tbuckley/cabot-search huggingface dataset:
Atrial and ventricular pacing after open heart surgery
Authors: J. D. Wisheart, J. E. C. Wright, F. L. Rosenfeldt, J. K. Ross
Journal: Thorax (1973)

The effect of cardiac pacing, through a wide range of pacing rates, has been studied in 13 patients in stable sinus rhythm within 24 hours of operation. Using first atrial and then ventricular pacing, the cardiac rate was raised to 60% above control value. The effects of atrial and ventricular pacing were compared by observing the differences in the various parameters measured at corresponding paced heart rates. With atrial pacing there was no significant difference in the cardiac output, mean aortic pressure, mean left atrial pressure, or left ventricular work. During ventricular pacing there were significant falls in cardiac output (p&lt;0·05), mean aortic pressure (p&lt;0·01), and left ventricular work (p&lt;0·01). There was a significant rise in mean left atrial pressure (p&lt;0·01). In this study atrial pacing had no significant effect on the parameters measured, through a wide range of cardiac rates. An inotropic effect resulting from increase of rate was not seen. Reported increases in cardiac output following pacing must therefore have resulted from correction of a dysrhythmia. Ventricular pacing incurs a definite haemodynamic penalty if used in patients with an intact atrioventricular conducting pathway. If atrial pacing is not available, this penalty must be balanced against the possible haemodynamic advantage of suppressing a dysrhythmia.
Impact of Dialysis Dose and Membrane on Infection-Related Hospitalization and Death
Authors: Michael Allon, Thomas A. Depner, Milena Radeva, James Bailey, Srinivasan Beddhu, David Butterly, Daniel W. Coyne, Jennifer J. Gassman, Allen M. Kaufman, George A. Kaysen, Julia A. Lewis, Steve J. Schwab
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Infection is the second most common cause of death among hemodialysis patients. A predefined secondary aim of the HEMO study was to determine if dialysis dose or flux reduced infection-related deaths or hospitalizations. The effects of dialysis dose, dialysis membrane, and other clinical parameters on infection-related deaths and first infection-related hospitalizations were analyzed using Cox regression analysis. Among the 1846 randomized patients (mean age, 58 yr; 56% female; 63% black; 45% with diabetes), there were 871 deaths, of which 201 (23%) were due to infection. There were 1698 infection-related hospitalizations, yielding a 35% annual rate. The likelihood of infection-related death did not differ between patients randomized to a high or standard dose (relative risk [RR], 0.99 [0.75 to 1.31]) or between patients randomized to high-flux or low-flux membranes (RR, 0.85 [0.64 to 1.13]). The relative risk of infection-related death was associated (P < 0.001 for each variable) with age (RR, 1.47 [1.29 to 1.68] per 10 yr); co-morbidity score (RR, 1.46 [1.21 to 1.76]), and serum albumin (RR, 0.19 [0.09 to 0.41] per g/dl). The first infection-related hospitalization was related to the vascular access in 21% of the cases, and non–access-related in 79%. Catheters were present in 32% of all study patients admitted with access-related infection, even though catheters represented only 7.6% of vascular accesses in the study. In conclusion, infection accounted for almost one fourth of deaths. Infection-related deaths were not reduced by higher dose or by high flux dialyzers. In this prospective study, most infection-related hospitalizations were not attributed to vascular access. However, the frequency of access-related, infection-related hospitalizations was disproportionately higher among patients with catheters compared with grafts or fistulas. E-mail: [email protected]
VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis
Authors: Laura I. Cosen-Binker, Marcelo G. Binker, Cheng-Chun Wang, Wanjin Hong, Herbert Y. Gaisano
Journal: Journal of Clinical Investigation (2008)

