tbuckley/cabot-search huggingface dataset:
Impulse Propagation in Synthetic Strands of Neonatal Cardiac Myocytes With Genetically Reduced Levels of Connexin43
Authors: Stuart P. Thomas, Jan P. Kucera, Lilly Bircher-Lehmann, Yoram Rudy, Jeffrey E. Saffitz, André G. Kléber
Journal: Circulation Research (2003)

Connexin43 (Cx43) is a major determinant of the electrical properties of the myocardium. Closure of gap junctions causes rapid slowing of propagation velocity (theta), but the precise effect of a reduction in Cx43 levels due to genetic manipulation has only partially been clarified. In this study, morphological and electrical properties of synthetic strands of cultured neonatal ventricular myocytes from Cx43+/+ (wild type, WT) and Cx+/- (heterozygote, HZ) mice were compared. Quantitative immunofluorescence analysis of Cx43 demonstrated a 43% reduction of Cx43 expression in the HZ versus WT mice. Cell dimensions, connectivity, and alignment were independent of genotype. Measurement of electrical properties by microelectrodes and optical mapping showed no differences in action potential amplitude or minimum diastolic potential between WT and HZ. However, maximal upstroke velocity of the transmembrane action potential, dV/dtmax, was increased and action potential duration was reduced in HZ versus WT. theta was similar in the two genotypes. Computer simulation of propagation and dV/dtmax showed a relatively small dependence of theta on gap junction coupling, thus explaining the lack of observed differences in theta between WT and HZ. Importantly, the simulations suggested that the difference in dV/dtmax is due to an upregulation of INa in HZ versus WT. Thus, heterozygote-null mutation of Cx43 produces a complex electrical phenotype in synthetic strands that is characterized by both changes in ion channel function and cell-to-cell coupling. The lack of changes in theta in this tissue is explained by the dominating role of myoplasmic resistance and the compensatory increase of dV/dtmax.
Vasomodulation by Skeletal Muscle–Derived Nitric Oxide Requires α-Syntrophin–Mediated Sarcolemmal Localization of Neuronal Nitric Oxide Synthase
Authors: Gail D. Thomas, Philip W. Shaul, Ivan S. Yuhanna, Stanley C. Froehner, Marvin E. Adams
Journal: Circulation Research (2003)

Neuronal nitric oxide synthase (nNOS) is abundantly expressed in skeletal muscle where it associates with the dystrophin complex at the sarcolemma by binding to the PDZ domain of alpha-syntrophin. Nitric oxide (NO) produced by skeletal muscle nNOS is proposed to regulate blood flow in exercising muscle by diffusing from the skeletal muscle fibers to the nearby microvessels where it attenuates alpha-adrenergic vasoconstriction. In the present study, we hypothesized that sarcolemmal localization of nNOS is a critical determinant of the vasoregulatory effect of skeletal muscle-derived NO. To test this hypothesis, we performed experiments in alpha-syntrophin null mice and in transgenic mice expressing a mutated alpha-syntrophin lacking the PDZ domain (DeltaPDZ), both of which are characterized by reduced sarcolemmal nNOS. We found that modulation of alpha-adrenergic vasoconstriction was greatly impaired in the contracting muscles of the alpha-syntrophin null mice and transgenic DeltaPDZ mice compared with wild-type mice and transgenic mice expressing full-length alpha-syntrophin. These in vivo mouse studies highlight the functional importance of appropriate membrane targeting of nNOS by the dystrophin-associated protein alpha-syntrophin and may have implications for the development of potential gene therapy strategies to treat muscular dystrophy or other muscle-related diseases.
Tomatoes, Tomato-Based Products, Lycopene, and Cancer: Review of the Epidemiologic Literature
Authors: E. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (1999)

