tbuckley/cabot-search huggingface dataset:
QVA149 reduces the risk of moderate-to-severe exacerbations compared with open-label tiotropium in patients with severe COPD: The SPARK study
Authors: Jadwiga A. Wedzicha, Marc Decramer, Petter Olsson, Hungta Chen, Robert Fogel, Donald Banerji
Journal: European Respiratory Journal (2014)

Introduction   QVA149 is an approved once-daily (o.d.) dual bronchodilator combination of the LABA, indacaterol, and the LAMA, glycopyrronium (GLY), for the maintenance treatment of patients (pts) with symptomatic COPD. Here we present the results of a post-hoc analysis conducted to evaluate the rate ratio (RR) of exacerbations in pts with severe COPD in the SPARK study. 1    Methods   This 64 week, multicentre, double-blind, parallel-group, active-controlled (open-label TIO and GLY) study randomised pts with severe-to-very severe COPD and a history of ≥1 exacerbation in the previous year to receive o.d. QVA149 110/50µg, GLY 50µg or TIO 18µg.   Results   Of the 2224 pts randomised, 1744 had severe COPD (QVA149=579; GLY=584; TIO=581). QVA149 reduced the risk of moderate-to-severe exacerbations vs. GLY by 11% (RR 0.89; 95% CI 0.77, 1.04) and TIO by 15% (RR 0.85; 95% CI 0.73, 0.98) in pts with severe COPD. In a majority of subgroups QVA149, compared with TIO, reduced the risk of moderate-to-severe exacerbations (Figure). A similar reduction in risk of moderate-to-severe exacerbations was also seen with QVA149 compared with GLY in most of the subgroups.   Conclusions   Risk of moderate-to-severe exacerbation was reduced in severe patients with COPD who were treated with QVA149 compared with GLY and TIO.   Reference   1. Wedzicha et al. Lancet Respir Med 2013;1:199–209.
The ‘Holding Function’ of Dynamic Psychotherapy in a Custodial Setting: A Review
Authors: Murray Cox
Journal: Journal of the Royal Society of Medicine (1986)

The dual connotation of words such as security or identity, which both forensic psychiatry and dynamic psychology regard as their own, is nowhere more evident than in relation to the words ‘hold’ and ‘holding’. The dictionary entry under ‘hold’ includes ‘keep fast, keep possession, detain, remain unbroken, grasp, not give way, adhere to, maintain, hold out — hope — possibility’. Whereas, a group of patients at Broadmoor, an alternative source of information, offered the following associations: ‘We are held … we can't walk through the gates … we hold ourselves here by what we've done … we need to be able to hold out … we need someone to hold us … we need someone to hold on to’. Indeed, one patient felt that he had let go of the therapist ‘too soon’, thus recalling the words of Stevie Smith: ‘You have weaned me too soon, you must nurse me again’ ( The Wanderer).
Day-Case Surgery: Enhanced Recovery with Flumazenil
Authors: B R P Birch, K M Anson, E Clifford, R A Miller
Journal: Journal of the Royal Society of Medicine (1990)

In an open, randomized, parallel group study of 84 adult patients undergoing elective day-case urological surgery the specific benzodiazepine antagonist flumazenil was shown to reverse effectively subjective postoperative sedation due to midazolam and enabled 83% of patients to recover and be ready for potential discharge within 15 min of surgery (control group 24% p&lt;0.001). The significantly shorter recovery time has benefits in terms of increased patient cooperation and reduced demands on postoperative nursing care. The implications of these findings for day-case surgery are discussed.
Nutritional status in patients with bronchiectasis
Authors: Leila Boussoffara, Nadia Boudawara, Imen Touil, Mouna Ben Khelifa, Mounira Sakka, Jalel Knani
Journal: European Respiratory Journal (2012)

Introduction: the association between nutritional depletion and chronic respiratory diseases has been recognised for years and mainly documented in chronic obstructive pulmonary disease. However little information is available regarding nutritional depletion in patients with bronchiectasis.

Aims of the study: this study was carried out to determine the nutritional status in patients with bronchiectasis and the relationship between the extent of these bronchiectasis on the C-T scan and nutritional depletion.

Methods: in 45 patients with bronchiectasis, body mass index (BMI), serum albumin, C-reactive protein and spirometry were recorded.

Results: BMI was  6mg/l in 80% and were higher essentially in patients who had more than one pulmonary lobe affected by bronchiectasis. BMI was not correlated to the extent of bronchiectasis, but serum albumin was correlated with p=0,02. BMI and serum albumin were not correlated with Post-bronchodilator FEV1 and long-term oxygen therapy.

