bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids induce an activated, anti-inflammatory monocyte subset in mice that resembles myeloid-derived suppressor cells
Authors: Varga Georg , Ehrchen Jan , Tsianakas Athanasios , Tenbrock Klaus , Rattenholl Anke , Seeliger Stephan , Mack Matthias , Roth Johannes , Sunderkoetter Cord 
Published: July 2008

AbstractGlucocorticoids (GC) are still the most widely used immunosuppressive agents in clinical medicine. Surprisingly, little is known about the mechanisms of GC action on monocytes, although these cells exert pro- and anti-inflammatory effects. We have shown recently that GC induce a specific monocyte phenotype with anti-inflammatory properties in humans. We now investigated whether this also applies for the murine system and how this subset would relate to recently defined murine subtypes. After treatment with dexamethasone for 48 h, monocytes up-regulated scavenger receptor CD163 and Gr-1, down-regulated CX3CR1, and shared with human GC-treated monocytes functional features such as low adhesiveness but high migratory capacity. They specifically up-regulated anti-inflammatory IL-10, but not TGF-β, and in contrast to their human counterparts, they down-regulated IL-6. Although GC-induced monocytes down-regulated CX3CR1, a distinctive marker for classical/proinflammatory human and murine monocytes (CX3CR1loCCR2+Ly6Chi), they differed from this physiologically occurring subset, as they remained Ly6Cmed and unactivated (CD62 ligand++). In addition to their immunosuppressive effects, they were CD11b+Gr-1+ and expressed the IL-4Rα chain (CD124), a recently described, signature molecule of tumor-induced myeloid-derived suppressor cells (MDSC). We therefore generated murine MDSC in B16 melanoma-bearing mice and indeed found parallel up-regulation of CD11b+Gr-1+ and CD124 on GC-induced monocytes and MDSC. These data allow us to speculate that the GC-induced subtype shares with inflammatory monocytes the ability to migrate quickly into inflamed tissue, where they, however, exert anti-inflammatory effects and that similarities between GC-induced monocytes and MDSC may be involved in progression of some tumors observed in patients chronically treated with GC.
Prevalence of Adenomas and Hyperplastic Polyps in Mismatch Repair Mutation Carriers Among CAPP2 Participants: Report by the Colorectal Adenoma/Carcinoma Prevention Programme 2
Authors: Liljegren Annelie , Barker Gail , Elliott Faye , Bertario Lucio , Bisgaard Marie Luise , Eccles Diana , Evans Gareth , Macrae Finlay , Maher Eamonn , Lindblom Annika , Rotstein Samuel , Nilsson Bo , Mecklin Jukka-Pekka , Möslein Gabriela , Jass Jeremy , Fodde Riccardo , Mathers John , Burn John , Bishop D. Timothy 
Published: July 2008

Purpose To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously in smaller studies, and the results have been found to be variable. Patients and Methods Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before the chemoprevention study were the focus of this study. The number, histology, size, and location of polyps found at the participants' first ever colonoscopy were analyzed in a cross-sectional study. Results Seventy-four patients (10.6%) were found to have at least one adenoma at first colonoscopy, whereas 37 (5.3%) had at least one hyperplastic polyp. The frequency of an adenoma at first colonoscopy increased from 5.0% (95% CI, 2.8% to 8.3%) in patients younger than 35 years old to 18.9% (95% CI, 9.4% to 32.0%) in patients age at least 55 years (P = .0001 for trend). No such trend was observed for hyperplastic polyps. No sex differences were found for either type of polyp. A marginal association was found between the co-occurrence of adenomas and hyperplastic polyps. Adenomas tended to be more proximally distributed through the colon, whereas hyperplastic polyps tended to be located in the distal colon. Conclusion Adenoma prevalence increases with age among MMR mutation carriers, whereas hyperplastic polyp prevalence is consistent. No sex differences were observed for either type of lesion.
Increased EGFR Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non–Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy
Authors: Hirsch Fred R. , Herbst Roy S. , Olsen Christine , Chansky Kari , Crowley John , Kelly Karen , Franklin Wilbur A. , Bunn Paul A. , Varella-Garcia Marileila , Gandara David R. 
Published: July 2008

