tbuckley/cabot-search huggingface dataset:
Influence of players' physique on rugby football injuries.
Authors: A J Lee, J L Myers, W M Garraway
Journal: British Journal of Sports Medicine (1997)

To determine whether there is an association between a player's physique and injuries incurred while playing rugby football.A cohort study was carried out involving all senior rugby clubs in the Scottish Borders during the 1993-1994 rugby season. Somatotype estimates were determined for 1152 (95%) of the 1216 eligible players. Body mass index (BMI), chest to waist ratio, and the ponderal index (PI) were used to classify players' physique as endomorphic (obese), mesomorphic (muscular), and ectomorphic (linear).A strong association was found between physique and age (chi 2 test: chi 2 = 317.2, df = 10, P < 0.0001). More younger players were ectomorphs. Older players were more often endomorphic. The physiques of forwards and backs were significantly different (chi 2 test: chi 2 = 58.6, df = 2, P < 0.0001), with forwards being of a heavier build than three-quarters, even after adjustment for age. Endomorphic players were more likely than ectomorphs to be injured in a match after adjustment for age (age-adjusted mean BMI for players who were injured in a match was 25.4 compared with 24.6 for players who were not injured in a match, P < 0.0001; adjusted chest to waist ratio means were 1.136 and 1.125 respectively, P = 0.0307; adjusted PI means were 0.414 and 0.417 respectively, P = 0.0056). Increased risk of injury may occur when players play out of position, since one fifth of all injuries occurred in this circumstance.Further research needs to be conducted using a more objective method of measuring somatotype on a further cohort of players so that the risk of injury for different body types can be examined more closely and related to other potential confounding factors. The level of increased risk for individuals playing out of their usual playing position needs to be established with a greater degree of certainty.
Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease
Authors: R Junker
Journal: Cardiovascular Research (2001)

Objective: Recently, an association between the homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infants with congenital neural tube defects or congenital oral clefts has been shown. However, no data are available so far with respect to the MTHFR 677TT genotype in children with underlying structural congenital heart disease (CHD). Methods: We investigated the MTHFR genotype in 114 Caucasian CHD patients aged newborn to 16 years (median 0.6 years; 53% male) and in 228 age- and sex-matched healthy controls. Results: In childhood patients with CHD the homozygous MTHFR 677TT genotype was found in 21 out of 114 subjects (18.4%) compared with 21 out of 228 controls (9.2%; odds ratio (OR) 2.2, 95%-confidence interval (CI) 1.2–4.3; P=0.027). In patients with pulmonary valve stenosis, hypoplastic left heart syndrome, coarctation of the aorta, aortic valve stenosis or subaortic stenosis the frequency of the TT genotype varied between 38 and 67% with corresponding ORs from 6.1 (CI, 1.4–27.5; P=0.034) to 20.4 (CI, 1.8–235.0; P=0.025), whereas in other structural CHD the frequency of this genotype was not significantly different from the controls. Conclusions: With the present study we can show for the first time that the embryonal MTHFR 677TT genotype is significantly associated with the development of structural congenital heart malformations during early pregnancy. It remains to be clarified, whether this genotype is at least a risk marker or a risk factor for structural congenital heart malformations.
Safety and immunogenicity of a Pseudomonas aeruginosa O-polysaccharide toxin A conjugate vaccine in humans.
Authors: S J Cryz, E Fürer, A S Cross, A Wegmann, R Germanier, J C Sadoff
Journal: Journal of Clinical Investigation (1987)

