bluuebunny/crossref_metadata_2025_split huggingface dataset:
Courting the expert: a clash of culture?
Authors: Caldwell P. 
Published: June 2005

SummaryThis article reviews the utility of expert opinion in legal proceedings and the deployment of expert witnesses in adversarial litigation. The use of expert witnesses to assist courts in making just and fair conclusions may be contrasted with the partisan interests of those who call them. An adversarial system is a bad method of scientific enquiry and undermines the court's capacity to reach the ‘right’ answer. As a consequence, courts may reach the wrong conclusion based on bad science. The role of the expert as a witness places strain on an expert to provide certainty, where in fact there may be none. Recent reforms in the civil courts have changed little and the problem is even more acute in criminal trials. The expert can rely solely on the integrity of his or her own opinion, tempered with a little humility. However, when filtered through the rhetoric and advocacy of a court arena, even this may be compromised.
Low‐dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma
Authors: Kyriakou Charalampia , Thomson Kirsty , D'Sa Shirley , Flory Angela , Hanslip Judith , Goldstone Anthony H. , Yong Kwee L. 
Published: June 2005

SummaryThe feasibility and efficacy of a triple regimen of oral weekly cyclophosphamide, monthly pulsed dexamethasone and low‐dose Thalidomide (CDT) was studied in 52 patients with relapsed or refractory multiple myeloma (MM). All 52 patients were evaluable for response with a median follow up of 18 (4–29) months. About 17% achieved complete response (CR), 62% partial response (PR), 11% minimal response (MR), 6% stable disease (SD) and 4% progressive disease (PD), resulting in an objective response rate (≥MR) of 90%. Subsequent to successful response, nine patients received high‐dose therapy (HDT) followed by stem cell transplantation (SCT) and 34 received thalidomide monotherapy as maintenance. Response rate was not influenced by disease status, prior HDT or age. The regimen was successfully delivered to all patients except for one patient who developed abnormal liver function at 7 weeks. Infective complications were minimal and there were no infection‐related deaths. The estimated overall and event‐free survival (EFS) at 2 years was 73% and 34%, respectively, and the median time to progression has not been reached. We conclude that the CDT regimen is safe, well tolerated and effective in patients with relapsed and refractory myeloma.
Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long‐term results in 30 patients
Authors: Cervantes Francisco , Alvarez‐Larrán Alberto , Domingo Abel , Arellano‐Rodrigo Eduardo , Montserrat Emili 
Published: June 2005

SummaryAndrogens are considered the treatment of choice for the anaemia of myelofibrosis with myeloid metaplasia (MMM). Good results have been reported in a few patients treated with danazol, a synthetic attenuated androgen. The long‐term efficacy and tolerability of danazol as treatment for the anaemia of MMM was evaluated in 30 patients, who received 600 mg/d, with progressive tapering to the minimum effective dose in the responders after 6 months. Complete response (CR) was defined as transfusion cessation with normal Hb and partial response (PR) as an Hb increase ≥1·5 g/dl with transfusion‐independent Hb values >10 g/dl maintained for at least 8 weeks. Median follow‐up was 20·5 months (range: 3·5–58 months). Response was achieved in 11 patients (37%), including eight CRs and three PRs. Median time to response was 5 months (range: 1–9 months). Four patients stopped responding at 6–24 months, two responders discontinued treatment because of toxicity, and five maintained response at 3·5–42 months. Pretreatment variables associated with response were lack of transfusion requirement (P= 0·001) and higher Hb at treatment start (P= 0·02). Toxicity was usually moderate, leading to treatment withdrawal in only two cases. Danazol is effective and well tolerated in a substantial proportion of MMM patients with anaemia.
Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH‐binding lobe of cytochrome b5 reductase
Authors: Percy M. J. , Crowley L. J. , Davis C. A. , McMullin M. F. , Savage G. , Hughes J. , McMahon C. , Quinn R. J. M. , Smith O. , Barber M. J. , Lappin T. R. J. 
Published: June 2005

