tbuckley/cabot-search huggingface dataset:
Points: Potentiation of oral anticoagulants by ketoconazole
Authors: J G Simpson, C. Cunningham, P. Whiting
Journal: BMJ (1984)

which is more likely to be detrusor inhibition mediated at the level of the sacral cord "bladder centre."Further research is indicated to assess the interaction of both limbs of the autonomic nervous system with the various peptidergic systems in the control of lower urinary tract function to evaluate their future therapeutic importance.
Small animals in the study of pathological effects of asbestos
Authors: Paul F. Holt
Journal: Environmental Health Perspectives (1974)

The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies.The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos.Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 μm long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal.This clearance mechanism is inhibited by other factors: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly.The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs.
Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States
Authors: Jeffrey I. Cohen, Elaine S. Jaffe, Janet K. Dale, Stefania Pittaluga, Helen E. Heslop, Cliona M. Rooney, Stephen Gottschalk, Catherine M. Bollard, V. Koneti Rao, Adriana Marques, Peter D. Burbelo, Siu-Ping Turk, Rachael Fulton, Alan S. Wayne, Richard F. Little, Mitchell S. Cairo, Nader K. El-Mallawany, Daniel Fowler, Claude Sportes, Michael R. Bishop, Wyndham Wilson, Stephen E. Straus
Journal: Blood (2011)
The University Group Diabetes Program
Authors: Jerome Cornfield
Journal: JAMA (1971)

The basic conclusion of  University Group Diabetes Program on tolbutamide is: the findings of this study indicate that  combination of diet and tolbutamide therapy is no more effective than diet alone in prolonging life. Moreover,  findings suggest that tolbutamide and diet may be less effective than diet alone or than diet and insulin at least in so far as cardiovascular mortality is concerned. 1 With no evidence of efficacy and a definite possibility of toxicity  investigators concluded that  safety of  patients still receiving tolbutamide therapy required its discontinuance and that  factual basis for this decision needed to be communicated to  biomedical scientific community. This prudent decision and moderately worded conclusion has been received by some critics with a hostility which has no discernible scientific basis. The following analysis is largely confined to Dr. Schor's analysis (see page 1671).  In general, independent repetition
The Treatment of Psychotic Major Depression: Is There a Role for Adjunctive Psychotherapy?
Authors: Brandon A. Gaudiano, Ivan W. Miller, James D. Herbert
Journal: Psychotherapy and Psychosomatics (2007)

Psychotic depression is a relatively prevalent mood disorder associated with greater symptom severity, a poorer course of illness and higher levels of functional impairment compared with nonpsychotic depression. Separate lines of investigation suggest that various forms of cognitive-behavioral therapy are efficacious for treating severe forms of nonpsychotic depression as well as primary psychotic disorders. However, there currently are no empirically supported psychotherapies specifically designed for treating psychotic depression.We review the efficacy of current somatic treatments for the disorder and discuss the limited data to date on potentially useful psychotherapeutic approaches. In particular, we describe the clinical improvement observed in a subgroup of hospitalized patients with psychotic depression treated with Acceptance and Commitment Therapy as part of a larger clinical trial.Pilot results demonstrated that Acceptance and Commitment Therapy was associated with clinically significant reductions in acute symptom severity and impairment compared with treatment as usual.The findings suggest that patients with psychotic depression can benefit from psychotherapy. Clinical and research recommendations in this area are presented.
Interacting with the BMJ to solve clinical problems
Authors: R. Smith
Journal: BMJ (2003)

employment than those without day care, but they did not have higher household incomes (p 906).At 18 months' follow up, 25% more mothers with access to day care were in paid employment, but they were no more likely than those without access to reach a weekly household income of £200.The government has said that day care is important in helping reduce poverty, by increasing maternal paid employment.The authors argue that without simultaneously tackling low pay and the benefits structure, providing day care is not an effective strategy to reduce poverty.
Biology of tooth replacement in amniotes
Authors: John A Whitlock, Joy M Richman
Journal: International Journal of Oral Science (2013)

