tbuckley/cabot-search huggingface dataset:
Standards of care for occupational asthma: an update
Authors: David Fishwick, Christopher Michael Barber, Lisa M Bradshaw, Jon G Ayres, Richard Barraclough, Sherwood Burge, Jonathan M Corne, Paul Cullinan, Timothy Laszlo Frank, David Hendrick, Jennifer Hoyle, Andrew D Curran, Robert Niven, Tony Pickering, Peter Reid, Alastair Robertson, Chris Stenton, Christopher J Warburton, Paul J Nicholson
Journal: Thorax (2011)

The British Thoracic Society (BTS) Standards of Care (SoC) Committee produced a standard of care for occupational asthma (OA) in 2008, based on a systematic evidence review performed in 2004 by the British Occupational Health Research Foundation (BOHRF).BOHRF updated the evidence base from 2004-2009 in 2010.This article summarises the changes in evidence and is aimed at physicians, nurses and other healthcare professionals in primary and secondary care, occupational health and public health and at employers, workers and their health, safety and other representatives.Various recommendations and evidence ratings have changed in the management of asthma that may have an occupational cause.
Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus.
Authors: J H van Es, F H Gmelig Meyling, W R van de Akker, H Aanstoot, R H Derksen, T Logtenberg
Journal: The Journal of Experimental Medicine (1991)

The processes that govern the generation of pathogenic anti-DNA autoantibodies in human systemic lupus erythematosus (SLE) are largely unknown. Autoantibodies may arise as a consequence of polyclonal B cell activation and/or antigen-driven B cell activation and selection. The role of these processes in humoral autoimmunity may be studied by molecular genetic analysis of immunoglobulin (Ig) variable (V) regions of antibodies that are characteristic of SLE. We have analyzed the gene elements that encode a high affinity, IgG anti-double-stranded DNA autoantibody secreted by a monoclonal Epstein-Barr virus (EBV)-transformed cell line derived from a patient with active SLE. In addition, we have identified, cloned, and sequenced the germline counterparts of the VH and VL genes expressed in this autoantibody. The comparison of both sets of gene elements shows that the autoantibody VH and VL regions harbor numerous somatic mutations characteristic of an antigen-driven immune response. The light chain expressed in this autoantibody is a somatically mutated variant of the kv325 germline gene that is frequently associated with paraproteins having autoantibody activity and with Ig molecules produced by malignant B cells that express the CD5 antigen. Furthermore, the utilized DH segment has been repeatedly found in multireactive, low affinity IgM anti-DNA autoantibodies from SLE patients and healthy individuals. These results suggest that pathogenic IgG anti-DNA autoantibodies in human SLE may arise through antigen-driven selection of somatic mutations in the gene elements that frequently encode multireactive IgM autoantibodies.
A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts
Authors: Michael Malinchoc, Patrick S. Kamath, Fredric D. Gordon, Craig J. Peine, Jeffrey Rank, Pieter C.J. ter Borg
Journal: Hepatology (2000)

Transjugular intrahepatic portosystemic shunts (TIPS) may worsen liver function and decrease survival in some patients. The Child-Pugh classification has several drawbacks when used to determine survival in such patients. The survival of 231 patients at 4 medical centers within the United States who underwent elective TIPS was studied to develop statistical models to (1) predict patient survival and (2) identify those patients whose liver-related mortality post-TIPS would be 3 months or less. Among these elective TIPS patients, 173 had the procedure for prevention of variceal rebleeding and 58 for treatment of refractory ascites. Death related to liver disease occurred in 110 patients, 70 within 3 months. Cox proportional-hazards regression identified serum concentrations of bilirubin and creatinine, international normalized ratio for prothrombin time (INR), and the cause of the underlying liver disease as predictors of survival in patients undergoing elective TIPS, either for prevention of variceal rebleeding or for treatment of refractory ascites. These variables can be used to calculate a risk score (R) for patients undergoing elective TIPS. Patients with R &gt; 1.8 had a median survival of 3 months or less. This model was superior to both the Child-Pugh classification, as well as the Child-Pugh score, in predicting survival. Using logistic regression and the same variables, we also developed a nomogram that indicates which patients survive less than 3 months. Finally, the model was validated among an independent set of 71 patients from the Netherlands. This Mayo TIPS model may predict early death following elective TIPS for either prevention of variceal rebleeding or for treatment of refractory ascites.
Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C
Authors: Michaela Auer-Grumbach, Andrea Olschewski, Lea Papić, Hannie Kremer, Meriel E McEntagart, Sabine Uhrig, Carina Fischer, Eleonore Fröhlich, Zoltán Bálint, Bi Tang, Heimo Strohmaier, Hanns Lochmüller, Beate Schlotter-Weigel, Jan Senderek, Angelika Krebs, Katherine J Dick, Richard Petty, Cheryl Longman, Neil E Anderson, George W Padberg, Helenius J Schelhaas, Conny M A van Ravenswaaij-Arts, Thomas R Pieber, Andrew H Crosby, Christian Guelly
Journal: Nature Genetics (2009)
Long-Term Follow-Up of a Prospective Study of Combined Modality Therapy for Stage I–II Indolent Non-Hodgkin’s Lymphoma
Authors: John F. Seymour, Barbara Pro, Lillian M. Fuller, John T. Manning, Fredrick B. Hagemeister, Jorge Romaguera, Maria A. Rodriguez, Chul S. Ha, Terry L. Smith, Ana Ayala, Mark Hess, James D. Cox, Fernando Cabanillas, Peter McLaughlin
Journal: Journal of Clinical Oncology (2003)

Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients.A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT.The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields.With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.
Inspiratory duty cycle responses to flow limitation predict nocturnal hypoventilation
Authors: H. Schneider, V. Krishnan, L. E. Pichard, S. P. Patil, P. L. Smith, A. R. Schwartz
Journal: European Respiratory Journal (2009)

Upper airway obstruction (UAO) can elicit neuromuscular responses that mitigate and/or compensate for the obstruction. It was hypothesised that flow-limited breathing elicits specific timing responses that can preserve ventilation due to increases in inspiratory duty cycle rather than respiratory rate. By altering nasal pressure during non-rapid eye movement (non-REM) sleep, similar degrees of UAO were induced in healthy males and females (n = 10 each). Inspiratory duty cycle, respiratory rate and minute ventilation were determined for each degree of UAO during non-REM sleep and compared with the baseline nonflow-limited condition. A dose-dependent increase in the inspiratory duty cycle and respiratory rate was observed in response to increasing severity of UAO. Increases in the inspiratory duty cycle, but not respiratory rate, helped to acutely maintain ventilation. Heterogeneity in these responses was associated with variable degrees of ventilatory compensation, allowing for the segregation of individuals at risk for hypoventilation during periods of inspiratory airflow limitation. Upper airway obstruction constitutes a unique load on the respiratory system. The inspiratory duty cycle, but not the respiratory rate, determine the individual's ability to compensate for inspiratory airflow limitation during sleep, and may represent a quantitative phenotype for obstructive sleep apnoea susceptibility.
A Control Model to Evaluate Pharmacotherapy for Allergic Rhinitis in Children
Authors: Gary Rachelefsky, Judith Rosen Farrar
Journal: JAMA Pediatrics (2013)

Although the question of whether early diagnosis and treatment of pediatric allergic rhinitis (AR) improve disease control is important, a more crucial question is whether we can evaluate the effect of treatment on disease control using an impairment-risk model.To conduct a systematic review evaluating application of a control model based on domains of impairment and risk (similar to that used for asthma) in pharmacotherapy for children with AR.We searched the MEDLINE and EMBASE databases (January 1, 1996, through May 31, 2012) for controlled studies lasting 2 weeks or longer in children with confirmed diagnoses of AR, including measures assessing impairment and/or risk of comorbid conditions.Sixteen controlled clinical trials, including more than 3000 children (aged 2-18 years) with AR (seasonal, n = 2290; perennial, n = 800), met the study criteria. All medication classes improved impairment related to AR, but between-treatment comparisons were limited because of different assessments. Intranasal steroids improved risk outcomes associated with asthma and obstructive sleep apnea. Small single studies suggested possible effects of oral antihistamines on asthma and sleep-disordered breathing. No risk data were available for nasal antihistamines or montelukast sodium.Treatment of AR, particularly with intranasal steroids, improves disease control in children by reducing disease-associated impairment and risk. All AR medications with proved efficacy probably improve impairment, paralleling symptom reduction. Intranasal steroids may reduce the likelihood of comorbidities that increase health care use. These observations, although limited by different protocols and outcomes measures among studies, support current practice recommendations. Studies that use standardized measures of impairment to permit better comparison and appropriate protocols for risk evaluation are needed.
The clinical potential of microRNAs
Authors: Anuradha Budhu, Junfang Ji, Xin W Wang
Journal: Journal of Hematology & Oncology (2010)

MicroRNAs are small noncoding RNAs that function to control gene expression. These small RNAs have been shown to contribute to the control of cell growth, differentiation and apoptosis, important features related to cancer development and progression. In fact, recent studies have shown the utility of microRNAs as cancer-related biomarkers. This is due to the finding that microRNAs display altered expression profiles in cancers versus normal tissue. In addition, microRNAs have been associated with cancer progression. In this review, the mechanisms to alter microRNA expression and their relation to cancer will be addressed. Moreover, the potential application of microRNAs in clinical settings will also be highlighted. Finally, the challenges regarding the translation of research involving microRNAs to the clinical realm will be discussed.
Improving chemotherapeutic drug penetration in tumors by vascular targeting and barrier alteration
Authors: Flavio Curnis, Angelina Sacchi, Angelo Corti
Journal: Journal of Clinical Investigation (2002)

