tbuckley/cabot-search huggingface dataset:
Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial
Authors: Harold O. Conn, Norman D. Grace, Jaime Bosch, Roberto J. Groszmann, Joan Rodés, Steven C. Wright, Daniel S. Matloff, Guadalupe Garcia-Tsao, Rosemarie L. Fisher, Miguel Navasa, Steven J. Drewniak, Colin E. Atterbury, Jose M. Bordas, Emanuel Lerner, Christina Bramante
Journal: Hepatology (1991)

To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a double-blind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p less than 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival.
Can video recording revolutionise medical quality?
Authors: Martin A Makary, Tim Xu, Timothy M Pawlik
Journal: BMJ (2015)

It’s time to hit the “record” button

In June 2015, a man living in Virginia returned home from a routine colonoscopy to discover a big surprise. Hoping to record the instructions he received from medical staff, the patient had actually recorded the entire procedure on his phone. To his shock, he learnt that the anaesthesiologist and gastroenterologist had viciously insulted him while he was sedated and had entered a false diagnosis in his medical record.1 The man sued his physicians, and the jury awarded him a large payment for medical malpractice. 

It seems unlikely that this type of behaviour would have been detected by any existing hospital mechanisms. Current systems to detect poor behaviour require staff to overcome their fear of retaliation and turn in a colleague. Rather than rely on individuals to report lapses in quality, new technology has the ability to record how we perform at our jobs. As well as detecting unprofessional behaviour it has the potential to radically improve quality through increased accountability—as witnessed in other businesses such as child care. Video recording …
Association of decrease in serum dehydroepiandrosterone sulfate levels with the progression to type 2 diabetes in men of a Japanese population: The Fungata Study
Authors: Wataru Kameda, Makoto Daimon, Toshihide Oizumi, Yumi Jimbu, Minako Kimura, Akihiko Hirata, Hiroshi Yamaguchi, Hiroshi Ohnuma, Masahiko Igarashi, Makoto Tominaga, Takeo Kato
Journal: Metabolism (2005)
Oral diamorphine: lack of effect on dyspnoea and exercise tolerance in the "pink puffer" syndrome
Authors: N Eiser, W T Denman, C West, P Luce
Journal: European Respiratory Journal (1991)

The aim of this study was to assess the effects of diamorphine on breathlessness and exercise tolerance in patients with severe chronic airflow obstruction and normal arterial carbon dioxide tension (PCO2) levels ("pink puffer" syndrome). In this double-blind, cross-over, randomized study we examined both acute and chronic effects of single and multiple doses of oral diamorphine in 14 "pink puffer" patients. Their mean resting forced expiratory volume in one second (FEV1) was 36% predicted normal, mean arterial oxygen tension (PaO2) was 9.2 kPa and mean PaCO2 was 5.2 kPa. Ten patients took either diamorphine 2.5 or 5 mg or placebo elixir 6 hourly for 2 weeks, recording on a diary card dyspnoea, sleepiness and well-being on a visual analogue scale (VAS). The final treatment was given 30 min before measuring spirometry, arterial blood gases, plasma morphine levels, 6 min walking distances, time walked on treadmill and self-assessment of dyspnoea on a VAS scale after exercise. On two further days, eight patients took two doses, 4 h apart, of either diamorphine 7.5 mg or placebo elixir. Spirometry, 6 min walking distance with a VAS score for dyspnoea were measured before and at 1 h after each dose. Morphine levels and blood gases were also measured. Whether given in single or repeated doses, oral diamorphine had no significant effect on exercise tolerance and breathlessness when compared with placebo. Diamorphine 2.5-7.5 mg produced neither sleepiness nor a deterioration in blood gases. However, plasma levels associated with analgesic efficacy were not achieved with these doses. Thus, as given in this study, oral diamorphine is unlikely to have therapeutic potential in the treatment of dyspnoea in the "pink puffer" syndrome.
VEGF-mediated angiogenesis is impaired by angiotensin type 1 receptor blockade in cardiomyopathic hamster hearts
Authors: T SHIMIZU, H OKAMOTO, S CHIBA, Y MATSUI, T SUGAWARA, M AKINO, J NAN, H KUMAMOTO, H ONOZUKA, T MIKAMI
Journal: Cardiovascular Research (2003)

