tbuckley/cabot-search huggingface dataset:
Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us
Authors: Scott F Dowell, Mei Shang Ho
Journal: The Lancet Infectious Diseases (2004)

The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.
The Role of Virus-specific Immunoglobulin E in Airway Hyperresponsiveness
Authors: Azzeddine Dakhama, Jung-Won Park, Christian Taube, Kosuke Chayama, Annette Balhorn, Anthony Joetham, Xu-Dong Wei, Rhi-Hua Fan, Christina Swasey, Nobuaki Miyahara, Taku Kodama, Alberto Alvarez, Katsuyuki Takeda, Erwin W. Gelfand
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis during infancy and is associated with subsequent wheezing and asthma, but the nature of this association is not fully understood. We investigated the role of RSV-specific IgE antibodies in the pathophysiology of virus-induced airway dysfunction in a mouse model. Lung infection with RSV resulted in significant increases in mRNA expression for IgE and both of its high- and low-affinity receptors. In serum, virus-specific IgE antibodies reached peak levels by Day 21 after infection. Data from in vitro experiments show that RSV can induce mast cell degranulation, but only if these cells are sensitized with specific IgE. When passively sensitized in vivo with virus-specific IgE, mice developed exaggerated airway responsiveness to methacholine on airway infection, an effect that required the high-affinity receptor of IgE. These data suggest that RSV-specific IgE may contribute to the pathophysiology of airway dysfunction in children who develop this class of specific antibody.
Regeneration pattern of blood vessels and nerves in cultured keratinocyte grafts assessed by confocal laser scanning microscopy
Authors: X.H GU, G. TERENGHI, T. KANGESU, H.A. NAVSARIA, D.R SPRINGALL, I.M. LEIGH, C.J. GREEN, J.M POLAK
Journal: British Journal of Dermatology (1995)

The aim of this study was to investigate the pattern of both neovascularization and reinnervation, and the relationship between the two processes, in keratodermal grafts, using confocal laser scanning microscopy, at different time points during the healing process. Keratodermal grafts were prepared in pigs by combining autologous dermis with cultured autologous keratinocytes. Immunohistochemistry was carried out on thick cryostat sections (100-150 microns), using antisera to the endothelial marker von Willebrand factor (vWf) and the pan-neuronal marker protein gene product 9.5 (PGP9.5). The results suggest that the neovascularization and reinnervation in the cultured keratodermal graft is almost complete at 6 weeks. Neovascularization precedes innervation, reaching the surface covered by the keratinocytes at 2 weeks, initially with a linear vascular pattern. From 3 weeks, there is a gradual arborization of the vessels to form a typical vascular plexus. The process of reinnervation is similar in pattern to that of neovascularization, although slower in developing a full network of fibres. In conclusion, the use of confocal microscopy allows the precise definition of complex patterns of neovascularization and nerve growth, which are not fully apparent when using conventional microscopy. Because angiogenesis occurs first, it probably plays a leading role in the survival of keratodermal grafts during wound healing. Indeed, new blood vessels form a pathway for the subsequent innervation process, and quickly reach the epidermal layer which, in turn, may play a key role in the tropism of both blood vessels and nerves.
PLASMAPHERESIS EDEMA. II. THE EFFECT OF REDUCTION OF SERUM PROTEIN ON THE ELECTROLYTE PATTERN AND CALCIUM CONCENTRATION
Authors: Daniel C. Darrow, Edward B. Hopper, M. Katharine Cary
Journal: Journal of Clinical Investigation (1932)

