tbuckley/cabot-search huggingface dataset:
Combination therapy with intrapleural doxycycline and talc in reduced doses for pleurodesis
Authors: Khaled Hassaan
Journal: European Respiratory Journal (2012)

Background: We hypothesized that combining doxycycline and talc in half the  doses would be synergistic in inducing pleurodesis. Objective : The aim of the study was to evaluate safety and efficacy of low-dose doxycycline combined with low-dose talc for pleurodesis. Methods: In a prospective study, 20 consecutive patients with recurrent and biopsy-proven malignant effusions and 4 patients with recurrent pneumothorax were included. All pleurodesis was performed with talc plus doxycycline as the sclerosing agents. Doses of doxycycline (250 mg) and talc (2.5 grams) were half the usual doses. the sclerosing agents were administered via tube thoracostomy. Post-pleurodesis postero-anterior (PA) radiographs were obtained after tube removal and 30 days following the procedure. Successful therapy was defined as a complete absence or minor re-accumulation of pleural effusion one month after pleurodesis. Results: Twenty –four cases were identified (8 women, 16 men, Mean age was 65.2 years). No immediate perioperative complications were noted. Chest tube duration averaged 4.3±2.5 days. Length of stay after the procedure 4.8 ±3.2 days. Eight patients (33%) reported persistence or worsening dyspnea in the immediate postoperative period. Only one developed respiratory distress; no any parenchymal changes on chest radiography and no required ventilatory support. Other immediate postoperative events included chest pain in 10 patients (42%) and fever in 2(8%) patients. Twenty patients (83%) had successful pleurodesis and 4 (17%) failed. Conclusions : The combination of low-dose doxycycline with low-dose talc appears to be a safe and rational approach to pleurodesis with reasonable side-effects.
Withdrawal from labour force due to work disability in patients with ankylosing spondylitis
Authors: A Boonen
Journal: Annals of the Rheumatic Diseases (2001)

To investigate withdrawal from the labour force because of inability to work owing to ankylosing spondylitis (AS) and to determine the characteristics of patients with no job because of work disability attributable to AS.A postal questionnaire was sent to 709 patients with AS aged 16-60 years followed up by a rheumatologist. Kaplan-Meier survival statistics were used to assess the time lapse between diagnosis and withdrawal from work. Standardised incidence ratios were calculated to compare withdrawal from the labour force in patients with AS and the general population. Determinants of withdrawal were assessed by Cox's proportional hazard regression analysis using variables assumed to be time independent. Cross sectional characteristics of patients without a job owing to disability were further analysed by simple and multiple regression analyses.A total of 658 patients returned the questionnaire. Of 529 patients with a paid job before diagnosis of AS, 5% had left the labour force within the first year after the diagnosis, 13% after 5 years, 21% after 10 years, 23% after 15 years, and 31% after 20 years. Age and sex adjusted risk for withdrawal was 3.1 (95% CI 2.5 to 3.7) times higher than in the general population. In patients with AS, determinants of withdrawal from work were older age at diagnosis, manual work, and coping strategies characterised by limiting or adapting activities. Patients with work disability at the time of the study were older, came from a lower social class, and were more likely to have total hip replacement, peripheral arthritis, or comorbidity. Moreover, they reported worse physical function (BAS-FI), experienced lower quality of life, and more often had extraspinal disease than those with a job.Withdrawal from work is 3.1 times higher in patients with AS than expected in the general population. Within patients, higher age at diagnosis, manual work, and unfavourable coping strategies are important determinants of withdrawal. Patients without a job experience a lower quality of life.
Multiple symmetric lipomatosis: a defect in adrenergic-stimulated lipolysis.
Authors: G Enzi, E M Inelmen, A Baritussio, P Dorigo, M Prosdocimi, F Mazzoleni
Journal: Journal of Clinical Investigation (1977)