In rodents and humans, alcohol exposure has been shown to predispose the pancreas to cholinergic or viral induction of pancreatitis. We previously developed a rodent model in which exposure to an ethanol (EtOH) diet, followed by carbachol (Cch) stimulation, redirects exocytosis from the apical to the basolateral plasma membrane of acinar cells, resulting in ectopic zymogen enzyme activation and pancreatitis. This redirection of exocytosis involves a soluble NSF attachment receptor (SNARE) complex consisting of syntaxin-4 and synapse-associated protein of 23 kDa (SNAP-23). Here, we investigated the role of the zymogen granule (ZG) SNARE vesicle-associated membrane protein 8 (VAMP8) in mediating basolateral exocytosis. In WT mice, in vitro EtOH exposure or EtOH diet reduced Cch-stimulated amylase release by redirecting apical exocytosis to the basolateral membrane, leading to alcoholic pancreatitis. Further reduction of zymogen secretion, caused by blockade of both apical and basolateral exocytosis and resulting in a more mild induction of alcoholic pancreatitis, was observed in Vamp8–/– mice in response to these treatments. In addition, although ZGs accumulated in Vamp8–/– acinar cells, ZG-ZG fusions were reduced compared with those in WT acinar cells, as visualized by electron microscopy. This reduction in ZG fusion may account for reduced efficiency of apical exocytosis in Vamp8–/– acini. These findings indicate that VAMP8 is the ZG-SNARE that mediates basolateral exocytosis in alcoholic pancreatitis and that VAMP8 is critical for ZG-ZG homotypic fusion.
Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Authors: Lisa B. Signorello, John J. Mulvihill, Daniel M. Green, Heather M. Munro, Marilyn Stovall, Rita E. Weathers, Ann C. Mertens, John A. Whitton, Leslie L. Robison, John D. Boice
Journal: Journal of Clinical Oncology (2011)

Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses.Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression.One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors.Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.
Transient Induction of ING4 by Myc Drives Prostate Epithelial Cell Differentiation and Its Disruption Drives Prostate Tumorigenesis
Authors: Penny L. Berger, Sander B. Frank, Veronique V. Schulz, Eric A. Nollet, Mathew J. Edick, Brittany Holly, Ting-Tung A. Chang, Galen Hostetter, Suwon Kim, Cindy K. Miranti
Journal: Cancer Research (2014)

Abstract The mechanisms by which Myc overexpression or Pten loss promotes prostate cancer development are poorly understood. We identified the chromatin remodeling protein, ING4, as a crucial switch downstream of Myc and Pten that is required for human prostate epithelial differentiation. Myc-induced transient expression of ING4 is required for the differentiation of basal epithelial cells into luminal cells, while sustained ING4 expression induces apoptosis. ING4 expression is lost in &amp;gt;60% of human primary prostate tumors. ING4 or Pten loss prevents epithelial cell differentiation, which was necessary for tumorigenesis. Pten loss prevents differentiation by blocking ING4 expression, which is rescued by ING4 re-expression. Pten or ING4 loss generates tumor cells that co-express basal and luminal markers, indicating prostate oncogenesis occurs through disruption of an intermediate step in the prostate epithelial differentiation program. Thus, we identified a new epithelial cell differentiation switch involving Myc, Pten, and ING4, which when disrupted leads to prostate tumorigenesis. Myc overexpression and Pten loss are common genetic abnormalities in prostate cancer, whereas loss of the tumor suppressor ING4 has not been reported. This is the first demonstration that transient ING4 expression is absolutely required for epithelial differentiation, its expression is dependent on Myc and Pten, and it is lost in the majority of human prostate cancers. This is the first demonstration that loss of ING4, either directly or indirectly through loss of Pten, promotes Myc-driven oncogenesis by deregulating differentiation. The clinical implication is that Pten/ING4 negative and ING4-only negative tumors may reflect two distinct subtypes of prostate cancer. Cancer Res; 74(12); 3357–68. ©2014 AACR.
A modest proposal for the medical profession to introduce humane and civilized executions
Authors: Thomas Bewley
Journal: Journal of the Royal Society of Medicine (2009)

