bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcitonin gene-related peptide and islet amyloid polypeptide stimulate insulin secretion in RINm5F cells through a common receptor coupled to a generation of cAMP
Authors: Barakat A. , Skoglund G. , Boissard C. , Rosselin G. , Marie J.-C. 
Published: July 2005

The question as to whether the homologous peptides CGRP and IAPP can regulate insulin secretion in RINm5F cells was addressed. Chicken CGRP displayed a reproducible inhibitory effect on insulin secretion within 0.1 and 1 nM concentrations and a stimulatory effect at higher concentrations. The maximal stimulatory effects on insulin secretion were obtained with 1.0 μM of chicken CGRP (cCGRP), human α-CGRP (h α-CGRP) and human IAPP (hIAPP) which caused 246 ± 22, 302 ± 63 and 224 ± 14 percent increases of control levels, respectively (p &lt; 0.001). Similarly, maximal accumulations of cAMP were obtained with 1.0 μM of cCGRP, h α-CGRP and hIAPP with the respective percent increases of control levels of 587 ± 24, 436 ± 41 and 410 ± 25 (p &lt; 0.005). Thus the stimulatory effects on insulin secretion in RINm5F cells by cCGRP, h α-CGRP and hIAPP appear to be mediated by the cAMP pathway. Chicken CGRP, the most potent peptide tested, displayed a correlated dose response stimulation of intracellular cAMP and insulin release within the concentration range of 10–1000nM. The EC50 values of cCGRP for cAMP accumulation and insulin release were similar (20nM and 10 nM respectively). The stimulatory effect of IAPP on cAMP was not additive with that of cCGRP suggesting that IAPP action was mediated by CGRP receptors. This hypothesis was further sustained by a preferential inhibition of125I[His]h α-CGRP binding to RINm5F cells by cCGRP as compared to IAPP.
We conclude that CGRP and IAPP, through a direct action on a chicken CGRP preferring receptor present in β cells, stimulated insulin by a cAMP mediated pathway.
10‐year follow‐up of chronic non‐malignant pain patients: Opioid use, health related quality of life and health care utilization
Authors: Jensen Marianne K. , Thomsen Annemarie B. , Højsted Jette 
Published: July 2005

AbstractBackgroundIn Denmark, opioids have been used liberally for many years in the treatment of non‐malignant pain, but long‐term consequences as tolerance and influence on health related quality of life remain unknown.AimAdherence to medical treatment, opioid dose escalation, health related quality of life, anxiety, depression, coping strategies and health care utilization were evaluated in chronic pain patients 10 years after treatment in a multidisciplinary pain centre.MethodsInformation was gathered from medical records, postal questionnaires and a central hospital register.ResultsOpioid dose escalation occurred in only a few patients. Increase and decrease in opioid dose were almost equally frequent. Sixty percent of those discharged on long acting opioids were still on that treatment at follow‐up. Twenty‐eight percent of the patients initiated opioid treatment after discharge from the pain centre. Occupational status was identified as a determining factor for future opioid use. Opioid users had a lower health related quality of life, higher occurrence of depression and more frequent use of coping strategies like ‘Catastrophizing’ and ‘Hoping and Praying'. Adjuvant analgesics were highly discontinued. Multidisciplinary pain treatment reduced the number of hospital admissions and in‐hospital days.ConclusionWe recommend that future research on opioid treatment does not only focus on biological issues. The effect of opioids needs to be viewed in a much more complex context where consequences like health related quality of life, depression and the role of various coping strategies are included.
Volume conductor effects involved in the genesis of the P wave
Authors: van Dam Peter M. , van Oosterom Adriaan 
Published: July 2005

Abstract

Aim
To assess the effect of inhomogeneities in the conductivity of different tissues, such as blood and lung tissue, on the body surface potentials generated by atrial electrical activity.