The epidemiologic literature in the English language regarding intake of tomatoes and tomato-based products and blood lycopene (a compound derived predominantly from tomatoes) level in relation to the risk of various cancers was reviewed. Among 72 studies identified, 57 reported inverse associations between tomato intake or blood lycopene level and the risk of cancer at a defined anatomic site; 35 of these inverse associations were statistically significant. No study indicated that higher tomato consumption or blood lycopene level statistically significantly increased the risk of cancer at any of the investigated sites. About half of the relative risks for comparisons of high with low intakes or levels for tomatoes or lycopene were approximately 0.6 or lower. The evidence for a benefit was strongest for cancers of the prostate, lung, and stomach. Data were also suggestive of a benefit for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix. Because the data are from observational studies, a cause-effect relationship cannot be established definitively. However, the consistency of the results across numerous studies in diverse populations, for case-control and prospective studies, and for dietary-based and blood-based investigations argues against bias or confounding as the explanation for these findings. Lycopene may account for or contribute to these benefits, but this possibility is not yet proven and requires further study. Numerous other potentially beneficial compounds are present in tomatoes, and, conceivably, complex interactions among multiple components may contribute to the anticancer properties of tomatoes. The consistently lower risk of cancer for a variety of anatomic sites that is associated with higher consumption of tomatoes and tomato-based products adds further support for current dietary recommendations to increase fruit and vegetable consumption.
Cardiovascular effects of octreotide in patients with hepatic cirrhosis
Authors: Aiden P. McCormick, Jason Chin, Lynda Greenslade, Stelios Karatapanis, Robert Dick, Neil McIntyre, Andrew K. Burroughs
Journal: Hepatology (1995)

Octreotide is thought to reduce splanchnic and variceal blood flow with minimal effects on the systemic circulation in cirrhotic patients with portal hypertension. However, we noticed significant bradycardia in some patients immediately after administration of bolus doses of octreotide. Therefore, we investigated the effect of intravenous octreotide on systemic hemodynamics in 59 patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32 patients received a 25-micrograms bolus and 20 patients received an infusion of 50-micrograms/hr of octreotide/placebo. Immediately after the bolus dose of octreotide was administered, there were significant reductions in pulse rate (77 +/- 3 vs. 65 +/- 3 beats per minute, P < .01) and cardiac output (9.2 +/- 0.8 vs. 7.9 +/- 0.8 L/min; P < .01) and significant increases in mean arterial pressure (81 +/- 3 vs. 87 +/- 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 +/- 1.0 vs. 16.6 +/- 1.5 mm Hg; P < .01), right atrial pressure (3.8 +/- 0.8 vs. 6.6 +/- 1.0 mm Hg; P < .01), right ventricular pressure (7.1 +/- 0.6 vs. 12.5 +/- 1.3 mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 +/- 0.8 vs. 11.2 +/- 1.4 mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance. Thirty minutes after the start of the infusion, there were significant increases in mean right atrial pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. This study suggests that intravenous octreotide has significant effects on the systemic circulation in patients with cirrhosis and that these effects appear to be more marked after administration of bolus doses.
Rheumatoid arthritis in Kenya. I. Clinical observations.
Authors: L R Bagg, D P Hansen, C Lewis, V Houba
Journal: Annals of the Rheumatic Diseases (1979)

76 Kenyan Africans with classical or definite rheumatoid arthritis are described. Their age, sex ratio, and pattern of joint involvement closely resembled that seen in Europe and the USA and differed from that described in West Africa and rural South Africa. However, they showed a marked lack of systemic nonarticular complications, with relatively little functional incapacity. Radiological grading was carried out on 58 cases, and the changes were found to resemble more closely those seen in an English series than in a Nigerian series.
Effects of bretylium tosylate on inhomogeneity of refractoriness and ventricular fibrillation threshold in canine hearts with quinidine-induced long QT interval
Authors: H. INOUE, I. TODA, A. NOZAKI, H. MATSUO, T. SUGIMOTO
Journal: Cardiovascular Research (1985)

