tbuckley/cabot-search huggingface dataset:
Anaesthesia for Hip Replacement in Ankylosing Spondylitis
Authors: F W Wittmann, P A Ring
Journal: Journal of the Royal Society of Medicine (1986)

Thirteen total hip replacements in 8 patients with ankylosing spondylitis are reviewed. Complications of the disease which can lead to anaesthetic difficulties are discussed, and the importance of a preoperative visit and the value of indirect laryngoscopy emphasized. As intubation problems may occur, especially in undiagnosed cases, equipment for emergency intubation should always be readily available. The results fully justify the operation.
The Rotterdam study: why fall in COPD?
Authors: Pampa De, Sourin Bhuniya
Journal: European Respiratory Journal (2015)

Lahousse et al. [1] have conducted an interesting study to investigate the association of chronic obstructive pulmonary disease (COPD) with various gait domains and explored a potential risk with falling. They have stressed the temporal gait parameter (rhythm) and have concluded that people who fall with COPD had worse rhythm. However, they have not tried to evaluate the other probable causes of disturbed rhythm in their subjects. The causes resulting in falls or disordered rhythm in COPD patients, could also be present primarily in the musculoskeletal and neurological systems because most of the subjects enrolled in the study were elderly, and problems related to musculoskeletal and neurological systems are more common in an elderly population [2]. The exclusion of such groups of people from the study has not been mentioned in the exclusion criteria. There were 152 participants with physical inability but the nature of physical inability is obscure. It would have been more rational or rather elucidative to assess other probable causes resulting in falls or decreased cadence in such elderly population with COPD. Association of poor gait and falling in Rotterdam study may be due to factors that were not considered <http://ow.ly/RZbUI>
Enzyme Pathology of Human Mesotheliomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: O Greengard, J F Head, A P Chahinian, S L Goldberg
Journal: JNCI Journal of the National Cancer Institute (1987)

In samples of 16 surgically resected mesotheliomas arising from the pleura of the human lung, 6 enzymes from different metabolic pathways, DNA, and mitotic frequency were quantified. The mesotheliomas, irrespective of cell type or grade, showed lower gamma-glutamyl transpeptidase (GGT) concentration than 36 of the 38 pulmonary adenocarcinomas. The mean concentration of this enzyme in the 15 mesotheliomas was an eighth of that in the 56 carcinomas, whereas their DNA content was similar. The quantitative correlation of thymidine kinase (TK), uridine kinase (UK), and phosphoserine phosphatase to mitotic frequency was highly significant for mesotheliomas, as well as for carcinomas. As estimated from their TK [and its recently established quantitative correlation to volume doubling time (DT)], the DT of the 16 mesotheliomas ranged from 50 to over 700 days, with a somewhat longer median than the median for pulmonary carcinomas. Subject survival, though shortest for the 2 sarcomatous mesothelioma cases, varied over an overlapping range for mesotheliomas with epithelial or mixed cell type. The biopsy samples' TK and UK concentrations, however, showed a significant inverse correlation with months of survival after diagnosis. Survival time after the first appearance of symptoms decreased linearly (on log scales) with TK concentration (P less than .001) over the 14 cases. The results of this first quantitative study of a spectrum of biochemical constituents of mesotheliomas identify GGT as an enzyme whose measurement guards against mistaking mesotheliomas and adenocarcinomas for one another and show that the TK concentrations of these mesothelioma samples bear a highly significant, inverse correlation to the postdiagnosis survival time of the individual subjects.
Abstract 1449: A Soluble Form Of Ldl Receptor Gene Family Member, Lr11, Is Essential For Angiotensin Ii -induced Smc Migration
Authors: meizi jiang, hideaki bujo, kenji ohwaki, mao takahashi, kohji shirai, Wolfgang J Schneider, yasushi saito
Journal: Circulation (2007)

