tbuckley/cabot-search huggingface dataset:
Long-term effects of therapy on respiratory health
Authors: C Fuhrman, P Ernst, F Kauffmann
Journal: European Respiratory Journal (1996)

Only scant information is available on the long-term consequences to respiratory health of treatment with bronchodilators and oral corticosteroids. In the present study, we aimed to gain more information about these consequences. We examined 712 men working in the Paris area, by means of a subjective assessment of whether their respiratory health worsened or improved from 1960 to 1972, the decline in forced expiratory volume in one second (FEV1) over this time-period, and mortality from 1972 to 1992, in relation to respiratory therapy dispensed during a 2 year period in 1970-1971, as recorded in social security reimbursement records. As expected, subjects with respiratory symptoms or airflow limitation were more likely to have been prescribed respiratory therapy. After accounting for the effect of lung function level and smoking, subjects dispensed inhaled beta-agonists were likely to feel their condition had worsened and had a greater decline in FEV1 from 1960 to 1972. Among subjects with airflow limitation who reported asthma or persistent wheeze, having been dispensed oral corticosteroids on an intermittent basis was associated with improved survival (relative risk (RR) 0.32; 95% confidence interval (95% CI): 0.10-0.91) after adjusting for FEV1 level and smoking category. Our results add to the evidence that regular use of beta-agonist bronchodilators may be associated with adverse effects on respiratory health, whilst intermittent use of corticosteroids may be of long-term benefit.
Microalbuminuria, Preeclampsia, and Preterm Delivery in Pregnant Women With Type 1 Diabetes
Authors: Dorte M. Jensen, Peter Damm, Per Ovesen, Lars Mølsted-Pedersen, Henning Beck-Nielsen, Jes G. Westergaard, Margrethe Moeller, Elisabeth R. Mathiesen
Journal: Diabetes Care (2009)

OBJECTIVE To study the association between microalbuminuria and development of preeclampsia and preterm delivery in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS This was a population-based prospective study in 846 normoalbuminuric or microalbuminuric women with type 1 diabetes without antihypertensive treatment in early pregnancy. Data were collected prospectively by one to three caregivers in each center and reported to a central registry. RESULTS The prevalence of microalbuminuria in the first trimester was 10%, median diabetes duration was 11 years, and third-trimester A1C was 6.6%. The frequencies of preeclampsia and preterm delivery before 34 weeks in the microalbuminuric group were 40 and 13%, both significantly higher than those in the normoalbuminuric group (12 and 6%, respectively, P &amp;lt; 0.001). After adjustments for possible confounders, significant predictors for development of preeclampsia were microalbuminuria (odds ratio 4.0 [95% CI]), nulliparity (3.1 [1.9–5.1]), and third-trimester A1C (1.3 [1.1–1.5] per 1% increase). Delivery before 34 weeks was associated with early microalbuminuria in univariate analyses, but in multivariate analyses A1C was the only significant predictor of this outcome. Preeclampsia was associated with a threefold higher risk of delivery before 34 weeks. CONCLUSIONS The presence of microalbuminuria in early pregnancy is associated with a fourfold increased risk of developing preeclampsia. A1C values during pregnancy are highly predictive of both preeclampsia and preterm delivery. Future research with antihypertensive treatment in normotensive, microalbuminuric pregnant women to prevent preeclampsia is proposed.
Oxidized phosphatidylserine–CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells
Authors: Michael E. Greenberg, Mingjiang Sun, Renliang Zhang, Maria Febbraio, Roy Silverstein, Stanley L. Hazen
Journal: The Journal of Experimental Medicine (2006)

