tbuckley/cabot-search huggingface dataset:
Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B
Authors: Renate G. van der Molen, Dave Sprengers, Rekha S. Binda, Esther C. de Jong, Hubert G. M. Niesters, Johannes G. Kusters, Jaap Kwekkeboom, Harry L. A. Janssen
Journal: Hepatology (2004)

Dendritic cells (DC) play an important role in the induction of T-cell responses. We hypothesize that the hampered antiviral T-cell response in chronic hepatitis B patients is a result of impaired dendritic cell function. In this study, we compared the number, phenotype and functionality of two important blood precursor DC, myeloid DC (mDC) and plasmacytoid DC (pDC), of chronic hepatitis B patients with healthy volunteers. No differences in percentages of mDC and pDC in peripheral blood mononuclear cells were observed between chronic hepatitis B patients and healthy controls. The allostimulatory capacity of isolated and in vitro matured mDC, but not of pDC, was significantly decreased in patients compared to controls. Accordingly, a decreased percentage of mDC expressing CD80 and CD86 was observed after maturation, compared to controls. In addition, mDC of patients showed a reduced capacity to produce tumor necrosis factor α after a stimulus with synthetic double-stranded RNA and interferon γ. Purified pDC from patients produced less interferon α, an important antiviral cytokine, in response to stimulation with Staphylococcus aureus Cowan strain I than pDC isolated from controls. In conclusion , mDC and pDC are functionally impaired in patients with chronic hepatitis B. This might be an important way by which hepatitis B virus evades an adequate immune response, leading to viral persistence and disease chronicity. (Hepatology 2004;40:738-746.)
Motivation Problems Related to Secondary Prevention in Industrial Mental Health
Authors: WILLIAM E. POWLES, WALTER W. WINSLOW, EDWARD P. RUBIN, W. DONALD ROSS
Journal: American Journal of Psychiatry (1966)

Efforts at secondary prevention (early case finding and treatment) made during an industrial mental health project were less successful in securing follow-through of treatment recommendations than the more traditional consultation by a psychiatrist. The authors suggest a new kind of industrial mental health program, combining the two approaches and carried out in two stages—the first by supervisory personnel in the plant and the second by medical personnel with consultation from mental health specialists.
Differential micro-RNA expression in primary CNS and nodal diffuse large B-cell lymphomas
Authors: Lars Fischer, Michael Hummel, Agnieszka Korfel, Dido Lenze, Korrina Joehrens, Eckhard Thiel
Journal: Neuro-Oncology (2011)

Most primary CNS lymphomas (PCNSL) are diffuse large B-cell lymphomas (DLBCL). However, clinical behavior and prognosis differ considerably from those for nodal DLBCL (nDLBCL), and their pathogenesis is still not fully understood. Micro-RNAs (miRNAs) have been associated with cancer development and progression. We investigated a large miRNA panel for differential expression in PCNSL and nDLBCL, to determine new mechanisms potentially involved in PCNSL pathogenesis. Using paraffin-embedded biopsy specimens from 21 HIV-negative patients with newly diagnosed PCNSL (n = 11) and nDLBCL (n= 10), we measured the expression of 365 miRNA species by quantitative real-time PCR using low-density PCR arrays. We found that 18 miRNAs were differentially expressed: median expression levels of 13 miRNAs were 2.1-13.1 times higher in PCNSL, and median expression levels of 5 miRNAs were 2.6-3.3 times higher in nDLBCL. MiRNAs upregulated in PCNSL were associated with the Myc pathway (miR-17-5p, miR-20a, miR-9), with blocking of terminal B-cell differentiation (miR-9, miR-30b/c), or with upregulation by inflammatory cytokines (miR-155). Putative tumor-suppressor miRNAs (miR-199a, miR-214, miR-193b, miR-145) were downregulated in PCNSL. There was no overlap of miRNAs dysregulated in PCNSL with those differentially expressed between immunohistologically defined germinal center B cell-like (GCB) and non-GCB types or, apart from miR-9, with miRNAs known to be overexpressed in human brain. We conclude that PCNSL exhibits a distinct pattern of miRNA expression compared with nDLBCL. This argues for the involvement of different molecular mechanisms in the pathogenesis of these two lymphoma types.
An amateur badminton player with juvenile dermatomyositis: courage and questions
Authors: L Özçakar, R Topaloglu
Journal: British Journal of Sports Medicine (2003)

