tbuckley/cabot-search huggingface dataset:
Differential Activation of Mitogen-Activated Protein Kinase Cascades and Apoptosis by Protein Kinase C ε and δ in Neonatal Rat Ventricular Myocytes
Authors: Maria C. Heidkamp, Allison L. Bayer, Jody L. Martin, Allen M. Samarel
Journal: Circulation Research (2001)

Protein kinase C (PKC) ε and PKCδ translocation in neonatal rat ventricular myocytes (NRVMs) is accompanied by subsequent activation of the ERK, JNK, and p38 MAPK cascades; however, it is not known if either or both novel PKCs are necessary for their downstream activation. Use of PKC inhibitors to answer this question is complicated by a lack of isoenzyme specificity, and the fact that many PKC inhibitors stimulate JNK and p38 MAPK activity. Therefore, replication-defective adenoviruses (Advs) encoding constitutively active (ca) mutants of PKCε and PKCδ were used to test if either or both of these PKCs are sufficient to activate ERKs, JNKs, and/or p38 MAPK in NRVMs. Adv-caPKCε infection (1 to 25 multiplicities of viral infection (MOI); 4 to 48 hours) increased total PKCε levels in a time- and dose-dependent manner, with maximal expression observed 8 hours after Adv infection. Adv-caPKCε induced a time- and dose-dependent increase in phosphorylated p42 and p44 ERKs, as compared with a control Adv encoding β-galactosidase (Adv-neβgal). Maximal ERK phosphorylation occurred 8 hours after Adv infection. In contrast, JNK was only minimally activated, and p38 MAPK was relatively unaffected. Adv-caPKCδ infection (1 to 25 MOI, 4 to 48 hours) increased total PKCδ levels in a similar fashion. Adv-caPKCδ (5 MOI) induced a 29-fold increase in phosphorylated p54 JNK, and a 15-fold increase in phosphorylated p38 MAPK 24 hours after Adv infection. In contrast, p42 and p44 ERK were only minimally activated. Whereas neither Adv induced NRVM hypertrophy, Adv-caPKCδ, but not Adv-caPKCε, induced NRVM apoptosis. We conclude that the novel PKCs differentially regulate MAPK cascades and apoptosis in an isoenzyme-specific and time-dependent manner.
Alpha‐1‐antitrypsin genotyping with mouthwash specimens
Authors: R.A. Stockley, E.J. Campbell
Journal: European Respiratory Journal (2001)

α 1 ‐antitrypsin (α 1 ‐AT) deficiency is diagnosed as a two-stage procedure (concentration and phenotype). However the latter does not provide clues to the presence of null genes without family studies and obtaining blood from patients at a distance often proves difficult. The aim of the study was to assess the feasibility of genotyping α 1 ‐AT using buccal cells. Mouthwash specimens were sent by 84 patients (with a variety of phenotypes of α 1 ‐antitrypsin) through the post. Deoxyribonucleic acid (DNA) was isolated from buccal cells in each sample and subjected to polymerase chain reaction (PCR) using a genotyping kit to detect the S and Z alleles. Eighty-three of 84 samples received were suitable for amplification. The specific primers successfully identified the S and Z alleles in each case. However, five of the 35 samples obtained from patients thought to be Z allele homozygotes were found to be heterozygotes for another severe deficiency allele. These data confirm the feasibility of “at distance” testing for α 1 ‐antitrypsin deficiency alleles using buccal cells from mouthwash samples. The results raise the possibility that other deficiency alleles are more common than has previously been suspected.
Association of a Television in the Bedroom With Increased Adiposity Gain in a Nationally Representative Sample of Children and Adolescents
Authors: Diane Gilbert-Diamond, Zhigang Li, Anna M. Adachi-Mejia, Auden C. McClure, James D. Sargent
Journal: JAMA Pediatrics (2014)

