tbuckley/cabot-search huggingface dataset:
Increased tumour necrosis factor production in mesenteric lymph nodes of cirrhotic patients with ascites
Authors: J Genesca
Journal: Gut (2003)

Background: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with bacterial translocation may participate in circulatory alterations of cirrhosis. Aim: To investigate whether cirrhotic patients present an increased local generation of cytokines in mesenteric lymph nodes. Methods: Mesenteric lymph nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis factor α (TNF) and interleukin 6 mRNA and protein expression by competitive reverse transcription-polymerase chain reaction, and by enzyme immunoassay and immunohistochemistry, respectively. Results: Interleukin 6 levels were not different between cirrhotics and controls. Protein and mRNA TNF levels in mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05). Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics. Ascitic patients showed higher TNF levels (47 (34–54) pg/mg protein) than patients without ascites (18 (17–25) pg/mg protein) (p<0.001). Elevated TNF levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin and blood TNF levels. The strongest association, confirmed by multivariate analysis, was with the presence of ascites (p<0.001). Bacterial infections after transplantation, mainly by enteric bacteria, were only detected in patients with high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). Conclusion: Patients with advanced liver cirrhosis, and especially with ascites, have increased local production of TNF in mesenteric lymph nodes that, in common with experimental cirrhosis, may also be induced by bacterial translocation.
Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach
Authors: H. T. M. van Schie, R. J. de Vos, S. de Jonge, E. M. Bakker, M. P. Heijboer, J. A. N. Verhaar, J. L. Tol, H. Weinans
Journal: British Journal of Sports Medicine (2009)

Objective To assess whether three-dimensional imaging of the Achilles tendon by ultrasonographic tissue characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. Design Case-control study. Setting Sports Medical Department of the Hague Medical Centre. Patients Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The “matched” control group consisted of 26 asymptomatic tendons. Interventions Symptomatic and asymptomatic tendons were scanned using the UTC procedure. One researcher performed the ultrasonographic data collection. These blinded data were randomised, and outcome measures were determined by two independent observers. Main outcome measurements The raw ultrasonographic images were analysed with a customdesigned algorithm that quantifies the three-dimensional stability of echo patterns, qua intensity and distribution over contiguous transverse images. This threedimensional stability was related to tendon structure in previous studies. UTC categorises four different echotypes that represent (I) highly stable; (II) medium stable; (III) highly variable and (IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated, and the maximum tendon thickness was measured. Finally, the inter-observer reliability of UTC was determined. Results Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% vs 76.6%, p&lt;0.001), thus less three-dimensional stability of the echo pattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p&lt;0.001). The Intraclass Correlation Coefficient (ICC) for the interobserver reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. Conclusion UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such, UTC might be useful to monitor treatment protocols.
Developing an HbA1c-Based Equation to Estimate Blood Glucose in Maintenance Hemodialysis Patients
Authors: Junichi Hoshino, Miklos Z. Molnar, Kunihiro Yamagata, Yoshifumi Ubara, Kenmei Takaichi, Csaba P. Kovesdy, Kamyar Kalantar-Zadeh
Journal: Diabetes Care (2012)

Hemoglobin A1c (HbA(1c)) has been widely used as a clinically important assessment tool for outcome analyses related to glycemic control. However, because of special conditions in dialysis patients, including the uremic milieu, there is no HbA(1c) blood glucose (BG) equation specific for patients on dialysis. In this study, we sought to develop HbA(1c)-BG equation models for hemodialysis patients.We examined associations between HbA(1c) and random serum BG over time in a contemporary cohort of diabetic patients with hemodialysis treated in DaVita dialysis clinics. We identified 11,986 patients (63 ± 12 years old and 49% male) with 69,764 paired measurements of HbA(1c) and BG over the course of 5 years (2001-2006). Bootstrapping method was used to estimate average BG and corresponding HbA(1c) levels. The association was adjusted by patient factors using linear regression.Linear regression analyses yielded the following three regression equations: BG = 59.2 + 29.4 × HbA(1c) - 20.8 × Alb (R(2) = 0.483); BG = 104.8 + 29.7 × HbA(1c) - 18.4 × Alb - 4.7 × Hb (R(2) = 0.486); and BG = 82.9 + 30.7 × HbA(1c) - 16.5 × Alb - 5.4 × Hb + 0.3 × age + race (R(2) = 0.491). All our models showed stronger association than previous equation models (R(2) = 0.468 in the Diabetes Control and Complications Trial and A1c-Derived Average Glucose equations).The association between HbA(1c) and BG in hemodialysis patients is different than that of patients with normal kidney function. Our analysis suggests that equations including serum albumin or hemoglobin are better for hemodialysis patients.
Characterization and localization of the enzymatic deacylation of lipoteichoic acid in group A streptococci.
Authors: R E Kessler, I van de Rijn, M McCarty
Journal: The Journal of Experimental Medicine (1979)

