tbuckley/cabot-search huggingface dataset:
Alveolar macrophages that suppress T-cell responses may be crucial to the pathogenetic outcome of pulmonary sarcoidosis
Authors: MA Spiteri, SW Clarke, LW Poulter
Journal: European Respiratory Journal (1992)

The alveolar macrophage (AM) population is widely recognized to be heterogeneous; distinct subpopulations can be identified by the use of macrophage-specific monoclonal antibody (MoAb) probes. We have isolated a macrophage subset that appears to react with both MoAbs that have previously discriminated between dendritic cells and classic macrophages. In the bronchoalveolar lavage (BAL) of patients with active sarcoidosis the proportion of this specific AM subpopulation increases dramatically (30.4 +/- 4.01% compared to 6.14 +/- 1.56% in normal BAL). This AM subset not only increases in direct proportion to the lavage lymphocytosis, but also exhibits sarcoid-related differences in surface receptor expression, physiology and induction of T-cell responses. An increased number of these AM expressed a separate antigen RFD9 (which identified epithelioid cells), and had raised fibronectin content, increased phagocytosis, and high lysosomal enzyme activity. Of functional significance, we found that while in normal volunteers this specific AM subset was capable of down-regulating by as much as 40% the induction of T-cell responses set up by other stimulator macrophages, in sarcoid patients this suppressor activity was enhanced, such that T-cell responses were completely abolished. In some studies this action was masked by the reduced enhancing capacity of sarcoid inducer AM. We postulate that the presence of an increased proportion of these suppressor AM (together with their sarcoid-specific features) in active sarcoidosis is of crucial significance in determining the fate of granulomata in the lungs of these patients.
Omentopexy in rabbit for the repair of diaphragmatic defect and adhesion assessment of viscera to propylene mesh
Authors: Abdoulhossein Davoodabadi, Mehrdad Housseinpour, Naser Golestani
Journal: European Respiratory Journal (2011)

Background:  The use of synthetic mesh for the repair of major congenital diaphragmatic hernia may cause visceral adhesion to prosthesis and ongoing complications. In present study the use of propylen mesh for the repair of diaphragmatic hernia and its role in eliminating of visceral adhesion to repair site is evaluated.   Materials & methods:  This experimental study was carried out on 20 adult New Zealand rabbits (age: 6 months) assigned randomly into two equal groups. In one group, after laparatomy a defect (size: 1×1 cm) was created on the diaphragm. The suture was then repaired by sterile propylen mesh and nylon suture (thickness: 3/0 - 4/0). In another group, omentum was fixed on the mesh using a nylon suture (thickness: 3/0). After 30 days the two groups were operated and the visceral adhesion to repair site was compared using Mazuji scale.   Results:  Nine (90%) out of 10 rabbits with propylen mesh repair had visceral adhesion to the repair site. On classifying the grade of adhesion among the cases, one, three, four and two rabbits were assigned the “0”, “I”, “II”, and “III” grades, respectively. On the other hand, 4 (40%) out of 10 rabbits, in which the diaphragm was repaired by propylen mesh and omentopexy method, visceral adhesion (grade “I”) was seen to the site of repair. The rest of animals displayed no such adhesion (P=0.015).   Conclusions:  Omentoplasty after, repair of large diaphragmatic defect with propylen mesh reduces the visceral adhesion to propylen mesh, so in itraabdominal operations which propylen mesh is used, omentoplasty also is recommended
Impact of obstructive sleep apneas/hypopneas on blood pressure during a short period of stable sleep. A relevance for blood pressure variation?
Authors: Richard Staats, Dina Fernandes, João Valença, Margarida Aguiar, Moreira Susana, Inês Claro, Luís Ferreira Moita, Antόnio Bugalho de Almeida
Journal: European Respiratory Journal (2011)

Introduction:  There is evidence that obstructive sleep apneas (OSA) are involved in the development of hypertension. However, the precise mechanism is still under discussion.   Methods:  We anlysed 34 patients via polysomnography and simultaneous beat to beat measurement of systolic (Sys) and diastolic (Dia) blood pressure (BP) (NexfinHD). Group1: apnea/hypopnea index (AHI) 0-15/h, n=16; Group2: AHI >15/h n=18. All results during 10 min. stable N2 sleep were calculated after data export using the SPSS software. A p   Results:  In group1 BP decreased during N2 sleep (Sys -1,9±1.8 mmHg; Dia -1.3mmHg ±1.36 mmHg) while in group2 Sys showed no change (-0,05±1.6 mmHg) and Dia increased (+0.41 mmHg ±1.1 mmHg). However, these results did not reach significance. BP changes did not correlate with the AHI, desaturation-index, percent of oxygen   Discussion:  We could show, that in OSAS patients during a short period of sleep the changes of BP are not directly correlated with the expected sleep or respiratory parameters but with the variation of blood pressure values. The relevance of this result for the development of hypertension remains to be proven.  This work was supported by the Fundacao para a Ciencia e a Tecnologia PIC/IC/82991/2007
Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group.
Authors: P A Bunn, J Crowley, K Kelly, M B Hazuka, K Beasley, C Upchurch, R Livingston, G R Weiss, W J Hicks, D R Gandara
Journal: Journal of Clinical Oncology (1995)