Obesity affects health in children and adolescents. Television viewing is an established risk factor for obesity in youth. No prospective study has assessed whether a bedroom television confers an additional risk for obesity in youth.To assess the prospective association between the presence of a bedroom television and change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), independent of television viewing, in a nationally representative sample of US children and adolescents.We conducted a random-digit prospective telephone survey that captured children and adolescents from across the United States. Participants included 6522 boys and girls aged 10 to 14 years at baseline who were surveyed via telephone about media risk factors for obesity.Weighted regressions assessed adiposity at 2- and 4-year follow-up, controlling for television and movie viewing, video-game playing, parenting, age, sex, race or ethnicity, household income, and parental educational level.Report of having a television in the bedroom at baseline.Age- and sex-adjusted BMI based on self-report and parent report of weight and height at 2- and 4-year follow-up.Distributions for age, sex, race or ethnicity, and socioeconomic status were similar to census estimates for the US population. Sample weighting methods accounted for higher dropout rates among ethnic minorities and those with lower socioeconomic status. Bedroom televisions were reported by 59.1%of participants at baseline, with boys, ethnic minorities, and those of lower socioeconomic status having significantly higher rates. In multivariate analyses, having a bedroom television was associated with an excess BMI of 0.57 (95%CI, 0.31-0.82) and 0.75 (0.38-1.12) at years 2 and 4, respectively, and a BMI gain of 0.24 (0.02-0.45) from years 2 to 4.Having a bedroom television is associated with weight gain beyond the effect of television viewing time. This association could be the result of uncaptured effects of television viewing or of disrupted sleep patterns. With the high prevalence of bedroom televisions, the effect attributable to this risk factor among US children and adolescents is excess weight of 8.7 million kg/y.
Carcinoma Complicated by Proximal Motor Neuropathy Due to Vitamin-B Deficiency
Authors: P. L. d. V. Hart
Journal: BMJ (1954)

By the use of laxatives it was possible to increase the faecal excretion of sodium during the ingestion of cation- exchange resins.However, a great increment in sodium excretion was obtained only when the stools were kept fluid.Vigorous treatment of this kind is not recommended, as, besides the discomfort, purgatives greatly augment the excre- tion of potassium in the stool water.During treatment with cation-exchange resins the aim should be to keep the motions loose but not actually fluid, and to supplement the dietary intake of potassium.Saline laxatives, the cations of which become bound to the resin, and liquid paraffin, which coats the resin with a water-repellent film, must of course be avoided. SummaryThe net uptake of cations by an exchange resin was determined at different levels of the intestinal tract in man.The rates of turnover of Na24 and K42 to and from the resin were also measured in the small and large intestines of the rat.A series of dynamic equilibria are established be- tween the cations on the exchange resin and those in the intestinal fluids.These transfers are continuous throughout the gut, but the rates of turnover and the net uptake of cations by the resin change as it passes onwards from the stomach to the rectum.Cations throughout the body continually exchange with those on the resin by way of the intestinal fluids.These concepts have been used to interpret the results obtained during the treatment of patients with cation- exchange resins.
Safety and Efficacy of Two Different Doses of Capecitabine in the Treatment of Advanced Breast Cancer in Older Women
Authors: Emilio Bajetta, Giuseppe Procopio, Luigi Celio, Luca Gattinoni, Silvia Della Torre, Luigi Mariani, Laura Catena, Riccardo Ricotta, Raffaella Longarini, Nicoletta Zilembo, Roberto Buzzoni
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the safety and efficacy of capecitabine in older women with advanced breast cancer. Patients and Methods Seventy-three eligible patients (median age, 73 years; range, 65 to 89 years) were enrolled. The first 30 patients received oral capecitabine 1,250 mg/m 2 twice daily on days 1 to 14 every 21 days. Due to the occurrence of two toxic deaths, capecitabine 1,000 mg/m 2 twice daily was given to the subsequent 43 patients. Results All patients were assessable for safety and efficacy. A total of 351 treatment cycles were administered (median, six per patient; range, one to eight cycles). Dose reductions due to toxicities were required in 30% of patients in the standard-dose group, but capecitabine was given without a dose reduction to 95% of patients in the low-dose group. Capecitabine demonstrated a favorable safety profile. The overall incidence of grade 3/4 toxicities was low: the most common events reported in ≤ 10% of the patients were fatigue, diarrhea, dyspnea, and nausea. In the standard-dose group, the response rate was 36.7% (95% CI, 19.9% to 56.1%). An additional seven patients had disease stabilization at ≥ 24 weeks. In the low-dose group, the response rate was 34.9% (95% CI, 21% to 50.9%). An additional 15 patients had prolonged stabilization. The median time to disease progression was 4 months in either group. Conclusion This study shows that capecitabine is safe and effective in the elderly breast cancer patient. Based on the overall results, the capecitabine dose of 1,000 mg/m 2 twice daily merits consideration as “standard” for older patients who do not have severely impaired renal function.
The effect of physician gender on length of patient consultations: observational findings from the UK hospital setting and synthesis with existing studies
Authors: Laura Jefferson, Karen Bloor, Catherine Hewitt
Journal: Journal of the Royal Society of Medicine (2015)