Migration of vascular smooth muscle cells (SMCs) from the media to the intima plays a key role in the development of atherosclerosis. Considerable amounts of the soluble form of LR11 (sLR11) are produced by intimal SMCs and enhance migration of SMCs in vitro via upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. Circulating levels of sLR11 are increased in subjects with coronary artery diseases. Here, we show that targeted disruption of the LR11 gene greatly reduces intimal thickening of arteries through attenuation of angiotensin II (Ang II)-induced migration of SMCs. The intimal thickness of femoral arteries after cuff placement was decreased in Lr11 −/− mice. In cultured Lr11 −/− SMCs, AngII-stimulated migration and particularly, attachment, were almost completely abolished. In SMCs, sLR11 caused membrane ruffle formation via activation of focal adhesion kinase (FAK)/extracellular signal-regulated protein kinase (ERK)/Rac1, accompanied by formation of a complex between uPAR and integrin αvβ3. AngII accelerated membrane ruffling through an increase in sLR11-mediated formation of this complex. Overproduction of sLR11 resulted in the reduced sensitivity of AngII-induced activation pathways to inhibition by an AngII type 1 receptor blocker in mice. These results show that AngII-induced SMC migration is mediated by sLR11- induced signal activation for membrane ruffle formation. Our discovery of involvement of LR11 in AngII-induced SMC migration possibly leads to an establishment of novel approach for regulating plaque formation.
Long-term impact of exercise adherence in COPD
Authors: Ana Graz, Josefina Podestá, Martin Sivori, Marta de Almeida, Cesar Saenz
Journal: European Respiratory Journal (2011)

There9re scarce studies evaluating long-term impact of exercise adherence after a respiratory rehabilitation program (RR) in Chronic Obstructive Pulmonary Disease (COPD) patients.   Objectives:  To compare impact on BODE, mortality, health-related quality of life (HRQL) and health-resources consumption in two groups of COPD patient: intense physical activity (IPA) and low physical activity (LPA) at long-term.   Methods:  COPD patients (GOLD definition) were followed up after a RR program completed (from 1997 to 2009). Patients were evaluated by BODE, HRQL (SGRQ), pulmonary function, health-consumption and survival on 2009. Patients were classified according to Garcia Aymerich questionnaire (Thorax 2006): IPA (>2 hours/week of physical activity) and LPA (   Results:  99 COPD patients were analyzed after follow-up: 66 patients were alive and 33 died (33.33%). 71 patients were in LPA and 28 in IPA group respectively. Both groups are comparable at the start of follow up, except in sex (40% was female in LPA and 60% was male in IPA; p=0.00004). They have severe airway obstruction (38-40 FEV1% predictive) and 66 to 68 years.   Conclusion:  Evaluated at long-term after a RR, only 30% of patients were with IPA. IPA group had better outcomes in survival, BODE, HRQL and health-resources consumption than LPA group.
Ly-6 in kidney is widely expressed on tubular epithelium and vascular endothelium and is up-regulated by interferon gamma.
Authors: P G Blake, J Madrenas, P F Halloran
Journal: Journal of the American Society of Nephrology (1993)

Ly-6 is a multigene family of murine polymorphic cell membrane proteins that are glycosydlphosphatidylinositol anchored, widely expressed on lymphoid tissue, and homologous to the recently described human CD59. An unexpected feature of Ly-6 is its high level of expression in the kidney. This renal expression and its interferon (IFN)-gamma inducibility in murine strains expressing different Ly-6 haplotypes were studied with monoclonal antibodies and cDNA probes that recognize Ly-6A/E and Ly-6C. Ly-6 expression was much more extensive in the kidney than in other parenchymal organs. Ly-6A.1/E.2 was extensively expressed on vascular endothelium and on tubular epithelium, particularly in the distal nephron. Pattern of expression differed between strains expressing A and E alleles. Ly-6C was not detected by monoclonal antibodies but was detected by oligonucleotide-specific probes. Treatment with recombinant IFN-gamma or IFN-inducing agents increased Ly-6 expression markedly, particularly on the luminal aspect of the proximal tubular epithelium, where Ly-6A/E became prominent. This luminal expression is typical for glycosydlphosphatidylinositol-anchored proteins but contrasts with that of other molecules, such as major histocompatibility classes I and II, which are generally expressed on the basolateral surface of the tubular epithelium. Up-regulation occurred within 6 h of IFN-gamma treatment and returned to normal by 48 h. Similar up-regulation of Ly-6 was seen in murine lupus nephritis and in mercuric chloride nephropathy. The characteristics of renal Ly-6, such as its IFN-gamma responsiveness, endothelial and tubular expression, polymorphism, strong antigenicity, and possible allelic regulation, make it a candidate to be a target molecule in alloresponses. The renal expression of Ly-6 is similar to that of CD59 in the human kidney, supporting the suggestion that these proteins are closely related.
Abstract 16707: Cheyne-Stokes Respiration in Patients with Congestive Heart Failure: Association with Malignant Arrhythmic Events and Effects of Adaptive Servoventilation Therapy - an Observational Study
Authors: Thomas Bitter, Nina Westerheide, Christoph Langer, Christian Prinz, Dieter Horstkotte, Olaf Oldenburg
Journal: Circulation (2010)

