tbuckley/cabot-search huggingface dataset:
Prognosis in post-infective irritable bowel syndrome: a six year follow up study
Authors: K R Neal, L Barker, R C Spiller
Journal: Gut (2002)

<b>Background:</b> Irritable bowel syndrome developing following infective gastroenteritis accounts for approximately 1 in 10 of unselected IBS patients. <b>Aims:</b> To define the long term natural history of post-infective IBS (PI-IBS). <b>Methods:</b> A total of 436 individuals, who had previously responded to a questionnaire on their bowel habits following an acute episode of gastroenteritis, were sent a questionnaire about their current bowel habits and physical and mental health six years after their initial illness. <b>Results:</b> Complete data on original bowel habit, episodes of gastroenteritis, mental health history, and subsequent bowel habit at six years were obtained in 192 individuals. Of these, there were 14 cases of “post-infective IBS” (PI-IBS) and 13 who had IBS prior to infection (previous IBS). Over the six year follow up period there were 20 “new non-infective IBS cases” (new IBS). The strongest risk factor for developing any type of IBS was female sex (relative risk 2.2, p&lt;0.05). Compared with new IBS, those with PI-IBS had significantly more days with loose stools (p&lt;0.05) but a similar number of days with pain, urgency, and bloating. Six of 14 (43%) PI-IBS and four of 13 (31%) previous IBS patients recovered by six years (NS). Of 27 IBS patients followed for six years, only 1/8 with a history of anxiety or depression recovered compared with 9/19 without such a history (p=0.19). <b>Conclusion:</b> PI-IBS differs from non-infective IBS by having more diarrhoeal features. Less than half of both PI-IBS and non-infective IBS cases recover over six years. A history of anxiety and depression severe enough to warrant treatment may impair recovery but larger numbers are needed to prove this.
Sarcoma of the Pulmonary Artery
Authors: R. H. Elphinstone, R. G. Spector
Journal: Thorax (1959)

Primary sarcomata of the great vessels are so rare that Jores, in 1924, dismissed all cases described up to that time, for lack of evidence of their nature.Eight 4fases of sarcoma of the main pulmonary artery have been published since.In this paper we summarize them and describe a new case of our own, in an endeavour to form a composite clinical and pathological picture by which the disease may be recognized in life.Froboese's (1928) patient was a woman of 64 who died in heart failure four weeks after admission to hospital.She had had symptoms of cardiac insufficiency for two years.At necropsy the pulmonary artery and its main branches were filled by what appeared to be an embolism.This was removed easily, bringing the intima away from the media ; on microscopy it was found to be a spindle cell sarcoma replacing the intima and invading the media.In the same year Eschbach (1928) described a similar case in a man of 58.The growth appeared to have arisen from the pulmonary conus, and had grown along the intima of the artery, but had not invaded the media.Kudlich and Schuh (1934) gave no clinical details of their patient, a man of 27, apart from the statement that he had tumours of the lung and mediastinum.At necropsy, tumour masses were found in both lungs and within and around the pulmonary artery.The pulmonary valves were invaded.The sarcoma contained many multi- nucleated giant cells and spread in the intima of the artery and in the endocardium, also involving the media and adventitia of the artery and neighbouring lymph nodes.Goedel's (1935) patient, a man of 47, died of heart failure after a few weeks' illness.The pathological findings resembled those of Kudlich and Schuh.Martin, Tuohy, and Will (1939) described the case of a woman of 46 who died in heart failure four months after the onset of symptoms.The tumour, a polymorphic cell sarcoma, involved the *Present address: Bernhard Baron Memorial Research Labora- recurred each night.The cough became productive of yellow sputum.Four weeks previously he passed blood in the urine on one occasion.Three weeks previously breathlessness became much worse and on July 23,
The effect of D-penicillamine on polymorphonuclear leukocyte function.
Authors: H Chwalinska-Sadowska, J Baum
Journal: Journal of Clinical Investigation (1976)

