bluuebunny/crossref_metadata_2025_split huggingface dataset:
The c.−1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients
Authors: Montes Ramón , Ruiz de Gaona Estefanía , Martínez‐González Miguel Ángel , Alberca Ignacio , Hermida José 
Published: February 2006

SummaryMuch of the variability in the sensitivity to warfarin in anticoagulated patients is associated with the c.−1639G > A polymorphism of the vitaminK‐epoxide reductase (VKORC1) gene. However, its association with the acenocoumarol dose in patients under anticoagulant therapy has not been studied. The c.−1639G > A genotype of VKORC1 was determined in 113 patients on stable anticoagulation requiring low (n = 42), medium (n = 42) or high (n = 21) acenocoumarol doses. To evaluate the association between acenocoumarol requirements and the c.−1639G > A variant, multivariate logistic regression models were fitted, adjusting for age, gender, and the c.430C > T and c.1075A > C variants of cytochrome P450 2C9 (CYP2C9). A total of 90·5% of the patients in the low acenocoumarol dose group carried the A allele of VKORC1:c.−1639G > A. The A allele independently increased the odds of requiring a low acenocoumarol dose [odds ratio (OR) 9·4; 95% confidence interval (CI) 1·9–46·4; P = 0·006], especially when the homozygous form was present (OR 44·2; 95% CI 5·5–354·6; P < 0·001). The A allele was less frequent in the high dose group showing an inverse association with the requirement for high doses (OR 0·04; 95% CI 0·01–0·22; P < 0·001). The A allele of the c.−1639G > A polymorphism of VKORC1 is therefore associated with a low‐dose requirement for acenocoumarol in patients receiving anticoagulant therapy.
Apolipoprotein E genotype is related to plasma levels of C‐reactive protein and lipids and to longevity in nonagenarians
Authors: Rontu Riikka , Ojala Petri , Hervonen Antti , Goebeler Sirkka , Karhunen Pekka J. , Nikkilä Matti , Kunnas Tarja , Jylhä Marja , Eklund Carita , Hurme Mikko , Lehtimäki Terho 
Published: February 2006

SummaryObjective  Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C‐reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians.Design and patients  This cross‐sectional study consisted of 291 Finnish nonagenarians and three previously described and genotyped control populations from the same area (i.e. newborns, 40‐year‐olds, and 70‐year‐olds).Results  In all nonagenarians and especially in women (P= 0.038), CRP level decreased linearly in the genotype order of ɛ2/2, ɛ2/3, ɛ3/3, ɛ2/4, ɛ3/4 and ɛ4/4. Total (P= 0.009) and low‐density lipoprotein (LDL) cholesterol (P = 0.076) levels, in turn, were increased in the ɛ4 allele carriers. In newborns, the ɛ4 frequency was 0.192, in 40‐year‐olds 0.181, in 70‐year‐olds 0.179 and in nonagenarians 0.095 (P < 0.0001). The decrease in the ɛ4 allele frequency in the elderly was more clearly seen in women than in men.Conclusions  APOEɛ4 allele seems to be associated with decreased inflammatory response as measured by CRP among nonagenarians. This finding may partly explain why some ɛ4 allele carriers can reach very old age despite increased risk of hypercholesterolaemia.
Quality of life in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomized controlled trial
Authors: Eustatia‐Rutten C. F. A. , Corssmit E. P. M. , Pereira A. M. , Frölich M. , Bax J. J. , Romijn J. A. , Smit J. W. A. 
Published: February 2006

