tbuckley/cabot-search huggingface dataset:
A Longitudinal, Population-Based, Cohort Study of Childhood Asthma Followed to Adulthood
Authors: Malcolm R. Sears, Justina M. Greene, Andrew R. Willan, Elizabeth M. Wiecek, D. Robin Taylor, Erin M. Flannery, Jan O. Cowan, G. Peter Herbison, Phil A. Silva, Richie Poulton
Journal: New England Journal of Medicine (2003)

The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse.We assessed children born from April 1972 through March 1973 in Dunedin, New Zealand, repeatedly from 9 to 26 years of age with questionnaires, pulmonary-function tests, bronchial-challenge testing, and allergy testing.By the age of 26 years, 51.4 percent of 613 study members with complete respiratory data had reported wheezing at more than one assessment. Eighty-nine study members (14.5 percent) had wheezing that persisted from childhood to 26 years of age, whereas 168 (27.4 percent) had remission, but 76 (12.4 percent) subsequently relapsed by the age of 26. Sensitization to house dust mites predicted the persistence of wheezing (odds ratio, 2.41; P=0.001) and relapse (odds ratio, 2.18; P=0.01), as did airway hyperresponsiveness (odds ratio for persistence, 3.00; P<0.001; odds ratio for relapse, 3.03; P<0.001). Female sex predicted the persistence of wheezing (odds ratio, 1.71; P=0.03), as did smoking at the age of 21 years (odds ratio, 1.84; P=0.01). The earlier the age at onset, the greater the risk of relapse (odds ratio, 0.89 per year of increase in the age at onset; P<0.001). Pulmonary function was consistently lower in those with persistent wheezing than in those without persistent wheezing.In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission. The factors predicting persistence or relapse were sensitization to house dust mites, airway hyperresponsiveness, female sex, smoking, and early age at onset. These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.
Alteration of immunoglobulin phenotype in cell culture-adapted lines of two mouse plasmacytomas.
Authors: S J Hausman, M J Bosma
Journal: The Journal of Experimental Medicine (1975)

Murine plasmacytomas can be adapted to continuous in vitro culture by alternate passage between culture and animal. We have found that the kinetics of adaptation reflect a selection for the growth of variant plasmacytoma cells. The inclusion of an altered immunoglobulin phenotype in such variant cells could explain the Ig-producing variants that we observed in two of six transplantable lines of plasmacytomas that were adapted to culture. The first variant, an IgM-producing cell line (104-76), was adapted from a transplanted line of MOPC 104E that had stopped producing IgM with binding specificity for alpha1-3 Dextran. Unlike MOPC 104E, the IgM of 104-76 contains kappa- instead of lambda-light chains and probably contains an altered or different mu-heavy chain. A second variant (352-57) was found in an IgG2b-producing tumor (MOPC 352) which was induced in a BALB/c mouse strain (CB-6) that carried Ig genes of the C57BL/Ka allotype. This cell line apparently switched from producing IgG2b molecules of the C57BL allotype (H9) and of a known idiotype to IgG1 molecules of the BALB/c allotype (F19) without the idiotype marker. The propagation of a biclonal plasmacytoma from the time of original tumor induction does not appear as a likely explanation for these results. Rather, we seem to be dealing with plasmacytoma variants or with the possible induction of secondary tumors of host origin.
Stem Cell Model May Shed Light on Pathogenesis of Mental Illness
Authors: Tracy Hampton
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Actions of Diphenylhydantoin on the Electrical Properties of Isolated Rabbit and Canine Atria
Authors: HAROLD C. STRAUSS, J. THOMAS BIGGER, ARTHUR L. BASSETT, BRIAN F. HOFFMAN
Journal: Circulation Research (1968)

The effects of diphenylhydantoin (DPH), 10 -8 to 10 -4 M, were studied on the various types of cells in the isolated right atrial preparation and on the specialized cells of Bachmann's bundle in atrial preparations obtained from puppies. High concentrations of DPH (10 -4 M) slowed sinoatrial rate but lower concentrations had little effect. These chronotropic effects of DPH were direct. DPH in concentrations above 10 -5 M decreased the slope of phase 4 depolarization in cells in the sinoatrial node and venous automatic tissue. DPH in concentrations of 10 -8 to 10 -6 M had no effect on transmembrane action potentials recorded from any cell studied; concentrations of 10 -4 M, however, prolonged the terminal phase of repolarization. High concentrations (10 -4 M) also prolonged the effective refractory period of Bachmann's bundle and ordinary atrial and perinodal fibers by an average of 10%. DPH markedly increased the dv/dt of phase 0 of the action potential and membrane responsiveness of ordinary atrial and specialized Bachmann's bundle fibers under control conditions and produced more striking increases when these two variables had been decreased by ouabain. DPH was also proved capable of reversing ouabain-induced sinoatrial block. This unique ability of DPH to enhance membrane responsiveness and to improve conduction in the absence of significant effects on the effective refractory period and automaticity of atrial cells suggests that this may be the sole mechanism of its antiarrhythmic action.
Randomized Phase II Study of Erlotinib Combined With Bevacizumab Compared With Bevacizumab Alone in Metastatic Renal Cell Cancer
Authors: Ronald M. Bukowski, Fairooz F. Kabbinavar, Robert A. Figlin, Keith Flaherty, Sandy Srinivas, Ulka Vaishampayan, Harry A. Drabkin, Janice Dutcher, Sarah Ryba, Qi Xia, Frank A. Scappaticci, David McDermott
Journal: Journal of Clinical Oncology (2007)