The phagocytosis of apoptotic cells within an organism is a critical terminal physiological process in programmed cell death. Evidence suggests that apoptotic cell engulfment and removal by macrophages is facilitated by phosphatidylserine (PS) displayed at the exofacial surface of the plasma membrane; however, neither the macrophage receptors responsible for PS recognition, nor characterization of the PS molecular species potentially involved, have been clearly defined. We show that the class B scavenger receptor CD36 plays an essential role in macrophage clearance of apoptotic cells in vivo. Further, macrophage recognition of apoptotic cells via CD36 is shown to occur via interactions with membrane-associated oxidized PS (oxPS) and, to a lesser extent, oxidized phosphatidylcholine, but not nonoxidized PS molecular species. Mass spectrometry analyses of oxPS species identify structures of candidate ligands for CD36 in apoptotic membranes that may facilitate macrophage recognition. Collectively, these results identify oxPS–CD36 interactions on macrophages as potential participants in a broad range of physiologic processes where macrophage-mediated engulfment of apoptotic cells is involved.
Coding sports injury surveillance data: has version 10 of the Orchard Sports Injury Classification System improved the classification of sports medicine diagnoses?
Authors: L E Hammond, J Lilley, W J Ribbans
Journal: British Journal of Sports Medicine (2008)

To compare versions 8 and 10 of the Orchard Sports Injury Classification System (OSICS) to determine whether the revised version of OSICS has improved its use in a sports medicine setting, and to assess the inter-rater reliability of OSICS-10.Injury surveillance data, gathered over a 2 year period in professional football, cricket and rugby union to produce 335 diagnoses, were coded with both OSICS-8 and OSICS-10. Code-diagnosis agreement was assessed for OSICS-8 in terms of whether a diagnosis was codeable or noncodeable, and for OSICS-10 by evaluating the highest available OSICS-10 tier of coding. Eight clinicians coded a list of 20 diagnoses, comprising a range of pathologies to all gross anatomical regions, which were compared to assess inter-rater reliability.All diagnoses could be assigned an appropriate code with OSICS-10, compared with 87% of diagnoses that could be assigned an OSICS-8 code. Contusions comprised almost half of OSICS-8 noncodeable diagnoses. OSICS-10 tier 2 codes accounted for 20% of diagnoses coded with the updated system. Of these 20%, almost half contained a more detailed diagnosis that did not have an available OSICS-10 tier 3 or 4 code. Inter-rater reliability increased with decreasing diagnostic detail, with an overall level shown to be moderate (k = 0.56).OSICS-10 is a more encompassing system than OSICS-8 to use in classifying sports medicine diagnoses, and has a moderate level of inter-rater reliability. Further minor revision may be required to address lack of detail in some strain, effusion and contusion codes.
Diabetes-induced alterations in atrial natriuretic peptide gene expression in Wistar-Kyoto and spontaneously hypertensive rats.
Authors: H Matsubara, Y Mori, J Yamamoto, M Inada
Journal: Circulation Research (1990)

We investigated the effects of streptozotocin-induced diabetes on atrial natriuretic peptide (ANP) synthesis, hemodynamic parameters, blood volume, and histopathology, as well as the reversibility of such effects with insulin therapy in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). The biatrial ANP messenger RNA (mRNA) levels in the diabetic WKY rats increased by 16-17% compared with those in the age-matched WKY rats at 12 weeks after the onset of diabetes, whereas their ventricular ANP mRNA levels showed increases of 190% in left ventricles and 160% in right ventricles at 8 weeks. In the diabetic SHRs, the left atrial ANP mRNA levels increased by 36% compared with those in the age-matched SHRs, as early as 4 weeks after diabetes onset. Their ventricular ANP mRNA levels also showed 80-82% increases in left and right ventricles at 4 weeks. In proportion to changes in cardiac ANP synthesis, the biventricular end-diastolic pressures were significantly elevated at 8 weeks in the diabetic WKY rats and at 4 weeks in the diabetic SHRs. The blood volume significantly increased at 8 weeks in the diabetic WKY rats and remained higher thereafter, whereas it did not change in the diabetic SHRs throughout the experimental period. The left ventricular peak dP/dt was depressed in the 8-week diabetic SHRs, whereas in the diabetic WKY rats, its depression was observed at 12 weeks after diabetes onset. Histopathological studies showed that diabetic changes in ANP synthesis and hemodynamic parameters described above occurred before the cardiomyopathic histological changes. Cardiac ANP synthesis in the diabetic rats completely reverted to control levels after insulin therapy, accompanied by normalization of hemodynamic parameters. The present study indicates that 1) ANP synthesis is significantly augmented in the streptozotocin-induced diabetic rat compared with that in the normal rat, and the combination of diabetes and hypertension produces an earlier and greater effect in stimulating cardiac ANP synthesis than does either disease alone; 2) an elevation in the intraventricular filling pressure that occurs before observable cardiomyopathic histopathological alterations might be involved partially in the augmented ANP synthesis; and 3) the reversibility with insulin therapy suggests that the streptozotocin-induced alterations observed in cardiac ANP synthesis and hemodynamics result from insulin-deficient diabetes mellitus, not from cardiac toxicity of streptozotocin.
The Involvement of Bax in Zinc-Induced Mitochondrial Apoptogenesis in Malignant Prostate Cells
Authors: Pei Feng, Tieluo Li, Zhixin Guan, Renty B Franklin, Leslie C Costello
Journal: Molecular Cancer (2008)

