tbuckley/cabot-search huggingface dataset:
Autoregulation versus defaecation: An unusual side effect of CPAP
Authors: Helen Stone, Faruq Fazal, Harmesh Moudgil, Nawaid Ahmad, Thirumalairengarajan Naicker, Koottalai Srinivasan
Journal: European Respiratory Journal (2014)

Introduction Continuous Positive Airway Pressure is the first line treatment for symptomatic moderate to severe obstructive sleep apnoea. Side effects of CPAP are well known; however faecal incontinence secondary to CPAP is not documented. We present the case of a patient with OSA who developed this on commencing CPAP.  Case A 50 year old female with ulcerative colitis had a total colectomy in 1992 and a subsequent ileo-anal pouch reconstruction. She was referred to the sleep clinic as she was experiencing daytime somnolence (Epworth score of 15/24). Her sleep study demonstrated severe obstructive sleep apnoea with an apnoea-hypopnoea index of 35.2, and for 12.5% of the study, her Sa02 were below 90%. She was commenced on CPAP using auto titration. Initially, she experienced problems with faecal leakage - defecating up to 4 times per night. During this time her mean CPAP pressure had been 17cm water. She was subsequently converted CPAP at 10cms fixed maximum pressure and now tolerates CPAP very well; having a degree of faecal leakage only 2 or 3 times a week, rather than every night as previously. Her Epworth score has now fallen to 9/24, her AHI is 2.5 and her OSA symptoms have improved, leading to better treatment compliance.  Conclusion It was hypothesised that the patient9s problems were related to increased intra-thoracic pressure from the CPAP, resulting in raised intra-abdominal pressure, putting a strain on the ileo-anal pouch reconstruction giving rise to the faecal incontinence. This resolved with lower CPAP pressures, resolving the faecal frequency whilst still adequately treating the OSA. Limiting pressures should be considered in the future in patients with colorectal disease to avoid faecal incontinence.
Confrontation in the Climacteric
Authors: Joel Wilbush
Journal: Journal of the Royal Society of Medicine (1994)

Why is an increasing number of women dissatisfied with their doctors' help in their climacteric? Why do so many object to hormone replacement therapy (HRT)? Why do they generally feel it is not ‘natural’? Though many object to getting old, want to continue flaunting their ‘eternal youth’, many more, women and men, embrace retirement, wish to rest and slow down. There is no mistaking these extremes, for while the first grasp at every possible treatment, the last are but seldom medically seen. It is the middle majority, their demands, censure, disapproval, even open confrontation with those who try to help them which is difficult to understand. This paper briefly reviews the manner in which Western climacteric women have, during two hundred, but mainly last fifty, years confronted their world: their protests at societal attitudes, their private marital conflicts, their demands of doctors and, finally, their present criticism of them. It also pays detailed attention to the key concept of ‘natural’ treatment. Finally it suggests that much of present climacteric confrontation is a displacement activity, born of concurrent conflicting desires for both youth and retirement, rather than aimed specifically at doctors.
Who looks after people with diabetes: Primary or secondary care?
Authors: Kamlesh Khunti, Sumita Ganguli
Journal: Journal of the Royal Society of Medicine (2000)

Summary Because the prevalence of type 2 diabetes has increased greatly over the past decade, UK general practitioners have been encouraged to develop services for people with diabetes and to offer structured diabetes care. The resultant shift from secondary care can place considerable demands on primary health care teams. Data were obtained from 108 practices in two English health districts followed up in primary and secondary care. Nearly two-thirds of the people with diabetes were being followed up only in general practice, the remainder in hospital or both. The proportion managed in primary care varied from 5.6% to 94.6%. The settings where diabetes care was most likely to be offered were training practices, practices with good nursing support, practices with a high prevalence of diabetes, and practices in which a high proportion of diabetic patients were controlled by diet or hypoglycaemic agents. Tight control of glycaemia and blood pressure is now seen as important in diabetes, and is best achieved in general practice. This survey revealed large variations in delivery of general-practice diabetes care that need to be addressed by better organization and funding.
Blockade of Tissue Factor
Authors: Martha Sue Carraway, Karen E. Welty-Wolf, Debra L. Miller, Thomas L. Ortel, Steven Idell, Andrew J. Ghio, Lars C. Petersen, Claude A. Piantadosi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Blockade of tissue factor before lethal sepsis prevents acute lung injury and renal failure in baboons, indicating that activation of coagulation by tissue factor is an early event in the pathogenesis of acute lung injury and organ dysfunction. We hypothesized that blockade of tissue factor would also attenuate these injuries in established sepsis by prevention of further fibrin deposition and inflammation. Twelve male baboons received heat-killed Escherichia coli intravenously followed 12 hours later by live E. coli infusion. Six animals were treated 2 hours after the live bacteria with site-inactivated Factor VIIa, a competitive tissue factor inhibitor, and six animals were vehicle-treated sepsis control subjects. Animals were ventilated and monitored for 48 hours. Physiologic and hematologic parameters were measured every 6 hours, and pathologic evaluation was performed after 48 hours. Animals treated with site inactivated Factor VIIa had less severe lung injury, with preserved gas exchange, better lung compliance and histology scores, and decreased lung wet/dry weight. In treated animals, urine output was higher, metabolic acidosis was attenuated, and renal tubular architecture was protected. Coagulopathy was attenuated, and plasma interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-1 levels were significantly lower in the treated animals. These results show that blockade of coagulation attenuates acute lung and renal injury in established Gram-negative sepsis accompanied by antiinflammatory effects of therapy.
Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.
Authors: V Leblond, T Ben-Othman, E Deconinck, A L Taksin, J L Harousseau, M A Delgado, A Delmer, F Maloisel, X Mariette, P Morel, J P Clauvel, P Duboisset, S Entezam, O Hermine, M Merlet, I Yakoub-Agha, O Guibon, H Caspard, N Fort
Journal: Journal of Clinical Oncology (1998)

