tbuckley/cabot-search huggingface dataset:
Community treatment is effective for drug resistant tuberculosis
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Outpatient treatment by community workers achieved an 83% cure rate for multidrug resistant tuberculosis in a deprived area of Lima, Peru, says a report in the New England Journal of Medicine (2003:348;119-28). The investigators were from the Harvard Medical School and School of Public Health in Boston and from the Sergio E. Bernales Hospital and Servicios Basicos de Salud in Lima.

Principal investigator Dr Paul Farmer said the study showed that patients from poor countries with chronic multidrug resistant tuberculosis could be successfully treated on an ambulatory basis outside referral centres.

The programme used …
Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels
Authors: Mehrdad Haghpassand, Patricia-Ann K. Bourassa, Omar L. Francone, Robert J. Aiello
Journal: Journal of Clinical Investigation (2001)

Excess accumulation of cholesterol in macrophages results in foam cell production and lesion development. Recent studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) is highly regulated in macrophages and mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for HDL formation. The goal of this study was to determine the contribution of monocyte/macrophage ABCA1 to HDL formation in vivo. We generated mice expressing ABCA1 in macrophages and mice with selected inactivation of ABCA1 in macrophages by bone marrow transplantation in ABCA1-deficient (ABC1–/–) and wild-type (WT) mice. At all times, the level of HDL in ABC1–/– recipient mice remained low relative to WT recipient mice irrespective of the genotype of the donor macrophage ABCA1 or high-fat feeding. Expression of WT macrophage ABCA1 in ABC1–/– mice resulted in a small but significant increase in apoA-I levels starting 2 weeks after transplantation. No further increase in apoAI was observed up to 14 weeks after transplantation. The increase in apoAI was accompanied by a small but significant increase in HDL cholesterol 6 weeks after transplantation. The HDL formed as a consequence of the expression of WT macrophage ABCA1 migrated to the alpha position in a two-dimensional gel electrophoresis. These results demonstrate that monocyte/macrophage ABCA1 contributes to HDL formation; however, the contribution to the overall plasma HDL levels is minimal.
Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma
Authors: Torsten O. Nielsen, Forrest D. Hsu, Kristin Jensen, Maggie Cheang, Gamze Karaca, Zhiyuan Hu, Tina Hernandez-Boussard, Chad Livasy, Dave Cowan, Lynn Dressler, Lars A. Akslen, Joseph Ragaz, Allen M. Gown, C. Blake Gilks, Matt van de Rijn, Charles M. Perou
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. Experimental Design: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. Results: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. Conclusions: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.
The Surgical Treatment of Parkinson’s Disease
Authors: Kenneth A. Follett
Journal: Annual Review of Medicine (2000)

▪ Abstract Surgical treatment of Parkinson’s disease (PD) can provide gratifying symptomatic improvements for many individuals who suffer from persistent disabling symptoms despite the best available medical management. Current surgical therapies include ablative techniques (thalamotomy and pallidotomy), augmentative techniques (nondestructive) (deep brain stimulation), and restorative techniques (tissue transplantation and gene therapy). Ablative procedures can provide substantial clinical benefit, but the current trend is toward deep brain stimulation, which can provide similar symptomatic improvement in a nondestructive manner. Restorative techniques, such as tissue transplantation and gene therapy, are exciting but have significant obstacles to overcome before their promise can be realized. Until the underlying pathological defect of PD can be identified and treated, surgical intervention is likely to remain important in the symptomatic treatment of this disabling disease.
Disruption of Transforming Growth Factor-β Signaling by Five Frequently Methylated Genes Leads to Head and Neck Squamous Cell Carcinoma Pathogenesis
Authors: Kristi L. Bennett, Todd Romigh, Charis Eng
Journal: Cancer Research (2009)

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with low survival rates in advanced stages. To facilitate timely diagnosis and improve outcome, early detection markers (e.g., DNA methylation) are crucial for timely cancer diagnosis. In a recent publication, an epigenome-wide screen revealed a set of genes that are commonly methylated and downregulated in head and neck cancers (SEPT9, SLC5A8, FUSSEL18, EBF3, and IRX1). Interestingly, these candidates are potentially involved in the transforming growth factor-β (TGF-β) signaling pathway, which is often disrupted in HNSCC. Therefore, we sought to determine coordinated epigenetic silencing of these candidate genes in HNSCC as potential key disruptors of TGF-β signaling, which could ultimately result in HNSCC progression. Through immunoprecipitation studies, all five of the investigated candidate genes were found to interact with components of the TGF-β pathway. Overexpression of SLC5A8, EBF3, and IRX1 resulted in decreased mitotic activity and increased apoptosis. In addition, EBF3 was found to increase p21 promoter activity, and SMAD2 significantly increased IRX1 promoter activity. These findings are significant because they reveal a set of genes that interact with components of the TGF-β pathway, and their silencing via methylation in HNSCC results in coordinated decrease in apoptosis, increased proliferation, and decreased differentiation. [Cancer Res 2009;69(24):9301–5]
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Ronald S. Goor, A. M. Pappenheimer, Elizabeth Ames
Journal: The Journal of Experimental Medicine (1967)

Inhibition of soluble transferase II activity in cell-free systems by diphtheria toxin and NAD can be prevented or reversed in the presence of a sufficient concentration of nicotinamide. Quantitative studies on inhibition of peptide bond formation in cell-free extracts by toxin and NAD have indicated that two successive reversible reactions are involved. First, toxin and NAD interact mole for mole to form a relatively dissociable complex. This toxin-NAD complex then reacts with transferase II to form an enzymatically inactive product that is but slightly dissociated. In the presence of sufficient nicotinamide, however, the latter complex can be broken down to yield active transferase II once more. Based on the above model, an equation has been derived that accurately predicts the per cent inhibition of amino acid incorporation in cell-free systems at any given toxin and NAD level. The observed inhibition appears to be independent of the sensitivity to toxin of the cell species from which the extracts were derived, and depends only on the toxin and NAD concentrations. Although the model satisfactorily explains inhibition of peptide bond formation by toxin in cell-free systems, further assumptions are needed to explain how still lower concentrations of toxin are able to arrest protein synthesis completely in the living cell.
Prognostic and Predictive Markers in Metastatic Renal Cell Carcinoma
Authors: Muhammad A. Khattak, Farrah Bakr, Marcin Krzystanek, Zoltan Szallasi, Marco Gerlinger, Claudio Santos, Charles Swanton, Lisa M. Pickering, Martin E. Gore, James M.G. Larkin
Journal: Journal of Clinical Oncology (2013)

astatic renal cell carcinoma (mRCC) has been made over the last 5 years, with a plethora of targeted agents currently approved in different clinical settings. However, not all mRCC patients respond to treatment with these drugs and currently there are no validated biomarkers to predict clinical outcome. We therefore read with interest Armstrongetal’s 1 reportoftheprognosticandpredictivesignificance of baseline serum lactate dehydrogenase (LDH) in patients with intermediate- and-poor risk mRCC treated in a first-line trial of the mammalian target of rapamycin (mTOR) inhibitor temsirolimus, interferon-alfa, or both in combination. As expected, in multivariate analysis,overallsurvival(OS)wassignificantlyshorterinpatientswith LDHmorethan1theupperlimitofnormal(ULN)comparedwith patients with LDH 1ULN at baseline. The importance of a high baseline LDH as a predictor of response to temsirolimus was also examined: in patients with LDH more than ULN, median OS with temsirolimus was 6.9 months versus 4.2 months with interferon-alfa (hazard ratio, 0.56; 95% CI, 0.38 to 0.81; P .002). There was no difference in risk of death between temsirolimus and interferon-alfa treatment in patients with normal LDH. However, patients with an elevatedLDHinthistrialweremorelikelytobeofpoorriskbyMotzer criteria and it is unlikely that interferon-alfa provided any benefit in this group 2 and, given the associated toxicity, it may even have been detrimental. Survival comparisons between temsirolimus and interferon-alfa should therefore be viewed with caution. The prognostic impact of baseline LDH was evaluated in the RECORD-1(Renal Cell Cancer Treatment With Oral RAD001 Given Daily) trial of the mTOR inhibitor everolimus in mRCC refractory to anti‐vascular endothelial growth factor (VEGF) therapy. 3 High LDH was found to be prognostic for OS, but not progression free survival (PFS)inunivariateanalysis,butitwasnotincludedinthefinalmodel of multivariate analysis because of its nonlinear effect. High pretreatmentLDHishoweveraprognosticmarkerforbothPFSandOSinthe first-line setting during treatment with the VEGF receptor tyrosine kinase inhibitor sunitinib and interferon-alfa in predominantly good or intermediate risk (93%) mRCC 4 as well as for OS in the sunitinibrefractory setting during treatment with the VEGF receptor tyrosine kinase inhibitor axitinib. 5 To examine further the relationship betweenprognosisandLDHduringeverolimustherapy,weevaluatedall
Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology
Authors: K. R. Porter, B. J. McCarthy, S. Freels, Y. Kim, F. G. Davis
Journal: Neuro-Oncology (2010)