Bevacizumab (Bev) has clinical activity in advanced renal cell carcinoma (RCC), and, when combined with erlotinib (Erl), has shown encouraging objective response rate (ORR) and progression-free survival (PFS). We performed a phase II, randomized, double-blind, multicenter, placebo-controlled trial to assess whether Erl provides additional clinical benefit with regard to PFS and ORR when combined with Bev in first-line treatment of metastatic RCC.One hundred four patients received intravenous Bev (10 mg/kg) every 2 weeks in combination with oral Erl (150 mg) or placebo daily. Patients were treated until progression or toxicity.A landmark analysis was performed 9 months after enrollment was completed (median follow-up, 9.8 months). Sixty-five patients had discontinued therapy; time to study discontinuation did not differ between the two treatment groups. The median PFS was 9.9 months (Bev + Erl [B+E]) versus 8.5 months (Bev; hazard ratio = 0.86; 95% CI, 0.5 to 1.49; P = .58). ORR (complete plus partial) was 14% (B+E) versus 13% (Bev). One complete response occurred in the B+E group. Median survival was 20 months for B+E but not reached for Bev. The most common grade 3/4 adverse events (> 5% of patients) were hypertension, rash, proteinuria, diarrhea, and hemorrhage. One treatment-related death occurred on study (GI perforation, B+E group).The addition of Erl to Bev was well tolerated, but did not provide additional clinical benefit compared with Bev alone. Bev has encouraging clinical activity for previously untreated metastatic RCC patients.
The Ontario Trial of Active Compression-Decompression Cardiopulmonary Resuscitation for In-Hospital and Prehospital Cardiac Arrest
Authors: Ian G. Stiell
Journal: JAMA (1996)

To compare the impact of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest.Randomized controlled trial with blinding of allocation using a sealed container.(1) Emergency departments, wards, and intensive care units of 5 university hospitals and (2) all locations outside hospitals in 2 midsized cities.A total of 1784 adults who had cardiac arrest.Patients received either standard or ACD CPR throughout resuscitation.Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination (MMSE).All characteristics were similar in the standard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients. For in-hospital patients, there were no significant differences between the standard (n = 368) and ACD (n = 405) CPR groups in survival for 1 hour (35.1% vs 34.6%; P = .89), in survival until hospital discharge (11.4% vs 10.4%; P = .64), or in the median MMSE score of survivors (37 in both groups). For patients who collapsed outside the hospital, there were also no significant differences between the standard (n = 510) and ACD (n = 501) CPR groups in survival for 1 hour (16.5% vs 18.2%; P = .48), in survival to hospital discharge (3.7% vs 4.6%; P = .49), or in the median MMSE score of survivors (35 in both groups). Exploration of clinically important subgroups failed to identify any patients who appeared to benefit from ACD CPR.ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest.
Effect of human antileucoprotease on experimental emphysema
Authors: A Rudolphus, JA Kramps, JH Dijkman
Journal: European Respiratory Journal (1991)

Antileucoprotease (ALP), a potent inhibitor of human neutrophil elastase (HNE), may be a modulating factor in the pathogenesis of emphysema. Investigating the clearance of intratracheally-instilled ALP in hamsters, we observed a rapid clearance from the airway lumen within 60 min, whereafter the remaining 40% slowly decreased with a calculated half-life (T0.5) of 2.8 h. Lung tissue-associated ALP showed a peak at 40 min and slowly decreased (T0.5 approximately 3 h). In vivo efficacy of ALP on HNE-induced pulmonary lesions was studied by instillation of either 365 micrograms or 730 micrograms ALP, followed after 1 h by 420 micrograms HNE. Emphysema, haemorrhage and secretory cell metaplasia (SCM) were quantified 21 days after instillations. ALP was found to be able to inhibit emphysema and haemorrhage in a dose-related way, the decrease of haemorrhage being less pronounced. SCM was minimally affected. These results show that ALP inhibits efficiently the development of HNE-induced emphysema and, to a lesser extent, haemorrhage. We speculate that tissue-associated ALP might be responsible for this protection.
Overexpression of the Serine Elastase Inhibitor Elafin Protects Transgenic Mice From Hypoxic Pulmonary Hypertension
Authors: Syed H.E. Zaidi, Xiao-Mang You, Sorana Ciura, Mansoor Husain, Marlene Rabinovitch
Journal: Circulation (2002)