PURPOSE This phase III randomized trial was designed to determine if granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicity and morbidity induced by chemoradiotherapy in limited-stage small-cell lung cancer (SCLC). METHODS This multicenter prospective trial randomized 230 patients to receive chemotherapy and radiotherapy (RT) with or without GM-CSF given on days 4 to 18 of each of six cycles. The primary end point was hematologic toxicity. Secondary end points included the following: nonhematologic toxicities; days of (1) fever, (2) antibiotics, (3) hospitalization, and (4) infection; number of transfusions; drug doses delivered; and response rates and survival. RESULTS There was a statistically significant increase in the frequency and duration of life-threatening thrombocytopenia (P &lt; .001) in patients randomized to GM-CSF. GM-CSF patients had significantly more toxic deaths (P &lt; .01), more nonhematologic toxicities, more days in hospital, a higher incidence of intravenous (IV) antibiotic usage, and more transfusions. Patients randomized to GM-CSF had higher WBC and neutrophil nadirs (P &lt; .01), but no significant difference in the frequency of grade 4 leukopenia or neutropenia. Patients randomized to GM-CSF had a lower complete response rate (36% v 44%), but the differences were not significant (P = .29). There were no significant differences in survival (median, 14 months on GM-CSF and 17 months on no GM-CSF; P = .15). CONCLUSION GM-CSF, as delivered in this study, should not be included with concurrent chemoradiotherapy treatment programs for limited-stage SCLC. The simultaneous use of hematopoietic colony-stimulating factors (CSFs) and chemoradiotherapy should be performed only in experimental settings. Chemoradiotherapy programs with cisplatin and etoposide ([VP-16] PE) and simultaneous chest RT produce grade 4 neutropenia and thrombocytopenia in a small-enough proportion of patients that prophylactic hematopoietic growth factors are clinically unnecessary.
Effect of heated humidification during initiation of home mechanical ventilation (HMV): A randomised cross-over trial
Authors: Swapna Mandal, Eui-Sik Suh, Michelle Ramsay, John Moxham, Nicholas Hart
Journal: European Respiratory Journal (2013)

INTRODUCTION:  Heated humidification(HH) use during HMV is controversial. We hypothesised HH would reduce comfort during HMV initiation due to increased dead space and reduced triggering performance.  METHODS:  Consecutive patients were enrolled.Patients received NIV with HH(MR810 Fisher Paykel NZ) or without(NH) for 3 weeks, then crossed over.Patients underwent overnight studies after each 3 week period with parasternal electromyogram(EMGpara), respiratory inductance plethysmography, mask pressure, transcutaneous oxygen(SpO 2 ) and carbon dioxide(TcCO 2 ) monitoring.Health related quality of life(HRQL) measures:Severe Respiratory Insufficiency(SRI) questionnaire and comfort with visual analogue scores(VAS).  RESULTS:  12 patients(5males) have been recruited to date(age 61±10years).Paired data are presented for 9.There was a difference in bicarbonate(mmol/l) between baseline and the end of each treatment period(baseline34±3, NH32±4 and HH31±4; p 2  between the groups, however, there was a fall from baseline in the HH group.There was a significant difference between the IPAP and mask pressure during NH arm(p=0.03).There was no difference in overall HRQL and VAS between the groups, however some components in the SRI improved during HH.  CONCLUSIONS:  These data demonstrate HH does not adversely affect HMV and may enhance ventilation shown by the greater fall in TcCO 2 .
GP training should prepare juniors for work as locums, says doctors' association
Authors: A. Rimmer
Journal: BMJ (2015)

General practice training should prepare doctors to work as locums, the head of the National Association of Sessional GPs (NASGP) has said.

Speaking to BMJ Careers, Richard Fieldhouse said that, although many GPs chose to become locums, at no point did their training focus on how to do the job. “GPs in training do not get any training at all on how to work as a locum,” he warned.