Political power was once described as ‘the right of making laws with penalties of death’.1 The ultimate penalty for the most heinous crimes in the past has always been judicially approved execution. Today there is such a revulsion against this punishment that most nations have abolished it,2 but law-abiding citizens in China and Texas will be delighted by new possible developments in executing criminals. Up to the present all judicially approved executions have fallen short of what is necessary to be neither cruel nor unusual. It is a boon to mankind that 21st-century medical technical developments may now enhance the practice to make it more humane and beneficent.
2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial
Authors: Baptist Gallwitz, Julio Rosenstock, Thomas Rauch, Sudipta Bhattacharya, Sanjay Patel, Maximilian von Eynatten, Klaus A Dugi, Hans-Juergen Woerle
Journal: The Lancet (2012)
Disruption of the <i>Bcl6</i> Gene Results in an Impaired Germinal Center Formation
Authors: Tetsuya Fukuda, Takehiko Yoshida, Seiji Okada, Masahiko Hatano, Tohru Miki, Kazuki Ishibashi, Shinichiro Okabe, Haruhiko Koseki, Shinsaku Hirosawa, Masaru Taniguchi, Nobuyuki Miyasaka, Takeshi Tokuhisa
Journal: The Journal of Experimental Medicine (1997)

The Bcl6 gene has been identified from the chromosomal translocation breakpoint in B cell lymphomas, and its products are expressed highly in germinal center (GC) B cells. To investigate the function of Bcl6 in lymphocytes, we have generated RAG1-deficient mice reconstituted with bone marrow cells from Bcl6-deficient mice (Bcl6−/−RM). Lymphogenesis in primary lymphoid tissues of Bcl6−/−RM is normal, and Bcl6−/−RM produced control levels of primary IgG1 antibodies specific to T cell–dependent antigens. However, GCs were not found in these mice. This defect was mainly due to the abnormalities of B cells. Therefore, Bcl6 is essential for the differentiation of GC B cells.
Inhibition of Adrenergic Outflow to Peripheral Blood Vessels by Vagal Afferents from the Cardiopulmonary Region in the Dog
Authors: GIUSEPPE MANCIA, DAVID E. DONALD, JOHN T. SHEPHERD
Journal: Circulation Research (1973)

In closed-chest atropinized dogs anesthetized with chloralose and ventilated artificially, the aortic nerves were cut beneath the nodose ganglion, and the carotid sinuses were either denervated or vascularly isolated and maintained at a pressure of 40 mm Hg. Denervation was established by the failure of the pressoreceptor systems to respond to mechanical stimulation. Cold block or section of the cervical vagi resulted in statistically significant increases in arterial blood pressure (18%), heart rate (3%), central venous pressure (13%), hind-limb perfusion pressure (12%), pressure within the occluded spleen (18%), and efferent renal sympathetic nerve activity (28%). There was no change in saphenous vein perfusion pressure. The vascular responses were abolished by a-receptor blockade and were not affected by section of the vagi at the diaphragm. When the pressure in the vascularly isolated innervated carotid sinuses was varied from 40 to 220 mm Hg, the vascular responses to vagal block decreased steeply between 100 and 160 mm Hg and were absent at 200 mm Hg. Thus, receptors in the cardiopulmonary region with afferent vagal fibers exert a continuous restraint on the sympathetic adrenergic outflow to resistance and capacitance vessels, especially when the input from the carotid baroreceptors is decreased.
The validation of matrix metalloproteinase-9 mRNA gene expression as a predictor of outcome in patients with metastatic gastric cancer
Authors: S.-E. Al-Batran, C. Pauligk, R. Wirtz, D. Werner, K. Steinmetz, N. Homann, H. Schmalenberg, R.-D. Hofheinz, J.T. Hartmann, A. Atmaca, H.-M. Altmannsberger, E. Jäger
Journal: Annals of Oncology (2011)
Tumour necrosis factor blockade reduces circulating N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis: results from a prospective cohort study
Authors: M. J. L. Peters, P. Welsh, I. B. McInnes, G. Wolbink, B. A. C. Dijkmans, N. Sattar, M. T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2009)