Conclusion: Malnutrition is coming to be highly prevalent in patients with bronchiectasis. Assessing this nutritional depletion may be offers benefits to patients with bronchiectasis.
Prevalence of germline BRCA1 and BRCA2 deleterious and of unknown clinical significance (UCS) mutations in positive hormone receptor female breast cancer patients.
Authors: M. D. Estevez-Diz, S. Maistro, K. A. Escobar, F. S. Pasini, I. M. Snitcovsky, M. Brentani, P. M. Hoff, M. H. Federico
Journal: Journal of Clinical Oncology (2010)

e12006 Background: Breast cancer patients' carriers of germline mutations of BRCA1/2 needs specific screening, prophylaxis and treatment strategies. Recent data suggested an increasing chance of positive hormonal receptor (HR+) breast cancer in older pts with BRCA1 mutation. Several algorithms were proposed to North American and European population but none was validated to Brazilian pts. The definition of the profile of BRCA1/2 mutation and appropriated screening criteria for DNA sequencing is important to identify these high-risk breast cancer pts and families. Methods: Female breast cancer patients under treatment in a Brazilian university hospital from September 2005 to July 2006 were invited to be evaluated for hereditary breast cancer risk. Germline BRCA1/2 mutations risk was estimated by Frank, BRCAPRO and Evans algorithms and 10% or higher in any was considered as high risk. Pts with personal or familiar histories suggestive of other hereditary syndromes were excluded. Demographic data and tumor pathological features were extracted from prospectively registered medical records. Results: 180 pts were evaluated (68.3% of invited) and 60 were classified as high risk. DNA sequencing was done in 40 pts with HR+ cancer. Diagnosis mean age was 47.8y (28-71), 50% pre menopause; 40/40 DIC and 8 (20%) bilateral breast cancer. Familiar history was positive in 31 pts (77.7%), 10 (34.1%) had at least two first- or second-degree relatives with breast/ ovarian cancer. 17/40 had a risk ≥ 10% in all three algorithms. 51 UCS mutations were identified, 44 in BRCA1 and 7 in BRCA2. Deleterious mutations were identified in 5 pts, R71G at exon 5 in BRCA1 and 4 in BRCA2: R3128X at exon 25 (2pts), 5844del5 and 6633del5 at exon 11. Familiar history was positive in all, in 4/5 diagnosis was made before 50y (mean 45y), and two (40%) had bilateral breast cancer pts with deleterious mutations. Several polymorphisms were found in all pts. Conclusions: New screening methodology needs to be developed to Brazilian pts as the role of unknown clinical significance mutations in these high risk patients. No significant financial relationships to disclose.
Aerobic exercise training attenuates the decrease in heart rate variability induced by exposure to cigarette smoke in mice
Authors: Alessandra C. Toledo, Josemara Brito, Renato M. Magalhães, Agostinho C. Caleman-Neto, Bernardo Camilo, Francine Almeida, Petra Mello, Clarice R. Olivo, Fernanda D.T.Q.S. Lopes, Chin J. Lin, Paulo H.N. Saldiva, Mílton A. Martins
Journal: European Respiratory Journal (2011)

Smoking has been shown to influence the tone of the autonomic nervous system as reflected by heart rate variability (HRV) a predictor of increased cardiac risk and aerobic exercise (AE) training has been described as capable to modulate the HRV.   Objective:  This study evaluated the temporal effects of aerobic exercise in the HRV in mice exposed to cigarette smoke (CS).   Methods:  C57Bl6 mice were divided in 4 groups: Control, Smoke, Exercise and Smoke/Exercise. Smoke groups were exposed to CS for 30min/day (twice), 5days/week for 12 weeks. Exercise groups were trained at moderate intensity for 60min/day, 5days/week for 12 weeks. HRV was measured at baseline and 2, 4, 6, 8, 10 and 12 weeks after the last CS exposure and/or AE session. HRV was measured by a cuff (noninvasive tool) applied to the base of the mouse tail coupled to PowerLab system. The following parameters were used: heart rate (HR), HRV for time domain (standart deviation of normal beats [SDNN] and root mean square of successive differences in the heart beat interval [RMSSD]) and frequency domain (low frequency [LF], high frequency [HF] and LF/HF ratio).   Results:  Exposure to CS decreased SDNN and RMSSD values after 6 weeks (p   Conclusion:  Our results suggest that AE training at moderate intensity have beneficial effects on cardiac autonomic nervous function, a clinically relevant predictor of cardiovascular morbidity and mortality, in mice exposed to cigarette smoke.
Renal Hemodynamics and Ammoniagenesis
Authors: Guy Lemieux, Patrick Vinay, Pierre Cartier
Journal: Journal of Clinical Investigation (1974)