SummaryType I recessive congenital methaemoglobinaemia (RCM), caused by the reduced form of nicotinamide adenine dinucleotide (NADH)‐cytochrome b5 reductase (cytb5r) deficiency, manifests clinically as cyanosis without neurological dysfunction. Two mutations, E255‐ and G291D, have been identified in the NADH‐binding lobe of cytb5r in previously reported patients, and we have detected a further novel mutation, D239G, in this lobe in two unrelated Irish families. Although one family belongs to the genetically isolated Traveller Community, which separated from the general Irish population during the 1845–48 famine, the D239G mutation was present on the same haplotype in both families. Three known cytb5r mutations were also identified, including the R159‐ mutation, which causes loss of the entire NADH‐binding lobe and had previously been reported in an individual with type II RCM. Characterization of the three NADH‐binding lobe mutants using a heterologous expression system revealed that all three variants retained stoichiometric levels of flavin adenine dinucleotide with spectroscopic and thermodynamic properties comparable with those of native cytb5r. In contrast to the E255‐ and G291D variants, the novel D239G mutation had no adverse impact on protein thermostability. The D239G mutation perturbed substrate binding, causing both decreased specificity for NADH and increased specificity for NADPH. Thus cytb5r deficient patients who are heterozygous for an NADH‐binding lobe mutation can exhibit the clinically less severe type I phenotype, even in association with heterozygous deletion of the NADH‐binding lobe.
Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana‐Farber Cancer Institute protocols: effect of age and risk stratification of disease
Authors: Athale Uma H. , Siciliano Sabrina A. , Crowther Mark , Barr Ronald D. , Chan Anthony K. C. 
Published: June 2005

SummaryChildren with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL‐associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana‐Farber Cancer Institute (DFCI)‐ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high‐risk (HR) patients receive thrice the steroid‐dose given to standard‐risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI‐ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (≥10 years) compared with three of 75 (4%) younger patients developed TE (P < 0·0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0·0006). Gender, ALL‐immunophenotype, steroid‐type or ASP dosing schedule did not alter the risk but older age and HR‐disease were factors predisposing to TE associated with DFCI‐ALL protocols. Age‐related risk may partly reflect the effect of ALL‐risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients.
Hepatitis C virus‐related thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura
Authors: Rajan Sandeep K. , Espina Byron M. , Liebman Howard A. 
Published: June 2005

SummaryThrombocytopenia can be a complication of hepatitis C viral (HCV) infection. However, there is little published data regarding the clinical and laboratory manifestations of HCV‐related thrombocytopenia (HCV‐TP) compared with adult chronic immune thrombocytopenic purpura (CITP). We reviewed the medical records for all patients evaluated for chronic thrombocytopenia by the Haematology Service between January 1996 and June 2000. All patients were screened for HCV infection at the time of initial diagnosis. Of 250 patients who fulfilled American Society of Hematology criteria for CITP, 76 (30%) were HCV seropositive. HCV‐TP patients were older [mean age (±SD) 54·9 ± 8 years vs. 40·3 ± 8 years, P ≤ 0·001] and equally distributed between both sexes. HCV‐TP patients had less severe thrombocytopenia, defined as platelet count ≤10 × 109/l (4% vs. 46% for CITP, P ≤ 0·001). However, 56 (74%) had a platelet count ≤50 × 109/l. Symptoms and signs of thrombocytopenia were less frequent in HCV‐TP, but major bleeding was more frequent (25% vs. 10%, P = 0·0059). Serum cryoglobulins and anticardiolipin antibodies were more frequent in HCV‐TP (90% and 62% respectively), but rare in CITP (7% and 15%, P ≤ 0·001 compared with HCV‐TP). HCV infection can be associated with significant thrombocytopenia and appears to be a distinct clinical entity.
The effect of atorvastatin on serum lipoproteins in acromegaly
Authors: Mishra Manoj , Durrington Paul , Mackness Mike , Siddals Kirk W. , Kaushal Kalpana , Davies Rob , Gibson Martin , Ray David W. 
Published: June 2005

