tbuckley/cabot-search huggingface dataset:
Mutations in the Cardiac Ryanodine Receptor Gene ( <i>hRyR2</i> ) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Silvia G. Priori, Carlo Napolitano, Natascia Tiso, Mirella Memmi, Gabriele Vignati, Raffaella Bloise, Vincenzo Sorrentino, Gian Antonio Danieli
Journal: Circulation (2001)

Background —Catecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene ( hRyR2 ) a likely candidate for this genetically transmitted arrhythmic disorder. Methods and Results —Twelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction–amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. Conclusions —We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia.
Structural remodelling during chronic atrial fibrillation: act of programmed cell survival
Authors: V Thijssen
Journal: Cardiovascular Research (2001)

Atrial fibrillation is the most common cardiac arrhythmia with an overall prevalence of almost 1%. Increasing prevalence and associated risks such as stroke and mortality have increased the need for better and more reliable therapeutic treatment. This has stimulated research to elucidate the pathophysiological mechanisms underlying atrial fibrillation. Atrial fibrillation is primarily characterised by electrical remodelling and functional deterioration. Both phenomena are reversible but after prolonged duration of atrial fibrillation, a discrepancy occurs between rapid electrical remodelling and slow recovery of contractile function. Recent studies have indicated that morphological remodelling might underlie this incongruity. In experimental models of lone atrial fibrillation, the remodelling involves cellular changes that are reminiscent of dedifferentiation and are characterised by cellular volume increase, myolysis, glycogen accumulation, mitochondrial changes and chromatin redistribution. The absence of clear signs of degeneration in these models points towards cardiomyocyte adaptation or a mechanism of programmed cell survival. In patients with atrial fibrillation cardiomyocyte degeneration does occur along with dedifferentiation which might be the result of underlying cardiac pathologies or longer duration of atrial fibrillation. In this review we focus on structural remodelling during atrial fibrillation. The different aspects of histological and ultrastructural changes as well as their role in atrial dysfunction and cardiomyocyte survival are discussed. We briefly describe the underlying molecular remodelling. and possible mechanisms responsible for remodelling involving calcium overload and stretch are presented.
Attention-deficit/hyperactivity disorder (ADHD): Delay-of-reinforcement gradients and other behavioral mechanisms
Authors: A. Charles Catania
Journal: Behavioral and Brain Sciences (2005)

sagvolden, johansen, aase, and russell (sagvolden et al.) examine attention-deficit/hyperactivity disorder (adhd) at levels of analysis ranging from neurotransmitters to behavior. at the behavioral level they attribute aspects of adhd to anomalies of delay-of-reinforcement gradients. with a normal gradient, responses followed after a long delay by a reinforcer may share in the effects of that reinforcer; with a diminished or steepened gradient they may fail to do so. steepened gradients differentially select rapidly emitted responses (hyperactivity), and they limit the effectiveness with which extended stimuli become conditioned reinforcers, so that observing behavior is less well maintained (attention deficit). impulsiveness also follows from steepened gradients, which increase the effectiveness of smaller, more immediate consequences relative to larger, more delayed ones. individuals who vary in the degree to which their delay gradients are steepened will show different balances between hyperactivity and attention deficit. given the range of adhd phenomena addressed, it may be unnecessary to appeal to additional behavioral processes such as extinction deficit. extinction deficit is more likely a derivative of attention deficit, in that failure to attend to stimuli differentially correlated with extinction should slow its progress. the account suggests how relatively small differences in delay gradients early in development might engender behavioral interactions leading to very large differences later on. the steepened gradients presumably originate in properties of neurotransmitter function, but behavioral interventions that use consistently short delays of reinforcement to build higher-order behavioral units as a scaffolding to support complex cognitive and social skills may nonetheless be feasible.
Squamous metaplasia of the rectum associated with ulcerative colitis diagnosed using narrow-band imaging
Authors: K. Fu, Y. Tsujinaka, Y. Hamahata, K. Matsuo, O. Tsutsumi
Journal: Endoscopy (2008)

