tbuckley/cabot-search huggingface dataset:
L-Arginine Therapy in Acute Myocardial Infarction
Authors: Steven P. Schulman, Lewis C. Becker, David A. Kass, Hunter C. Champion, Michael L. Terrin, Sandra Forman, Kavita V. Ernst, Mark D. Kelemen, Susan N. Townsend, Anne Capriotti, Joshua M. Hare, Gary Gerstenblith
Journal: JAMA (2006)

The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Prior studies suggest that L-arginine has the potential to reduce vascular stiffness.To determine whether the addition of L-arginine to standard postinfarction therapy reduces vascular stiffness and improves ejection fraction over 6-month follow-up in patients following acute ST-segment elevation myocardial infarction.Single-center, randomized, double-blind, placebo-controlled trial with enrollment from February 2002 to June 2004.A total of 153 patients following a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older.Patients were randomly assigned to receive L-arginine (goal dose of 3 g 3 times a day) or matching placebo for 6 months.Change in gated blood pool-derived ejection fraction over 6 months in patients 60 years or older randomized to receive L-arginine compared with those assigned to receive placebo. Secondary outcomes included change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events.Baseline characteristics, vascular stiffness measurements, and left ventricular function were similar between participants randomized to receive placebo or L-arginine. The mean (SD) age was 60 (13.6) years; of the participants, 104 (68%) were men. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study group. However, 6 participants (8.6%) in the L-arginine group died during the 6-month study period vs none in the placebo group (P = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment.L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-arginine should not be recommended following acute myocardial infarction. Clinical Trial Registration ClinicalTrials.gov, NCT00051376.
Prednisone in COPD exacerbation requiring ventilatory support: an open-label randomised evaluation
Authors: Fekri Abroug, Lamia Ouanes-Besbes, Mohamed Fkih-Hassen, Islem Ouanes, Samia Ayed, Fahmi Dachraoui, Laurent Brochard, Souheil ElAtrous
Journal: European Respiratory Journal (2013)

Recommendation of the use of systemic steroids in chronic obstructive disease (COPD) exacerbation rely on trials that excluded patients requiring ventilatory support. In an open-label, randomised evaluation of oral prednisone administration, 217 patients with acute COPD exacerbation requiring ventilatory support were randomised (with stratification on the type of ventilation) to usual care (n=106) or to receive a daily dose of prednisone (1 mg·kg(-1)) for up to 10 days (n=111). There was no difference regarding the primary end-point, intensive care unit mortality, which was 17 (15.3%) deaths versus 15 (14%) deaths in the steroid-treated and control groups, respectively (relative risk 1.08, 95% CI 0.6-2.05). Analysis according to ventilation modalities showed similar mortality rates. Noninvasive ventilation failed in 15.7% and 12.7% (relative risk 1.25, 95% CI 0.56-2.8; p=0.59), respectively. Both study groups had similar median mechanical ventilation duration and intensive care unit length of stay, which were 6 (interquartile range 6-12) days versus 6 (3.8-12) days and 9 (6-14) days versus 8 (6-14) days, respectively. Hyperglycaemic episodes requiring initiation or alteration of current insulin doses occurred in 55 (49.5%) patients versus 35 (33%) patients in the prednisone and control groups, respectively (relative risk 1.5, 95% CI 1.08-2.08; p=0.015). Prednisone did not improve intensive care unit mortality or patient-centred outcomes in the selected subgroup of COPD patients with severe exacerbation but significantly increased the risk of hyperglycaemia.
Follow-up of Nutritional and Metabolic Problems After Bariatric Surgery
Authors: Ken Fujioka
Journal: Diabetes Care (2005)