Objective: Coronary microcirculation plays an important role in the progression of cardiac remodeling. Among angiogenic factors, it has been reported that angiotensin II may contribute to neovascularization. However, it is unknown whether inhibition of the renin–angiotensin system suppresses angiogenesis, especially within the heart. Our aim was to evaluate the effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor type I blocker valsartan on cardiac microvasculature, function, vascular endothelial growth factor (VEGF) expression, and survival in cardiomyopathic hamsters. Methods: Male cardiomyopathic hamsters (BIO TO2) were administered either a placebo (group C), enalapril (30 mg/kg/day) (group E), or valsartan (40 mg/kg/day) (group V), starting at the age of 6 weeks. This continued until death. Hemodynamic study, histological analysis, and northern blot analysis were performed at 39 weeks. Results: Group V showed significant increases in percent fibrosis, end diastolic pressure, and LV dP/dt min, and significant decreases in percent fractional shortening, LV dP/dt max, capillary density, and the level of mRNA expression of VEGF compared with group C. Group E showed significant increases in percent fractional shortening while the capillary density and level of mRNA expression of VEGF were unchanged. The 300-day survival rate was significantly lower in group V (25.0%) but higher in group E (100%) than that of group C (66.7%). Conclusions: Therapy with valsartan may have adverse effects on survival rate concomitant with the progression of cardiac remodeling owing to impaired VEGF-mediated angiogenesis. Therapy with enalapril has a neutral effect on VEGF-mediated angiogenesis, leading to the suppression of cardiac remodeling and an increase in life expectancy.
Pten loss in the bone marrow leads to G-CSF–mediated HSC mobilization
Authors: Melania Tesio, Gabriela M. Oser, Irène Baccelli, William Blanco-Bose, Hong Wu, Joachim R. Göthert, Scott C. Kogan, Andreas Trumpp
Journal: The Journal of Experimental Medicine (2013)

The phosphatase and tumor suppressor PTEN inhibits the phosphoinositol-3-kinase (PI3K) signaling pathway and plays a key role in cell growth, proliferation, survival, and migration. Pten conditional deletion using MxCre or Scl-CreER(T) leads to splenomegaly and leukemia formation, which occurs after the relocation of normal hematopoietic stem cells (HSCs) from the bone marrow to the spleen. Unexpectedly, dormant HSCs in the bone marrow do not enter the cell cycle upon Pten loss, they do not lose self-renewal activity, and they are not exhausted. Instead, Pten deficiency causes an up-regulation of the PI3K pathway in myeloid cells, but not in HSCs. Strikingly, myeloid cells secrete high levels of G-CSF upon Pten loss, leading to the mobilization of HSCs from the bone marrow and accumulation in the spleen. After deletion of Pten in mice lacking G-CSF, the splenomegaly, myeloproliferative disease, and splenic HSC accumulation are rescued. Our data show that although PTEN has little if any role in normal HSCs, it is essential to prevent overt G-CSF production by myeloid and stromal cells which otherwise causes HSCs to relocate to the spleen followed by lethal leukemia initiation.
EFFECT OF CIMETIDINE ON SURVIVAL AFTER GASTRIC CANCER
Authors: Hanne Tønnesen, Steffen Bülow, Kaj Fischerman, Allan Hjortrup, Vilhelm Møller Pedersen, Lars Bo Svendsen, Ulrich Knigge, Peter Damm, Peter Hesselfeldt, Ib Krogh Pedersen, Ole Julius Siemssen, Poul Martin Christiansen
Journal: The Lancet (1988)
Gout and Male Pseudo-Hermaphrodism: Report of a Case
Authors: E. F. Rosenberg
Journal: Annals of the Rheumatic Diseases (1941)

