tbuckley/cabot-search huggingface dataset:
A chest physician's guide to mechanisms of sinonasal disease
Authors: V. Hox, T. Maes, W. Huvenne, C. Van Drunen, J. A. Vanoirbeek, G. Joos, C. Bachert, W. Fokkens, J. L. Ceuppens, B. Nemery, P. W. Hellings
Journal: Thorax (2015)

The upper and lower airways are closely linked from an anatomical, histological and immunological point of view, with inflammation in one part of the airways influencing the other part. Despite the concept of global airway disease, the upper airways tend to be overlooked by respiratory physicians. We provide a clinical overview of the most important and recent insights in rhinitis and rhinosinusitis in relation to lower airway disease. We focus on the various exogenous and endogenous factors that play a role in the development and aggravation of chronic upper airway inflammation. In addition to the classical inhaled allergens or microorganisms with well-defined pathophysiological mechanisms in upper airway disease, environmental substances such as cigarette smoke, diesel exhaust particles and occupational agents affecting lower airway homeostasis have recently gained attention in upper airway research. We are only at the beginning of understanding the complex interplay between exogenous and endogenous factors like genetic, immunological and hormonal influences on chronic upper airway inflammation. From a clinical perspective, the involvement of upper and lower airway disease in one patient can only be fully appreciated by doctors capable of understanding the interplay between upper and lower airway inflammation.
Type B Hepatitis after Needle-Stick Exposure: Prevention with Hepatitis B Immune Globulin
Authors: L. B. SEEFF
Journal: Annals of Internal Medicine (1978)

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAg)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P < 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBe). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.
Analysis of restriction fragment length polymorphism in lymphokine genes of normal and autoimmune mice.
Authors: G Richter, Z H Qin, T Diamantstein, T Blankenstein
Journal: The Journal of Experimental Medicine (1989)

Analysis of RFLP has been employed in lymphokine genes of autoimmune and normal mice. No polymorphism could be detected in the loci containing IL-2, IL-2 receptor, IL-5, and IFN-gamma in NZB, NZW, BxSB, and MRL/lpr mice when compared with normal mice. Allelic forms were identified in the IL-1 alpha gene of BALB/c and in the IL-4 gene of NZW. The frequency of the Bam HI RFLP in the TNF-alpha gene of NZW which has been proposed to be associated with the development of autoimmune disease in (NZB x NZW)F1 mice has been analyzed in a number of different inbred strains and in wild mice. Since the same allele is inherited in most autoimmune, healthy laboratory and wild mice the TNF-alpha gene does not seem to be one of the causal agents that contributes to the development of autoimmunity in (NZB x NZW)F1 mice.
Increases in invasive melanoma in England, 1979–2006, by anatomical site
Authors: S.C. Wallingford, R.D. Alston, J.M. Birch, A.C. Green
Journal: British Journal of Dermatology (2011)