Silence on clinical fundamentalsYour point about lifesaving hand washing to prevent diarrhoeal illness 1 is well made.I have found that the inattention you have noted to such clinical fundamentals in textbooks on sports medicine is mirrored by the absence of any notation, affirmative or otherwise, in many textbooks on pain, correlating the symptom (pain) with the physical sign (tenderness), a rudimentary clinical confirmation of the validity of pain, according to my clinical training in Ireland, that could distinguish malingering from a genuine complaint of pain, for example.Perhaps I have received a false impression but, if so, the utility of eliciting tenderness, a longstanding custom during physical examination, seems a mystery.In November 2002, I attended a conference in Florida on prescribing addictive drugs.None of the purportedly expert presenters mentioned the issue spontaneously.When I collared one of them after his lecture and enquired specifically about the point, he claimed that chronic, non-malignant pain and tenderness are usually ''dissociated''that is, a patient can suffer chronic, nonmalignant pain in the absence of tenderness of the painful part, on physical examination.This assertion seemed contrary to my own, admittedly anecdotal, experience over some 24 years.Furthermore, it would seem to (a) render chronic, non-malignant pain, and maybe all pain, unknowable and undetectable (except perhaps to the alleged sufferer, although nobody else can tell), (b) place the assessment of pain in the realm of ''pathological science'', 5 and (c) invalidate the very idea of regulation of narcotic drugs to ensure that the practitioner prescribe one only when it ''corresponds to the ailment''. 5 The silence on the subject in the medical literature seemed anomalous.A Boolean Pubmed search on the keywords ''pain'' and ''tenderness'' revealed no relevant articles.I examined all 114 textbooks on pain in the medical library of the University of Southern California (USC) and found two 2 3 that addressed the issue.
The abnormal red-cell oxalate transport is a risk factor for idiopathic calcium nephrolithiasis
Authors: G Gambaro, F Marchini, A Piccoli, M A Nassuato, F Bilora, B Baggio
Journal: Journal of the American Society of Nephrology (1996)

An abnormal erythrocyte transmembrane oxalate flux was described in recurrent idiopathic calcium nephrolithiasis. To verify whether it might represent a risk marker of renal stone disease, two prospective studies were carried out. One hundred ninety patients with idiopathic calcium nephrolithiasis who were enrolled at their first episode of lithiasis during the period 1984 to 1986, form the basis of the first prospective study. The impact of erythrocyte oxalate transport anomaly, gender, familial occurrence of nephrolithiasis, hypercalciuria, hyperoxaluria, and hyperuricosuria on stone recurrence by both bivariate and multivariate analysis of frequencies was assessed. The predictive value of the erythrocyte anomaly for a patient's becoming a stone former was also assessed in five nephrolithiasis families. Recurrence occurred in 57.9% of patients; this was significantly associated with the erythrocyte anomaly, hyperoxaluria, and male gender. However, when using multivariate analysis, only gender and the erythrocyte anomaly were statistically significant and were independent predictors of recurrency. The probability of stone recurrency predicted by the logistic model ranged from 30.1% for women with normal erythrocyte oxalate transport, to 73.4% for men with the erythrocyte anomaly. The family follow-up showed that only subjects with the erythrocyte abnormality become renal stone-formers in the 8-yr survey. By showing the predictive value of the erythrocyte oxalate anomaly for recurrent calcium nephrolithiasis, our findings support the notion that this anomaly is a risk factor in renal stone disease.
Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?
Authors: Adrienne D. Cox, Channing J. Der, Mark R. Philips
Journal: Clinical Cancer Research (2015)

Abstract RAS proteins require membrane association for their biologic activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTI) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anticancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes, and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated posttranslational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. Clin Cancer Res; 21(8); 1819–27. ©2015 AACR. See all articles in this CCR Focus section, “Targeting RAS-Driven Cancers.”
Comparison among three screening questionnaires for COPD diagnosis in the primary care
Authors: Dionisios Spyratos, Diamantis Chloros, Anna-Bettina Haidich, Nikolaos Hatzidimitriou, A. Karoulias, Dimitra Nella, Lazaros Sichletidis
Journal: European Respiratory Journal (2013)

Background:  Underdiagnosis of COPD is a common problem in primary care. The aim of the present study was the comparison among three screening COPD questionnaires.   Methods:  24 general practice clinics were included. Pulmonologists, in cooperation with GPs, visited every center and examined all subjects >40 year old (smokers, ex-smokers) who were invited via newsletter posters. All subjects answered the three questionnaires (IPAG questionnaire, COPD Population Screener and Lung Function Questionnaire) and underwent spirometry post-bronchodilation. We used predefined cut-off points according to published validation studies and also calculated best cut-off points for our study sample.   Results:  1,557 subjects were included in the study. Out of those, 203 were diagnosed with COPD (FEV 1 : 1.8±0.6 L, 68.5±18.4 %pred.) while 95 had no previous medical diagnosis of the disease. Table 1 shows diagnostic accuracy of the three questionnaires. We found that best cut-off points were: >19 for IPAG, ≥5 for COPD Population Screener and ≤17 for Lung Function Questionnaire. Positive predictive value was considerably higher in subjects ≥70 years old compared with those    Conclusion:  Screening questionnaires are useful tools in primary care setting, everyone has specific diagnostic accuracy while we propose a new cut-off point especially for IPAG.
Improved Patient Survival Using a Modified Resuscitation Protocol for Out-of-Hospital Cardiac Arrest
Authors: Alex G. Garza, Matthew C. Gratton, Joseph A. Salomone, Daniel Lindholm, James McElroy, Rex Archer
Journal: Circulation (2009)

Cardiac arrest continues to have poor survival in the United States. Recent studies have questioned current practice in resuscitation. Our emergency medical services system made significant changes to the adult cardiac arrest resuscitation protocol, including minimizing chest compression interruptions, increasing the ratio of compressions to ventilation, deemphasizing or delaying intubation, and advocating chest compressions before initial countershock.This retrospective observational cohort study reviewed all adult primary ventricular fibrillation and pulseless ventricular tachycardia cardiac arrests 36 months before and 12 months after the protocol change. Primary outcome was survival to discharge; secondary outcomes were return of spontaneous circulation and cerebral performance category. Survival of out-of-hospital arrest of presumed primary cardiac origin improved from 7.5% (82 of 1097) in the historical cohort to 13.9% (47 of 339) in the revised protocol cohort (odds ratio, 1.80; 95% confidence interval, 1.19 to 2.70). Similar increases in return of spontaneous circulation were achieved for the subset of witnessed cardiac arrest patients with initial rhythm of ventricular fibrillation from 37.8% (54 of 143) to 59.6% (34 of 57) (odds ratio, 2.44; 95% confidence interval, 1.24 to 4.80). Survival to hospital discharge also improved from an unadjusted survival rate of 22.4% (32 of 143) to 43.9% (25 of 57) (odds ratio, 2.71; 95% confidence interval, 1.34 to 1.59) with the protocol. Of the 25 survivors, 88% (n=22) had favorable cerebral performance categories on discharge.The changes to our prehospital protocol for adult cardiac arrest that optimized chest compressions and reduced disruptions increased the return of spontaneous circulation and survival to discharge in our patient population. These changes should be further evaluated for improving survival of out-of-hospital cardiac arrest patients.
Increased type I procollagen mRNA transcripts in the lungs of mice during the development of bleomycin-induced fibrosis
Authors: S Shahzeidi, PK Jeffery, GJ Laurent, RJ McAnulty
Journal: European Respiratory Journal (1994)

In this study, in situ hybridization has been used to investigate the localization of type I procollagen messenger ribonucleic acid (mRNA) in normal lung, and in the lungs of mice during the development of bleomycin-induced pulmonary fibrosis. Lung fibrosis was induced by a single intratracheal instillation of bleomycin sulphate (6 mg.kg-1 body weight), and tissues examined at times up to 35 days thereafter. Tissue transcripts of alpha 2(I) procollagen mRNA were visualized after hybridization with 35S-labelled riboprobes. Hybridization signals were associated with alveolar interstitial cells throughout the normal lung, with additional areas of dense hybridization signals observed subpleurally. Three days following administration of bleomycin, there was no apparent change in the pattern of hybridization. By 10 days, foci of intense hybridization signals indicative of gene activation were observed associated with individual cells in the alveolar interstitium. At 21 days, the increase in hybridization signals appeared to be associated with greater numbers of cells rather than highly activated cells. These results demonstrate that procollagen genes are normally expressed in the mouse lung, and that during bleomycin-induced pulmonary fibrosis hybridization signals increase, suggesting that both enhanced gene expression by individual cells and increased numbers of cells expressing the type I procollagen gene are involved in the pathogenetic mechanism.
Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments
Authors: E.J. van Zuuren, Z. Fedorowicz
Journal: British Journal of Dermatology (2015)

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high‐quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high‐quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high‐quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low‐quality evidence). For oral treatments there was moderate‐quality evidence for the effectiveness of tetracycline based on two old studies, and high‐quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low‐quality evidence). Low‐dose isotretinoin appeared to be slightly more effective than doxycycline 50–100 mg (high‐quality evidence). Laser and light‐based therapies for erythema in rosacea were effective (low‐quality evidence). Further RCTs are required for ocular rosacea.
Influence of breathing pattern on lung deposition and bronchodilator response to nebulised salbutamol in patients with stable asthma.
Authors: B M Zainudin, S E Tolfree, M Short, S G Spiro
Journal: Thorax (1988)

