tbuckley/cabot-search huggingface dataset:
Clinical Events as a Function of Proton Pump Inhibitor Use, Clopidogrel Use, and Cytochrome P450 2C19 Genotype in a Large Nationwide Cohort of Acute Myocardial Infarction
Authors: Tabassome Simon, Philippe Gabriel Steg, Martine Gilard, Didier Blanchard, Laurent Bonello, Michel Hanssen, Hervé Lardoux, Pierre Coste, Thierry Lefèvre, Elodie Drouet, Geneviève Mulak, Vincent Bataille, Jean Ferrières, Céline Verstuyft, Nicolas Danchin
Journal: Circulation (2011)

Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs.The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively.PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles.
Morality for the Medical–Industrial Complex
Authors: H T Engelhardt, M A Rie
Journal: New England Journal of Medicine (1988)

Gainful employment has traditionally been one of medicine's goals.1 Even the Hippocratic corpus includes suggestions about gaining the respect and attracting the business of patients.2 Because of physicians' economic concerns, the history of medicine is rich with controversies about the setting of fees, the control of competitors, and the improvement of the financial status of physicians.3 4 5 It should come as no surprise that medicine as a cottage industry was practiced at least partly for profit. Nor is this in itself evil. Medicine is not an endeavor of amateurs nor usually of mendicant friars.To acquire an adequate appreciation of medical . . .
Relation of Glycemic Control to Diabetic Microvascular Complications in Diabetes Mellitus
Authors: Ronald Klein
Journal: Annals of Internal Medicine (1996)

Objective: To describe the relation between glycated hemoglobin and the incidence or progression, or both, of diabetic microvascular complications in persons with insulin-dependent (IDDM) and non–insulin-dependent diabetes mellitus (NIDDM). Design: Population-based cohort study. Setting: An 11-county area in southern Wisconsin. Patients: All persons with IDDM diagnosed before age 30 and taking insulin (n = 996) and a probability sample (based on duration of disease) of persons diagnosed with diabetes at age 30 or older who were either taking insulin (n = 674) or not taking insulin (n = 696) and who participated in a baseline examination from 1980 to 1982. Survivors of the cohort were re-examined again in 1984 to 1986 and 1990 to 1992. Measurements: The incidence and progression of diabetic retinopathy was determined by masked grading of stereoscopic color fundus photographs using the modified Early Treatment Diabetic Retinopathy Study severity scale. Gross proteinuria was determined using a dipstick. Ten-year incidence of renal dialysis or transplantation or loss of tactile sensation or of temperature sensitivity was based on self-reported history. Results: The glycated hemoglobin level at baseline was strongly related to the incidence or progression, or both, of diabetic retinopathy, the incidence of gross proteinuria, and the incidence of loss of tactile sensation or temperature sensitivity in persons with either IDDM or NIDDM. Conclusions: These prospective epidemiologic data suggest that glycemic control is similarly related to the incidence and progression of diabetic microvascular complications in both IDDM and NIDDM. However, further evidence from clinical trials in persons with NIDDM is necessary to assess the risks and benefits of such treatment in preventing these complications.
Intestinal Bypass for Obesity
Authors: Stephen Kantor
Journal: JAMA (1967)

To the Editor:—  In the May 15 issue ( 200 :638), in an editorial on Complications of Intestinal Bypass for Obesity, a rather discouraging picture was painted about the outcome and complications of these operations. The original article in question, in the May issue of the Archives of Surgery ( 94 :707), goes as far as to conclude that, at the present time we cannot advocate the use of intestinal bypass procedure as a routine operation for the control of human obesity. I heartily agree with their conclusion, but I am quick to point out that perhaps therein lies the problem with their complications, and the key word here is routine . No operation should be routine; one does not do a routine gastric resection or a routine vagotomy-pyloroplasty. After adequate evaluation, the operation is tailored to the patient and not vice versa. In the words of Dr. J.H. Payne, who has done
Family Medicine: The Medical Life History of Families
Authors: Kevin Patrick
Journal: JAMA (1983)

Family medicine is now in its "adolescence" as an academic discipline in American medical schools. As an adolescent among a group of well-established "adults," it finds itself no longer in need of the constant nurturance of a child but still in need of an accepting, tolerant environment in which to form its identity. Some would deny that environment based on the assumption that, after all, there really is nothing special about family medicine. This book challenges that assumption and does so with power and eloquence. Based on 30 years of meticulously documented medical practice in a small community in Holland, the author presents evidence for a fundamental tenet of family medicine: that the family is a legitimate unit of medical process and, thereby, inquiry. This is hard to deny when viewing the book's charts, which both temporally and concurrently display for each member of a family all medical contacts, reasons
Advances in Inflammation Research
Authors: K A Brown
Journal: Annals of the Rheumatic Diseases (1985)

