bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended‐release Divalproex in Child and Adolescent Outpatients with Epilepsy
Authors: Kernitsky Lydia , O'Hara Kathryn A. , Jiang Ping , Pellock John M. 
Published: February 2005

Summary:  Purpose: To determine whether valproic acid [divalproex (DVP)] extended‐release, administered at a higher proportionate once‐daily dosage, can be safely substituted for delayed‐release or sprinkle in pediatric patients with epilepsy. Methods: Patients between ages 6 and 17 years with stable epilepsy taking DVP were randomized to 7 days of either DVP delayed‐release/sprinkle (at the usual daily dose taken before study entry) or extended‐release DVP (daily dose, 8% to 25% higher than their usual dose), and then (crossed over to) 7 days of the comparator formulation. Patient's clinical status was evaluated at a screening visit and on days 8 and 15, and with telephone follow‐up 1 month after study completion. Results: No statistically significant difference in mean plasma VPA levels measured at the end of treatment was observed: 99, 92, and 103 μg/ml with the delayed‐release tablets (n = 4), the sprinkle formulation (n = 11), and the extended‐release tablets (n = 16), respectively. Seizure‐control rates were stable during patients' use of the extended‐release formulation. None of the study patients experienced a treatment‐related adverse event. Conclusions: The total daily dose for patients taking the delayed‐formulation may need to be increased by ≤20% when they are switched to the extended‐release formulation. When switching from sprinkles to the extended‐release formulation, individual variability must be considered. In patients who have VPA levels near the very high end of the therapeutic range (>100 μg/ml), it may be more prudent to make only minor modifications to the total daily dose during conversion and then to individualize the DVP extended‐release dose based on plasma levels.
Book Reviews
Authors: Smith Preston G. 
Published: February 2005

Books reviewed in this issue: ▪The Innovator's Solution: Creating and Sustaining Successful Growth▪Seeing What's Next: Using the Theories of Innovation to Predict Industry Change▪The Second Century: Reconnecting Customer and Value Chain through Build‐to‐Order: Moving beyond Mass and Lean Production in the Auto Industry▪Balancing Agility and Discipline: A Guide for the Perplexed▪Organizing Business Knowledge: The MIT Process Handbook▪Leading Pharmaceutical Innovation: Trends and Drivers for Growth in the Pharmaceutical Industry
Nefazodone treatment of cocaine dependence with comorbid depressive symptoms
Authors: Ciraulo Domenic A. , Knapp Clifford , Rotrosen John , Sarid‐Segal Ofra , Ciraulo Ann Marie , LoCastro Joseph , Greenblatt David J. , Leiderman Deborah 
Published: February 2005

ABSTRACTAims  In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5‐HT2A receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use.Design  An 8‐week, double blind, placebo‐controlled design was used.Setting  The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center.Participants  Subjects (n = 69) met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher.Intervention  Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n = 34) or matching placebo (n = 35). All subjects received individual counseling.Measurements  Urinary measurements of benzoylecgonine (BE, three times per week) and self‐reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning.Findings  Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self‐reported cocaine use.Conclusions  These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels.
Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence
Authors: Ciraulo Domenic A. , Sarid‐Segal Ofra , Knapp Clifford M. , Ciraulo Ann Marie , LoCastro Joseph , Bloch Daniel A. , Montgomery Margaret A. , Leiderman Deborah B. , Elkashef Ahmed 
Published: February 2005

ABSTRACTAims  The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence.Design  A multi‐arm, modified blinded, placebo‐controlled design was used.Setting  The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).Participants  Participants met criteria for cocaine dependence during a 2‐week screening period.Intervention  Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.Measurements  Urine benzoylecgonine (BE) concentrations, self‐report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.Findings  None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end‐point compared to the placebo group. Significant within‐group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self‐reported cocaine use declined over the study period. Overall, the active medications were well tolerated.Conclusions  This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.
Comparison of the relationship of age and beta cell function in three ethnic groups
Authors: Chiu Ken C. , Martinez Dorothy S. , Chu Audrey 
Published: February 2005