National melanoma incidence trends with details of anatomical site have not been previously described for England.To describe site-specific trends in cutaneous melanoma for England as a whole during the last three decades.Anonymized data, 1979-2006, were obtained from national cancer registrations of all patients in England up to age 89years with incident primary invasive cutaneous melanomas (n=124055). Sex-specific age-standardized incidence rates and average annual percentage change in rates were calculated for each broad anatomical site.Overall incidence rates of cutaneous melanoma in England, 1979-2006, were 81 and 100 per million, in males and females, respectively. Site-specific rates were consistently highest on the lower limbs in females followed by the trunk in males. Greatest annual increases occurred on the trunk in both sexes over 45years (males 9·9%, females 6·8%), then upper limbs (males 8·7%, females 6·8%). Incidence trends in males relative to females varied little across sites apart from a more rapid rise in head/neck melanomas in males than in females after the 1980s.Invasive melanoma rates continue to rise in England, particularly on the trunk and arms, and in males on the head/neck. The steeper increases in melanoma rates among males are consistent with their greater sun exposure and poorer compliance with sun protection measures than females.
Recovery of PdiTwitch Following the Induction of Diaphragm Fatigue in Normal Subjects
Authors: JOHN M. TRAVALINE, SHRIVAS SUDARSHAN, GERARD J. CRINER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Low frequency diaphragm fatigue (LFF) may play a major role in the pathogenesis of ventilatory failure; however, recovery from LFF is not well studied. We measured transdiaphragmatic twitch pressure (PdiT) at FRC (using a reduction of PdiT as an index of LFF) and maximum transdiaphragmatic pressure (Pdimax) before and after the induction of diaphragm fatigue in seven normal subjects, age 31 ± 3 yr (mean ± SD). Fatigue was induced by breathing through an inspiratory resistive load. PdiT produced by bilateral transcutaneous supramaximal electrophrenic stimulation was measured at baseline, 15, 30 min, 1, 2, 3, 4 h, and then 1 to 3 times between hour 20–25 post-fatigue. Pdimax estimated by twitch occlusion was measured at baseline, 30 min, 2–3, and 20–25 h post-fatigue. Pre-fatigue values (mean ± SE) were: PdiT 23.6 ± 2.5 cm H2O. The mean ± SD time to fatigue was 25.3 ± 12.3 min. Post-fatigue PdiT was reduced to 50%, and by 3 h was 72% of the initial value; 100% by 25 h. Pdimax was reduced to 75% post-fatigue, but recovered to 87% by 3 h, and 100% by 25 h. We concluded that recovery of PdiT and Pdimax in normal subjects starts to occur within the first few hours following diaphragm fatigue, and is complete by 25 h.
Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection
Authors: Thais Mauad, Ludhmila A Hajjar, Giovanna D Callegari, Luiz F F da Silva, Denise Schout, Filomena R B G Galas, Venancio A F Alves, Denise M A C Malheiros, Jose O C Auler, Aurea F Ferreira, Marcela R L Borsato, Stephania M Bezerra, Paulo S Gutierrez, Elia T E G Caldini, Carlos A Pasqualucci, Marisa Dolhnikoff, Paulo H N Saldiva
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection.Objectives: The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure.Methods: Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-γ, tumor necrosis factor-α, CD8+ T cells and granzyme B+ cells in the lungs was investigated by immunohistochemistry.Measurements and Main Results: Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diffuse alveolar damage was present in 20 individuals. In six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-γ and a large number of CD8+ T cells and granzyme B+ cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure.Conclusions: Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, where three distinct histological patterns can be identified. We also show evidence of ongoing pulmonary aberrant immune response. Our results reinforce the usefulness of autopsy in increasing the understanding of the novel human influenza A (H1N1) infection.
John Brian Walker
Authors: A. Beale
Journal: BMJ (2015)

John Brian Walker was born in Catford, London, and studied medicine at New College, Oxford before completing his studies at the Royal London.

As a final year medical student during the second world war, Brian and some colleagues were asked to go to Holland in 1945. He was immediately diverted to help manage the liberation of the Belsen concentration camp. Brian was one of the first to witness the …
Major histocompatibility complex class II expression distinguishes two distinct B cell developmental pathways during ontogeny.
Authors: K P Lam, A M Stall
Journal: The Journal of Experimental Medicine (1994)

All mature B cells coexpress major histocompatibility complex (MHC) class II molecules, I-A and I-E, which are restriction elements required for antigen presentation to CD4+ T cells. However, the expression of class II during the early stages of B cell development has been unclear. We demonstrate here that there is a difference in the expression of class II during murine B cell development in the fetal liver and adult bone marrow (BM). These differences define two distinct B cell developmental pathways. The Fetal-type (FT) pathway is characterized by pre-B and immature IgM+ B cells generated in the fetal liver which initially lack all class II expression. In contrast, the Adult-type (AT) pathway is typified by B cells developing in the adult BM which express class II molecules from the pre-B cell stage. In vitro stromal cell cultures of sorted fetal liver and adult BM pro-B cells indicated that the difference in I-A expression during B cell development is intrinsic to the progenitors. In addition, we show that FT B cell development is not restricted to the fetal liver but occurs in the peritoneal cavities, spleens, liver, and BM of young mice up to at least 1 mo of age. The AT B cell development begins to emerge after birth but is, however, restricted to the BM environment. These findings indicate that there are two distinct B cell developmental pathways during ontogeny, each of which could contribute differentially to the immune repertoire and thus the functions of B cell subsets and lineages.
RESPONSES - Re: Trends in Reported Incidence of Primary Malignant Brain Tumors in Children in the United States
Authors: W. C. Black
Journal: JNCI Journal of the National Cancer Institute (1999)

