tbuckley/cabot-search huggingface dataset:
Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial
Authors: I. Flytström, B. Stenberg, Å. Svensson, I-M. Bergbrant
Journal: British Journal of Dermatology (2007)

Background When this study was initiated, no previous studies comparing methotrexate and ciclosporin for moderate to severe plaque psoriasis had been performed. Objectives To compare the effectiveness, quality of life and side‐effects of methotrexate and ciclosporin treatments in a context reflecting normal clinical practice. Methods Eighty‐four patients with moderate to severe plaque psoriasis were randomized to treatment with methotrexate or ciclosporin for 12 weeks. The primary outcome was the Psoriasis Area and Severity Index (PASI). The secondary outcome was quality of life, measured by the Dermatology Life Quality Index (DLQI) and the 36‐item Short Form Health Survey (SF‐36). A visual analogue scale (VAS) was used for patients' assessment. Results Sixty‐eight patients started treatment and were included in the analysis. Dropout before initiation of treatment was higher in the ciclosporin group. Mean PASI change from baseline at 12 weeks was 58% in the methotrexate group and 72% in the ciclosporin group, showing ciclosporin to be more effective than methotrexate. Improvement of the VAS score was higher in the ciclosporin group. The methotrexate group showed a greater improvement in the subscale Physical Functioning of the SF‐36. No significant difference between the groups was found for DLQI. Conclusions Treatment with methotrexate or ciclosporin for chronic plaque psoriasis brings satisfactory disease control, improved quality of life and tolerable side‐effects. A statistically significant difference in effectiveness between treatment groups was recorded, showing ciclosporin to be more effective than methotrexate in a short‐term perspective.
Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood.
Authors: J Garrett, J M Fenwick, G Taylor, E Mitchell, J Stewart, H Rea
Journal: Thorax (1994)

BACKGROUND--Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated. METHODS--A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later. RESULTS--At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use. CONCLUSIONS--The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland).
Abstract 13961: A Single Cognitive Behavior Therapy Session Improves Short-Term Depressive Symptoms in Hospitalized Patients with Heart Failure
Authors: Rebecca L Dekker, Elizabeth G Tovar, Lynn V Doering, Alison L Bailey, Charles L Campbell, Jesse H Wright, Malachy L Bishop, Debra K Moser
Journal: Circulation (2014)

Background: Hospitalized patients with heart failure (HF) are at high risk for depressive symptoms which contribute to poorer outcomes. Interventions are needed to manage depressive symptoms in these patients.

Purpose: To test the effects of a single cognitive behavior therapy (CBT) session on depressive symptoms one week post-hospital discharge.

Methods: This was a combined data analysis of two sequential randomized, controlled pilot studies testing a brief CBT intervention for the treatment of depressive symptoms. Similar inclusion and exclusion criteria were used in both studies. Patients were randomly assigned to usual care or a 30-minute CBT session, delivered by the same cardiac nurse prior to hospital discharge. A total of 24 patients with HF and depressive symptoms were included (57 ± 9 years, 44% female, 48% NYHA Class III). Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Repeated measures analysis of variance was used to describe changes in depressive symptoms between groups, and chi square analysis was used to compare the proportion of patients in each group with moderate to severe depressive symptoms (PHQ-9 score ≥ 10) one week after discharge.

Results: Both groups had similar clinical characteristics and depressive symptom levels at baseline. There was a significant interaction effect between group and time with depressive symptoms (see Figure). At one week, the average PHQ-9 score in the usual care group remained above the cut point for major depression, while the average score for the intervention group fell below the cut-point. Furthermore, only 23% of the intervention group had moderate to severe depressive symptoms, compared to 77% in the usual care group (p = .015).

Conclusion: These results suggest nurses caring for hospitalized patients with HF can deliver a brief intervention that improves short-term depressive symptoms. Future research is needed to determine the long-term effects of the intervention.