Purpose Epidermal growth factor receptor (EGFR) gene copy number detected by fluorescent in situ hybridization (FISH) has proven to be useful for selection of non–small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy. Patients and Methods Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin) with cetuximab. Results EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive (four or more gene copies per cell in ≥ 40% of the cells or gene amplification) in 59.2%. Response (complete response/partial response) was numerically higher in FISH-positive (45%) versus FISH-negative (26%) patients (P = .14), whereas disease control rate (complete response/partial response plus stable disease) was statistically superior (81% v 55%, respectively; P = .02). Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients (P = .0008). Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative. (P = .04). Furthermore, survival favored FISH-positive patients receiving concurrent therapy. Conclusion These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy. Prospective validation of these findings is warranted.
Phase II Evaluation of Imatinib Mesylate in the Treatment of Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study
Authors: Schilder Russell J. , Sill Michael W. , Lee Roger B. , Shaw Tanya J. , Senterman Mary K. , Klein-Szanto Andres J. , Miner Zoe , Vanderhyden Barbara C. 
Published: July 2008

Purpose This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. The association between the expression of certain markers and clinical outcome was investigated. Patients and Methods Primary measure of clinical efficacy was progression-free survival (PFS) at 6 months. Mutational analysis of KIT, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay for markers (KIT, platelet-derived growth factor [PDGF] receptor [-R], AKT2, phosphorylated AKT [p-AKT], stem cell factor [SCF], and PDGF) were performed. Results Fifty-six eligible patients were evaluated. Nine patients were progression free for at least 6 months including one complete responder. The median PFS and survival were 2 and 16 months, respectively. The most common grade 3 and 4 toxicities were neutropenia, GI, dermatologic effects, pain, and electrolyte disturbances. At least one target of imatinib (KIT, PDGFR-α, or PDGFR-β) was expressed in all tumors, and most tumors expressed all three receptors. Higher expression of p-AKT and PDGFR-β were associated with shorter PFS, and higher IHC scores (% immunopositive cells × staining intensity) of SCF and p-AKT were associated with decreased overall survival. No sequence mutations were detected in the KIT gene. Higher pretreatment plasma concentrations of PDGF-AB, PDGF-BB, and vascular endothelial growth factor (VEGF) were individually associated with shorter PFS and survival. Conclusion Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma. No marker was identified that would predict activity of imatinib; however, tumor p-AKT and plasma VEGF levels were associated with poor outcome.
Disclosure of Incurable Illness to Spouses: Do They Want to Know? A Swedish Population-Based Follow-Up Study
Authors: Dahlstrand Hanna , Hauksdóttir Arna , Valdimarsdóttir Unnur , Fürst Carl-Johan , Bergmark Karin , Steineck Gunnar 
Published: July 2008

Purpose Awareness of the cancer patient's terminal state decreases the risk of psychological morbidity of the bereaved. We wanted to determine whether male spouses of cancer patients who died from their disease had received information that the illness was incurable and to determine their preferences of disclosure. Participants and Methods The study included 907 widowers whose wives had died of cancer. In an anonymous questionnaire, we asked whether the widower had received information that his wife's illness was incurable and about his attitudes towards receiving this information. Results Six hundred ninety-one widowers (76%) participated. Eighty percent of the widowers reported that they were told that the wife's cancer was incurable, and 21% reported that they had been informed within 1 week before the patient's death. Although 14% of the widowers did not think the next of kin should be told immediately when the patient's cancer is beyond cure, 39% of the men did not want the patient to be immediately informed. Furthermore, 71% of the men who were never informed about the incurable illness believed that the next of kin should receive that information immediately. Conclusion Although a large majority of men prefer an immediate disclosure about the incurable stage of their wife's illness, 41% of the husbands received this information during the last week of the patient's life or not at all. These findings indicate that there is room for improvement in the level of communication between health providers and the husbands of women with incurable cancer.
Nocturnal Glucose Metabolism after Bedtime Injection of Insulin Glargine or Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes
Authors: Linn Thomas , Fischer Britta , Soydan Nedim , Eckhard Michael , Ehl Julia , Kunz Clemens , Bretzel Reinhard G. 
Published: July 2008

Aims/Hypothesis: Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning.
Methods: In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6′]2H2 glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion.
Results: Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 μmol/kg−1·min−1 (95% confidence interval 4.7–6.9) and reducing EGP −5.7 (−5.0 to −6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine’s reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021).
Conclusion/Interpretation: Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin.
Insulin-Like Factor 3 Levels in Second-Trimester Amniotic Fluid
Authors: Bay Katrine , Cohen Arieh S. , Jørgensen Finn Stener , Jørgensen Connie , Lind Anne Marie , Skakkebæk Niels E. , Andersson Anna-Maria 
Published: July 2008