In a previous paper (1) it was shown that, when the concentration of serum protein had been reduced to about three per cent by plasmaphere- sis, dogs became edematous.The type of edema produced in this way is probably most closely analogous to that of nutritional edema.In connection with the work on dogs reported in that paper, certain studies of serum and ascitic electrolytes were undertaken and will be discussed in this paper.Physiological saline was injected into two addi- tional dogs to determine the effect of this procedure on serum electrolytes under conditions similar to those of the plasmapheresis experiments.METHODS About eighteen hours after previous bleedings or administration of salt solution, blood was withdrawn from a femoral artery or jugular vein and was allowed to clot under oil.Serum was used for all analyses.Ascitic fluid was taken at necropsy in Experiments III and V but in the other cases by abdomi- nal paracentesis.The following chemical methods were used: Bicarbonate, manometric' method of Van Slyke and Neill (2) using 0.2 ml.; chloride, Van Slyke (3) using potassium permanganate.to oxidize the proteins; phosphate, Benedict and Theis (4); total base, Stadie and Ross's (5) modification of the Fiske method without removing phosphate or applying a correction for phos- phate; nitrogen by gross Kjeldahl on 1 ml. of serum using thirty per cent hydrogen peroxide to facilitate complete oxidation; nonprotein nitrogen, Folin and Wu (6); and calcium, Clark and Collip's (7) modification of Kramer and Tis- dall's method.Albumin was determined by the Howe (8) method of precipitating globulin with Na2SO4 in the first two experiments and in the third experiment up to the eighth day.Thereafter, Howe's method using a mixture of KH2PO4 and K2HPO4 (1: 2) to precipitate the globulin was adopted.The two methods give essentially identical results but we have found the phosphate method somewhat more consistent from day to day.Total nitrogen minus nonprotein nitrogen was multiplied by 6.25 to obtain protein.All determina- tions except phosphate and nonprotein nitrogen were run in duplicate.All analyses are expressed in milli-equivalents (m.eq.) of univalent base per liter of serum.In converting protein to equivalents of base, the factors of Van Slyke, Hastings, Hiller and Sendroy (9) were used, namely, albumin per cent X 2.73 and globulin per cent X 1.87.Total carbon dioxide was con- verted to bicarbonate at pH 7.38 by multiplying carbon dioxide volumes per VB VB VB VB AB VB AbFl AB VB AB VB AB VB AbFl VB VB VB VB AB VB AbFl VB VB VB VB VB VB VB VB VB VB AB VB AbFl VB VB VB VB VB VB
Case-control study of childhood leukaemia and cancer in Scotland: findings for neonatal intramuscular vitamin K
Authors: P. A McKinney, E. Juszczak, E. Findlay, K. Smith
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To test the hypothesis of an association between neonatal intramuscular vitamin K and childhood leukaemia and other cancers. <b>Design:</b> Population based case-control study with data abstracted from hospital records. <b>Setting:</b> Scotland. <b>Subjects:</b> Children aged 0-14 years resident in Scotland from 1991-4 and diagnosed with leukaemia (150), lymphomas (46), central nervous system tumours (79), a range of other solid tumours (142), and a subset of acute lymphoblastic leukaemia (129). Controls were 777 children matched for age and sex, providing 417 matched sets (360 triplets and 57 pairs) for analysis. <b>Main outcome measure:</b> Odds ratios for the risk of childhood leukaemia and cancer and intramuscular vitamin K versus a combined group of oral doses, none, and no record. Results are given for information recorded in medical notes and data supplemented by hospital policy. <b>Results:</b> Odds ratios based on medical record abstractions showed no significant positive association for leukaemias (odds ratio 1.30; 95% confidence interval 0.83 to 2.03), acute lymphoblastic leukaemia (1.21; 0.74 to 1.97), lymphomas (1.06; 0.46 to 2.42), central nervous system tumours (0.74; 0.40 to 1.34), and other solid tumours (0.59; 0.37 to 0.96). There was no association with acute lymphoblastic leukaemia in children aged 1 to 6 years. Imputation of exposure from hospital policy gave similar results. Adjustment for deprivation and type of delivery moved risk estimates closer to unity for all major diagnostic groups. <b>Conclusions:</b> The observation of an increased risk of childhood leukaemia and cancer associated with intramuscular vitamin K is not confirmed by this independent population based study. <h3>Key messages</h3> Debate continues over the role neonatal intramuscular administration of vitamin K may have in the subsequent development of childhood cancer Most previous epidemiological studies have failed to demonstrate an overall significant association No significant risk is evident from a population based study in Scottish children that used data from hospital records No relation was found for leukaemias, central nervous system tumours, or any other subgroup of childhood malignancy
Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells
Authors: Dörte Hamann, Paul A. Baars, Martin H.G. Rep, Berend Hooibrink, Susana R. Kerkhof-Garde, Michèl R. Klein, René A.W. van Lier
Journal: The Journal of Experimental Medicine (1997)

Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA−CD45R0+ cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon γ, tumor necrosis factor α, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27− population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-γ and TNF-α. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27− cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.
Octreotide Inhibits the Meal–Induced Increases in the Portal Venous Pressure of Cirrhotic Patients With Portal Hypertension: A Double–Blind, Placebo–Controlled Study
Authors: Aiden P. McCormick, Maria Rosa Biagini, Robert Dick, Lynda Greenslade, Jason Chin, Fabrizio Cardin, Donald Wagstaff, Neil McIntyre, Andrew K. Burroughs
Journal: Hepatology (1992)

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.
Transversus abdominis: a different view of the elephant
Authors: Paul Hodges
Journal: British Journal of Sports Medicine (2008)

It is good to see that clinical and research hypotheses are debated in the literature. The purpose of science is to challenge ideas and to consider alternative interpretations of observations. Within this, the place for neurophysiological/biomechanical studies in clinical research is not to predict the potential efficacy of a clinical approach, but to try to understand the mechanisms that underlie it. This is helpful as it provides a means to refine, improve, and direct intervention and provides a platform to develop rationales for intervention, particularly when we are faced with complex patients who do not fit the clinical prediction rule or the narrow criteria adopted for inclusion in clinical trials. If we understand the mechanisms we have a powerful tool to rationalise and test interventions. The developing debate about the role of transversus abdominis is healthy for rational consideration of motor control interventions for back pain.

I welcome this opportunity to comment on the opinions and interpretations of Allison et al 1 and Cook.2 As indicated by Allison et al in their paper published in JOSPT,3 it is not the data that are questioned; it is the interpretation. It seems that we have a recurrence of the issue of the six blind men and the elephant, where we see the same animal, but from different perspectives, and draw different conclusions. There are a number of assumptions that require consideration to challenge the interpretation of Allison et al 1 and the opinion of Cook.2 A key issue is that to conclude that a single observation from a single task refutes the conclusion of a whole range of different methodologies/tasks seems unfounded.

In response to the editorial by Cook,2 the first thing to consider is that the results of physiological/biomechanical studies cannot be used to challenge the outcomes …
The histamine H<sub>3</sub> receptor agonist<i>N</i><sup>α</sup>-methylhistamine produced by<i>Helicobacter pylori </i>does not alter somatostatin release from cultured rabbit fundic D-cells
Authors: I L P Beales, J Calam
Journal: Gut (1998)

Background —The mechanisms underlying the suppression of somatostatin dependent reflexes in Helicobacter pylori infection are not fully determined. The H pylori product N α -methylhistamine and inflammatory mediators such as tumour necrosis factor-α (TNF-α) may be responsible for the alterations in somatostatin release. Aims —To examine the effect of N α -methylhistamine on somatostatin release from cultured somatostatin-secreting D-cells. Methods —Rabbit fundic D-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation and cultured for 40 hours. The effects of N α -methylhistamine on somatostatin release soon after stimulation (two hours) and after more prolonged exposure (24 hours) were assessed. Results — N α -Methylhistamine (1 nM–1 μM) had no effect on basal or carbachol or adrenaline stimulated release over two hours. Similarly with prolonged exposure no effect on somatostatin cell content or release was identified. In contrast, TNF-α (24 hours) led to a dose dependent fall in both somatostatin content and release. Conclusions — N α -Methylhistamine had no direct inhibitory effects on D-cells, but TNF-α both significantly reduced the cellular content and inhibited release. Inflammatory cytokines, rather than N α -methylhistamine, are therefore likely to be responsible for directly inhibiting D-cell function in H pylori infection.
Quantitative studies on T cell diversity. I. Determination of the precursor frequencies for two types of streptococcus A-specific helper cells in nonimmune, polyclonally activated splenic T cells.
Authors: K Eichmann, I Falk, I Melchers, M M Simon
Journal: The Journal of Experimental Medicine (1980)