Research carried out by the association last year found that 28% (17 190) of the 60 630 GPs working …
Abstract 680: KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C
Authors: Stephen G Miller, Constance Crowley, Jan Lundstrom, Christopher J Larson, Kent E Prior, Bernard D King
Journal: Circulation (2007)

Introduction: KC706 is a novel p38 MAP kinase inhibitor with anti-inflammatory properties. In rats and monkeys, KC706 administration was associated with a 50 – 60% ↑ in HDL-C. Because HDL-C is an important target for the treatment of CV disease a Phase 2a study was designed to determine whether KC706 administration would elevate HDL-C levels in patients with dyslipidemia. Methods: A double-blind, placebo-controlled, 6-week study was conducted in patients with ↓ HDL-C and ↑ triglyceride (TG) levels. Patients (N = 115) were randomized to placebo or to KC706 (150 or 300 mg po qd). Standard chemistry and hematology parameters and lipid, metabolic, inflammatory, and thrombotic markers were monitored. The primary end point was an increase in HDL-C in treatment v. placebo groups. Results: Patients were primarily male (59%) and white (97%). At baseline, 35% were receiving statins, 44% were hypertensive, 15% had CV disease, 70% fulfilled ATPIII criteria for metabolic syndrome, and 43% had CRP &gt; 3 mg/L. The primary endpoint of the study was met at both dose levels. Compared to baseline, HDL-C ↓ 2.9% in the placebo group, ↑ 18.6% in the 150 mg group (p &lt; 0.0001 v. placebo) and ↑ 11.6% in the 300 mg group (p = 0.0003 v. placebo) after 6 wks of treatment. Effects were noted in men and women, whether patients were receiving statins or not, and whether CRP was elevated or not at baseline. ApoAI ↑ significantly in the 150 mg group (p = 0.0056 v. placebo). TG, LDL-C, and VLDL-C were unchanged. CRP levels trended downward in patients with ↑ baseline CRP levels. HDL/Total cholesterol (+22%), ApoA1/ApoB100 (+14%), and HDL/LDL (+31%) increased in the KC706 150 mg group. Mean HDL particle size (measured in a subset of patients) increased from 8.4 to 8.7 nm in the KC706 150 mg group (p = 0.04), from 8.5 to 8.7 nm in the KC706 300 mg group (p = 0.01) but not in the placebo group (8.3 v. 8.4 nm, p = 0.66). No increases in either systolic or diastolic blood pressures were observed in any group. One patient in the 150 mg group and 4 in the 300 mg group had a reversible elevation in either AST and/or ALT of &gt; 3X ULN. Adverse events were similar in the 3 treatment groups. Conclusions: KC706, an oral p38 MAP kinase inhibitor with anti-inflammatory properties, increased HDL and ApoA1 in patients with dyslipidemia and was well tolerated.
Abstract 19169: Is Left Ventricular Twisting Obtained Using Three-dimensional Ultrasound Speckle Tracking Imaging Useful in Assessing Left Ventricular Function?-Comparison with Invasive Parameters
Authors: Kazuaki Wakami, Nobuyuki Ohte, Hiroo Sonoda, Shohei Kikuchi, Noriyuki Ikehara, Toshihiko Goto, Hidekatsu Fukuta, Tomomitsu Tani, Genjiro Kimura
Journal: Circulation (2010)

Background:  During systole the left ventricle (LV) presents an opposite rotation between the apical and the basal levels, that is, LV twisting. A novel 3-dimensional ultrasound speckle tracking imaging (3D-STI) enables us to evaluate these motions simultaneously. We investigated whether LV twisting or untwisting had relations with invasively obtained LV systolic and early diastolic function parameters.   Methods:  Study subjects consisted of consecutive 27 patients who underwent diagnostic cardiac catheterization and echocardiographic examination simultaneously. We acquired 3D images (Artida, Toshiba) at rest lying in the supine position with recording LV pressure simultaneously during cardiac catheterization. Frame rate ranged was from 30 to 35 frames per second. Seven of them were excluded from analyses due to insufficient image quality. The twisting of LV was calculated by a newly developed software (Ultra-Extend, Toshiba). Twisting of LV was expressed in degrees, negative if clockwise and positive if counterclockwise. Peak twisting during systole was obtained as the difference between apical and basal rotation. Amplitude of untwisting during early diastole was also calculated. From the recorded pressure waves in cardiac catheterization, both peak positive and negative dP/dt were determined and then the time constant τ of LV isovolumic relaxation was also calculated.   Results:  Peak twisting during systole significantly correlated with both negative dP/dt (r=0.76, p   Conclusions:  These findings indicate that LV relaxation is related not only to the amplitude of LV untwisting during early diastole but also to the peak LV twisting during systole. Twisting of LV plays a crucial role in producing LV elastic recoil and is closely related to LV relaxation.
Abstract P149: CPR Feedback Improves the Quality of Chest Compressions Performed by Healthcare Providers
Authors: Mary Ann Peberdy, Annemarie Silver, Phyllis Faulkenberry, Lisa Ferland, Joseph Ornato
Journal: Circulation (2008)