SummaryDesign  Prevalence of type 2 diabetes and glucose intolerance increase with age. It has been demonstrated that beta cell function declines at about 1% per year in glucose tolerant Caucasians. However, this relationship is not known to exist in other ethnic groups.Subjects and Measurements  We investigated the relationship of age to beta cell function (%B) and insulin sensitivity (%S), estimated by the homeostasis model assessment, in a nationally representative sample of healthy US adults who participated in a cross‐sectional study, the third National Health and Nutrition Examination Survey. Only those subjects who had never been told to have diabetes by a physician, with HbA1C < 6% and fasting plasma glucose concentration < 5·56 mmol/l with proper fasting glucose and insulin concentration were included in this analysis (560 non‐Hispanic whites, 231 non‐Hispanic blacks and 298 Hispanics).Results  Age was positively correlated to HbA1C and fasting glucose concentration, but it was negatively correlated to %B in all three ethnic groups. In contrast, ageing had no influence on %S in all three ethnic groups. Pair‐wise comparison showed age had a similar influence among three ethnic groups on fasting glucose concentration, HbA1C and %B, respectively. Multivariate analysis confirmed an independent influence of age on fasting glucose concentration, HbA1C and %B among three ethnic groups.Conclusions  We observed %B declines at about 1% per year among all three ethnic groups. The age‐related rising fasting plasma glucose concentration and HbA1C is most likely a consequence of age‐related decline in beta cell function.
Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia‐1
Authors: Jap Tjin‐Shing , Chiu Chih‐Yang , Won Justin Ging‐Shing , Wu Yi‐Chi , Chen Harn‐Shen 
Published: February 2005

SummaryObjective  To identify MEN1 gene mutations and characterize clinical manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1) in Taiwan.Patients and Methods  Eight unrelated subjects (one male and seven females, age range 26–70 years) with clinical manifestations of MEN1 were analysed. In addition, 45 relatives that included 10 affected (three males and seven females, age range 32–53 years) and 35 unaffected (17 males and 18 females, age range 15–80 years) subjects were evaluated. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis were performed according to standard procedures.Results  We identified heterozygous MEN1 gene mutations in all eight probands and 10 affected subjects as well as in 13 clinically asymptomatic relatives. Novel mutations included a missense mutation in a heterozygous mutation in exon 9 (GAC → CAC) resulting in a substitution of aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon 556 of exon 10 (GAG → TAG) resulting in a stop codon and termination (family 2); a missense mutation in exon 2 (GGG → GAG) causing the substitution of glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion mutation in nucleotide 1200 of exon 8 resulting in frameshift and early termination (family 4). Affected subjects in families 5–7 shared the same C insertion at nucleotide 1650 of exon 10, similar to that previously described as a hotspot for mutation, and proband 8 had a previously described mutation in intron 4 of the MEN1 gene (IVS4–9 G → A). We also found that 18 (58%) of our 31 MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical abnormalities without clinical symptoms, and nine (29%) were unaffected both clinically and biochemically.Conclusions  We have identified four novel mutations in the MEN1 gene in patients with MEN1 in Taiwan.
Normal opioid tone and hypothalamic–pituitary–adrenal axis function in chronic fatigue syndrome despite marked functional impairment
Authors: Inder Warrick J. , Prickett Timothy C. R. , Mulder Roger T. 
Published: February 2005