The development and progression of prostate cancer requires the transformation of normal zinc-accumulating epithelial cells to malignant cells that have lost the ability to accumulate zinc. This metabolic transformation is essential so that the tumor suppressive effects of zinc can be eliminated and the malignant process can proceed. One of the major effects of zinc is its prevention of prostate cell growth by its induction of apoptosis. The accumulation of cellular zinc has a direct effect on the mitochondria that results in the release of cytochrome c, which initiates the caspase cascade that leads to apoptosis. This effect is associated with the mitochondrial pore-forming process, but the mechanism by which zinc induces the release of cytochrome c and induces mitochondrial apoptogenesis has not been resolved. The present report provides for the first time information that implicates Bax in the zinc induction of mitochondrial apoptogenesis.The effects of zinc treatment on the Bax levels of PC-3 cells and on the mitochondria were determined. The exposure of isolated mitochondria to zinc results in an increase in membrane bound Bax, which is due to the mitochondrial insertion of endogenous resident Bax. The mitochondrial Bax/Bcl-2 ratio is increased by zinc treatment. Zinc treatment of PC-3 cells also increases the mitochondrial level of Bax. In addition, zinc treatment increases the cellular level of Bax and the cellular Bax/Bcl2 ratio. Down regulation of Bax in PC-3 cells eliminates the zinc induction of apoptosis. The increase in cellular Bax level appears to involve zinc induction of Bax gene expression.This report extends and confirms that physiological levels of zinc induce apoptosis in prostate cells. The study provides evidence that zinc is directly involved in facilitating a Bax-associated pore formation process that initiates mitochondrial apoptogenesis. This is enhanced by an additional effect of zinc on increasing the cellular level of Bax. To avoid the anti-tumor apoptogenic effects of zinc, the malignant cells in prostate cancer posses genetic/metabolic adaptations that prevent the cellular accumulation of zinc.
Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
Authors: Christine I. Chen, P. Leif Bergsagel, Harminder Paul, Wei Xu, Anthea Lau, Nimisha Dave, Vishal Kukreti, Ellen Wei, Chungyee Leung-Hagesteijn, Zhi Hua Li, Joseph Brandwein, Mariela Pantoja, James Johnston, Spencer Gibson, Tiffany Hernandez, David Spaner, Suzanne Trudel
Journal: Journal of Clinical Oncology (2010)

Purpose Lenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant cell growth. Based on encouraging reports of lenalidomide in relapsed and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line use of single-agent lenalidomide in CLL. Patients and Methods Using a starting dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis, fatal sepsis) in the first two patients enrolled. The study was halted and the protocol amended to a more conservative regimen: starting dose of lenalidomide 2.5 mg with monthly escalations to a target dose of 10 mg, and extended tumor lysis prophylaxis and monitoring. Gene expression profiles from patient samples before and after 7 days of lenalidomide were performed. Results Twenty-five patients were enrolled on the amended protocol. No further tumor lysis events were reported. Tumor flare was common (88%) but mild. Grade 3 to 4 neutropenia occurred in 72% of patients, with only five episodes of febrile neutropenia. The overall response rate was 56% (no complete responses). Although rapid peripheral lymphocyte reductions were observed, rebound lymphocytoses during the week off-therapy were common. Lenalidomide-induced molecular changes enriched for cytoskeletal and immune-related genes were identified. Conclusion Lenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL.
Preventing Ventilator-Associated Pneumonia
Authors: Jean Chastre
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Glomerular-Specific Gene Excision In Vivo
Authors: Vera Eremina, Mark Andrew Wong, Shiying Cui, Lois Schwartz, Susan E. Quaggin
Journal: Journal of the American Society of Nephrology (2002)