Lipid A-free polysaccharide (PS) isolated from Pseudomonas aeruginosa immunotype 5 lipopolysaccharide (LPS) was covalently coupled to toxin A via reductive amination. The PS-toxin A conjugate was comprised of 29.8% PS and 70.2% toxin A, possessed a molecular weight of greater than 1 X 10(6), was nontoxic for animals and was nonpyrogenic for rabbits at a dose of 50 micrograms/kg body wt when administered intravenously. The conjugate evoked only mild, transient reactions upon subcutaneous administration to human volunteers. Vaccination engendered immunoglobulin G (IgG) antibody, which neutralized the cytotoxic effect of toxin A and promoted the uptake and killing of P. aeruginosa in the presence of human polymorphonuclear leukocytes. Passively transferred IgG isolated from the serum of immunized donors was far more effective at preventing fatal P. aeruginosa burn wound sepsis than paired preimmunization serum. These studies establish the potential usefulness of such a PS-toxin A conjugate as a vaccine against P. aeruginosa.
Urokinase activates macrophage PON2 gene transcription via the PI3K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-β
Authors: Bianca Fuhrman, Anna Gantman, Jasmin Khateeb, Nina Volkova, Sven Horke, Julia Kiyan, Inna Dumler, Michael Aviram
Journal: Cardiovascular Research (2009)

AimsWe have recently shown that urokinase plasminogen activator (uPA) increases oxidative stress (OS), cholesterol biosynthesis, and paraoxonase 2 (PON2) expression in macrophages via binding to its receptor, the uPAR. Since PON2 is regulated by both OS and cholesterol content, we hypothesized that uPA elicits a cascade of signal transduction events shared by NADPH oxidase and cholesterol biosynthesis that culminates in PON2 gene expression. Here, we investigated the signalling pathway that leads to the expression of PON2 in macrophages in response to uPA.
Hepatitis C virus infection of salivary gland epithelial cells
Authors: Gloria Taliani, Domenico Celestino, Maria Concetta Badolato, Alfredo Pennica, Alessandro Bozza, Giuseppina Poliandri, Valeria Riccieri, Guido Benfari, Antonio Sebastiani, Carlo De Bac, Giorgio Quaranta, Antonio Aceti
Journal: Journal of Hepatology (1997)
Retinoids in Lung Cancer: Friend, Foe, or Fellow Traveler?
Authors: Fadlo R. Khuri, Reuben Lotan
Journal: Journal of Clinical Oncology (2004)

An Initial Era of Optimism The study of retinoids in lung and upper aerodigestive tract cancer dates back to seminal observations by Wohlbach and Howe, who discovered that vitamin A deprivation of cattle led to an increased incidence of lung and upper aerodigestive tract cancers. Subsequent studies have demonstrated enhanced lung carcinogenesis in vitamin A-deficient animals exposed to the tobacco carcinogen benzo[a]pyrene, possibly due to enhanced binding of the carcinogen to tracheal epithelial DNA. These findings have paved the way to vitamin A intervention in experimental lung carcinogenesis. The extension of these studies to human lung carcinogenesis and prevention was supported by epidemiologic studies, which suggested that significant dietary intake of vitamin A and carotenoids plays an important role in decreased cancer incidence. Pharmacologically, it would be several decades before Hong et al and others would show that high-doses of a synthetic retinoid (13-cis-retinoic acid or isotretinoin) could reverse oral premalignant lesions. Further trials by Hong et al and Pastorino et al showed that high-doses of synthetic or natural vitamin A could reduce the incidence of second primary head and neck and lung tumors in patients with a prior history of tobacco-related cancer. While the highdoses, in particular of the synthetic vitamin A derivatives, were too toxic to administer to a broad patient population, this optimism led to further development of retinoids in tobacco-related cancers, as well as the biologic implications of loss or gain of function of retinoid-related genes.
DNA DEGRADATION IN DEVELOPMENT AND PROGRAMMED CELL DEATH
Authors: Shigekazu Nagata
Journal: Annual Review of Immunology (2004)