Objectives To investigate the effect of physician gender on consultation length in UK hospital outpatient clinics and compare this, through meta-analysis, with previous studies outside the UK. Design Observational data on clinic times were analysed and findings were combined in a meta-analysis with existing studies investigating the effect of physician gender on consultation length. Setting UK hospital practice. Participants A total of 174 observations of outpatient consultations with 10 hospital specialists (consultants) from different specialties in two UK hospital trusts. Main outcome measures Clinic times were recorded and analysis of consultation length was undertaken with physician gender as a covariate. Data were then synthesised through meta-analysis with 10 existing studies in this field. Results No statistically significant difference was found in the length of consultations for male and female doctors in these UK hospital settings. When pooled with existing studies, consultations with women doctors were found to be approximately two minutes longer than with men ( p = 0.01). Conclusions Findings from this analysis of clinic consultations in the UK National Health Service do not support previous studies, which were undertaken predominantly in North America and primary care settings. Overall, meta-analysis suggests doctors’ gender may influence consultation length. Gender differences in communication should be considered in training clinicians and in overall clinical practice.
The Carcinoid Syndrome and Angioedema
Authors: A.N.M. Wymenga
Journal: Annals of Internal Medicine (1995)

Letters15 October 1995The Carcinoid Syndrome and AngioedemaA.N.M. Wymenga, MD, J.G.R. de Monchy, MD, PhD, and E.G.E. de Vries, MD, PhDA.N.M. Wymenga, MDUniversity Hospital; 9713 EZ Groningen; the NetherlandsSearch for more papers by this author, J.G.R. de Monchy, MD, PhDUniversity Hospital; 9713 EZ Groningen; the NetherlandsSearch for more papers by this author, and E.G.E. de Vries, MD, PhDUniversity Hospital; 9713 EZ Groningen; the NetherlandsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-8-199510150-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Patients with a metastatic carcinoid tumor can present with various symptoms, which depend on tumor site and size, the distribution of metastases, and hormonal activity [1]. These patients can present diagnostic and treatment challenges as a result of peculiar, disabling syndromes that are caused by massive hormone production. We describe a patient with the carcinoid syndrome and Quincke edema that improved after treatment with terfenadine (a selective histamine-1 [H1]-receptor antagonist) and ranitidine (a selective H2-receptor antagonist).Our patient was a 50-year-old man with a history of hypertension. Sixteen years earlier, he had had a malignant midgut carcinoid ...References1. Moertel CG. An odyssey in the land of small tumors. J Clin Oncol. 1987; 5:1503-22. Google Scholar2. Reisberg IR, Oyakawa S. Mastocytosis with malabsorption, myelofibrosis and massive ascites. Am J Gastroenterol. 1987; 82:54-60. Google Scholar3. de Vries EG, Kema IP, Slooff MJ, Verschueren RC, Kleibeuker JH, Mulder NH, et al. Recent developments in diagnosis and treatment of metastatic carcinoid tumours. Scand J Gastroenterol. 1993; 28(Suppl 200):87-93. Google Scholar4. Platt AJ, Heddle RM, Rake MO, Smedley H. Ondansetron in carcinoid syndrome [Letter]. Lancet. 1992; 339:1416. Google Scholar5. Jacobsen MB. Ondansetron in carcinoid syndrome [Letter]. Lancet. 1992; 340:185. Google Scholar Author, Article, and Disclosure InformationAuthors: A.N.M. Wymenga, MD; J.G.R. de Monchy, MD, PhD; E.G.E. de Vries, MD, PhDAffiliations: University Hospital; 9713 EZ Groningen; the Netherlands PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUrticaria as initial finding of a patient with carcinoid tumorBiochemical Markers in the Follow-up of Medullary Thyroid CancerAngioedema as a single manifestation of carcinoid syndrome in a bronchial carcinoid tumorMastocytosis with skin manifestations: current statusCarcinoid Tumors 15 October 1995Volume 123, Issue 8Page: 636KeywordsCarcinoid tumorEdemaHistamineInflammationMast cellsMastocytosisPatientsProstaglandinsSerotoninTongue ePublished: 15 August 2000 Issue Published: 15 October 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study
Authors: Howard I Scher, Tomasz M Beer, Celestia S Higano, Aseem Anand, Mary-Ellen Taplin, Eleni Efstathiou, Dana Rathkopf, Julia Shelkey, Evan Y Yu, Joshi Alumkal, David Hung, Mohammad Hirmand, Lynn Seely, Michael J Morris, Daniel C Danila, John Humm, Steve Larson, Martin Fleisher, Charles L Sawyers
Journal: The Lancet (2010)
Blood component support in acquired coagulopathic conditions: Is there a method to the madness?
Authors: Trailokya Nath Pandit, Ravindra Sarode
Journal: American Journal of Hematology (2012)