Patients with rheumatoid arthritis (RA) are at increased risk of heart failure and vascular events. Small increases in circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with an increased risk of a cardiovascular event, and high levels signal left ventricular dysfunction. Data on the effects of tumour necrosis factor alpha(TNFalpha) blocking agents on circulating NT-proBNP levels in patients with active RA are lacking but may be informative.171 consecutive patients with RA (28-joint disease activity score >3.2) without congestive heart failure (NYHA class III or IV) were scheduled to receive adalimumab once every 2 weeks. Serum NT-proBNP concentrations were measured simultaneously on stored baseline and 16-week samples. Paired sample t tests were used to observe differences in biomarkers before and after adalimumab administration. Correlations between the biomarkers and changes in circulating log NT-proBNP levels were evaluated with the Pearson test and multivariable linear regression analyses of correlates were performed (forward selection procedure).Circulating levels of NT-proBNP decreased significantly after 16 weeks of adalimumab administration (median NT-proBNP 83.0 pg/ml vs 69.5 pg/ml, p=0.004). Changes in NT-proBNP levels were associated with changes in pulse pressure (r=0.18, p=0.02), systolic blood pressure (r=0.16, p=0.04) and erythrocyte sedimentation rate (r=0.18, p=0.02). On multivariable analysis, changes in pulse pressure and erythrocyte sedimentation rate remained independently associated with changes in circulating NT-proBNP levels.These observations show that blocking TNFalpha in patients with RA without evident heart failure decreases NT-proBNP levels by about 18%. This suggests no treatment-induced deterioration in cardiac function and a potential cardiovascular risk benefit.
PSYCHIATRIC RECORD-KEEPING IN THE MILITARY
Authors: STEPHEN J. BARRETT
Journal: American Journal of Psychiatry (1964)

Since the military health record is a permanent one which has many uses and which will go through many hands, the question of what the psychiatrist should record is an important one. This article has discussed a rationale for psychiatric recordkeeping which meets the administrative needs of the military while at the same time safeguards the confidentiality of the doctor-patient relationship as much as possible. After carefully considering the future fate of the records, protection can be given to whoever needs it most.
Dyspnea: Physiological and Pathophysiological Mechanisms
Authors: Karlman Wasserman, Richard Casaburi
Journal: Annual Review of Medicine (1988)

Dyspnea, the sensation of feeling breathless, is a symptom experienced under conditions in which there is an inordinately high ventilatory demand relative to the ability to breathe. Its major physical sign is tachypnea. New developments in monitoring ventilation during exercise have improved our ability to evaluate the symptom of dyspnea and to understand pathophysiological mechanisms contributing to the symptom. We briefly describe the range of mechanisms that determine exercise ventilation and their possible relationship to dyspnea. Questionnaires and psychophysical testing have been used to quantify dyspnea, but there is variability in dyspnea grade from these methods. Dyspnea-producing stimuli and the mechanisms by which they act are reviewed. Disorders producing dyspnea and the pathophysiological mechanisms underlying each are discussed. Perception of dyspnea is obviously through the central nervous system, where dyspnea-producing stimuli are integrated. The specific integration site is probably in the region of the brain stem, since occasional patients with brain stem lesions do not experience dyspnea despite the presence of a number of dyspnea-producing stimuli.
DETERMINATION OF ANTIBODY CLASS IN A SYSTEM OF COOPERATING ANTIGENIC DETERMINANTS
Authors: Volker Schirrmacher, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (1970)

19S and 7S memory is analyzed in a system of cooperating antigenic determinants. Cooperation occurs in the induction of both 19S and 7S secondary antibodies, and for both responses carrier specificity can be entirely accounted for by presensitization of the animal to carrier determinants. The class distribution of secondary anti-hapten antibody depends on the dose of the hapten primary-carrier conjugate used for priming, and on the time interval between priming with the hapten primary-carrier conjugate and secondary injection. The conditions of priming with the secondary carrier influence the extent of the secondary response but not the class distribution of secondary antibody. The data confirm the cooperation hypothesis of antibody induction. Specifically, we interpret them to mean that in hapten-carrier cooperation, the hapten-specific memory cells are predetermined for the class of the emerging antibodies. Together with the hapten-specific memory cells, the carrier-specific helpers are responsible for the extent of the secondary response.
FOOD SAFETY REGULATION:Reforming the Delaney Clause
Authors: Richard A. Merrill
Journal: Annual Review of Public Health (1997)