PURPOSE There is no consensus on the treatment of patients with Waldenström's macroglobulinemia (WM) who develop primary or secondary resistance to frontline therapies. We report our experience on the activity and toxicity of fludarabine in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND METHODS From January 1991 to June 1995, 71 patients were included in this retrospective study. The median age, median time from diagnosis to treatment, median immunoglobulin M (IgM) level, and median number of previous treatments were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5 to 126), and two (range, one to four), respectively. RESULTS Seventy-one patients received a median of six courses of fludarabine. Twenty-one (30%) responded with a partial response and 50 (70%) were considered as treatment failures. Forty-six patients died: 10 in the responder group and 36 in the failure group. Twenty-five patients were alive with a median follow-up time of 34 months. The overall median survival time of all treated patients was 23 months. The time to treatment failure was 32 months. The only factor that favorably influenced the response to fludarabine was a longer interval between the first treatment and the start of fludarabine. Pretreatment factors associated with shorter survival in the entire population were hemoglobin level less than 95 g/L (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.
Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients Undergoing Cardiac Surgery
Authors: Alexander Zarbock, Christoph Schmidt, Hugo Van Aken, Carola Wempe, Sven Martens, Peter K. Zahn, Britta Wolf, Ulrich Goebel, Christian I. Schwer, Peter Rosenberger, Helene Haeberle, Dennis Görlich, John A. Kellum, Melanie Meersch
Journal: JAMA (2015)

No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery.To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery.In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle.Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation.The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers.Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL2/1000; difference, 0.61; 95% CI, 0.27-0.86; P < .001). No adverse events were reported with remote ischemic preconditioning.Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation.German Clinical Trials Register Identifier: DRKS00005333.
Effect of computerised evidence based guidelines
Authors: J. D Emery
Journal: BMJ (2003)

Computer support is complex intervention EDITOR-Eccles et al's rigorous approach to the evaluation of a computerised decision support system for the management of angina and asthma accounted for many of the flaws in previous trials of computer support.1They were no doubt disappointed that no effect was seen, probably due to low usage of the system.Although not discussed in the paper, a possible explanation for this is that, given the comparatively high use of computers required for inclusion in the trial, the practices already used simpler computerised templates to promote collection of process of care data.Practitioners may therefore have perceived little further to be gained by using the more detailed decision support system, particularly if it did not allow easy switching between the guideline and the clinical system.The study by Eccles et al shows the complexity of interventions in primary care that incorporate computerised decision support systems.This complexity needs to be fully accounted for in designing and evaluating such interventions.2Even with an apparently well developed piece of software, the trial assumed that offering brief training to a minority of practitioners in each practice would be sufficient for it to be incorporated into the increasingly complex care provided in routine general practice consultations.Trials of computer support in primary care need to acknowledge this complexity by embedding use of the software in a carefully specified model of care.For the high quality management of chronic disease, 1/26/2017 Effect of computerised evidence based guidelines | The BMJ http://www.bmj.
Heart rate and ventilation in a group of burned sugar cane cutters (Brazil): Estimative of particulate matter (PM2,5) exposure load
Authors: Izabela Cozza, Danilo Nambu, Frederico Fernandes, Marcos Bussacos, Renato Paceli, Gustavo Prado, Mario Terra-Filho, Ubiratan Santos
Journal: European Respiratory Journal (2012)