I read with some concern the editorial by Black (1) for the article written by Smith et al. (2) reporting on the trends in reported incidence of primary malignant brain tumors in children in the United States.In their article, Smith et al. (2) offer fairly complex statistical arguments that purport to show no increase in the incidence of primary brain tumors in children.The authors (1,2) argue that the increased incidence relates to improved diagnostic techniques.I believe that they overlooked two critical points.Malignant brain tumors of childhood are not silent diseases.If indeed there was an increased sensitivity to diagnosis made in 1984, certainly in the subsequent 10-year interval, those cases that may have been missed would have become clinically evident.This point was not made by either the editorial or the article.Secondly, there is a diminishing, albeit very slight, mortality, and this may be attributable to the considerable improvements that have been made in neurosurgical techniques during this period.The fact that the mortality has not diminished further argues for an increasing incidence.The Journal highlighted the article by Smith et al. by having an editorial written that states that we would be better off not seeking reasons for this increasing incidence and rather that we should place our efforts elsewhere.This emphasis is all the more troubling to me, since this article appeared in the popular media, in both newspapers and television.
How neural is the neural blackboard architecture?
Authors: Yoonsuck Choe
Journal: Behavioral and Brain Sciences (2006)

The target article does not provide insight into how the proposed neural blackboard architecture can be mapped to known neural structures in the brain. There are theories suggesting that the thalamus may be a good candidate. However, the experimental evidence suggests that the cortex may be involved (if in fact the blackboard is implemented in the brain). Issues arising from such a mapping will be discussed.
Emerging inhaled bronchodilators: an update
Authors: M. Cazzola, M. G. Matera
Journal: European Respiratory Journal (2009)

Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field. The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients. A variety of beta(2)-agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development. The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.
The Addition of Bevacizumab to Standard Radiation Therapy and Temozolomide Followed by Bevacizumab, Temozolomide, and Irinotecan for Newly Diagnosed Glioblastoma
Authors: James J. Vredenburgh, Annick Desjardins, David A. Reardon, Katherine B. Peters, James E. Herndon, Jennifer Marcello, John P. Kirkpatrick, John H. Sampson, Leighann Bailey, Stevie Threatt, Allan H. Friedman, Darell D. Bigner, Henry S. Friedman
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. Experimental Design: A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days. The primary endpoint was the proportion of patients alive 16 months after informed consent. Results: The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervous system hemorrhage, came off study during radiation therapy. Seventy patients started the postradiation therapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity. The median overall survival was 21.2 months (95% CI: 17.2–25.4), and 65% of the patients were alive at 16 months (95% CI: 53.4–74.9). The median progression-free survival was 14.2 months (95% CI: 12–16). Conclusion: The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established. Clin Cancer Res; 17(12); 4119–24. ©2011 AACR.
The value of faecal calprotectin in the investigation of suspected early-onset inflammatory bowel disease
Authors: S. J. Lawrence, P. Henderson, A. Casey, K. Kingstone, P. Rogers, P. M. Gillett, D. C. Wilson
Journal: Gut (2011)