The cellularity of normal and lipomatous adipose tissue and its response to different lipolytic agents have been studied in a group of 10 patients with multiple symmetric lipomatosis (MSL). In MSL patients, fat cells from lipomatous tissue are smaller than normal, uninvolved adipocytes. Fat cells from lipomata show minimal variations in size following conspicuous increase of lipomatous masses. These findings suggest that the growth of lipomata can be attributed to the neoformation of adipocytes rather than to an enlargement in the single fat cells. The incidence of reduced glucose tolerance and of hyperlipoproteinemia is similar in MSL patients and in controls. A significant reduction in plasma free fatty acids was observed in MSL patients after a 24-h fast as well as after noradrenaline infusion. A specific insensitivity of lipomatous tissue to the lipolytic effect of noradrenaline and isoprenaline was observed in vitro, as indicated by glycerol release in the medium, whereas response to theophylline and to dibutyryl cyclic AMP was retained. The lipolytic response to catecholamines was retained. The lipolytic response to catecholamines was normal in the nonlipomatous adipose tissue of MSL patients. In basal conditions ATP concentrations were similar in normal and in lipomatous adipose tissue. However, incubation with noradrenaline induced a significant fall in intracellular ATP levels in normal tissue, whereas no variations were observed in lipomatous tissue. Theophylline, instead, induced a prompt and significant decrease in intracellular ATP levels in lipomatous tissue. These observations indicate that the block in catecholamine-stimulated lipolysis in lipomatous tissue of MSL patients can be localized at a level preceding the formation of cyclic AMP.
Genetics mediate relation of birth weight to childhood IQ
Authors: D I Boomsma, C E M van Beijsterveldt, M J H Rietveld, M Bartels, G C M van Baal
Journal: BMJ (2001)

EDITOR—Matte et al reported an association between birth weight and childhood IQ.1 To control for confounding by maternal and family factors they examined this relation in sibships of the same sex and found an association between birth weight and IQ within male sibships. This association may be mediated by genetic factors.

The impact of genetic factors on this association can be determined through the investigation of birth weight and IQ in twin pairs. Differences within dizygotic twin pairs are a function of both genetic and non-genetic factors, whereas differences within …
Approval Summary: Azacitidine for Treatment of Myelodysplastic Syndrome Subtypes
Authors: Edvardas Kaminskas, Ann Farrell, Sophia Abraham, Amy Baird, Li-Shan Hsieh, Shwu-Luan Lee, John K. Leighton, Hasmukh Patel, Atiqur Rahman, Rajeshwara Sridhara, Yong-Cheng Wang, Richard Pazdur
Journal: Clinical Cancer Research (2005)

Abstract Purpose: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. Experimental Design: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. Results: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P &amp;lt; 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. Conclusions: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.
The Wisheart affair: responses to Dunn The Bristol cardiac disaster Editor's response to Stephen Bolsin A patient's perspective
Authors: S. N Bolsin, J. Stewart
Journal: BMJ (1998)

<b>Background:</b> In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces. <b>Methods:</b> Male Sprague–Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to <sup>51</sup>Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy. <b>Results:</b> Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8±7.1 pmol/cm<sup>2</sup> vs 5.8±2.1 pmol/cm<sup>2</sup>) (p&lt;0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin). <b>Conclusions:</b> Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.
315 Fasting-induced upregulation of basolateral hepatic bile salt transporters in rats is mediated by the PGC-1α/HNF-4α pathway
Authors: I. Martin, C.G. Dietrich, A.C. Porn, M. Ananthanarayanan, C. Trautwein, C. Gartung, A. Geier
Journal: Journal of Hepatology (2006)
The Role of Interpersonal and Social Rhythm Therapy in Improving Occupational Functioning in Patients With Bipolar I Disorder
Authors: Ellen Frank, Isabella Soreca, Holly A Swartz, Andrea M Fagiolini, Alan G Mallinger, Michael E Thase, Victoria J Grochocinski, Patricia R Houck, David J Kupfer
Journal: American Journal of Psychiatry (2008)

Objective: Recent studies demonstrate the poor psychosocial outcomes associated with bipolar disorder. Occupational functioning, a key indicator of psychosocial disability, is often severely affected by the disorder. The authors describe the effect of acute treatment with interpersonal and social rhythm therapy on occupational functioning over a period of approximately 2.5 years. Method: Patients with bipolar I disorder were randomly assigned to receive either acute and maintenance interpersonal and social rhythm therapy, acute and maintenance intensive clinical management, acute interpersonal and social rhythm therapy and maintenance intensive clinical management, or acute intensive clinical management and maintenance interpersonal and social rhythm therapy, all with appropriate pharmacotherapy. Occupational functioning was measured with the UCLA Social Attainment Scale at baseline, at the end of acute treatment, and after 1 and 2 years of maintenance treatment. Results: The main effect of treatment did not reach conventional levels of statistical significance; however, the authors observed a significant time by initial treatment interaction. Participants initially assigned to interpersonal and social rhythm therapy showed more rapid improvement in occupational functioning than those initially assigned to intensive clinical management, primarily accounted for by greater improvement in occupational functioning during the acute treatment phase. At the end of 2 years of maintenance treatment, there were no differences between the treatment groups. A gender effect was also observed, with women who initially received interpersonal and social rhythm therapy showing more marked and rapid improvement. There was no effect of maintenance treatment assignment on occupational functioning outcomes. Conclusions: In this study, interpersonal and social rhythm therapy, with its emphasis on amelioration of interpersonal and role functioning, improved occupational functioning significantly more rapidly than did a psychoeducational and supportive approach with no such emphasis on functional capacities.
Unwillingly to school.
Authors: D M Bowker
Journal: BMJ (1980)

