tbuckley/cabot-search huggingface dataset:
Cerebral Microbleeds Are Associated With an Increased Risk of Stroke
Authors: Saloua Akoudad, Marileen L.P. Portegies, Peter J. Koudstaal, Albert Hofman, Aad van der Lugt, M. Arfan Ikram, Meike W. Vernooij
Journal: Circulation (2015)

Background— Cerebral microbleeds are highly prevalent in people with clinically manifest cerebrovascular disease and have been shown to increase the risk of stroke recurrence. Microbleeds are also frequently found in healthy elderly, a population in which the clinical implication of microbleeds is unknown. Methods and Results— In the population-based Rotterdam Study, the presence, number, and location of microbleeds were assessed at baseline on brain MRI of 4759 participants aged ≥45 years. Participants were followed for incident stroke throughout the study period (2005–2013). We used Cox proportional hazards to investigate if people with microbleeds were at increased risk of stroke in comparison with those without microbleeds, adjusting for demographic, genetic, and cardiovascular risk, and cerebrovascular imaging markers. Microbleed prevalence was 18.7% (median count 1 [1–111]). During mean follow-up of 4.9 years (standard deviation, 1.6) 93 strokes occurred (72 ischemic, 11 hemorrhagic, and 10 unspecified). Microbleed presence was associated with an increased risk of all strokes (hazard ratio, 1.93; 95% confidence interval, 1.25–2.99). The risk increased with greater microbleed count. In comparison with those without microbleeds, participants with microbleeds in locations suggestive of cerebral amyloid angiopathy (lobar with or without cerebellar microbleeds) were at increased risk of intracerebral hemorrhage (hazard ratio, 5.27; 95% confidence interval, 1.38–20.23). Microbleeds at other locations were associated with an increased risk of both ischemic stroke and intracerebral hemorrhage. Conclusions— Microbleeds on MRI are associated with an increased risk of stroke in the general population. Our results strengthen the notion that microbleeds mark progression of cerebrovascular pathology and represent a precursor of stroke.
Hospitalized but Not Admitted
Authors: Ann M. Sheehy, Ben Graf, Sreedevi Gangireddy, Robert Hoffman, Mary Ehlenbach, Cynthia Heidke, Sheilah Fields, Barbara Liegel, Elizabeth A. Jacobs
Journal: JAMA Internal Medicine (2013)

The Centers for Medicare & Medicaid Services (CMS) defines observation status for hospitalized patients as a "well-defined set of specific, clinically appropriate services," usually lasting less than 24 hours, and that in "only rare and exceptional cases" should last more than 48 hours. Although an increasing proportion of observation care occurs on hospital wards, studies of patients with observation status have focused on the efficiency of dedicated units.To describe inpatient and observation care.Descriptive study of all inpatient and observation stays between July 1, 2010, and December 31, 2011, at the University of Wisconsin Hospital and Clinics, a 566-bed tertiary academic medical center.All patients with observation or inpatient stays during the study period.Patient demographics, length of stay, difference between cost and reimbursement per stay, and percentage of patients discharged to skilled nursing facilities.Of 43,853 stays, 4578 (10.4%) were for observation, with 1141 distinct diagnosis codes. Mean observation length of stay was 33.3 hours, with 44.4% of stay durations less than 24 hours and 16.5% more than 48 hours. Observation care had a negative margin per stay (-$331); the inpatient margin per stay was positive (+$2163). Adult general medicine patients accounted for 2404 (52.5%) of all observation stays; 25.4% of the 9453 adult general medicine stays were for observation. The mean length of stay for general medicine observation patients was 41.1 hours, with 32.6% of stay durations less than 24 hours and 26.4% more than 48 hours. Compared with observation patients on other clinical services, adult general medicine had the highest percentage of patients older than 65 years (40.9%), highest percentage female patients (57.9%), highest percentage of patients discharged to skilled nursing facilities (11.6%), and the most negative margin per stay (-$1378).In an academic medical center, observation status for hospitalized patients differed markedly from the CMS definition. Patients had a wide variety of diagnoses; lengths of stay were typically more than 24 hours and often more than 48 hours. The hospital lost money, primarily because reimbursement for general medicine patients was inadequate to cover the costs. It is uncertain what role, if any, observation status for hospitalized patients should have in the era of health care reform.
Early Use of the Pulmonary Artery Catheter and Outcomes in Patients With Shock and Acute Respiratory Distress Syndrome&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Christian Richard, Josiane Warszawski, Nadia Anguel, Nicolas Deye, Alain Combes, Didier Barnoud, Thierry Boulain, Yannick Lefort, Muriel Fartoukh, Frederic Baud, Alexandre Boyer, Laurent Brochard, Jean-Louis Teboul
Journal: JAMA (2003)