Tooth replacement is a common trait to most vertebrates, including mammals. Mammals, however, have lost the capacity for continuous tooth renewal seen in most other vertebrates, and typically have only 1-2 generations of teeth. Here, we review the mechanisms of tooth replacement in reptiles and mammals, and discuss in detail the current and historical theories on control of timing and pattern of tooth replacement and development.
A Haemoglobinopathy Involving Haemoglobin H and a New (Q) Haemoglobin
Authors: F. Vella, R. H. C. Wells, J. A. M. Ager, H. Lehmann
Journal: BMJ (1958)

The technique of electrophoresis was first used success- fully in the study of adult haemoglobin by Pauling, Itano, Singer, and Wells (1949), when they demonstrated that haemolysates obtained from the erythrocytes of patients suffering from sickle-cell anaemia exhibited properties which differed greatly from those of haemolysates of erythrocytes from normal adult individuals.This discovery of the usefulness of electro- phoresis in the study of haemoglobin has led to the recognition of other variants of adult human haemo- globin, whose genetic control, somatic effects, and geographlical distribution have been under intensive study ever since.It is the purpose of the present communication to describe in detail the properties of a new haemoglobin which was detected in association with haemoglobin H and to give the clinical and other findings in the patient presenting this new haemoglobinopathy. Case ReportA Chinese man aged 24 was first admitted to the general Hospital, Singapore, in August, 1953, with a history of short- ness of breath, palpitations, giddiness, blurring of vision, and precordial pain on exertion, associated with anorexia and generalized oedema.The onset of these symptoms had been insidious over a period of about three months.
Peritoneal dialysis adequacy: A model to assess feasibility with various modalities
Authors: Jose A. Diaz-Buxo, Frank A. Gotch, Tom I. Folden, Shelden Rosenblum, James Zazra, Nancy Lew, Terri L. Crawford, Brenda Youngblood, Angie Pesich, J. Michael Lazarus
Journal: Kidney International (1999)
Incomplete filling and incoordinate contraction as mechanisms of hypotension during ventricular tachycardia in man.
Authors: J A Lima, J L Weiss, P A Guzman, M L Weisfeldt, P R Reid, T A Traill
Journal: Circulation (1983)

