bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma
Authors: Jagannath Sundar , Durie Brian G. M. , Wolf Jeffrey , Camacho Elber , Irwin David , Lutzky Jose , McKinley Marti , Gabayan Eli , Mazumder Amitabha , Schenkein David , Crowley John 
Published: June 2005

SummaryBortezomib, as a single agent and in combination with dexamethasone, was examined as first‐line treatment in 32 consecutive patients with untreated symptomatic multiple myeloma. Patients received bortezomib 1·3 mg/m2 for a maximum of six 3‐week cycles; oral dexamethasone 40 mg was added if a less than partial response (PR) was achieved after two cycles or a less than complete response (CR) was achieved after four cycles. The response rate (CR + PR) was 88%, with undetectable paraprotein (CR) in 6%, and detectable by immunofixation only in 19% [near (n)CR]. All 32 patients completed the first two cycles of bortezomib alone, of whom 3% achieved CR, 9% nCR, and 28% PR. Ten patients received single‐agent bortezomib on study, and dexamethasone was added in 22, leading to 15 improved responses. The most common adverse events ≥grade 2 included sensory neuropathy (31%), constipation (28%), myalgia (28%) and fatigue (25%). Sensory neuropathy grade 2 or 3 was reversible within a median of 3 months in five of 10 patients. Bortezomib treatment did not affect stem cell mobilization in eight or transplantation in six patients. Bortezomib alone or in combination with dexamethasone is an effective induction therapy with a high CR and nCR rate and manageable toxicities in previously untreated patients with myeloma.
LISA: a web‐based decision‐support system for trial management of childhood acute lymphoblastic leukaemia
Authors: Bury Jonathan , Hurt Chris , Roy Anindita , Cheesman Louise , Bradburn Mike , Cross Simon , Fox John , Saha Vaskar 
Published: June 2005

SummaryContinuation chemotherapy is a key component of the treatment of childhood acute lymphoblastic leukaemia. During this treatment phase, weekly dose adjustments are carried out based on current and historical full blood counts (FBCs). The dose decision pathway is complex and suboptimal therapy may result if information on FBC results is not readily available and/or the prescriber is inexperienced. A web‐based decision‐support system (Leukaemia Intervention Scheduling and Advice, ‘LISA’) was designed to facilitate access to FBC information across geographical locations and to assist with dosage adjustments. A balanced‐block crossover analysis was performed to evaluate the system. Thirty‐six clinicians with varying degrees of experience were each asked to decide on appropriate oral chemotherapy dosages for eight simulated cases: four using LISA and four without. LISA significantly reduced the number of erroneous prescriptions (zero of 144 with LISA vs. 54 of 144 without; P < 0·0001) without affecting the number of times subjects deliberately overrode the protocol (seven of 144 times using LISA and six of 144 without). Using LISA reduced the time taken by novices to reach a decision for each case but increased the time taken by experts. Thirty‐five of 36 subjects said they would be likely to use the system if it were available. A system like LISA is likely to be acceptable to clinicians, and has the potential to increase protocol compliance and decrease prescribing errors while allowing clinicians to override the protocol in specific cases where sound reasons exist for doing so.
Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS)
Authors: Kumar Ashim , Woods Keslie S. , Bartolucci Alfred A. , Azziz Ricardo 
Published: June 2005

SummaryObjective  To determine the prevalence of adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) using age‐ and race‐specific normative values.Design  Cross‐sectional observational study.Patients  One hundred and eight‐two (88 Black and 94 White) age‐matched healthy eumenorrhoeic nonhirsute women (controls) and 213 (27 Black and 186 White) women with PCOS were recruited.Measurements  Total testosterone (T), free T, androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and glucose, were measured in plasma.Results  The mean total T, free T, A4, DHEAS and body mass index (BMI) were higher in women with PCOS than in control women. DHEAS levels were significantly lower in Black controls than White controls, whereas fasting insulin and BMI were higher in Black controls. In control and Black PCOS women, DHEAS levels did not correlate with BMI, waist‐to‐hip ratio (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated negatively with BMI and fasting insulin. DHEAS levels decreased similarly with age in control and PCOS women of either race. For each race and age group the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level were assessed. The prevalence of supranormal DHEAS levels was 33·3% and 19·9%, respectively, among Black and White women with PCOS.Conclusions  The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age‐ and race‐adjusted normative values. This study also indicates that the age‐associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.
Growth hormone secretion in adult patients with thalassaemia
Authors: La Rosa Clementina , De Sanctis Vincenzo , Mangiagli Antonino , Mancuso Michele , Guardabasso Vincenzo , Galati Maria Concetta , Caruso‐Nicoletti Manuela 
Published: June 2005