ANY PHYSICIANS BELIEVEthat the pulmonary artery catheter (PAC) is useful for the diagnosis and treatment of cardiopulmonary disturbances and for assessing volume status in critically ill patients. 1,2However, investigators have raised doubts about the safety of the PAC 3,4 because its use may be associated with direct complications 5 or harmful effects related to inappropriate decisions resulting from misinterpretation of the data. 6he most serious concern was raised by the retrospective study by Connors et al, 4 which suggested that the use of PAC within 24 hours following admission
Prevention of Ventricular Fibrillation Episodes in Brugada Syndrome by Catheter Ablation Over the Anterior Right Ventricular Outflow Tract Epicardium
Authors: Koonlawee Nademanee, Gumpanart Veerakul, Pakorn Chandanamattha, Lertlak Chaothawee, Aekarach Ariyachaipanich, Kriengkrai Jirasirirojanakorn, Khanchit Likittanasombat, Kiertijai Bhuripanyo, Tachapong Ngarmukos
Journal: Circulation (2011)

The underlying electrophysiological mechanism that causes an abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (Vt/VF) in patients with the Brugada syndrome (BrS) remains unelucidated. However, several studies have indicated that the right ventricular outflow tract (RVOT) is likely to be the site of electrophysiological substrate. We hypothesized that in patients with BrS who have frequent recurrent VF episodes, the substrate site is the RVOT, either over the epicardium or endocardium; abnormal electrograms would be identified at this location, which would serve as the target site for catheter ablation.We studied 9 symptomatic patients with the BrS (all men; median age 38 years) who had recurrent VF episodes (median 4 episodes) per month, necessitating implantable cardioverter defibrillator discharge. Electroanatomic mapping of the right ventricle, both endocardially and epicardially, and epicardial mapping of the left ventricle were performed in all patients during sinus rhythm. All patients had typical type 1 Brugada ECG pattern and inducible Vt/VF; they were found to have unique abnormal low voltage (0.94±0.79 mV), prolonged duration (132±48 ms), and fractionated late potentials (96±47 ms beyond QRS complex) clustering exclusively in the anterior aspect of the RVOT epicardium. Ablation at these sites rendered Vt/VF noninducible (7 of 9 patients [78%]; 95% confidence interval, 0.40 to 0.97, P=0.015) and normalization of the Brugada ECG pattern in 89% (95% confidence interval, 0.52 to 0.99; P=0.008). Long-term outcomes (20±6 months) were excellent, with no recurrent Vt/VF in all patients off medication (except 1 patient on amiodarone).The underlying electrophysiological mechanism in patients with BrS is delayed depolarization over the anterior aspect of the RVOT epicardium. Catheter ablation over this abnormal area results in normalization of the Brugada ECG pattern and prevents Vt/VF, both during electrophysiological studies as well as spontaneous recurrent Vt/VF episodes in patients with BrS.
IMMUNOCHEMISTRY OF THE COMMON ANTIGEN OF ENTEROBACTERIACEAE (KUNIN)
Authors: Sten Hammarström, Hans Erik Carlsson, Peter Perlmann, Sigfrid Svensson
Journal: The Journal of Experimental Medicine (1971)

Preparations of E. coli 014 lipopolysaccharide (LPS) contain a common enterobacterial antigen (CA) in large amounts or in an immunogenic form. Chemical analysis revealed, in addition to o-acetyl groups, only those sugars which are present in the basal core structure of the E. coli or Salmonella LPS (e.g., galactose, glucose, glucosamine, heptose, and ketodeoxyoctonate). On treatment with acetic acid (pH 3.2) at 100 degrees C for 1.5 hr, a fragment was liberated which after gel filtration on Sephadex G-50 appeared in the molecular weight range of 2-3 x 10(3). The fragment inhibited precipitation of alkali-treated E. coli 014 LPS by antibodies to CA from anti-E. coli 014 serum. It also inhibited hemagglutination between anti-CA antibodies and red cells coated with E. coli 08 LPS. Chemical analysis of the fragment indicated that it corresponded to the core region of E. coli 014 LPS. It contained a heptose and ketodeoxyoctonate in addition to glucose and galactose. However the fraction lacked glucosamine. Enterobacterial CA has previously been found to cross-react with colon antigen of ulcerative colitis. These results should provide a chemical basis for further studies of this cross-reactivity.
Constrictive pericarditis following Coxsackie virus infection
Authors: J. D. Matthews, S. J. Cameron, M. George
Journal: Thorax (1970)

