tbuckley/cabot-search huggingface dataset:
Methacholine challenge and sputum induction
Authors: N R. LABIRIS, F E HARGREAVE;, A. SPANEVELLO, M. CONFALONIERI, M. VIGNOLA, V. BRUSASCO
Journal: Thorax (1999)

We agree with Richard Coker 1 that the vast majority of non-compliant cases of tuberculosis can be dealt with by a mixture of directly observed therapy (DOT) and inducements.However, when DOT fails in a few cases each year, despite intensive team eVort and carrots such as housing or food vouchers, the Public Health Act may have to be invoked.We have had recourse to this measure four times in the past six months but, though providing valuable breathing space, it is extremely costly and proved ineVectual as a solution each time.Once the patient is admitted there are still potential problems.Treatment cannot be enforced and patients can abscond.There have also been instances of patients assaulting staV, physically and sexually, issuing death threats, breaking hospital property, and terrorising other patients, even interfering with others' oxygen therapy.Dealing with such patients puts hospital staV and patients under unacceptable pressure and requires extra staYng for security purposes.NHS hospitals were not designed for, nor are they staVed adequately for, custodial purposes.There is an urgent need to review the Public Health Act and make provisions for small specialist units staVed by nurses with training in and an aptitude for interpersonal skills.Admission to the unit would usually only be required for short periods of time until precipitating circumstances were resolved and alternative arrangements made.The threat of compulsory admission, or a short period thereof, may induce a behavioural change in the patient, allowing DOT to be successful after failing previously.In addition, a centrally based mobile unit of trained staV could be available to help tide teams over emergencies and could reduce the need for the specialist unit, enabling more non-adherent patients to be managed in the community.We call upon the Department of Health to examine and implement these proposals.
Failure of left atrial distension to alter renal function in the nonhuman primate.
Authors: J P Gilmore, I H Zucker
Journal: Circulation Research (1978)

Experiments were undertaken to determine the influence of increasing left atrial pressure on renal function in the nonhuman primate. Significant elevations of left atrial pressure, produced by using an intra-atrial balloon, had no effect on salt or water excretion, renal plasma flow, or glomerular filtration rate. There were no significant changes in heart rate or blood pressure. We conclude that, unlike those in the dog, atrial receptors in the nonhuman primate play little or no role in modulating salt and water excretion.
Treatment Course With Antidepressant Therapy in Late-Life Depression
Authors: Yvette I. Sheline, Brianne M. Disabato, Jennifer Hranilovich, Carrie Morris, Gina D’Angelo, Carl Pieper, Tommaso Toffanin, Warren D. Taylor, James R. MacFall, Consuelo Wilkins, Deanna M. Barch, Kathleen A. Welsh-Bohmer, David C. Steffens, Ranga R. Krishnan, P. Murali Doraiswamy
Journal: American Journal of Psychiatry (2012)

Objective In order to assess the effect of gray matter volumes and cortical thickness on antidepressant treatment response in late-life depression, the authors examined the relationship between brain regions identified a priori and Montgomery-Åsberg Depression Rating Scale (MADRS) scores over the course of an antidepressant treatment trial. Method In a nonrandomized prospective trial, 168 patients who were at least 60 years of age and met DSM-IV criteria for major depression underwent MRI and were enrolled in a 12-week treatment study. Exclusion criteria included cognitive impairment or severe medical disorders. The volumes or cortical thicknesses of regions of interest that differed between the depressed group and a comparison group (N=50) were determined. These regions of interest were used in analyses of the depressed group to predict antidepressant treatment outcome. Mixed-model analyses adjusting for age, education, age at depression onset, race, baseline MADRS score, scanner, and interaction with time examined predictors of MADRS scores over time. Results Smaller hippocampal volumes predicted a slower response to treatment. With the inclusion of white matter hyperintensity severity and neuropsychological factor scores, the best model included hippocampal volume and cognitive processing speed to predict rate of response over time. A secondary analysis showed that hippocampal volume and frontal pole thickness differed between patients who achieved remission and those who did not. Conclusions These data expand our understanding of the prediction of treatment course in late-life depression. The authors propose that the primary variables of hippocampal volume and cognitive processing speed, subsuming other contributing variables (episodic memory, executive function, language processing) predict antidepressant response.
Effect of repeated invitations on uptake of colorectal cancer screening using faecal occult blood testing: analysis of prevalence and incidence screening
Authors: R. J. C. Steele, I. Kostourou, P. McClements, C. Watling, G. Libby, D. Weller, D. H. Brewster, R. Black, F. A. Carey, C. Fraser
Journal: BMJ (2010)