SummaryBackground and Objectives  Growth retardation and short stature are frequent clinical features of patients with beta‐thalassaemia major. Dysfunction of the GH–IGF‐1 axis has been described in many thalassaemic children and adolescents with short stature and reduced growth velocity. Several studies have demonstrated that recombinant GH treatment improves growth velocity in these patients, although response to the treatment is variable and not predictable. A reassessment of the GH–IGF‐1 axis must be performed in young adults with childhood‐onset GH deficiency (GHD), after attainment of final height, to select those who are candidates for replacement therapy as adults. To our knowledge there are no data available on retesting the GH–IGF‐1 axis in adult thalassaemic patients with childhood‐onset GHD. The aim of our study was to investigate GH secretion in adult thalassaemic patients with childhood‐onset GHD.Design  We reassessed GH secretion in a group of adult thalassaemic patients in whom partial GHD had been diagnosed during childhood.Patients and Methods  We performed an arginine plus GH‐releasing hormone (GHRH) stimulation test in 16 thalassaemic patients (10 males, six females) with a mean age of 24·8 ± 3·6 years. The cut‐off level for GH response was set at 9 µg/l, according to the literature. Ferritin, IGF‐1, liver enzymes and lipid levels were also determined.Results  We found persisting GHD in three patients, one patient had borderline values (GH peak = 10·4 µg/l), whereas the others had a normal response. These results are in accordance with the data on GH retesting in adult patients with idiopathic partial childhood‐onset GHD.Conclusion  We conclude that GH status should be retested in adult thalassaemic patients with childhood‐onset GHD. If the diagnosis of adult GHD is established, GH treatment may be considered as it could contribute to improve heart function and bone mineral density, which are frequently impaired in adult thalassaemic patients.
Decreased type 1 iodothyronine deiodinase expression might be an early and discrete event in thyroid cell dedifferentation towards papillary carcinoma
Authors: De Souza Meyer Erika L. , Dora José Miguel , Wagner Márcia S. , Maia Ana Luiza 
Published: June 2005

SummaryObjective  Type I iodothyronine deiodinase (D1) catalyses the 5′ monodeiodination of T4 and is highly expressed in normal human thyroid gland. We have investigated D1 expression in a series of benign and malignant differentiated thyroid neoplasias.Design  Surgically isolated thyroid tumour fragments were used. D1 expression was determined by reverse transcription polymerase chain reaction (RT‐PCR) and enzymatic assay.Patients  Tumours and adjacent normal tissues were obtained from 28 unselected patients (papillary carcinoma, n = 14; follicular adenoma, n = 7; follicular carcinoma, n = 6; anaplastic carcinoma, n = 1).Measurements  D1 mRNA levels were determined using specific primers for the human D1 gene and enzymatic assays were performed using T4 as substrate.Results  In papillary thyroid carcinoma (PTC), D1 mRNA and activity levels were decreased compared with the surrounding tissue (0·25 ± 0·24 vs. 1·09 ± 0·54 arbitrary units (AU), P < 0·001 and 0·08 ± 0·07 vs. 0·24 ± 0·15 pmol T4/min/mg protein, P = 0·045, respectively). Decreased D1 expression was consistent and was observed in all histological subtypes and clinical stages analysed, including microcarcinomas. By contrast, significantly higher D1 mRNA levels and enzyme activity were present in follicular adenoma (1·9 ± 1·5 vs. 0·83 ± 0·58 AU, P = 0·028 and 2·67 ± 1·42 vs. 0·22 ± 0·06 pmol T4/min/mg protein, P = 0·044, respectively) and in follicular thyroid carcinoma (FTC) than in surrounding normal tissue (1·2 ± 0·46 vs. 0·67 ± 0·18 AU, P = 0·038 and 1·20 ± 0·58 vs. 0·20 ± 0·10 pmol T4/min/mg protein, P < 0·001, respectively). Type II iodothyronine deiodinase (D2) activity was also significantly higher in metastatic FTC samples than in normal thyroid tissues (5·20 ± 0·81 vs. 0·30 ± 0·27 fmol T4/min/mg protein, P < 0·001).Conclusions  These findings suggest that thyroid cell dedifferentiation promotes changes in D1 gene expression by pretranscriptional mechanisms and indicate that decreased D1 expression might be an early and discrete event in thyroid cell dedifferentiation towards papillary thyroid carcinoma.
The nadir growth hormone after an octreotide test dose predicts the long‐term efficacy of somatostatin analogue therapy in acromegaly
Authors: Gilbert J. A. , Miell J. P. , Chambers S. M. , McGregor A. M. , Aylwin S. J. B. 
Published: June 2005