SummaryObjective  The impact of prolonged subclinical hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH‐suppressive thyroxine therapy as a model for subclinical hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life.Design  We performed a prospective, single‐blinded, placebo‐controlled, randomized trial of 6 months’ duration with two parallel groups.Patients and methods  Twenty‐four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH‐suppressive therapy with L‐thyroxine completed the study. L‐thyroxine dose was replaced by study medication containing L‐thyroxine or L‐thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low‐TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires.Results  At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low‐TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low‐TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index‐20, P = 0·003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form‐36; P = 0·050) was observed. No improvement in the SDQ score was observed.Conclusion  In summary, quality of life in patients with DTC and long‐term subclinical hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.
Levels of dyslipidaemia and improvement in its management in England: results from the Health Survey for England 2003
Authors: Primatesta Paola , Poulter Neil R. 
Published: February 2006

SummaryObjective  To evaluate blood lipid levels in the adult English population and to report changes in the use and efficacy of lipid‐lowering treatment between 1998 and 2003.Design  Cross‐sectional surveys.Participants  Nationally representative sample of 8269 non‐institutionalized adults (≥ 16 years) living in England, taking part in the Health Survey for England 2003.Measurements  Mean levels of total, HDL, non‐HDL and total : HDL cholesterol ratio; prevalence of hypercholesterolaemia; use of lipid‐lowering agents and lipid levels among those on treatment; blood pressure. Information on smoking and history of cardiovascular events and diabetes were recorded by the interviewer.Results  In 2003 69·9% of adults had a total cholesterol ≥ 5 mmol/l and 6·2% reported lipid‐lowering treatment. Treatment rates among those with a total cholesterol ≥ 5 mmol/l and a history of coronary heart disease or stroke, hypertension or diabetes were 71·1%, 32·7% and 50·9%, respectively in men; and 55·8%, 22·4% and 50·0% in women. In all these groups, more than half of those treated were controlled (< 5 mmol/l).Only small changes in levels of dyslipidaemia were seen since 1998 (when 67·5% of adults had a total cholesterol ≥ 5 mmol/l), but use of lipid‐lowering treatment has more than doubled and control rates have increased by approximately fourfold.Conclusions  Treatment and control rates of lipids have improved importantly between 1998 and 2003 but remain suboptimal. Reductions in major cardiovascular events are likely to result from these changes and may be further enhanced by adherence to the new general practitioner contract.
The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males
Authors: De Rosa Michele , Ciccarelli Antonio , Zarrilli Stefano , Guerra Ermelinda , Gaccione Maria , Di Sarno Antonella , Lombardi Gaetano , Colao Annamaria 
Published: February 2006

SummaryBackground  Alterations of sperm number and motility are found in hyperprolactinaemic men. Cabergoline treatment reverses alterations in semen. No information is currently available on the quality of seminal tests in hyperprolactinemia in response to cabergoline treatment.Objective  To further investigate the effect of hyperprolactinaemia and its treatment with cabergoline on semen quality.Patients  Forty‐three men with hyperprolactinaemia (32 macro‐ and 11 micro‐prolactinomas); 60 healthy men served as control.Methods  Live spermatozoa count, sperm membrane function, kinetic index, nuclear DNA integrity, sperm curvilinear and linear velocity and amplitude of lateral movement of the sperm head were investigated before and after 6 and 24 months of treatment with cabergoline.Study design  Open prospective.Results  At study entry, semen functional tests were severely and similarly impaired both in patients with macro‐ and micro‐prolactinomas compared to controls. After 6 and 12 months of treatment there was a significant improvement of semen quality in patients achieving normalization of prolactin levels, although most of the parameters remained lower than in controls. After 24 months of treatment, seminal fluid characteristics were similar to the controls except for live spermatozoa count, sperm membrane function, sperm kinetic index and sperm nuclear DNA integrity, which remained abnormal in 9·3–53% of the patients.Conclusions  Twenty‐four months of cabergoline treatment restored gonadal function in 66·7% of men with hyperprolactinaemia.
Personality characteristics and quality of life in patients treated for Cushing's syndrome
Authors: Sonino Nicoletta , Bonnini Stefano , Fallo Francesco , Boscaro Marco , Fava Giovanni A. 
Published: February 2006