D-Penicillamine, a reducing and chelating agent used in the treating of rheumatoid arthritis, was tested for its effects of polymorphonuclear leukocyte chemotaxis, phagocytosis, and lysosomal enzymes. beta-Glucuronidase release from polymorphonuclear leukocytes after phagocytosis of latex particles was not affected by D-penicillamine at concentrations ranging from 25 to 400 mg/liter. No direct effect was seen on enzyme activity at the maximum concentration of the drug. There was no inhibition of latex particle ingestion. No cell damage was found at 400 mg/liter penicillamine as measured by lactic dehydrogenase release. At this drug concentration there was only a 15% reduction in hemolytic complement levels. Chemotaxis was significantly decreased at concentrations of 50 mg/liter with a dose-dependent effect at higher concentrations which showed a plateau from 200 to 400 mg/liter. The parent compound D-cysteine was also tested in these systems. The same lack of effect of phagocytosis and enzyme release was found. D-Cysteine did inhibit chemotaxis but to a lesser degree than D-penicillamine. This dicotomy of drug effect may indicate that the beneficial action of D-penicillamine in the treatment of rheumatoid arthritis is due to the decreased chemotaxis of polymorphonuclear leukocytes into the joint, while the absence of an effect of phagocytosis and lysosomal enzymes shows the cells can still function to ingest and destroy bacteria. This latter effect correlates with the absence of infection in patients treated with this compound.
Rapamycin Ameliorates Proteinuria-Associated Tubulointerstitial Inflammation and Fibrosis in Experimental Membranous Nephropathy
Authors: Ramon G B Bonegio, Robert Fuhro, Zhiyong Wang, C Robert Valeri, Christopher Andry, David J Salant, Wilfred Lieberthal
Journal: Journal of the American Society of Nephrology (2005)

Proteinuria is a risk factor for progression of chronic renal failure. A model of proteinuria-associated tubulointerstitial injury was developed and was used to examine the therapeutic effect of rapamycin. Two studies were performed. In study A, proteinuric rats were given sheep anti-Fx1A to induce experimental membranous nephropathy; control rats received normal sheep serum. Four weeks later, groups were subdivided and underwent laparotomy alone (two kidneys), nephrectomy alone (one kidney), or nephrectomy with polectomy (0.6 kidney). Renal function and morphology were evaluated 4 wk later. Whereas control rats never developed proteinuria, anti-Fx1A induced severe proteinuria. Proteinuria was unaffected by renal mass reduction. Proteinuric rats developed tubulointerstitial disease that was most severe in rats with 0.6 kidneys. Renal function (GFR) was reduced by loss of renal mass and was reduced further in proteinuric rats with 0.6 kidneys. In study B, the effect of rapamycin on the expression of candidate proinflammatory and profibrotic genes and the progression of proteinuria-associated renal disease were examined. All rats received an injection of anti-Fx1A and were nephrectomized and then divided into groups to receive rapamycin or vehicle. Gene expression, renal morphology, and GFR were evaluated after 4, 8, and 12 wk. Rapamycin reduced expression of the proinflammatory and profibrotic genes (monocyte chemotactic protein-1, vascular endothelial growth factor, PDGF, TGF-beta(1), and type 1 collagen). Tubulointerstitial inflammation and progression of interstitial fibrosis that were present in vehicle-treated rats were ameliorated by rapamycin. Rapamycin also completely inhibited compensatory renal hypertrophy. In summary, rapamycin ameliorates the tubulointerstitial disease associated with chronic proteinuria and loss of renal mass.
Exhaled breath temperature in airways disease
Authors: J.B. McCafferty, J.A. Innes
Journal: European Respiratory Journal (2003)

To the Editor: 

It was with interest that we read the study of Paredi et al. 1 which reports a slower rise in exhaled breath temperature in patients with chronic obstructive pulmonary disease (COPD). It is intriguing to think that altered airway heat transfer may provide a noninvasive marker of airways inflammation or remodelling. However, heat transfer in the airway has long been known to be a complex process and we feel this study leaves important questions unanswered.