Drug delivery and penetration into neoplastic cells distant from tumor vessels are critical for the effectiveness of solid-tumor chemotherapy. We have found that targeted delivery to tumor vessels of picogram doses of TNF-α (TNF), a cytokine able to alter endothelial barrier function and tumor interstitial pressure, enhances the penetration of doxorubicin in tumors in murine models. Vascular targeting was achieved by coupling TNF with CNGRC, a peptide that targets the tumor neovasculature. This treatment enhanced eight- to tenfold the therapeutic efficacy of doxorubicin, with no evidence of increased toxicity. Similarly, vascular targeting enhanced the efficacy of melphalan, a different chemotherapeutic drug. Synergy with chemotherapy was observed with 3–5 ng/kg of targeted TNF (intraperitoneally), about 106-fold lower than the LD50 and 105-fold lower than the dose required for nontargeted TNF. In addition, we have also found that targeted delivery of low doses of TNF to tumor vessels does not induce the release of soluble TNF receptors into the circulation. The delivery of minute amounts of TNF to tumor vessels represents a new approach for avoiding negative feedback mechanisms and preserving its ability to alter drug-penetration barriers. Vascular targeting could be a novel strategy for increasing the therapeutic index of chemotherapeutic drugs.
The Psychiatrist and Medical Home Care: Geriatric Psychiatry in the Harlem Community
Authors: SHELDON ZIMBERG
Journal: American Journal of Psychiatry (1971)

The author describes his experience as a psychiatric consultant to a medical home care program dealing largely with geriatric patients. His participation in the program included psychiatric evaluations in the patients' homes, case consultations, and staff educacation. The author also points out some of the additional possibilities for the further involvement of psychiatrists in such programs.
IL-32 and Streptococcus pyogenes cell wall fragments synergise for IL-1-dependent destructive arthritis via upregulation of TLR-2 and NOD2
Authors: B. Heinhuis, M. I. Koenders, F. A. van de Loo, P. L. E. M. van Lent, S.-H. Kim, C. A. Dinarello, L. A. B. Joosten, W. B. van den Berg
Journal: Annals of the Rheumatic Diseases (2010)

To investigate the potential synergism between interleukin (IL) 32γ and Streptococcus pyogenes cell wall (SCW) fragments in the development of destructive arthritis.An adenoviral vector encoding human IL-32γ (AdIL-32γ) was constructed and validated in HeLa cells. Fibroblast-like synoviocytes (FLS) were transduced with AdIL-32γ and stimulated with Toll-like receptor 2 (TLR-2) and nucleotide oligomerisation domain (NOD) 2 ligands. Expression levels of several proinflammatory cytokines, chemokines, matrix degrading enzymes, TLR-2 and NOD2 were measured by quantitative real-time PCR. Furthermore, IL-6 and CXCL8 protein levels were determined. In-vivo synergy between IL-32γ and SCW was studied by intra-articular injection of AdIL-32γ in C57Bl/6 mice followed by SCW injection. The contribution of endogenous IL-1 was assessed in mice deficient for both IL-1α and IL-1β.IL-32γ synergise with TLR-2/NOD2 ligands to induce proinflammatory cytokines, chemokines and matrix degrading enzymes in AdIL-32γ-transduced FLS. In mice, AdIL-32γ transduction followed by the injection of SCW displayed aggravated joint inflammation and cartilage destruction. However, IL-1-deficient mice were protected against IL-32γ/SCW-induced joint changes, indicating a requirement for IL-1 in downstream events triggered by IL-32γ plus SCW. To elucidate the synergistic mechanism, the authors investigated the expression of two pattern recognition receptors involved in sensing SCW fragments. TLR-2 and NOD2 receptor expression was enhanced by IL-32γ and Pam3Cys/muramyl dipeptide stimulation in FLS.Here the authors show that IL-32γ aggravates SCW-induced arthritis by the upregulation of TLR-2/NOD2 expression and promotes severe joint erosion in an IL-1-dependent fashion. Targeting of IL-32γ may provide a novel therapy to prevent destructive arthritis.
Cured Meat Consumption, Lung Function, and Chronic Obstructive Pulmonary Disease among United States Adults
Authors: Rui Jiang, David C. Paik, John L. Hankinson, R. Graham Barr
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Cured meats are high in nitrites. Nitrites generate reactive nitrogen species that may cause nitrative and nitrosative damage to the lung resulting in emphysema.To test the hypothesis that frequent consumption of cured meats is associated with lower lung function and increased odds of chronic obstructive pulmonary disease (COPD).Cross-sectional study of 7,352 participants in the Third National Health and Nutrition Examination Survey, 45 years of age or more, who had adequate measures of cured meat, fish, fruit, and vegetable intake, and spirometry.After adjustment for age, smoking, and multiple other potential confounders, frequency of cured meat consumption was inversely associated with FEV(1) and FEV(1)/FVC but not FVC. The adjusted differences in FEV(1) between individuals who did not consume cured meats and those who consumed cured meats 1 to 2, 3 to 4, 5 to 13, and 14 or more times per month were -37.6, -11.5, -42.0, and -110 ml, respectively (p for trend < 0.001). Corresponding differences for FEV(1)/FVC were -0.91, -0.54, -1.13, and -2.13% (p for trend = 0.001). These associations were not modified by smoking status. The multivariate odds ratio for COPD (FEV(1)/FVC <or= 0.7 and FEV(1) < 80% predicted) was 1.78 (95% confidence interval, 1.29-2.47) comparing the highest with the lowest category of cured meat consumption. The corresponding odds ratios for mild, moderate, and severe COPD were 1.11, 1.46, and 2.41, respectively.Frequent cured meat consumption was associated independently with an obstructive pattern of lung function and increased odds of COPD. Additional studies are required to determine if cured meat consumption is a causal risk factor for COPD.
Molecular Basis of Electrocardiographic ST-Segment Elevation
Authors: Ronald A. Li, Michelle Leppo, Takashi Miki, Susumu Seino, Eduardo Marbán
Journal: Circulation Research (2000)