<h3>Abstract</h3> Despite the ubiquity of pollutants in the environment, their long-term ecological consequences are not always clear and still poorly studied. This is the case concerning the radioactive contamination of the environment following the major nuclear accident at the Chernobyl nuclear power plant. Notwithstanding the implications of evolutionary processes on the population status, few studies concern the evolution of organisms chronically exposed to ionizing radiation in the Chernobyl exclusion zone. Here, we examined genetic markers for 19 populations of Eastern tree frog (<i>Hyla orientalis</i>) sampled in the Chernobyl region about thirty years after the nuclear power plant accident to investigate microevolutionary processes ongoing in local populations. Genetic diversity estimated from nuclear and mitochondrial markers showed an absence of genetic erosion and higher mitochondrial diversity in tree frogs from the Chernobyl exclusion zone compared to other European populations. Moreover, the study of haplotype network permitted us to decipher the presence of an independent recent evolutionary history of Chernobyl exclusion zone’s Eastern tree frogs caused by an elevated mutation rate compared to other European populations. By fitting to our data a model of haplotype network evolution, we suspected that Eastern tree frog populations in the Chernobyl exclusion zone have a high mitochondrial mutation rate and small effective population sizes. These data suggest that Eastern tree frogs populations might offset the impact of deleterious mutations because of their large clutch size, but also question the long term impact of ionizing radiation on the status of other species living in the Chernobyl exclusion zone.
Pacemaker Failure in Complete Heart Block
Authors: HAROLD M. ALBERT, BERT A. GLASS, JACK A. ANDONIE, KENNETH C. CRANOR
Journal: Circulation Research (1962)

Atrioventricular conduction blocks were produced in dogs, and ventricular stimulation was accomplished by the use of electrodes implanted either into normal myocardium or scar tissue on the myocardium. Stimulation through scar tissue requires several times the power necessary for stimulation through normal myocardium, but both are well within the limit of standard, commercially available, transistorized pacemakers. Failure of stimulation of the ventricle was not due to excessive scarring. Failure of stimulation was in every instance due to wire breakage or actual loss of contact between the wire and the myocardium.
Physical activity in the UK: a unique crossroad?
Authors: Richard Weiler, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2010)

Recent objective evidence from England and the USA suggests that low physical activity is the most prevalent chronic disease risk factor, with 95% of the adult population not meeting the modest physical activity guidelines.1 ,2 In the UK, the annual cost of physical inactivity has been estimated at £8.2 billion, whereas the annual cost of smoking has been estimated at £1.5 billion,3 alcohol at £3.0 billion4 and obesity at £4.2 billion.1

However, despite this enormous burden on our public health and finances, the relative importance of physical inactivity as a primary cause of many chronic diseases is largely neglected within modern medicine and by health strategy. Surrogate risk factors for disease, such as hypertension, type II diabetes, obesity and dyslipidaemia, receive ample attention in medical education, have incentivised interventions embedded within primary care and are routinely reviewed during visits to a general practitioner (GP). Yet, despite physical inactivity being the most prevalent modifiable affliction and possibly the greatest chronic disease risk factor,5 it is still not receiving the attention that scientific and clinical evidence would seem to merit.

There is a unique structure to general practice and primary care within the UK National Health Service (NHS). UK GPs, who are usually the first point of contact for patients, have a unique position and opportunity to combat physical inactivity and its numerous associated comorbidities. Through the Quality and Outcomes Framework (QOF), GPs are financially rewarded for achieving healthcare targets. Setting up a new QOF point is relatively very cheap, costing approximately £1 million across the UK, and GPs have proved adept at reaching QOF targets.6 GPs are not trained to give lifestyle modification advice, but last year QOF included physical activity for the first time under a ‘cardiovascular risk assessment and management’ indicator. Specifically, …
Legionnaires' disease: a review of 79 community acquired cases in Nottingham.
Authors: M A Woodhead, J T Macfarlane
Journal: Thorax (1986)