Methods
A 64-lead ECG from a healthy subject was recorded. The subject's geometries of torso, lungs, heart, and blood cavities were derived by magnetic resonance imaging. These geometries were used to construct a numerical volume conductor model. The boundary element method was applied to simulate the potentials on the surface of the thorax generated by the atria. The equivalent double layer served as the source description during depolarization. Recorded body surface potentials were used as a check on the simulations. Subsequently, the conductivities in the model were varied to determine their influence on P wave morphology and amplitude.

Results
The model with realistic conductivity values for blood and lungs produced potentials that closely matched the measured ones (correlation 98%). The subsequent variation of conductivity of blood and lungs revealed a major influence on P wave morphology and amplitude: a mean reduction in amplitude by 42%, with pronounced inter-lead differences.

Conclusion
The inhomogeneities of lungs and atrial blood cavities need to be incorporated in volume conductor models linking atrial electric activity to body surface potentials.
Anatomy of the inferior interatrial route in humans
Authors: Mitrofanova Lubov , Ivanov Vitaly , Platonov Pyotr G. 
Published: July 2005

AbstractAimsTo explore the morphology of the proximal coronary sinus (CS) and the surrounding tissues in order to identify possible routes for interatrial conduction.MethodSpecimens containing interatrial septum and proximal CS were taken from 21 necropsied hearts and sliced into 10-μm thick parallel histological sections in 1-mm steps starting from the valve plane, up to the atrial roof (40–80 sections per heart). The sections were stained with van Gieson's stain.ResultsMedia in the proximal CS consists of smooth muscle cells that do not form a continuous layer. CS was not surrounded by striated atrial myocardium in 10 specimens in which posterior CS wall was covered by epicardial fat only. In seven specimens, striated muscle bundles of up to 2-mm width connected the myocardium surrounding the CS with the left atrium. Regardless of their presence, variable posterior and/or anterior interatrial muscular connections were identified in all specimens.ConclusionVariability of the striated atrial myocardium surrounding proximal CS may affect interatrial conduction. Striated muscular fascicles connecting the proximal CS with the left atrium are not obligatory cardiac structures and may be considered as supplementary to the larger interatrial connections outside the CS.
Modelling of short QT syndrome in a heterogeneous model of the human ventricular wall
Authors: Weiss Daniel L. , Seemann Gunnar , Sachse Frank B. , Dössel Olaf 
Published: July 2005

Abstract

Aims
A percentage of sudden cardiac death events occur in individuals with structurally normal hearts due to an abnormality in the ion channel activity. While the majority of these hereditary syndromes are well-established, little is known about the significance of the short QT syndrome.

Methods
This study is based on discovered insights into the molecular basis of the originally described form of this disease. A biophysically detailed model of cellular electrophysiology was adapted to emulate the behaviour of cells affected by the short QT syndrome. Simulations were performed in single cell and homogeneous as well as heterogeneous anisotropic multi-cellular environment describing the human left ventricle.

Results
The short QT mutation increased the activity of the repolarizing outward potassium current IKr. The heterogeneous abbreviation of the action potential duration decreased the dispersion of repolarization in heterogeneous tissue. Repolarization was homogenized and the final repolarization was shifted to epicardial sites. The transmural ECG showed a shortened QT interval and a T wave with reduced amplitude.

Conclusion
The altered characteristics of the mutant IKr current were consistent with experimental findings. The heterogeneous reduction of the action potential duration and the reduced T wave amplitude need to be verified by measurements.
Can orthogonal lead indicators of propensity to atrial fibrillation be accurately assessed from the 12-lead ECG?
Authors: Carlson Jonas , Havmöller Rasmus , Herreros Alberto , Platonov Pyotr , Johansson Rolf , Olsson Bertil 
Published: July 2005

Abstract

Aims
When analyzing P-wave morphology, the vectorcardiogram (VCG) has been shown useful to identify indicators of propensity to atrial fibrillation (AF). Since VCG is rarely used in the clinical routine, we wanted to investigate if these indicators could be accurately determined in VCG derived from standard 12-lead ECG (dVCG).