Purpose : Healthcare providers are often unable to perform chest compressions (CC) consistently within AHA guideline recommendations of 100 CC/minute at a depth of 1.5–2 in. The present study examined the effect of audiovisual CPR feedback on the quality of CC performed by healthcare providers. Methods: One hundred twenty-five ACLS and BCLS trained hospital based healthcare professionals participated in “CPR challenges” at 14 U.S. hospitals. Participants performed 2 minutes of CC on a manikin without any feedback initially. Following a ≥90 second rest period and ~20 second orientation to the audiovisual feedback prompts, participants repeated 2 minutes of CC with feedback prompts. Data were recorded using a ZOLL AED Plus. Rescuers were categorized based upon mean depth of CC without feedback: 1) under-performers (depth&lt;1.5in; n=60); 2) within guideline-performers (depth&lt;1.5–2in; n=52); and 3) over-performers (depth&gt;2in; n=13). Results: Mean depth of CC improved with CPR feedback (1.57±0.36in without feedback vs. 1.71±0.13in with feedback, mean±SD, p&lt;0.0001) and the percentage of CC within 1.5–2in increased from 38 to 87% (p&lt;0.0001). In under-performers, depth of CC substantially increased with CPR feedback (1.30±0.12 vs. 1.66±0.13in; p&lt;0.0001) and the percentage of CC within 1.5–2in improved from 9 to 81% (p&lt;0.0001). Over-performers were corrected to meet AHA guidelines for depth with feedback (2.31±0.40 vs. 1.83±0.07in, p=0.001). The percentage of CC within 1.5–2 in improved from 13 to 90% with feedback (p&lt;0.0001). For within guideline-performers, depth of CC was similar with and without feedback (1.70±0.14 vs.1.74±0.10in, p=0.08) but the percentage of CC within 1.5–2 in increased with feedback from 79 to 92% (p&lt;0.0001). Rate of CC was corrected with CPR feedback in under-performers (110±17 vs. 100±4 CC/min, p&lt;0.0001) but was unchanged with feedback in within guideline-performers (103±15 vs. 100±3 CC/min, p=0.2) and over-performers (97±14 vs. 100±8 CC/min, p=0.4). Conclusions: Audiovisual feedback improves the quality of CC provided by hospital-based healthcare professionals in a manikin testing scenario. Healthcare providers can improve consistency of CC with CPR feedback regardless of their performance without feedback.
Antibodies to Bovine Leukemia Virus and Presence of Malignant Lymphoma in Slaughtered California Dairy Cattle&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Mark C. Thurmond, Charles H. Holmberg, John P. Picanso
Journal: JNCI Journal of the National Cancer Institute (1985)

Rates of malignant lymphoma (ML) in California dairy cattle and relationships between ML and presence of antibodies to bovine leukemia virus (BLV) were investigated. An excessively high rate of lymphoma was found in the population studied and a previously unknown relationship between ML and p-24 antibodies to BLV was identified. Sera from slaughtered California holstein dairy cows were tested by agar gel immunodiffusion for presence of antibodies to the gp-51 and p-24 antigens of BLV. Of the 7,760 cows slaughtered, 32% and 10% had gp-51 and p-24 antibodies, respectively, and 52 cows (0.67%) were condemned for ML. Lymphoma was diagnosed histopathologically in 37 (86%) of 43 cows sampled from those 52 condemned. Highly elevated prevalence rates of ML in gp-51 and p-24 antibody-positive cows were 172.6 and 511.5 per 10,000 cows, respectively. A prevalence rate of lymphoma not associated with presence of BLV antibodies was estimated for the first time to be 1.55 per 10,000 cows. A highly significant (P less than .00001) and strong (odds ratio = 26.0) association was found between presence of p-24 antibodies and presence of ML for cows with gp-51 antibodies. When results of serologic tests were compared in regard to diagnosis of ML, the highest sensitivity was with use of gp-51 serology alone (97.3%) and highest specificity was with use of p-24 serology alone (90.4%). False-negative and false-positive rates of diagnosis of ML for gp-51-positive, p-24-negative and gp-51-positive, p-24-positive cows were 0.21 and 94.8%, respectively.
Effect of cigarette smoke on proteasome function in alveolar epithelial cells
Authors: Sabine van Rijt, Alessandra Mossina, Oliver Eickelberg, Silke Meiners
Journal: European Respiratory Journal (2011)