Acquired coagulopathies are often detected by laboratory investigation in clinical practice. There is a poor correlation between mild to moderate abnormalities of laboratory test and bleeding tendency. Patients who are bleeding due to coagulopathy are often managed with various blood components including plasma, platelets, and cryoprecipitate. However, prophylactic transfusion of these products in a nonbleeding patient to correct mild to moderate abnormality of a coagulation test especially preprocedure is not evidence-based. This article reviews the management of bleeding due to oral anticoagulants and antiplatelet agents, disseminated intravascular coagulation, chronic liver disease, and trauma.
Characteristics of hospitalised patients with 2009 H1N1 influenza in Chile
Authors: R. Riquelme, M. Riquelme, M. L. Rioseco, C. Inzunza, Y. Gomez, C. Contreras, J. Riquelme, P. Peyrani, T. Wiemken, J. Ramirez
Journal: European Respiratory Journal (2010)

As the pandemic of 2009 H1N1 influenza A virus progressed, more patients required hospitalisation. The objective of this study is to describe the characteristics and clinical course of hospitalised patients with 2009 H1N1 virus infection in Chile. This was a prospective, observational study of 100 consecutive hospitalised patients with RT-PCR-confirmed 2009 H1N1 influenza A, admitted to Puerto Montt General Hospital (Puerto Montt, Chile). Information was obtained regarding contact history, demographics, laboratory values and clinical course. The primary reason for hospitalisation was pneumonia, in 75% of patients. Rapid influenza A test was positive in 51% of patients. Prior exposure to 2009 H1N1 virus was documented in 21% of patients. Clinical failure, documented in 18% of cases, was characterised by respiratory failure and acute respiratory distress syndrome. Failure was more common in patients with obesity, tachypnoea, confusion and multilobar infiltrates. When evaluating a patient hospitalised with influenza-like illness, a negative rapid test for influenza A or negative contact with a suspected case should not alter physicians' considerations regarding the likelihood of 2009 H1N1 virus infection. Patients with 2009 H1N1 virus infection with obesity, tachypnoea, confusion and multilobar infiltrates should be closely monitored since they are at high risk for clinical failure.
Change in objectively measured physical activity during the transition to adolescence
Authors: Kirsten Corder, Stephen J Sharp, Andrew J Atkin, Simon J Griffin, Andrew P Jones, Ulf Ekelund, Esther M F van Sluijs
Journal: British Journal of Sports Medicine (2013)

Background Physical activity (PA) declines during adolescence but change in different PA intensities across population subgroups is rarely explored. We describe change in sedentary (SED) time, light (LPA), moderate (MPA) and vigorous PA (VPA) assessed at three time points over 4 years. Methods Accelerometer-assessed PA (min) was obtained at baseline (N=2064), 1 and 4 years later among British children (baseline mean±SD 10.2±0.3-year-old; 42.5% male). Change in SED (&lt;100 counts/min (cpm)), LPA (101–1999 cpm), MPA (2000–3999 cpm) and VPA (≥4000 cpm) was studied using three-level (age, individual and school) mixed-effects linear regression including participants with data at ≥2 time points (N=990). Differences in change by sex, home location and weight status were explored with interactions for SED, LPA and moderate and vigorous PA (MVPA). Results SED increased by 10.6 (95% CI 9.1 to 12.2) min/day/year. MPA and VPA decreased by 1.4 (1.0 to 1.8) and 1.5 (1.1 to 1.8) min/day/year, respectively. VPA decreased more than MPA as a percentage of the baseline value. MVPA declined more steeply among boys (3.9 (3.0 to 4.8)) versus girls (2.0 (1.2 to 2.7) min/day/year) despite lower MVPA among girls at all ages; rural (4.4 (3.5 to 5.2)) versus urban individuals (1.3 (0.4 to 2.3) min/day/year) and on weekends (6.7 (5.2 to 8.1)) versus weekdays (2.8 (1.9 to 3.7) min/day/year). MVPA was consistently lower among overweight/obese individuals (−17.5 (−3.9 to −2.5) min/day/year). Conclusions PA decreases and is replaced by SED during early adolescence in British youth. Results indicate the urgency of PA promotion among all adolescents but especially girls and in rural areas. Increasing VPA and targeting PA promotion during weekends appear important.
Ca <sup>2+</sup> Influx Through T- and L-Type Ca <sup>2+</sup> Channels Have Different Effects on Myocyte Contractility and Induce Unique Cardiac Phenotypes
Authors: Naser Jaleel, Hiroyuki Nakayama, Xiongwen Chen, Hajime Kubo, Scott MacDonnell, Hongyu Zhang, Remus Berretta, Jeffrey Robbins, Leanne Cribbs, Jeffery D. Molkentin, Steven R. Houser
Journal: Circulation Research (2008)