Most mammalian cells have nuclei that contain DNA, which replicates during cell proliferation. DNA is destroyed by various developmental processes in mammals. It is degraded during programmed cell death that accompanies mammalian development. The nuclei of erythrocytes and eye lens fiber cells are also removed during their differentiation into mature cells. If DNA is not properly degraded in these processes, it can cause various diseases, including tissue atrophy, anemia, cataract, and autoimmune diseases, which indicates that DNA can be a pathogenic molecule. Here, I present how DNA is degraded during programmed cell death, erythroid cell differentiation, and lens cell differentiation. I discuss what might be or will be learned from understanding the molecular mechanisms of DNA degradation that occurs during mammalian development.
Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients.
Authors: C Azar, J Van de Stadt, F Rickaert, M Deviere, M Baize, G Kloppel, M Gelin, M Cremer
Journal: Gut (1996)

The clinical presentation, pancreatographic findings, and outcome of patients with intraductal papillary mucinous tumours have not been reported in a large patient series in the English literature. This study reviewed 32 patients diagnosed between 1980 and 1994, with special attention to these features.Data on 24 operated and eight non-operated patients were abstracted from inpatient, outpatient, and procedure records.Acute pancreatitis was the most common presentation seen in 56% of patients. Relapses occurred during an average of 43 months before diagnosis. A patulous papilla was observed in 55% of the cases. Endoscopic pancreatography showed communicating cysts, a diffusely dilated main pancreatic duct, and amorphous defects in 42, 71, and 97% respectively. An invasive carcinoma was found in nine of 24 (37.5%) of operated patients: six of the patients (66%) died or developed metastases within three years after surgery. No mortality was related to the tumour in absence of invasive carcinoma. Benign recurrence on the remaining pancreas was unusual and occurred late after surgery.Intraductal papillary mucinous tumours must be considered in the differential diagnosis of relapsing pancreatitis. Despite slow growing, these tumours have an obvious malignant potential and a very poor prognosis when invasive carcinoma has developed. Early recognition and resection are the cornerstones of treatment.
Paying Physicians to Prescribe Generic Drugs and Follow-On Biologics in the United States
Authors: Ameet Sarpatwari, Niteesh K. Choudhry, Jerry Avorn, Aaron S. Kesselheim
Journal: PLoS Medicine (2015)

Points• Spending on brand-name prescription medications, particularly brand-name biologic drugs, continues to increase.• Considerable savings and improvements in medication adherence are possible from greater use of more affordable generic drugs and imminently available follow-on biologics.• Strategies to promote greater prescribing of generic drugs and follow-on biologics include traditional information-supplying programs such as formulary decision support and academic detailing and more novel financial incentives.• While private insurers, qualified health plans, and employers may legally offer physicians financial incentives to prescribe generic drugs and follow-on biologics, marginally greater risks and a developing evidence base militates against physician payment for therapeutic or noninterchangeable follow-on biologic substitution, and-at this timefor bioequivalent substitution of narrow therapeutic index (NTI) drugs or interchangeable follow-on biologic substitution.• Implementation of the various physician-centered strategies to promote greater prescribing of generic drug and follow-on biologics must be accompanied by comparative cost-utility studies assessing patient health outcomes.
Roles of Radiotherapy and Smoking in Lung Cancer Following Hodgkin's Disease
Authors: F. E. van Leeuwen, W. J. Klokman, M. Stovall, A. Hagenbeek, A. W. van den Belt-Dusebout, R. Noyon, J. D. Boice, J. M. V. Burgers, R. Somers
Journal: JNCI Journal of the National Cancer Institute (1995)