SummaryObjective To determine whether the functional impairment seen in chronic fatigue syndrome (CFS) is associated with reduced levels of central opioids and/or deficiency of the hypothalamic–pituitary–adrenal (HPA) axis.Design Single‐blinded case–control study measuring functional and psychological status, basal hormonal parameters and ACTH/cortisol response to naloxone and ovine corticotrophin‐releasing hormone (oCRH)vs.placebo in people with CFS and healthy controls.Patients Twelve people with CFS and 11 age‐matched controls.Measurements Hormonal parameters: basal levels of 09:00 h plasma cortisol, dehydroepiandrosterone sulfate (DHEAS) and IGF‐1. 24‐h urinary free cortisol. Plasma ACTH and cortisol response to naloxone 125 µg/kg, oCRH 1 µg/kg and placebo (normal saline). Psychological parameters: SF‐36, Hamilton Depression Score, Hospital Anxiety and Depression Scale and Fatigue Scale.Results There were highly significant differences between the CFS subjects and the controls with respect to the measures of fatigue and physical functioning. However, there were no differences in basal levels of 09:00 h cortisol (367 ± 37vs.331 ± 39 nmol/l,P = 0·51), DHEAS (4·2 ± 0·6vs.4·0 ± 0·5 µmol/l,P = 0·81), 24‐h urinary free cortisol (182 ± 27vs.178 ± 21 nmol/24 h,P = 0·91) or IGF‐1 (145 ± 19vs.130 ± 11 µg/l,P = 0·52) between the CFS group and controls, respectively. There was also no difference between the groups with respect to the ACTH and cortisol response to either oCRH or naloxone.Conclusions Our data do not support an aetiological role for deficiency in central opioids or the HPA axis in the symptoms of CFS.
No association of the codon 55 methionine to valine polymorphism in the SUMO4 gene with Graves’ disease
Authors: Jennings Claire E. , Owen Catherine J. , Wilson Valerie , Pearce Simon H. S. 
Published: February 2005

SummaryObjective  A functional polymorphism at codon 55 of the small ubiquitin‐like modifier‐4 (SUMO4) gene (methionine to valine; M55V) has recently been associated with type 1 diabetes mellitus (T1D). We aimed to establish whether this locus also contributes towards the genetic susceptibility to Graves’ disease (GD) and autoimmune Addison's disease.Design  A case–control analysis was performed using genomic DNA samples from 595 unrelated white GD subjects, 104 white autoimmune Addison's disease subjects and 467 healthy white control subjects. The SUMO4 M55V single nucleotide polymorphism (SNP) was genotyped using polymerase chain reaction (PCR) amplification followed by digestion with the restriction enzyme MseI.Results  There was no association of the SUMO4 M55V alleles with either GD, thyroid‐associated orbitopathy or autoimmune Addison's disease when compared to controls; P = 0·28, 0·46 and 0·91, respectively, by χ2 testing.Conclusion  We cannot confirm a generalized role for SUMO4 in autoimmune endocrinopathy. The SUMO4 codon 55 methionine to valine polymorphism may be exclusively associated with susceptibility to T1D, or the effect of the locus in GD and Addison's disease may be much less than that found in T1D patients.
Vitamin D and the elderly
Authors: Mosekilde Leif 
Published: February 2005