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Archetypal trajectories of social, psychological, and spiritual wellbeing and distress in family care givers of patients with lung cancer: secondary analysis of serial qualitative interviews
Authors: S. A. Murray, M. Kendall, K. Boyd, L. Grant, G. Highet, A. Sheikh
Journal: BMJ (2010)

<b>Objective</b> To assess if family care givers of patients with lung cancer experience the patterns of social, psychological, and spiritual wellbeing and distress typical of the patient, from diagnosis to death. <b>Design</b> Secondary analysis of serial qualitative interviews carried out every three months for up to a year or to bereavement. <b>Setting</b> South east Scotland. <b>Participants</b> 19 patients with lung cancer and their 19 family carers, totalling 88 interviews (42 with patients and 46 with carers). <b>Results</b> Carers followed clear patterns of social, psychological, and spiritual wellbeing and distress that mirrored the experiences of those for whom they were caring, with some carers also experiencing deterioration in physical health that impacted on their ability to care. Psychological and spiritual distress were particularly dynamic and commonly experienced. In addition to the "Why us?" response, witnessing suffering triggered personal reflections in carers on the meaning and purpose of life. Certain key time points in the illness tended to be particularly problematic for both carers and patients: at diagnosis, at home after initial treatment, at recurrence, and during the terminal stage. <b>Conclusions</b> Family carers witness and share much of the illness experience of the dying patient. The multidimensional experience of distress suffered by patients with lung cancer was reflected in the suffering of their carers in the social, psychological, and spiritual domains, with psychological and spiritual distress being most pronounced. Carers may need to be supported throughout the period of illness not just in the terminal phase and during bereavement, as currently tends to be the case.
Expression and localization of proteins of the complement system in human skin.
Authors: N Dovezenski, R Billetta, I Gigli
Journal: Journal of Clinical Investigation (1992)

The complement system participates in the immune recognition of foreign antigens, many of which may penetrate the skin by physical injury or transcutaneous adsorption. In this study, we examined the presence of complement components and complement regulatory proteins in the human skin and cultured human keratinocytes. Immunofluorescence studies showed C3, Factor B, decay accelerating factor, the C3b receptor (CR1), and C3d receptor (CR2), distributed among cells of the epidermis as well as on cultured keratinocytes. Immunoblot analysis of keratinocytes supernatants showed the presence of C3 with a molecular weight of approximately 180 kD. The decay accelerating factor was localized as previously reported on elastic fibers; additionally it was observed in the basement membrane zone. In situ hybridization studies suggest the expression of CR1 and CR2 mRNA in human epidermis. These results show the presence in the human epidermis of complement components that are capable of generating the initial C3 convertase of the alternative pathway. The presence of complement regulatory proteins could endow keratinocytes with immune functions such as the regulation of complement activation and endocytosis of C3 opsonized particles.
Modulation of responsiveness of chronic myelogenous leukemia granulocyte‐macrophage colony‐forming cells to growth regulation following in vivo treatment with recombinant γ‐interferon
Authors: Louis M. Pelus, Saroj Vadhan‐Raj
Journal: American Journal of Hematology (1988)

Abstract A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant γ‐interferon (rγ‐IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte‐macrophage colony‐forming cells (CFU‐GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA‐DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU‐GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive‐phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU‐GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with rγ‐IFN can modulate some of the abnormal growth characteristics of CFU‐GM observed in CML.
Association of the G-protein and 2-adrenergic receptor gene and plasma norepinephrine level with clonidine improvement of the effects of diuretics in patients with cirrhosis with refractory ascites: a randomised clinical trial
Authors: Y. Y. Yang, H. C. Lin, W. P. Lee, C. J. Chu, M. W. Lin, F. Y. Lee, M. C. Hou, J. S. Jap, S. D. Lee
Journal: Gut (2010)