We sought to determine mechanisms for decrease of cardiac output and for hypotension during ventricular tachycardia (VT) in man. Two-dimensional and M mode echocardiograms and left ventricular pressure from micromanometer-tipped catheters were obtained in 20 patients before, during, and at the end of induced hypotensive VT. Patients were divided into two groups according to left ventricular function in sinus rhythm as assessed by angiographic ejection fraction (EF) before electrophysiologic study. Group 1 (n = 8) had angiographic EF greater than or equal to 50% in normal sinus rhythm, and group 2 (n = 12) had EF less than or equal to 40%. During VT, left ventricular cavity volume (as indexed by short- and long-axis two-dimensional end-diastolic cavity areas) was markedly reduced in group 1, from 19.7 +/- 2 to 8.6 +/- 2 cm2 (p less than .001) and from 32.0 +/- 8 to 22.5 +/- 7 cm2 (p less than .001), respectively, but was only slightly reduced in group 2, from 34.1 +/- 6 to 31.5 +/- 7 cm2 (p = .044) and from 45.0 +/- 8 to 49.4 +/- 7 cm2 (p = NS), respectively. Conversely, left ventricular systolic function during VT (as indexed by fractional reduction in two-dimensional short- and long-axis areas) was markedly depressed in group 2, from 25.6 +/- 6% to 4.2 +/- 4% (p = .005) and from 13.7 +/- 3% to 1.8 +/- 0.8% (p less than .001), respectively, but remained at control levels in group 1. Left ventricular end-diastolic pressures increased in group 1, from 11.8 +/- 2 to 27.7 +/- 8 mm Hg (p = .005) and did not change in group 2 during VT. Pressure-dimension loops from left ventricular pressure and M mode echocardiographically determined cavity dimensions generated from the end of the VT episodes showed that diastolic pressure-dimension relationships returned to control levels with the first prolonged diastolic interval in group 1 patients, indicating that incomplete relaxation was the mechanism responsible for reduction of cardiac output during VT in these patients. Coordination of contraction and relaxation (indicated by the percent ratio of the pressure-dimension loop area to the area of the rectangle just enclosing the loop) decreased from 37 +/- 11% to 16 +/- 13% in group 2 patients during VT (p = .013) but remained at control levels in group 1 patients. Thus, during VT patients with impaired left ventricular function in sinus rhythm (group 2) developed severe discoordination, and patients with normal or near-normal function (group 1) developed incomplete relaxation to account for stroke volume deterioration and hypotension.
Long-term treatment with low doses of interferon ALFA-2B (rIFNa2b) in patients with chronic non-A, non-B (NANB) hepatitis: Data of a multicenter randomized prospectively controlled trial
Authors: R. Müller, R. Baumgarten, R. Markus, K.H. Beckh, K. Loeschke, W. Stremmel, C. Niederau, K.-H. Wiedmann, P. Weber
Journal: Journal of Hepatology (1990)
Increased Glucocorticoid Receptor β Alters Steroid Response in Glucocorticoid-insensitive Asthma
Authors: Elena Goleva, Ling-bo Li, P. Taylor Eves, Matthew J. Strand, Richard J. Martin, Donald Y. M. Leung
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Glucocorticoids (GCs) are highly effective in the treatment of asthma. However, some individuals have GC-insensitive asthma.To evaluate the functional response to steroids of bronchoalveolar lavage (BAL) cells from sites of airway inflammation from patients with GC-insensitive versus GC-sensitive asthma. As well, to attempt to define the functional role of glucocorticoid receptor (GCR)beta (a splicing variant, and dominant negative inhibitor of, the classic GCRalpha) in controlling GCRalpha nuclear translocation and transactivation at a molecular level.Fiberoptic bronchoscopy with collection of BAL fluid was performed on seven patients with GC-sensitive asthma and eight patients with GC-insensitive asthma. GCRalpha cellular shuttling in response to 10(-6) M dexamethasone treatment and GCRbeta expression were analyzed in BAL cells by immunofluorescence staining. The effects of overexpression and silencing of GCRbeta mRNA on GCRalpha function were assessed.Significantly reduced nuclear translocation of GCRalpha in response to steroids was found in BAL cells from patients with GC-insensitive asthma. BAL macrophages from patients with GC-insensitive asthma had significantly increased levels of cytoplasmic and nuclear GCRbeta. It was demonstrated that GCRalpha nuclear translocation and its transactivation properties were proportionately reduced by level of viral transduction of the GCRbeta gene into the DO-11.10 cell line. RNA silencing of GCRbeta mRNA in human BAL macrophages from patients with GC-insensitive asthma resulted in enhanced dexamethasone-induced GCRalpha transactivation.GC insensitivity is associated with loss of GCRalpha nuclear translocation in BAL cells and elevated GCRbeta, which may inhibit GCRalpha transactivation in response to steroids.
Fungi and allergic lower respiratory tract diseases
Authors: Alan P. Knutsen, Robert K. Bush, Jeffrey G. Demain, David W. Denning, Anupma Dixit, Abbie Fairs, Paul A. Greenberger, Barbara Kariuki, Hirohito Kita, Viswanath P. Kurup, Richard B. Moss, Robert M. Niven, Catherine H. Pashley, Raymond G. Slavin, Hari M. Vijay, Andrew J. Wardlaw
Journal: Journal of Allergy and Clinical Immunology (2012)
Patients' Compliance With Health Regimens
Authors: Irwin M. Rosenstock
Journal: JAMA (1975)