The only published analytical data from the Bath group describe a method which measures either free penicilla- mine and penicillamine disulphide or total D-penicillamine after treatment with dithiothreitol.'It is not clear from their recent report' how the method has been modified in order to quantify mixed disulphides accurately.Previous work with direct determination of the mixed disulphides on amino acid analysers has shown that the major plasma metabolite is cysteine penicillamine disulphide, a result inconsistent with data derived from reference 4. We have also been unable to reduce penicillamine disulphide reproducibly using dithiothreitol, which may be due to difficulties either with the reduction or the artefactual chromatography.6We have recently reviewed the various approaches to thiol analysis7 and do not consider that the method so far described by the Bath group provides a true description of the complex metabolism of D-penicillamine in plasma.To our knowledge only one published study approaches that ideal.
Twelve hour overnight oesophageal pH monitoring in patients with reflux symptoms.
Authors: S Boesby, L Wallin, T Myrhoj, L I Andersen
Journal: Gut (1991)

Results of continuous 12 hour overnight pH monitoring (duration of pH less than 4) were reviewed in 112 patients with heartburn or regurgitation, or both, and in 56 normal subjects. Patients had more reflux than normal subjects. Medically controlled patients (n = 51) had less acid reflux than patients who subsequently underwent reflux surgery (n = 61), but there was a considerable overlap between those two groups. Surgery was followed by a reduction in acid reflux to a value similar to that in normal subjects. Patients in whom surgery was deemed to have failed had more reflux after the operation than those in whom it was successful, but no difference could be found in the preoperative reflux values of these two subgroups. Monitoring pH is not of value in selecting candidates for surgery since the results are not a good predictor of outcome, but it is useful in the objective evaluation of surgical results.
Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia
Authors: J Skavland, K M Jørgensen, K Hadziavdic, R Hovland, I Jonassen, Ø Bruserud, B T Gjertsen
Journal: Blood Cancer Journal (2011)

Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial.
Typhoid catatonia responsive to ECT.
Authors: W R Breakey, A K Kala
Journal: BMJ (1977)

Twelve patients with typhoid fever presented with a catatonic syndrome that persisted after other signs of the fever had disappeared. The syndrome was distinct from the delirium seen in typhoid fever and did not have the characteristics of an affective or schizophrenic illness. Electric convulsion therapy produced rapid and lasting improvement.
Tumor Antigen Epitopes Interpreted by the Immune System as Self or Abnormal-Self Differentially Affect Cancer Vaccine Responses
Authors: Sean O. Ryan, Michael S. Turner, Jean Gariépy, Olivera J. Finn
Journal: Cancer Research (2010)

Epitope selection is an important consideration in the design of cancer vaccines, but factors affecting selection are not fully understood. We compared the immune responses to peptides and glycopeptides from the common human tumor antigen MUC1, a mucin that is coated with O-linked carbohydrates in its variable number of tandem repeats (VNTR) region. MUC1 expressed on tumor cells is characteristically underglycosylated, creating peptide and glycopeptide neoepitopes that are recognized by the immune system. The response to VNTR peptides is weaker in MUC1-transgenic mice (MUC1-Tg mice) than in wild-type (WT) mice, whereas the response to VNTR glycopeptides is equally strong in the two strains. Thus, glycopeptides seem to be recognized as foreign, whereas peptides, although immunogenic, are perceived as self. To explore this further, we generated MUC1 peptide- and glycopeptide-specific T-cell receptor transgenic mice and studied the function of their CD4 T cells when adoptively transferred into MUC1-Tg or WT mice. Peptide-specific T-cell precursors were not centrally deleted in MUC1-Tg mice and did not acquire a T regulatory phenotype. However, their response to the cognate peptide was reduced in MUC1-Tg mice compared with WT mice. In contrast, glycopeptide-specific CD4 T cells responded equally well in the two hosts and, when simultaneously activated, also enhanced the peptide-specific T-cell responses. Our data show that the immune system differentially recognizes various epitopes of tumor-associated antigens either as self or as foreign, and this controls the strength of antitumor immunity. This represents an important consideration for designing safe and effective cancer vaccines.
New Index for Evaluation of Oral Glucose Tolerance Test Results
Authors: W. Z. Billewicz, J. Anderson, T. Lind
Journal: BMJ (1973)