Infection with Coxsackie B<sub>2</sub> virus is described in a 49-year-old farmer in whom myopericarditis and pneumonitis was followed over a period of 10 months by constrictive pericarditis. The differentiation between restrictive cardiomyopathy and constrictive pericarditis was not achieved without exploratory thoracotomy. The adherent pericardium was successfully excised with complete relief. The literature is reviewed and it is suggested that the development of constriction following Coxsackie pericarditis must be considered at subsequent examinations of the patient.
Systematic Review: Agranulocytosis Induced by Nonchemotherapy Drugs
Authors: Frank Andersohn, Christine Konzen, Edeltraut Garbe
Journal: Annals of Internal Medicine (2007)

Background: Nonchemotherapy drug–induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 × 109 cells/L due to immunologic or cytotoxic mechanisms. Purpose: To systematically review case reports of drugs that are definitely or probably related to agranulocytosis. Data Sources: English-language and German-language reports in MEDLINE (1966 to 2006) or EMBASE (1989 to 2006) and in bibliographies of retrieved articles. Study Selection: Published case reports of patients with nonchemotherapy drug–induced agranulocytosis. Data Extraction: One reviewer abstracted details about cases and assessed causality between drug intake and agranulocytosis by using World Health Organization assessment criteria. Data Synthesis: Causality assessments of 980 reported cases of agranulocytosis were definite in 56 (6%), probable in 436 (44%), possible in 481 (49%), and unlikely in 7 (1%). A total of 125 drugs were definitely or probably related to agranulocytosis. Drugs for which more than 10 reports were available (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine) accounted for more than 50% of definite or probable reports. Proportions of fatal cases decreased between 1966 and 2006. More patients with a neutrophil count nadir less than 0.1 × 109 cells/L had fatal complications than did those with a neutrophil count nadir of 0.1 × 109 cells/L or greater (10% vs. 3%; P < 0.001). Patients treated with hematopoietic growth factors had a shorter median duration of neutropenia (8 days vs. 9 days; P = 0.015) and, among asymptomatic patients at diagnosis, had a lower proportion of infectious or fatal complications (14% vs. 29%; P = 0.030) than patients without such treatment. Limitations: Case reports cannot provide rates of drug-induced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes. Conclusions: Many drugs can cause nonchemotherapy drug–induced agranulocytosis. Case fatality may be decreasing over time with the availability of better treatment.
Pulmonary infection in Wegener's granulomatosis and idiopathic pulmonary fibrosis
Authors: N. K. Harrison
Journal: Thorax (2009)

adults in the analysis by Ku ¨nzli et al. 15 The authors speculate that they did not find an effect of distance to roadway because their study design was longitudinal, and this variable did not change over time for most subjects.Moreover, they contend that the modelled traffic-related particulate matter exposures which they assigned to their subjects captured the spatial and temporal heterogeneity of individual exposures better than can be achieved with distance to roadway metrics.They suggest that this greater heterogeneity of exposure allowed their analysis to achieve statistical significance despite the relatively small number of new cases of asthma in the SAPALDIA cohort.Similar reasoning can be applied to the study by Jerrett et al which captured spatial heterogeneity in traffic exposures by using nitrogen dioxide concentrations measured immediately outside the children's homes as a proxy for the traffic-related pollution mixture. 10 Perhaps the greatest research challenge regarding the impact of traffic-related pollution on asthma is to determine what specific constituents of the mixture are responsible for the observed effects.While diesel exhaust particles have clearly been shown to induce both cytotoxic and immune adjuvant responses in toxicological studies 16 as well as acute lung function decrements in subjects with asthma, 17 it has been difficult to distinguish diesel effects from those of other components of the traffic mixture in epidemiological studies, largely due to an inability to assess exposure properly.Until we develop better exposure assessment methods, we will be unable to meet this challenge.Without good data about the causative agents in the traffic pollution mixture, our ability to control exposures to protect the health of people with asthma will continue to be handicapped.
Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice
Authors: Kinya Inoue, Takuji Torimura, Toru Nakamura, Hideki Iwamoto, Hiroshi Masuda, Mitsuhiko Abe, Osamu Hashimoto, Hironori Koga, Takato Ueno, Hirohisa Yano, Michio Sata
Journal: Clinical Cancer Research (2012)