SummaryObjective  Psychological distress does not always disappear upon proper endocrine treatment of Cushing's syndrome, and quality of life may still be compromised. Little is known on the personality correlates that may be involved. The aim of this study was to provide a controlled assessment of personality characteristics and quality of life in patients successfully treated for Cushing's syndrome.Design  A single‐centred, controlled, prospective study.Patients  Twenty‐four consecutive outpatients who were in remission upon proper treatment of Cushing's syndrome for at least 1 year and no more than 3 years (20 with pituitary‐dependent Cushing's disease and four with a cortisol‐secreting adrenal adenoma; 5 M/19 F; mean age 34·5, SD = 10·6; range 18–57 years) were compared with 24 healthy control subjects matched for sociodemographic variables.Measurements  Both patients and controls were administered two self‐rating scales:

tridimensional personality questionnaire (TPQ), a 100‐item inventory that yields three scales: novelty seeking, harm avoidance and reward dependence.
symptom rating test (SRT), a 46‐item scale for assessing psychological distress and quality of life with six subscales (anxiety, depression, somatic symptoms, anger‐hostility, cognitive symptoms, psychotic symptoms).

Results  There were no significant differences in personality dimensions, as measured by the TPQ, between patients and controls. The results did not change when the four patients with an adrenal adenoma were excluded and only the 20 with pituitary‐dependent Cushing's disease were considered. As to the SRT scale, patients with Cushing's syndrome displayed significantly higher scores in anxiety (P= 0·046), depression (P= 0·013), and psychotic symptoms (P= 0·006), with a generalized compromised quality of life (P= 0·02). Again, no differences were found in evaluating the 20 patients with Cushing's disease separately.Conclusions  Even though personality traits other than those explored here may be involved, the results seem to exclude the presence of latent dysfunctional attitudes and beliefs contributing to long‐standing psychological disturbances, even in the pituitary‐dependent form of Cushing's syndrome. Data from larger populations might provide further insight in this field. The findings of a compromised quality of life are in agreement with the recent literature and have implications for the long‐term management of patients.
Frequent occurrence of pituitary apoplexy in patients with non‐functioning pituitary adenoma
Authors: Nielsen E. Husted , Lindholm J. , Bjerre P. , Christiansen J. Sandahl , Hagen C. , Juul S. , Jørgensen J. , Kruse A. , Laurberg P. 
Published: February 2006

SummaryBackground and objective  There is agreement in the literature that pituitary apoplexy is a rare disorder. As our experience differs from this view, we analysed the incidence in patients operated on for a nonfunctioning pituitary adenoma.Patients and design  One hundred ninety‐two consecutive patients with a suprasellar, clinically inactive adenoma operated on during the period 1985–1996 were retrospectively reviewed. A diagnosis of pituitary apoplexy was made from relevant neurological symptoms together with pertinent findings at operation.Results  Pituitary apoplexy occurred in 41 patients (21%), in 23 patients within 12 days prior to the operation. The male/female ratio was 1·9. Median follow‐up time was 13·7 years (range 8·9–19·9). During this period, 12 patients had died, yielding a standard mortality ratio of 1·09 (95% CI 0·62–1·92), similar to that in the patients who had not sustained pituitary apoplexy. Postoperatively, 24% of the patients had normal pituitary function, 38% were panhypopituitary and partial pituitary insufficiency was present in 38%. Subnormal GH secretion was present in virtually all patients tested. Two patients died within 60 days of surgery and in two no or incomplete data were available, although they most likely were panhypopituitary.Conclusion  Most of our findings add little to what is known about pituitary apoplexy. On one point, however, they are contrary to previously presented data. We found a much higher incidence of pituitary apoplexy despite rather rigorous criteria for the diagnosis. The outcome as regards survival and endocrine function was not different from that in patients with a nonfunctioning adenoma who did not suffer pituitary apoplexy.
High variability in CYP21A2 mutated alleles in Spanish 21‐hydroxylase deficiency patients, six novel mutations and a founder effect
Authors: Loidi Lourdes , Quinteiro Celsa , Parajes Silvia , Barreiro Jesús , Lestón Domingo G. , Cabezas‐Agrícola José M. , Sueiro Aurelio M. , Araujo‐Vilar David , Catro‐Feijóo Lidia , Costas Javier , Pombo Manuel , Domínguez Fernando 
Published: February 2006