Over the next several years, the number of patients who will have had bariatric surgery for morbid obesity will reach close to a million. Several well-described nutritional problems such as B12 and iron deficiency will be noted in these patients. Many of these patients will be lost to the original surgeon and will now be in the care of the “other physicians.” These and other mineral and vitamin problems will need to be screened and treated. If these problems are left undiagnosed, severe and irreparable problems can result. Early problems, such as vomiting and dumping syndrome, will be easily recognized and treated, but other long-term problems, such as changes in bone metabolism, will need to be monitored. Again, if some of these long-term problems are not addressed in a timely fashion, then eventual treatment becomes much more difficult. This commentary will cover the common as well newer problems that are now developing in the patient who has had bariatric surgery. Patients who have undergone bariatric surgery require medical follow-up for reasons that are often determined by the type of surgical procedure performed. The majority of this review will deal with patients who have had the standard Roux-en-Y gastric bypass, which is a primarily restrictive procedure with a mild component of noncaloric malabsorption. At the end of this report, a short section will be devoted to the problems associated with the malabsorptive procedures.
Impact of Clozapine on Negative Symptoms and on the Deficit Syndrome in Refractory Schizophrenia
Authors: Robert Rosenheck, Lawrence Dunn, Michael Peszke, Joyce Cramer, Weichun Xu, Jonathan Thomas, Dennis Charney, None the Department of Veterans Affairs Cooperative Study Group o
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: This study compared the effect of clozapine and haloperidol on positive and negative symptoms of schizophrenia and in patients with high levels of negative symptoms or the deficit syndrome. METHOD: Patients were participants in a 15-site double-blind, random-assignment Veterans Administration trial comparing clozapine (N=205) and haloperidol (N=217) in hospitalized patients with refractory schizophrenia. Analysis of covariance examining change at 6 weeks, 3 months, and 1 year evaluated 1) clozapine's effect on positive and negative syndromes; 2) clozapine's effect on each syndrome, statistically controlling for the other; and 3) the interaction of clozapine treatment and the presence or absence of high levels of negative symptoms at baseline and the deficit syndrome. RESULTS: Patients treated with clozapine showed significantly greater improvement than control subjects on positive symptoms at all time points and on negative symptoms at 3 months. Clozapine had no independent effect on negative symptoms at any time after control for positive symptoms, but its effects on positive symptoms persisted after control for negative symptoms at 6 weeks only. There were no significant differences in response to clozapine between patients with high and low levels of negative symptoms at baseline or between patients with and without the deficit syndrome. CONCLUSIONS: The greater effectiveness of clozapine as compared to conventional medications in refractory schizophrenia is not specific to either negative clinical symptoms or clinical subtypes defined by prominent negative symptoms or evidence of the deficit syndrome.
FRATERNITY IN COMBAT
Authors: D. E. JOHNSON, J. T. THICKSTUN
Journal: American Journal of Psychiatry (1945)

On admission to the sick list, 3 brothers presented the picture of an anxiety reaction. Their symptoms were similar, but varied in intensity. The opportunity to observe a reaction so common in wartime in individuals with very much the same protoplasmic posisibilities and environmental background, seemed unique. Upon study, it is seen that the brothers illustrate three types of neurotic disability seen frequently in this war. It would appear that their common symptom, anxiety, stems from their common inheritance and back-ground. The individual course and prognosis of that anxiety would likewise seem to depend on personal differences which are somewhat less apparent. I. M. had already displayed symptoms of emotional maladjustment during childhood, adolescence and adulthood prior to service. His combat experience in 3 invasions was severe, but somewhat less so than that of his brothers. Anxiety symptoms reached severe proportions rather rapidly. His old neurotic pattern was revealed in the Rorschach, Minnesota and Thematic Apperception tests. During the treatment period of several months, he responded slowly but definitely, retaining his anxiety longer than C., but releasing it more rapidly than R. He now (3-14-45) reveals only a slight increase over his pre-enlistment anxiety. His combat experiences have only colored to some extent an otherwise drab, neurotic personality. II. C., during childhood and adolescence, had been somnambulistic, stammered, chewed his nails, and been quick tempered. On enlistment, however, no neurotic symptoms had been apparent for several years. His anxiety had increased along with that of his brothers, until his fortunate (?) wounding by shrapnel, which removed him from almost the entire Guam campaign. Projective tests confirmed the impression that he was the least neurotic of the 3. Under treatment, he responded rapidly and in a few weeks his anxiety was dispelled. III. Prior to service, R. had demonstrated the least evidence of neurotic reaction. There was suggestion of maternal rejection, however, and he stated that he was "rather quick-tempered," and had been a nail biter since age 10. He experienced the most severe combat and displayed the most marked anxiety. A temporary solution to his unbearable anxiety took the form of an amnesic episode, probably hysterical in nature. After treatment over a period of 4 months, moderate anxiety persists. His outlook for the future remains a matter for conjecture; Rorschach and Minnesota performance suggest the potentiality of its developing into a more fixed neurosis.
Diagnostic Accuracy of Point-of-Care Testing for Diabetic Ketoacidosis at Emergency-Department Triage
Authors: Sanjay Arora, Sean O. Henderson, Theodore Long, Michael Menchine
Journal: Diabetes Care (2011)