A limiting-dilution system is described that makes use of T cell growth factor T cell expansion and allows the determination of precursor frequencies for various regulatory and effector T cells in nonimmune, polyclonally, or specifically activated T cell populations. Two different sets, a frequent and a rare set, of T helper cell precursors with specificity for trinitrophenyl-group A streptococcal vaccine, could be identified: the frequent set is of the Lyt-123 phenotype, and is present at frequencies of from 1/1,000 to 1/6,000 splenic T cells. It is only active at low cell numbers, whereas it is completely inactivated at greater cell numbers, presumably by suppressor T cells of lower frequency but greater potency. The rare set is of the Lyt-1 phenotype, is present at frequencies of from 1/10,000 to 1/70,000, and is not sensitive to suppressor cells present within the tested cell numbers. We suggest that the frequent set contains primiary helper cell precursors, whereas the rare set contains helper T memory cells preselected by previous exposure to other antigens. The results are discussed with respect to other reports on the involvement of more than one set of helper cells in antibody production.
Factors related to early mortality in cirrhotic patients bleeding from varices and treated by urgent sclerotherapy.
Authors: O Le Moine, M Adler, N Bourgeois, M Delhaye, J Deviere, M Gelin, A Vandermeeren, A Van Gossum, A Vereerstraeten, P Vereerstraeten
Journal: Gut (1992)

Variceal haemorrhage in cirrhotic patients carries a high early mortality even when balloon tamponade or emergency sclerotherapy are applied. The aim of this study to identify patients dying within six weeks of their first variceal haemorrhage. One hundred and twenty one patients with parenchymal cirrhosis presenting with the first variceal bleeding episode between June 1983 and December 1988 were studied. Nineteen patients were excluded for various reasons. Emergency sclerotherapy was carried out in cases of active bleeding or where there were endoscopic signs of recent bleeding, and then regularly repeated afterwards. Of the 24 variables studied and included in a multivariate analysis using a logistic regression model, three had an independent prognostic value: encephalopathy, prothrombin time, and the number of blood units transfused within the 72 hours of time zero. The subsequent regression equation was able to predict 89% of the patients who will die and 97% of the patients who will still be alive six weeks after their first variceal haemorrhage treated by sclerotherapy. Pugh score was less discriminatory than these last three variables in terms of accuracy of adjustment, goodness of fit to the model, receiver operating characteristic curves, and percentage correct prediction. To measure the accuracy of the prediction rule, our model was applied to another series of 28 cirrhotic patients admitted with their first variceal bleeding during the next period (January 1989 to May 1990). Death and survival were correctly predicted in respectively 82% and 94% of the cases. The use of this score is recommended for the selection of patients with high early mortality after variceal bleeding despite sclerotherapy, and for the design of new therapeutic trials.
Results of nationwide performance measurement programme for community-acquired pneumonia in German federal state Hessen in 2012
Authors: Katrin Wolf, Margarete Bosing, Björn Misselwitz, Thomas O. Wagner, Tim O. Hirche
Journal: European Respiratory Journal (2014)

Aim: Community-acquired pneumonia (CAP) is the most frequent cause of death related to infection in Germany. Since 2005, CAP was included in the nationwide mandatory performance measurement programme in Germany. The present work analyses the implementation of this programme and the influence on clinically relevant outcome parameters in the German federal state Hessen in 2012.

Results: In Hessen 16.726 data sets on patients hospitalised for CAP were documented in 2012. The data reveal ongoing improvement of almost all CAP indicators that are mandatory in the programme. Except for the breathing rate , all indicators were obtained and documented in accordance with predefined reference values. The 2012 data demonstrate that essential prognostic parameters, as measurement of blood oxygen and time to antibiotics after hospital admission are increasingly well accepted in hospitals throughout Hessen.

The main indicator for outcome quality, mortality of CAP , was markedly reduced in Hessen in 2012. A significant reduction of death rate was observed for the entirety of CAP Patients as well as following stratification of subgroups according to CRB-65 risk classes.

Conclusion: The data presented suggest a causal relationship of the nationwide mandatory performance measurement programme and declining mortality of CAP in Germany. The quality indicators in the programme were developed on the basis of the current German S3-CAP-guidelines and it is postulated that obligation for a quality assurance programme reinforces closer orientation on the guideline recommendations in clinical practice, resulting in improved outcome quality.
RAF/MEK Dependence of <i>KRAS</i>-Mutant Pancreatic Ductal Adenocarcinomas
Authors: Aphrothiti J. Hanrahan, David B. Solit
Journal: Cancer Discovery (2012)

Abstract Summary: Studies using genetically engineered mouse models indicate that RAF activation is sufficient to induce pancreatic intraepithelial neoplasms, suggesting that mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase (ERK) kinase (MEK) inhibitor–based combination approaches may have clinical use in patients with pancreatic ductal adenocarcinomas. Cancer Discov; 2(8); 666–9. ©2012 AACR. Commentary on Collisson et al., p. 685.