<b>Objective</b> To analyse the effects of prevalence and incidence screening on uptake and detection of cancer in an ongoing, dynamic programme for colorectal screening using faecal occult blood testing. <b>Design</b> Analysis of prevalence and incidence screening. <b>Setting</b> Three rounds of biennial colorectal screening using the guaiac faecal occult blood test in east and north east Scotland, March 2000 to May 2007. <b>Participants</b> Adults aged 50-69. <b>Main outcome measures</b> Uptake of screening, test positivity (percentage of those invited who returned a test that was positive and triggered an invitation for colonoscopy), positive predictive value, and stage of cancer. <b>Results</b> Of 510 990 screening episodes in all three rounds, 248 998 (48.7%) were for prevalence, 163 483 (32.0%) were for first incidence, and 98 509 (19.3%) were for second incidence. Uptake of a first invitation for prevalence screening was 53% and for a second and third invitation was 15% and 12%. In the cohort invited for the first round, uptake of prevalence screening rose from 55% in the first round to 63% in the third. The uptake of first incidence screening on a first invitation was 54% and on a second invitation was 86% and on a first invitation for second incidence screening was 46%. The positivity rate in prevalence screening was 1.9% and the uptake of colonoscopy was 87%. The corresponding values for a first incidence screen were 1.7% and 90% and for a second incidence screen were 1.1% and 94.5%. The positive predictive value of a positive faecal occult blood test result for cancer was 11.0% for prevalence screening, 6.5% for the first incidence screen, and 7.5% for the second incidence screen. The corresponding values for the positive predictive value for adenoma were 35.5%, 29.4%, and 26.7%. The proportion of cancers at stage I dropped from 46.5% for prevalence screening to 41% for first incidence screening and 35% for second incidence screening. <b>Conclusions</b> Repeat invitations to those who do not take up the offer of screening increases the number of those who accept, for both prevalence screening and incidence screening. Although the positive predictive value for both cancer and adenomas fell between the prevalence screen and the first incidence screen, they did not fall between the first and second incidence screens. The deterioration in cancer stage from prevalence to incidence screening suggests that some cancers picked up at incidence screening may have been missed on prevalence screening, but the stage distribution is still favourable. These data vindicate the policies of continuing to offer screening to those who fail to participate and continuing to offer biennial screening to those who have accepted previous offers.
Properties of a store-operated nonselective cation channel in airway smooth muscle
Authors: P. B. Helli, L. J. Janssen
Journal: European Respiratory Journal (2008)

Passive depletion of internal Ca 2+ stores in airway smooth muscle (ASM) activates nonselective cation channels (NSCCs) that mediate capacitative Ca 2+ entry. However, the single channel properties of these cation channels have yet to be resolved and their regulation by cytosolic Ca 2+ levels ([Ca 2+ ] i ) still remains unclear. NSCC currents and changes in [Ca 2+ ] i during passive depletion of internal Ca 2+ stores were monitored in isolated bovine tracheal myocytes. Loading cells with 1,2-bis( o -aminophenoxy)ethane- N,N,N′,N′ -tetracetic acid acetyl methyl ester (BAPTA-AM) to reduce [Ca 2+ ] i and thereby deplete the store augmented a basal Gd 3+ - and La 3+ -sensitive, Ca 2+ -permeable NSCC current. This current mimics that which is evoked by store depletion using the sarcoplasmic reticulum Ca 2+ pump inhibitor cyclopiazonic acid (which concurrently and transiently elevates [Ca 2+ ] i ). Both interventions activated an ∼25-pS NSCC with properties identical to both spontaneous (basal) and BAPTA-AM-evoked single channel currents. In summary, the present study provides novel evidence that a lanthanide-sensitive, 25-pS nonselective cation channel underlies both basal and store depletion-evoked membrane currents in airway smooth muscle and that this conductance likely contributes to the regulation of resting [Ca 2+ ] i and capacitative Ca 2+ entry.
Effect of Nurse-Directed Diabetes Care in a Minority Population
Authors: Mayer B. Davidson
Journal: Diabetes Care (2003)