Seventy nine cases of sporadic, community acquired legionnaires9 disease have been reviewed. Annual and seasonal variation in incidence was noted. The mean age of the patients was 53 years and 50 (63%) were male. Pre-existing chronic diseases were present in only 23 (29%), including two patients receiving immunosuppressive treatment. Common symptoms included unproductive cough, dyspnoea, chest pain, headache, confusion, nausea, vomiting, and diarrhoea. Respiratory symptoms were absent, however, in 17 (22%). Localising chest signs were present in 74 (95%) cases. Frequent laboratory findings included lymphopenia, high erythrocyte sedimentation rate, hyponatraemia, raised urea and creatinine concentrations, abnormal liver function, hypophosphataemia, hypoalbuminaemia, proteinuria, and haematuria. Thirteen patients died (16%), including nine of 20 who received assisted ventilation. The mortality rate in patients treated with erythromycin (11%) was lower than in those who received other antibiotics (23%), but this difference was not statistically significant. Of the features noted on admission, only a high plasma urea concentration was significantly associated with death. Sporadic community acquired legionnaires9 disease is a not uncommon disorder, which with appropriate treatment has a prognosis similar to that of other forms of community acquired pneumonia.
Airway smooth muscle relaxation.
Authors: A J Knox, A E Tattersfield
Journal: Thorax (1995)

Bronchodilators are important agents in the treatment of asthma and chronic obstructive airways disease.Beta agonists, theophyllines, and antimuscarinic agents are the main drugs in current use, but others are under investigation.Although other actions may be important, these drugs produce bronchodilation either by a direct effect on airway smooth muscle or by inhibiting neural pathways.As our understanding of airway smooth muscle relaxant mechanisms increases, new therapeutic possibilities are being realised.Several recent findings con- tradict established dogma -for example, the assumption that ; agonists and theophyllines act solely via cyclic adenosine monophosphate (cAMP)-linked intracellular pathways has been questioned and studies with atrial natriuretic peptide and nitrates suggest that cyclic gua- nosine monophosphate (cGMP) may be an important relaxant second messenger.The role of potassium channel activators is being ex- plored with the development of drugs which relax airway smooth muscle by a direct action on cell membrane ion channels.In this review we discuss what is known of the likely mech- anisms of action of the airway smooth muscle Respiratory Medicine relaxants in current use and their effects on Unit, City Hospital, calcium homeostasis, and suggest how de- Nottingham NG5 IPB, velopments in our understanding of relaxant A J Knox mechanisms may aid the development of treat-A E Tattersfield ment for airways obstruction in the future.
T cell receptor gene usage in the response to lambda repressor cI protein. An apparent bias in the usage of a V alpha gene element.
Authors: M Z Lai, S Y Huang, T J Briner, J G Guillet, J A Smith, M L Gefter
Journal: The Journal of Experimental Medicine (1988)

The T cell response to the lambda repressor cI protein is directed to the same region of the protein (residues 12-26) in both BALB/c and A/J mice. A panel of T cell hybridomas specific for P12-26 in the context of either I-Ek or I-Ad have been isolated To further understand the molecular interaction between the TCR and the Ia-P12-26 complex, the primary structures of the TCR of five T cell hybridomas have been determined. Southern and Northern analyses indicate that two members of the V alpha 3 gene family are used by 13 out of 14 I-Ek-restricted T cells. Four different V beta genes are used by these T cell hybridomas, while the majority (8 out of 13) express V beta 1 in combination with the J beta 2.1 element. No clear correlation can be seen in this system between gene usage and MHC restriction. In addition, the fine specificity of I-Ek-restricted T cells to a single amino acid substitution [Phe22/His22]P12-26 is not attributed to the usage of particular V alpha and V beta elements. The V alpha 3 family gene is also used by a few I-Ad-restricted T cells. Interestingly, these I-Ad T cells share a reactivity pattern more similar to that of I-Ek-restricted T cells than other I-Ad-restricted T cells. The nonrandom selection V alpha 3 is also demonstrated by the fact that V alpha 3 is used by P12-26-specific, but not by cytochrome c- or staphylococcal nucleus-specific, I-Ek-restricted T cells. This suggests that although antigen specificity may not be accounted for by either chain of the TCR, the members of V alpha 3 genes may be selected by the antigen (P12-26).
β-2 Adrenoceptor genetic variation is associated with genetic predisposition to essential hypertension: The Bergen Blood Pressure Study
Authors: B Timmermann, R Mo, F C Luft, E Gerdts, A Busjahn, P Omvik, G H Li, H Schuster, T F Wienker, M R Hoehe, P Lund-Johansen
Journal: Kidney International (1998)