Methods
ECG and VCG recordings from 21 healthy subjects and 20 patients with a history of AF were studied. dVCG was calculated from ECG using the inverse Dower transform. Following signal averaging of P-waves, comparisons were made between VCG and dVCG, where three parameters characterizing signal shape and 15 parameters describing the P-wave morphology were used to assess the compatibility of the two recording techniques. The latter parameters were also used to compare the healthy and the AF groups.

Results
After transformation, P-wave shape was convincingly preserved. P-wave morphology parameters were consistent within the respective groups when comparing VCG and dVCG, with better preservation observed in the healthy group.

Conclusion
VCG derived from routine 12-lead ECG may be a useful alternate method for studying orthogonal P-wave morphology.
The influence of spatio-temporal egg production variability on the modelled survival of the early life history stages of mackerel (Scomber scombrus) in the eastern North Atlantic
Authors: Bartsch Joachim 
Published: July 2005

Abstract
An individual-based model (IBM) that simulates the transport, growth, and mortality of mackerel (Scomber scombrus) eggs and larvae, is used to determine the modelled survival of mackerel post-larvae in the eastern North Atlantic. Larval and post-larval growth is modelled as a function of length, temperature, and food distribution; mortality is modelled as a function of length and absolute growth rate. Simulations have previously been carried out for the years 1998, 1999, and 2000, in all cases using the same 1998 initial egg distribution as the input field. In the present contribution, the effects of varying the input field are examined by comparing simulations for 1998 and 2001 using initial egg distributions for 1998 and 2001, respectively, and also for a 2001 simulation using the 1998 egg data as input. Results showed that, for the first two cases, the estimated number of survivors for the years 1998 and 2001 was similar, although total egg production (i.e. the magnitude of the input field) in 2001 was only ∼65% of that during 1998. The higher relative survival rate in 2001 results from differences in the timing of peak production, which was 5 weeks later in 2001 than in 1998, and also from greater overall food availability in 2001. Modelling survival for 2001 using 1998 egg data as the initial input field “wrongly” increases survival by 60% compared with using actual 2001 egg data for initialization. This is mainly a function of the increased egg production in 1998 compared with 2001.
Temporal evolution of sediment supply in Lago Puyehue (Southern Chile) during the last 600 yr and its climatic significance
Authors: Bertrand Sébastien , Boës Xavier , Castiaux Julie , Charlet François , Urrutia Roberto , Espinoza Cristian , Lepoint Gilles , Charlier Bernard , Fagel Nathalie 
Published: July 2005

AbstractShort-term climate changes in Southern Chile are investigated by a multi-proxy analysis of a 53-cm-long sedimentary sequence selected among eight short cores retrieved in Lago Puyehue (Chile, 40°S). This core contains a 600-yr-long undisturbed record of paleo-precipitation changes. Two measurement methods for sediment density, organic matter and biogenic silica contents are compared and the most appropriate techniques are selected. Together with aluminium and titanium concentrations, grain size and geochemical properties of the organic matter, these proxies are used to demonstrate paleo-precipitation changes around 40°S. Increase of terrigenous particle supply between A.D. 1490 and A.D. 1700 suggests a humid period. Contemporaneously, δ13C data show increasing lake productivity, in response to the high nutrient supply. The A.D. 1700–1900 interval is characterized by a decreasing terrigenous supply and increasing δ13C values, interpreted as a drying period. The magnetic susceptibility signal, reflecting the terrigenous/biogenic ratio, demonstrates that similar variations occur in all the undisturbed sedimentary environments of Lago Puyehue. The A.D. 1490–1700 wet period is associated with the onset of the European Little Ice Age (LIA) and interpreted as its local signature. This work supports the fact that the LIA was a global event, not only restricted to the Northern Hemisphere.
Electrogene transfer of an Epstein–Barr virus‐based plasmid replicon vector containing the diphtheria toxin A gene suppresses mammary carcinoma growth in SCID mice
Authors: Shibata Masa‐Aki , Miwa Yoshihiro , Miyashita Minoru , Morimoto Junji , Abe Hideaki , Otsuki Yoshinori 
Published: July 2005