<h3>Objective</h3> Clonidine is an α<sub>2</sub>-adrenoceptor agonist which, by coupling with G-protein, has been proposed as an alternative treatment for refractory ascites of patients with cirrhosis for several years. Genetic polymorphisms of β-adrenoceptor and angiotensin II type 1 receptor blockers have been reported to affect drug response in patients with cirrhosis. This study evaluated the clonidine–diuretic response rate, favourable predictors and genetic components of the clonidine–diuretic response in patients with cirrhosis with refractory ascites. <h3>Methods</h3> 270 patients with cirrhosis with refractory ascites were randomised equally into two treatment groups to receive diuretics alone or the clonidine–diuretics association. The primary end point was clonidine–diuretic response rate. Secondary end points were mean daily dose of diuretics, times of paracentesis, ascites-related readmission and 1-year survival rate. <h3>Results</h3> Good clonidine responders had better natriuresis and diuresis as well as a significant decrease in abdominal circumference, plasma renin, aldosterone and norepinephrine levels. The overall clonidine–diuretics response rate was 55–60%. In patients with cirrhosis, the prevalence of ARDA<sub>2</sub>C WD/DD and GNB3 CT/TT genotypes was 71% and 77%, respectively. Among the responders, 71% of patients with cirrhosis had the ARDA<sub>2</sub>C WD/DD genotype and 67% has the GNB3 CT/TT genotype. Besides higher baseline norepinephrine levels, the presence of both ARDA<sub>2</sub>C WD/DD and GNB3 CT/TT genotypes showed a positive predictive value of 82% and a negative predictive value of 79% for good clonidine response. <h3>Conclusions</h3> These results suggest that neurohormonal and genetic testing may be used as predictive factors for the additive effects of clonidine on the diuresis and natriuresis effects of diuretics in patients with cirrhosis with refractory ascites.
Molecular Time
Authors: Tami A. Martino, Michael J. Sole
Journal: Circulation Research (2009)

Abstract: Diurnal rhythms influence cardiovascular physiology such as heart rate and blood pressure and the incidence of adverse cardiac events such as heart attack and stroke. For example, shift workers and patients with sleep disturbances, such as obstructive sleep apnea, have an increased risk of heart attack, stroke, and sudden death. Diurnal variation is also evident at the molecular level, as gene expression in the heart and blood vessels is remarkably different in the day as compared to the night. Much of the evidence presented here indicates that growth and renewal (structural remodeling) are highly dependent on processes that occur during the subjective night. Myocardial metabolism is also dynamic with substrate preference also differing day from night. The risk/benefit ratio of some therapeutic strategies and the appearance of biomarkers also vary across the 24-hour diurnal cycle. Synchrony between external and internal diurnal rhythms and harmony among the molecular rhythms within the cell is essential for normal organ biology. Cell physiology is 4 dimensional; the substrate and enzymatic components of a given metabolic pathway must be present not only in the right compartmental space within the cell but also at the right time. As a corollary, we show disrupting this integral relationship has devastating effects on cardiovascular, renal and possibly other organ systems. Harmony between our biology and our environment is vital to good health.
Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes.
Authors: G Targher, L Bertolini, L Zenari, V Cacciatori, M Muggeo, G Faccini, G Zoppini
Journal: Diabetes Care (2000)

OBJECTIVE: The purposes of this study were to compare plasma total homocysteine (tHcy) levels, a recognized cardiovascular risk factor, in nondiabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma tHcy concentrations were measured in 60 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 30 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects (12.5 +/- 4.8 vs. 10.3 +/- 2.2 micromol/l, P = 0.01). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, creatinine, blood pressure, glycometabolic control, diabetes duration, and microvascular complications that were superimposable on their nonsmoking counterparts. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers versus nonsmokers (15.5 +/- 5.7 vs. 10.6 +/- 3 pmol/l, P &amp;lt; 0.0001) in a dose-dependent fashion (P &amp;lt; 0.0001, by analysis of variance when subjects were categorized for the number of cigarettes smoked daily). CONCLUSIONS: Chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes.
Association between Autoregulation and Pressure Dependency of Renal Vascular Responsiveness in Dogs
Authors: JOHN L. MCNAY, TAKETOSHI KISHIMOTO
Journal: Circulation Research (1969)