Several studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known. This study was undertaken to investigate the effects of radiation dose, chemotherapy, and smoking on the risk of lung cancer following treatment of Hodgkin's disease. We conducted a case-control study in a cohort of 1939 patients treated for Hodgkin's disease from 1966 through 1986 in The Netherlands. Detailed treatment information was collected from the medical records for 30 case patients with lung cancer following Hodgkin's disease and 82 matched control subjects who had not developed lung cancer. Multiple sources were used to obtain as complete smoking histories of the study participants as possible. For each case-control set, the radiation dose received by the area of the lung where the case patient developed the tumor was estimated on the basis of radiotherapy charts and experimental simulations of treatments. The estimates of relative risk (RR) for lung cancer associated with specific exposures were obtained from logistic regression methods, and all tests of statistical significance were two-sided. A statistically significant increase in risk of lung cancer was observed with increasing radiation dose ( P for trend =.01) with an RR of 9.6 (95% confidence interval [CI] = 0.93–98) for patients who received 9 Gy or more compared with those who received less than 1 Gy. Patients who smoked more than 10 pack-years after the diagnosis of Hodgkin's disease had a sixfold increase in the risk of lung cancer compared with patients who smoked less than 1 pack-year ( P =.03). Positive interaction on a multiplicative scale was observed between the carcinogenic effects of smoking and radiation. The increase in risk of lung cancer with increasing radiation dose was much greater among the patients who smoked after diagnosis of Hodgkin's disease than among those who refrained from smoking ( P =.04). There was no increase in lung cancer risk in relation to the number of cycles of chemotherapy or the cumulative doses of the drugs mechlorethamine and procarbazine. The excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung. Smokers experience a significantly greater risk attributable to radiotherapy than nonsmokers. Physicians in charge of patient treatment should make a special effort to dissuade Hodgkin's disease patients from smoking after receiving radiotherapy. [J Natl Cancer Inst 1995; 87:1530–7]
Lower Serum Creatinine Is a New Risk Factor of Type 2 Diabetes
Authors: Nobuko Harita, Tomoshige Hayashi, Kyoko Kogawa Sato, Yoshiko Nakamura, Takeshi Yoneda, Ginji Endo, Hiroshi Kambe
Journal: Diabetes Care (2008)

OBJECTIVE—Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS—The study participants were nondiabetic Japanese men (n = 8,570) aged 40–55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was ≥126 mg/dl or if participants were taking oral hypoglycemic medication or insulin. RESULTS—During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44–2.54) compared with those who had levels between 0.71 and 0.80 mg/dl. CONCLUSIONS—Lower serum creatinine increased the risk of type 2 diabetes.
Cognitive therapy is as good as drugs for depression
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Cognitive therapy is as effective as treatment with antidepressants in moderate to severe depression, a randomised placebo controlled US trial has shown ( Archives of General Psychiatry 2005;62:409-16). A follow-up study in the same issue of the journal shows that patients who had completed their course of cognitive therapy were less likely to relapse after treatment had ended than those who completed their course of antidepressants (2005;62:417-22). The findings contradict the American Psychiatric Association's guidelines, which say that most moderately and severely depressed patients will medication.

Patients who entered the study had a score of 20 or higher on the modified Hamilton depression rating scale, a questionnaire widely used to …
The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson’s disease: a randomized, double-blind, double-dummy, parallel-group study
Authors: Ying Wang, Shenggang Sun, Suiqiang Zhu, Chunfeng Liu, Yiming Liu, Qing Di, Huifang Shang, Yan Ren, Changhong Lu, Mark Forrest Gordon, Nolwenn Juhel, Shengdi Chen
Journal: Translational Neurodegeneration (2014)

To evaluate the non-inferiority of pramipexole extended-release (ER) versus immediate-release (IR) in Chinese patients with Parkinson's disease (PD) in a double-blind, randomized, parallel-group study.Subjects were Chinese patients with idiopathic PD with diagnosis ≥ 2 years prior to trial, age ≥ 30 years old at diagnosis, and Modified Hoehn and Yahr score 2-4 during 'on'-time. Subjects received treatment with pramipexole ER (n=234) or IR (n=239). Non-inferiority was based on the primary endpoint, the change from baseline to end of maintenance (week 18) in the UPDRS (Parts II + III) total score.For the primary endpoint, the adjusted mean changes (standard error) of UPDRS Parts II + III at week 18 were -13.81 (0.655) and -13.05 (0.643) for ER and IR formulations, respectively, using ANCOVA adjusted for treatment and centre (fixed effect) and baseline (covariate). The adjusted mean between group difference was 0.8 for the 2-sided 95% CI (-1.047, 2.566). Since the lower limit of the 2-sided 95% CI (-1.047) for treatment difference was higher than the non-inferiority margin of -4, non-inferiority between pramipexole ER and IR was demonstrated. The incidence of adverse events (AEs) was 68.8% in the ER arm and 73.6% in the IR arm with few severe AEs (ER: 2.1%; IR: 3.8%).Based on the UPDRS II + III score, pramipexole ER was non-inferior to pramipexole IR. The safety profiles of pramipexole ER and IR were similar. These results were based on comparable mean daily doses and durations of treatment for both formulations.
Primary Prevention of Cardiovascular Disease Endpoints Using β-Blockers
Authors: Leszek Michalewiz
Journal: JAMA (1997)