The authors hypothesise that patients with COPD have alterations in bronchial blood flow that affect the rise in exhaled air temperature. Heat transfer in the …
A Case of Recurrence of Laryngeal Papillomata in a Child after Tracheotomy
Authors: E. M. Sympson
Journal: BMJ (1901)

of Diseases of Children, said he had seen a case in which the growths recurred after tracheotomy.No details were given of this most unusual occurrence, nor has it been confirmed by any other observer, and I am therefore disinclined to accept it as a record of an actual fact.
Designing road vehicles for pedestrian protection
Authors: J R Crandall
Journal: BMJ (2002)

Collisions between pedestrians and road vehicles present a major challenge for public health, trauma medicine, and traffic safety professionals. More than a third of the 1.2 million people killed and the 10 million injured annually in road traffic crashes worldwide are pedestrians.1 Compared with injured vehicle occupants, pedestrians sustain more multisystem injuries, with concomitantly higher injury severity scores and mortality.2 Although a disproportionately large number of these crashes occur in developing and transitional countries, pedestrian casualties also represent a huge societal cost in industrialised nations. In Britain pedestrian injuries are more than twice as likely to be fatal as injuries to vehicle occupants3 and result in an average cost to society of £57 400, nearly twice that of injuries to vehicle occupants.4

#### Summary points

Pedestrian-vehicle crashes are responsible for more than a third of all traffic related fatalities and injuries worldwide

Lower limb trauma is the commonest pedestrian injury, while head injury is responsible for most pedestrian fatalities

Standardised tests that simulate the most common pedestrian-vehicle crashes are being used to evaluate vehicle countermeasures to reduce pedestrian injury

Energy absorbing components such as compliant bumpers, dynamically raised bonnets, and windscreen airbags are being developed for improved pedestrian protection

Despite the size of the pedestrian injury problem, research to reduce traffic related injuries has concentrated almost exclusively on increasing the survival rates for vehicle occupants. Most attempts made to reduce pedestrian injuries have focused solely on isolation techniques such as pedestrian bridges, public education, and traffic regulations and have not included changes to vehicle design. The lack of effort devoted to vehicle modifications for pedestrian safety has stemmed primarily from a societal view that the injury caused by a large, rigid vehicle hitting a small, fragile pedestrian cannot be significantly reduced by alterations to the vehicle structure. Crash engineers, …
ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo
Authors: David R. Gibb, Mohey El Shikh, Dae-Joong Kang, Warren J. Rowe, Rania El Sayed, Joanna Cichy, Hideo Yagita, John G. Tew, Peter J. Dempsey, Howard C. Crawford, Daniel H. Conrad
Journal: The Journal of Experimental Medicine (2010)

The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10−/− mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell–specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer.
Monitoring disease activity by stool analyses: from occult blood to molecular markers of intestinal inflammation and damage
Authors: D Foell, H Wittkowski, J Roth
Journal: Gut (2009)

It is a common experience that gastrointestinal symptoms urge us to differentiate inflammatory bowel disease (IBD) from functional disorders. Furthermore, in patients with proven IBD the disease activity has to be accurately monitored. Faecal markers of neutrophil influx into the mucosa are promising indicators of intestinal inflammation. Some neutrophil-derived proteins may be linked to the pathogenesis of IBD due to their functions as damage-associated molecular pattern molecules (DAMPs). Phagocyte-specific DAMPs of the S100 family are released from neutrophils or monocytes, followed by pro-inflammatory activation of pattern recognition receptors. The complex of S100A8/S100A9 was termed "calprotectin" and has been in use as a faecal marker for 10 years. More recently, faecal S100A12 has been reported to be an even more accurate faecal marker of inflammation. We review the biology of this novel group of molecules which can be used as surrogate markers directly linked to the molecular mechanisms of gut inflammation.
Distribution of arterial lesions and collateral pathways in the pulmonary hypertension of congenital heart disease: a computer aided reconstruction study.
Authors: G Yaginuma, H Mohri, T Takahashi
Journal: Thorax (1990)