AbstractObjective Acromegaly is associated with long‐term adverse effects on cardiovascular mortality and morbidity. Reducing growth hormone secretion improves well‐being and symptoms, but may not significantly improve the lipoprotein profile. An additional approach to cardiovascular risk reduction in acromegaly may therefore be to target lipoprotein metabolism directly. In this study we investigated the effect of statin treatment.Design Double blind, placebo‐controlled, crossover study of the effects on circulating lipoproteins of atorvastatin 10 mg daily vs. placebo. Each treatment was given for 3 months in random order.Subjects Eleven patients with acromegaly.Measurements Lipids, lipoproteins, apolipoproteins, enzyme activity and calculated cardiovascular risk.Results Atorvastatin treatment compared to placebo resulted in a significant decrease in serum cholesterol (5·85 ± 1·04 mmol/l vs. 4·22 ± 0·69 mmol/l; mean ± SD; P < 0·001), low‐density lipoprotein (LDL) cholesterol (2·95 ± 1·07 mmol/l vs. 1·82 ± 0·92 mmol/l; P < 0·001), very low‐density lipoprotein (VLDL) cholesterol (0·31 (0·21–0·47) mmol vs. 0·23 (0·13–0·30) mmol/l median (interquartile range); P < 0·05), apolipoprotein B (111 ± 28 mg/dl vs. 80 ± 18 mg/dl; P < 0·001), and calculated coronary heart disease risk (6·8 (3·3–17·9) vs. 2·8 (1·5–5·7)% over next 10 years; P < 0·01). Serum triglyceride was 1·34 (1·06–1·71) mmol/l on placebo and 1·14 (0·88–1·48) mmol/l on atorvastatin (ns). HDL cholesterol, apolipoprotein A1 and Lp(a) concentrations and cholesteryl ester transfer protein and lecithin: cholesterol acyl transferase activities were also not significantly altered.Conclusion Atorvastatin treatment was safe, well tolerated and effective in improving the atherogenic lipoprotein profile in acromegaly.
The pattern of growth hormone secretion during the menstrual cycle in normal and depressed women
Authors: Kasa‐Vubu Josephine Z. , Dimaraki Eleni V. , Young Elizabeth A. 
Published: June 2005

SummaryObjective  Major depression is associated to altered hypothalamic‐pituitary function. Stress is linked to elevated cortisol as well as menstrual cycle disturbance; however, there is no known relationship between depression and menstrual cycle disruption. The aim of this study was to investigate changes of growth hormone (GH) secretion during the menstrual cycle in normal and depressed women.Design  Case‐control study.Patients and methods  Nineteen women affected with depression and 24 normal controls were included. The two groups had comparable body mass index (BMI), and age (29·4 ± 9·8 vs. 28·6 ± 9·7 years). Nine depressed and 10 controls were studied in the follicular phase, while 10 depressed and 14 controls were studied in the luteal phase of the cycle. GH was sampled every 10 min for 24 h, and the data were analysed by the cluster pulse detection method.Results  There was no difference in 24‐h mean GH concentrations between depressed and control subjects (P = 0·93), even after accounting for menstrual cycle phase (P = 0·38). GH pulse frequency was higher during the follicular phase of the cycle (P = 0·032), and nocturnal GH was higher in the follicular phase of the cycle (P = 0·05, and after adjusting for 24‐h GH, P = 0·0138) regardless of whether the subjects were depressed or healthy.Conclusions  In studies of GH secretion in women with or without depression, it is necessary to control for the phase of menstrual cycle.
Morning cortisol does not mediate the association of size at birth with blood pressure in children born from full‐term pregnancies
Authors: Koupil Ilona , Mann Vera , Leon David A. , Lundberg Ulf , Byberg Liisa , Vågerö Denny 
Published: June 2005