To determine whether diabetes care directed by nurses following detailed protocols and algorithms and supervised by a diabetologist results in meeting the evidence-based American Diabetes Association (ADA) process and outcome measures more often than care directed under usual care in a minority population.Studies were mainly conducted in two Los Angeles County clinics. In clinic A, nurse-directed diabetes care was provided to 252 patients (92% Hispanic and 2% African-American) referred by their primary care providers. These patients were hierarchically matched with 252 diabetic patients in clinic B (79% Hispanic and 19% African American). When nurse-directed care was abruptly discontinued in clinic A for administrative reasons, it was reestablished in clinic B. Those patients were randomly selected from a teaching clinic, and the outcomes in 114 patients who completed 1 year were compared with outcomes derived the year before receiving nurses' care. The following process and outcome measures were assessed in the study: 1) number of visits, 2) diabetes education, 3) nutritional counseling, 4) HbA(1c), 5) lipid profiles, 6) eye exams, 7) foot exams, 8) renal evaluations, and 9) ACE inhibitor therapy in appropriate patients.For patients under nurse-directed diabetes care in both clinics A and B, almost all process measures were carried out significantly more frequently than for the appropriate control patients. Under the care of nurses in clinic A, HbA(1c) levels fell 3.5% from 13.3 to 9.8% in the 120 patients who were followed for at least 6 months, as compared with a 1.5% fall from 12.3 to 10.8% under usual (physician-directed) care in clinic B. During the year before enrolling in nurse-directed care in clinic B, mean HbA(1c) levels decreased from 10.0 to 8.5%. At the end of a year under the nurses' care, the values fell further to 7.1%. The median value fell from 8.3 to 6.6%.Specially trained nurses who follow detailed protocols and algorithms under the supervision of a diabetologist can markedly improve diabetes outcomes in a minority population. This approach could help blunt the increased morbidity and mortality noted in minority populations.
Depletion of T-tubules and specific subcellular changes in sarcolemmal proteins in tachycardia-induced heart failure
Authors: R Balijepalli
Journal: Cardiovascular Research (2003)

The T-tubule membrane network is integrally involved in excitation-contraction coupling in ventricular myocytes. Ventricular myocytes from canine hearts with tachycardia-induced dilated cardiomyopathy exhibit a decrease in accessible T-tubules to the membrane-impermeant dye, di8-ANNEPs. The present study investigated the mechanism of loss of T-tubule staining and examined for changes in the subcellular distribution of membrane proteins essential for excitation-contraction coupling.Isolated ventricular myocytes from canine hearts with and without tachycardia-induced heart failure were studied using fluorescence confocal microscopy and membrane fractionation techniques using a variety of markers specific for sarcolemmal and sarcoplasmic reticulum proteins.Probes for surface glycoproteins, Na/K ATPase, Na/Ca exchanger and Ca(v)1.2 demonstrated a prominent but heterogeneous reduction in T-tubule labeling in both intact and permeabilised failing myocytes, indicating a true depletion of T-tubules and associated membrane proteins. Membrane fractionation studies showed reductions in L-type Ca(2+) channels and beta-adrenergic receptors but increased levels of Na/Ca exchanger protein in both surface sarcolemma and T-tubular sarcolemma-enriched fractions; however, the membrane fraction enriched in junctional complexes of sarcolemma and junctional sarcoplasmic reticulum demonstrated no significant changes in the density of any sarcolemmal protein or sarcoplasmic reticulum protein assayed.Failing canine ventricular myocytes exhibit prominent depletion of T-tubules and changes in the density of a variety of proteins in both surface and T-tubular sarcolemma but with preservation of the protein composition of junctional complexes. This subcellular remodeling contributes to abnormal excitation-contraction coupling in heart failure.
Dynamin-Related Protein 1–Mediated Mitochondrial Mitotic Fission Permits Hyperproliferation of Vascular Smooth Muscle Cells and Offers a Novel Therapeutic Target in Pulmonary Hypertension
Authors: Glenn Marsboom, Peter T. Toth, John J. Ryan, Zhigang Hong, Xichen Wu, Yong-Hu Fang, Thenappan Thenappan, Lin Piao, Hannah J. Zhang, Jennifer Pogoriler, Yimei Chen, Erik Morrow, E. Kenneth Weir, Jalees Rehman, Stephen L. Archer
Journal: Circulation Research (2012)