A 61-year-old-man with ulcerative colitis attended our hospital for a surveillance colonoscopy. He had been diagnosed with left-sided ulcerative colitis, which had been well controlled by oral 5-aminosalicylic acid for 6 years. No active inflammation was detected in the colon or rectum at colonoscopy, but a small whitish area with a clearly demarcated border, about 5 mm in size, was found in the lower part of rectum ([Fig. 1]). Small reddish spots were seen within the whitish area, which was surrounded by hyperplastic normal rectal mucosa. Chromoendoscopy using 0.4 % indigo carmine dye highlighted the demarcation line of the whitish area ([Fig. 2]). Narrow-band imaging showed dark-brown dots corresponding to the reddish spots seen in the conventional view, and these were considered to resemble the intraepithelial capillary loops observed in normal esophageal squamous epithelium ([Fig. 3]) [1]. A biopsy specimen was taken from the whitish area for histological evaluation, and this was reported as squamous-cell epithelium without dysplasia. A final diagnosis of squamous metaplasia associated with ulcerative colitis was made.
683.Adenoviral Vector-Mediated Expression of Bone Morphogenetic Protein-4 in Mesenchymal Stem Cells Induces Differentiation into the Osteoblastic Lineage and Bone Production In Vivo
Authors: Barbara Lombardo, Rosa Di Noto, Maria Teresa Esposito, Sabrina Battista, Gabriela Ciapetti, Ombretta Capitani, Luigi Nicolais, Paolo Netti, Francesco Salvatore, Lucio Pastore
Journal: Molecular Therapy (2005)

Bone regeneration is critical to the effective management of many bone and muscoloskeletal disorders, such as fracture healing, spinal fusion and osteoporosis. Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and play an important role in embryonic development and bone formation; at least 15 types of BMPs have been identified in humans and several forms of BMPs, mostly rhBMP-2 rhBMP-4 and rhBMP-7, have been shown to induce bone formation in vitro and in vivo. BMPs have also been used in combination with human mesenchymal stem cells (hMSC) that have the capacity to differentiate into bone cell lineages and have generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering.
Do single handed practices offer poorer care? Cross sectional survey of processes and outcomes
Authors: J. Hippisley-Cox, M. Pringle, C. Coupland, V. Hammersley, A. Wilson
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether there are important differences in performance between group practices and singlehanded general practitioners and the extent to which any differences are explained by practice characteristics such as deprivation. <b>Design:</b> Cross sectional survey. <b>Setting:</b> 206 singlehanded practices and 606 partnerships in Trent region, United Kingdom. <b>Method:</b> Comparison of process and outcome measures derived from routinely collected data on hospital admissions and target payments for singlehanded practices and partnerships. Multivariate analysis was used to adjust for the confounding effects of general practice characteristics—deprivation (Townsend score), percentage of Asian residents, percentage of black residents, proportion of men over 75 years, proportion of women over 75 years, rurality, presence of a female general practitioner, and vocational training status. <b>Results:</b> Differences in achievement of immunisation and cytology targets apparent on univariate analysis were not seen after adjustment for other general practice characteristics. Similarly, significant differences (&gt;15%; P&lt;0.01) for three types of hospital admission seen on univariate analysis were not present after adjustment for other practice characteristics. <b>Conclusions:</b> This study provides no evidence that singlehanded general practitioners are underperforming clinically. Our results offer insight into the structural difference between the two types of practice and underline the importance of the effect of other practice characteristics on process and outcome measures. <h3>What is already known on this topic</h3> Singlehanded general practitioners tend to work in areas of high deprivation and need Patients like singlehanded practices because of good communication, personal rapport, availability, and continuity of care Concerns have been expressed about professional isolation and quality standards for singlehanded practice, on the basis of little evidence <h3>What this study adds</h3> This study provides no evidence that singlehanded general practitioners are underperforming clinically The results offer insight into the structural differences between the two types of practice and underline the importance of other practice characteristics such as deprivation
Health services administration and health services research
Authors: M. Warren
Journal: BMJ (1982)