SummaryObjective To detect common as well as rare and novel CYP21A mutations in 21‐hydroxylase deficiency patients. To estimate the distribution of mutations and compare them with other European studies. To construct haplotypes linked to a recurrent novel mutation.Design Genetic analysis by sequencing the entire CYP21A2 gene plus Southern blot.Patients A total of 138 unrelated Spanish patients: 122 nonclassical forms (NCF) and 16 classical forms (CF) were studied.Results Among the 266 nonrelated mutated alleles; CYP21A2 deletions/conversions and a spectrum of 27 different mutated alleles were found: 15 different single point mutations, 8 nucleotide deletions in exon 3, 3 mutation clusters in exon 6, 9 alleles with more than one mutation, one 21‐nucleotide duplication in exon 10, and one allele with CYP21A2 duplicated and both copies mutated. The most frequent mutation in NCF alleles is V281L (71·8%). Among CFs, the most common is I2 g (20%) and Q318X (16%) and rare alleles (21·9%). Six novel causative mutations were found, four associated with CF: I46+1nt, R444X, P463L and M473_R479dup and two associated with NCF: W302 and D322G. The R444X mutation was found in seven unrelated patients and it appeared only once in an ancestral haplotype. In addition, we found a novel single nucleotide polymorphism with a 31·5% frequency for the rare allele.Conclusion A great diversity of haplotypes with a large spectrum of mutated alleles was found. The frequency of the V281L mutation was the highest reported and the relatively high frequency of R444X was the result of a founder effect.
First‐line octreotide‐LAR therapy induces tumour shrinkage and controls hormone excess in patients with acromegaly: results from an open, prospective, multicentre trial
Authors: Colao Annamaria , Pivonello Rosario , Rosato Francesca , Tita Patrizia , De Menis Ernesto , Barreca Antonina , Ferrara Roberto , Mainini Franco , Arosio Maura , Lombardi Gaetano 
Published: February 2006

SummaryBackground  The majority of patients with acromegaly have large tumours and the outcome of conventional management remains poor.Objective  To investigate the clinical application of octreotide‐LAR as primary treatment in newly diagnosed patients with GH‐secreting pituitary tumours.Design  Open, prospective, multicentre, 24‐week follow‐up study.Patients  Thirty‐four patients were enrolled (20 men, 14 women; mean age, 50 years); 13 had microadenoma [median tumour volume 327 mm3 (range 31–629 mm3)], 21 had macroadenoma [median tumour volume 1325 mm3 (range 503–11583 mm3)].Interventions  Octreotide‐LAR at the dosage of 20 mg every 28 days for the first 12 weeks increased to 30 mg every 28 days to control GH and/or IGF‐I excess in 20 patients (64·7%).Main outcome measures  Primary endpoints were control of GH (fasting < 2·5 µg/l) and IGF‐I secretion (gender‐ and age‐normalized) and presence and entity of tumour mass shrinkage. Secondary endpoint was improvement of symptoms score.Results  In patients with micro‐ and macroadenomas GH levels decreased to < 2·5 µg/l in 84·6% and 45%, serum IGF‐I levels normalized for age and gender in 61·5% and 35% of cases. Failure in achieving either GH < 2·5 µg/l or normal IGF‐I levels was found in none of the patients with micro‐ and in 45% of patients with macroadenoma. Median tumour volume was reduced by 54% (range: −90% to +350%) in micro‐ and by 49% (range −94% to −14%) in macroadenomas. Headache, perspiration and osteo‐arthralgias disappeared in 21%, paresthesias in 38%, fatigue in 26% and carpal tunnel syndrome in 15%. The treatment was well tolerated: more frequent adverse events were gastrointestinal (in 44%).Conclusions  In both patients with micro‐ or macroadenoma, primary octreotide‐LAR treatment controls hormone excess, induces tumour shrinkage and improves symptoms of acromegaly with limited side effects and can be therefore successfully employed in patients with contraindications for surgery or in those who refuse surgery.
Soil moisture, carbon and nitrogen dynamics following incorporation and surface application of labelled crop residues in soil columns
Authors: Coppens F. , Garnier P. , De Gryze S. , Merckx R. , Recous S. 
Published: February 2006