Renal production of ammonia by the left kidney was studied in 31 acidotic dogs (NH(4)Cl) after acute constriction of the renal artery. Renal ammoniagenesis fell in direct proportion with the reduction in glomerular filtration rate and renal plasma flow. The renal extraction of glutamine by the experimental kidney fell in direct proportion with the reduction in renal hemodynamics. Extracted glutamine remained greater than filtered glutamine indicating that both the luminal and antiluminal transport sites were operative. The relationship between renal extraction of glutamine and ammoniagenesis observed during control was maintained after renal artery constriction (1.7 mumol NH(3) produced for each mumol of glutamine extracted). Systemic venous or renal intra-arterial infusion of glutamine during arterial constriction increased renal production of ammonia to or above control values. These observations indicate that the mechanisms responsible for glutamine extraction and ammonia production were operating normally despite reduced hemodynamics. When measured immediately after arterial clamping, the renal venous pNH(3) was found to rise significantly decreasing progressively thereafter towards control values. The extracted fraction of total glutamine delivered to the kidney (31%) did not change after acute reduction of the glutamine load. Thus, the antiluminal extraction site was incapable of lowering renal venous plasma glutamine concentration below 0.33 muM/ml. In a second series of experiments, the properties of the antiluminal site of transport for glutamine were studied after complete occlusion of the left ureter in acidotic and nonacidotic animals. Under these circumstances, it was demonstrated that the antiluminal site is capable of extracting sufficient glutamine to maintain total ammonia production at 60% or more of control. In acidotic animals, changes in cellular pNH(3) appeared to play a key role on the antiluminal extraction of glutamine since the significant rise in renal blood flow often observed after ureteral occlusion prevented the rise in pNH(3) noted when blood flow remained constant. Thus, when renal blood flow rose glutamine extraction and ammonia production were maintained at control values. In these acidotic animals, glutamine infusion failed to influence ammonia production until luminal transport was restored by release of ureteral clamp and resumption of glomerular filtration. The latter observation establishes that reabsorbed glutamine is utilized at least in part for ammonia production.
Tabetic Charcot's Spine
Authors: D. J. Campbell, J. O. Doyle
Journal: BMJ (1954)

With 'the improvement in medical care of the syphilitic woman at the time of marriage-and during pregnancy, congenital syphilis is becoming a comparative rarity.Many working outside special centres have never had the opportunity of examining an infant who is suffering from the disease.The following is a case history of a patient presenting in the classical manner.Case Report A full-term male child born on December 13, 1952, was brought to the casualty department on February 25, 1953, with the history that after an outing in his perambulator the preceding afternoon he had refused to move the left upper limb.When his mother attempted to move the arm the child screamed with pain.He was referred to the fracture clinic as a possible case of pulled elbow or as a doubtful case of greenstick fracture of the left upper humerus.Clinical examination showed a normal healthy-looking baby of 10 weeks.Movements of all the limbs except the left upper limb were normal.That limb was held by the side, and any attempt at movement was resented.There was tenderness on palpation over the metaphysis at both the proximal and the distal end of the left humerus.A doubtful greenstick fracture of the upper humeral shaft without displacement was demonstrated radiologically.The arm was placed in a collar-and-cuff sling and an appoint- ment was made for the child to be seen in a week's time.The next day the mother returned to the clinic stating that not only did the child resent movement of the arm but he now refused to move the left lower limb.Further clinical examination confirmed the loss of fLnc- tion of both the left upper and lower limbs.(There were no visible physical signs other than the " paralysis," but the metaphysial regions of all four limbs were found to be tender on palpation.Radiographic examination demon- strated well-marked osteochondritis and chondro-epipihysitis in the long bones of all four limbs.Figs. 1 and 2 (Special Plate) show the right upper limb and the left lower limb.
Interleukin-10 Inhibits Expression of Both Interferon – and Interferon γ– Induced Genes by Suppressing Tyrosine Phosphorylation of STAT1
Authors: Satoshi Ito, Parswa Ansari, Minoru Sakatsume, Harold Dickensheets, Nancy Vazquez, Raymond P. Donnelly, Andrew C. Larner, David S. Finbloom
Journal: Blood (1999)
Abstract 4366: Relation of Functional and Morphological Changes in Mitochondria to Myocardial Contractile and Relaxation Reserves in Asymptomatic to Mildly Symptomatic Patients with Hypertrophic Cardiomyopathy
Authors: Kazumasa Unno, Satoshi Isobe, Hideo Izawa, Xian W Cheng, Masakazu Kobayashi, Akihiro Hirashiki, Yosuke Murase, Hiroyuki Asano, Takashi Yamada, Satoru Ohshima, Takao Nishizawa, Akiko Noda, Kohzo Nagata, Toyoaki Murohara, Mitsuhiro Yokota
Journal: Circulation (2008)

