tbuckley/cabot-search huggingface dataset:
Loss of transforming growth factor β signalling in the intestine contributes to tissue injury in inflammatory bowel disease
Authors: K-B Hahm, Y-H Im, T W Parks, S-H Park, S Markowitz, H-Y Jung, J Green, S-J Kim
Journal: Gut (2001)

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract caused by an abnormal and uncontrolled immune response to one or more normally occurring gut constituents.Given the effects of transforming growth factor beta1 (TGF-beta1) on both the immune system and extracellular matrix, we postulated that alterations in TGF-beta signalling in intestinal epithelial cells may play an important role in the development of IBD.TGF-beta signalling was inactivated in mouse intestine by expressing a dominant negative mutant form of the TGF-beta type II receptor under the control of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF-dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia, and anal prolapse when not maintained under specific pathogen free (SPF) conditions. Under SPF conditions we induced colitis by mixing dextran sodium sulphate (DSS) in drinking water to examine the significance of loss of TGF-beta signalling in the pathogenesis of IBD.Transgenic mice showed increased susceptibility to DSS induced IBD, and elicited increased expression of major histocompatibility complex class II, generation of autoantibodies against intestinal goblet cells, and increased activity of matrix metalloproteinase in intestinal epithelial cells compared with wild-type littermates challenged with DSS.Deficiency of TGF-beta signalling specifically in the intestine contributes to the development of IBD. Maintenance of TGF-beta signalling may be important in regulating immune homeostasis in the intestine
Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma
Authors: Maura L. Gillison, Anil K. Chaturvedi, William F. Anderson, Carole Fakhry
Journal: Journal of Clinical Oncology (2015)

Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention.
Effect of airway opening manoeuvres on thoraco-abdominal asynchrony in anaesthetized children
Authors: A. Reber, S.A. Bobbià, J. Hammer, F.J. Frei
Journal: European Respiratory Journal (2001)

Thoraco-abdominal asynchrony is frequently encountered during inhalation anaesthesia in children with adenotonsillar hypertrophy causing an upper airway obstruction. The study goal was to evaluate the impact of different airway opening manoeuvres on thoraco-abdominal asynchrony as a measure of airway obstruction. Thirty anaesthetized children (aged 2–8 yrs; sevoflurane 3% in 50% oxygen/nitrous oxide) were studied prior to elective adenotonsillectomy using respiratory inductance plethysmography to record ribcage and abdominal wave forms as a basis for calculation of the phase angle. Five airway situations were compared: 1) baseline (unsupported mandible); 2) chin lift; 3) chin lift combined with continuous positive airway pressure of 10 cmH 2 O; 4) jaw thrust; and 5) jaw thrust combined with continuous positive airway pressure of 10 cmH 2 O. Three children had complete upper airway obstruction at baseline and were excluded from the study. With chin lift, thoraco-abdominal asynchrony improved in three patients, worsened in three patients and was unchanged in 21 patients. Additional continuous positive airway pressure during chin lift did not markedly reduce thoraco-abdominal asynchrony (phase angle 89±43°, p=0.33). Jaw thrust resulted in a significant decrease of the phase angle (from 106±53° at baseline to 65±49°, p&lt;0.01); when combined with continuous positive airway pressure, no further effect on thoraco-abdominal asynchrony was found (72±44°). In anaesthetized children with adenotonsillar hypertrophy, airway opening manoeuvres have distinct effects on thoraco-abdominal asynchrony. Delivery of continuous positive airway pressure and jaw thrust can be the first airway opening manoeuvres to improve breathing patterns. Chin lift without additional continuous positive airway pressure should be used with caution in these patients because it may convert partial into almost complete airway obstruction.
Interlaboratory Variation of GHb Assays in Victoria, Australia
Authors: Richard E Gilbert, Ian Goodall, Val Young, George Jerums
Journal: Diabetes Care (1996)

To determine the extent of interlaboratory variation and accuracy in the measurement of glycated hemoglobin (GHb).All laboratories that measure glycated hemoglobin in the State of Victoria, Australia, were invited to participate, and positive responses were received from 27 to 30 laboratories. An aliquot of blood drawn from three patients with diabetes and varied glycemia and from one nondiabetic subject was sent to each participating laboratory. Distribution of results was analyzed according to the reported results and their variance from an assigned reference value and were expressed as differing from this latter value as percentage bias and in absolute terms. A bias > or = 10% or an absolute difference of > or = 1% HbA1c from the reference value was considered significant.Reported results for the same blood sample ranged from 4.1 to 5.8%, 5.1 to 8.2%, 6.7 to 9.3%, and 10.1 to 14.7% for the specimens from the nondiabetic subject and the diabetic patients with good, moderate, and poor glycemic control, respectively. The proportion of laboratories with results that differed by > or = 10% bias from the reference value were 39% (12 of 30), 29% (9 of 30), 16% (5 of 30), and 32% (10 of 30), and the proportion reporting results that differed by > or = 1% HbA1c in absolute terms from the reference values were 3% (1 of 30), 6% (2 of 30), 16% (5 of 30), and 23% (7 of 30) for the specimens from the nondiabetic subject and the diabetic patients with good, moderate, and poor glycemic control, respectively.A substantial degree of interlaboratory variation for GHb measurement exists in Victoria, Australia. This may lead to difficulties in interpretation when GHb is assayed by different laboratories in the same patient over time. Interlaboratory standardization may be achievable by calibration to a standard assigned by a reference laboratory and distributed to all laboratories measuring GHb.
Starting Insulin Treatment as an Outpatient
Authors: R. Malcolm Wilson
Journal: JAMA (1986)