<h3>Background</h3> Healthcare associated infections, including ventilator associated pneumonia, are difficult to diagnose and treat, and are associated with significant morbidity, mortality and cost. We aimed to demonstrate proof of concept that breath volatile profiles were associated with the presence of clinically relevant pathogens in the lower respiratory tract. <h3>Methods</h3> Patients with sterile brain injury requiring intubation and ventilation on the intensive care unit were eligible for inclusion. Serial clinical and breath data were obtained three times a week, from admission up to a maximum of 10 days. Bronchial lavage for semiquantitative culture was collected immediately prior to breath sampling. Breath samples were collected in triplicate for off-line analysis by thermal-desorption/gas chromatography/time-of-flight mass spectrometry. Breath data were recorded as retention time/mass ion pairs, and analysed (pathogen present vs absent) by ANOVA-mean centre principal component analysis. <h3>Results</h3> Samples were collected from 46 patients (mean (SD) age 49 (19) years; 27 male). The dominant factors affecting breath sample analysis were the individual breath profile and duration of intubation. When these were taken into account, clear separation was seen between breath profiles at each time point by the presence/absence of pathogens. Loadings plots identified consistent metabolite peaks contributing to this separation at each time point. <h3>Conclusions</h3> Breath volatile analysis is able to classify breath profiles of patients with and without significant pathogen load in the lower respiratory tract. If validated in independent cohorts, these findings could lead to development of rapid non-invasive point-of-care surveillance systems and diagnostics for lower respiratory tract infection in the intensive care unit.
Flashes, floaters, and a field defect
Authors: A. A. Khan, R. J. Kelly, Z. I. Carrim
Journal: BMJ (2013)

A 65 year old woman presents to her general practitioner with a three day history of flashing lights in her right eye. She has also noticed a new floater in her temporal field of vision. She describes this as resembling a “fly” or “cobweb.” Reassuringly, she has not been aware of a shadow in her field of vision. Flashes, also known as photopsia, and floaters are a common complaint in primary care. Most patients with this complaint will have a simple, innocuous collapse of the vitreous gel, called a posterior vitreous detachment (figure⇓). However, some may have more serious pathology. A rapid, systematic, assessment can facilitate appropriate management. Diagram of the eye showing normal anatomy, posterior vitreous detachment with floaters (small opacities), and retinal detachment caused by a tear Ask about
Mannose-Binding Lectin Genotype and Phenotype in Patients With Type 2 Diabetes and Myocardial Infarction
Authors: L.G. Mellbin, A. Hamsten, K. Malmberg, R. Steffensen, L. Rydén, J. Öhrvik, T.K. Hansen
Journal: Diabetes Care (2010)

OBJECTIVE The present study characterizes mannose-binding lectin (MBL), an activator of the complement system and thereby important for inflammatory activation, in patients with diabetes and myocardial infarction. RESEARCH DESIGN AND METHODS Serum (S)-MBL was determined at hospital admission in 387 patients with type 2 diabetes (median age 70 years; 68% male) with myocardial infarction, and genotyping was performed in 287 patients. Cardiovascular events (cardiovascular mortality and nonfatal myocardial infarction or stroke) were recorded during 2.5 years. RESULTS Median S-MBL was 1,212 μg/l (interquartile range [IQR] 346–2,681 μg/l). Of the subjects, 54% in the geno- and phenotype subgroup had a high-coding MBL genotype (median S-MBL = 2,658 μg/l [IQR 1,715–3,829]) and 46% a low-coding MBL genotype (373 μg/l [100–765]). S-MBL did not correlate with age, BMI, creatinine clearance, glucose, or A1C. Cardiovascular events occurred in 136 (35%) patients. S-MBL did not predict events in univariable analyses (hazard ratio 0.93 [95% CI 0.85–1.01]; P = 0.09). In unadjusted analyses, the risk of events was lower in patients with a high genotype and S-MBL above the median for their genotype (0.49 [0.26–0.92]; P = 0.026) than for patients with a low genotype and S-MBL below the median for their genotype. The prediction capacity of the geno- and phenotype model was of borderline significance in adjusted Cox regression. CONCLUSIONS Patients with type 2 diabetes and myocardial infarction have MBL genotypes that are similar to those known in the general population. The combination of a low-coding MBL genotype with a low S-MBL appears to be prognostically unfavorable, but the association is blunted by traditional risk markers.
Relationship Between Short Stature and Postchallenge Glycemia in Pregnancy
Authors: Simone Kew, Ying Qi, Mathew Sermer, Philip W. Connelly, Anthony J.G. Hanley, Bernard Zinman, Ravi Retnakaran
Journal: Diabetes Care (2010)