<h3>To the Editor.</h3> —In their meta-analysis of the effect of antihypertensive therapies on preventing disease end points, such as stroke, coronary heart disease, congestive heart failure, and total and cardiovascular mortality, Dr Psaty and colleagues<sup>1</sup>concluded that the data provide strong support for the use of β-blockers and diuretics as first-line agents. However, after a closer look at their data, these conclusions are not supported by the data in the case of β-blockers. When calculating the relative risk associated with β-blocker therapy, the authors used 4 studies: (1) Medical Research Council trial of treatment of mild hypertension (MRC)<sup>2</sup>; (2) Medical Research Council trial of treatment of hypertension in older adults (MRC-O)<sup>3</sup>; (3) Swedish Trial in Old Patients With Hypertension (STOP-H)<sup>4</sup>; and (4) Coope and Warrender.<sup>5</sup>By doing so, they glossed over the fact that in STOP-H, two thirds of the patients in the active treatment
Treatment with the α-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes
Authors: Kazuki Mochizuki, Nanae Fukaya, Yutaro Tanaka, Masahiro Fuchigami, Toshinao Goda
Journal: Metabolism (2011)
Safety and Toxicity Analysis of Oxaliplatin Combined With Fluorouracil or as a Single Agent in Patients With Previously Treated Advanced Colorectal Cancer
Authors: Ramesh K. Ramanathan, Jeffery W. Clark, Nancy E. Kemeny, Heinz-Josef Lenz, Kim O. Gococo, Daniel G. Haller, Edith P. Mitchell, Carl G. Kardinal
Journal: Journal of Clinical Oncology (2003)

Purpose: Two consecutive compassionate use studies of oxaliplatin were conducted in the United States and Canada in more than 5,000 patients with locally advanced or metastatic colorectal carcinoma who had experienced treatment failure after at least one prior chemotherapy regimen. Patients and Methods: The main focus was safety. Patients were assigned to treatment with either single-agent oxaliplatin or oxaliplatin in combination with fluorouracil (FU) and with or without leucovorin (LV) in various regimens. Response data collection was not a trial objective, but time to treatment failure (TTF) was recorded in the first cohort (1,370 patients). Results: All treatment regimens were well tolerated, with an overall incidence of grade 3 or 4 hematologic toxicity of 23.2%, grade 3 or 4 treatment-related gastrointestinal toxicity of 26.4% (including diarrhea, vomiting, and mucositis), and grade 3 neurosensory toxicity 3.9%. Similar results were reported in the second cohort (3,806 patients), in which the eligibility criteria were much less restrictive. In the first cohort (in which 83% received prior irinotecan), median TTF was 14 weeks, and was similar for the five regimens combining oxaliplatin and FU with or without LV, but significantly shorter for the single-agent oxaliplatin arm. The overall dose-intensity of oxaliplatin was maintained at 85.5% (range, 80.6% to 94.3%) of that prescribed by protocol (average 36.7 mg/m 2 /wk). Conclusion: These data in a heavily pretreated patient population confirm that oxaliplatin is safe when used as a single agent or with a variety of FU-based regimens as salvage therapy in patients with advanced colorectal cancer.