AbstractObjective It had been suggested that programming of the hypothalamo‐pituitary‐adrenal axis may underlie the associations of reduced size at birth with raised blood pressure in later life. We investigated whether morning salivary cortisol mediates the inverse association of birthweight with systolic blood pressure in children.Design Subjects and measurements – a historical cohort study involving 1152 Swedish children aged 5–14 years, who took part in a family study comprised of mother, father, and two full‐sibs delivered in 1987–1995 after 38–41 weeks gestation within 36 months of each other. Birthweight and gestational age were available from obstetric records. Blood pressure, weight, height and puberty stage were measured at a clinic. Cortisol was measured by radioimmunoassay in morning salivary samples taken at home, within 30 min of waking.Results Morning cortisol showed a weak negative association with length of gestation in siblings, was not related to birthweight or to systolic or diastolic blood pressure. There was no change in the strength of the negative association between birthweight and systolic blood pressure on adjustment for cortisol (−1·4 mmHg/kg, 95% CI −2·7, −0·2; adjusted for age, sex, puberty stage, weight and height, and cortisol).Conclusions Morning cortisol was not associated with size at birth, and did not mediate the birthweight–blood pressure association in children born from full‐term pregnancies. It is possible that basal cortisol levels are of more importance in explaining associations of size at birth with later blood pressure in older subjects, or in populations with more varied length of gestation. Alternatively, our results may be caused by misclassification of the hypothalamo–pituitary‐adrenal activity.
Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism
Authors: Glintborg Dorte , Andersen Marianne , Hagen Claus , Hermann Anne Pernille 
Published: June 2005

SummaryObjective  The mechanisms leading to higher bone mineral density (BMD) in hirsute patients than in healthy controls have seldom been examined. We compared the metabolic, hormonal and bone metabolic parameters in hirsute patients and female controls and correlated BMD and bone metabolic parameters with testosterone, oestradiol and metabolic parameters.Patients  Fifty‐one Caucasian, reproductive‐aged, hirsute patients referred to the outpatient clinic of an academic tertiary‐care medical centre and 63 healthy, female Caucasian controls matched for season, weight and age.Measurements  BMD (hip, neck, lumbar and total BMD), bone metabolic parameters (osteocalcin, alkaline phosphatase, PTH, ionized calcium, phosphate and 25‐hydroxyvitamin D (25OHD)) and endocrine profiles (androgen status, oestradiol and insulin) were evaluated during follicular phase. Oestradiol measurement was repeated during cycle days 8–12.Results  Lumbar and neck BMD levels were significantly higher in hirsute patients than in controls: (mean ± SD): lumbar BMD 1·10 ± 0·12 vs. 1·06 ± 0·10 g/cm2 and neck BMD 0·91 ± 0·11 vs. 0·87 ± 0·12 g/cm2, P < 0·05. Fasting insulin and free testosterone levels were significantly higher in hirsute patients than in controls. Free testosterone correlated positively with neck and hip BMD levels in hirsute patients. During multiple regression analysis, testosterone, oestradiol and waist/hip ratio (WHR) were found to have positive effects on BMD levels independent of body mass index (BMI). 25OHD levels were significantly lower in hirsute patients [42 (13–131)] than in controls [72 (27–196)] nmol/l (geometric mean ± 2SD), P < 0·001].Conclusion  Hirsute patients demonstrated significantly higher bone mineral density levels than controls, which could be explained by hyperinsulinaemia and higher testosterone levels in hirsute patients compared with controls. The pathogenesis for significantly lower 25‐hydroxyvitamin D levels in hirsute patients compared with controls needs to be evaluated in future studies.
Adult growth hormone replacement therapy and neuroimaging surveillance in brain tumour survivors
Authors: Jostel Andreas , Mukherjee Annice , Hulse Paul A. , Shalet Stephen M. 
Published: June 2005

