonstrate similar inhibitory effects. Concentrations of 2-hydroxyestrone (2-OHE) and 16α-hydroxyestrone (16-OHE) in urine reflect the relative activity of the 2- and 16α-hydroxylation pathways of 17β-estradiol.Objective: The objective of this study was to determine the relationship between SBP and the ratio of 2-OHE to 16-OHE in urine.Design and Participants: This was a cross-sectional study of 80 postmenopausal women living in Cook County, Illinois.Setting: This study was performed in an academic clinical laboratory.Main Outcome Measure: The main outcome measure was SBP.Results: Women taking hormone replacement therapy had higher levels of urinary 2-OHE and 16-OHE, but their mean 2:16-OHE ratio and SBP did not differ from that of women not taking hormone replacement therapy. In a multivariate regression model that controlled for age, body mass index, race/ethnicity, and antihypertensive medication use, a sd increase in the 2:16-OHE ratio was associated with a 6.7-mm Hg decrease (P &lt; 0.05) in SBP.Conclusions: The ratio of urinary 2-OHE to 16-OHE is a significant predictor of SBP among postmenopausal women and may reflect the effects of 2-hydroxyestradiol, a potent inhibitor of vascular smooth muscle cell proliferation.
Clinical and laboratory indices of cholelithiasis in adult Nigerians with sickle-cell anaemia
Authors: Ajayi A O , Bojuwoye B J , Braimoh K , Ndububa D A 
Published: February 2006

The clinical and laboratory indices of cholelithiasis in adult Nigerians with homozygous sickle-cell disease (SCD) were studied in 100 consecutive patients attending the adult SS clinic of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. The study examined the role of clinical (sickle cell (SS) crises, body mass indices [BMIs]), haematological (reticulocyte count, haemoglobin) and biochemical (serum bilirubin, serum alkaline phosphatase and serum amino transaminases) indices in predicting the likelihood of finding cholelithiasis in patients with SS anaemia. A positive correlation was found between the BMI, SS crises, reticulocyte count, serum bilirubin, serum alanine and asparate transferases on one hand and the development of cholelithiasis (at P values of 0.04, 0.03, 0.05, 0.01 and 0.04, respectively) on the other. No such association was found between the other indices studied and cholelithiasis.
Preliminary reports of autologous blood transfusion in a plastic surgery unit
Authors: Olaitan P B , Onah I I , Ogbonnaya I S 
Published: February 2006

We commenced autologous blood transfusion at the plastic surgery unit of the National Orthopaedic Hospital, Enugu, Nigeria in January 2001. Forty-three patients who have so far had autologous blood transfusion up to June 2004 are reviewed. Autologous blood was found to be cheaper than homologous blood with no untoward reactions. We conclude that autologous blood is safe, cheap and should be considered in elective surgical cases.
Clinical and laboratory features of brucellosis in two university hospitals in Southeast Turkey
Authors: Kokoglu Omer Faruk , Hosoglu Salih , Geyik Mehmet Faruk , Ayaz Celal , Akalın Serife , Buyukbese Mehmet Akif , Cetinkaya Ali 
Published: February 2006

This prospective study was carried out in two university hospitals between January 2000 and December 2002. The diagnosis of brucellosis was made with compatible clinical findings, positive Brucella agglutination 1/160 titres, and/or the isolation of Brucella species. The patients were followed up without intervention. One hundred and thirty-eight patients with active brucellosis were evaluated. Of the participants, 79 (57.2%) cases were acute, 23 (16.7%) sub-acute and 36 (26.1%) chronic. Brucella melitensis was isolated in the specimens of 24 (26.9%) out of 89 patients. The most frequent symptoms were fever (78.3%), arthralgia (77.5%) and sweating (72.5%). The most common physical findings were fever (40.6%), splenomegaly (36.2%), and hepatomegaly (26.8%). The osteoarticular involvement was found in 64 patients (46.4%). Ten (7.5%) patients had orchiepididymitis. Meningitis, pulmonary involvement, endocarditis, and hepatitis were found in five (3.6%), three (2.1%), two (1.5%) and one (0.7%) patient, respectively. Relative lymphomonocytosis was found in 80 cases (58.8%), anaemia in 46 (33.3%) and leucopoenia in 30 cases (21.7%). Clinical relapse was observed in 14 patients (10.1%).
Economics of blood screening: in search of an optimal blood screening strategy
Authors: Chinkhumba Jobiba 
Published: February 2006

The objectives of this retrospective study were to assess the economic impact that the practice of 'family replacement donor system' has on the operational costs of a rural blood bank and to rationalize efficient blood screening protocols with a view to minimizing blood screening costs without compromising blood safety. Prevalence of transfusion-transmissible infections such as HIV, hepatitis B and syphilis were ascertained from records of 870 potential donors screened over a period of 6 months. Costs of screening tests were approximated by summing up costs of materials used per test. Overhead and labour costs were not factored in. Average and marginal costs of a fully-screened blood unit were calculated using different blood screening protocols. The average and marginal costs of a fully-screened blood unit vary greatly depending on the order in which screening tests are conducted. Although the variation in average costs per blood unit among different protocols is narrow, US&dollar; 29.44 to US&dollar; 33, the variation in marginal costs is significantly wider ranging from US&dollar; 22.79 to US&dollar; 51.85. Overall, 78 (9%) of the potential donors had HIV infection while 25 (3.2%) had hepatitis B infections and nine (1.2%) donors had syphilis. Co-infection rate was very low at 1.4%. The study shows that it is possible to prioritize blood screening tests for the selection of safe blood donors simply and cost-effectively in a developing country hospital. In the face of rapid rises in health-care spending, it is very important that essential health services such as blood screening are safely delivered with as little expenditure of financial resources as possible. To make sound economic decisions, average cost is not what matters but marginal cost, the cost of one more test.