tbuckley/cabot-search huggingface dataset:
A Systematic Review of Treatments for Refractory Depression in Older People
Authors: Claudia Cooper, Cornelius Katona, Kostas Lyketsos, Dan Blazer, Henry Brodaty, Peter Rabins, Carlos Augusto de Mendonça Lima, Gill Livingston
Journal: American Journal of Psychiatry (2011)

The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older).The authors conducted an electronic database search and reviewed the 14 articles that fit predetermined criteria. Refractory depression was defined as failure to respond to at least one course of treatment for depression during the current illness episode. The authors rated the validity of studies using a standard checklist and calculated the pooled proportion of response to any treatment reported by at least three studies.All the studies that met inclusion criteria investigated pharmacological treatment. Most were open-label studies, and the authors found no double-blind randomized placebo-controlled trials. The overall response rate for all active treatments investigated was 52% (95% CI=42-62; N=381). Only lithium augmentation was assessed in more than two trials, and the response rate was 42% (95% CI=21-65; N=57). Only two studies included comparison groups receiving no additional treatment, and none of the participants in these groups responded. In single randomized studies, extended-release venlafaxine was more efficacious than paroxetine, lithium augmentation more than phenelzine, and selegiline more than placebo.Half of the participants responded to pharmacological treatments, indicating the importance of managing treatment-refractory depression actively in older people. The only treatment for which there was replicated evidence was lithium augmentation. Double-blind randomized controlled trials for management of treatment-refractory depression in older people, encompassing pharmacological and nonpharmacological therapies and populations that reflect the levels of physical and cognitive impairment present in the general older population with depression, are needed.
MORPHOLOGY AND THICKNESS OF THE HUMAN STRATUM CORNEUM
Authors: CICELY BLAIR
Journal: British Journal of Dermatology (1968)

SUMMARY.— The method of exhibiting the layers of cells of the stratum corneum described by Kligman and Christophers has been employed and elaborated, and has proved to be practical and reproducible. The cells can be counted and observations made on their morphology.



The shape of the cells treated by this method has been shown to be different at various sites and at different levels of the stratum corneum, and in pathological states.



The stratum corneum is probably more compact than has been hitherto supposed.



Differences in susceptibility to alkali have been demonstrated in the horny cells surrounding the eccrine sweat ducts and the pilosebaceous orifices.



There are also age differences in the susceptibility of the stratum corneum to alkali and possibly in its thickness.
Two Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Plus Extended-Field Radiotherapy Is Superior to Radiotherapy Alone in Early Favorable Hodgkin's Lymphoma: Final Results of the GHSG HD7 Trial
Authors: Andreas Engert, Jeremy Franklin, Hans Theodor Eich, Corinne Brillant, Susanne Sehlen, Claudio Cartoni, Richard Herrmann, Michael Pfreundschuh, Markus Sieber, Hans Tesch, Astrid Franke, Peter Koch, Maike de Wit, Ursula Paulus, Dirk Hasenclever, Markus Loeffler, Rolf-Peter Müller, Hans Konrad Müller-Hermelink, Eckhart Dühmke, Volker Diehl
Journal: Journal of Clinical Oncology (2007)