Background:  In patients (pts) with chronic heart failure (CHF) Cheyne-Stokes respiration (CSR) is an independent predictor for the manifestation of malignant arrhythmias. Aim of this study was to investigate, whether treatment of CSR by Adaptive Servoventilation (ASV) reduces the risk of malignant arrhythmic events in pts with CHF and CSR.   Methods:  Of 403 pts. with CHF (LVEF ≤ 45%, NYHA-class ≥ 2) and implanted CRT-D or ICD device, 221 pts presented with mild or no CSR (Apnea-Hypopnea-Index (AHI)    Results:  Kaplan-Meyer-Plot on event-free survival from appropriately monitored ventricular arrhythmias (Fig.1) and appropriate cardioverter-defibrillator therapies (Fig.2) as well as results from multiple COX proportional hazard regression analysis (,,backward selection“ with AIC), adjusted for all significant cofactors are shown below.   Conclusions:  ASV therapy reduces the risk of malignant arrhythmic events in CHF pts with CHF and moderate to severe CSR. Mechanisms involved as well as implications on total mortality need to be determined.
Vitamin D levels in patients with non-CF bronchiectasis
Authors: Louise Anning, Charlotte Carmichael, Philip Mitchelmore, Bervin Teo, Nicholas Withers
Journal: European Respiratory Journal (2014)

Low levels of vitamin D, measured as 25-hydroxyvitamin-D (25-OHD), in patients with non-CF bronchiectasis (NCFB) have previously been correlated with more rapid deterioration in lung function, higher bacterial colonisation rates, and increased frequency of infective exacerbations (Chalmers, J.D.  et al . Thorax 2013; 68:39-47).  Electronic records of 120 patients (68% female; median age 67 years) attending a bronchiectasis clinic in 2013 were reviewed retrospectively to ascertain the incidence of low levels of vitamin D and its relationship with bacterial colonisation and exacerbations.  Levels of 25-OHD were measured in only 44 (37%) of patients. Levels were deficient or insufficient (low) in 15 (34%) of these. Of these 44, those with low 25-OHD levels had fewer sputum isolations of  Pseudomonas aeruginosa  and non-tuberculous mycobacteria (40% vs. 45% and 7% vs. 10% respectively), but more frequent isolation of  Haemophilus influenzae  (40% vs. 31%). There were fewer exacerbations requiring intravenous antibiotics in those with low 25-OHD (7% vs. 28%). None of these differences reached statistical significance. Those with low 25-OHD were more likely to have had it measured in winter or spring. There was no difference in prescription of either calcium or combined calcium and vitamin D supplements between groups.  In this small study we have not shown any link between vitamin D levels and exacerbations or sputum colonisation in our NCFB patients. However, sample size was small and the majority of patients had not had vitamin D measured. Finally, vitamin D levels are known to fluctuate seasonally. If they are to be included in the assessment of NCFB patients it would make sense to standardise the time of level measurement.
Fluoridated Drinking Water and the Occurrence of Cancer
Authors: Robert N. Hoover, Frank W. McKay, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1976)

A recent report by the National Health Federation, a private agency, related cancer mortality patterns in the United States to fluoridation of water supplies, triggering much public health concern and some political response. To clarify the issues raised, we studied cancer mortality and incidence statistics for U.S. counties, 1950-69. No trends could be ascribed to the consumption of water that is artificially or naturally fluoridated.
Lithium carbonate in the treatment of tardive dyskinesia
Authors: F A Reda, J I Escobar, J M Scanlan
Journal: American Journal of Psychiatry (1975)