OBJECTIVE In the emergency department, hyperglycemic patients are screened for diabetic ketoacidosis (DKA) via a urine dipstick. In this prospective study, we compared the test characteristics of point-of-care β-hydroxybutyrate (β-OHB) analysis with the urine dipstick. RESEARCH DESIGN AND METHODS Emergency-department patients with blood glucose ≥250 mg/dL had urine dipstick, chemistry panel, venous blood gas, and capillary β-OHB measurements. DKA was diagnosed according to American Diabetes Association criteria. RESULTS Of 516 hyperglycemic subjects, 54 had DKA. The urine dipstick had a sensitivity of 98.1% (95% CI 90.1–100), a specificity of 35.1% (30.7–39.6), a positive predictive value of 15% (11.5–19.2), and a negative predictive value of 99.4% (96.6–100) for DKA. Using the manufacturer-suggested cutoff of &amp;gt;1.5 mmol/L, β-OHB had a sensitivity of 98.1% (90.1–100), a specificity of 78.6% (74.5–82.2), a positive predictive value of 34.9% (27.3–43), and a negative predictive value of 99.7% (98.5–100) for DKA. CONCLUSIONS Point-of-care β-OHB and the urine dipstick are equally sensitive for detecting DKA (98.1%). However, β-OHB is more specific (78.6 vs. 35.1%), offering the potential to significantly reduce unnecessary DKA work-ups among hyperglycemic patients in the emergency department.
From cultural cohesion to rules and competition: the trajectory of senior management culture in English NHS hospitals, 2001–2008
Authors: Russell Mannion, Stephen Harrison, Rowena Jacobs, Frederick Konteh, Kieran Walshe, Huw TO Davies
Journal: Journal of the Royal Society of Medicine (2009)

Summary Objectives To assess changes in senior management culture in English NHS hospitals between 2001 and 2008. Design Longitudinal study comprising cross-sectional surveys of board levels managers at three time-points using a validated culture measurement instrument – the Competing Values Framework. Setting English NHS hospital trusts. Main outcomes There has been a decline in ‘Clan’ and an increase in more competitive ‘Rational’ cultures among senior management teams in NHS hospital trusts during the period 2001–2008. Conclusions Government policy for the NHS has espoused the desirability of competition, particularly since 2002. Our data suggest that corresponding changes in the cultures of senior management teams in NHS hospital trusts is beginning to occur, with the expectation that these organizations will pursue more competitive strategies.
Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype
Authors: T. Rampias, E. Pectasides, M. Prasad, C. Sasaki, P. Gouveris, A. Dimou, P. Kountourakis, C. Perisanidis, B. Burtness, T. Zaramboukas, D. Rimm, G. Fountzilas, A. Psyrri
Journal: Annals of Oncology (2013)
CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
Authors: M Mamtani, B Rovin, R Brey, J F Camargo, H Kulkarni, M Herrera, P Correa, S Holliday, J-M Anaya, S K Ahuja
Journal: Annals of the Rheumatic Diseases (2007)

There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE.We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5.Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-Delta32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual's CCL3L1-CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE.CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1-CCR5 axis in the pathogenesis of SLE.
THE HISTOLOGICAL DISTRIBUTION OF BLOOD GROUP SUBSTANCES A AND B IN MAN
Authors: Aron E. Szulman
Journal: The Journal of Experimental Medicine (1960)

The mapping out of the histologic distribution of blood group antigens A and B in human tissues was performed by means of the fluorescent antibody technique. Human hyperimmune sera were conjugated with fluorescein isocyanate and applied to frozen sections of human material obtained at autopsy or after surgical removal. The material examined encompassed A, B, and AB subjects. In the latter the anti-A and the anti-B conjugate elicited the same picture. Group O tissues were used for controls and were uniformly negative. The secretor status of subjects was determined from the saliva or by the Lewis typing of erythrocytes. The results fall into the following main divisions: Endothelia of Vessels.—Widespread localization was demonstrated in the cell walls of endothelium of capillaries, veins, arteries, and of sinusoidal cells of spleen. Stratified Epithelia.—These showed good outlining of cells of the Malpighian (and the granular, when present) layers. In transitional epithelia, cells of the basal and contiguous layers gave specific staining. Mucus-Secreting Apparatus.—Positive staining was obtained in glands, goblet cells, and secreting surface epithelia. In non-secretors there was no identifiable antigen with the important exception of the deeper parts of gastric foveolae, deeper parts of crypts of Lieberkühn of bowel mucosa and Brunner's glands of the duodenum. Various Organs of Secretion and Excretion.—The pancreas (exocrine portion) and the sweat glands were found to produce the antigen irrespectively of secretor status. Breast, prostate, and endometrial glands on the other hand apparently secrete the antigen in conformity with the subject's secretor:non-secretor make-up. Thus the secretor:non-secretor status governs principally the antigens associated with mucous secretions and this in most but not all locations. The possible nature of this control is briefly discussed.
Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?
Authors: Agnès Fournier, Sylvie Mesrine, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon
Journal: Journal of Clinical Oncology (2009)