To investigate whether combined-modality treatment (CMT) with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by extended-field radiotherapy (EF-RT) is superior to EF-RT alone in patients with early favorable Hodgkin's lymphoma (HL).Between 1993 and 1998, 650 patients with newly diagnosed, histology-proven HL in clinical stages IA to IIB without risk factors were enrolled onto this multicenter study and randomly assigned to receive 30 Gy EF-RT plus 10 Gy to the involved field (arm A) or two cycles of ABVD followed by the same radiotherapy (arm B). Results At a median observation time of 87 months, there was no difference between treatment arms in terms of complete response rate (arm A, 95%; arm B, 94%) and overall survival (at 7 years: arm A, 92%; arm B, 94%; P = .43). However, freedom from treatment failure was significantly different, with 7-year rates of 67% in arm A (95% CI, 61% to 73%) and 88% in arm B (95% CI, 84% to 92%; P <or= .0001). This was due mainly to significantly more relapses after EF-RT only (arm A, 22%; arm B, 3%). No patient treated with CMT experienced relapse before year 3. Relapses were treated mainly with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, or with the combination cyclophosphamide, vincristine, procarbazine, and prednisone/ABVD; treatment of relapse was significantly more successful in arm A than in arm B (P = .017). In total, there were 39 second malignancies, with 21 in arm A and 18 in arm B, respectively. The incidence was approximately 0.8% per year during years 2 to 9 and was highest in older patients (P < .0001) and those with "B" symptoms (P = .012).CMT consisting of two cycles of ABVD plus EF-RT is more effective than EF-RT alone.
Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function
Authors: R. Amin, P. Subbarao, A. Jabar, S. Balkovec, R. Jensen, S. Kerrigan, P. Gustafsson, F. Ratjen
Journal: Thorax (2010)

<h3>Background and aims</h3> Sensitive outcome measures to assess the efficacy of therapeutic interventions in patients with cystic fibrosis (CF) with mild lung disease are currently lacking. Our objective was to study the ability of the lung clearance index (LCI), a measure of ventilation inhomogeneity, to detect a treatment response to hypertonic saline inhalation in paediatric patients with CF with normal spirometry. <h3>Methods</h3> In a crossover trial, 20 patients with CF received 4 weeks of hypertonic saline (HS) and isotonic saline (IS) in a randomised sequence separated by a 4 week washout period. The primary end point was the change in the LCI due to HS versus IS. <h3>Results</h3> Baseline characteristics including the LCI were not significantly different between both study periods. Four weeks of twice-daily HS inhalation significantly improved the LCI compared with IS (1.16, 95% CI 0.26 to 2.05; p=0.016), whereas other outcome measures such as spirometry and quality of life failed to reach statistical significance. Randomisation order had no significant impact on the treatment effect. <h3>Conclusions</h3> The LCI, but not spirometry was able to detect a treatment effect from HS inhalation in patients with CF with mild disease and may be a suitable tool to assess early intervention strategies in this patient population. <h3>Clinical trial number</h3> NCT00635141.
Association Between Lipid Levels and Major Adverse Cardiovascular Events in Rheumatoid Arthritis Compared to Non–Rheumatoid Arthritis Patients
Authors: Katherine P. Liao, Jun Liu, Bing Lu, Daniel H. Solomon, Seoyoung C. Kim
Journal: Arthritis & Rheumatology (2015)

Lower levels of low-density lipoprotein (LDL) cholesterol may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study was undertaken to determine whether the complex relationship between levels of LDL and high-density lipoprotein (HDL) cholesterol and CV risk is different in RA patients as compared to non-RA controls.Using data from a US health insurance plan (2003-2012), we conducted a cohort study that included patients with RA and non-RA control subjects matched with regard to age, sex, and index date. The nonlinearity of associations between lipid levels and incidence of major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipid levels and RA status in relation to the risk of MACE, after adjustment for CV risk factors.In total, 16,085 RA patients and 48,499 non-RA controls were studied. The mean age was 52.6 years and 78.6% were women. The relationship between LDL cholesterol levels and incidence of MACE was nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.72). No significant increase in CV risk was observed between the lowest quintile of LDL cholesterol levels (≤91.0 mg/dl) and the second, third, or fourth quintiles, whereas the highest quintile (>190.0 mg/dl) conveyed a 40% increase in risk of MACE (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.17-1.68). The relationship between HDL cholesterol levels and incidence of MACE was also nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.39). Compared to the lowest quintile of HDL cholesterol levels, each successive quintile was associated with a reduced risk of MACE (HR 0.45, 95% CI 0.48-0.72 for lowest quintile [≤43.0 mg/dl] versus highest quintile [>71.0 mg/dl]).The complex relationship between LDL cholesterol levels, HDL cholesterol levels, and risk of MACE was nonlinear in RA patients and also not statistically significantly different from that in an age- and sex-matched non-RA cohort.
High-resolution computed tomography scanning in α<sub>1</sub>-antitrypsin deficiency: relationship to lung function and health status
Authors: L.J. Dowson, P.J. Guest, S.L. Hill, R.L. Holder, R.A. Stockley
Journal: European Respiratory Journal (2001)