Short stature has been identified as a risk factor for gestational diabetes mellitus (GDM), although the pathophysiological basis for this association is not clear (1–3). In this context, we sought to evaluate the relationship between height and parameters of glucose homeostasis, including insulin sensitivity and β-cell function, in 671 Caucasian women undergoing a 3 h 100-g oral glucose tolerance test (OGTT) in late pregnancy. As previously described (4), the OGTT stratified subjects into three groups: GDM ( n = 126), gestational impaired glucose tolerance (GIGT) ( n = 117), and normal glucose tolerance (NGT) ( n = 428). Insulin sensitivity and β-cell function were assessed by the insulin sensitivity index for OGTT (ISOGTT) and the Insulin Secretion-Sensitivity Index-2 (ISSI-2), respectively.

After adjustment for age, current weight, and family history of diabetes, mean height decreased from NGT (164.1 cm) to GIGT (163.9 cm) to GDM (162.5 cm) ( P = …
1110 BASELINE PREDICTORS FOR SAFETY-RELATED DOSE REDUCTIONS OR TREATMENT DISCONTINUATIONS AMONG PEGINTERFERON ALFA-2A (40KD)/RIBAVIRIN-TREATED PATIENTS AND THEIR IMPACT ON EARLY TREATMENT RESPONSES: GUARD-C INTERIM ANALYSIS
Authors: G.R. Foster, C. Coppola, M.F. Derbala, P. Ferenci, A. Orlandini, L. Tallarico, S. Ahlers, F. Tatsch, T. Hassanein
Journal: Journal of Hepatology (2012)
The Dupuytren Contracture Controversy
Authors: Stephen W. Meagher
Journal: JAMA (1962)

Radical fasciectomy has been regarded as the only suitable treatment for the Dupuytren contracture. Recent interest in limited fasciectomy and subcutaneous fasciotomy has given rise to a controversy in the treatment of this disease. The proponents of radical fasciectomy feel that it is the only means of curing an established contracture. Those who oppose this procedure point to the higher postoperative morbidity of the radical procedure and the longer duration of disability from operation to employment. Limited fasciectomy and subcutaneous fasciotomy possess the handicap of a higher recurrence rate; the latter procedure bears with it a risk of accidental division of tendons, vessels, and nerves. Since there is disagreement as to the relative merits of radical versus the limited procedure, it is important to determine the most suitable indications for each.
Predicting Risk of Progressive Multifocal Leukoencephalopathy from Natalizumab
Authors: Allan H. Ropper
Journal: New England Journal of Medicine (2012)

After a century of futility in the treatment of multiple sclerosis, there is now a deluge of drugs that alter the course of the disease. The half-dozen new oral drugs have excited the most interest, but the monoclonal antibodies, and specifically natalizumab, have a more focused biologic activity and are more potent. It is ironic that natalizumab can cause not just a second neurologic disease, progressive multifocal leukoencephalopathy (PML), but one that, like multiple sclerosis itself, affects the oligodendrocytes and central nervous system myelin.Once it was apparent that PML was related to natalizumab treatment, and the drug was withheld . . .
Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia.
Authors: M H Ginsberg, A Lightsey, T J Kunicki, A Kaufmann, G Marguerie, E F Plow
Journal: Journal of Clinical Investigation (1986)