EVERY practicing physician soon learns that the proper diagnosis and recommended treatment of disease constitutes only half his task. The other half, of equal importance, concerns the extent to which the patient complies with his recommendations. A variety of studies have shown noncompliance rates that vary between 30% and 70% over a wide range of conditions and recommended actions, but apparently average about 50%; ie, 50% of your patients will not follow prescribed regimens precisely as ordered or for the full period of time of the prescription. This may come as no surprise when one considers such areas as obesity, cigarette smoking, and exercise, but it may surprise some physicians that these figures hold even for the taking of relatively simple medications that do not involve marked changes in life-style. <h3>Reasons for Noncompliance</h3> Within the past few years, accumulating evidence has thrown considerable light on the reasons for noncompliance with
8 POTENT HCV PROTEASE INHIBITORS WITH THE POTENTIAL FOR ONCE-DAILY DOSING AND BROAD GENOTYPE COVERAGE
Authors: L.J. Jiang, Y. Gai, T. Middleton, K. Kurtz, L. Lu, S. Liu, T. Phan, X. Luo, T. Poon, B. Brasher, K. McDaniel, D. Kempf, Y.S. Or
Journal: Journal of Hepatology (2009)
Temporal Trends in the Utilization of Diagnostic Testing and Treatments for Cardiovascular Disease in the United States, 1993–2001
Authors: F.L. Lucas, Michael A. DeLorenzo, Andrea E. Siewers, David E. Wennberg
Journal: Circulation (2006)

Rates of invasive testing and treatment for coronary artery disease have increased over time. Less is known about trends in the utilization of noninvasive cardiac testing for coronary artery disease. The objective of this study was 2-fold: to explore temporal trends in the utilization of noninvasive and invasive cardiac services in relation to changes in the prevalence of cardiac disease, and to examine whether temporal increases have been targeted to potentially underserved populations. We performed an annual cross-sectional population-based study of Medicare patients from 1993 to 2001. We identified stress testing, cardiac catheterization, and revascularization procedures, as well as hospitalizations for acute myocardial infarction, during each year and calculated population-based rates for each using the total fee-for-service Medicare population as the denominator and adjusting for age, gender, and race. We observed marked growth in the utilization rates of cardiac services over time, with relative rates nearly doubling for most services. Acute myocardial infarction hospitalization rates have remained stable over the study period. Although rates of all procedures except coronary artery bypass increased in all subgroups, differences in rates of cardiac testing and treatment between nonblack men and other subgroups persisted over time. Temporal increases in the use of noninvasive and invasive cardiac services are not explained by changes in disease prevalence and have not succeeded in narrowing preexisting treatment differences by gender and race. Such increases, although conferring benefit for some, may expose others to risk and cost without benefit.
Activation and Localization of Transcription Factor, Nuclear Factor- κ B, in Asthma
Authors: LORRAINE A. HART, VIJAYA L. KRISHNAN, IAN M. ADCOCK, PETER J. BARNES, K. FAN CHUNG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Asthma is associated with increased expression of inflammatory proteins including cytokines, enzymes, and adhesion molecules. Induction of many of the genes for these proteins is regulated by the transcription factor, nuclear factor- κ B (NF- κ B). We therefore examined whether airway cells from patients with asthma show increased activation of NF- κ B. Nuclear proteins were extracted from cells of induced sputum and from bronchial biopsies of normal subjects and patients with asthma. NF- κ B-binding to its consensus DNA binding site, as investigated with 32P-labeled oligonucleotides and electrophoretic-mobility-shift assay, showed a 2.5-fold increase (p < 0.003) in NF- κ B–DNA binding in induced sputum of asthma patients. Nuclear staining, representing activated NF- κ B, was observed in macrophages of induced sputum. Immunohistochemical examination of bronchial biopsy specimens with an antibody to p65, a constituent of NF- κ B, showed more airway epithelial cells with nuclear staining in asthma patients (45.1 ± 7.2% versus 20.7 ± 3.9%; n = 9; p < 0.01), and a 2.5-fold greater number of cells with cytoplasmic staining in the mucosal region (p < 0.05). Pooled nuclear extracts of bronchial biopsy specimens from asthma patients showed a 44% greater level of NF- κ B–DNA binding. Activation of NF- κ B may be the basis for increased expression of many inflammatory genes and for the perpetuation of chronic airway inflammation in asthma.
Paradoxical Pressor Effects of β-Blockers in Standing Elderly Patients With Mild Hypertension
Authors: T.J. Cleophas, I. Grabowsky, M.G. Niemeyer, W.M. Mäkel, E.E. van der Wall
Journal: Circulation (2002)