SummaryObjective  In the treatment of acromegaly, a ‘test dose’ of octreotide is recommended prior to the use of depot somatostatin analogue (SSA) therapy. However, there remains no consensus regarding the criteria that predict a response to treatment. The ability to select patients who may benefit most from medical therapy is potentially of great value in clinical practice. The aim of the study was to determine the predictive value of both the nadir GH and the mean GH following an octreotide test dose in identifying patients who subsequently achieved disease remission with depot SSA therapy. Remission was defined as a mean GH < 5 mU/l (< 2 µg/l).Design  Retrospective case–control study.Patients  A group of 41 patients with acromegaly underwent an octreotide test dose where GH was measured hourly for a total of 6 h following an injection of octreotide 50 µg subcutaneously. Nadir GH and mean GH following the octreotide test dose were determined. Thirty‐three patients were subsequently treated with depot SSA therapy and mean GH and IGF‐I levels were determined at follow‐up.Results  The nadir GH demonstrated superior predictive power to that of mean GH across a range of GH cut‐off values. A nadir GH < 5 mU/l demonstrated 80% sensitivity and 83% specificity in predicting remission with depot SSA therapy. A nadir GH < 10 mU/l demonstrated 100% sensitivity and 56% specificity.Conclusions  The nadir GH following an octreotide test dose is a useful predictive marker of achieving disease remission with depot SSA therapy used as either a primary or an adjuvant agent.
Lymphoid tyrosine phosphatase (PTPN22/LYP) variant and Graves’ disease in a Polish population: association and gene dose‐dependent correlation with age of onset
Authors: Skórka Agata , Bednarczuk Tomasz , Bar‐Andziak Ewa , Nauman Janusz , Ploski Rafal 
Published: June 2005

SummaryObjective  Susceptibility to Graves’ disease (GD) is to a significant extent determined by genetic factors of which the best known are those associated with the HLA and the CTLA4 locus. Recently, two studies on British Caucasians reported that a single nucleotide polymorphism, 1858 C>T in PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which is a negative regulator of T‐cell activation, increases the risk of GD. The purpose of our study was to investigate whether the PTPN22‘T’ allele is associated with GD and/or its subsets, defined by clinical or genetic parameters, in a Polish population.Subjects and design  A cohort of 290 patients and 310 controls was genotyped using a PCR‐RFLP method. The distribution of PTPN22 alleles and genotypes among patients and controls was compared, and correlation was sought between PTPN22‘T’ and sex, tobacco smoking status, family history of GD, age of disease onset, presence (and severity) of ophthalmopathy, and presence of the CTLA4 A49G or DRB1*03 alleles.Results  Association between GD and the PTPN22‘T’ allele was confirmed (OR 1·7, P < 0·0008). Furthermore, a significant correlation between the PTPN22 genotype and the age of GD onset was demonstrated (r = −0.18, P = 0·0019). The PTPN22‘TT’ and ‘CC’ genotypes defined groups characterized by more than twofold difference in median age of disease onset (20·8 years vs. 42 years, P < 0·003) whereas the ‘CT’ genotype was associated with an intermediate value (35 years). There were no statistically significant correlations with other analysed clinical or genetic parameters.Conclusions  We replicated the association between Graves’ disease and PTPN22‘T’ reported in British Caucasians. We also found a gene dose‐dependent effect of PTPN22‘T’ on the age of onset of Graves’ disease.
Circulating cortisone levels are associated with biochemical markers of bone formation and lumbar spine BMD: the Hertfordshire Cohort Study
Authors: Cooper Mark S. , Syddall Holly E. , Fall Caroline H. D. , Wood Peter J. , Stewart Paul M. , Cooper Cyrus , Dennison Elaine M. 
Published: June 2005