SummaryOne way to increase the amount of carbon sequestered in agricultural land is to convert conventional tillage into no‐tillage systems. This greatly affects the location of crop residues in soil. To investigate the impact of the location of residues on soil physical and biological properties and how the interactions between those properties influence the fate of carbon and nitrogen in soil, we did a laboratory experiment with repacked soil in columns. Doubly labelled 13C15N oilseed rape residues were incorporated in the 0–10 cm layer or left on the soil surface. The columns were incubated for 9 weeks at 20°C and were submitted to three cycles of drying and wetting, each of them induced by a rain simulator. The location of the residues affected the water dynamics and the distribution of C and N in the soil, which in turn influenced microbial activity and the decomposition rate of the added residues. After 9 weeks of’incubation, 18.4 ± 1.5% of the surface applied residue‐C and 54.7 ± 1.3% of the incorporated residue‐C was mineralized. We observed a nitrate accumulation of 10.7 mg N kg−1 with residues at the soil surface, 3.6 mg N kg−1 with incorporated residues and 6.3 mg N kg−1 without addition of fresh organic matter, which entailed net N mineralization in soil under mulch and immobilization of N with residue incorporation compared with the control soil. We concluded that application of oilseed rape residues at the soil surface increased the storage of fresh organic C in soil in the short term, compared with the incorporation treatment, but increased the risk of nitrate leaching.
A pattern‐based approach for multiple removal applied to a 3D Gulf of Mexico data set
Authors: Guitton Antoine 
Published: February 2006

ABSTRACTSurface‐related multiples are attenuated for one sail line and one streamer of a 3D data set (courtesy of Compagnie Générale de Géophysique). The survey was carried out in the Gulf of Mexico in the Green Canyon area where salt intrusions close to the water‐bottom are present. Because of the complexity of the subsurface, a wavefield method incorporating the full 3D volume of the data for multiple removal is necessary. This method comprises modelling of the multiples, where the data are used as a prediction operator, and a subtraction step, where the model of the multiples is adaptively removed from the data with matching filters. The accuracy of the multiple model depends on the source/receiver coverage at the surface. When this coverage is not dense enough, the multiple model contains errors that make successful subtraction more difficult. In these circumstances, one can either (1) improve the modelling step by interpolating the missing traces, (2) improve the subtraction step by designing methods that are less sensitive to modelling errors, or (3) both. For this data set, the second option is investigated by predicting the multiples in a 2D sense (as opposed to 3D) and performing the subtraction with a pattern‐based approach. Because some traces and shots are missing for the 2D prediction, the data are interpolated in the in‐line direction using a hyperbolic Radon transform with and without sparseness constraints. The interpolation with a sparseness constraint yields the best multiple model. For the subtraction, the pattern‐based technique is compared with a more standard, adaptive‐subtraction scheme. The pattern‐based approach is based on the estimation of 3D prediction‐error filters for the primaries and the multiples, followed by a least‐squares estimation of the primaries. Both methods are compared before and after prestack depth migration. These results suggest that, when the multiple model is not accurate, the pattern‐based method is more effective than adaptive subtraction at removing surface‐related multiples while preserving the primaries.