Podocytes (glomerular visceral epithelial cells) are highly specialized cells that are found in the renal glomerulus and make up a major portion of the filtration barrier between the blood and urinary spaces. Recently, the identification of a number of genes responsible for both autosomal dominant and recessive forms of human nephrotic syndrome has provided insight into a number of molecules responsible for unique features of the podocyte such as the slit diaphragms. Despite these major advances in our understanding of podocyte biology, the function of many genes expressed in the podocyte remains unknown. Targeted gene disruption using homologous recombination in murine embryonic stem cells (ES cells) is a powerful tool to determine the biologic function of genes in vivo. However, resulting embryonic lethal or pleiotropic phenotypes often preclude the analysis of genes in specific renal cell types. To overcome this problem, a glomerular-specific Cre-recombinase transgenic murine line under the control of the Nphs1 (nephrin) promoter (Neph-Cre) was generated. This article reports successful Cre-mediated excision of a 'floxed' transgene specifically in podocytes in vivo. This murine founder line represents a powerful new tool for the manipulation of the expression of genes in podocytes and will provide valuable insight into podocyte biology in the whole animal.
Kidney function and risk of cardiovascular disease and mortality in women: a prospective cohort study
Authors: T. Kurth, P. E d. Jong, N. R Cook, J. E Buring, P. M Ridker
Journal: BMJ (2009)

<b>Objective</b> To evaluate the association of kidney function with cardiovascular disease and mortality among apparently healthy women. <b>Design</b> Prospective cohort study. <b>Setting</b> Women's Health Study, United States. <b>Participants</b> 27 939 female health professionals aged ≥45 who were free of cardiovascular disease and other major disease and who provided a blood sample at study entry. <b>Main outcome measures</b> Time to cardiovascular disease (non-fatal stroke, non-fatal myocardial infarction, coronary revascularisation procedures, or death from cardiovascular cause), specific cardiovascular disease events, and all-cause mortality. End points were confirmed after review of medical records and death certificates. <b>Results</b> Glomerular filtration rate (GFR) was estimated with the abbreviated Modification of Diet in Renal Disease Study equation. At baseline, 1315 (4.7%) women had GFR &lt;60 ml/min/1.73 m<sup>2</sup>. During 12 years of follow-up, 1199 incident cardiovascular disease events and 856 deaths (179 from cardiovascular disease) occurred. Compared with women with GFR ≥90 ml/min/1.73 m<sup>2</sup>, the multivariable adjusted hazard ratios for any first cardiovascular disease were 0.95 (95% CI 0.83 to 1.08), 0.84 (0.70 to 1.00), and 1.00 (0.79 to 1.27) among women with GFR of 75-89.9, 60-74.9, and &lt;60 ml/min/1.73 m<sup>2</sup>, respectively; the equivalent hazard ratios for all cause mortality were 0.93 (0.79 to 1.09), 1.03 (0.85 to 1.26), and 1.09 (0.83 to 1.45). Similar null findings were observed for myocardial infarction, stroke, coronary revascularisation, and non-cardiovascular death. However, an increased risk of death from cardiovascular disease was found among women with GFR &lt;60 ml/min/1.73 m<sup>2</sup> (hazard ratio 1.68 (1.02 to 2.79)). <b>Conclusions</b> In this large cohort of women, a glomerular filtration rate &lt;60 ml/min/1.73 m<sup>2</sup> was associated with increased risk of cardiovascular disease death but not other cardiovascular disease events or non-cardiovascular disease mortality. We observed no increase in risk of any of the outcomes among women with less severe impairment of kidney function.
The Role of Osteopontin in the Development of Albuminuria
Authors: Johan Lorenzen, Rajshree Shah, Alisha Biser, Serban A. Staicu, Thiruvur Niranjan, Ana Maria Garcia, Antje Gruenwald, David B. Thomas, Ibrahim F. Shatat, Katarine Supe, Robert P. Woroniecki, Katalin Susztak
Journal: Journal of the American Society of Nephrology (2008)