The development of computed tomography (CT) has enabled emphysema to be assessed noninvasively. Objective quantification of lung density correlates well with lung function in patients with chronic obstructive pulmonary disease and has been shown to be a sensitive tool for monitoring disease progression. In order to determine the clinical impact of changes seen on high-resolution computed tomography (HRCT), the relationship between the objective quantification of emphysema on HRCT, lung function and health status in 111 patients with alpha1-antitrypsin deficiency was examined (PiZ). The degree of HRCT scan abnormality correlated well (p<0.001 for all comparisons) with forced expiratory volume in one second (r = -0.60- -0.75), specific airway conductance (r = -0.67-0.76), residual volume/total lung capacity (r = 0.46-0.58) and transfer factor of the lung for carbon monoxide (r = -0.64- -0.81). In addition, the CT scans correlated (p<0.001) with health status as assessed by the St. George's Respiratory Questionnaire (SGRQ total: r = -0.38-0.50) and the Short-Form health survey (e.g. physical functioning: r = -0.39-0.54). In summary, other workers have shown high-resolution computed tomography to be a sensitive indicator of disease progression. This study confirms the relationship between high-resolution computed tomography and lung physiology, and suggests the relationship is even stronger in patients with predominantly lower zone pan-lobular emphysema than in usual chronic obstructive pulmonary disease. High-resolution computed tomography also relates to patients disability and impairment as defined by health status questionnaires and, therefore, should be considered as an alternative outcome measure particularly in alpha1-antitrypsin deficiency.
Potassium balance and the control of renin secretion
Authors: Jean E. Sealey, Irwin Clark, Marcia B. Bull, John H. Laragh
Journal: Journal of Clinical Investigation (1970)

Plasma renin activity and renin substrate were measured in nine groups of rats which were maintained for 7 wk on diets in which the proportions of sodium and potassium were varied. Balance data indicated that the highest dietary intake of potassium employed (92 mEq K(+)/100 g food) consistently induced sodium depletion. With less consistency, the highest sodium intake employed (52 mEq Na(+)/100 g food) tended to induce potassium depletion.In accordance with previous reports, sodium deprivation induced significant increases in plasma renin activity. But the present results indicated that changes in potassium intake exerted a highly significant modulating influence on this characteristic response. The results describe an inverse relationship between potassium administration and the concurrent level of plasma renin activity. The highest serum renin levels of all occurred in the potassium-depleted animals and the usual renin response to sodium deprivation was virtually abolished in the presence of a high potassium diet. Neither the suppressing effect of K(+) administration nor the stimulating effect of K(+) depletion on plasma renin activity could be explained in terms of any predicted changes in aldosterone secretion or observed changes in sodium balance. Therefore, the effect seems to be mediated by a direct influence of potassium ions on renal renin secretion, perhaps via induced changes in sodium load to the macula densa.These studies point to an important role for potassium in the regulation of renin secretion. The results in turn raise the possibility that renin secretion per se may be importantly involved in effecting potassium conservation and potassium elimination. The means by which these interactions are finally mediated remain to be clarified.
Inhaled phosphodiesterase type 5 inhibitors restore chloride transport in cystic fibrosis mice
Authors: B. Lubamba, J. Lebacq, G. Reychler, E. Marbaix, P. Wallemacq, P. Lebecque, T. Leal
Journal: European Respiratory Journal (2010)