<h3>Introduction</h3> The measurement of faecal calprotectin (FC) in patients with suspected bowel inflammation has become routine in many centres in recent years. Although FC levels have been shown to correspond with radio-nucleotide labelled neutrophil scans and endoscopic appearances in those with inflammatory bowel disease (IBD), it is still unclear as to the value of FC to inform IBD diagnosis, especially with regard to endoscopic investigation. <h3>Methods</h3> The records of the cohort of all IBD patients who were diagnosed (using standard endoscopic assessment) within the Department of Paediatric Gastroenterology in Edinburgh between 1 January 2005 and 30 June 2010 (aged 1–17 years), with a FC performed during initial workup were identified. The local laboratory results system and endoscopy lists were reviewed and a matched non-IBD control who had similarly undergone endoscopy and also had a referral FC level available was identified. Only FC values taken at referral or initial investigation (not repeat samples) in those without any previous gastroenterological diagnosis were included. Patients who provided insufficient samples (&lt;2 g) and those less than 1 year of age were excluded. <h3>Results</h3> A total of 218 patient samples met the inclusion criteria. These included samples from patients with IBD (n=109) (63 Crohn9s disease, 22 ulcerative colitis, 24 IBD-U) and 109 controls. The IBD and control group consisted of 49 females:60 males and 41 females: 67 males respectively (p=0.364). In the IBD group 103/109 (94%) had a FC level &gt;50 μg/g compared to 49/109 (45%) in the control group (p=&lt;0.0001). However, the number of controls with values greater than &gt;200 μg/g was significantly lower – 19/109 (17%) compared to 99/109 (91%) for IBD (p=&lt;0.0001). Using the standard laboratory lower reference range of &lt;50 μg/g the sensitivity of FC for IBD diagnosis was 94% (95% CI 88 to 98), specificity 55% (95% CI 45 to 65) with a PPV of 68% (95% CI 60 to 75) and NPV of 91% (95% CI 81 to 97). However, using the locally accepted clinical normal range of &lt;200 μg/g the specificity increased dramatically to 83% (95% CI 74 to 89) with sensitivity 91% (95% CI 84 to 96), PPV 84% (95% CI 76 to 90) and NPV 90% (95% CI 82 to 95). <h3>Conclusion</h3> It can be seen that FC is a useful tool in determining those who may require endoscopy for suspected bowel inflammation. Those with IBD have significantly higher FC levels at referral and therefore elevated values &gt;200 μg/g should prompt further GI investigation.
Combined Analysis of CSF Tau Levels and [<sup>123</sup>I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer’s Disease
Authors: Nobuyuki Okamura, Hiroyuki Arai, Masahiro Maruyama, Makoto Higuchi, Toshifumi Matsui, Haruko Tanji, Takashi Seki, Hisao Hirai, Hiroshi Chiba, Masatoshi Itoh, Hidetada Sasaki
Journal: American Journal of Psychiatry (2002)

The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment.Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex.Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease.The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.
Fasting Plasma Total Homocysteine Levels and Mortality and Allograft Loss in Kidney Transplant Recipients
Authors: Wolfgang C Winkelmayer, Reinhard Kramar, Gary C Curhan, Anil Chandraker, Georg Endler, Manuela Födinger, Walter H Hörl, Gere Sunder-Plassmann
Journal: Journal of the American Society of Nephrology (2004)

Homocysteine is implicated to be an atherogenic amino acid and has been associated with increased risk of adverse cardiovascular outcomes. The prognostic significance of plasma total homocysteine (tHcy) levels for mortality and allograft loss in kidney transplant recipients has not been established. A total of 733 kidney transplant recipients who were seen for a routine visit at this transplant clinic in 1996 to 1998 were studied prospectively. During that visit, clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplant procedure and the organ donor was obtained from the Eurotransplant Foundation database. Patients were followed prospectively using the Austrian Dialysis and Transplant Registry. With the use of proportional-hazards regression, the independent relations of fasting plasma tHcy levels to the risk of death from any cause and kidney allograft loss were examined. During a median follow-up of 6.1 yr, 154 participants died and 260 kidney allografts were lost. After adjustment for several important risk factors, elevated tHcy levels (>/=12 micromol/L) were associated with 2.44 times the mortality risk of patients with normal tHcy levels (hazards ratio 2.44; 95% confidence interval 1.45 to 4.12; P < 0.001). Similarly, elevated tHcy levels were associated with 1.63 times increased risk of kidney allograft loss (hazards ratio 1.63; 95% confidence interval 1.09 to 2.44; P = 0.02). In this single-center sample, baseline fasting plasma tHcy levels were independently associated with the risk of death and kidney allograft loss. The clinical utility of homocysteine-lowering therapy, such as multivitamin therapy, to reduce the rates of these end points needs to be studied.
Mesenchymal Stem Cells as Therapeutics
Authors: Biju Parekkadan, Jack M. Milwid
Journal: Annual Review of Biomedical Engineering (2010)

Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics.