tbuckley/cabot-search huggingface dataset:
Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations
Authors: Fadi Fakhouri, Lubka Roumenina, François Provot, Marion Sallée, Sophie Caillard, Lionel Couzi, Marie Essig, David Ribes, Marie-Agnès Dragon-Durey, Frank Bridoux, Eric Rondeau, Veronique Frémeaux-Bacchi
Journal: Journal of the American Society of Nephrology (2010)

In contrast to pregnancy-associated thrombotic thrombocytopenic purpura, the pathogenesis and presentation of pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) remain ill-defined. We conducted a retrospective study to assess the presentation and outcomes of patients presenting with P-aHUS and the prevalence of alternative C3 convertase dysregulation. P-aHUS occurred in 21 of the 100 adult female patients with atypical HUS, with 79% presenting postpartum. We detected complement abnormalities in 18 of the 21 patients. The outcomes were poor: 62% reached ESRD by 1 month and 76% by last follow-up. The risk for P-aHUS was highest during a second pregnancy. Thirty-five women, 26 (74%) of whom had complement abnormalities, had at least one pregnancy before the onset of a non-pregnancy-related aHUS. Outcomes did not differ between patients with pregnancy-related and non-pregnancy-related aHUS. Mutations in the SCR19-20 domains of factor H were less frequent in P-aHUS patients compared with non-pregnancy-related aHUS. Pregnancies in female patients with complement abnormalities (n = 44) were complicated by fetal loss and preeclampsia in 4.8% and 7.7%, respectively. Better understanding of complement dysregulation in pregnancy complications is essential, especially to guide development of pharmacologic agents to modulate this system.
Digestive Endoscopy Is Not a Major Risk Factor for Transmitting Hepatitis C Virus
Authors: Alessia Ciancio, Paola Manzini, Franco Castagno, Sergio D'Antico, Paolo Reynaudo, Laura Coucourde, Giovannino Ciccone, Mario Del Piano, Marco Ballarè, Sergio Peyre, Roberto Rizzi, Claudio Barletti, Mauro Bruno, Stefania Caronna, Patrizia Carucci, Wilma De Bernardi Venon, Claudio De Angelis, Anna Morgando, Alessandro Musso, Alessandro Repici, Mario Rizzetto, Giorgio Saracco
Journal: Annals of Internal Medicine (2005)

Background: The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial. Objective: To evaluate the role of digestive endoscopy in transmitting HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors. Design: Prospective cohort study. Setting: 3 endoscopic units and 2 blood banks in northwestern Italy. Patients: The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51 230 healthy, anti-HCV–negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38 280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95 317 person-years of observation). Measurements: Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction. Results: All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test. Limitations: In the endoscopy cohort, 8.3% of patients were lost to follow-up. Conclusions: These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.
Is This Child Dehydrated?
Authors: Michael J Steiner, Darren A DeWalt, Julie S Byerley
Journal: JAMA (2004)

The ability to assess the degree of dehydration quickly and accurately in infants and young children often determines patient treatment and disposition.To systematically review the precision and accuracy of symptoms, signs, and basic laboratory tests for evaluating dehydration in infants and children.We identified 1561 potential articles by multiple search strategies of the MEDLINE database through PubMed. Searches of bibliographies of retrieved articles, the Cochrane Library, textbooks, and private collections of experts in the field yielded an additional 42 articles.Twenty-six of 1603 reviewed studies contained original data on the precision or accuracy of findings for the diagnosis of dehydration in young children (1 month to 5 years).Two of the 3 authors independently reviewed and abstracted data for estimating the likelihood ratios (LRs) of diagnostic tests. We eliminated 13 of the 26 studies because of the lack of an accepted diagnostic standard or other limitation in study design. The other 13 studies were included in the review.The most useful individual signs for predicting 5% dehydration in children are an abnormal capillary refill time (LR, 4.1; 95% confidence interval [CI], 1.7-9.8), abnormal skin turgor (LR, 2.5; 95% CI, 1.5-4.2), and abnormal respiratory pattern (LR, 2.0; 95% CI, 1.5-2.7). Combinations of examination signs perform markedly better than any individual sign in predicting dehydration. Historical points and laboratory tests have only modest utility for assessing dehydration.The initial assessment of dehydration in young children should focus on estimating capillary refill time, skin turgor, and respiratory pattern and using combinations of other signs. The relative imprecision and inaccuracy of available tests limit the ability of clinicians to estimate the exact degree of dehydration.
Viral Vector Delivery in Solid-State Vehicles: Gene Expression in a Murine Prostate Cancer Model
Authors: D. R. Siemens
Journal: JNCI Journal of the National Cancer Institute (2000)

Although there are increasingly more clinical trials involving gene therapy, efficient gene transfer remains a major hurdle to success. To enhance the efficiency of delivery of viral vectors in gene therapy protocols, we evaluated the effect of various matrices to act as a vehicle for recombinant virus during intratumoral injection.The ability of several vehicles (catgut spacer, polyglycolic acid, chromic catgut, and gelatin sponge matrix) to deliver the canarypox virus ALVAC to the cells of the murine prostate cancer cell line RM-1 was studied in vitro and in vivo. ALVAC recombinants encoding the murine cytokines interleukin 2 (IL-2), interleukin 12 (IL-12), and tumor necrosis factor-alpha (TNF-alpha) were used to assess enhancement of antitumor activity after intratumoral inoculation. Confirmatory experiments were conducted by use of another mouse prostate cancer cell line, RM-11, and a mouse bladder cancer cell line, MB-49. All statistical tests were two-sided.The gelatin sponge matrix proved to be the most effective solid-state vehicle for delivering viral vectors to cells in culture. In addition, this matrix statistically significantly enhanced expression of ALVAC-delivered reporter genes in tumor models when compared with fluid-phase delivery of virus (P =.037 for the RM-1 model and P =.03 for the MB-49 model). Statistically significant growth inhibition of established tumors was observed when a combination of the three recombinant ALVAC viruses expressing IL-2, IL-12, and TNF-alpha was delivered with the matrix in comparison with 1) fluid-phase intratumoral injection of the ALVAC recombinants, 2) no treatment, or 3) treatment with parental ALVAC (all P<.05).Viral vector delivery in a solid-state vehicle resulted in improved recombinant gene expression in vivo and translated to greater inhibition of tumor growth in an immunotherapy protocol for heterotopic tumor nodules. The efficient delivery of reporter genes described herein may prove useful in many solid tumor gene therapy protocols.
P83 Should children from HHT families undergo screening thoracic CT scans for the diagnosis of pulmonary arteriovenous malformations? Survey data on breast cancer incidence
Authors: AE Hosman, HL Devlin, BM Silva, AH Elphick, CL Shovlin
Journal: Thorax (2013)

<h3>Background</h3> Limiting thoracic radiation burden is a driving force for development of diagnostics, with the use of childhood CT scans particularly linked to increased cancer incidence [1]. Imaging of children with known or suspected hereditary haemorrhagic telangiectasia (HHT) has been performed for more than 30 years, in order to diagnose and/or treat pulmonary arteriovenous malformations (PAVMs). Childhood screening thoracic CT scans are currently recommended international practice [2]. Our aim was to explore if breast cancer rates differed in HHT patients compared to controls. <h3>Methods</h3> To provide sufficient power to compare breast cancer rates in HHT patients and controls, we developed a questionnaire capturing data on multiple relatives per respondent, powered to detect differences in breast cancer rates. Blinded to cancer responses, reports of HHT-specific features allowed assignment of participants and relatives as HHT-subject, unknown, or control. <h3>Results</h3> By data download on 30.6.2012, 1,307 participants (including 1,012 HHT-subjects, 142 controls) had completed the international questionnaire, with the majority of respondents residing in North America. Ages (medians 55/53 ys), gender (65/65% female) and general demographics were similar between the groups. Combining data of participants and relatives resulted in a control-arm of 2,817 (52% female), and HHT-arm of 2,166 (58% female). Median ages were 77ys [IQR 65–82] and 66ys [IQR 53–77] respectively. Rates of breast cancer in the control group matched the age standardised frequency reported by Globocan for the general population, with a ratio of observed/expected incidence of 1.22. As expected, cancer rates increased with age (p &lt; 0.0001, all cancers). Following age-adjustment, breast cancer was reported significantly more frequently for the HHT group than controls (quadratic regression age-adjusted OR 1.52 (1.07, 2.14, p = 0.018). <h3>Conclusions</h3> Individuals with HHT may be more likely to develop breast cancer. Further study is required to validate, and to assess if any excess is related to radiation exposure, or other factors. Nevertheless, given the rationale for PAVM screening programmes relates to risk reductions in adult life, the data support the widespread view that PAVM screening CT scans should be postponed until after puberty. <h3>References</h3> Matthews <i>et al</i>, <i>BMJ</i>. 2013 May 21;346:f2360. Faughnan et al, <i>J Med Genet</i>. 2011 Feb;48(2):73–87.
FGF2 induces RANKL gene expression as well as IL1β regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells
Authors: Chiara Bocelli-Tyndall, Emanuele Trella, Audrey Frachet, Paul Zajac, Dennis Pfaff, Jeroen Geurts, Stefan Heiler, Andrea Barbero, Marcus Mumme, Therese J Resink, Stefan Schaeren, Giulio C Spagnoli, Alan Tyndall
Journal: Annals of the Rheumatic Diseases (2013)

Human bone marrow mesenchymal stromal cells (hBM-MSC) are being applied in tissue regeneration and treatment of autoimmune diseases (AD). Their cellular and immunophenotype depend on isolation and culture conditions which may influence their therapeutic application and reflect their in vivo biological functions. We have further characterised the phenotype induced by fibroblast growth factor 2 (FGF2) on healthy donor hBM-MSC focusing on the osteoimmunological markers osteoprotegerin (OPG), receptor activator of nuclear factor kB (RANK), RANK ligand (RANKL) and HLA-DR and their regulation of expression by the inflammatory cytokines IL1β and IFNγ.RANK, RANKL, OPG and HLA-DR expression in hBM-MSC expanded under specific culture conditions, were measured by RT-PCR and flow cytometry. MAPKs induction by FGF2, IL1β and IFNγ in hBM-MSC was analysed by immunoblotting and RT-PCR.In hBM-MSC, OPG expression is constitutive and FGF2 independent. RANKL expression depends on FGF2 and ERK1/2 activation. IL1β and IFNγ activate ERK1/2 but fail to induce RANKL. Only IL1β induces P38MAPK. The previously described HLA-DR induced by FGF2 through ERK1/2 on hBM-MSC, is suppressed by IL1β through inhibition of CIITA transcription. HLA-DR induced by IFNγ is not affected by IL1β in hBM-MSC, but is suppressed in articular chondrocytes and lung fibroblasts.RANKL expression and IL1β regulated MHC-class II, both induced via activation of the ERK1/2 signalling pathway, are specific for progenitor hBM-MSC expanded in the presence of FGF2. HLA-DR regulated by IL1β and ERK1/2 is observed on hBM-MSC during early expansion without FGF2 suggesting previous in vivo acquisition. Stromal progenitor cells with this phenotype could have an osteoimmunological role during bone regeneration.
LIMITATIONS OF MEDICAL TRADITIONS ON COMMUNITY MENTAL HEALTH PROGRAMS
Authors: LAWRENCE C. KOLB, VIOLA W. BERNARD, RAY E. TRUSSELL, MARGARET W. BARNARD, BRUCE P. DOHRENWEND, BARBARA KOHLSAAT, ROBERT WEISS
Journal: American Journal of Psychiatry (1961)

A series of entrenched medical traditions has been recognized as obstructive for the development of effective mental health practices and the on-going assessments of patient care. Traditional patterns of isolation within and between medical and non-medical facilities of the community's resources contribute to maintenance of weak patterns of coordination, communication and fulfillment of responsibility with consequent antitherapeutic fractionation, discontinuity and inflexibility of services. Some organizational traditions in state hospital systems, such as distance from the patient's home and poor liaison with other community facilities, impede postdischarge re-adjustment. In general hospitals the old tradition of placing those with greater professional experience on inpatient services which led to enhancement of their prestige is detrimental to the growth and strengthening of the admissions office and the outpatient departments which have major importance for community mental health programs and require high levels of professional expertness. These factors are reflected in traditional organizational features of general hospitals, and influence staffing patterns and admissions procedures and policies that are now adverse to early detection and treatment of psychiatric illness. They lead to incomplete and inaccurate recording of psychiatric diagnoses and minimal attention to outpatient charts. By identifying these traditions and the obstacles they raise, it is hoped that appropriate revisions come about which will lead to more effective patient care.
Changes in Carbohydrate Metabolism of Cardiac and Striated Muscle in Hypothermic Rats
Authors: S. ITZHAKI, E. WERTHEIMER
Journal: Circulation Research (1957)

The following represents a study of the influence of hypothermia on the carbohydrate metabolism of rat heart slices in comparison to rat diaphragm. The effect of thyroid on the induced metabolic changes in both types of muscle is investigated.
Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction
Authors: Nancy R. Cook
Journal: Circulation (2007)

The c statistic, or area under the receiver operating characteristic (ROC) curve, achieved popularity in diagnostic testing, in which the test characteristics of sensitivity and specificity are relevant to discriminating diseased versus nondiseased patients. The c statistic, however, may not be optimal in assessing models that predict future risk or stratify individuals into risk categories. In this setting, calibration is as important to the accurate assessment of risk. For example, a biomarker with an odds ratio of 3 may have little effect on the c statistic, yet an increased level could shift estimated 10-year cardiovascular risk for an individual patient from 8% to 24%, which would lead to different treatment recommendations under current Adult Treatment Panel III guidelines. Accepted risk factors such as lipids, hypertension, and smoking have only marginal impact on the c statistic individually yet lead to more accurate reclassification of large proportions of patients into higher-risk or lower-risk categories. Perfectly calibrated models for complex disease can, in fact, only achieve values for the c statistic well below the theoretical maximum of 1. Use of the c statistic for model selection could thus naively eliminate established risk factors from cardiovascular risk prediction scores. As novel risk factors are discovered, sole reliance on the c statistic to evaluate their utility as risk predictors thus seems ill-advised.
Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts. Evidence for cardiac "memory".
Authors: A Costard-Jäckle, B Goetsch, M Antz, M R Franz
Journal: Circulation (1989)