Background— Baroreflex sensitivity declines with age, creating a fall in systolic blood pressure and pulse pressure when standing. If, in addition, blood pressure is reduced as a result of antihypertensive medication, compensatory mechanisms may be inadequate and orthostatic problems may occur. This may be less true in patients on β-blockers. β-blockers cause pressor effects in standing patients with autonomic neuropathy, but their effects on standing pulse pressures in elderly subjects with mild hypertension have not been systematically studied. Methods and Results— We studied 3741 patients with mild hypertension for 6 months who were being treated with the β-blocker nebivolol 5 mg daily. Blood pressures were measured after 10 minutes in the supine position and after 1 minute in the standing position. Overall, systolic and diastolic blood pressures rose slightly while standing, whereas pulse pressures remained unchanged. When previously untreated patients (n=2085) &gt;60 and &lt;60 years of age were assessed separately, supine pulse pressures were consistently higher in the elderly group compared with those of the younger subjects by 6 to 11 mm Hg ( P &lt;0.001 to 0.0001). However, while standing, pulse pressures rose in the younger subjects, whereas they tended to fall in the elderly group. After 6 months of β-blockade, this pattern was unchanged in the younger subjects but reversed into significant rise of pulse pressures in the elderly group by 4 (SD 1) mm Hg ( P &lt;0.001). In the patients previously treated with other classes of antihypertensive drugs (n=712), the effects were essentially the same. Conclusions— In elderly patients with mild hypertension, a depressor trend of pulse pressure while standing can be turned into a significant pressor response by treatment with a β-blocker.
Peripheral blood T lymphocytes in seasonal bronchial asthma
Authors: J. Monteseirín, P. Guardia, J. Delgado, E. Llamas, J. Palma, A. Conde, J. Conde
Journal: Allergy (1995)

Variations in T lymphocytes in asthmatic patients are related to disease severity. However, the effects of natural exposure to pollens on peripheral blood T lymphocytes have not been clarified. In this paper, the effects on peripheral blood CD4 and CD8 lymphocytes from pollen‐sensitive subjects and from nonatopic donors were studied during and outside the pollen season. In patients who suffer from seasonal asthma, we found an increase in the CD4/CD8 bright ratio and a decrease in the mean number of CD4 receptors per cell during the pollen season. No variation was observed in healthy subjects. These results suggest that CD4 lymphocytes may be causally linked to the pathogenesis of seasonal bronchial asthma.
Abnormal Surfactant Metabolism and Function in Preterm Ventilated Baboons
Authors: STEVEN R. SEIDNER, ALAN H. JOBE, JACQUELINE J. COALSON, MACHIKO IKEGAMI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We evaluated surfactant metabolism and function and the effects of antenatal glucocorticoids in very preterm baboons. Pregnant baboons were randomized to receive saline (controls) or 6 mg betamethasone (beta) 48 and 24 h before delivery at 125 ± 2 d gestation (term is 184 d). The newborn baboons were treated with [14C]dipalmitoylphosphatidylcholine-labeled surfactant and ventilated for 6 d. Lung function for six control and six betamethasone-treated animals was similar. Recoveries of 14C-saturated phosphatidylcholine (Sat PC) were similar: 4.8% (control) and 3.6% (beta) in alveolar wash and 15.4% (control) and 17.7% (beta) in total lungs. Alveolar and total lung pool sizes of Sat PC were about 23 and 190 μ mol/kg, respectively. The preterm baboons secreted 8.7% (control) and 6.5% (beta) of de novo synthesized Sat PC labeled with 3H-palmitate from Day 5 to Day 6. These preterm baboons had high estimated Sat PC synthetic and net tissue accumulation rates but low secretion of Sat PC. The large aggregate surfactant fractions from the preterm baboons had high minimal surface tensions and were less effective when used to treat surfactant-deficient preterm rabbits than surfactant from newborn or adult baboons. Ventilation of the preterm baboon was associated with surfactant functional and metabolic abnormalities that were not altered by antenatal glucocorticoids.