Protoplasts of a group A streptococcal strain were shown to contain enzymatic activity capable of converting lipoteichoic acid (LTA) to deacylated lipoteichoic acid (dLTA). The enzyme(s) appear to be located mainly in the membrane, although activity was also found in the cytoplasm. Determination of the sites of cleavage within the LTA molecule was approached by comparing the chemical composition of LTA and native dLTA. Native dLTA, as distinguished from chemically deacylated LTA, was isolated from buffer in which live streptococci had been resuspended and incubated. The chemical data suggest that the enzyme(s) was(were) lipolytic in nature; that is, the conversion of LTA to dLTA was the result of cleavage of the ester linkages between the fatty acids and the remainder of the LTA molecule.
Privilege Delineation in a Demanding New Environment
Authors: J S Roberts, M H Radany, D B Nash
Journal: Annals of Internal Medicine (1988)

The delineation of clinical privileges is one of the most important means for hospitals to ensure high-quality care. Competition, cost control, and public accountability have created the need for hospitals to assure effective privilege delineation processes. Hospitals should focus on issues of practice variation, continuity of care, volume of services provided and planned, and the integration of ethical considerations into clinical decisions. How information is obtained, verified, and acted upon is reviewed within the organizational framework of the hospital. Several leaders within the hospital, such as the clinical department chairs and members of the medical staff executive committee, have important functions in the clinical privilege delineation process. Granting clinical privileges is a critical hospital function that requires a commitment by the governing body, management, and medical staff leaders.
Relationships Between Gastric Emptying, Postprandial Glycemia, and Incretin Hormones
Authors: Chinmay S. Marathe, Christopher K. Rayner, Karen L. Jones, Michael Horowitz
Journal: Diabetes Care (2013)

The importance of achieving tight glycemic control, usually assessed by glycated hemoglobin (HbA1c), for both the prevention and delay in the progression of diabetes-related microvascular complications, is established, and the American Diabetes Association/European Association for the Study of Diabetes joint committee has recommended an HbA1c <7% as the goal in patients with type 2 diabetes (1). The relative contributions of pre- and postprandial glycemia to HbA1c have been clarified during the last decade following the seminal report by Monnier et al. (2) indicating that in type 2 diabetes, postprandial glycemic excursions account for about 70% of variability when HbA1c is <7.3%, while the contribution of “fasting” glycemia is greater in less well-controlled patients. Subsequent studies have confirmed the predominance of postprandial glycemia in determining overall glycemic control in “well-controlled” type 2 diabetic patients managed by oral hypoglycemic agents or basal insulin (3). The importance of postprandial glycemia to overall glycemic control is not surprising considering that 1 ) humans in modern societies spend only about 3 or 4 h before breakfast in a truly fasting state because in health, gastric emptying of meals occurs at an overall rate of 1–4 kcal/min (4), and 2 ) postprandial hyperglycemia occurs frequently in diabetes (1). The relevance of postprandial glycemia is further increased by the recognition that it may represent an independent risk factor for adverse cardiovascular outcomes in both diabetic and nondiabetic populations (5).

The determinants of postprandial glycemia include preprandial glycemic levels, meal composition, gastric emptying, insulin secretion, small intestinal glucose absorption, and hepatic and peripheral glucose metabolism. Furthermore, the relative contribution of each of these factors may vary over time during the postprandial state. Nevertheless, both the rate of gastric emptying and the secretion and action of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide …
Impairment of Coronary Circulation by Acute Hyperhomocysteinemia in Type 2 Diabetic Patients
Authors: Antonino Coppola, Costantino Astarita, Michele Oliviero, Dario Fontana, Giuseppe Picardi, Katherine Esposito, Raffaele Marfella, Ludovico Coppola, Dario Giugliano
Journal: Diabetes Care (2004)

Hyperhomocysteinemia increases the risk of death in type 2 diabetic patients (1,2), although the causal relationship with regard to cardiovascular mortality still remains elusive. Acute elevations in circulating homocysteine levels have been shown to impair endothelial function in coronary microcirculation in normal subjects (3). The objective of the present study was to investigate the effect of acute hyperhomocysteinemia on coronary circulation in patients with type 2 diabetes. Coronary flow velocity reserve (CFVR) assessment by transthoracic Doppler echocardiography (TTDE) is a noninvasive method to evaluate coronary flow reserve and provides important information about coronary endothelial function (4).