Rationale: Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction caused, in part, by pulmonary artery smooth muscle cell (PASMC) hyperproliferation. Mitochondrial fragmentation and normoxic activation of hypoxia-inducible factor-1α (HIF-1α) have been observed in PAH PASMCs; however, their relationship and relevance to the development of PAH are unknown. Dynamin-related protein-1 (DRP1) is a GTPase that, when activated by kinases that phosphorylate serine 616, causes mitochondrial fission. It is, however, unknown whether mitochondrial fission is a prerequisite for proliferation. Objective: We hypothesize that DRP1 activation is responsible for increased mitochondrial fission in PAH PASMCs and that DRP1 inhibition may slow proliferation and have therapeutic potential. Methods and Results: Experiments were conducted using human control and PAH lungs (n=5) and PASMCs in culture. Parallel experiments were performed in rat lung sections and PASMCs and in rodent PAH models induced by the HIF-1α activator, cobalt, chronic hypoxia, and monocrotaline. HIF-1α activation in human PAH leads to mitochondrial fission by cyclin B1/CDK1–dependent phosphorylation of DRP1 at serine 616. In normal PASMCs, HIF-1α activation by CoCl 2 or desferrioxamine causes DRP1-mediated fission. HIF-1α inhibition reduces DRP1 activation, prevents fission, and reduces PASMC proliferation. Both the DRP1 inhibitor Mdivi-1 and siDRP1 prevent mitotic fission and arrest PAH PASMCs at the G2/M interphase. Mdivi-1 is antiproliferative in human PAH PASMCs and in rodent models. Mdivi-1 improves exercise capacity, right ventricular function, and hemodynamics in experimental PAH. Conclusions: DRP-1–mediated mitotic fission is a cell-cycle checkpoint that can be therapeutically targeted in hyperproliferative disorders such as PAH.
Effect of Evolocumab or Ezetimibe Added to Moderate- or High-Intensity Statin Therapy on LDL-C Lowering in Patients With Hypercholesterolemia
Authors: Jennifer G. Robinson, Bettina S. Nedergaard, William J. Rogers, Jonathan Fialkow, Joel M. Neutel, David Ramstad, Ransi Somaratne, Jason C. Legg, Patric Nelson, Rob Scott, Scott M. Wasserman, Robert Weiss
Journal: JAMA (2014)