ST elevation is a classical hallmark of acute transmural myocardial ischemia. Indeed, ST elevation is the major clinical criterion for committing patients with chest pain to emergent coronary revascularization. Despite its clinical importance, the mechanism of ST elevation remains unclear. Various studies have suggested that activation of sarcolemmal ATP-sensitive potassium (K ATP ) channels by ischemic ATP depletion may play a role, but little direct evidence is available. We studied mice with homozygous knockout (KO) of the Kir6.2 gene, which encodes the pore-forming subunit of cardiac surface K ATP channels. Patch-clamp studies in cardiomyocytes confirmed that surface K ATP current was indeed absent in KO, but robust in cells from wild-type mice (WT). We then measured continuous electrocardiograms in anesthetized adult mice before and after open-chest ligation of the left anterior descending artery (LAD). Whereas ST elevation was readily evident in WT after LAD ligation, it was markedly suppressed in KO. Such qualitative differences persisted for the rest of the 60-minute observation period of ischemia. In support of the concept that K ATP channels are responsible for ST elevation, the surface K ATP channel blocker HMR1098 (5 mg/kg IP) suppressed early ST elevation in WT. Thus, the opening of sarcolemmal K ATP channels underlies ST elevation during ischemia. These data are the first to link a specific gene product with a common electrocardiographic phenomenon.
A comparative description of mitochondrial DNA differentiation in selected avian and other vertebrate genera.
Authors: L G Kessler, J C Avise
Journal: Molecular Biology and Evolution (1985)

Levels of mitochondrial DNA (mtDNA) sequence divergence between species within each of several avian (Anas, Aythya, Dendroica, Melospiza, and Zonotrichia) and nonavian (Lepomis and Hyla) vertebrate genera were compared. An analysis of digestion profiles generated by 13-18 restriction endonucleases indicates little overlap in magnitude of mtDNA divergence for the avian versus nonavian taxa examined. In 55 interspecific comparisons among the avian congeners, the fraction of identical fragment lengths (F) ranged from 0.26 to 0.96 (F = 0.46), and, given certain assumptions, these translate into estimates of nucleotide sequence divergence (p) ranging from 0.007 to 0.088; in 46 comparisons among the fish and amphibian congeners, F values ranged from 0.00 to 0.36 (F = 0.09), yielding estimates of P greater than 0.070. The small mtDNA distances among avian congeners are associated with protein-electrophoretic distances (D values) less than approximately 0.2, while the mtDNA distances among assayed fish and amphibian congeners are associated with D values usually greater than 0.4. Since the conservative pattern of protein differentiation previously reported for many avian versus nonavian taxa now appears to be paralleled by a conservative pattern of mtDNA divergence, it seems increasingly likely that many avian species have shared more recent common ancestors than have their nonavian taxonomic counterparts. However, estimates of avian divergence times derived from mtDNA- and protein-calibrated clocks cannot readily be reconciled with some published dates based on limited fossil remains. If the earlier paleontological interpretations are valid, then protein and mtDNA evolution must be somewhat decelerated in birds. The empirical and conceptual issues raised by these findings are highly analogous to those in the long-standing debate about rates of molecular evolution and times of separation of ancestral hominids from African apes.