Twenty newly diagnosed (within 6 months of diagnosis) type 2 diabetic patients (14 men and 6 women, age 49 ± 8 years, BMI 26.1 ± 1.8 kg/m2) and 20 healthy control subjects, who were matched for age, sex, and BMI, volunteered for this study after informed written consent was obtained. All subjects (both patients and control subjects) were taking no medication or vitamin supplements, and the protocol was approved by the local ethics committee. The diabetic patients were normotensive, had cholesterol levels within normal ranges, and were free from both micro- and macro- …
Inferior Interatrial Pathway in the Dog
Authors: Benjamin J. Scherlag, Billy K. Yeh, Morton J. Robinson
Journal: Circulation Research (1972)

In 20 anesthetized dogs, close bipolar electrograms consisting of two deflections were recorded along the ligament of Marshall in the posterior left atrium. At the inferior portion of the ligament the deflections were separated by an interval of 10-15 msec and at the level of the left superior pulmonary vein by an interval of 60 msec or more. Histological and electrophysiological studies indicated that both deflections were associated with striated cardiac muscle; the first deflection was designated as a left atrial muscle potential and the second as a left atrial tract potential. Although the left atrial muscle potential was coincident with the middle portion of the P wave, the left atrial tract potential occurred during some part of the P-R segment. Conduction to the left atrial tract potential was altered, delayed, or completely blocked during retrograde conduction in the atrium, rapid pacing of the atrium (300-500/min), or local cooling at the point where the ligament of Marshall joined the inferior left atrium near the origin of the coronary sinus. Crushing Bachmann's bundle caused delay in conduction to the left atrial muscle but not to the left atrial tract. Left cardiac sympathetic nerve stimulation induced an atrial activation pattern consistent with pacemaker activity in the inferior left atrium, with inversion of the P wave in lead II. Pacing from the edge of the ligament of Marshall in the posterior left atrium produced the same change in P-wave morphology. These data indicate that the left atrial tract represents a terminal, insulated tract which is activated through an inferior interatrial pathway connecting the inferior right and left atria along the coronary sinus. The terminal end of the tract showed no reinsertion into atrial musculature.
Mechanism of Ventricular Defibrillation
Authors: Anne M. Gillis, Vladimir G. Fast, Stephan Rohr, André G. Kléber
Journal: Circulation (2000)

Background —The geometry of the myocardium may influence changes in transmembrane potential (ΔVm) during defibrillation. To test this hypothesis, specific nonlinear structures (bifurcations, expansions, and curved strands or “bends”) were created in patterned cultures of neonatal rat myocytes. Methods and Results —Extracellular field stimuli (EFS; 7 to 11 V/cm field strength) were applied parallel to the strands. Changes in Vm were measured with microscopic resolution using optical mapping techniques. In bifurcations, EFS produced 2 ΔVm maxima (so-called secondary sources) at the shoulder of each limb that were separated by a decrease of either hyperpolarization or depolarization at the insertion of the stem strand. In expansions, EFS produced a significant decrease in ΔVm at the insertion site of the expansion compared with the ΔVm maxima measured at the lateral borders. In 50% of experiments, tertiary sources of opposite polarity appeared in the strand due to local electrotonic currents. New action potentials were propagated from the sites of ΔVm maxima located at the lateral borders of the expansions. In bends, the strand oriented in parallel to the field dominated electrotonically and partially cancelled the sources produced by the perpendicular segment. Conclusions —In electrically well-coupled nonlinear structures, EFS produced changes in Vm at resistive boundaries that were determined by the electrotonic interaction between sources of different, direction-dependent strength. In addition, the interaction between localized secondary sources at nonlinear boundaries generated local current circuits, which gave rise to further changes in Vm (tertiary sources).
Insulin, Estrogen, Inflammatory Markers, and Risk of Benign Proliferative Breast Disease
Authors: Chelsea Catsburg, Marc J. Gunter, Chu Chen, Michele L. Cote, Geoffrey C. Kabat, Rami Nassir, Lesley Tinker, Jean Wactawski-Wende, David L. Page, Thomas E. Rohan
Journal: Cancer Research (2014)

Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 controls. Levels of insulin, estradiol, C-reactive protein (CRP), and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate ORs for the association of each factor with BPBD risk. Among nonusers of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile = 1.80; 95% confidence interval, CI, 1.16-2.79; Ptrend = 0.003) as were levels of estradiol (OR for highest vs. lowest tertile = 1.89; 95% CI, 1.26-2.83; Ptrend = 0.02) and CRP (OR for highest vs. lowest quartile = 2.46; 95% CI, 1.59-3.80; Ptrend < 0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile = 0.47; 95% CI, 0.31-0.71; Ptrend < 0.001). These associations persisted after mutual adjustment, but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP, and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin, and inflammation pathways are associated with the early stages of breast cancer development.
Newer Pathologic Assessment Techniques for Colorectal Carcinoma
Authors: Roderick R. Turner, Carolyn Li, Carolyn C. Compton
Journal: Clinical Cancer Research (2007)