In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy.To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin.Phase 3, 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries.Patients (n = 2067) were randomized to 1 of 24 treatment groups in 2 steps. Patients were initially randomized to a daily, moderate-intensity (atorvastatin [10 mg], simvastatin [40 mg], or rosuvastatin [5 mg]) or high-intensity (atorvastatin [80 mg], rosuvastatin [40 mg]) statin. After a 4-week lipid-stabilization period, patients (n = 1899) were randomized to compare evolocumab (140 mg every 2 weeks or 420 mg monthly) with placebo (every 2 weeks or monthly) or ezetimibe (10 mg or placebo daily; atorvastatin patients only) when added to statin therapies.Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) level at the mean of weeks 10 and 12 and at week 12.Evolocumab reduced LDL-C levels by 66% (95% CI, 58% to 73%) to 75% (95% CI, 65% to 84%) (every 2 weeks) and by 63% (95% CI, 54% to 71%) to 75% (95% CI, 67% to 83%) (monthly) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; the LDL-C reductions at week 12 were comparable. For moderate-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36%, 40%, and 39% of evolocumab-, ezetimibe-, and placebo-treated patients, respectively. The most common adverse events in evolocumab-treated patients were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%).In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia, evolocumab added to moderate- or high-intensity statin therapy resulted in additional LDL-C lowering. Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering.clinicaltrials.gov Identifier: NCT01763866.
Increased interleukin 6, but reduced interleukin 1, in delayed pressure urticaria
Authors: F. LAWLOR, C. BIRD, R.D.R. CAMP, R. BARLOW, R.M. BARR, A. KOBZA-BLACK, M.R. JUDGE, M.W. GREAVES
Journal: British Journal of Dermatology (1993)

Journal Article Increased interleukin 6, but reduced interleukin 1, in delayed pressure urticaria Get access F. LAWLOR, F. LAWLOR St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Dr Frances Lawlor, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SEI 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. BIRD, C. BIRD National Institute for Biological Standards and Control, South Mimms, Hertfordshire, U. K. Search for other works by this author on: Oxford Academic Google Scholar R.D.R. CAMP, R.D.R. CAMP St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. BARLOW, R. BARLOW St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.M. BARR, R.M. BARR St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. KOBZA‐BLACK, A. KOBZA‐BLACK St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.R. JUDGE, M.R. JUDGE St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.W. GREAVES M.W. GREAVES St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 128, Issue 5, 1 May 1993, Pages 500–503, https://doi.org/10.1111/j.1365-2133.1993.tb00225.x Published: 01 May 1993 Article history Accepted: 10 November 1992 Published: 01 May 1993
Methylation and Messenger RNA Expression of <i>p15INK4b</i> but Not <i>p16INK4a</i> Are Independent Risk Factors for Ovarian Cancer
Authors: Zhensheng Liu, Li-E Wang, Luo Wang, Karen H. Lu, Gordon B. Mills, Melissa L. Bondy, Qingyi Wei
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The purpose of this research was to compare methylation status and mRNA expression of p15INK4b and p16INK4a in serous epithelial ovarian cancer tissues and normal ovarian tissues. Experimental Design: We analyzed the DNA methylation status and mRNA expression of p15INK4b and p16INK4a in 52 ovarian cancer specimens and 40 normal ovarian specimens by using methylation-specific PCR and real-time reverse transcription-PCR, respectively. Results: Although the p15INK4b and p16INK4a mRNA expression levels were highly correlated with each other (P &amp;lt; 0.001), the methylation status did not seem to be linked with levels of mRNA expression, as no association between the two events was found for either gene. Promoter hypermethylation of p15INK4b was more common in ovarian cancer (30.8% for the 52 cases) than in normal ovaries (5% for the 40 controls without ovarian cancer; P = 0.005) but not methylation of p16INK4a (25% for cancer versus 37.5% for normal; P = 0.288). The relative mRNA expression levels of p15INK4b were significantly lower in ovarian cancer (12.9%) than in normal ovaries (41.7%; P = 0.008) but not those of p16INK4a (27% for cases versus 32.8% for controls; P = 0.754). Only high methylation rate and low mRNA expression of p15INK4b were independent risk factors for ovarian cancer (adjusted odds ratio, 5.67; 95% confidence interval, 0.85-37.9 for high methylation rate and odds ratio, 8.98; 95% confidence interval, 1.58-50.9 for low mRNA expression, respectively). Conclusions: Our results suggest that epigenetic alterations in p15INK4b but not p16INK4a have an important role in ovarian carcinogenesis and that mechanisms other than methylation may exist to reduce gene expression of p15INK4b in ovarian cancer.