Cigarette smoke is the major risk factor for chronic obstructive pulmonary disease (COPD), which accounts for several million deaths annually world-wide. The generation of reactive oxygen species (ROS) is considered to be the major contribution to smoke-induced inflammation, DNA damage and posttranslational modifications resulting in subsequent misfolding of cellular proteins. The ubiquitin proteasome system is essential for the turnover of the majority of cellular proteins. The proteasome also plays a vital role in protein quality control as it degrades abnormal and misfolded proteins, among them oxidatively-modified proteins. Conditions of massive oxidative stress, however, may result in impairment of proteasome function as ROS can directly modify the proteasome complex. In the present study, we have investigated proteasome function in response to cigarette smoke extract (CSE) of human and mouse epithelial cells. Treatment of these cells with CSE resulted in a time and dose-dependent increase in ROS levels. The proteolytic activities of the proteasome were assessed using peptide substrates. Two of the three main proteasome activities, namely the chymotrypsin-like and caspase-like activity, showed a time and dose-dependent alteration in response to CSE treatment. The altered proteasomal activity corresponded to accumulation of oxidatively modified and polyubiquitinated proteins. The effect of CSE on the ratio and composition of 26S and 20S proteasomes was analysed by native gel electrophoresis, immunoprecipitation and subsequent mass-spec analysis. Preliminary data reveal posttranslational modifications of proteasomal subunits which may be responsible for the alteration of proteasome activity.
Dose escalation study in healthy male subjects to investigate safety, tolerability and systemic exposure of orally inhaled single-doses of AP301
Authors: Helmut Pietschmann, Hendrik Fischer, Susan Tzotzos, Bernhard Fischer, Markus Zeitlinger, Rudolf Lucas, Robert Hermann, Hermann Mascher
Journal: European Respiratory Journal (2012)

Pulmonary edema is a major complication of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) which is associated with higher mortality.  AP301 is a synthetic peptide whose structure is based on the lectin-like domain of human Tumour Necrosis Factor alpha. The water soluble peptide can be administered into the lung by oral inhalation. AP301 was designed to activate the pulmonary epithelial sodium channel (ENaC) in type II alveolar cells to accelerate alveolar liquid clearance.  We report the early clinical development of AP301: In the Phase I monocentric FiM trial “Dose escalation study in healthy male subjects to investigate safety, tolerability and systemic exposure of orally inhaled single-doses of AP301” the safety, tolerability and pharmacokinetic profile of AP301 was evaluated in a double-blind, randomized, placebo-controlled, parallel group study that started in April 2011 and was completed in October 2011 at the General Hospital in Vienna. 48 healthy young males received escalating doses of aerosolized AP301 in 6 dose groups between 0.07 mg/kg to 2 mg/kg AP301 per inhalation.  Lung function parameters like FEV1 or PEF were not affected by AP301. Exhaled nitric oxide did not increase. Physical examinations showed no inhalation-related clinical signs or symptoms of paradoxical bronchospasm. No local reactions in the mouth like severe xerostomia or burning sensation were described. Vital signs, ECG and safety laboratory parameters showed no pathological findings. AP301 did not accumulate in plasma.  This phase I trial demonstrated that orally inhaled AP301 was safe and well-tolerated by all study subjects.
Lethal extrapulmonary mycobacteriosis
Authors: S Kos, J Dura, J Jirasek
Journal: European Respiratory Journal (1989)

A 60 yr old previously healthy man was treated for gradually elevating fever and rash followed by leucopenia and mycosis of the gastrointestinal tract; he died within 6 weeks of the first symptoms appearing. Histologic examination revealed disseminated tuberculosis of paratracheal lymph nodes, liver, spleen and bone marrow with the presence of acid fast bacilli by smear examination. Multiple colonies of the same strain of Mycobacterium kansasii were isolated by bacteriological examination of lymph node and spleen tissue. Neither macroscopical nor histological examination showed any evidence of lung tuberculosis. The final diagnosis of the described acute disease and rapid death was stated as generalized extrapulmonary mycobacteriosis, which is a rare observation.