Most textbooks advise that newly diagnosed insulin-dependent diabetics be admitted to the hospital. Nevertheless, if they are not acutely ill, we start insulin treatment on an outpatient basis. We report herein the logistics, efficacy, and safety of our system. Over two years, 115 newly diagnosed insulin-dependent diabetics were seen in our hospital. Fifteen (66% of them ketoacidotic) were admitted. The other 100 were treated as outpatients by a nurse specialist with a starting dosage of 6 to 10 units of intermediate-acting insulin twice daily. Hemoglobin A1 concentration at diagnosis was 15.2%±2.7% (mean±SD); at six months, 10.9%±2.9%; and at one year, 10.6%±2.8%. Only three outpatient starters were hospitalized in the first year, one for hypoglycemia and two with respiratory tract infections. Our findings suggest that outpatient stabilization is both safe and cost-effective. (<i>JAMA</i>1986;256:877-880)
Analysis of long-term results and prognostic factors among 138 patients with advanced Hodgkin's disease treated with the alternating MOPP/ABVD chemotherapy
Authors: E. Brusamolino, E. Orlandi, E. Morra, G. Castelli, G. Pagnucco, A. Livraghi, C. Astori, A. Santagostino, M. Lazzarino, C. Bernasconi
Journal: Annals of Oncology (1994)
Drug points: Neuropsychiatric complications of nevirapine treatment
Authors: M E J. Wise
Journal: BMJ (2002)

We should interpret these findings cautiously.The study relied on self reports of bullying, and a higher response rate would have been desirable.Nevertheless, the findings suggest that disturbingly high levels of bullying and mistreatment during training are part of many junior doctors' perceptions and experience.Thanks to Jon Deeks for statistical comments and to Annette Barrett, Sarah Bell, and Lesley Marquis for help with data collection.
The Effect of Glutathione and <i>N</i>-Acetylcysteine on Lipoperoxidative Damage in Patients with Early Septic Shock
Authors: ORESTE ORTOLANI, ANNA CONTI, ANGELO RAFFAELE DE GAUDIO, ELISA MORALDI, QUIRINA CANTINI, GIANPAOLO NOVELLI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Both the hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock. This study examined whether the antioxidants glutathione (GSH) and N-acetyl-L-cysteine (NAC) play a protective role against damage by OFR in early septic shock. We randomly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis. All of the patients received septic shock therapy, including parenteral nutrition, antibiotics, and volume-expanding and inotropic agents. One group (Group B) also received 70 mg/kg/d of intravenous GSH, and a second group (Group C), 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC. The protection against OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, erythrocyte deformability, complement activation, and clinical scores at admission and on Days 3 and 5 of treatment. A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values. The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved. In conclusion, the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock.
Comparison of platelet aggregation response and receptor occupancy of RPR 109891 administered intravenously in patients with recent acute coronary syndromes (TIMI15A)
Authors: L. Jennings, R. Wise, K. Ramsey, M. Jacoski, J.F. Tamby, S. May, M. White, S. Cholera, C. Mendoza, M. Todd, J. Rush, R. Giugliano
Journal: Journal of the American College of Cardiology (1998)
Interferon Beta Use and Disability Prevention in Relapsing-Remitting Multiple Sclerosis
Authors: Benjamin M. Greenberg, Laura Balcer, Peter A. Calabresi, Bruce Cree, Anne Cross, Teresa Frohman, Ralf Gold, Eva Havrdova, Bernhard Hemmer, Bernd C. Kieseier, Robert Lisak, Aaron Miller, Michael K. Racke, Lawrence Steinman, Olaf Stuve, Heinz Wiendl, Elliot Frohman
Journal: JAMA Neurology (2012)