Experimental mammary cancer therapy in mice was conducted using electrogene transfer of a non‐viral EBV‐based plasmid vector (reduced size of the oriP gene), containing the DT‐A gene. Because the EBV‐based plasmid vector exhibits high transfer efficiency and strong persistent transgene expression due to autonomous replication in human cells, it is particularly suitable as a tool for cancer gene therapy. In vitro, 79% of MDA‐MB231 human mammary carcinoma cells died as a result of the EBV‐based vector containing DT‐A (pEB‐DTA) by 48 h after transfection. DNA synthesis was also significantly decreased as compared to levels with a control vector. In vivo, mammary tumors induced by inoculation of SCID mice with MDA‐MB231 cells were subsequently treated by direct injection of pEB‐DTA vector or pEB‐GFP vector as a control once a week for 5 weeks. After each injection, the tumors were subjected to in vivo electrogene transfer. Significantly reduced tumor volumes were observed for the pEB‐DTA group in experimental week 1 and thereafter throughout the study. At necropsy, strong and extent expression of GFP was still observed in tumors receiving pEB‐GFP 6 days after the last electrogene transfer. The ratio of histological necrotic area to viable area was significantly increased in the pEB‐DTA‐treated tumors, where levels of apoptosis were significantly higher than those observed in the pEB‐GFP group. DNA synthesis showed a tendency to decrease in the pEB‐DTA group but this was not significant. The incidence and multiplicity of lung metastasis were similar between the groups. There was also no difference in the density of microvessels between groups. We therefore conclude that the EBV‐based plasmid vector system combined with in vivo electrogene transfer can result in efficient gene transfection and that the non‐viral replicon vector containing DT‐A suppresses tumor growth due to apoptotic cell death in this model. (Cancer Sci 2005; 96: 434–440)
Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and gastric cardia
Authors: RUBENSTEIN J. H. , DAVIS J. , MARRERO J. A. , INADOMI J. M. 
Published: July 2005

SummaryBackground:  Obesity is a risk factor for adenocarcinomas of the oesophagus and gastric cardia. Diabetes mellitus might mediate that association.Aim:  To estimate the risk of diabetes mellitus on the development of adenocarcinoma of distal oesophagus and gastric cardia beyond that of gastro‐oesophageal reflux disease.Methods:  A case–control study was performed using a national administrative database of the Veterans Administration.Results:  A total of 311 cases of cancer and 10 154 controls were identified. Gender, age, and race were risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of controls (P = 0.60). Multiple logistic regression confirmed the absence of an association between cancer and diabetes (odds ratio 1.1, 95% confidence interval 0.8–1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6–1.3), adjusting for age, gender, and race.Conclusions:  Within the limitations of this case–control study, there is no evidence of an association between diabetes and adenocarcinoma of the oesophagus or gastric cardia among US veterans with gastro‐oesophageal reflux disease.
α‐fetoprotein response predicts survival benefits of thalidomide in advanced hepatocellular carcinoma
Authors: CHEN L.‐T. , LIU T.‐W. , CHAO Y. , SHIAH H.‐S. , CHANG J.‐Y. , JUANG S.‐H. , CHEN S.‐C. , CHUANG T.‐R. , CHIN Y.‐H. , WHANG‐PENG J. 
Published: July 2005