SummaryThis review summarizes current knowledge on vitamin D status in the elderly with special attention to definition and prevalence of vitamin D insufficiency and deficiency, relationships between vitamin D status and various diseases common in the elderly, and the effects of intervention with vitamin D or vitamin D and calcium. Individual vitamin D status is usually estimated by measuring plasma 25‐hydroxyvitamin D (25OHD) levels. However, reference values from normal populations are not applicable for the definition of vitamin D insufficiency or deficiency. Instead vitamin D insufficiency is defined as the lowest threshold value for plasma 25OHD (around 50 nmol/l) that prevents secondary hyperparathyroidism, increased bone turnover, bone mineral loss, or seasonal variations in plasma PTH. Vitamin D deficiency is defined as values below 25 nmol/l. Using these definitions vitamin D deficiency is common among community‐dwelling elderly in the developed countries at higher latitudes and very common among institutionalized elderly, geriatric patients and patients with hip fractures. Vitamin D deficiency is an established risk factor for osteoporosis, falls and fractures. Clinical trials have demonstrated that 800 IU (20 µg) per day of vitamin D in combination with 1200 mg calcium effectively reduces the risk of falls and fractures in institutionalized patients. Furthermore, 400 IU (10 µg) per day in combination with 1000 mg calcium or 100 000 IU orally every fourth month without calcium reduces fracture risk in individuals over 65 years of age living at home. Yearly injections of vitamin D seem to have no effect on fracture risk probably because of reduced bioavailability. Simulation studies suggest that fortification of food cannot provide sufficient vitamin D to the elderly without exceeding present conventional safety levels for children. A combination of fortification and individual supplementation is proposed. It is argued that all official programmes should be evaluated scientifically. Epidemiological studies suggest that vitamin D insufficiency is related to a number of other disorders frequently observed among the elderly, such as breast, prostate and colon cancers, type 2 diabetes, and cardiovascular disorders including hypertension. However, apart from hypertension, causality has not been established through randomized intervention studies. It seems that 800 IU (20 µg) vitamin D per day in combination with calcium reduces systolic blood pressure in elderly women.
Neck recurrence from thyroid carcinoma: serum thyroglobulin and high‐dose total body scan are not reliable criteria for cure after radioiodine treatment
Authors: Bachelot Anne , Leboulleux Sophie , Baudin Eric , Hartl Dana M. , Caillou Bernard , Travagli Jean Paul , Schlumberger Martin 
Published: February 2005

SummaryBackground  Local and regional recurrences occur in up to 20% of patients with papillary and follicular thyroid carcinoma. Diagnostic work‐up and treatment modalities are still controversial, because nodal control is difficult to ascertain. We assessed the value of serum thyroglobulin (Tg) determination and of high‐dose 131I total body scan (TBS) for ascertaining the absence of disease in patients who had already been treated with radioiodine and who subsequently underwent surgery.Methods  Between 1990 and 2000, 105 patients who had been treated with radioiodine for lymph node recurrence with initial 131I uptake were included in a standardized protocol performed after withdrawal of thyroid hormone treatment: on day 1, serum Tg determination and administration of 3·7 GBq 131I; on day 4, 131I TBS; on day 5, surgery; on day 8, 131I TBS.Results  In 25 patients the serum Tg obtained following thyroid hormone withdrawal was undetectable: for these patients, the 131I TBS showed uptake foci in 21 and pathology disclosed neoplastic foci in 19. In 32 patients the serum Tg ranged from 1 to 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 26 and pathology disclosed neoplastic foci in 28. In 48 patients the serum Tg level was above 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 38 and pathology disclosed neoplastic foci in 46. Thus, no uptake was found preoperatively in 20 patients, among whom pathology disclosed lymph node metastases in 16. However, both tests were negative in only two of the 93 patients in whom pathology disclosed neoplastic foci.Conclusion  Serum Tg levels and 131I TBS cannot be considered as reliable indicators for the absence of disease in patients already treated with 131I. However, when both tests are negative, the risk of persistent disease is minimal.
Inheritance of the F4ab, F4ac and F4ad E. coli receptors in swine and examination of four candidate genes for F4acR
Authors: Python P. , Jörg H. , Neuenschwander S. , Asai‐Coakwell M. , Hagger C. , Bürgi E. , Bertschinger H.U. , Stranzinger G. , Vögeli P. 
Published: February 2005