Three dimensional computer aided reconstructions of pulmonary vessels were used to investigate the distribution of vascular changes and the formation of collateral channels in 11 patients with congenital heart disease. In the patients with less severe grades of hypertensive pulmonary vascular disease obstructive changes were unevenly distributed, whereas in those with disease of grade 4 or more distribution became more even. Plexiform lesions occurred rather more frequently in supernumerary arteries arising laterally from a large parent vessel, whereas cellular or fibrous intimal thickening tended to affect dichotomous branches at the periphery. Hypertensive changes were confined to arteries of 100-150 microns diameter running along the necks of acini. Various types of collateral channels were found. In particular, the reconstructions suggest that pulmonary arterial blood at high pressure could flow into bronchial arteries via proximal bronchopulmonary arterial anastomoses, and thence by way of dilatation lesions to the alveolar capillaries.
Effects of FK-506 on Contraction and Ca <sup>2+</sup> Transients in Rat Cardiac Myocytes
Authors: Eileen McCall, Li Li, Hiroshi Satoh, Thomas R. Shannon, Lothar A. Blatter, Donald M. Bers
Journal: Circulation Research (1996)

FK-506 binding protein (FKBP) has been reported to be closely associated with the ryanodine receptor in skeletal and cardiac muscle and to modulate sarcoplasmic reticulum (SR) Ca 2+ release channel gating in isolated channels. FK-506 can inhibit the activity of FKBP, thereby reversing its effects on SR Ca 2+ release. We investigated the function of FKBP during normal contractions and Ca 2+ transients in intact rat ventricular myocytes loaded with fluorescent Ca 2+ indicators. FK-506 significantly increased steady state twitch Ca 2+ transients and contraction amplitudes even under conditions in which the SR Ca 2+ load and Ca 2+ current were unaltered, suggesting that FK-506 increases the fraction of SR Ca 2+ released during excitation-contraction (E-C) coupling. Action potentials were somewhat prolonged, consistent with the larger Ca 2+ transients causing greater inward Na + -Ca 2+ exchange current. FK-506 did not affect SR Ca 2+ uptake but modestly decreased Ca 2+ extrusion via Na + -Ca 2+ exchange in intact cells (although no effect on Na + -Ca 2+ exchange was seen in sarcolemmal vesicles). In most cells, FK-506 caused an increase in SR Ca 2+ content during steady state stimulation, as assessed by caffeine-induced contractures. This was probably due to the inhibition of Ca 2+ efflux via Na + -Ca 2+ exchange. FK-506 also accelerated the rest decay of SR Ca 2+ content and increased the frequency of resting Ca 2+ sparks about fourfold. The increase in frequency of these basic Ca 2+ release events was not associated with changes in the amplitude or duration of the Ca 2+ sparks. We conclude that FK-506 increases the fraction of SR Ca 2+ released during normal twitches and enhances the rate of SR Ca 2+ release during rest. FK-506 also inhibits Na + -Ca 2+ exchange, although this effect may be indirect. These effects are consistent with an important SR-stabilizing effect of FKBP in intact rat ventricular myocytes.
Methotrexate combined with isoniazid treatment for latent tuberculosis is well tolerated in patients with rheumatoid arthritis: experience from an urban arthritis clinic
Authors: A Mor, C O Bingham, M Kishimoto, P M Izmirly, J D Greenberg, S Reddy, P B Rosenthal
Journal: Annals of the Rheumatic Diseases (2007)