The influence of breathing pattern on lung deposition and bronchodilator response to nebulised salbutamol is uncertain. Three different breathing patterns were assessed in eight patients with chronic stable asthma. Salbutamol solution (2.5 mg in 4 ml) mixed with technetium-99m labelled human serum albumin was nebulised by an Acorn nebuliser at a flow rate of 6 litres a minute. Particles with a mass median aerodynamic diameter of 4.8 microns were produced for inhalation by (a) tidal breathing, (b) six tidal breaths followed by three deep breaths, and (c) six tidal breaths followed by three deep breaths with a five second breath hold after each breath. Each breathing pattern was continued for four minutes. There was no significant difference in the percentage of radioaerosol deposited in the lung or in the distribution of radioaerosol within the lung as assessed by gamma camera imaging. Changes in bronchodilator responses as measured by peak expiratory flow rate (PEF), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) 30, 45, and 60 minutes after inhalation were similar for the three studies. The mean (SEM) maximum percentage change in FEV1 was 44 (7.1), 47 (9.2), and 51 (8.4) for studies 1, 2, and 3 respectively. The percentage of nebulised solution deposited in the body was also similar for the three breathing patterns--that is, 11-13%, of which 98% entered the lung. This study shows that inhaling a nebulised aerosol by tidal breathing, the simplest method, is as effective as tidal breathing with deep breaths with or without a breath hold.
Basal cell naevus syndrome: an update on genetics and treatment
Authors: A.M. John, R.A. Schwartz
Journal: British Journal of Dermatology (2015)

Basal cell naevus syndrome is an autosomal dominant disorder that stems from mutations in multiple genes, most commonly patched 1 (PTCH1). The classic triad of symptoms consists of basal cell carcinomas, jaw keratocysts and cerebral calcifications, although there are many other systemic manifestations. Because of the broad range of symptoms and development of several types of tumours, early diagnosis and close monitoring are essential to preserve quality of life. Targeting treatment is often difficult because of tumour prevalence. Newer inhibitors of the hedgehog signalling pathway and proteins involved in proliferative growth have shown therapeutic promise. In addition, preventive medications are being devised. We propose a method for determining appropriate treatment for cutaneous tumours.
Compliance, satisfaction, and quality of life of patients with colorectal cancer receiving home chemotherapy or outpatient treatment: a randomised controlled trial
Authors: J M Borras
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To compare chemotherapy given at home with outpatient treatment in terms of colorectal cancer patients9 safety, compliance, use of health services, quality of life, and satisfaction with treatment. <b>Design:</b> Randomised controlled trial. <b>Setting:</b> Large teaching hospital. <b>Participants:</b> 87 patients receiving adjuvant or palliative chemotherapy for colorectal cancer. <b>Interventions:</b> Treatment with fluorouracil (with or without folinic acid or levamisole) at outpatient clinic or at home. <b>Main outcome measures:</b> Treatment toxicity; patients9 compliance with treatment, quality of life, satisfaction with care, and use of health resources. <b>Results:</b> 42 patients were treated at outpatient clinic and 45 at home. The two groups were balanced in terms of age, sex, site of cancer, and disease stage. Treatment related toxicity was similar in the two groups (difference 7% (95% confidence interval −12% to 26%)), but there were more voluntary withdrawals from treatment in the outpatient group than in the home group (14% <i>v</i> 2%, difference 12% (1% to 24%)). There were no differences between groups in terms of quality of life scores during and after treatment. Levels of patient satisfaction were higher in the home treatment group, specifically with regard to information received and nursing care. There were no significant differences in use of health services. <b>Conclusions:</b> Home chemotherapy seemed an acceptable and safe alternative to hospital treatment for patients with colorectal cancer that may improve compliance and satisfaction with treatment. <h3>What is already known on this topic</h3> Home chemotherapy programmes have been proposed as an alternative to hospital treatment However, they are more costly, and there is little evidence on their impact on outcomes such as compliance, quality of life, or use of other health services <h3>What this study adds</h3> Home chemotherapy was not associated with an increased use of health services such as primary care or emergency departments Home chemotherapy had no effect on patients9 quality of life but increased their compliance with treatment and satisfaction, particularly with regard to nursing care Home chemotherapy seems an acceptable and safe alternative to outpatient treatment that may improve compliance with treatment
Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes
Authors: Maritta Pykäläinen, Riikka Kinos, Sanna Valkonen, Pia Rydman, Maritta Kilpeläinen, Lauri A. Laitinen, Jussi Karjalainen, Markku Nieminen, Mikko Hurme, Juha Kere
Journal: Journal of Allergy and Clinical Immunology (2005)