<h3>Context: </h3>Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established.<h3>Objective: </h3>To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS.<h3>Design, Setting, and Patients: </h3>Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts.<h3>Main Outcome Measures: </h3>The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at &gt;150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication.<h3>Results: </h3>The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta–treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results.<h3>Conclusion: </h3>Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.
Ceramide Is Increased in the Lower Airway Epithelium of People with Advanced Cystic Fibrosis Lung Disease
Authors: Malcolm Brodlie, Michael C. McKean, Gail E. Johnson, Joe Gray, Andrew J. Fisher, Paul A. Corris, James L. Lordan, Christopher Ward
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Ceramide accumulates in the airway epithelium of mice deficient in cystic fibrosis transmembrane conductance regulator, resulting in susceptibility to Pseudomonas aeruginosa infection and inflammation.Objectives: To investigate quantitatively ceramide levels in the lower airway of people with cystic fibrosis compared with pulmonary hypertension, emphysema, and lung donors.Methods: Immunohistochemistry was performed on the lower airway epithelium of explanted lungs (eight cystic fibrosis, emphysema, and pulmonary hypertension, respectively) and eight donor lungs using ceramide, neutrophil elastase, and myeloperoxidase antibodies. High-performance liquid chromatography–mass spectrometry was performed on tissue from five lungs with cystic fibrosis and five with pulmonary hypertension.Measurements and Main Results: Staining for ceramide was significantly increased in the lower airway epithelium of people with cystic fibrosis (median, 14.11%) compared with pulmonary hypertension (3.03%; P = 0.0009); unused lung donors (3.44%; P = 0.0009); and emphysema (5.06%; P = 0.01). Ceramide staining was increased in emphysematous lungs compared with pulmonary hypertension (P = 0.0135) and unused donors (P = 0.0009). The number of neutrophil elastase– and myeloperoxidase-positive cells in the airway was positively correlated with the percentage of epithelium staining for ceramide (P = 0.001). Ceramide staining was significantly increased in lungs colonized with Pseudomonas aeruginosa (10.1%) compared with those not colonized (3.14%; P = 0.0106). Significantly raised levels of ceramides C16:0, C18:0, and C20:0 were detected by mass spectrometry in lungs with cystic fibrosis compared with pulmonary hypertension. Differences in C22:0 were not significant.Conclusions: Immunoreactive ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis. Detected by mass-spectrometry ceramide species C16:0, C18:0, and C20:0 but not C22:0 are increased.
The association of diabetic status, age, and race to withdrawal from dialysis.
Authors: C B Nelson, F K Port, R A Wolfe, K E Guire
Journal: Journal of the American Society of Nephrology (1994)

Higher rates of withdrawal from dialysis have been shown among young diabetic patients. This study examined the hypothesis that diabetic status has a joint effect with age as the result of an age-related increase in co-morbid conditions among nondiabetic ESRD patients. Using data collected during the 1980s by the Michigan Kidney Registry, the experience of 4,753 white and 2,988 black Michigan dialysis patients (13,863 patient years) is analyzed. During follow-up, 364 white and 80 black patients withdrew from dialysis. By use of a Cox analysis, adjusted rates of withdrawal were shown to be higher among white than black patients (rate ratio (RR) = 3.34; P < 0.001), without significant differences by diabetic status. Rates increased with age (RR = 7.9 for 80+ versus 20 to 35 yr; P < 0.001), without significantly different patterns by race. Adjusted withdrawal rates among diabetics were 2.3 times that of nondiabetics overall (P < 0.001), with a statistically significant joint effect with age, the RR being highest among young patients. Among white patients, nondiabetics using continuous ambulatory peritoneal dialysis had a lower relative withdrawal rate than those using hemodialysis (RR = 0.73; P = 0.07), whereas diabetics using continuous ambulatory peritoneal dialysis showed slightly higher although statistically insignificant rates than their counterparts using hemodialysis (RR = 1.21; P = 0.50). Between 1980 and 1989, withdrawal rates for white patients aged 20 to 34 yr tended to decrease by 20% per year (P = 0.05), whereas they increased by 11% per year for patients aged 50 to 69 yr (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Improving the Methodologic and Ethical Validity of Best Supportive Care Studies in Oncology: Lessons From a Systematic Review
Authors: Nathan I. Cherny, Amy P. Abernethy, Florian Strasser, Rama Sapir, David Currow, S. Yousuf Zafar
Journal: Journal of Clinical Oncology (2009)