Impairment of myocardial relaxation reserve and subsequent impairment of contractile reserve constitute a primary manifestation of hypertrophic cardiomyopathy (HCM). Although these reserves reflect energy-consuming processes, the relation between their impairment and mitochondrial function in HCM has remained unclear. Thirty HCM patients underwent biventricular cardiac catheterization analysis both at rest and during atrial pacing as well as myocardial 99m Tc-sestamibi (MIBI) scintigraphy at rest. MIBI washout rate (WR) was calculated from initial and delayed left ventricular (LV) planar images. Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopic observation. The HCM patients were divided into two groups: Group A consisted of 15 patients showing a normal force-frequency relation (FFR) and pressure half-time ( T 1/2 ) of &lt;30 ms, whereas group B consisted of 15 patients showing an abnormal FFR or T 1/2 of ≥30 ms. The MIBI WR was significantly correlated with T 1/2 at the peak pacing rate for all patients ( r = 0.74, P &lt;0.01). It was also significantly greater in group B (29.2 ± 6.3%) than in group A (19.3 ± 3.1%). The abundance of mRNAs for mitochondrial electron transport-related enzymes was significantly higher in group A than in group B. Mitochondria showed a greater variation in size and were more disorganized in group B than in group A. Mitochondria showed functional impairment and morphological disorganization in the left ventricle of HCM patients without baseline systolic dysfunction. These mitochondrial changes were associated with impaired myocardial contractile and relaxation reserves.
Adjuvant chemotherapy for breast cancer: discordance between physicians' perception of benefit and the results of clinical trials.
Authors: S Rajagopal, P J Goodman, I F Tannock
Journal: Journal of Clinical Oncology (1994)

PURPOSE Decisions about management of patients depend on the perception of physicians about the results of clinical trials. We therefore determined whether physicians would recommend adjuvant chemotherapy for specified patients with breast cancer, and whether the perceived levels of benefit that led to these decisions were supported by the results of clinical trials. METHODS We mailed a questionnaire that presented two clinical scenarios to 515 American and European oncologists. Scenario A depicted a premenopausal woman with node-negative, estrogen receptor-negative (ER-) breast cancer, and scenario B depicted a post-menopausal woman with node-positive, ER- disease. Respondents were asked about the evidence that they required from clinical trials to recommend adjuvant chemotherapy for these patients. RESULTS Replies were received from 307 oncologists. American respondents were more likely to recommend adjuvant chemotherapy than Europeans (A, 93% v 68%; B, 85% v 67%; P &lt; .001 for both comparisons). Opinion was evenly divided as to whether improvement in the relapse-free survival (RFS) rate was sufficient to recommend treatment, or whether improvement in overall survival was necessary. Mean values of 12.9% to 14.6% improvement in RFS at 3 years, or 10.7% to 12.4% improvement in overall survival at 5 years, were required to offer treatment. An overview analysis of clinical trials suggests that adjuvant chemotherapy achieves absolute improvements of 6% to 9% in RFS rates at 3 years and 3% to 4% in overall survival rates at 5 years for patients in these scenarios. CONCLUSIONS Most oncologists recommended treatment in these scenarios, but require a level of treatment effect that has not been demonstrated in clinical trials. Our results suggest that oncologists' perceptions of the results of clinical trials overestimate the therapeutic gain from use of adjuvant chemotherapy for breast cancer.
The Storage Lipids in Tangier Disease
Authors: Saul S. Katz, Donald M. Small, Jacob G. Brook, Robert S. Lees
Journal: Journal of Clinical Investigation (1977)