Abstract The pathogenesis of colorectal carcinoma is characterized by progressive genetic abnormalities, which lead to proteomic and cellular changes that determine the cancer malignant phenotype. Phenotypic characteristics seen on histopathologic examination (e.g., tumor stage, histologic grade, and vasoinvasiveness) are essential to planning patient management and should continue to be the major focus of pathologists' efforts. Nonetheless, additional markers that improve the prognostic and predictive power of the pathologic analysis of the primary tumor have been the focus of intense research in recent years. Improved prognostic power may derive from advancements in histopathologic evaluation, more sensitive lymph node staging techniques, and specific molecular analysis methods, such as genetic tests or immunophenotypic profiles. Histopathologic improvements are needed to better standardize histologic grade determination and recognize tumor budding at the invasive front as a marker of aggressive biological behavior and an adverse parameter. Ultrastaging of mesenteric lymph nodes remains a controversial area. Genotypic studies are well developed in the areas of microsatellite instability and chromosome 18q deletion/loss of heterozygosity. Immunophenotypic studies are available in a range of areas including tumor suppressor gene/oncogene expression, proliferation/apoptosis, angiogenesis, and cell adhesion and signaling. Gene expression profiles identified by microarray techniques may help to subtype the large category of microsatellite-stable colorectal carcinoma and define immunophenotypic panels to subclassify tumors into prognostic and therapeutic groups. This brief review discusses the most promising of these approaches and evidence supporting their potential clinical utility.
Thrombopoietin expands erythroid progenitors, increases red cell production, and enhances erythroid recovery after myelosuppressive therapy.
Authors: K Kaushansky, V C Broudy, A Grossmann, J Humes, N Lin, H P Ren, M C Bailey, T Papayannopoulou, J W Forstrom, K H Sprugel
Journal: Journal of Clinical Investigation (1995)

Thrombopoietin (TPO), the ligand for the receptor protooncogene c-mpl, has been cloned and shown to be the critical regulator of platelet production. Several features of c-Mpl expression, including its presence on erythroid cell lines, and the panmyeloid transformation characteristic of myeloproliferative leukemia (MPL) viral disease led us to investigate whether this receptor-ligand system may play a role in erythropoiesis. We report that although TPO alone did not support the growth of either early or late erythroid progenitors, it acted in synergy with erythropoietin to expand these populations. Moreover, while the effects on erythropoiesis in normal animals were modest, TPO greatly expanded the number of erythroid progenitors and blood reticulocytes and was associated with accelerated red cell recovery in myelosuppressed mice. Together, these data strongly suggest that erythroid progenitors respond to TOP and that this newly cloned cytokine, critical for platelet production, can augment erythropoiesis in states of marrow failure.
Digital vascular responses and serum endothelin-1 concentrations in primary and secondary Raynaud's phenomenon
Authors: A E Smyth
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To determine circulating endothelin-1 levels (ET-1) in patients with primary or secondary associated Raynaud9s phenomenon (RP) under resting conditions and in response to cold provocation. <h3>METHODS</h3> Patients were categorised as primary RP (18) or scleroderma associated RP (14). Finger blood flow was measured by venous occlusion plethysmography at finger temperatures of 32°C and 24°C. Vasospasm was detected as a finger systolic pressure of 0 mm Hg after standardised provocative cooling. Severity of vasospasm was assessed by the level of cooling required to provoke spasm. Plasma ET-1 levels were measured in antecubital blood withdrawn under baseline conditions (finger 32°C) and at the point of vasospasm. Measurements were also made in 19 matched control subjects. <h3>RESULTS</h3> Finger blood flow was lower in patients with RP than in controls, with no difference between the two RP groups. Vasospasm occurred in all patients with RP but not in any control subjects and a grading system of severity was established. Baseline plasma ET-1 levels were similar in patients with RP and controls. Increases in ET-1 levels at the point of vasospasm in patients or corresponding timepoint in controls were also similar. There was no significant difference between the ET-1 levels in the two RP subgroups when the fingers were warm or when vasospasm was present. <h3>CONCLUSIONS</h3> These results do not support the hypothesis that ET-1 plays a part in the pathogenesis of RP. Objective testing is a useful adjunct to the clinical diagnosis of RP and allows assignment of a severity grade.