<h3>Background</h3> Travelling has always been an important factor in the spread of STI. In the last decades international travelling has become very popular and therefore the risk for spreading STI internationally has become higher. Here we examine determinants of casual travel sex among visitors of a large STI clinic in the Netherlands. With these results specific advice about safe casual travel sex might be given. <h3>Methods</h3> During three waves of the bi-annual anonymous survey (mid 2008–mid 2009), 2971 attendees of the STI clinic Amsterdam, were interviewed about risk factors for blood-borne and sexually transmitted infections and about casual travel sex in the past 6 months. Determinants of casual travel sex were analysed using logistic regression. Analyses were done combined and separately for participants with Western, Surinam, and other ethnicity. <h3>Results</h3> In total 949/2971 (32%) participants had casual travel sex in the 6 months preceding the visit to our STI clinic. Of these participants 265 (28%) were women, 299 (32%) heterosexual men and 385 (41%) MSM. Participants who had casual travel sex were more often heterosexual men (OR 1.66, 95% CI 1.37 to 2.01) or MSM (OR 3.03, 95% CI 2.50 to 3.68), were older (median 31 vs 27; p&lt;0.0001), had more often a history of STI (OR 1.66, 95% CI 1.42 to 1.94) and had a higher number of life time sexual partners (median 26 vs 13; p&lt;0.0001). Participants who had unsafe travel sex were younger (mean 29 vs 33; p&lt;0.001) and had less often a STI in the past (OR 1.41, 95% CI 1.08 to 1.82). In particular Western participants reported a high number of casual travel sex with discordant ethnic partners. In addition they reported more frequently unsafe sex with both discordant and concordant ethnic partners (see table). Around 60% of Western women, heterosexual men and MSM who had casual travel sex, had sex with a discordant ethnic partner. However, Western MSM were more likely to use a condom during casual travel sex (OR 2.39, 95% CI 1.45 to 3.92) than heterosexual men and women see Abstract P2-S4.07 Table 1. <h3>Conclusion</h3> Casual travel sex is very common among visitors of our STI clinic compared with the ca. 5% reported among visitors of a travel clinic, in particular among visitors who are older, with a high number of lifetime sex partners and with previous STI. These findings give insight in the risk of the international spread of STI and may be of help in providing specific pre-travel advice on safe sex abroad.
Induction Chemotherapy and Conformal Radiation Therapy for Very Young Children With Nonmetastatic Medulloblastoma: Children's Oncology Group Study P9934
Authors: David M. Ashley, Thomas E. Merchant, Douglas Strother, Tianni Zhou, Patricia Duffner, Peter C. Burger, Douglas C. Miller, Nancy Lyon, Melanie J. Bonner, Michael Msall, Allen Buxton, Russell Geyer, Larry E. Kun, Lee Coleman, Ian F. Pollack
Journal: Journal of Clinical Oncology (2012)

P9934 was a prospective trial of systemic chemotherapy, second surgery, and conformal radiation therapy (CRT) limited to the posterior fossa and primary site for children between 8 months and 3 years old with nonmetastatic medulloblastoma. The study was open from June 2000 until June 2006.After initial surgery, children received four cycles of induction chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa (18 or 23.4 Gy) and tumor bed (cumulative 50.4 or 54 Gy) and maintenance chemotherapy. Neurodevelopmental outcomes were evaluated and event-free survival (EFS) results were directly compared with a previous study of multiagent chemotherapy without irradiation (Pediatric Oncology Group [POG] trial 9233).Seventy-four patients met eligibility requirements. The 4-year EFS and overall survival probabilities were 50% ± 6% and 69% ± 5.5%, respectively, which compared favorably to the results from POG 9233. Analysis showed that the desmoplastic/nodular subtype was a favorable factor in predicting survival. Our 4-year EFS rate was 58% ± 8% for patients with desmoplasia. Whereas seven of 10 patients who had disease progression before CRT had primary-site failure, 15 of 19 patients who progressed after CRT had distant-site failure. Neurodevelopmental assessments did not show a decline in cognitive or motor function after protocol-directed chemotherapy and CRT.The addition of CRT to postoperative chemotherapy in young children with nonmetastatic medulloblastoma increased event-free survival compared with the use of postoperative chemotherapy alone. Future studies will use histopathologic typing (desmoplastic/nodular versus nondesmoplastic/nodular) to stratify patients for therapy by risk of relapse.
Increasing the Hematocrit Has a Beneficial Effect on Quality of Life and Is Safe in Selected Hemodialysis Patients
Authors: FUENSANTA MORENO, DÁMASO SANZ-GUAJARDO, JUAN MANUEL LÓPEZ-GÓMEZ, ROSA JOFRE, FERNANDO VALDERRÁBANO
Journal: Journal of the American Society of Nephrology (2000)