Background: According to animal studies, the testicular Leydig cell hormone insulin-like factor 3 (Insl3) exerts a fundamental role in abdominal testis translocation, which occurs in the beginning of the second trimester in humans. Despite this, human prenatal INSL3 production has been poorly investigated.
Methods: Amniotic fluid from 91 pregnant women undergoing amniocentesis was analyzed for INSL3 and testosterone (T) levels. Data were related to gestational age (15–25 wk) at amniocentesis and to sex (45 males and 48 females).
Results: INSL3 was present in amniotic fluid from all but one of the investigated male fetuses (range: &lt;0.02–0.36 ng/ml; mean ± sd: 0.12 ± 0.07), whereas the hormone was undetectable in the female fetuses. T was significantly higher in male (range: 0.54–1.71 nmol/liter; mean ± sd: 1.04 ± 0.30) as compared with in female amniotic fluid (range: 0.19–0.50 nmol/liter; mean ± sd: 0.34 ± 0.06) (P &lt; 0.001). In males there was no correlation between INSL3 and T. A statistically borderline negative association was found between INSL3 and gestational age (P = 0.07), whereas the corresponding association was not significant for T (P = 0.12). In contrast, T in females correlated positively with gestational age (P = 0.02).
Conclusions: INSL3 is clearly present in human male amniotic fluid in the second trimester, where abdominal testis translocation takes place. In contrast, the hormone is undetectable in female amniotic fluid. The prenatal presence of INSL3 supports the hypothesis that this hormone is essential for testicular descent in humans.
Risk of Thyroid Disease in Individuals with Celiac Disease
Authors: Elfström Peter , Montgomery Scott M. , Kämpe Olle , Ekbom Anders , Ludvigsson Jonas F. 
Published: July 2008

Background: It has been suggested that celiac disease is associated with thyroid disease. Earlier studies, however, have been predominately cross-sectional and have often lacked controls. There is hence a need for further research. In this study, we estimated the risk of thyroid disease in individuals with celiac disease from a general population cohort.
Methods: A total of 14,021 individuals with celiac disease (1964–2003) and a matched reference population of 68,068 individuals were identified through the Swedish national registers. Cox regression estimated the risk of thyroid disease in subjects with celiac disease. Analyses were restricted to individuals with a follow-up of more than 1 yr and with no thyroid disease before study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for subsequent celiac disease in individuals with thyroid disease.
Results: Celiac disease was positively associated with hypothyroidism [hazard ratio (HR) = 4.4; 95% confidence interval (CI) = 3.4–5.6; P &lt; 0.001], thyroiditis (HR = 3.6; 95% CI =1.9–6.7; P &lt; 0.001) and hyperthyroidism (HR = 2.9; 95% CI = 2.0–4.2; P &lt; 0.001). The highest risk estimates were found in children (hypothyroidism, HR = 6.0 and 95% CI = 3.4–10.6; thyroiditis, HR = 4.7 and 95% CI = 2.1–10.5; hyperthyroidism, HR = 4.8 and 95% CI = 2.5–9.4). In post hoc analyses, where the reference population was restricted to inpatients, the adjusted HR was 3.4 for hypothyroidism (95% CI = 2.7–4.4; P &lt; 0.001), 3.3 for thyroiditis (95% CI = 1.5–7.7; P &lt; 0.001), and 3.1 for hyperthyroidism (95% CI = 2.0–4.8; P &lt; 0.001).
Conclusion: Celiac disease is associated with thyroid disease, and these associations were seen regardless of temporal sequence. This indicates shared etiology and that these individuals are more susceptible to autoimmune disease.
Evaluation of a clinical examination skills training course in an undergraduate pharmacy programme
Authors: Wearn Andy , Bye Lynne , Bhoopatkar Harsh 
Published: July 2008

Abstract

Objective
To introduce and evaluate a short clinical examination skills course in a BPharm programme. The study objectives were to assess needs, explore attitudes, record perceived competence requirements and assess the value of physical examination skills learning.

Setting
BPharm programme in Auckland, New Zealand. Participants were students enrolled in years 3 and 4 of the programme (2003).

Method
The design was a longitudinal, dual cohort, educational intervention evaluation using a self-completed questionnaire. An examination skills component was added to the fourth year of the pharmacy programme. Year 3 and 4 students were recruited, and completed the questionnaire at two points. Year 3 students were sampled one year before and soon after the skills sessions. Year 4 students were sampled after the sessions and 18 months later (once registered). The questionnaire sought their attitudes towards clinical skills training and practical relevance for future practice, and evaluated their learning experience.