We studied the influence of perfusion pressure (arterial pressure minus venous pressure) on the magnitude of responses of renal blood flow to intraarterial injections of acetylcholine, norepinephrine, adenosine, and angiotensin. The left kidney of dogs anesthetized with pentobarbital was denervated, renal arterial flow measured with an electromagnetic flowmeter, and renal perfusion pressure varied by constricting the aorta or renal vein. The percent changes in renal blood flow produced by standardized doses of each vasoactive agent were considered an indication of vascular responsiveness. In kidneys having autoregulation, vascular responsiveness so defined was a function of renal perfusion pressure. In contrast, this correlation was not characteristic of denervated, non-autoregulating canine hindlegs. These experiments do not distinguish between the alternate possibilities that changes in renal vascular responsiveness may have a role in autoregulation or may be a consequence of it.
Sustained Hemodynamic Stress Disrupts Normal Circadian Rhythms in Calcineurin-Dependent Signaling and Protein Phosphorylation in the Heart
Authors: Nita Sachan, Asim Dey, David Rotter, D. Bennett Grinsfelder, Pavan K. Battiprolu, Devanjan Sikder, Victoria Copeland, Misook Oh, Erik Bush, John M. Shelton, James A. Bibb, Joseph A. Hill, Beverly A. Rothermel
Journal: Circulation Research (2011)

Despite overwhelming evidence of the importance of circadian rhythms in cardiovascular health and disease, little is known regarding the circadian regulation of intracellular signaling pathways controlling cardiac function and remodeling.To assess circadian changes in processes dependent on the protein phosphatase calcineurin, relative to changes in phosphorylation of cardiac proteins, in normal, hypertrophic, and failing hearts.We found evidence of large circadian oscillations in calcineurin-dependent activities in the left ventricle of healthy C57BL/6 mice. Calcineurin-dependent transcript levels and nuclear occupancy of the NFAT (nuclear factor of activated T cells) regularly fluctuated as much as 20-fold over the course of a day, peaking in the morning when mice enter a period of rest. Phosphorylation of the protein phosphatase 1 inhibitor 1 (I-1), a direct calcineurin substrate, and phospholamban, an indirect target, oscillated directly out of phase with calcineurin-dependent signaling. Using a surgical model of cardiac pressure overload, we found that although calcineurin-dependent activities were markedly elevated, the circadian pattern of activation was maintained, whereas, oscillations in phospholamban and I-1 phosphorylation were lost. Changes in the expression of fetal gene markers of heart failure did not mirror the rhythm in calcineurin/NFAT activation, suggesting that these may not be direct transcriptional target genes. Cardiac function in mice subjected to pressure overload was significantly lower in the morning than in the evening when assessed by echocardiography.Normal, opposing circadian oscillations in calcineurin-dependent activities and phosphorylation of proteins that regulate contractility are disrupted in heart failure.
Update on sputum methodology
Authors: O. Holz, J. Kips, H Magnussen
Journal: European Respiratory Journal (2000)

Over the past few years cellular and biochemical sputum examinations have become important instruments to assess airway inflammation. The aim of this review is to summarize new methodological developments and aspects, which are currently under investigation. The use of isotonic saline has increased safety of inductions in patients with severe asthma and in children. The origin of sputum is better understood, as is the need to standardize the volume and duration of induction. It also needs to be borne in mind that the induction procedure itself is able to cause changes in sputum composition. However, the basic induction and processing procedures have not changed much over the last few years, and therefore the method is still time consuming. The analysis of ECP in lysed sputum cells as a marker for the number of eosinophils has been suggested to overcome this problem, but needs further validation. Furthermore, storage of sputum has been studied, as well as early fixation or freezing of sputum cells to elongate the time between induction and processing. Differential cell counts by flow cytometry are still difficult, but the method has increased knowledge concerning lymphocyte subsets and the activation status of sputum cells. The use of induced sputum to noninvasively measure airway inflammation in clinical trials will offer additional information, but the proper use and interpretation of sputum outcome parameters will need further investigation.
Sudden death at work
Authors: J M Harrington
Journal: BMJ (1994)

The message of Cutting Edge's programme was that many deaths at work result from negligent work practices and that the guilty employers go unpunished. The programme concentrated its attention on the west midlands, where the local trades union advisory group had investigated all recent deaths at work and then hired the eminent QC Anthony Scrivener to review whether criminal charges could have been brought against the employer.

The programme's three sections were each devoted to one death, and a pattern emerged: relatives talking (rather eloquently I thought) …