Sildenafil and vardenafil, two selective inhibitors of phosphodiesterase type 5 (PDE5) are able, when applied by intraperitoneal injection, to activate chloride transport in cystic fibrosis (CF) mice homozygous for the F508del mutation. Oral treatment with the drugs may be associated with adverse haemodynamic effects. We hypothesised that inhaled PDE5 inhibitors are able to restore ion transport in F508del CF airway epithelium. We developed a restraint-free mouse chamber for inhalation studies. PDE5 inhibitors were nebulised for 15 min at concentrations adjusted from recommended therapeutic oral doses for male erectile dysfunction. We measured in vivo nasal transepithelial potential difference 1 h after a single inhalation of sildenafil, vardenafil or tadalafil in F508del CF and normal homozygous mice. After nebulisation with the drugs in F508del mice, chloride transport, evaluated by perfusing the nasal mucosa with chloride-free buffer containing amiloride followed by forskolin, was normalised; the forskolin response was increased, with the largest values being observed with tadalafil and intermediate values with vardenafil. No detectable effect was observed on sodium conductance. Our results confirm the role of PDE5 inhibitors in restoring chloride transport function of F508del CF transmembrane conductance regulator protein and highlight the potential of inhaled sildenafil, vardenafil and tadalafil as a therapy for CF.
Vascular bound recombinant extracellular superoxide dismutase type C protects against the detrimental effects of superoxide radicals on endothelium-dependent arterial relaxation.
Authors: T Abrahamsson, U Brandt, S L Marklund, P O Sjöqvist
Journal: Circulation Research (1992)

Extracellular superoxide dismutase type C (EC-SOD C) is a secretory SOD isoenzyme that, in vivo, is bound to heparan sulfate proteoglycans in the glycocalyx of various cell types (e.g., endothelial cells) and in the connective tissue matrix. The aim of this study was to investigate the efficacy of vascular bound EC-SOD C in protecting arterial relaxation mediated by endothelium-derived relaxing factor (EDRF) against the inhibitory effects of superoxide radicals. For comparison, the effect of CuZn SOD was also studied. This SOD isoenzyme lacks affinity toward heparan sulfate and does not bind to cell surfaces. Rings from rabbit aorta were mounted in an organ bath and acetylcholine-induced endothelium-dependent relaxation was then studied in preparations precontracted with phenylephrine. Pyrogallol (10(-4) M), used to generate superoxide radicals, reduced the maximal relaxant effect of acetylcholine from about 65% to 25%. When present in the buffer throughout the experiment, CuZn SOD and EC-SOD C caused a concentration-dependent prevention of the pyrogallol effect on EDRF-mediated relaxation, with a half-maximal effect at about 100 units/ml (KO2 assay). In a second set of experiments, the arterial rings were preincubated with 8,000 units/ml CuZn SOD (50 micrograms/ml) or EC-SOD C (69 micrograms/ml) during 30 minutes, followed by washing, before the effect of pyrogallol on EDRF-mediated relaxation was studied in SOD-free buffer.(ABSTRACT TRUNCATED AT 250 WORDS)
Obstructive sleep apnoea.
Authors: S G McNamara, R R Grunstein, C E Sullivan
Journal: Thorax (1993)

Of 49 patients undergoing operation for benign spontaneous pneumothorax, 28 (57%) were found to have a sharp first or second rib. In a series of 100 patients undergoing thoracotomy for other conditions, only eight (8%) were found to have a sharp rib. The association between sharp ribs, apical scars and bullae, and spontaneous pneumothorax is discussed.
The Effect of Vancomycin and Third-Generation Cephalosporins on Prevalence of Vancomycin-Resistant Enterococci in 126 U.S. Adult Intensive Care Units
Authors: Scott K. Fridkin, Jonathan R. Edwards, Jeanne M. Courval, Holly Hill, Fred C. Tenover, Rachel Lawton, Robert P. Gaynes, John E. McGowan
Journal: Annals of Internal Medicine (2001)