Key findings
Response rates at the four points were 42–67%. Year 3 students identified a similar set of appropriate skills to those actually taught in year 4. Overall, attitudes to introducing examination skills learning were positive at all points. At follow-up, both cohorts agreed more strongly that examination skills training should be core (significantly for registered pharmacists versus year 3, P &lt; 0.006). Measuring manual blood pressure was deemed the most difficult skill. All taught skills were used in practice except for respiratory rate; most used were body mass index (BMI), temperature and peak flow measurement.

Conclusions
There was a close correlation between what was offered in the course, what students felt they needed to learn and what was relevant in practice. Once registered, pharmacists were aware of their limitations and level of competence in relation to clinical skills. The small changes in attitudinal scores appear to reflect maturity and experience. The study design allowed us to adapt the educational component to student need. Health professional educators need to be aware of and respond to changes in professional scopes of practice.
Is there an association between referral population deprivation and antibiotic prescribing in primary and secondary care?
Authors: Curtis Christopher , Marriott John 
Published: July 2008

AbstractObjectiveThe study was designed to explore the presence of any relationship between NHS secondary care antibiotic prescribing rates or primary care antibiotic prescribing rates and the levels of deprivation experienced within the referred primary care population. The study also aimed to determine whether the antibiotic prescribing rates for each care sector were correlated.MethodThe study was conducted in 12 English hospital trusts of mixed size and case-mix. Antibiotic usage data (Anatomical Therapeutic Chemical (ATC) category J01) for the financial year, ending March 2001/2002 were used to calculate hospital trust prescribing rates (using the defined daily dose/finished consultant episode indicator). Primary care antibiotic prescribing data were obtained from the Prescription Pricing Authority (antibiotic items prescribed per 1000 residents) for the year 2001/2002. Index of Multiple Deprivation (IMD) 2000 deprivation data were obtained from the regional public health observatory websites for each of the primary care trusts within the relevant study areas.Key findingsNo correlation could be established between the weighted index of multiple deprivation of the treated population and antibiotic prescribing rates at each hospital trust. Primary care antibiotic prescribing rates were not found to correlate with antibiotic prescribing rates in the geographically associated hospital trust. Data from all 12 sites showed that the IMD 2000 measures and primary care prescribing rates were weakly correlated, with higher antibiotic prescribing rates being generally observed in areas of primary care exhibiting the worst levels of deprivationConclusionsThe likely explanations for the present findings are that deprivation-related illnesses are principally treated within primary care, whereas hospital antibiotic prescribing principally results from procedures isolated within secondary care or through the additional influence of nosocomial infection. Therefore, medicines management measures geared to controlling antibiotic prescribing in secondary care should not focus upon the levels of deprivation in the referred population, whereas those in primary care should.
Involving patients as advisors in pharmacy practice research: what are the benefits?
Authors: Sutton Jane , Weiss Marjorie 
Published: July 2008

Abstract

Objective
To describe the ways in which members of the public with a chronic condition were involved as advisors in a research project exploring pharmacist supplementary prescribing. The primary objective was to be able to reflect upon the benefits and difficulties of this approach so that the patient perspective can be accommodated more fully in future research.

Setting
University of Bath.

Method
Ten individuals were recruited from two clinical areas: a diabetes support group and a chronic lung disease group. None of the individuals had ever seen, or heard of, a pharmacist supplementary prescriber. They joined two members of the research team at each of six meetings held over a period of one year. This paper presents an ethnographic approach to the accounts of these meetings and reflects on the involvement of patients as members of the research team.

Key findings
Initially, the group was unaware of pharmacist prescribing and expressed a range of concerns. After gaining an understanding of pharmacist prescribing, they were able to influence the design and content of interview schedules and offered comments on completed interview transcripts. As the project progressed the patients began to take on a non-lay perspective of pharmacists, becoming more in favour of pharmacist prescribing over time. It may be useful in the future to introduce new patient members to such a group, from time to time, during the life of a project to maintain a lay or ‘outside’ perspective on key research issues. Nonetheless, the use of the patient group contributed to the direction and outcome of the study in a positive way and kept the project grounded in the patient's perspective.

Conclusion
We conclude that the benefits of including patients in the research process far outweigh the difficulties. Researchers are encouraged to adopt this approach in the future and listen to the patients but be clear about their role in the research process.