Six patients with tardive dyskinesia were treated with lithium carbonate in an open clinical trial. Evaluations using a new tardive dyskinesia rating scale showed statistically significant improvement in dyskinetic movements while the patients received lithium. This improvement was consistently observed in all patients but was relatively small when compared to the amount of pathology present.
The Effect of Inhaled Fluticasone Propionate in the Treatment of Young Asthmatic Children
Authors: HANS BISGAARD, JOHN GILLIES, MARCELLE GROENEWALD, CLAIRE MADEN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within the pediatric dose range. A total of 237 children (mean age 28 mo, range 12 to 47) with moderate asthmatic symptoms were studied in this multicenter, randomized, double-blind, parallel group, placebo-controlled study of 12 wk treatment following a 4-wk run-in period. The median use of rescue medication was 1 dose in 2 d during the run-in period. FP 50 μ g twice daily (FP100) and 100 μ g twice daily (FP200) was compared with placebo inhaled from a pressurized metered-dose inhaler (pMDI) and the Babyhaler spacer device. With FP200 there was a statistically significant improvement from baseline, as compared with the placebo group, in 8 of 10 diary card parameters, including the three symptom domains of wheeze, cough, and breathlessness, and use of rescue medication. FP100 produced a significant reduction in 5 of these 10 parameters, whereas no significant differences were found between the FP200 and FP100. The numbers of patients with at least one exacerbation during treatment with placebo, FP100, and FP200 were 37%, 26%, and 20%, respectively. This difference between placebo and FP200, as well as the dose-related order was significant (p < 0.05). Both FP doses were as well tolerated as placebo over the 12 wk treatment with a similar incidence of adverse effects. Asthmatic symptoms in 1- to 3-yr-old children responded in a significant and dose-related manner to treatment with FP within a pediatric dose range.
Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border
Authors: Ivy A. Rosales, A. Bernard Collins, Paula Alves S. do Carmo, Nina Tolkoff-Rubin, R. Neal Smith, Robert B. Colvin
Journal: Journal of the American Society of Nephrology (2015)

Immune complex tubulointerstitial nephritis due to antibodies to brush border antigens of the proximal tubule has been demonstrated experimentally and rarely in humans. Our patient developed ESRD and early recurrence after transplantation. IgG and C3 deposits were conspicuous in the tubular basement membrane of proximal tubules, corresponding to deposits observed by electron microscopy. Rare subepithelial deposits were found in the glomeruli. The patient had no evidence of SLE and had normal complement levels. Serum samples from the patient reacted with the brush border of normal human kidney, in contrast with the negative results with 20 control serum samples. Preliminary characterization of the brush border target antigen excluded megalin, CD10, and maltase. We postulate that antibodies to brush border antigens cause direct epithelial injury, accumulate in the tubular basement membrane, and elicit an interstitial inflammatory response.
Antihistamines in the treatment of asthma
Authors: J Bousquet, P Godard, FB Michel
Journal: European Respiratory Journal (1992)

Histamine is an important mediator of asthma. The new anti-histamines which block histamine at the H1-receptor level also possess some anti-allergic properties. At current dosages they appear to be safe. These drugs are effective in the treatment of rhinitis and conjunctivitis but their role in asthma is still under investigation. At a dose higher than usually recommended, they were shown to block exercise-induced asthma and, inconstantly, the early phase reaction after allergen challenge. Their effect on the late phase allergic reaction as well as their clinical efficacy during trials is, however, less consistent. The indication of H1-blockers in the treatment of asthma is therefore limited, especially since doses higher than recommended may lead to adverse reactions.
Conflict of Interest, Round 2
Authors: Robert Freedman, David A. Lewis, Robert Michels, Daniel S. Pine, Susan K. Schultz, Carol Tamminga, Sandra L. Patterson, John S. Mcintyre, Howard H. Goldman, Stuart C. Yudofsky, Robert E. Hales, Mark H. Rapaport, Deborah Hales, James Krajeski, David J. Kupfer, Mary Anne Badaracco, James H. Scully
Journal: American Journal of Psychiatry (2006)
Curious Discoveries in Antiviral Drug Development: The Role of Serendipity
Authors: Erik De Clercq
Journal: Medicinal Research Reviews (2015)