Target hematocrit/hemoglobin values in dialysis patients are still controversial. The Spanish Cooperative Renal Patients Quality of Life Study Group (including 34 hemodialysis units) conducted a prospective, 6-mo study of the effect on patient functional status and quality of life of using epoetin to achieve normal hematocrit in hemodialysis patients with anemia. The possible adverse effects of increased hematocrit, patient hospitalization, and epoetin requirements were also studied. The study included 156 patients (age range, 18 to 65 yr). Given the minimal experience in the safety of increasing hematocrit in dialysis patients to normal levels with epoetin, stable patients on hemodialysis who had received epoetin treatment for at least 3 mo and had a stable hemoglobin level of ≥9 g/dl were included in the study. Patients with antecedents of congestive cardiac failure, ischemic cardiopathy, diabetes mellitus, uncontrolled hypertension, cerebrovascular accident or seizures, malfunction of the vascular access or severe comorbidity (defined by a comorbidity index), and those over 65 yr of age were excluded from the study. Quality of life was measured with the Sickness Impact Profile (SIP) and Karnofsky scale. Patients completed questionnaires at home at onset and conclusion of the 6-mo study. Mean hematocrit increased from 30.9 to 38.4% and hemoglobin from 10.2 to 12.5 g/dl during the study. Health indicator scores improved significantly: mean Physical Dimension (SIP) from 5.38 to 4.1 (P < 0.005); mean Psychosocial Dimension from 9.2 to 7 (P < 0.001); mean global SIP from 8.9 to 7.25 (P < 0.001); mean Karnofsky scale score from 75.6 to 78.4 (P < 0.01). (SIP is scaled so that lower scores represent better functional status, and vice versa for the Karnofsky scale). Therefore, functional status and quality of life improved with increased hematocrit. No deaths occurred. Three patients (2%) were censored for hypertension and nine (5.7%) for thrombosis of the vascular access. The cumulative probability of thrombosis of the vascular access was 0.067. The average epoetin dose rose from 93 ± 62 U/kg per wk at onset to 141 ± 80 U/kg per wk at conclusion, a 51% increase. The number of patients hospitalized decreased and hospital lengths of stay were shorter during the study period than in the same patients in the 6-mo period preceding the study (P < 0.05). Nine patients (5.7%) had thrombosis of the vascular access. There were no changes in the prevalence of arterial hypertension, but three patients (2%) showed hypertension that was difficult to control. It is concluded that normalization of hematocrit in selected hemodialysis patients, i.e., nondiabetic patients without severe cardiovascular or cerebrovascular comorbidities, improves quality of life and decreases morbidity without significant adverse effects.
The Efficacy of Abatacept in Reducing Synovial T Cell Activation by CD1c Myeloid Dendritic Cells Is Overruled by the Stimulatory Effects of T Cell-Activating Cytokines
Authors: F. M. Moret, J. W. J. Bijlsma, F. P. J. G. Lafeber, J. A. G. van Roon
Journal: Arthritis & Rheumatology (2014)

To investigate whether the potential of abatacept to inhibit vigorous CD1c myeloid dendritic cell (MDC)-driven activation of naive and memory CD4 T cells is abrogated in the presence of T cell-activating cytokines.CD4 T cell subsets (naive [Tn], central memory [Tcm], and effector memory [Tem] T cells) were isolated from the peripheral blood (PB) of healthy controls and the PB and synovial fluid (SF) of rheumatoid arthritis (RA) patients. CD4 T cells were cocultured with autologous, thymic stromal lymphopoietin (TSLP)-primed CD1c MDCs in the presence or absence of abatacept (CTLA-4Ig) and/or interleukin-7 (IL-7) or IL-15. Subsequently, T cell proliferation and cytokine production were measured.The percentages of each CD4 T cell subset from the circulation of healthy controls and RA patients were comparable and mainly consisted of Tn and Tcm cells, whereas the SF of RA patients mainly consisted of Tcm and Tem cells. Activation of CD4 T cell subsets by TSLP-primed MDCs from the RA PB was completely blocked by abatacept. Addition of IL-7 or IL-15 to the cocultures strongly increased CD4 T cell activation and overruled the inhibitory capacity of abatacept. IL-7-induced reversal was associated with robust induction of interferon-γ, tumor necrosis factor α, and IL-17 secretion. Similarly, CD4 T cell proliferation induced by TSLP-primed MDCs from the SF of RA patients was strongly blocked by abatacept, but this inhibitory effect was vigorously overruled in the presence of IL-7.These findings indicate that the presence of T cell-activating cytokines such as IL-7 or IL-15 in the joints of RA patients reduces the capacity of abatacept to inhibit MDC-driven CD4 T cell activation. This mechanism may be one explanation for the partial, and sometimes absent, response to abatacept therapy in a subset of patients.
Defining the Transmurality of a Chronic Myocardial Infarction by Ultrasonic Strain-Rate Imaging
Authors: Frank Weidemann, Christoph Dommke, Bart Bijnens, Piet Claus, Jan D’hooge, Paul Mertens, Eric Verbeken, Alex Maes, Frans Van de Werf, Ivan De Scheerder, George R. Sutherland
Journal: Circulation (2003)

