bluuebunny/crossref_metadata_2025_split huggingface dataset:
A placebo‐controlled screening trial of celecoxib for the treatment of cocaine dependence
Authors: Reid Malcolm S. , Angrist Burt , Baker Sherryl , Woo Caroline , Schwartz Marion , Montgomery Ann , Majewska Dorota , Robinson James , Rotrosen John 
Published: February 2005

ABSTRACTAims  To conduct a medication screening trial study on the efficacy of celecoxib versus placebo for the treatment of cocaine dependence.Design  A modified blinded, parallel group study in an outpatient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design.Setting  The study was performed at the New York Medications Development Research Unit (MDRU).Participants  All participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2‐week screening period. Twenty‐three participants were enrolled in the treatment phase of the study.Intervention  After a 2‐week screening period, subjects were assigned randomly to receive either celebrex (200 mg/day) or placebo for an 8‐week treatment period. All subjects also received individual cognitive behavioral counseling during treatment.Measurements  Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self‐report of drug use and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs and extrapyramidal side‐effects tests.Results  Study retention was similar across both treatment groups and safety measures indicated that celecoxib was moderately tolerated. Cocaine use, as measured by self‐report and urine BE levels at end of treatment, indicated weaker improvement in the celecoxib group. Reductions in the intensity of cocaine craving were also weaker in the celecoxib group. Cocaine abstinence rates, global impression scores and all other related psychometric measures did not differ significantly between treatment groups.Conclusion  This study does not support the effectiveness of celecoxib for the treatment of cocaine dependence.
A placebo‐controlled screening trial of olanzapine, valproate, and coenzyme Q10/L‐carnitine for the treatment of cocaine dependence
Authors: Reid Malcolm S. , Casadonte Paul , Baker Sherryl , Sanfilipo Michael , Braunstein Dania , Hitzemann Robert , Montgomery Ann , Majewska Dorota , Robinson James , Rotrosen John 
Published: February 2005

ABSTRACTAims  To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L‐carnitine combination versus placebo for the treatment of cocaine dependence.Design  A four‐arm, modified blinded, parallel group study in an out‐patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design.Setting  The study was performed at the New York Medications Development Research Unit (MDRU).Participants  All participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2‐week screening period. Sixty‐eight participants were enrolled with 39 completing the study.Intervention  After a 2‐week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L‐carnitine (500 mg/day) combination or placebo for an 8‐week treatment period. All subjects also received individual cognitive behavioral counseling during treatment.Measurements  Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self‐report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side‐effects tests.Results  Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self‐report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed.Conclusion  This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/ L‐carnitine combination for the treatment of cocaine dependence.
Prospective screening for coeliac disease in patients with Graves’ hyperthyroidism using anti‐gliadin and tissue transglutaminase antibodies
Authors: Ch’ng Chin Lye , Biswas Moushmi , Benton Ann , Jones M. Keston , Kingham Jeremy G. C. 
Published: February 2005

SummaryIntroduction  Coeliac disease (CD) is associated with autoimmune thyroid disease (AITD) although its prevalence among those with Graves’ hyperthyroidism in the UK is unknown. We determined the prevalence and evaluated the role of screening for CD prospectively in a consecutive cohort of patients with Graves’ hyperthyroidism using IgA class antibodies to gliadin (AGA) and tissue transglutaminase (anti‐tTG).Methods  All patients with Graves’ hyperthyroidism attending the thyroid clinic over a 9‐month period were offered screening for CD using AGA (normal < 3 mg/l) and anti‐tTG (normal < 15 µ/ml). Comparison was made with an age‐ and sex‐matched healthy control group from the local population whose sera were tested for anti‐tTG. In patients with borderline or raised anti‐tTG (> 7 µ/ml) endomysial antibody (EmA) was measured. Serum IgA was also measured to exclude IgA deficiency. Patients with raised AGA, raised or borderline anti‐tTG, positive EmA, IgA deficiency or haematinic deficiencies were offered endoscopic duodenal biopsy.Results  A total of 115 patients (97 female and 18 male) with Graves’ hyperthyroidism were offered screening tests and 111 accepted. AGA was raised in 15 patients, anti‐tTG was raised in two (both positive for EmA) and equivocal in six (one positive for EmA). IgA deficiency was present in three. Four patients were known to have haematinic deficiencies. Twenty‐five patients were invited and 19 agreed to have endoscopic duodenal biopsy. Three new patients were found to have CD while two patients were already known to have CD, thus five of 111 patients with Graves’ hyperthyroidism had CD. One of 115 healthy controls had a strong positive anti‐tTG (> 200 µ/ml) and EmA indicating probable CD.Conclusions  Screening 111 consecutive patients with Graves’ hyperthyroidism revealed AGA in 14%, anti‐tTG in 2% and IgA deficiency in 3%. Two patients were known to have CD. Screening detected three new cases. The prevalence of CD in patients with Graves’ hyperthyroidism was 4·5% as compared with 0·9% in matched healthy controls. Routine screening for CD should be considered.
An update on the biochemical diagnosis of congenital ACTH insufficiency
Authors: Mehta Ameeta , Hindmarsh Peter C. , Dattani Mehul T. 
Published: February 2005