T-type Ca 2+ channels (TTCCs) are expressed in the developing heart, are not present in the adult ventricle, and are reexpressed in cardiac diseases involving cardiac dysfunction and premature, arrhythmogenic death. The goal of this study was to determine the functional role of increased Ca 2+ influx through reexpressed TTCCs in the adult heart. A mouse line with cardiac-specific, conditional expression of the α1G-TTCC was used to increase Ca 2+ influx through TTCCs. α1G hearts had mild increases in contractility but no cardiac histopathology or premature death. This contrasts with the pathological phenotype of a previously studied mouse with increased Ca 2+ influx through the L-type Ca 2+ channel (LTCC) secondary to overexpression of its β2a subunit. Although α1G and β2a myocytes had similar increases in Ca 2+ influx, α1G myocytes had smaller increases in contraction magnitude, and, unlike β2a myocytes, there were no increases in sarcoplasmic reticulum Ca 2+ loading. Ca 2+ influx through TTCCs also did not induce normal sarcoplasmic reticulum Ca 2+ release. α1G myocytes had changes in LTCC, SERCA2a, and phospholamban abundance, which appear to be adaptations that help maintain Ca 2+ homeostasis. Immunostaining suggested that the majority of α1G-TTCCs were on the surface membrane. Osmotic shock, which selectively eliminates T-tubules, induced a greater reduction in L- versus TTCC currents. These studies suggest that T- and LTCCs are in different portions of the sarcolemma (surface membrane versus T-tubules) and that Ca 2+ influx through these channels induce different effects on myocyte contractility and lead to distinct cardiac phenotypes.
Lipoprotein lipase secretion by human monocyte-derived macrophages.
Authors: A Chait, P H Iverius, J D Brunzell
Journal: Journal of Clinical Investigation (1982)

Human monocyte-derived macrophages in culture produced lipoprotein lipase. Although freshly isolated blood monocytes did not secrete much lipase activity, 1 d in culture was sufficient to trigger measureable enzyme production. During 3 wk in culture, maximal activity was attained after 7 d. At all times, the culture medium contained more enzyme activity than did a serum-heparin eluate or a detergent extract of the cell layer. The lipase activity was stimulated by serum and was inhibited by preincubation with antiserum to bovine lipoprotein lipase or when assayed at a high salt concentration. Furthermore, the enzyme bound to a heparin-Sepharose affinity column at physiological ionic strength. Cells cultured from a subject with primary lipoprotein lipase deficiency secreted no detectable enzyme. Since macrophages are prominent components of atherosclerotic lesions in man, their ability to synthesize and secrete lipoprotein lipase may be important to atherogenesis.
Challenges in Motor Vehicle Safety
Authors: Patricia F. Waller
Journal: Annual Review of Public Health (2002)

▪ Abstract Reductions in motor vehicle injury and death represent a major public health success. Since the advent of the federal program in highway safety in 1966, motor vehicle deaths have dropped dramatically, not only in rates per miles driven but also in absolute numbers. Key to this success has been the broad-based comprehensive approach promoted by the program's first administrator, a public health physician. The federal program provided leadership and coordination that leveraged national, state, and local programs to bring about safer vehicles, improved traffic records, more effective enforcement, enormously improved emergency medical services, more responsible judicial systems, and many other accomplishments. Although progress has been made on many fronts, major areas addressed here include federal motor vehicle safety standards, alcohol safety programs, occupant restraint laws and usage, and speed limits. The achievements in motor vehicle safety provide a model for other injury control efforts.