SummaryBackground: Radiographic measurements do not always reflect the biological response of hepatocellular carcinoma to drug therapy.Aims: To evaluate the clinical implications of tumour marker (α‐fetoprotein) response in advanced hepatocellular carcinoma patients with thalidomide treatment.Patients and methods: Forty‐two advanced hepatocellular carcinoma patients with baselineα‐fetoprotein levels above 200 ng/mL and thalidomide therapy were included. Serumα‐fetoprotein levels were measured every 4 weeks.α‐fetoprotein response was defined as a 50% or greater reduction ofα‐fetoprotein levels for 4 or more weeks during treatment. Radiographic response was assessed by World Health Organization criteria; survivals were estimated by Kaplan–Meier method and prognostic factors were assessed by Cox's proportional hazard model.Results: With intention‐to‐treat analysis, radiographic response andα‐fetoprotein response were obtained in 7% (three of 42, 95% confidence interval: 0–15) and 24% (10 of 42, 95% CI: 10–38) of patients, respectively. All radiographic response was observed inα‐fetoprotein responders. Multivariate analyses showedα‐fetoprotein response was independent prognostic factor for both progression‐free survival (relative risk = 0.394, 95% CI: 0.189–0.820,P = 0.013) and overall survival (relative risk = 0.241, 95% CI: 0.096–0.606,P =0.003), whereas radiographic response was not.Conclusion: α‐fetoprotein response can more accurately reflect the biological response of advanced hepatocellular carcinoma to thalidomide therapy than radiographic response.
Daily treatment with esomeprazole is superior to that taken on‐demand for maintenance of healed erosive oesophagitis
Authors: SJÖSTEDT S. , BEFRITS R. , SYLVAN A. , HARTHON C. , JÖRGENSEN L. , CARLING L. , MODIN S. , STUBBERÖD A. , TOTH E. , LIND T. 
Published: July 2005

SummaryBackground:  On‐demand therapy with esomeprazole is effective for long‐term treatment of non‐erosive gastro‐oesophageal reflux disease, but it has not been evaluated in erosive gastro‐oesophageal reflux disease.Aims:  To compare endoscopic and symptomatic remission over a 6‐month period when patients with healed erosive gastro‐oesophageal reflux disease are treated with esomeprazole 20 mg, either once daily or on‐demand.Methods:  Patients with verified erosive reflux oesophagitis of Los Angeles grades A–D were enrolled. Following 4–8 weeks treatment with esomeprazole 40 mg daily, those who were endoscopically healed and had symptom control during the last week were randomized to maintenance therapy for 6 months with esomeprazole 20 mg, taken either once daily or on‐demand.Results:  Of 539 enrolled patients, 494 (91%) were healed at 8 weeks and 477 were randomized to maintenance therapy with esomeprazole 20 mg, 243 once daily and 234 on‐demand. After once daily treatment, 81% of patients were still in remission at 6 months, compared with only 58% who took on‐demand treatment (P < 0.0001). A difference in remission was found irrespective of baseline grade of oesophagitis, but it was more pronounced for the more severe grades. There was no difference in overall symptomatic remission between the two treatments, although heartburn was significantly more prevalent in the on‐demand group.Conclusions:  Once daily esomeprazole 20 mg was better than that taken on‐demand for maintaining healed erosive oesophagitis, regardless of baseline Los Angeles grade.
Continuing challenges in childhood non‐Hodgkin's lymphoma
Authors: Pinkerton Ross 
Published: July 2005

SummaryNon‐Hodgkin's lymphoma in children includes a number of different pathological subtypes and, with improved diagnostic techniques and better understanding of the natural history of each type, treatment strategies have become more tumour‐specific. Original staging systems are now less useful in determining treatment stratification and there is a need for careful analysis of large cohorts of patients, treated in the same manner, to determine the clinical and biological features that, with current therapies, are of prognostic value. Novel imaging techniques, such as positron emission tomography, and molecular techniques to detect low‐level marrow involvement are likely to be incorporated into new risk grouping. These will be used to determine the extent of initial disease and evaluate more accurately the speed and quality of response to chemotherapy. With high cure rates, it becomes particularly important to minimize late effects of therapy and the introduction of monoclonal antibodies in combination with chemotherapy may provide a method for improving outcome in poor risk groups and reducing sequelae by allowing reduction in chemotherapy in good risk patients.
Efficacy of the interleukin‐2 receptor antagonist basiliximab in steroid‐refractory acute graft‐versus‐host disease
Authors: Schmidt‐Hieber Martin , Fietz Thomas , Knauf Wolfgang , Uharek Lutz , Hopfenmüller Werner , Thiel Eckhard , Blau Igor Wolfgang 
Published: July 2005

SummaryAcute graft‐versus‐host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant‐related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid‐refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin‐2 (IL‐2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty‐three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82·5% with four patients (17·5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL‐2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1‐year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid‐refractory aGVHD and merits further evaluation.