SummaryObjective  Congenital ACTH insufficiency due to disorders of the hypothalamo–pituitary axis is life threatening. However, the optimal method for establishing the diagnosis remains controversial. The standard Synacthen test (SST) is safe and easy to perform in infancy, but its performance has not been well evaluated in infants and children with ACTH insufficiency.Design, Patients and Measurements  We aimed to determine the value of the SST by comparing the 30‐min SST cortisol concentration with physiological (spontaneous) cortisol secretion (2‐hourly measurements for 24 h) in 28 patients (13 male; age range 0–5·1 years) with one or a combination of optic nerve (25) midline forebrain (17) and other pituitary hormone (17) abnormalities. Spontaneous cortisol secretion (mean < 145 nmol/l) was arbitrarily used as the ‘gold‐standard’ in the diagnosis of ACTH insufficiency as it offered a reflection of endogenous cortisol mileu. A normal SST was defined as a 30‐min serum cortisol > 540 nmol/l.Results  The SST basal, 30‐min and 60‐min serum cortisol concentrations were significantly (P < 0·001) lower in patients with ACTH insufficiency (mean spontaneous cortisol < 145 nmol/l). 3/13 patients without and 12/15 patients with ACTH insufficiency failed the SST (specificity 76·9%; sensitivity 80%). Two out of three patients with ACTH insufficiency who passed the test were symptomatic with fatigue, poor growth and hypoglycaemia that resolved with hydrocortisone treatment. An 08:00 h serum cortisol cut‐off of 175 nmol/l provided a sensitivity of 93·3% and a specificity of 92·3% as compared with spontaneous cortisol secretion. The 30‐min increment and the 60‐min SST cortisol concentrations although highly specific (100%) had reduced sensitivity (40% and 60%, respectively).Conclusions  A normal SST does not rule out ACTH insufficiency and measurement of physiological cortisol secretion may be required to confirm the diagnosis. A combination of 08:00 h serum cortisol > 175 nmol/l and a 30‐min SST serum cortisol > 540 nmol/l to exclude ACTH insufficiency (sensitivity 69%, specificity 100%) would ensure that no child with ACTH insufficiency would be missed and hence would prevent serious consequences, although it may lead to over‐diagnosis in some cases.
Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults
Authors: Giannoulis M. G. , Boroujerdi M. A. , Powrie J. , Dall R. , Napoli R. , Ehrnborg C. , Pentecost C. , Cittadini A. , Jørgensen J. O. L. , Sonksen P. H. 
Published: February 2005