Antiviral drug development has often followed a curious meandrous route, guided by serendipity rather than rationality. This will be illustrated by ten examples. The polyanionic compounds (i) polyethylene alanine (PEA) and (ii) suramin were designed as an antiviral agent (PEA) or known as an antitrypanosomal agent (suramin), before they emerged as, respectively, a depilatory agent, or reverse transcriptase inhibitor. The 2′,3′-dideoxynucleosides (ddNs analogues) (iii) have been (and are still) used in the "Sanger" DNA sequencing technique, although they are now commercialized as nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV infections. (E)-5-(2-Bromovinyl)-2′-deoxyuridine (iv) was discovered as a selective anti-herpes simplex virus compound and is now primarily used for the treatment of varicella-zoster virus infections. The prototype of the acyclic nucleoside phosphonates (ANPs), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (v) was never commercialized, although it gave rise to several marketed products (cidofovir, adefovir, and tenofovir). 1-[2-(Hydroxyethoxy)methyl]-6-(phenylthio)thymine (vi) and TIBO (tetrahydroimidazo[4,5,1-jk][1,4-benzodiazepin-2(1H)]-one and -thione) (vii) paved the way to a number of compounds (i.e., nevirapine, delavirdine, etravirine, and rilpivirine), which are now collectively called non-NRTIs. The bicyclam AMD3100 (viii) was originally described as an anti-HIV agent before it became later marketed as a stem cell mobilizer. The S-adenosylhomocysteine hydrolase inhibitors (ix), while active against a broad range of (–)RNA viruses and poxviruses may be particularly effective against Ebola virus, and for (x) the O-ANP derivatives, the potential application range encompasses virtually all DNA viruses.
Maximal respiratory pressure and maximal voluntary ventilation in Brazilian health population: A multicentre study
Authors: Guilherme Fregonezi, Palomma Russelly Araujo, Vanessa Resqueti, Ester Silva, Marlene Moreno, Jasiel Nascimento Junior, Larissa Carvalho, Ana Gabriela Cavalcanti, Armele de Fátima Dornelas de Andrade
Journal: European Respiratory Journal (2012)

Maximal respiratory pressures (MRP) and maximal voluntary ventilation (MVV) are worldwide measures used to assess respiratory muscle strength and endurance. Although there are references values established to Brazilian population different methodological procedure used in previous studies could contribute to wide variation in values published.This study was conducted in three centers in Brazil, Natal-RN, Recife-PE and Piracicaba-SP. Subject was evaluated in relation to anthropometrics parameters, physical activity profile, maximal inspiratory/expiratory pressure and MVV. Correlation and multiple linear regressions were used to predicted male and female MRP and MVV equations.We studied 244 subjects (114 male/130 female) distributed in different age group from 20 to 80 years old. The results showed a significantly positive correlation between MIP/MEP and height in female; negative correlation with age in both genders. A positive correlation between MVV, weight and height in male were found; in female, we found a positive correlation with height and negative correlation with age. In the multiple linear regression analysis only age continued to have an independent predictive role for dependent variables in MIP/MEP and MVV.

![Figure][1] 



The results of this study provide a reliable reference equations of MRP and MVV for health Brazilian population from 20 to 80 years old.

 [1]: pending:yes
K<sup>+</sup> Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation
Authors: Colleen E. Clancy, Junko Kurokawa, Michihiro Tateyama, Xander H.T. Wehrens, Robert S. Kass
Journal: The Annual Review of Pharmacology and Toxicology (2003)

Pharmacological intervention, often for the purpose of treating syndromes unrelated to cardiac disease, can increase the vulnerability of some patients to life-threatening rhythm disturbances. This may be due to an underlying propensity stemming from genetic defects or polymorphisms, or structural abnormalities that provide a substrate allowing for the initiation of arrhythmic triggers. A number of pharmacological agents that have proven useful in the treatment of allergic reactions, gastrointestinal disorders, and psychotic disorders, among others, have been shown to reduce repolarizing K(+) currents and prolong the QT interval on the electrocardiogram. Understanding the structural determinants of K(+) channel blockade may provide new insights into the mechanism and rate-dependent effects of drugs on cellular physiology. Drug-induced disruption of cellular repolarization underlies electrocardiographic abnormalities that are diagnostic indicators of arrhythmia susceptibility.