Introduction: The sugar cane harvesting exposes workers to pollutants released by sugar cane burning held hours before. The workers earn per ton cut, what carries considerable physical effort with consequent increase in heart rate (HR) and ventilation (Ve). The HR keeps a good correlation with oxygen uptake and consequently with Ve. Its measurement is a useful method to estimate Ve, which allows estimating the exposure load of pollutants. Objectives: Develop an equation of the linear correlation between HR and Ve and apply it to estimate the pollutant exposure load in sugar cane cutters. Methods: Was developed an equation of the regression line, through data from HR and Ve obtained in ergoespirometry tests of 26 sugar cane cutters. The equation was used to estimate the exposure load in another group of 84 cutters, after registration of HR (using POLAR), during a working day, with concomitant registration of PM2,5 environmental concentration. Results: The PM2,5 average concentration was 61µg/m³ (IIQ: 41.3-86.8 µg/m³). The individual equations obtained from the 26 workers, showed a high correlation with average R2=0.9. The general equation (26) =0.97548+0.01965-LogVe5xCF, showed lowest correlation: R2=0.78. The estimation of exposure/ workday in the group of 84 workers ranged from 282.5 to 1140.1µg/m³ (677.4 ± 190.7 µg/m³). Discussion/Conclusion: Exposure to pollutants was high and there was great variation in daily load exposure among workers. Although the general equations are less suitable than the individual equation to estimate the pollutants load inhaled by an individual, it can help in exposure estimation in population groups.
Predictive value of 6 MWD and derived indices 3 months after initial PAH therapy for the necessity of a combination therapy in patients with pulmonary arterial hypertension
Authors: David Korte, Andreas Rolf, Werner Seeger, Ardeschir Ghofrani, Robert Voswinckel
Journal: European Respiratory Journal (2013)

Aims and objectives

6MWD based prediction of the necessity of future therapy escalation in pulmonary arterial hypertension.

Methods

We retrospectively analyzed 145 PAH patients. Parameters were assessed at initial presentation and 3 months after initiation of PAH monotherapy, time until extension of therapy was documented.

Parameters:6MWD, Borg scale, 6MWD reference equations (RE; Troosters, Enright, Gibbons), percentage of 6MWD related to RE. We introduced an index containing Borg results related to RE (Index = (CR10 + 1) / a6MWD; CR10: Borg CR10 value, a6MWD: ratio of 6MWD related to RE's).

Results

Among all parameters, the BORG incorporating index based on Enright’s RE showed largest AUC (0.6031). Youden index optimal cut-off was 5.74 (68% sensitivity, 57% specificity). Mean therapy escalation free survival was 1767 days (1412 – 2122 95% CI) for patients below the cut-off and 906 days (706 – 1105 95% CI) for patients above the cut-off (p = 0.0001). Univariate Cox proportional hazards model showed that the likelihood of therapy escalation more than doubles, if the patient has an index above the cut-off (hazard ratio 2.3 (1.4 - 3.78 95% CI, p=0.001)). The 6MWD as single parameter showed a sensitivity and specifity of 37% and 80% respectively, AUC of 0.582, hazard ratio 2.0 (1.25 - 3.28 95% CI, p=0.004).

Conclusions

Our newly introduced 6MWD index, generated 3 months after PAH thearpy initiation, had the highest prognostic relevance to predict therapy escalation in PAH.
Novel sequence-based assay for detection of pyrazinamide-resistant mycobacterium tuberculosis in clinical specimens from patients with pulmonary tuberculosis in Russia
Authors: Maria Alvarez Figueroa, Maria Gordukova, Galina Lobashova
Journal: European Respiratory Journal (2011)

Pyrazinamide (PZA) is an important first-line antituberculous drug used in all regimens recommended by the WHO. However PZA susceptibility testing is not routinely performed in many laboratories so comprehensive surveillance studies of pyrazinamide resistance are rare. The aim of our study was to determine the occurrence of PZA-resistant  M.tuberculosis . We developed the diagnostic kit based on direct sequencing of  pncA  gene that was expected to detect all type of mutations. We have examined 143 respiratory specimens obtained from 140 Russian patients with pulmonary tuberculosis. All patients have been classified into 5 groups depending on duration of treatment. The first group consists of patients with newly diagnosed tuberculosis who did not received antituberculous drugs previously or taken them less than a month. The second group included patients from 1 to 3 months of such treatment. PZA-resistance has been found in 9 (10.3%) cases from 87 patients of the first group. The frequency of PZA-resistance of patients from the second group has been amounted to 41.6%. In half of these cases we found heterogeneous populations of bacilli consisted of wild and mutation types. PZA-resistance strains were detected in 7 (36.8%) of 19 patients from the third group with a duration of treatment from 3 to 6 months, in 6 (75.0%) of 8 patients with a duration of treatment from 6 to 9 months, and in 4 (80.0%) of 5 patients receiving antituberculous drugs from 9 to 12 months. These data suggest that the sequencing assay may be useful for the direct and rapid detection of PZA-resistant  M.tuberculosis  in clinical specimens.
Abstract 308: Targeted Inhibition of Cardiac Ankyrin Repeat Protein Disrupts Sarcomeric ERK-GATA4 Signaling at the Titin I-band and Abrogates Agonist-Induced Cardiac Hypertrophy
Authors: Chee Lim, Lin Zhong, Manuel Chiusa, Adrian Cadar, Susan Samaras, Jeffrey M Davidson
Journal: Circulation Research (2014)