Background — Increased serine elastase activity has been implicated in the vascular remodeling associated with chronic hypoxia-related pulmonary hypertension in rats. Methods and Results — In this study we determined the time course of hypoxia-induced serine elastase activity in the murine lung and related this to initiation of a proteolytic cascade characterized by an increase in matrix metalloproteinases (MMPs). We then used transgenic mice in which overexpression of the selective serine elastase inhibitor elafin was targeted to the cardiovascular system to determine whether upregulation of a naturally occurring serine elastase inhibitor suppresses MMPs and the hemodynamic and structural response to chronic hypoxia (air at 380 mm Hg). In nontransgenic but not in elafin-transgenic mice, we documented a transient increase in serine elastase activity after 12 hours of hypoxic exposure attributed to a 30-kDa protein as determined by elastin zymography and fluorophosphonate/fluorophosphate-biotin labeling. Two days after hypoxia, the pro-forms of MMP-2 and MMP-9 were induced in the nontransgenic mice, but MMP-9 was suppressed in elafin-transgenic mice. Acute hypoxic vasoconstriction was similar in nontransgenic and elafin-transgenic littermates. Chronic hypoxia for 26 days resulted in &gt;1-fold increase in right ventricular pressure ( P &lt;0.004) in nontransgenic compared with control or elafin-transgenic littermates. In the latter mice, normalization of the right ventricular pressure was associated with reduced muscularization and preservation of the number of distal vessels ( P &lt;0.04 for both comparisons). Conclusions — Modulation of the severity of chronic hypoxia-induced pulmonary vascular disease could be a function of endogenously expressed serine elastase inhibitors.
Long-Term Results of the International Adjuvant Lung Cancer Trial Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer
Authors: Rodrigo Arriagada, Ariane Dunant, Jean-Pierre Pignon, Bengt Bergman, Mariusz Chabowski, Dominique Grunenwald, Miroslaw Kozlowski, Cécile Le Péchoux, Robert Pirker, Maria-Izabel Sathler Pinel, Michèle Tarayre, Thierry Le Chevalier
Journal: Journal of Clinical Oncology (2009)

Purpose Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non–small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up. Patients and Methods Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration. Results The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06). Conclusion These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.
Creatine kinase activity in patients with brittle asthma treated with long term subcutaneous terbutaline.
Authors: A P Sykes, N Lawson, J A Finnegan, J G Ayres
Journal: Thorax (1991)

Infused beta 2 agonists have been shown to cause focal myocardial necrosis. Serum creatine kinase activity was compared in 13 patients with brittle asthma currently being treated with subcutaneous terbutaline and an age and sex matched control group of patients with moderate asthma having inhaled treatment only. The median serum total creatine kinase activity for patients receiving subcutaneous terbutaline (211 units/l) was greater than that for the control group (120 units/l). The cardiac specific isoenzyme component of creatine kinase was not raised in either group, and the electrocardiograms and serum aspartate aminotransferase activity were normal. Electromyograms in five patients receiving subcutaneous terbutaline with high creatine kinase activity showed changes consistent with myositis in two, one of whom was subsequently shown to have a metabolic myopathy, which is thought to be long standing. No pathological changes were seen in the myocardium at necropsy in a patient who died from an acute attack of asthma while taking subcutaneous terbutaline. These results suggest that the raised creatine kinase activity seen in patients receiving this treatment is unlikely to be myocardial in origin.
Meta-Regression Analysis of Placebo Response in Antipsychotic Trials, 1970–2010
Authors: Ofer Agid, Cynthia O. Siu, Steven G. Potkin, Shitij Kapur, Eric Watsky, Douglas Vanderburg, Robert B. Zipursky, Gary Remington
Journal: American Journal of Psychiatry (2013)