VEGF, EGF, and TGF-α are expressed in hepatocellular carcinomas (HCC) and play a role in its growth. Vandetanib, a multikinase inhibitor, suppresses the phosphorylation of VEGF receptor 2 (VEGFR-2) and EGF receptor (EGFR). The aim of this study was to clarify the antitumor effect of vandetanib in mouse HCCs.We evaluated the effects of vandetanib on proliferation of human umbilical vein endothelial cells (HUVEC) and three hepatoma cell lines, as well as the phosphorylation of VEGFR-2 and EGFR in these cells. Mice were implanted with hepatoma cells subcutaneously or orthotopically in the liver and treated with 50 or 75 mg/kg vandetanib. We analyzed the effects of treatment on tumor cell proliferation and apoptosis, vessel density, phosphorylation of VEGFR-2 and EGFR, and production of VEGF, TGF-α, and EGF in tumor tissues. Adverse events on vandetanib administration were also investigated.Vandetanib suppressed phosphorylation of VEGFR-2 in HUVECs and EGFR in hepatoma cells and inhibited cell proliferation. In tumor-bearing mice, vandetanib suppressed phosphorylation of VEGFR-2 and EGFR in tumor tissues, significantly reduced tumor vessel density, enhanced tumor cell apoptosis, suppressed tumor growth, improved survival, reduced number of intrahepatic metastases, and upregulated VEGF, TGF-α, and EGF in tumor tissues. Treatment with vandetanib was not associated with serious adverse events, including alanine aminotransferase abnormality, bone marrow suppression, or body weight loss.The antitumor effects of vandetanib in mice suggest that it is a potentially suitable and safe chemotherapeutic agent for HCCs.
Modulation of Transforming Growth Factor-β Signaling and Extracellular Matrix Production in Myxomatous Mitral Valves by Angiotensin II Receptor Blockers
Authors: Arnar Geirsson, Mansher Singh, Rahmat Ali, Hussain Abbas, Wei Li, Juan A. Sanchez, Sabet Hashim, George Tellides
Journal: Circulation (2012)

Little is known about the pathophysiology of myxomatous degeneration of the mitral valve, the pathological hallmark of mitral valve prolapse, associated with symptomatic mitral regurgitation, heart failure, and death. Excess transforming growth factor (TGF)-β signaling is known to cause mitral valve degeneration and regurgitation in a mouse model of Marfan syndrome. We examined if TGF-β signaling is dysregulated in clinical specimens of sporadic mitral valve prolapse compared with explanted nondiseased mitral valves and we tested the effects of angiotensin II receptor blockers on TGF-β signaling in cultured human mitral valve cells.Operative specimens, cultured valve tissues, and cultured valvular interstitial cells were obtained from patients with mitral valve prolapse undergoing mitral valve repair or from organ donors without mitral valve disease. Increased extracellular matrix in diseased valve tissue correlated with an upregulation of TGF-β expression and signaling as evidenced by SMAD2/3 phosphorylation. Both TGF-β ligand and signaling mediators colocalized primarily to valvular interstitial cells suggesting autocrine/paracrine activation. In cultured valve tissue, exogenous TGF-β increased basal extracellular matrix production, whereas serological neutralization of TGF-β inhibited disease-driven extracellular matrix overproduction. TGF-β-induced extracellular matrix production in cultured valvular interstitial cells was dependent on SMAD2/3 and p38 signaling and was inhibited by angiotensin II receptor blockers.TGF-β has a profibrotic role in the pathogenesis of sporadic mitral valve prolapse. Attenuation of TGF-β signaling by angiotensin II receptor blockers may represent a mechanistically based strategy to modulate the pathological progression of mitral valve prolapse in patients.
Inhibition of c-Jun NH2-terminal kinase switches Smad3 signaling from oncogenesis to tumor- suppression in rat hepatocellular carcinoma
Authors: Hiromitsu Nagata, Etsuro Hatano, Masaharu Tada, Miki Murata, Koji Kitamura, Hiroyuki Asechi, Masato Narita, Atsuko Yanagida, Nobuyuki Tamaki, Shintaro Yagi, Iwao Ikai, Koichi Matsuzaki, Shinji Uemoto
Journal: Hepatology (2009)