SummaryObjectives  Exercise is a potent physiological stimulus of GH secretion. We hypothesized that exogenous recombinant human growth hormone (rhGH) administration through an increase in GH and IGF‐I levels would blunt the GH response to exercise. The aim of the study was to examine and compare the impact of rhGH on the exercise‐induced GH response in healthy normal men and women.Design and Measurements  Sixty‐nine subjects (36 men, 33 women) were randomized to receive low‐dose rhGH (0·1 U/kg/day), high dose rhGH (0·2 U/kg/day), or placebo. Subjects were matched for age (24 ± 3·1), and body mass index (BMI). rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days. All subjects exercised to exhaustion (maximal oxygen consumption – VO2max) before rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise (time 0), immediately after exercise (time 0′) and at 15, 30, 60, 90 and 120 min postexercise. Baseline IGF‐I levels were measured before exercise on days 0 and 28.Results  Baseline IGF‐I levels showed no gender differences (42·3 women vs. 38·8 nmol/l men) but basal GH values were higher in women (9·9 vs. 1·8 mU/l, P < 0·001). The areas under the GH response curve, for Test 1 were similar in men and women. Peak GH values were higher in women than men (37·9 vs. 23·5 mU/l, but this did not quite reach statistical significance (P = 0·055). In men, administration of rhGH resulted in a significant increase in IGF‐I levels over the basal state in both the LD and HD groups (P < 0·0001). In women, the increase in lGF‐I levels reached significance only in the HD group (P < 0·0001). On day 28, GH secretion in response to exercise was calculated from the areas under the GH response curve correcting for an exogenous rhGH component (ΔAUC). In men, the ΔAUC, for Test 2 were similar in all three groups. In women, the ΔAUC was higher in the placebo group, than in the HD group (P < 0·02). Free T4 levels decreased significantly in men, and free T3 increased in both men and women, in HD group after the rhGH administration. TSH levels were suppressed only in women. No changes in sex hormones were found in men or women in any of the treatment groups.Conclusions  In terms of IGF‐I, men are more responsive to rhGH treatment than women. In addition, as men, but not women, were able to overcome the negative feedback control of the elevated IGF‐I levels, it seems that exercise may be a more robust stimulus to GH release in men compared to women.
Determination of large bowel length and loop complexity in patients with acromegaly undergoing screening colonoscopy
Authors: Renehan Andrew G. , Painter John E. , Bell G. Duncan , Rowland Roger S. , O'Dwyer Sarah T. , Shalet Stephen M. 
Published: February 2005

SummaryBackground  Patients with acromegaly are at moderately increased risk of developing colorectal cancer and may be considered for screening colonoscopy. In turn, large bowel dimensions may be increased in these patients, factors that predict for increased risk of serious complications such as perforation.Objective  To evaluate this risk potential, we measured large bowel length and loop complexity using magnetic endoscopic imaging (MEI).Design  Case–control study in 25 unselected patients with acromegaly (mean age 56 years) vs. 41 nonacromegalic controls (mean age 60 years) undergoing screening colonoscopy.Measurements  MEI parameters were determined and age‐ and sex‐adjusted mean differences calculated. The dependency of total large bowel length on various demographic and disease‐related factors (e.g. GH exposure, IGF‐I and IGFBP‐3 concentrations) was assessed using regression techniques.Results  Total large bowel length was increased by 20%[95% confidence interval (CI) 9–31%] in patients with acromegaly compared with controls (unadjusted and adjusted; P‐values < 0·001). Acromegaly was also associated with increased time taken to reach the caecum (P = 0·01) and increased pelvic loop complexities (5/25 vs. 1/41, Fisher's exact test: P = 0·03). Total large bowel length was predicted by age at colonoscopy (P = 0·003) and patient height (P = 0·03), but not by surrogate biochemical markers of disease activity.Conclusions  Acromegaly is associated with increased large bowel length and loop complexity making colonoscopy technically challenging, and theoretically increasing the risk of serious complications. Patients need to be counselled accordingly, and appropriate resources with experienced staff allocated.
β‐Cell dysfunction and low insulin clearance in insulin‐resistant human immunodeficiency virus (HIV)‐infected patients with lipodystrophy
Authors: Haugaard Steen B. , Andersen Ove , Vølund Aage , Hansen Birgitte R. , Iversen Johan , Andersen Ulrik B. , Nielsen Jens Ole , Madsbad Sten 
Published: February 2005