Objectives: Reactivation of Mycobacterium tuberculosis (TB) is a significant problem with all available tumour necrosis factor (TNF) antagonists when used to treat rheumatoid arthritis (RA), psoriatic arthritis, psoriasis and other inflammatory diseases. Concerns have been raised regarding the appropriate management of patients with latent TB (LTB) exposure (or active TB infection) before initiating TNF antagonists as the safety data of combined treatment with two potentially hepatotoxic medications, methotrexate (MTX) and isoniazid (INH), is lacking. The goal of this study was to investigate the toxicity of MTX and INH treatment in patients with RA before initiating TNF antagonists. Methods: To investigate the toxicity of MTX and INH treatment in patients with RA we performed a retrospective chart review of patients seen at the Bellevue Hospital Arthritis Clinic in New York City between 2002 and 2006. Forty-four patients who were concomitantly treated with both drugs were included. The primary outcome investigated was increase in liver function tests (LFT). Results: Transient increases in LFT were seen in 11% of patients, but in no case was this more than twice the upper limit of normal values. All abnormal LFT resolved spontaneously without intervention. In addition, no patient has developed signs or symptoms of TB reactivation. Conclusions: The use of INH for LTB was well tolerated in patients with RA on a background regimen of MTX. While the risks and benefits of all treatment must always be considered, in our experience the additive risk of INH to MTX in terms of hepatotoxicity was low. None the less it is prudent to follow LFT closely on patients taking this combination.
The Genetics of Castration-Resistant Prostate Cancer: What Can the Germline Tell Us?
Authors: Nima Sharifi, William L. Dahut, William D. Figg
Journal: Clinical Cancer Research (2008)

Abstract Androgen deprivation therapy (ADT) is the cornerstone treatment for advanced prostate cancer. Despite frequent responses, the majority of metastatic tumors will progress to castration-resistant prostate cancer. Numerous molecular and genetic perturbations have been described in castration-resistant prostate cancer, which are attributable for gain-of-function changes in the androgen receptor, allowing for cell survival and proliferation with castrate levels of testosterone. The utility of these somatic perturbations, which are selected for in the tumor after ADT, for prognostication of response and response duration in metastatic prostate cancer, is problematic. Here, we discuss recent studies that describe germline polymorphisms that determine the response to ADT. Coding and noncoding germline polymorphisms in genes involved in the androgen pathway affect the response to ADT. These polymorphisms require further study and validation. However, they have the potential to be useful for prognosticating the response to ADT, designing clinical trials for patients who have poor germline prognostic features and designing novel therapies targeted against genes that influence the response to ADT.
TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to <i>Mycobacterium tuberculosis </i>
Authors: Andre Bafica, Charles A. Scanga, Carl G. Feng, Cynthia Leifer, Allen Cheever, Alan Sher
Journal: The Journal of Experimental Medicine (2005)

To investigate the role of Toll-like receptor (TLR)9 in the immune response to mycobacteria as well as its cooperation with TLR2, a receptor known to be triggered by several major mycobacterial ligands, we analyzed the resistance of TLR9−/− as well as TLR2/9 double knockout mice to aerosol infection with Mycobacterium tuberculosis. Infected TLR9−/− but not TLR2−/− mice displayed defective mycobacteria-induced interleukin (IL)-12p40 and interferon (IFN)-γ responses in vivo, but in common with TLR2−/− animals, the TLR9−/− mice exhibited only minor reductions in acute resistance to low dose pathogen challenge. When compared with either of the single TLR-deficient animals, TLR2/9−/− mice displayed markedly enhanced susceptibility to infection in association with combined defects in proinflammatory cytokine production in vitro, IFN-γ recall responses ex vivo, and altered pulmonary pathology. Cooperation between TLR9 and TLR2 was also evident at the level of the in vitro response to live M. tuberculosis, where dendritic cells and macrophages from TLR2/9−/− mice exhibited a greater defect in IL-12 response than the equivalent cell populations from single TLR9-deficient animals. These findings reveal a previously unappreciated role for TLR9 in the host response to M. tuberculosis and illustrate TLR collaboration in host resistance to a major human pathogen.