The physical states and phase behavior of the lipids of the spleen, liver, and splenic artery from a 38-yr-old man with Tangier disease were studied. Many intracellular lipid droplets in the smectic liquid crystalline state were identified by polarizing microscopy in macrophages in both the spleen and liver, but not in the splenic artery. The droplets within individual cells melted sharply over a narrow temperature range, indicating a uniform lipid composition of the droplets of each cell. However different cells melted over a wide range, 20-53°C indicating heterogeneity of lipid droplet composition between cells. Furthermore, most of the cells (81%) had droplets in the liquid crystalline state at 37°C. X-ray diffraction studies of splenic tissue at 37°C revealed a diffraction pattern typical of cholesterol esters in the smectic liquid crystalline state. Differential scanning calorimetry of spleen showed a broad reversible transition from 29-52°C, with a maximum mean transition temperature at 42°C, correlating closely with the polarizing microscopy observations. The enthalpy of the transition, 0.86±0.07 cal/g of cholesterol ester, was quantitatively similar to that of the liquid crystalline to liquid transition of pure cholesterol esters indicating that nearly all of the cholesterol esters in the tissue were free to undergo the smectic-isotropic phase transition.
Tracheal Microaspiration in Adult Cystic Fibrosis
Authors: M J Ledson, G E Wilson, J Tran, M J Walshaw
Journal: Journal of the Royal Society of Medicine (1998)

Gastro-oesophageal reflux (GOR) has been implicated in the aetiology of lung disease. Cystic fibrosis (CF) patients have a high incidence of GOR symptoms with demonstrable episodes of oesophageal acidification. We studied 24-hour ambulatory tracheal and oesophageal pH in 11 CF patients with GOR symptoms to identify any episodes of tracheal acidification and define their temporal relation to oesophageal reflux and respiratory symptoms. 8 patients had evidence of significant GOR (DeMeester score mean 58; range 17-107) and in 6 it was gross (DeMeester score > 30). 4 patients had tracheal acidification (defined as tracheal pH < 5.5): all had greatly raised DeMeester scores. Two patterns of lowered tracheal pH were seen: a gradual drift downwards of tracheal pH to < 5.5 which recovered slowly, and an acute fall in tracheal pH to < 5.5 with rapid recovery. Only one patient had a fall in peak expiratory flow in conjunction with a decline in tracheal pH, and no association was found between the presence of tracheal microaspiration and pulmonary function. We conclude that tracheal acidification occurs in adult CF patients with GOR.
Patients with chronic back pain of short duration from the SPACE cohort: which MRI structural lesions in the sacroiliac joints and inflammatory and structural lesions in the spine are most specific for axial spondyloarthritis?
Authors: Manouk de Hooge, Rosaline van den Berg, Victoria Navarro-Compán, Monique Reijnierse, Floris van Gaalen, Karen Fagerli, Robert Landewé, Maikel van Oosterhout, Roberta Ramonda, Tom Huizinga, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To investigate the extent and performance of MRI lesions in the sacroiliac joint (MRI-SI) and spine (MRI-spine) in patients with suspected axial spondyloarthritis (axSpA). <h3>Methods</h3> MRI-SI/spine of patients with chronic back pain (onset &lt;45 years) in the SPondyloArthritis Caught Early (SPACE) cohort were scored by two well-trained readers for inflammation, fatty lesions, erosions, sclerosis/ankylosis and syndesmophytes. MRI performances were tested against the Assessment of Spondyloarthritis international Society (ASAS) axSpA criteria (<i>positive</i>: imaging-arm+ or clinical-arm+; <i>negative</i>: possible axSpA (few spondyloarthritis (SpA) features present) or no SpA). Arbitrary cut-off levels for MRI lesions were set to assure at least 95% specificity (tested in the no SpA group). <h3>Results</h3> In total 126 patients were ASAS criteria positive (73 imaging-arm+ (22 by modified New York criteria (mNY)+; 51 by MRI+mNY−); 53 clinical-arm+) and 161 were ASAS criteria negative (89 possible axSpA and 72 no SpA). On MRI-SI (n=287), at least three fatty lesions (or at least three erosions) were seen in 45.5 (63.6)% of mNY+ patients, 15.7 (47.1)% of MRI+mNY− patients and 15.1 (13.2)% of clinical-arm+ patients versus 3.4 (6.7)% of possible axSpA patients and 2.8 (4.2)% of no SpA patients. A combined rule (at least five fatty lesions and/or erosions) performed equally well. Sclerosis and ankylosis were too rare to analyse. On MRI-spine (n=284), at least five inflammatory lesions (or at least five fatty lesions) were seen in 27.3 (18.2)% of mNY+ patients, 13.7 (21.6)% of MRI+mNY− patients and 3.8 (1.9)% of clinical-arm+ patients versus 4.5 (6.7)% of possible SpA patients and 2.9 (4.3)% of no SpA patients. <h3>Conclusions</h3> The presence of (1) at least five fatty lesions and/or erosions on MRI-SI, (2) at least five inflammatory lesions or (3) at least five fatty lesions on MRI-spine allows an acceptable discrimination of axSpA and no SpA, while assuring &gt;95% specificity.