Hypertrophic cardiomyocyte growth occurs in response to various stress stimuli including biomechanical stress and neurohormonal factors. Accumulating evidence suggest that sarcomere signaling complexes play a pivotal role in the cardiomyocyte hypertrophic response by transmitting signals to the nucleus to induce gene expression. Cardiac ankyrin repeat protein (CARP, Ankrd1) is a transcriptional regulatory protein that also associates with the titin I-band spring domain, however the exact role of CARP in the heart remains to be elucidated. We report that CARP directly interacts with mitogen activated protein kinase ERK1/2 and cardiac transcription factor GATA4. Phenylephrine (PE) stimulation in cardiomyocytes induced ERK1/2 and GATA4 to transiently co-localize with sarcomeric CARP, followed by translocation of CARP and GATA4 to the nucleus. Four-and-a-half-LIM (FHL) domains proteins are part of a sarcomeric ERK2 sensory complex and knockdown of CARP by small interfering RNA (siRNA) resulted in disruption of FHL1 and FHL2. Moreover, loss of CARP attenuated PE-induced phosphorylation of ERK1/2 and GATA4, decreased GATA4 DNA binding, and prevented PE-induced cardiomyocyte growth. Mice lacking CARP have decreased FHL1 levels, and PE stimulation in wild-type mice resulted in elevated GATA4 phosphorylation and a hypertrophic response, which were completely abrogated in CARP-KO mice. We demonstrate that CARP plays an important role in PE-induced hypertrophic signaling by recruiting ERK2 and GATA4 into a titin I-band macro-molecular complex to induce GATA4 activation, followed by translocation of CARP and GATA4 to the nucleus to enhance GATA4 DNA binding and hypertrophic gene expression. Loss of CARP destabilizes FHL1 and FHL2, resulting in disruption of the PE-induced sarcomeric complex and abrogation of the cardiomyocyte hypertrophic response. These data reveal a novel role for sarcomeric titin I-band as a transcription factor activation hub that induces downstream nuclear signaling in response to agonist-induced hypertrophic stimuli.
Brentuximab in the Treatment of CD30-Positive Enteropathy-Associated T-Cell Lymphoma
Authors: Waleed F. Khalaf, Meghan E. Caldwell, Nishitha Reddy
Journal: Journal of the National Comprehensive Cancer Network (2013)

Enteropathy-associated T-cell lymphoma (EATL) is a rare aggressive lymphoma that confers a poor prognosis with current treatment strategies. Given the rarity of this disease, prospective randomized trials are limited, and thus a standard validated treatment strategy is lacking. This report presents the disease course of a patient with EATL who was treated with single-agent brentuximab vedotin, an anti-CD30 conjugated antibody.
Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity
Authors: Yael Zlotnikov-Klionsky, Bar Nathansohn-Levi, Elias Shezen, Chava Rosen, Sivan Kagan, Liat Bar-On, Steffen Jung, Eric Shifrut, Shlomit Reich-Zeliger, Nir Friedman, Rina Aharoni, Ruth Arnon, Oren Yifa, Anna Aronovich, Yair Reisner
Journal: Immunity (2015)
The nosologic status of borderline personality: clinical and polysomnographic study
Authors: Hagop S Akiskal, Boghos I. Yerevanian, Glenn C. Davis, Doug King, Helio Lemmi
Journal: American Journal of Psychiatry (1985)

The REM latencies of 24 nonschizotypal borderline outpatients--who were not in the midst of a major depressive episode--were in the range of those of 30 patients with primary major depression but were significantly shorter than those of 16 patients with nonborderline personality disorders and 14 nonpsychiatric controls. Also, more of the borderline subjects had lifetime diagnoses of affective disorder, such as dysthymic, cyclothymic, and bipolar II disorder, and of a spectrum of anxiety and somatization disorders. The authors conclude that contemporary operational criteria for borderline disorder identify a wide net of temperamental disorders with strong affective coloring rather than a unitary nosologic entity.