Prevalence is the best indicator of cancer survivorship in the population, but few studies have focused on brain tumor prevalence because of previous data limitations. Hence, the full impact of primary brain tumors on the healthcare system in the United States is not completely described. The present study provides an estimate of the prevalence of disease in the United States, updating an earlier prevalence study. Incidence data for 2004 and survival data for 1985–2005 were obtained by the Central Brain Tumor Registry of the United States from selected regions, modeled under 2 different survival assumptions, to estimate prevalence rates for the year 2004 and projected estimates for 2010. The overall incidence rate for primary brain tumors was 18.1 per 100 000 person-years with 2-, 5-, 10-, and 20-year observed survival rates of 62%, 54%, 45%, and 30%, respectively. On the basis of the sum of nonmalignant and averaged malignant estimates, the overall prevalence rate of individuals with a brain tumor was estimated to be 209.0 per 100 000 in 2004 and 221.8 per 100 000 in 2010. The female prevalence rate (264.8 per 100 000) was higher than that in males (158.7 per 100 000). The averaged prevalence rate for malignant tumors (42.5 per 100 000) was lower than the prevalence for nonmalignant tumors (166.5 per 100 000). This study provides estimates of the 2004 (n = 612 770) and 2010 (n = 688 096) expected number of individuals living with primary brain tumor diagnoses in the United States, providing more current and robust estimates for aiding healthcare planning and patient advocacy for an aging US population.
Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis
Authors: C. Witt, A. C Borges, M. John, I. Fietze, G. Baumann, A. Krause
Journal: Annals of the Rheumatic Diseases (1999)

The clinical course of fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) may vary considerably from stable condition for years to continuous fatal progression. This prospective study aimed at identifying the prognostic value of bronchoalveolar lavage fluid (BALF) analysis in FASSc.Seventy three consecutive patients with SSc and clinical signs of pulmonary involvement were enrolled. Every patient underwent clinical examination, lung function tests, computed tomography (CT), gallium scan, echocardiography, and bronchoalveolar lavage (BAL). Forty nine patients, 26 with pathological and 23 with normal BALF findings were prospectively followed up for two years and re-evaluated annually.At baseline, 51 subjects (70%) showed radiological signs of lung fibrosis and/or alveolitis by CT and diffusion capacity for carbon monoxide (DLco) was decreased in 47 patients (64%). Thirty five patients (48%) had pathological BALF findings. BALF differential counts included BALF granulocytosis in 18, BALF lymphocytosis in 12, and a mixed increase of both granulocytes and lymphocytes in five patients. On follow up, a progression of FA with a significant decrease of DLco was only observed in patients with BALF granulocytosis. In contrast, patients with BALF lymphocytosis or normal BALF cell count had stable lung function parameters during the study period. In none of our patients echocardiography showed evidence of pulmonary hypertension.BALF granulocytosis predicts progression of FA with deterioration of lung function, which is most sensitively monitored by DLco. Immunosuppressive treatment is recommended in patients with granulocytic FASSc.
The impact and cost-effectiveness of strategies to detect drug-resistant tuberculosis
Authors: O. Oxlade, D. Falzon, D. Menzies
Journal: European Respiratory Journal (2011)

Drug-resistant tuberculosis (TB) is a serious emerging problem in many low-resource countries. TB control programmes are uncertain of which drug susceptibility tests (DSTs) to use and when to test patients. We predicted the potential cost-effectiveness of different DST strategies, in settings with varying prevalence of drug resistance. Using decision analysis, we assessed the cost-effectiveness of conventional and rapid DSTs for previously diagnosed smear-positive TB cases. Five different time-points were considered for administering DSTs. Different initial drug resistance and HIV scenarios were also considered. All DST scenarios in the wide range of settings considered were found to be cost-effective. The strategy of performing a rapid DST that detects any form of isoniazid (INH) and rifampicin (RIF) resistance for all patients before the initiation of treatment was predicted to be the most cost-effective strategy. In a setting with moderate drug resistance, the cost per disability-adjusted life year gained was as low as US$744. Our findings support the roll-out of rapid drug susceptibility testing at the moment of diagnosis to detect any form of INH and RIF resistance in all countries with moderate or greater burdens of drug-resistant TB.
Pharmacological Therapy of Lupus Nephritis
Authors: Derek M. Fine
Journal: JAMA (2005)

Kidney involvement is common in systemic lupus erythematosus, occurring in up to 60% of affected adults during the course of their disease. Diffuse proliferative lupus nephritis (World Health Organization class IV), the most ominous variant, has traditionally been treated with cyclophosphamide and glucocorticoids. With cyclophosphamide, women of childbearing potential must weigh the risks of sustained amenorrhea, infertility, increased susceptibility to infection, bone marrow suppression, hemorrhagic cystitis, and malignancy against the benefits of better disease control compared with glucocorticoids alone. Because of the host of adverse effects associated with cyclophosphamide, alternative approaches to the treatment of lupus nephritis are desirable. A 31-year-old woman developed class IV lupus nephritis in the postpartum period. Seeking to preserve fertility and avoid other known toxicities of cyclophosphamide, she chose to undergo therapy with mycophenolate mofetil. In the treatment of severe lupus nephritis, mycophenolate mofetil has emerged as an alternative to cyclophosphamide, offering a major advance in the therapy of lupus nephritis.
Risk factors for groin/hip injuries in field-based sports: a systematic review
Authors: Julianne Ryan, Neasa DeBurca, Karen Mc Creesh
Journal: British Journal of Sports Medicine (2014)

Background Groin/hip injuries are common in the athletic population, particularly in sports requiring kicking, twisting, turning and rapid acceleration and deceleration. Chronic hip, buttock and groin pain account for 10% of all attendances to sports medicine centres. Understanding risk factors for field-based sports (FBS) players is important in developing preventive measures for injury. Objective This systematic review aims to identify and examine the evidence for groin/hip injury risk factors in FBS. Methods 14 electronic databases were searched using keywords. Studies were included if they met the inclusion criteria and investigated one or more risk factors with relation to the incidence of groin/hip injuries in FBS. Studies were accumulated and independently analysed by two reviewers under a 12-point quality assessment scale (modified CASP (for cohort study design) assessment scale). Owing to the heterogeneity of studies and measures used, a meta-analysis could not be conducted. As a result risk factors were pooled for analysis and discussion. Results Of the 5842 potentially relevant studies, 7 high-quality studies were included in this review. Results demonstrated that previous groin/hip injury was the most prominent risk factor, identified across four studies (OR range from 2.6 (95% CI 1.1 to 6.11) to 7.3, (p=0.001)), followed by older age (OR 0.9, p=0.05) and weak adductor muscles (OR 4.28, 95% CI 1.31 to 14.0, p=0.02) each identified in two studies. Eight other significant risk factors were identified once across the included studies. Conclusions 11 significant risk factors for groin/hip injury for FBS players were identified. The most prominent risk factor identified was previous groin/hip injury. Future research should include a prospective study of a group of FBS players to confirm a relationship between the risk factors identified and development of groin/hip injuries.
Randomized, Double-Blinded Phase II Evaluation of Docetaxel with or without Doxercalciferol in Patients with Metastatic, Androgen-Independent Prostate Cancer
Authors: Steven Attia, Jens Eickhoff, George Wilding, Douglas McNeel, Jules Blank, Harish Ahuja, Alcee Jumonville, Michael Eastman, Daniel Shevrin, Michael Glode, Dona Alberti, Mary Jane Staab, Dottie Horvath, Jane Straus, Rebecca Marnocha, Glenn Liu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1α-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC. Experimental Design: Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days 1, 8, and 15) with or without doxercalciferol (10 μg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat. Results: Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade ≥3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785). Conclusions: Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.