Patient-specific risk factors for acquisition of vancomycin-resistant enterococci (VRE) among hospitalized patients are becoming well defined. However, few studies have reported data on the institutional risk factors, including rates of antimicrobial use, that predict rates of VRE. Identifying modifiable institutional factors can advance quality-improvement efforts to minimize hospital-acquired infections with VRE.To determine the independent importance of any association between antimicrobial use and risk factors for nosocomial infection on rates of VRE in intensive care units (ICUs).Prospective ecologic study.126 adult ICUs from 60 U.S. hospitals from January 1996 through July 1999.All patients admitted to participating ICUs.Monthly use of antimicrobial agents (defined daily doses per 1000 patient-days), nosocomial infection rates, and susceptibilities of all tested enterococci isolated from clinical cultures.Prevalence of VRE (median, 10%; range, 0% to 59%) varied by type of ICU and by teaching status and size of the hospital. Prevalence of VRE was strongly associated with VRE prevalence among inpatient non-ICU areas and outpatient areas in the hospital, ventilator-days per 1000 patient-days, and rate of parenteral vancomycin use. In a weighted linear regression model controlling for type of ICU and rates of VRE among non-ICU inpatient areas, rates of vancomycin use (P < 0.001) and third-generation cephalosporin use (P = 0.02) were independently associated with VRE prevalence.Higher rates of vancomycin or third-generation cephalosporin use were associated with increased prevalence of VRE, independent of other ICU characteristics and the endemic VRE prevalence elsewhere in the hospital. Decreasing the use rates of these antimicrobial agents could reduce rates of VRE in ICUs.
Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils
Authors: Hyunsil Han, Alexander Stessin, Julia Roberts, Kenneth Hess, Narinder Gautam, Margarita Kamenetsky, Olivia Lou, Edward Hyde, Noah Nathan, William A. Muller, Jochen Buck, Lonny R. Levin, Carl Nathan
Journal: The Journal of Experimental Medicine (2005)

Through chemical screening, we identified a pyrazolone that reversibly blocked the activation of phagocyte oxidase (phox) in human neutrophils in response to tumor necrosis factor (TNF) or formylated peptide. The pyrazolone spared activation of phox by phorbol ester or bacteria, bacterial killing, TNF-induced granule exocytosis and phox assembly, and endothelial transmigration. We traced the pyrazolone's mechanism of action to inhibition of TNF-induced intracellular Ca2+ elevations, and identified a nontransmembrane (“soluble”) adenylyl cyclase (sAC) in neutrophils as a Ca2+-sensing source of cAMP. A sAC inhibitor mimicked the pyrazolone's effect on phox. Both compounds blocked TNF-induced activation of Rap1A, a phox-associated guanosine triphosphatase that is regulated by cAMP. Thus, TNF turns on phox through a Ca2+-triggered, sAC-dependent process that may involve activation of Rap1A. This pathway may offer opportunities to suppress oxidative damage during inflammation without blocking antimicrobial function.
Stand up for health—avoiding sedentary behaviour might lengthen your telomeres: secondary outcomes from a physical activity RCT in older people
Authors: Per Sjögren, Rachel Fisher, Lena Kallings, Ulrika Svenson, Göran Roos, Mai-Lis Hellénius
Journal: British Journal of Sports Medicine (2014)

Background Telomere length has been associated with a healthy lifestyle and longevity. However, the effect of increased physical activity on telomere length is still unknown. Therefore, the aim was to study the relationship between changes in physical activity level and sedentary behaviour and changes in telomere length. Methods Telomere length was measured in blood cells 6 months apart in 49, 68-year-old, sedentary, overweight individuals taking part in a randomised controlled physical activity intervention trial. The intervention group received individualised physical activity on prescription. Physical activity was measured with a 7-day diary, questionnaires and a pedometer. Sitting time was measured with the short version of The International Physical Activity Questionnaire. Results Time spent exercising as well as steps per day increased significantly in the intervention group. Reported sitting time decreased in both groups. No significant associations between changes in steps per day and changes in telomere length were noted. In the intervention group, there was a negative correlation between changes in time spent exercising and changes in telomere length (rho=−0.39, p=0.07). On the other hand, in the intervention group, telomere lengthening was significantly associated with reduced sitting time (rho=−0.68, p=0.02). Conclusions Reduced sitting time was associated with telomere lengthening in blood cells in sedentary, overweight 68-year-old individuals participating in a 6-month physical activity intervention trial.