SummaryObjective  To obtain a better understanding of the physiological aspects of glucose homeostasis in human immunodeficiency virus (HIV)‐infected patients with lipodystrophy, we evaluated separately β‐cell function and insulin sensitivity after an oral glucose load.Design   β‐Cell function was investigated during an oral glucose tolerance test (OGTT) (75 g, 180 min) in 16 lipodystrophic HIV‐infected patients and in 15 age‐ and weight‐matched nonlipodystrophic HIV‐infected patients. All participants were sedentary Caucasian males, who were on highly active antiretroviral therapy with no history of diabetes mellitus or impaired glucose tolerance. Prehepatic insulin secretion rates were estimated by deconvolution of C‐peptide concentrations. A composite measure of insulin sensitivity was derived from the OGTT.Results  β‐Cell secretory capacity (i.e. the rate of change in insulin secretion per unit change in glucose concentration) was similar in lipodystrophic and nonlipodystrophic patients (6·2 ± 1·0 mU kg−1 min−1 mg−1 dl vs. 5·4 ± 0·4, P > 0·4), but insulin sensitivity was reduced by 61% in lipodystrophic patients (P < 0·004). The disposition index (insulin capacity multiplied with insulin sensitivity) and insulin clearance rate were reduced in lipodystrophic patients (−55%, P < 0·003 and −31%, P < 0·004). Insulin clearance rate correlated strongly with insulin sensitivity (r = 0·82, P < 0·001). More lipodystrophic than nonlipodystrophic patients exhibited impaired glucose tolerance and diabetes mellitus (63%vs. 20%, P < 0·05).Conclusions  Our data support the concept that impaired glucose tolerance in lipodystrophic HIV‐infected patients relates to a failure of the β‐cells to fully compensate for decrements in insulin sensitivity despite simultaneous reduction in insulin clearance.
Neonatal leptin levels are strongly associated with female gender, birth length, IGF‐I levels and formula feeding
Authors: Petridou Eleni , Mantzoros Christos S. , Belechri Maria , Skalkidou Alkistis , Dessypris Nick , Papathoma Eugenia , Salvanos Heraklis , Lee Jennifer H. , Kedikoglou Simeon , Chrousos George , Trichopoulos Dimitrios 
Published: February 2005

SummaryObjective  To investigate predictors of circulating leptin in healthy full‐term newborns and to explore the relationship with anthropometric variables, serum levels of adiponectin and the major components of the IGF system at birth. To explore whether leptin levels are regulated by breastfeeding vs. formula feeding.Design  Observational cross‐sectional study.Patients  Three hundred and nineteen healthy full‐term newborns delivered during 1999 in Athens, Greece.Measurements  Anthropometric measurements, formula feeding information and blood samples were obtained. Leptin and adiponectin determinations were performed using a radioimmunoassay (RIA).Results  Multivariate regression analyses showed that leptin levels were positively associated with female gender, newborn length, ponderal index and IGF‐I levels, but not with adiponectin levels. Newborns who were fed exclusively with milk formulas had more than twice the leptin levels of those who were exclusively breastfed.Conclusions  Leptin levels are positively related to female gender and anthropometric characteristics of neonates but, contrary to studies in adults, are not correlated with adiponectin levels. We also found evidence that formula feeding imparts a considerable increase in leptin levels in newborns.
Analysis of polymorphic PRNP microsatellite and ORF sites in German sheep breeds
Authors: Preuss S. , Kuss A. W. , He H. , Bartenschlager H. , Geldermann H. 
Published: February 2005

SummaryPolymorphic microsatellite and open‐reading frame (ORF) sites in the prion protein coding gene (PRNP) were analysed in eight sheep breeds. The three microsatellite sites S11, S15 and S24 were genotyped by fragment length analysis, and the ORF codons 136, 154 and 171 were analysed after direct sequencing. Unexpected polymerase chain reaction (PCR) products of microsatellite sites and ORF haplotypes with more than one heterozygous site were submitted to cloning and then sequenced. The microsatellite sites were polymorphic in all breeds with two to five alleles per site. On average of breeds and sites, the microsatellites had higher degrees of polymorphism than the ORF sites. The ARR/ARR ORF genotype occurred always together with the microsatellite genotypes S11 152/152, S15 179/179 and S24 144/144. As ORF and microsatellite alleles of the PRNP were observed in typical combinations, the microsatellite genotypes were significantly associated with scrapie incidences or risk classes based on the ORF genotypes. The microsatellite sites were highly polymorphic and therefore are advantageous markers for evaluation of scrapie disposition and fine mapping of effects on scrapie pathogenesis within the gene.
The distribution of genetic founder contributions within and among selection and control lines of an experiment with laying hens
Authors: Hagger C. , Steiger D. 
Published: February 2005