An antiplatelet monoclonal antibody, PMI-1, reacts with glycoproteins (GP) GPIIb, free GPIIb, and the GPIIb-IIIa complex. This antibody binds to 40,900 sites per platelet, with a Kd = 0.95 microM, and its binding is inhibited by the presence of magnesium or calcium in the suspending medium (50% suppression at approximately 0.5 mM divalent cation). Regulation of the PMI-1 epitope is independent of disassembly of the GPIIb-IIIa heterodimer, because it occurred at 22 degrees C and in response to mM magnesium as well as calcium. PMI-1 binding inversely correlated with fibrinogen binding. In addition, we identified a variant of Glanzmann's thrombasthenia with near-normal platelet content of the GPIIb-IIIa heterodimer as judged by crossed immunoelectrophoresis and surface labeling. Binding of PMI-1 to these patients' platelets was not dependent on reduction of the divalent cation concentration. These data suggest that the surface orientation of GPIIb is important in the capacity of platelets to bind fibrinogen.
265 E2F1 Expression in chronic liver disease and hepatocellular carcinoma: A new player in the field of human hepatocarcinogenesis?
Authors: D.G. Tiniakos, J. Koskinas, K. Petraki, P. Karakaidos, L. Vassiliou, V.G. Gorgoulis, A.J. Archimandritis, Ch. Kittas
Journal: Journal of Hepatology (2006)
PHAGOCYTOSIS OF BACTERIA IN THE ABSENCE OF ANTIBODY AND THE EFFECT OF PHYSICAL SURFACE
Authors: Edwin M. Lerner
Journal: The Journal of Experimental Medicine (1956)

The present experiments have shown that phagocytosis occurs in the absence of specific antibody and in the absence of a "suitable physical surface", as further that the presence of a rough surface does not increase the in vitro phagocytosis of pneumococci by polymorphonuclear leukocytes. This held true during repetition of Wood's experiments, as well as when more controlled quantitative techniques were employed, when conditions were made optimal for phagocytosis by increasing bacterial concentrations, and when blood leukocytes were substituted for exudate leukocytes. Evidence has been presented previously that the stimulation of phagocytosis of E. coli, B. abortus, and Type IV Pneumococcus, after contact with filter paper or an active compound present in filter paper, is a chemical effect rather than a physical effect. This type of stimulation did not occur with the Type I A5 Pneumococcus. The leukocyte of the circulating blood was found to be definitely superior to the exudate leukocyte in phagocytic capacity, under all the experimental conditions tested.
470 INTERMEDIATE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS (IKCA) IN ACTIVATED HEPATIC STELLATE CELLS AS A NEW TARGET FOR ANTIFIBROTIC TREATMENT
Authors: S. Eisele, M. Ruehl, E. Patsenker, R. Koehler, U. Erben, J. Hoyer, F. Stickel, R. Somasundaram
Journal: Journal of Hepatology (2008)
A Simple Method of Artificial Respiration
Authors: J. A. Francis
Journal: BMJ (1886)

isF8iS 7Z17gv [)1,aafi JOLTEN4L.IMapqh 2O, 188I.2.The onc,rence of, bemrorage into the a44dogkui cav ity, due t tIie-rupture of a Graafian follicle duringmmenstruation, is undoubtedly pre ; i but it is, notwithstanding, admittedc by vapipus writers on,Ob- #tetiics, and notably Dr. Graily Hewitt.HasTirhe, in this case, evidently took plce very slowly, occupyinig -it least nine hours, while the quantity of blood extravasated wvas enormous.It seemed as if the whole body had been drainqd into the abdominal cayity; and the facts above stated, to opr.rqinds,:so clearly indicated tbe ovaries as the seat of the hwmorrhage, that, I had no hesitation in statirg such to be the cause of death at the coxoner's inquest.
Why does arthritis pain diminish with pregnancy?
Authors: Jaan Kangilaski
Journal: JAMA (1981)

Women with rheumatoid arthritis have said for years that the pain in their joints decreases during pregnancy, and a Texas investigator thinks he may be on the track of the explanation. Robert H. Persellin, MD, professor of medicine at the University of Texas Health Science Center in San Antonio, is not the first to study this tantalizing problem. But he may be making more progress than some others: He has isolated a serum protein, has shown that it can suppress the activity of monocytes (which are involved in inflammation), and is putting together a prospective clinical study. "So far, we have been able to follow three women all the way through their pregnancies," Persellin told a press conference at the American Rheumatism Association meeting in Boston. "They all had elevated levels of pregnancy a-glycoprotein, and the symptoms of all of them improved." Persellin and his associates have been able to