bluuebunny/crossref_metadata_2025_split huggingface dataset:
Willingness to pay to assess patient preferences for therapy in a Canadian setting
Authors: Marra Carlo A , Frighetto Luciana , Goodfellow Alan F , Wai Amy O , Chase M Lynn , Nicol Ruth E , Leong Carole A , Tomlinson Sally , Ferreira Barbara M , Jewesson Peter J 
Published: June 2005

Abstract
Background
Adult outpatient parenteral antibiotic therapy (OPAT) programs have been reported in the literature for over 20 years, however there are no published reports quantifying preference for treatment location of patients referred to an OPAT program. The purpose of this study was to elicit treatment location preferences and willingness to pay (WTP) from patients referred to an OPAT program.

Methods
A multidisciplinary, single centre, prospective study at a 1000-bed Canadian adult tertiary care teaching hospital. This study involved a WTP questionnaire that was administered over a 9-month study period. Eligible and consenting patients referred to the OPAT program were asked to state their preference for treatment location and WTP for a hypothetical treatment scenario involving intravenous antibiotic therapy. Multiple linear regression analysis was performed to determine predictors of WTP.

Results
Of 131 eligible patients, 91 completed the WTP questionnaire. The majority of participants were males, married, in their sixth decade of life and had a secondary school education or greater. The majority of participants were retired or they were employed with annual household incomes less than $60,000. Osteomyelitis was the most common type of infection for which parenteral therapy was required. Of those 87 patients who indicated a preference, 77 (89%) patients preferred treatment at home, 10 (11%) patients preferred treatment in hospital. Seventy-one (82%) of these patients provided interpretable WTP responses. Of these 71 patients, 64 preferred treatment at home with a median WTP of $490 CDN (mean $949, range $20 to $6250) and 7 preferred treatment in the hospital with a median WTP of $500 CDN (mean $1123, range $10 to $3000). Tests for differences in means and medians revealed no differences between WTP values between the treatment locations. The total WTP for the seven patients who preferred hospital treatment was $7,859 versus $60,712 for the 64 patients who preferred home treatment. Income and treatment location preference were independent predictors of WTP.

Conclusion
This study reveals that treatment at home is preferred by adult inpatients receiving intravenous antibiotic therapy that are referred to our OPAT program. Income and treatment location appear to be independently associated with their willingness to pay.
Unhappy doctors? A longitudinal study of life and job satisfaction among Norwegian doctors 1994 – 2002
Authors: Nylenna Magne , Gulbrandsen Pål , Førde Reidun , Aasland Olaf G 
Published: June 2005

Abstract

Background
General opinion is that doctors are increasingly dissatisfied with their job, but few longitudinal studies exist. This study has been conducted to investigate a possible decline in professional and personal satisfaction among doctors by the turn of the century.

Methods
We have done a survey among a representative sample of 1 174 Norwegian doctors in 2002 (response rate 73 %) and compared the findings with answers to the same questions by (most of) the same doctors in 1994 and 2000. The main outcome measures were self reported levels of life satisfaction and job satisfaction according to the Job Satisfaction Scale (JSS).

Results
Most Norwegian doctors are happy. They reported an average life satisfaction of 5.21 in 1994 and 5.32 in 2002 on a scale from 1 (extremely dissatisfied) to 7 (extremely satisfied). Half of the respondents reported a very high level of general life satisfaction (a score of 6 or 7) while only one third said they would have reported this high level of satisfaction five years ago. The doctors thought that they had a higher level of job satisfaction than other comparable professional groups. The job satisfaction scale among the same doctors showed a significant increase from 1994 to 2002. Anaesthesiologists and internists reported a lower and psychiatrists and primary care doctors reported a higher level of job satisfaction than the average.

Conclusion
Norwegian doctors seem to have enjoyed an increasing level of life and job satisfaction rather than a decline over the last decade. This challenges the general impression of unhappy doctors as a general and worldwide phenomenon.
Statins research unfinished saga: desirability versus feasibility
Authors: Fisman Enrique Z , Adler Yehuda , Tenenbaum Alexander 
Published: June 2005

Abstract
Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (the so-called "class effect"). However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin/fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients' outcome.
Free Mg2+ concentration in the calf muscle of glycogen phosphorylase and phosphofructokinase deficiency patients assessed in different metabolic conditions by 31P MRS
Authors: Malucelli Emil , Lodi Raffaele , Martinuzzi Andrea , Tonon Caterina , Barbiroli Bruno , Iotti Stefano 
Published: June 2005

Abstract

Background
The increase in cytosolic free Mg2+ occurring during exercise and initial recovery in human skeletal muscle is matched by a decrease in cytosolic pH as shown by in vivo phosphorus magnetic resonance spectroscopy (31P MRS). To investigate in vivo to what extent the homeostasis of intracellular free Mg2+ is linked to pH in human skeletal muscle, we studied patients with metabolic myopathies due to different disorders of glycogen metabolism that share a lack of intracellular acidification during muscle exercise.