SummaryObjective  Systematic collections of neuroimaging data are nonexistent in brain tumour survivors treated with adult growth hormone replacement therapy (AGHRT). We present our surveillance data.Design  In 1993, our unit implemented a policy of performing brain scans on every brain tumour survivor before starting AGHRT, with repeat neuroimaging at least once after 12–18 months’ treatment. Reports for baseline scans and most recent scans were analysed for this retrospective study.Patients  All brain tumour survivors who received AGHRT (60 patients) were included in the analysis.Measurements  Evidence and extent of residual tumour, tumour progression, tumour recurrence, and secondary neoplasms (SN) on baseline scan and latest follow‐up scan.Results  All patients had baseline scans performed. Follow‐up scans were available in 41/45 (91%) patients who received AGHRT for more than 1 year (mean duration ± SD of GHRT was 6·7 ± 3·6 years). Sixteen patients had residual tumours, and SNs (all meningiomas) were demonstrated in three patients on baseline scans. Appearances remained stable in 34 (83%) patients during follow‐up (extending to 17·4 ± 8·3 years after tumour diagnosis). Of the 16 residual primary tumours, an incurable ependymoma continued to grow, and one meningioma progressed slightly in size over 7·7 years. Follow‐up scans also revealed continued growth of the SNs detected at baseline, and five additional meningiomas (two in patients with a previous SN, confirming an excess risk in this subgroup, P = 0·02). All SNs occurred on average 22·8 (range 17–37) years after radiotherapy.Conclusions  Our data do not suggest an increased rate of recurrence or progression of childhood brain tumours during AGHRT. Nonetheless, vigilance and long‐term surveillance are needed in these patients in order to detect and monitor SNs, in particular in patients with a previous history of a SN. We endorse a proactive neuroimaging policy, preferably as part of a larger, controlled trial in the future.
Overproduction of an amino‐terminal form of PTH distinct from human PTH(1–84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery
Authors: Räkel Agnès , Brossard Jean‐Hugues , Patenaude Jean‐Victor , Albert Caroline , Nassif Edgard , Cantor Tom , Rousseau Louise , D’Amour Pierre 
Published: June 2005

SummaryObjective  Rare patients with severe primary hyperparathyroidism present with large parathyroid tumours, severe hypercalcaemia, very high PTH levels and osteitis fibrosa cystica. Some of these patients display a large amount of C‐PTH fragments in circulation and present with a higher C‐PTH/I‐PTH ratio than seen in less severe cases of primary hyperparathyroidism. We wanted to determine how PTH levels and circulating PTH high‐performance liquid chromatography (HPLC) profiles analysed with PTH assays having different epitopes could be affected by medical and surgical treatment in such patients.Design  A 55‐year‐old man with severe hypercalcaemia (Ca2+: 2·01 mmol/l), very high PTH levels (CA‐PTH 82·1 and T‐PTH 72 pmol/l) caused by a large parathyroid tumour (7·35 g) and accompanied by significant bone involvement (alkaline phosphatase of 185 UI/l and subperiostal bone resorption of hands) was referred to us. Blood was obtained at various time points during his medical treatment, before and after surgery, to measure parameters of calcium and phosphorus metabolism, and of bone turnover. HPLC separations of circulating PTH molecular forms were performed and analysed with PTH assays having 1–4 (CA), 12–18 (T), 26–32 (E) and 65–84 (C) epitopes.Results  Before surgery, serum Ca2+ was nearly normalized with hydratation, intravenous (IV) pamidronate and oral vitamin D administration. Despite a decrease in Ca2+ to 1·31 mmol/l, CA‐PTH and T‐PTH levels decreased by half in relation to a threefold increase in basal 1,25‐dihydroxyvitamin D [1,25(OH)2D] level (94 to 337 pmol/l). After this initial positive response, hypercalcaemia and elevated CA‐ and T‐PTH levels recurred even if 1,25(OH)2D levels remained elevated. The tumour was removed surgically and proved to be poorly differentiated with nuclear atypia and mitosis. After surgery, the Ca2+ level and PTH secretion normalized. The higher CA‐PTH level relative to the T‐PTH level observed before surgery in this patient was related to the oversecretion of an amino‐terminal (N) form of PTH recognized by PTH assays with (1–4) or (26–32) epitopes but not by the T‐PTH assay with a (12–18) epitope. This molecular form represented 50% of CA‐PTH measured in this patient, but only 7% in less severe cases of primary hyperparathyroidism. It was unaffected by medical therapy and disappeared after surgery.Conclusion  The relationship between the overexpression of this N‐PTH molecular form and severe primary hyperparathyroidism remains unclear. Further studies will be required in these rare patients to see whether N‐PTH is a marker of less well differentiated parathyroid tumours and/or relates to the overproduction of C‐PTH fragments in the presence of severe hypercalcaemia.