The safety of food has been an age-old concern. Early civilizations adopted laws that punished sellers of tainted food. In this country, before food safety became a responsibility of the federal government every state had enacted laws prohibiting the sale of food that contained poisonous substances. The modern scientific and legal instruments available to the US Food and Drug Administration and allied agencies have improved regulation and advances in food preparation, preservation, and storage have contributed to a safer food supply. Even so, some observers believe that contemporary threats to food safety have grown more serious, and they surely excite intense public concern. For nearly two decades Congress has been debating the adequacy of current laws governing food safety. In the closing months of the 104th Congress, both parties finally agreed on the first significant legislative change in over a generation. This chapter examines the origins of the issues that were the focus of this extended debate and analyzes the implications of their resolution.
Extra 8bn to NHS cannot fund seven day service, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2015)

Health think tanks have warned MPs that the £8bn of extra funding promised by the government for the NHS in England by 2020 will only maintain the status quo and not help create the seven day service that the government is set on.

The full scale of funding and staff needed for the NHS to cope with growing demand and to provide the same service seven days a week was far beyond what is currently planned, said the leaders of the King’s Fund and Nuffield Trust, giving evidence on 10 November to the House of Commons Health Committee’s inquiry into primary care.

The inquiry is focusing on the recommendations of the report of the Primary Care Workforce Commission published in July,1 whose recommendations included a broader range …
Toothpaste and Crohn's disease
Authors: A.T. Florence, P.U. Jani, D. Mccarthy, A.D.N. Scott, C. Uff, R.K.S. Phillips, Yoav Ben-Shlomo, Paulo Nadanovsky, PeterH. Evans, Eiji Yano, Naoko Urano, HenryD. Janowitz
Journal: The Lancet (1990)
Assessing Glycemia in Diabetes Using Self-monitoring Blood Glucose and Hemoglobin A<sub>1c</sub>
Authors: Christopher D. Saudek, Rachel L. Derr, Rita R. Kalyani
Journal: JAMA (2006)

With the increasing prevalence of diabetes, successful management of blood glucose control is increasingly important. Current approaches to assessing glycemia include the use of self-monitoring of blood glucose (SMBG) and hemoglobin A1c (HbA1c).To assess the evidence underlying the use of these 2 modalities, to evaluate confounders and sources of error in each test, to describe upcoming developments, and to reach evidence-based conclusions on their optimal use.Reports identified from MEDLINE searches (1976-2005) using relevant terms were selected for quality and relevance to the stated questions. Particular attention was paid to larger cohort studies, clinical trials, meta-analyses, and established recommendations.If used properly SMBG gives an acceptably accurate reflection of immediate plasma glucose levels. Study results vary, but in general, the evidence supports a positive effect of regular SMBG for improving glycemia, particularly in individuals treated with insulin. The best timing of SMBG and its frequency are controversial issues, but the clinical recommendation is for regular monitoring with frequency depending on the treatment and the instability of glycemia. In the relatively near term, SMBG could gradually be replaced by continuous glucose monitoring. HbA1c measures long-term glycemic control, reflecting a time-weighted mean over the previous 3 to 4 months. There are a number of physiologic and methodologic confounders that can affect HbA1c, but standardization of assays has been well established. The main value of HbA1c is its use as a predictor of diabetic complications and the proven effect of improved control of HbA1c on complication risk. A reasonable target value for HbA1c is less than 7%. A new method for measuring HbA1c may cause significant changes in the recommended levels, the numbers reported, and even the name of the test.Assessing glycemia in diabetes can be a challenge, but approaches are available that promote successful management of blood glucose and may thereby lead to a significant reduction in morbidity and mortality related to diabetes.