A simple numerical index is presented which describes the shape of an oral glucose tolerance response curve and appears to be a measure of the efficiency of homeostatic control. It is unaffected by the laboratory method of glucose estimation, the site of blood sampling, the amount of glucose given, and whether or not the patient has fasted overnight. The index satisfactorily differentiates clinically diabetic from non-diabetic individuals and seems to provide a sensitive method of describing small changes in glucose homeostatic control such as might occur, for example, in pregnancy.
Prevention of Hepatocellular Carcinoma by Universal Vaccination against Hepatitis B Virus: The Effect and Problems
Authors: Mei-Hwei Chang, Tony Hsiu-Hsi Chen, Hsu-Mei Hsu, Tzee-Chung Wu, Man-Shan Kong, Der-Cherng Liang, Yen-Hsuan Ni, Chien-Jen Chen, Ding-Shinn Chen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In spite of the success of hepatitis B immunization, still a significant proportion of childhood hepatocellular carcinoma (HCC) failed to be prevented by the hepatitis B immunization program. This study is aimed to investigate the problems in the HCC prevention in children. Experimental Design: All HCC children ages 6 to 14 diagnosed between 1981 and 2000 in Taiwan were collected from two national childhood HCC registry systems. We analyzed the causes of HCC prevention failure and the risk ratio of HCC among hepatitis B carriers born before versus after the vaccination program. Results: The incidence of HCC per 100,000 children declined from 0.54 to 0.20 in those born before versus after the vaccination program (risk ratio, 0.36). Vaccine failure (33.3-51.4%) and failure to receive hepatitis B immunoglobulin at birth (42.4-57.5%) were the main causes of HCC prevention failure. Mother-to-child transmission of hepatitis B virus infection is an important risk factor of HCC development. This is evidenced by the very high hepatitis B surface antigen seropositive rate in our HCC children (97%) and their mothers (96%). Hepatitis B carrier children born after the vaccination program had a higher risk of developing HCC than those born before the program (risk ratio, 2.3-4.5). Conclusions: Vaccine failure and failure to receive hepatitis B immunoglobulin are the main problems preventing eradication of HCC. Hepatitis B carrier children born after the immunization program have a higher risk of developing HCC than those born before.
Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study
Authors: M. Jadoul, J.M. Albert, T. Akiba, T. Akizawa, L. Arab, J.L. Bragg-Gresham, N. Mason, K.-G. Prutz, E.W. Young, R.L. Pisoni
Journal: Kidney International (2006)
Spatiotemporal Dynamics of β-Adrenergic cAMP Signals and L-Type Ca <sup>2+</sup> Channel Regulation in Adult Rat Ventricular Myocytes
Authors: Jérôme Leroy, Aniella Abi-Gerges, Viacheslav O. Nikolaev, Wito Richter, Patrick Lechêne, Jean-Luc Mazet, Marco Conti, Rodolphe Fischmeister, Grégoire Vandecasteele
Journal: Circulation Research (2008)

Steady-state activation of cardiac beta-adrenergic receptors leads to an intracellular compartmentation of cAMP resulting from localized cyclic nucleotide phosphodiesterase (PDE) activity. To evaluate the time course of the cAMP changes in the different compartments, brief (15 seconds) pulses of isoprenaline (100 nmol/L) were applied to adult rat ventricular myocytes (ARVMs) while monitoring cAMP changes beneath the membrane using engineered cyclic nucleotide-gated channels and within the cytosol with the fluorescence resonance energy transfer-based sensor, Epac2-camps. cAMP kinetics in the two compartments were compared to the time course of the L-type Ca(2+) channel current (I(Ca,L)) amplitude. The onset and recovery of cAMP transients were, respectively, 30% and 50% faster at the plasma membrane than in the cytosol, in agreement with a rapid production and degradation of the second messenger at the plasma membrane and a restricted diffusion of cAMP to the cytosol. I(Ca,L) amplitude increased twice slower than cAMP at the membrane, and the current remained elevated for approximately 5 minutes after cAMP had already returned to basal level, indicating that cAMP changes are not rate-limiting in channel phosphorylation/dephosphorylation. Inhibition of PDE4 (with 10 micromol/L Ro 20-1724) increased the amplitude and dramatically slowed down the onset and recovery of cAMP signals, whereas PDE3 blockade (with 1 micromol/L cilostamide) had a minor effect only on subsarcolemmal cAMP. However, when both PDE3 and PDE4 were inhibited, or when all PDEs were blocked using 3-isobutyl-l-methylxanthine (300 micromol/L), cAMP signals and I(Ca,L) declined with a time constant >10 minutes. cAMP-dependent protein kinase inhibition with protein kinase inhibitor produced a similar effect as a partial inhibition of PDE4 on the cytosolic cAMP transient. Consistently, cAMP-PDE assay on ARVMs briefly (15 seconds) exposed to isoprenaline showed a pronounced (up to approximately 50%) dose-dependent increase in total PDE activity, which was mainly attributable to activation of PDE4. These results reveal temporally distinct beta-adrenergic receptor cAMP compartments in ARVMs and shed new light on the intricate roles of PDE3 and PDE4.
The Cells of the Allergic Response
Authors: John J. Costa
Journal: JAMA (1997)