Background— In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. Methods and Results— After stenosing copper-coated stent implantation to produce circumflex artery endothelial proliferation, 18 pigs were followed up for 5 weeks. Posteuthanasia histology showed 10 to have a nontransmural and 8 a transmural infarction. Eight nonstented animals served as controls. Regional radial function was monitored by measuring ultrasound-derived peak systolic strain rates (SR SYS ) and systolic strains (ε SYS ) (1) before stent implantation and (2) at 5 weeks, at baseline (bs) and during an incremental dobutamine infusion. In controls, dobutamine induced a linear increase in SR SYS (dobutamine: bs, 4.8±0.4 s −1 ; 20 μg · kg −1 · min −1 , 9.9±0.7 s −1 ; P &lt;0.0001) and an initial increase of ε SYS at low dose (bs, 58±5%; at 5 μg · kg −1 · min −1 , 78±6%; P &lt;0.05) but a subsequent decrease during higher infusion rates. In the nontransmural group, bs SR SYS and ε SYS were significantly lower than prestent values (SR SYS , 2.9±0.5 s −1 and ε SYS , 32±6%, P &lt;0.05 versus prestent). During dobutamine infusion, SR SYS increased slightly at 5 μg · kg −1 · min −1 (4.7±0.6 s −1 , P &lt;0.05) but fell during higher infusion rates, whereas ε SYS showed no change. For nontransmural infarctions, transmural scar extension correlated closely with ε SYS at bs ( r =0.88). For transmural infarctions, SR SYS at bs was significantly reduced and ε SYS was almost not measurable (SR SYS , 1.8±0.3 s −1 ; ε SYS , 3±4%). Both deformation parameters showed no further change during the incremental dobutamine infusion. Conclusions— Ultrasonic deformation values could clearly differentiate chronic nontransmural from transmural myocardial infarction. The transmural extension of the scar could be defined by the regional deformation response.
Reactive Hyperemia Occurs Via Activation of Inwardly Rectifying Potassium Channels and Na <sup>+</sup> /K <sup>+</sup> -ATPase in Humans
Authors: Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno
Journal: Circulation Research (2013)

Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear.We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na(+)/K(+)-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans.In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 subjects and assessed RH in the following conditions. For group 1, we studied control (saline), KIR channel inhibition (BaCl2), combined inhibition of KIR channels and Na(+)/K(+)-ATPase (BaCl2 and ouabain, respectively), and combined inhibition of KIR channels, Na(+)/K(+)-ATPase, NO, and prostaglandins (BaCl2, ouabain, L-NMMA [N(G)-monomethyl-L-arginine] and ketorolac, respectively). Group 2 received ouabain rather than BaCl2 in the second trial. In protocol 2 (n=8), the following 3 RH trials were performed: control; L-NMMA plus ketorolac; and L-NMMA plus ketorolac plus BaCl2 plus ouabain. All infusions were intra-arterial (brachial). Compared with control, BaCl2 significantly reduced peak FBF (-50±6%; P<0.05), whereas ouabain and L-NMMA plus ketorolac did not. Total FBF (area under the curve) was attenuated by BaCl2 (-61±3%) and ouabain (-44±12%) alone, and this effect was enhanced when combined (-87±4%), nearly abolishing RH. L-NMMA plus ketorolac did not impact total RH FBF before or after administration of BaCl2 plus ouabain.Activation of KIR channels is the primary determinant of peak RH, whereas activation of both KIR channels and Na(+)/K(+)-ATPase explains nearly all of the total (AUC) RH in humans.