We studied effects of bretylium tosylate (6 mg X kg-1, injected intravenously over 60s) on ventricular refractoriness and its inhomogeneity, and ventricular fibrillation threshold (VFT) in canine hearts with quinidine-induced long QT interval. In 3 anaesthetised open chest dogs, 30 mg X kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. Effective refractory period (ERP) was determined at 8 test points of the right ventricle using extrastimuli. Temporal dispersion as an expression of inhomogeneity of ventricular refractoriness was estimated as the difference between the longest and the shortest ERP. VFT was determined using a train of pulses, 4 ms in duration and at 10 ms intervals. Effects of bretylium were determined from 30 to 60 min after injection. Quinidine-induced long QT interval did not change after bretylium (358 +/- 37 vs 348 +/- 26 ms) when transiently elevated blood pressure returned to the pre-bretylium level. Bretylium shortened ERP slightly (278 +/- 16 vs 268 +/- 14 ms, p less than 0.02) but did not shorten ERP after premature depolarisation (209 +/- 14 vs 209 +/- 15). However, temporal dispersion was significantly decreased by bretylium. VFT, which was lowered by quinidine (14.5 +/- 5.0 vs 8.5 +/- 2.9 mA, p less than 0.01), was elevated significantly by bretylium (21.9 +/- 6.9, p less than 0.001). These effects of bretylium might be attributed to the combination of its direct electrophysiology and indirect adrenergic actions.
Progressive Primary Sclerosing Cholangitis Requiring Liver Transplantation Is Associated With Reduced Need for Colectomy in Patients With Ulcerative Colitis
Authors: Udayakumar Navaneethan, Preethi G.K. Venkatesh, Saurabh Mukewar, Bret A. Lashner, Feza H. Remzi, Arthur J. McCullough, Ravi P. Kiran, Bo Shen, John J. Fung
Journal: Clinical Gastroenterology and Hepatology (2012)
Which Cyclin E Prevails as Prognostic Marker for Breast Cancer? Results from a Retrospective Study Involving 635 Lymph Node–Negative Breast Cancer Patients
Authors: Anieta M. Sieuwerts, Maxime P. Look, Marion E. Meijer-van Gelder, Mieke Timmermans, Anita M.A.C. Trapman, Roberto Rodriguez Garcia, Miranda Arnold, Anneke J.W. Goedheer, Vanja de Weerd, Henk Portengen, Jan G.M. Klijn, John A. Foekens
Journal: Clinical Cancer Research (2006)

To evaluate the prognostic value of cyclin E with a quantitative method for lymph node-negative primary breast cancer patients.mRNA transcripts of full-length and splice variants of cyclin E1 (CCNE1) and cyclin E2 (CCNE2) were measured by real-time PCR in frozen tumor samples from 635 lymph node-negative breast cancer patients who had not received neoadjuvant or adjuvant systemic therapy.None of the PCR assays designed for the specific splice variants of the cyclins gave additional prognosis-related information compared with the common assays able to detect all variants. In Cox multivariate analysis, corrected for the traditional prognostic factors, high levels of cyclin E were independently associated with a short distant metastasis-free survival [hazard ratio (HR), 3.40; P < 0.001 for CCNE1 and HR, 1.76; P < 0.001 for CCNE2, respectively]. After dichotomizing the tumors at the median level of 70% tumor cells, the multivariate analysis showed particularly strong results for CCNE1 in the group of 433 patients with stroma-enriched primary tumors (HR, 5.12; P < 0.001). In these tumors, the worst prognosis was found for patients with estrogen receptor-negative tumors expressing high CCNE1 (HR, 9.89; P < 0.001) and for patients with small (T1) tumors expressing high CCNE1 (HR, 8.47; P < 0.001).Our study shows that both CCNE1 and CCNE2 qualify as independent prognostic markers for lymph node-negative breast cancer patients, and that CCNE1 may provide additional information for specific subgroups of patients.
Renal Amyloid: A Report on Eleven Cases Proven by Renal Biopsy
Authors: R. H. Heptinstall, A. M. Joekes
Journal: Annals of the Rheumatic Diseases (1960)

Amyloid deposition in the kidneys and other organs represents an intriguing anomaly.The whole problem, with a discussion of so-called primary and secondary amyloidosis, has been fully reviewed in recent years (Symmers, 1956).Amyloidosis occurs secondarily to a variety of chronic diseases, in particular those with chronic suppuration, but also in association with such conditions as rheumatoid arthritis and multiple 11 F 26 2.10.59
Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells
Authors: Chendong Pan, Matthew S. Nelson, Morayma Reyes, Lisa Koodie, Joseph J. Brazil, Elliot J. Stephenson, Robert C. Zhao, Charles Peters, Scott B. Selleck, Sally E. Stringer, Pankaj Gupta
Journal: Blood (2005)
Online Access to MEDLINE in Clinical Settings
Authors: R B Haynes, K A McKibbon, C J Walker, N Ryan, D Fitzgerald, M F Ramsden
Journal: Annals of Internal Medicine (1990)