SummarySusceptibility to enterotoxigenic Escherichia coli with fimbriae F4ac is dominantly inherited in the pig. A three‐generation pedigree was created to refine the position of F4acR on chromosome 13 comprising 202 pigs: eight parents, 18 F1 and 176 F2 pigs. The 17‐point analysis indicates that F4acR lies between Sw207 and S0283. Recombinant offspring specify that the most probable order is Sw207–S0075–F4acR–Sw225–S0283. We observed six phenotypes for the three fimbrial variants F4ab, F4ac and F4ad. The two missing phenotypes F4abR−/F4acR+/F4adR+ and F4abR−/F4acR+/F4adR− indicate that pigs susceptible to F4ac are always susceptible to F4ab. Furthermore, a weak and a strong adhesion of F4ab and F4ad bacteria was observed. The weak receptor F4abR (F4abRw) was present only in pigs devoid of the receptor F4acR (F4abR+/F4acR−). In contrast, in pigs with the phenotype F4abR+/F4acR+, F4ab bacteria adhered to the majority of enterocytes. F4abRw constitutes a frequently observed phenotype whose inheritance is still unclear. Strong adhesion of F4ab and F4ac bacteria is most likely influenced by the same receptor that we name F4bcR. The number of F4ad bacteria that adhered to enterocytes was very variable in the adhesion test. Moreover, expression of F4adR was independent of age. Our segregation analyses indicated a dominant inheritance of F4adR, although the number of susceptible pigs was smaller than expected. We examined four genes as candidates for the F4acR locus: the transferrin receptor gene (TFRC) and three genes members of the glucosyl/galactosyltransferase family (B3GnT5, B3GALT3 and B4GALT4). Comparison of sequences from resistant and homozygous susceptible F4ac pigs did not reveal any causative single nucleotide polymorphism in the four genes. Two silent mutations at the positions 295 (C/T) and 313 (T/C) in B3GALT3 were found. Using the somatic cell hybrid panel, B3GnT5 and B3GALT3 were assigned to the chromosomal region SSC13q23‐q41. No mutations were found in the cDNA sequences of these genes associated with the F4acR genotypes.
Radiation hybrid mapping of genes and newly identified microsatellites in candidate regions for bovine arthrogryposis–palatoschisis and progressive ataxia based on comparative data from man, mouse and rat
Authors: Duchesne A. , Eggen A. 
Published: February 2005

SummaryA comparative pathology and mapping strategy was used to initiate a study on two bovine genetic diseases: arthrogryposis–palatoschisis and progressive ataxia, which affect mainly Charolais cattle. Bibliographic studies provided information on the pathology of these diseases, which helped to define similar diseases in other species. Animals affected by bovine arthrogryposis–palatoschisis display similar symptoms to those of muscular dysgenesis, mouse mutants and animals with progressive ataxia to those of Long Evans Shaker rat mutants. Candidate regions are respectively human chromosome 1q32 (BTA16) containing the gene CACNA1S and human chromosome 18q23 (BTA24) containing the gene myelin basic protein (MBP). Primer pairs were designed for 15 loci around each candidate gene, in a region of about 20 megabases and were used to screen a bovine Bacterial Artificial Chromosome (BAC) library. Eighteen microsatellites were found in the identified BAC clones, 11 on BTA24 and seven on BTA16. The genes and microsatellites were mapped by radiation hybrid (RH) analysis and a RH map was obtained for each region with 18 new localizations on BTA16 and 23 on BTA24. Comparative human–bovine analysis of the MBP region shows a good conservation of gene order while that of the CACNA1S region shows several breakpoints.
Sex reversal syndrome (64,XY; SRY‐positive) in a mare demonstrating masculine behaviour
Authors: Switonski M. , Chmurzynska A. , Szczerbal I. , Lipczynski A. , Yang F. , Nowicka‐Posłuszna A. 
Published: February 2005

SummaryA 5‐year‐old Thoroughbred mare was subjected to cytogenetic and molecular analysis because of infertility and masculine behaviour. Chromosome studies, including painting with the whole X chromosome specific probe, revealed a male chromosome complement (64,XY). The PCR amplification of the SRY and ZFY genes showed the presence of both those genes, while the endocrinological study demonstrated a high level of testosterone (9.7 nmol/l). Sequencing of the SRY gene (1121 bp), comprising also 5′‐ and 3′‐UTRs, did not reveal any differences when compared with the sequence of normal stallions. It was proposed that this mare represents the androgen insensitivity syndrome (testicular feminization syndrome).