Mast cells, basophils, and eosinophils have long been regarded as important effector cells in allergic disorders. Indeed, it is thought that the cells' cytoplasmic granule—associated or lipid mediators contribute to many of the signs and symptoms that are characteristic of these diseases. Mast cells, basophils, and eosinophils also probably contribute to protective host responses, especially to parasites. In addition, recent evidence shows that mast cells, basophils, and eosinophils can secrete a wide spectrum of cytokines and, in some cases, express functions that may permit them to regulate the development or perpetuation of allergic responses. Thus, mast cells, basophils, and eosinophils may express immunoregulatory activities, as well as serve as effector cells.
Hopkins Celebration This Month Prefaced by Science Writer Seminar
Authors: Phil Gunby
Journal: JAMA (1989)

THE JOHNS HOPKINS Medical Institutions' centennial, major events of which will take place in the next few days, is reviving some fascinating questions of American medical history. Would the university and hospital that bear his name ever have been founded if Baltimore banker Johns Hopkins had overcome family resistance and married the one woman he is said to have truly loved (instead of remaining a lifelong bachelor)? What would today's three-hospital system (55 000 inpatients and nearly 1 million outpatients annually) be like if physicians William H. Welch, William S. Halsted, William Osler, Howard Kelly, and John S. Billings had not served Hopkins in its early days? While there are no precise answers to questions like those, the quality of work being done today at Hopkins—In the hospitals and schools of medicine, public health, and nursing—speaks for itself. It is apparent in the reports in this theme issue of<i>JAMA</i>
What Prevents Professional Drivers from Following Physicians’ Cardiologic Advice?
Authors: Reza Emdad, Karen Belkic, Töres Theorell, Stella Cizinsky
Journal: Psychotherapy and Psychosomatics (1998)

&lt;b&gt;Background:&lt;/b&gt; There is a scarcity of published studies of the effects of cardiac counselling among professional drivers (PD). Aims of the study were: (1) to examine explanatory variables for two classical ‘driver’ risk factors – body mass index (BMI), and smoking – and to analyse the interrelations among smoking cessation, losing weight and work-related life changes; (2) to assess the effectiveness of risk factor counselling after 6 months, and (3) to gain insight into possible discrepancies between PD perception of needed changes and compliance with the physician’s advice. &lt;b&gt;Methods:&lt;/b&gt; There were 4 groups of male PD: 13 with ischemic heart disease, 12 hypertensives, 10 borderline hypertensives and 34 normotensives. Baseline cardiovascular risk factors as well as occupational and behavioral data were assessed via questionnaire. The counselling was aimed at smoking cessation, weight loss and promoting leisure-time physical activity. Qualitative methods were used to assess PD perceptions about the work environment and health promotion. &lt;b&gt;Results:&lt;/b&gt; Baseline smoking intensity was best predicted by the total burden of occupational stress and number of smoking years. Baseline BMI was best predicted by long work hours behind the wheel, low availability of attachment outside work and low self-reported job strain. Self-initiated smoking cessation was best predicted by few smoking years, low coffee intake and admitting fear during driving. Physical activity was significantly increased after 6 months. Losing weight was associated with: quitting or diminishing smoking and making other, work-related, life changes. None of the heavy smokers decreased their daily number of cigarettes after 6 months, although expressing the need to do so in self-generated statements. &lt;b&gt;Conclusions:&lt;/b&gt; Exposure to occupational stressors, mainly, long work hours and the concomitant denial of job strain, in combination with low availability of social attachment outside work, could contribute to maintenance of maladaptive behavior in PD. These findings could serve as a basis for designing standardized intervention trials and suggest that modification of the work environment, with participation of the drivers, is a needed component of such trials. Particular attention should be paid to the length and scheduling of work shifts.
Generalists neglect psychiatry
Authors: C. Williams, S. Curran
Journal: BMJ (1995)

EDITOR,--The recent report by the Royal Colleges of Physicians and Psychiatrists highlighting the psychological care of medical patients emphasises the importance of general doctors being able to detect and assess the presence of common psychiatric disorders.1 2 Most patients with psychiatric illness are not seen by psychiatrists, with only just over a quarter of psychiatrically ill patients actually being diagnosed.3 There must therefore be an increased emphasis on the detection of psychiatric illness …