To systematically review the best supportive care (BSC) literature and to evaluate the ethical and methodologic validity issues by using widely acknowledged criteria.Two search strings that included both cancer and supportive as terms (with random article type, or review or meta-analysis) explored databases from 1966 to 2008. Citations, abstracts, and papers were reviewed for inclusion criteria, and relevant data were extracted by two independent researchers. Data were validated for accuracy. Ethical and methodologic validity were evaluated by using the criteria derived from the Helsinki Requirements of the WMA; CONSORT statements for the evaluation of reports of randomized, controlled trials; and the universal requirements for ethical clinical research.Forty-three published papers were identified that described 32 studies, 20 of which incorporated the design of treatment plus supportive care (SC) versus SC alone, and 12 of which incorporated the design of treatment versus SC. Most of the studies had poor compliance to critical Helsinki requirements, to methodologic precautions derived from the CONSORT statement for studies involving a nonpharmacologic arm, and to four of seven universal requirements for ethical clinical research.Lack of rigor in BSC studies has contributed to a generation of research with widespread ethical and methodologic shortcomings. Ad hoc SC and lack of standardization of SC delivery may be sources of systematic bias or error in BSC trials. Rectifying these shortcomings in future studies demands greater vigilance toward these issues by researchers, institutional review boards, editors, and peer reviewers. Given the prevalence of overlooked problems that are later identified, currently open BSC studies should be reevaluated by institutional review boards and researchers to check for ethical and methodologic validity, and identified shortcomings should be addressed.
Impaired T- and B-cell development in Tcl1-deficient mice
Authors: Sang-Moo Kang, Maria Grazia Narducci, Cristina Lazzeri, Adriana M. Mongiovì, Elisabetta Caprini, Antonella Bresin, Fabio Martelli, Jay Rothstein, Carlo Maria Croce, Max D. Cooper, Giandomenico Russo
Journal: Blood (2004)
Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes
Authors: Marco Mielcarek, Barry E. Storer, Michael Boeckh, Paul A. Carpenter, George B. McDonald, H. Joachim Deeg, Richard A. Nash, Mary E. D. Flowers, Kristine Doney, Stephanie Lee, Kieren A. Marr, Terry Furlong, Rainer Storb, Frederick R. Appelbaum, Paul J. Martin
Journal: Blood (2008)
FISH AND THE HEART
Authors: MarkR Goldstein, R.A Riemersma, C.A Sargent, R.A Abraham, R.L Wright, M.F Oliver, Petr Skrabanek, G Hornstra, P.L Mclennan, J.S Charnock, K Sundrum, T.M Bridle, M.Y Abeywardena, MichaelL Burr, AnnM Fehily
Journal: The Lancet (1989)
Risk factors for community-acquired pneumonia in adults: a population-based case-control study
Authors: J Almirall, I Bolibar, X Balanzo, CA Gonzalez
Journal: European Respiratory Journal (1999)

Although community-acquired pneumonia (CAP) remains a major cause of hospitalization and death, few studies on risk factors have been performed. A population-based case-control study of risk factors for CAP was carried out in a mixed residential-industrial urban area of 74,610 adult inhabitants in the Maresme (Barcelona, Spain) between 1993 and 1995. All patients living in the area and clinically suspected of having CAP at primary care facilities and hospitals were registered. In total, 205 patients with symptoms, signs and radiographic infiltrate compatible with acute CAP participated in the study. They were matched by municipality, sex and age with 475 controls randomly selected from the municipal census. Risk factors relating the subject's characteristics and habits, housing conditions, medical history and treatments were investigated by means of a questionnaire. In the univariate analysis, an increased risk of CAP was associated with low body mass index, smoking, respiratory infection, previous pneumonia, chronic lung disease, lung tuberculosis, asthma, treated diabetes, chronic liver disease, and treatments with aminophiline, aerosols and plastic pear-spacers. In multivariate models, the only statistically significant risk factors were current smoking of &gt;20 cigarettes x day(-1) (odds ratio (OR)=2.77; 95% confidence interval (CI) 1.14-6.70 compared with never-smokers), previous respiratory infection (OR=2.73; 95% CI 1.75-4.26), and chronic bronchitis (OR=2.22; 95% CI 1.13-4.37). Benzodiazepines were found to be protective in univariate and multivariate analysis (OR=0.46; 95% CI 0.23-0.94). This population-based study provides new and better established evidence on the factors associated with the occurrence of pneumonia in the adult community.
STUDIES IN DIURNAL VARIATION OF WATER AND ELECTROLYTE EXCRETION: NOCTURNAL DIURESIS OF WATER AND SODIUM IN CONGESTIVE CARDIAC FAILURE AND CIRRHOSIS OF THE LIVER 12
Authors: Ralph Goldman
Journal: Journal of Clinical Investigation (1951)

Clinicians have been aware that nocturia is an important symptom of disease, yet there has been little investigation of the underlying mechanisms.The nocturias of obstruction with overflow, of cystitis, and of pregnancy, have had obvious ex- Arteriosclerotic heart dis- 46 ease Rheumatic heart disease 47 Br Arteriosclerotic heart dis- 55 ease Ba Rheumatic heart disease 49 Je Hypertensive and arterio- 62 sclerotic heart disease Pe Arteriosclerotic heart dis- 58 ease Si Cirrhosis 53 Do Cirrhosis 52 Re Cirrhosis 55 Le Cirrhosis 52 Ro Cirrhosis 55 Li Cirrhosis 61 He Cirrhosis with hepatoma 56