Study Objective: We introduced self-service access to the medical literature database, MEDLINE, into clinical settings to assess the frequency, patterns, purposes, and success of use. Design: Longitudinal descriptive study. Setting: Inpatient and outpatient services of a university medical center. Participants: All trainees and attending staff working at the service sites were invited to participate; 158 (84%) did so. Interventions: Free online access was provided to MEDLINE through GRATEFUL MED software. Participants were offered a 2-hour introduction to online searching and 2 hours of free search time. Measurements and Main Results: For each search, a computer program requested identification of the user and the question to be addressed. Search transactions were recorded automatically. Interviews were conducted after a random sample of searches, and search questions were given to more expert searchers to run for comparison with the original. Eighty-one percent of participants did searches oh study computers, at a mean rate of 2.7 searches per month. On comparison searches, participants retrieved 55% of the number of relevant articles retrieved by reference librarians (P = 0.024) and 50% more irrelevant articles (P < 0.001). Forty-seven percent of searches on patient problems affected clinical decisions, but often on scanty information. Conclusions: MEDLINE searching from clinical settings is feasible with brief training and affects clinical decisions. However, inexperienced searchers miss many relevant citations and search inefficiently. Further studies are needed to assess the impact of searching on physician performance and patient care.
Ventilatory and hemodynamic effects of continuous positive airway pressure in left heart failure.
Authors: F Lenique, M Habis, F Lofaso, J L Dubois-Randé, A Harf, L Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The ventilatory and hemodynamic effects of continuous positive airway pressure (CPAP) delivered via a face mask (at 0, 5, and 10 cm H2O, and after a return to 0 cm H2O) were studied in nine patients with acute left heart failure (pulmonary artery occlusion pressure [PAOP] > or = 18 mm Hg, and cardiac index [CI] < or = 2.8 L/min/m2). CPAP at 10 cm H2O induced an improvement in lung compliance (60 +/- 10 ml/cm H2O to 87 +/- 20 ml/cm H2O, p < 0.05) and in lung and airway resistance (5.7 +/- 1.0 cm H2O/L/s to 3.4 +/- 1.0 cm H2O/L/s, p < 0.05), a reduction in work of breathing (18 +/- 3 J/min to 12 +/- 2 J/min, p < 0.05), and in the pressure-time index of the respiratory muscles (279 +/- 22 cm H2O/s/min to 174 +/- 25 cm H2O/s/min, p < 0.05), without significant changes in breathing pattern. Despite a significant reduction in the negative swings in intrathoracic pressure (15.2 +/- 1.9 cm H2O to 10.8 +/- 1.8 cm H2O, p < 0.001), no significant change was observed in CI or stroke volume during CPAP. However, mean transmural filling pressures decreased significantly with CPAP, suggesting a better cardiac performance. Neither the level of stroke volume nor of PAOP, was predictive of changes in CI or in stroke volume. In patients with respiratory insufficiency caused by congestive heart failure (CHF), CPAP reduces respiratory muscle effort without altering cardiac output. The slight decrease in mean transmural left and right atrial pressures suggests an improvement in cardiac performance.
Life events, psychiatric illness and the irritable bowel syndrome.
Authors: M J Ford, P M Miller, J Eastwood, M A Eastwood
Journal: Gut (1987)

The frequency, severity, and characteristics of psychiatric illness and stressful life situations were assessed in 134 patients aged 18-60 years referred to a gastrointestinal clinic by their general practitioner. A functional disorder of the gastrointestinal tract was established in 72%. A formal psychiatric assessment in 64 randomly selected patients revealed a previous or current psychiatric disorder in 54% of the functional group and 12.5% of the organic group. Stressful life events before referral were assessed by a modification of the Bedford College methodology. Anxiety provoking life situations were found in 30%, a proportion which was not significantly different in the two groups. Psychiatric illness episodes and/or anxiety provoking situations, preceded the onset of bowel symptoms in two-thirds of the functional group, however, but in none of the organic group. Life situations alone did not appear to be associated with functional disorders unless they provoked an anxiety state.
Heparin-binding EGF-like growth factor mRNA is upregulated in the peri-infarct region of the remnant kidney model
Authors: G Kirkland, K Paizis, L L Wu, M Katerelos, D A Power
Journal: Journal of the American Society of Nephrology (1998)