SummaryObjective  Cortisone is an endogenous corticosteroid that has negligible intrinsic glucocorticoid activity but can be converted to the active corticosteroid cortisol by the enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1). 11β‐HSD1 is expressed in osteoblasts and may play a role in determining susceptibility to glucocorticoid‐induced osteoporosis. In intact osteoblasts enzyme activity, and thus cortisol generation, is dependent on substrate concentration with an almost linear increase in activity across the physiological range. We have therefore attempted to measure the impact of 11β‐HSD1 activity on bone in vivo by examining the association of circulating cortisone with bone markers, bone mineral density (BMD) and bone loss in a cohort of women and men.Design and subjects  Baseline cross‐sectional association study involving 135 women and 171 men aged 61–73 years from the Hertfordshire Cohort Study and a 4 year follow‐up study examining changes in BMD.Measurements  Serum cortisone, cortisol and osteocalcin, and urinary type I collagen cross‐linked N‐telopeptide (NTX) were measured at baseline. BMD at spine and hip was measured at baseline and 4 years later.Results  In men serum cortisone levels were negatively correlated with serum osteocalcin (r = −0·20, P = 0·01); a similar relationship was seen in women (r = −0·16, P = 0·06). No correlation was seen between serum cortisone and urinary NTX (r = 0·03, P = 0·74 for women; r = −0·03, P = 0·72 for men). A negative correlation was observed between serum cortisone and spine BMD in women (r = −0·18, P = 0·04); a similar relationship was also seen in men (r =−0·14, P = 0·07). However, cortisone did not correlate with BMD at the femoral neck or total hip or changes in BMD at any site over time. In analyses adjusted for adiposity, osteoarthritis grade and a range of life‐style variables, these relationships did not change substantially. All these relationships were independent of cortisol concentrations.Conclusions  The most plausible explanation for the association of circulating cortisone levels with osteocalcin is the presence of 11β‐HSD1 activity within osteoblasts. The measurement of serum cortisone may independently give insights into the action of glucocorticoids on bone.
The effects of 12 months of growth hormone replacement therapy on cardiac autonomic tone in adults with growth hormone deficiency
Authors: Tanriverdi F. , Eryol N. K. , Atmaca H. , Unluhizarci K. , Ozdogru I. , Sarikaya I. , Bayram F. , Kelestimur F. 
Published: June 2005