Large placebo response presents a major challenge for psychopharmacologic drug development and contributes to the increasing failure of psychiatric trials. The objective of this meta-regression analysis was to identify potential contributors to placebo response in randomized controlled trials of antipsychotic treatment in schizophrenia.The authors extracted trial design and clinical variables from eligible randomized controlled trials (N=50) identified through searches of MEDLINE (1960-2010) and other sources. Standardized mean change (SMC) was used as the effect size measure for placebo response, based on change scores on the Brief Psychiatric Rating Scale or the Positive and Negative Syndrome Scale from baseline to endpoint (2 to 12 weeks).The results suggest significant heterogeneities (Q=387.83, df=49) in the magnitude of placebo response (mean SMC, -0.33, range -1.4 to 0.9) and in study quality. Both placebo SMC and study quality increased over time. Younger age, shorter duration of illness, greater baseline symptom severity, and shorter trial duration were significantly associated with greater placebo response, while country (United States compared with other countries) was not. More study sites, fewer university or Veterans Affairs treatment settings, and a lower percentage of patients assigned to receive placebo were associated with a greater placebo response, but these were not independent of publication year. Study quality affected the variability but not mean levels of placebo response.This study identified important patient characteristics and trial design factors affecting the level of placebo response and hence the likelihood of detecting efficacy signals in randomized controlled trials. Future studies should test whether controlling these factors improves the detection of an antipsychotic effect.
Lifestyle Counseling for Type 2 Diabetes Risk Reduction in Dutch Primary Care
Authors: Paulina W.A. Vermunt, Ivon E.J. Milder, Frits Wielaard, Jeanne H.M. de Vries, Hans A.M. van Oers, Gert P. Westert
Journal: Diabetes Care (2011)

OBJECTIVE To study the overall effect of the Active Prevention in High-Risk Individuals of Diabetes Type 2 in and Around Eindhoven (APHRODITE) lifestyle intervention on type 2 diabetes risk reduction in Dutch primary care after 0.5 and 1.5 years and to evaluate the variability between general practices. RESEARCH DESIGN AND METHODS Individuals at high risk for type 2 diabetes (Finnish Diabetes Risk Score ≥13) were randomly assigned into an intervention group (n = 479) or a usual-care group (n = 446). Comparisons were made between study groups and between general practices regarding changes in clinical and lifestyle measures over 1.5 years. Participant, general practitioner, and nurse practitioner characteristics were compared between individuals who lost weight or maintained a stable weight and individuals who gained weight. RESULTS Both groups showed modest changes in glucose values, weight measures, physical activity, energy intake, and fiber intake. Differences between groups were significant only for total physical activity, saturated fat intake, and fiber intake. Differences between general practices were significant for BMI and 2-h glucose but not for energy intake and physical activity. In the intervention group, the nurse practitioners’ mean years of work experience was significantly longer in individuals who were successful at losing weight or maintaining a stable weight compared with unsuccessful individuals. Furthermore, successful individuals more often had a partner. CONCLUSIONS Risk factors for type 2 diabetes could be significantly reduced by lifestyle counseling in Dutch primary care. The small differences in changes over time between the two study groups suggest that additional intervention effects are modest. In particular, the level of experience of the nurse practitioner and the availability of partner support seem to facilitate intervention success.
Points from Letters: "Cures" for Leukaemia
Authors: M. J. Derbyshire
Journal: BMJ (1964)

Until benzidine was taken off the market because of carcinogenic risks to those engaged in its manufacture the test most widely used was the Gregersen slide-test.'It was in general use on the Continent and in America, and was becoming more generally used in this country.It was recommended in many of the textbooks.5In general practice and in hospital side- wards there are obvious objections to tests, such as the test-tube benzidine and ortho- tolidine tests commonly employed in clinical laboratories, which may give positive results with gum-bleeding and after the eating of meats in moderate amount.Ogilvie, who was the first in this country to describe the Gregersen slide-test,8 affirmed that with it a blue or green-blue colour appearing within 30 seconds is proof of the presence of occult blood irrespective of the patient's diet, with the obvious exceptions of foods with a high blood-pigment concentration such as liver, black pudding, and bone-marrow.Now it is recognized that salicylates also should be withheld.Bockus' employs the Gregersen slide-test as a routine procedure.Benzidine is now produced under safe con- ditions of manufacture and is again on the market.Put up in waxed paper the powders will last indefinitely.The Greger- sen slide-test is cheap and simple and can be performed just as quickly as the tablet tests.Its reliability has been widely proved over the years, and it should be finding its way back into our hospital side-rooms and our consulting-rooms.-Iam, etc., Edinburgh 9. S. LIPETZ.
Where and When does the What system play a role in eye movement control?
Authors: K. Doré-Mazars
Journal: Behavioral and Brain Sciences (1999)

This commentary focuses on Findlay &amp; Walker's model and more specifically, on its underestimation of the role of cognitive processes in eye movement control during complex activities such as text scanning. In particular, the issue of the complexity of the subject's task/behavior is discussed to stress the importance of the link between selection for perceptual processing on the one hand, and the selection of a target for a saccade, on the other. Future models will have to account for the fact that the goal of any saccade is to bring the eyes to a relevant object and that the selection of this saccade target is closely related to object recognition.