SummaryPedigree analysis was used to monitor genetic dynamics in retrospect in two identically selected lines (S1, S2) and a control (CL) of laying hens, originating from a common base. The pedigree of the last generation animals had nine generations of ancestors the members of the first known generation of ancestors were taken as founders. In each generation and in all lines one son was randomly chosen from each of 20 sires. Selection of females was randomly one daughter from each of 80 dams in CL and the best 80 according to a complex criterion in S1 and S2. The experiment included seven generations of selection. After three generations 51.6, 51.5 and 95.5% of the female founders of the base generation remained in S1, S2 and CL, respectively. The corresponding figures for the founder males were 67.7, 65.1 and 96.2%. These fractions did not change much in the following generations. On average 88.5, 87.1 and 78.8% of the remaining founders of the last generation were present in the pedigree of a last generation animal in S1, S2 and CL, respectively. The average genetic contribution of a founder male to the genome of the last generation was 1.22, 1.25 and 1.04% in S1, S2 and CL, respectively. The corresponding female contributions were 0.64, 0.60 and 0.49%, respectively. The most important founders of S1 and S2, which contributed 90% of the genome of their own line, contributed 80% of the genome of the other line and 73% of the one of CL in both cases. The most important founders of CL contributed 82% to the genomes of S1 and S2. The numbers of founder genome equivalents, were 9.8, 10.3 and 12.2 for S1, S2 and CL in the last generation and indicate a considerable loss of founder alleles in all lines. Effective population sizes calculated from average rate of inbreeding obtained from pedigrees were 91.1, 98.3 and 122.5 for S1, S2 and CL, respectively. Using the squared founder contributions for this purpose resulted in effective sizes of 0.966, 0.941 and 0.959 of the former values for S1, S2 and CL, respectively. Mating only animals with four different grand sires reduced inbreeding compared with random mating over the duration of the experiment. The effectiveness of this scheme was, however, strongly reduced in the last generation.
MECHANOSENSORY PERCEPTION: ARE THERE CONTRIBUTIONS FROM BONE‐ASSOCIATED RECEPTORS?
Authors: Rowe MJ , Tracey DJ , Mahns DA , Sahai V , Ivanusic JJ 
Published: February 2005

SUMMARY1. The identity of the receptors and afferent nerve fibres that mediate the sense of touch varies somewhat with body location. Those that have been most intensively characterized are associated with the distal glabrous skin of the limbs and, in primates, mediate the sense of touch in the fingertips and palms. In this glabrous skin region, there appear to be three or four principal classes of tactile sensory nerves that fall into two broad groups. One group, the so‐called slowly adapting (SA) receptors and afferent fibres, is responsive to static mechanical displacement of skin tissues and is made up of two classes, the type I (SAI) fibres that innervate Merkel receptors and the type II (SAII) fibres that innervate Ruffini endings. The second broad group displays a pure dynamic sensitivity to tactile stimuli and also falls into two principal classes, the rapidly adapting (RA) tactile fibres that are associated with Meissner corpuscle receptors and the Pacinian corpuscle (PC)‐associated class of tactile afferent fibres.2. In other regions of the skin, such as the hairy skin of the arms, legs and trunk, there are similar functional classes of tactile sensory nerves, although the receptor endings differ somewhat from those of the glabrous skin.3. Receptors in close association with the long bones of the limbs include groups of Pacinian corpuscles distributed along the interosseous membranes. These are highly sensitive to dynamic forms of mechanical stimuli, in particular vibrotactile disturbances. However, despite their close association with bone, these receptors probably cannot be legitimately considered ‘osseoreceptors’.4. Both the periosteum and the bone marrow are richly supplied by nerve fibres. However, much evidence indicates that these are largely or entirely in the fine‐diameter category of nerve fibres, whose roles may be confined to either nociception or to the efferent autonomic regulation of bone‐associated blood vessels.5. In conclusion, it remains uncertain whether any aspects of our innocuous touch or kinaesthetic senses, in either the limbs or in orofacial regions, can be ascribed to ‘osseoreceptors’ located in the periosteum or within the bone marrow itself.