Transforming growth factor beta (TGF-beta) signaling involves both tumor-suppression and oncogenesis. TGF-beta activates the TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TbetaRI-dependent pSmad3C transmits a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promotes carcinogenesis in human chronic liver disorders. The aim of this study is to elucidate how SP600125, a JNK inhibitor, affected rat hepatocellular carcinoma (HCC) development, while focusing on the domain-specific phosphorylation of Smad3. The rats received subcutaneous injections of either SP600125 or vehicle 11 times weekly together with 100 ppm N-diethylnitrosamine (DEN) administration for 56 days and were sacrificed in order to evaluate HCC development 28 days after the last DEN administration. The number of tumor nodules greater than 3 mm in diameter and the liver weight/body weight ratio were significantly lower in the SP600125-treated rats than those in the vehicle-treated rats (7.9 +/- 0.8 versus 17.7 +/- 0.9: P < 0.001; 6.3 +/- 1.2 versus 7.1 +/- 0.2%: P < 0.05). SP600125 significantly prolonged the median survival time in rats with DEN-induced HCC (113 versus 97 days: log-rank P = 0.0018). JNK/pSmad3L/c-Myc was enhanced in the rat hepatocytes exposed to DEN. However, TbetaRI/pSmad3C/p21(WAF1) was impaired as DEN-induced HCC developed and progressed. The specific inhibition of JNK activity by SP600125 suppressed pSmad3L/c-Myc in the damaged hepatocytes and enhanced pSmad3C/p21(WAF1), acting as a tumor suppressor in normal hepatocytes.Administration of SP600125 to DEN-treated rats shifted hepatocytic Smad3-mediated signal from oncogenesis to tumor suppression, thus suggesting that JNK could be a therapeutic target of human HCC development and progression.
Altered thermal sensitivity in facial skin in chronic whiplash-associated disorders
Authors: Birgitta Häggman-Henrikson, Ewa Lampa, Erik Nordh
Journal: International Journal of Oral Science (2013)

There is a close functional relationship between the jaw and neck regions and it has been suggested that trigeminal sensory impairment can follow whiplash injury. Inclusion of manageable routines for valid assessment of the facial sensory capacity is thus needed for comprehensive evaluations of patients exposed to such trauma. The present study investigated facial thermal thresholds in patients with chronic whiplash-associated disorders (WADs) with both a qualitative method and quantitative sensory testing (QST). Ten women with pain and dysfunction following a whiplash injury were compared to 10 healthy age-matched women. Thermal detection thresholds were assessed by qualitative chair-side testing and by QST according to the method-of-limits. Seven test sites in the facial skin (overlying each trigeminal branch bilaterally, and the midpoint of the chin) were examined. The detection warm and cold thresholds were defined as the mean values of 10 individual thresholds. For the WAD patients, the qualitative assessment demonstrated both reduced and increased sensitivity compared to the healthy, whereas QST systematically showed significantly higher detection thresholds (i.e., decreased sensitivity) for both cold and warm stimuli. For the individuals who were assessed as having increased sensitivity in the qualitative assessment, the QST displayed either normal or higher thresholds, i.e., decreased sensitivity. The results suggest that QST is more sensitive for detecting thermal sensory disturbances in the face than a qualitative method. The impaired thermal sensitivity among the patients corroborates the notion of altered thermal detection capacity induced by WAD-related pain.
An acquired bullous dermatosis due to an autoimmune reaction against uncein
Authors: Y. HORIGUCHI, M. UEDA, H. SHIMIZU, T. TANAKA, N. MATSUYOSHI, A. UTANI, K. IKAL, T. NISHIKAWA, S. IMAMURA
Journal: British Journal of Dermatology (1996)

A 59-year-old male showed acquired, mechanically induced, scarring blisters on the fingers, toes, scalp and abdomen, as well as in the oral cavity. Ultrastructural and immunohistochemical examination of the bullae revealed junctional epidermal-dermal separation and IgG deposits in the lamina lucida of the basement membrane zone (BMZ), where the reactivity of the 19-DEJ-1 monoclonal antibody was decreased. Anti-BMZ autoantibodies detected in his serum were reactive to the lower lamina lucida region of normal human skin. SDS-PAGE of affinity purified antigens from human keratinocytes with IgG from the patient's serum revealed three polypeptide bands at 165, 135 and 100 kDa, in reduced condition. The indirect immunofluorescence test of his serum was negative on skin cryosections from patients with lethal junctional epidermolysis bullosa. Pretreatment of normal human skin sections with the patient's serum, blocked the binding of 19-DEJ-1 monoclonal antibody but not that of the GB3 monoclonal antibody. This case is considered to be an acquired autoimmune bullous dermatosis due to an autoantibody reaction against uncein (19-DEJ-1 antigen), a component of anchoring filaments.