Several gene array studies have suggested that osteopontin (Opn) expression strongly correlates with albuminuria and glomerular disease. Urinary Opn concentration and kidney Opn immunoreactivity were found to be increased in patients with steroid-sensitive nephrotic syndrome. In addition, renal Opn mRNA was increased in the Ins2Akita mouse model of type 1 diabetic nephropathy, in the LPS-induced albuminuria model, and in glomeruli of puromycin aminonucleotide–induced nephrotic rats. Opn knockout mice did not develop albuminuria in response to LPS injection, and Opn knockout mice were protected from diabetes-induced albuminuria and mesangial expansion. In the glomerulus, Opn immunostaining was increased specifically in podocytes. Treatment of podocytes with recombinant Opn activated the NF-κB pathway, increased expression of urokinase plasminogen activator and matrix metalloproteinases 2 and 9, and increased podocyte motility. Taken together, these results indicate that Opn plays an important role in the development of albuminuria, possibly by modulating podocyte signaling and motility.
Diabetes in Residential Care Facilities: United States, 2010
Authors: Helaine E. Resnick, Gregory L. Foster
Journal: Diabetes Care (2013)

Although national data show that 25% of nursing home residents and 31% of home health patients have diabetes (1,2), little is known about diabetes among older adults living in residential care facilities (RCFs). The 2010 National Survey of Residential Care Facilities (3) provides nationally representative data on this population. Resident information, including demographics, health conditions, and physical and cognitive functioning was collected from respondents who were most knowledgeable about sampled residents. Respondents included facility directors, registered nurses, licensed practical nurses, and personal care aides. Analyses were conducted using SUDAAN 10.0 software to account for the strata, cluster, and weight variables that define the complex sampling approach in the National Survey of Residential Care Facilities.

Of the 733,000 individuals in RCFs, 17% …
Prognostic Value of Changes in Health-Related Quality of Life Scores During Curative Treatment for Esophagogastric Cancer
Authors: Therese Djärv, Chris Metcalfe, Kerry N.L. Avery, Pernilla Lagergren, Jane M. Blazeby
Journal: Journal of Clinical Oncology (2010)

Purpose Accumulating evidence suggests that health-related quality of life (HRQL) data before treatment predict survival, but the prognostic value of changes in HRQL scores after treatment is unknown. The aim of this study was to explore whether changes in HRQL scores in esophagogastric cancer predict survival. Patients and Methods Consecutive patients undergoing curative treatment completed HRQL questionnaires (EORTC QLQ-C30) at baseline and after six months and were followed up for at least five years. Cox proportional hazard models with adjustments assessed associations between baseline HRQL and survival and between changes in HRQL before and after treatment and survival. Results Overall, 216 patients initiated curative therapy, of whom169 completed treatment and survived 6 months. Of these, 132 (7%) had two complete HRQL assessments. Analyses adjusted for age, sex, performance status, tumor stage, and disease site revealed that a 10-point poorer dyspnea score at baseline was significantly associated with an 18% higher risk of death. Additional analyses to adjust for baseline HRQL and treatment showed that a 10-point change in physical function (hazard ratio [HR], 0.85; 95% CI, 0.76 to 0.96; P = .007), pain (HR, 1.20; 95% CI, 1.09 to 1.33; P &lt; .001), and fatigue (HR, 1.16; 95% CI, 1.04 to 1.30; P = .009) scores was associated with better survival. Conclusion This exploratory study found longer survival beyond the 6 months after starting treatment to be associated with fewer problems with dyspnea before treatment and better recovery of physical function, pain, and fatigue after treatment. More research to confirm these findings and understand the results is needed.