Purpose To investigate whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment initiation. Participants and Methods Between 1992 and 2005, 1,726 invasive breast cancers were identified among 53,310 postmenopausal women from the French E3N cohort (mean duration of follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox models, with MHT never users as the reference. Results Among recent users of EP-MHT, the risk of breast cancer varied according to the timing of treatment initiation. This variation was confined to short durations of use (≤ 2 years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for short treatments initiated later (P = .04 for homogeneity). However, this pattern of risks was not observed in users of EP-MHT containing progesterone, among whom there was no significantly increased risk associated with short duration of use (HR was 0.87 [95% CI, 0.57 to 1.32] for treatments initiated ≤ 3 years after menopause, and HR was 0.90 [95% CI, 0.45 to 1.81] for treatments initiated later). Longer durations of EP-MHT use were generally associated with increases in breast cancer risk, whatever the gap time. Conclusion Our results suggest that, for some EP-MHT, the timing of treatment initiation transiently modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen + progesterone combinations might be an exception in this regard.
Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible costimulator ligand
Authors: Maria Tsoumakidou, Sofia Tousa, Maria Semitekolou, Panagiota Panagiotou, Anna Panagiotou, Ioannis Morianos, Eleni Litsiou, Aikaterini I. Trochoutsou, Maria Konstantinou, Konstantinos Potaris, Joseph Footitt, Patrick Mallia, Spyros Zakynthinos, Sebastian L. Johnston, Georgina Xanthou
Journal: Journal of Allergy and Clinical Immunology (2014)
Medical progress and animal models: the importance of evidence
Authors: Simon Festing
Journal: Journal of the Royal Society of Medicine (2008)

The authors demonstrated that if there had been access to and synthesis of all the research data, the trial disaster and consequent harm to the research volunteers could have been avoided.Systematic reviews would tell us more about confounding variables and other characteristics of animal research that need to be accounted for (e.g.genetics, species differences, variations in feeding, location and laboratory practice), 5 the validity of animal models and whether a rigorous search for alternatives had been conducted.We are petitioning 6 the Prime Minister to make improvements to animal research which would have relevance for 'a systematic study of the use of animal models'.It is time that animal research was made more evidence-based.
Reducing risks to the unborn child
Authors: Bruce Currey, Beat Stoll, Philippe Chastonay
Journal: Journal of the Royal Society of Medicine (2013)

If clinicians are to play a leading role in reducing risks to the fetus, they have to think outside the box. Improved pregnancy outcomes require that medical and health professionals, including midwives and nurses, work with others far beyond the confines of the antenatal clinic and the delivery room. For the WHO-estimated 200 million plus conceptions globally each year,1 mostly among disadvantaged groups in disadvantaged (at-risk) areas, the first nine months of life are vulnerable to risks. These risks are not just medical, but also employment, agricultural, security, energy and climate risks. Improving care to reduce these varied risks to the fetus inside the womb challenges us to accept a very broad concept of integrated health2 – drawing from expertise far outside the traditional medical specialties.
Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy
Authors: Benjamin B. Davis, Amir A. Zeki, Jennifer M. Bratt, Lei Wang, Simone Filosto, William F. Walby, Nicholas J. Kenyon, Tzipora Goldkorn, Edward S. Schelegle, Kent E. Pinkerton
Journal: European Respiratory Journal (2012)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death. The statin drugs may have therapeutic potential in respiratory diseases such as COPD, but whether they prevent bronchial epithelial injury is unknown. We hypothesised that simvastatin attenuates acute tobacco smoke-induced neutrophilic lung inflammation and airway epithelial injury. Spontaneously hypertensive rats were given simvastatin (20 mg·kg −1 i.p. ) daily for either 7 days prior to tobacco smoke exposure and during 3 days of smoke exposure, or only during tobacco smoke exposure. Pretreatment with simvastatin prior to and continued throughout smoke exposure reduced the total influx of leukocytes, neutrophils and macrophages into the lung and airways. Simvastatin attenuated tobacco smoke-induced cellular infiltration into lung parenchymal and airway subepithelial and interstitial spaces. 1 week of simvastatin pretreatment almost completely prevented smoke-induced denudation of the airway epithelial layer, while simvastatin given only concurrently with the smoke exposure had no effect. Simvastatin may be a novel adjunctive therapy for smoke-induced lung diseases, such as COPD. Given the need for statin pretreatment there may be a critical process of conditioning that is necessary for statins’ anti-inflammatory effects. Future work is needed to elucidate the mechanisms of this statin protective effect.