Methods
We assessed by 31P MRS the cytosolic pH and free magnesium concentration ([Mg2+]) in calf muscle during exercise and post-exercise recovery in two patients with McArdle's disease with muscle glycogen phosphorylase deficiency (McArdle), and two brothers both affected by Tarui's disease with muscle phosphofructokinase deficiency (PFK).

Results
All patients displayed a lack of intracellular acidosis during muscle exercise. At rest only one PFK patient showed a [Mg2+] higher than the value found in control subjects. During exercise and recovery the McArdle patients did not show any significant change in free [Mg2+], while both PFK patients showed decreased free [Mg2+] and a remarkable accumulation of phosphomonoesters (PME). During initial recovery both McArdle patients showed a small increase in free [Mg2+] while in PFK patients the pattern of free [Mg2+] was related to the rate of PME recovery.

Conclusion
i) homeostasis of free [Mg2+] in human skeletal muscle is strongly linked to pH as shown by patients' [Mg2+] pattern during exercise;
ii) the pattern of [Mg2+] during exercise and post-exercise recovery in both PFK patients suggests that [Mg2+] is influenced by the accumulation of the phosphorylated monosaccharide intermediates of glycogenolysis, as shown by the increased PME peak signal.
iii) 31P MRS is a suitable tool for the in vivo assessment of free cytosolic [Mg2+] in human skeletal muscle in different metabolic conditions;
Surgical management of abdominal and retroperitoneal Castleman's disease
Authors: Bucher Pascal , Chassot Gilles , Zufferey Guillaume , Ris Frederic , Huber Olivier , Morel Philippe 
Published: June 2005

Abstract

Background
Abdominal and retroperitoneal Castleman's disease could present either as a localized disease or as a systemic disease. Castleman's disease is a lymphoid hyperplasia related to human Herpes virus type 8, which could have an aggressive behavior, similar to that of malignant lymphoid neoplasm mainly with the systemic type, or a benign one in its localized form.

Methods
The authors report two cases of localized Castleman's disease in the retroperitoneal space and review the current and recent progress in the knowledge of this atypical disease.

Cases presentation
The two patients were young healthy women presenting with a hyper vascular peri-renal mass suggestive of malignant tumor. Both have been resected in-toto. One of them had an extensive resection with nephrectomy, while the second had a kidney preserving surgery. Pathological examination revealed localized Castleman's disease and surgical margins were free of disease. Postoperative course was uneventful, and after more than 5-years of follow-up no recurrences have been observed.

Conclusion
Localized Castleman's disease should be considered when facing a solid hypervascular abdominal or retroperitoneal mass. A better knowledge of this disorder and its characteristic would help surgeon to avoid unnecessarily extensive resection for this benign disorder when dealing with abdominal or retroperitoneal tumors. Surgical resection is curative for the localized form, when complete, while splenectomy could be indicated for the systemic form.
Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries
Authors: Manni Luigi , Lundeberg Thomas , Holmäng Agneta , Aloe Luigi , Stener-Victorin Elisabet 
Published: June 2005

Abstract

Background
Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO.

Methods
In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR).

Results
It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR.

Conclusion
The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.
Transforming growth factor beta-1 decreases the yield of the second meiotic division of rat pachytene spermatocytes in vitro
Authors: Damestoy Anne , Perrard Marie-Hélène , Vigier Michèle , Sabido Odile , Durand Philippe 
Published: June 2005

Abstract

Background
TGF beta and its receptors are present in both germ cells and somatic cells of the male gonad. However, knock-out strategies for studying spermatogenesis regulation by TGF beta have been disappointing since TGF beta-or TGF beta receptor-null mice do not survive longer than a few weeks.

Methods
In the present study, we addressed the role of TGF beta-1 on the completion of meiosis by rat pachytene spermatocytes (PS) cocultured with Sertoli cells. Identification and counting of meiotic cells were performed by cytology and cytometry.

Results
Under our culture conditions, some PS differentiated into round spermatids (RS). When TGF beta-1 was added to the culture medium, neither the number of PS or of secondary spermatocytes nor the half-life of RS was modified by the factor. By contrast, the number of RS and the amount of TP1 mRNA were lower in TGF beta-1-treated cultures than in control cultures. Very few metaphase I cells were ever observed both in control and TGF beta-1-treated wells. Higher numbers of metaphase II were present and their number was enhanced by TGF beta-1 treatment. A TGF beta-like bioactivity was detected in control culture media, the concentration of which increased with the time of culture.