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent fibroblast and epithelial cell mitogen that may be important in wound healing. The aim of this study was to determine its distribution and possible function in segmental renal infarction. At day 1 postinfarction, in situ hybridization showed that HB-EGF mRNA was markedly increased by tubular epithelial cells bordering the infarcted zone. At day 3, typical myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA) were present in large numbers at the peri-ischemic border and, over succeeding days, were also seen within the infarcted area. Some of these cells expressed HB-EGF mRNA by in situ hybridization suggesting possible autocrine stimulation. Endothelial cells appeared to be more resistant to ischemia than tubules because some capillaries at the periphery of the infarct, surrounded by infarcted tubules, also expressed HB-EGF mRNA. The staining intensity of HB-EGF mRNA in individual tubules and endothelial cells was maximal at day 5 after infarction, although Northern blots of tissue from the peri-infarct area only showed significantly increased expression of HB-EGF mRNA at days 1 and 3, perhaps reflecting a smaller area of greater intensity of expression at day 5. Because tubular cells expressing high levels of HB-EGF mRNA were directly apposed to myofibroblasts, an attempt was made to determine whether HB-EGF contributed to upregulation of alpha-SMA by human fibroblasts. Although stimulation of the fibroblast cell line MRC-5 with transforming growth factor-beta1 (TGF-beta1) increased alpha-SMA, HB-EGF reduced expression. HB-EGF also strongly inhibited the increased expression of alpha-SMA due to TGF-beta1. Because HB-EGF is a potent fibroblast mitogen and TGF-beta is usually antiproliferative, this study suggests that HB-EGF may contribute to a local balance between fibroblast proliferation and differentiation into myofibroblasts during scarring.
Improved Survival of Children With Neuroblastoma Between 1979 and 2005: A Report of the Italian Neuroblastoma Registry
Authors: Riccardo Haupt, Alberto Garaventa, Claudio Gambini, Stefano Parodi, Giuliana Cangemi, Fiorina Casale, Elisabetta Viscardi, Maurizio Bianchi, Arcangelo Prete, Alessandro Jenkner, Roberto Luksch, Andrea Di Cataldo, Claudio Favre, Paolo D'Angelo, Giulio Andrea Zanazzo, Giampaolo Arcamone, Gian Carlo Izzi, Anna Rita Gigliotti, Guido Pastore, Bruno De Bernardi
Journal: Journal of Clinical Oncology (2010)

To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma.The study includes data from 2,216 children (age 0 to 14 years) diagnosed between 1979 and 2005. Overall survival (OS) was analyzed by clinical and biologic features at presentation and periods of diagnosis: 1979 to 1984, 1985 to 1991, 1992 to 1998, and 1999 to 2005. The relative risk of second malignant neoplasm (SMN) was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent.Yearly patient accrual increased over time from 58 to 102. Patients age 0 to 17 months represented 45.6% of the total population, and their incidence increased over time from 36.5% to 48.5%. The incidence of stage 1 patients increased over time from 5.8% to 23.2%. A total of 898 patients (40.5%) developed disease progression or relapse, 19 patients developed SMN, and two patients developed myelodysplasia. The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8.4 (95% CI, 5.1 to 13.2). A total of 858 patients (39%) died (779 of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications). Ten-year OS was 55.3% (95% CI, 53.0% to 57.6%) and increased over time from 34.9% to 65.0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%), but not afterward.The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN.
Impact of chart reminders on smoking cessation practices of pulmonary physicians.
Authors: H C Chang, L H Zimmerman, J M Beck
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Cigarette smoking remains one of the most preventable causes of premature death in our society, yet only a third to a half of smokers visiting a physician are counseled to quit. In the primary care setting, chart reminders can increase physician smoking cessation counseling rates. It is unclear, however, whether pulmonary physicians require prompting to discuss smoking cessation with patients. We hypothesized that chart reminders would improve the smoking cessation counseling and referral practices in our pulmonary clinic. Chart reviews were performed for two 1-mo periods and documentation of smoking status, counseling, and referrals to smoking cessation clinic were recorded. After the implementation of chart reminders, charts were reviewed at 1, 3, and 8 mo. Chart reminders increased documentation of smoking status from 33 to 83% (p = 0.0001). The proportion of all patients counseled increased from 6.0 to 13.2% (p = 0.01). The improvement in counseling to quit occurred primarily by increasing the identification of active smokers. Pulmonary physicians counseled 70% of smokers to quit once patients were identified as smokers. Chart reminders, an inexpensive and easily implemented smoking cessation intervention, increased the overall number and proportion of patients counseled to stop smoking by increasing the number of identified smokers. This simple intervention can improve counseling in populations at high risk for smoking related lung disease.