SummaryObjectives  Growth hormone deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors. Some abnormalities of cardiac structure and function have been reported in adult patients with GHD, but there are few data related to cardiac autonomic tone. Non‐invasive assessment of cardiac autonomic status can be achieved by heart rate variability (HRV), which can be measured by using time‐domain or frequency‐domain variables. To our knowledge, short‐term (6 months) effects of GH replacement therapy (GHRT) on HRV in a limited number of patients have been evaluated prospectively in only two previous studies. The present study was therefore designed to investigate the effects of GHD and 12 months of GHRT on cardiac autonomic tone in a larger number of adult patients with severe GHD.Patients and methods  HRV measurement, by using time‐domain variables, was performed in 22 patients with GHD (eight men, 14 women; mean age 45·4 ± 2·4 years) and 22 healthy controls (nine men, 13 women; mean age 40·8 ± 1·8 years) at baseline. The time‐domain variables (sympathetically influenced parameters SDNN and SDANN and parasympathetically influenced parameters RMSSD and PNN50) were derived from 24‐h electrocardiogram (ECG) recordings. In the patient group, cardiac autonomic tone was re‐evaluated after 6 and 12 months of GHRT.Results  Mean baseline values of SDNN and SDANN were significantly higher (higher values mean lower sympathetic activity) in GHD patients than in healthy controls (P < 0·05), but mean baseline values of RMSSD and PNN50 did not differ significantly in healthy controls and patients. After 6 and 12 months of GHRT, mean SDNN and SDANN were decreased significantly when compared with the baseline values before GHRT (P < 0·05). However, mean RMSSD and PNN50 did not differ significantly from baseline. When SDNN and SDANN measurements were evaluated individually for each patient, after 12 months of GHRT both of the sympathetically influenced parameters decreased in 90% of the patients.Conclusions  These data indicate that sympathetic tone is decreased in adult patients with severe GHD. Additionally, an increment in sympathetic activity and normalization of sympathovagal balance have been demonstrated after 6 and 12 months of GHRT. This result suggests that, at least at the doses used in this study, GHRT improves sympathetic tone, without an obvious arrhythmogenic effect.
A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure
Authors: Bülow Pedersen Inge , Laurberg Peter , Knudsen Nils , Jørgensen Torben , Perrild Hans , Ovesen Lars , Rasmussen Lone Banke 
Published: June 2005

SummaryObjective  Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism.Design  A population study including 4649 randomly selected subjects.Measurements  Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO‐Ab), thyroglobulin autoantibodies (Tg‐Ab), TSH, fT3 and fT4.Results  Thyroid volume was categorized as small (< 6·6 ml) in 4·7%, normal (6·6–14·9 ml) in 60·4% and large (> 14·9 ml) in 34·9% of participants. Thyroid nodules were found in 29·7%. Serum TSH was low (< 0·4 mIU/l) in 4·7%, normal (0·4–3·6) in 91·0% and high (> 3·6) in 4·3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0·62% and of subclinical autoimmune atrophic thyroiditis 0·24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0·001). An association between thyroid nodules and TPO‐Ab in univariate analyses (P < 0·001) was due to confounding by sex and age (multivariate model, P = 0·23).Conclusion  We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.
The metabolic syndrome in middle‐aged men according to different definitions and related changes in carotid artery intima‐media thickness (IMT) during 3 years of follow‐up
Authors: WALLENFELDT K. , HULTHE J. , FAGERBERG B. 
Published: June 2005

Abstract.Objectives.  To examine the occurrence over time of the metabolic syndrome (MetS) according to different definitions and the relation to change during follow‐up in carotid artery intima‐media thickness (IMT), measured by ultrasound.Design.  A cohort of 316, originally 58‐year‐old men, initially free of diabetes and cardiovascular disease, was followed for 3.2 ± 0.2 years. IMT was measured bilaterally by high‐resolution B‐mode ultrasound at baseline and follow‐up. The MetS was classified according to slightly modified World Health Organization (WHO) and National Cholesterol Education Program (NCEP) criteria.Results.  In 88% WHO and NCEP definitions resulted in identical classifications. IMT was larger both at baseline and after 3 years in men fulfilling the criteria for the MetS, according to either of the definitions, compared to those without factors in the syndrome. Men who fulfilled the WHO criteria for the MetS, at the initial and final examination showed a statistically significant increase in carotid artery IMT during the study [76 (95% CI: 14–130) μm, n = 37]. Men fulfilling the WHO criteria for the MetS at baseline tended to have a larger annual increase in IMT than those not fulfilling the criteria or having no risk factors in the syndrome.Conclusions.  More than 10% of the men had the MetS both at baseline and after 3 years, and this was associated with an increase in IMT using the WHO definition. Several of the components included in the MetS deteriorated during follow‐up, i.e. body mass index (BMI), waist‐to‐hip ratio (WHR), waist circumference, blood glucose and blood pressure.