Conclusion
These results indicate that TGF beta-1 did not change greatly, if any, the yield of the first meiotic division but likely enhanced a bottleneck at the level of metaphase II. Taken together, our results suggest strongly that TGF beta participates in an auto/paracrine pathway of regulation of the meiotic differentiation of rat spermatocytes.
Destructive effects of murine arthritogenic antibodies to type II collagen on cartilage explants in vitro
Authors: Crombie Duncan E , Turer Muhammed , Zuasti Beltzane Biurrun , Wood Bayden , McNaughton Don , Nandakumar Kutty Selva , Holmdahl Rikard , Van Damme Marie-Paule , Rowley Merrill J 
Published: June 2005

AbstractCertain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilage. Bovine cartilage explants were cultured over 21 days in the presence of two arthritogenic mAbs to CII (CIIC1 or M2139), a non-arthritogenic mAb to CII (CIIF4) or a control mAb (GAD6). Penetration of cartilage by mAb was determined by immunofluorescence on frozen sections and correlated with changes to the extracellular matrix and chondrocytes by morphometric analysis of sections stained with toluidine blue. The effects of mAbs on matrix components were examined by Fourier transform infrared microspectroscopy (FTIRM). A possible role of Fc-binding was investigated using F(ab)2 from CIIC1. All three mAbs to CII penetrated the cartilage explants and CIIC1 and M2139, but not CIIF4, had adverse effects that included proteoglycan loss correlating with mAb penetration, the later development in cultures of an abnormal superficial cellular layer, and an increased proportion of empty chondrons. FTIRM showed depletion and denaturation of CII at the explant surface in the presence of CIIC1 or M2139, which paralleled proteoglycan loss. The effects of F(ab)2 were greater than those of intact CIIC1. Our results indicate that mAbs to CII can adversely affect preformed cartilage, and that the specific epitope on CII recognised by the mAb determines both arthritogenicity in vivo and adverse effects in vitro. We conclude that antibodies to CII can have pathogenic effects that are independent of inflammatory mediators or Fc-binding.
Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells
Authors: Siddiqui Rafat A , Zerouga Mustapha , Wu Min , Castillo Alicia , Harvey Kevin , Zaloga Gary P , Stillwell William 
Published: June 2005

Abstract
Introduction
Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic–sedative agent employed today and is nontoxic to humans at high levels (50 μg/ml). Clinically relevant concentrations of propofol (3 to 8 μg/ml; 20 to 50 μM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA).

Methods
The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells.

Results
At low concentrations (25 μM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells.

Conclusion
These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.
Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats
Authors: Hakkak Reza , Holley Andy W , MacLeod Stewart L , Simpson Pippa M , Fuchs George J , Jo Chan Hee , Kieber-Emmons Thomas , Korourian Soheila 
Published: June 2005

Abstract
Introduction
High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity.

Method
Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment.

Results
The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats.

Conclusion
Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.
Study of Paclitaxel, Etoposide, and Cisplatin Chemotherapy Combined With Twice-Daily Thoracic Radiotherapy for Patients With Limited-Stage Small-Cell Lung Cancer: A Radiation Therapy Oncology Group 9609 Phase II Study
Authors: Ettinger David S. , Berkey Brian A. , Abrams Ross A. , Fontanesi James , Machtay Mitchell , Duncan Philip J. , Curran Walter J. , Movsas Benjamin , Byhardt Roger W. 
Published: June 2005

Purpose To determine the response rate, progression-free survival and overall survival, and toxicity of paclitaxel, etoposide, and cisplatin combined with accelerated hyperfractionated thoracic radiotherapy in patients with limited-disease (LD) small-cell lung cancer (SCLC). Patients and Methods LD-SCLC patients with measurable disease, Karnofsky performance score of ≥ 70, and adequate organ function who were previously untreated were eligible for the study. Treatment was as follows. In cycle 1 of chemotherapy, concurrent thoracic radiation therapy was administered. In cycles 2 to 4, chemotherapy was administered alone. In cycle 1, chemotherapy consisted of paclitaxel 135 mg/m2 intravenous over 3 hours on day 1, etoposide 60 mg/m2 intravenous on day 1 and 80 mg/m2 orally on days 2 and 3, and cisplatin 60 mg/m2 intravenous on day 1. In cycles 2 to 4, the paclitaxel dose was increased to 175 mg/m2, with the etoposide and cisplatin doses remaining the same as in cycle 1. The thoracic radiation therapy consisted of 1.5 Gy in 30 fractions (total dose, 45 Gy) administered 5 days a week for 3 weeks. Results Fifty-five patients were enrolled onto the study, and 53 were assessable. The major toxicities included grade 3 and 4 acute neutropenia (32% and 43%, respectively) and grade 3 and 4 esophagitis (32% and 4%, respectively). Two patients died as a result of therapy (one died of acute respiratory distress syndrome, and one died of sepsis). There was one late fatal pulmonary toxicity. The median survival time was 24.7 months. The 2-year survival rate was 54.7%. The median progression-free survival time was 13 months, with a 2-year progression-free survival rate of 26.4%. Conclusion Although this therapeutic regimen is effective in the treatment of patients with LD-SCLC, it is unlikely that the three-drug combination with thoracic radiation therapy will improve the survival times compared with the etoposide plus cisplatin chemotherapy regimen with thoracic radiation therapy in LD-SCLC patients.