Prolonged ventricular pacing induces T wave polarity changes that persist long after cessation of pacing. To examine how ventricular repolarization is modulated by prolonged changes in activation sequence, we studied the effect of ectopic pacing on the distribution of action potential durations (APDs) in nine isolated Langendorff-perfused rabbit hearts. A contact electrode probe was used to map right and left ventricular-epicardial monophasic action potentials during three consecutive changes in stimulus site, that is, 1) during 45 minutes of right atrial pacing, 2) during 120 minutes of right ventricular pacing, and 3) again, during 60 minutes of right atrial pacing. During each of these phases, the effect of activation sequence on repolarization was examined by linear-regression analysis of APD on activation time (AT). Results averaged for all nine hearts showed that during the initial atrial-pacing phase, APD was inversely related to AT (slope [S] = -1.63; r = 0.76), indicating that sites with earlier activation repolarized later. With the onset of ventricular pacing, the inverse correlation between AT and APD disappeared (S = -0.19; r = 0.31). Continuing ventricular pacing, however, produced slow changes in APD that restored the inverse relation (S = -0.71; r = 0.68 at 120 minutes; p less than 0.0002 versus 5 minutes). Switching from ventricular to atrial pacing again perturbed the inverse correlation (S = 0.28; r = 0.35) but at 60 minutes of atrial pacing, a significant inverse correlation was reestablished (S = -1.25; r = 0.53; p less than 0.01 versus 5 minutes). An inverse correlation between AT and APD tends to synchronize repolarization time (RT, the sum of AT and APD).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Deaminase Inhibition Attenuates Microvascular Dysfunction and Improves Survival in Sepsis
Authors: Elliott S. Cohen, William R. Law, Cordus R. Easington, Kenneth Q. Cruz, Beth A. Nardulli, Robert A. Balk, Joseph E. Parrillo, Steven M. Hollenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The ability of increased endogenous adenosine to mitigate microvascular derangements in sepsis was studied. Pentostatin (2′-deoxycoformycin), an inhibitor of adenosine deaminase, was administered to mice immediately after induction of sepsis by cecal ligation and puncture. Intravital video microscopy of cremasteric postcapillary venules was performed. Leukocyte rolling and adhesion were significantly increased in septic mice compared with control mice. Treatment of septic mice with pentostatin significantly decreased leukocyte rolling and adhesion (6.02 ± 0.09 versus 1.72 ± 0.12 rolling cells/min, 2.07 ± 0.04 versus 0.62 ± 0.05 adherent cells/100 μm per minute; p < 0.001). Albumin leakage (ratio) was significantly attenuated in septic animals treated with pentostatin (0.42 ± 0.05 versus 0.21 ± 0.04; p < 0.01). Circulating levels of interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor type II receptor were decreased in septic mice treated with pentostatin. Survival was significantly improved at 48 hours in mice treated with pentostatin. These results suggest an important role for adenosine in modulating both leukocyte-dependent and -independent mechanisms of endothelial injury in sepsis. Exploiting the advantageous action of endogenous adenosine represents a potentially useful and novel therapeutic approach for the treatment of sepsis.
TISSUE-DIGESTING ENZYME (HISTASE) OF STREPTOCOCCI
Authors: Martin Frobisher
Journal: The Journal of Experimental Medicine (1926)

1. An extracellular, proteolytic enzyme has been observed in more than 30 strains of beta type, aerobic and facultative hemolytic streptococci. 2. The enzyme is readily demonstrable in sterile filtrates of cooked meat cultures. 3. No gas or foul odor is produced. 4. It is partially inactivated by exposure to about 60 degrees C. for 45 minutes or longer. 5. The enzyme manifests itself in cooked meat cultures after about 48 hours incubation at 37 degrees C. The sterile filtrate from a 10 day old culture acts within 18 hours. 6. From 50 to 75 per cent of the meat in a tube of cooked meat medium may be digested in about 3 weeks at room temperature after 5 days initial growth at 37 degrees C. 7. No correlation is found, in the cases studied, between hemolysis and proteolysis. 8. Streptococci not digesting beef tissue will not digest human tissue, and those which do digest beef tissue also digest human tissue. This conclusion applies only to the nine strains studied. 9. Ability to digest animal tissues does not necessarily imply ability to digest casein, coagulated beef serum or gelatin. 10. The disappearance of the meat from cooked meat cultures of hemolytic streptococci is quantitatively roughly paralleled by increase of formol-titrable substances in the fluid portion of the medium. 11. The enzyme resembles trypsin in its action. Streptococci from a variety of sources, bovine, human and otherwise have shown varying degrees of proteolytic activity. 12. The name histase is proposed for this enzyme.
Diagnostic strategies used in primary care
Authors: C Heneghan, P Glasziou, M Thompson, P Rose, J Balla, D Lasserson, C Scott, R Perera
Journal: BMJ (2009)

The strategies used by general practitioners in making a diagnosis are being formally recognised; this article is the first in a series that will illustrate their application, and is accompanied by a case study (doi:10.1136/bmj.b1187)