tbuckley/cabot-search huggingface dataset:
Childhood immunisation with conjugate vaccines and prevention of pneumonia
Authors: Rashmi Ranjan Das
Journal: Thorax (2011)

end-of-life care may be more appropriate, but there are many other important issues that explain the observed outcomes.End of life in chronic obstructive pulmonary disease (COPD) exacerbations is a difficult area of care for which the guidelines are currently vague and where our own data have shown that in large-scale studies all predictors of outcome combined only explain a minority of the variance in outcome. 3 Finally studies of patient choice when offered IMV for respiratory failure in COPD have shown patient preference for intervention beyond that considered appropriate by intensivists in many cases. 4 In essence, this is an area where prospective research is required to better understand both the wishes of patients and the costs and benefits of interventionist or palliative choices.
Non-cirrhotic intrahepatic portal hypertension
Authors: K Madhu, B Ramakrishna, U Zachariah, C E Eapen, G Kurian
Journal: Gut (2008)

This is an introduction to the Gut tutorial “Non-cirrhotic intrahepatic portal hypertension” hosted on BMJ Learning—the best available learning website for medical professionals from the BMJ Group.

The diagnosis of non-cirrhotic intrahepatic portal hypertension is often not entertained by doctors due to lack of a clear understanding of this condition. The nomenclature of …
Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B
Authors: Irene Rapti, Evangelini Dimou, Panayota Mitsoula, Stephanos J. Hadziyannis
Journal: Hepatology (2007)

We studied the long-term efficacy of adefovir dipivoxil (ADV) treatment in 42 HBeAg-negative patients with chronic hepatitis B (CHB) who had developed genotypical lamivudine (LAM) resistance with virological and clinical breakthroughs under long-term LAM treatment. Patients were allocated in 2 treatment groups. In the first (n = 14), LAM was switched to ADV monotherapy whereas in the second (n = 28) ADV was added to LAM. The two groups did not differ in patients' characteristics, all of them having HBV genotype D infection with the precore stop codon mutation. Within 12 months from start of ADV treatment, serum HBV DNA became nondetectable and ALT normalized in 71% and 90% of patients, respectively, with no difference between the 2 arms. Patients with baseline HBV DNA levels less than 107 copies/ml experienced a significantly earlier and more frequent decline in serum HBV DNA to nondetectable levels as compared with patients with greater than 107 HBV DNA copies/ml at baseline ( P = 0.0013) This response has hitherto been maintained (median treatment duration 40 months) in all patients with ADV added to LAM, whereas virological and biochemical breakthroughs due to development of ADV signature resistance mutations occurred in 3 of 14 patients (21%) on ADV monotherapy 15 to 18 months from start of treatment ( P = 0.0174). Conclusion: Adding ADV to LAM in HBeAg-negative CHB patients with LAM resistance effectively suppresses HBV replication in most of them and induces biochemical remission that can be maintained in all of them at least for 3 years without any evidence of development of resistance to ADV.
Anatomy of the Normal Adrenal Vein
Authors: David T. Purtilo
Journal: JAMA (1971)

To the Editor.—  The recent article by Eagan and Page on  Insufficiency Following Bilateral Adrenal Venography (215:115-116, 1971) contained  statement that the adrenal insufficiency and hemorrhage was a result of fragile veins associated with the atrophic gland usually found in patients with primary  Brookstein et al1reported intramedullary hemorrhage in five of nine adrenals after venography in patients with aldosteronism. I have heard similar tales of woe in clinical presentations in both Boston and Minneapolis. At no time have I encountered  discussion of the histological factors of the normal adrenal vein which may predispose this vessel to catheter trauma and hemorrhage.  The intraparenchymal portion of the central adrenal vein has  unique thin-thick wall architecture2-4(Figure).  Knowledge of the normal histological structure of the adrenal vein wall has become increasingly relevant at this time when adrenal venography is done frequently. Some of the
Spontaneous bilateral tubal ectopic pregnancy
Authors: J. Brady
Journal: Journal of the Royal Society of Medicine (2005)

poses a significant risk.For example, a survey of complications associated with yellow fever immunization showed that 4 out of 23 vaccinees who developed vaccineassociated viscerotropic disease had an underlying thymoma (and, we presume, Good's syndrome). 5 Most thymomas are slow growing with a tendency to recur locally; they seldom metastasize and can usually be cured by surgical resection. 6 Primary intrapulmonary thymoma without an associated mediastinal component, as seen here, is exceptionally rare. 7 These tumours arise from ectopic embryonic tissue.As far as we are aware, this is the first reported case of hypogammaglobulinaemia associated with such a tumour.
Analysis of transformation with epstein‐barr virus and phenotypic characteristics of lymphoblastoid cell lines established from patients with hairy cell leukemia
Authors: Takeshi Sairenji, Robert C. Spiro, Patricia S. Reisert, Louise Paquin, Kiyoshi Sakamoto, Atsushi Shibuya, John L. Suilivan, Isao Katayama, Robert E. Humphreys
Journal: American Journal of Hematology (1983)

Abstract In order to assess the role of Epstein‐Barr virus (EBV) in patients with hairy cell leukemia (HCL), we have sought to characterize 1) the ability of EBV to infect and transform hairy leukemic cells in vitro and 2) the phenotypes of cell lines putatively derived from those leukemic cells. Analysis of EBV‐induced transformation and the kinetics of Epstein‐Barr nuclear antigen (EBNA) induction in leukemic preparations indicated that most leukemic cells were not susceptible to EBV infection but that at least a small subpopulation of leukemic cells could be infected with EBV. Lymphoblastoid cells lines were established after exposure of peripheral blood or splenic cells from HCL patients to B95‐8 or QIMR‐WIL EBV. Splenic leukemic cell preparations were more sensitive targets for EBV transformation than were peripheral blood cell samples. The newly established cell lines, but not long‐established B lines such as Raji, demonstrated high levels of synthesis of p35, (a protein complex expressed abundnatly by cells of a subset of HCL patients) and high levels of tartrate‐resistant acid phosphatase (an enzyme relatively diagnostic for HCL). Lymphoblastiod lines from one patient with HCL expressed lambda light chains and no kappa chains as did the patient's leukemic cells. Virus expression in these lines showed that HCL‐derived lines had spontaneous earley antigen (EA) and viral capsid antigen (VCA) expression Tranforming EBV could be rescued from HCL‐derived cell lines but not from cord blood‐derived lines.
Remodeling of atrial dimensions and emptying function in canine models of atrial fibrillation
Authors: Y Shi
Journal: Cardiovascular Research (2001)

Atrial tachycardia-induced remodeling (ATR) and ventricular tachypacing-induced heart failure (HF) create experimental substrates for atrial fibrillation (AF), and both have been reported to produce atrial dilation and hypocontractility. The relative importance of changes in atrial size and contractility in the two models is unknown. This study compared changes in atrial dimensions and emptying in ATR versus HF dog models and related them to AF promotion.In ATR dogs (n=11), the right atrium (RA) was paced at 400/min for 42 days. In HF dogs (n=10), the right ventricle was paced at 240 bpm for 2 weeks, followed by 3 weeks at 220 bpm. Transthoracic echocardiography was performed at baseline and weekly thereafter. At a terminal electrophysiological study, RA effective refractory period (ERP) was recorded and AF induced repeatedly by atrial burst pacing to measure mean AF duration (DAF).Left atrial (LA) systolic area increased by 10.0% in ATR versus 48.2% in HF dogs (P=0.008), with significant time-dependent changes in HF (P=0.0001), but not ATR (P=0.16). LA diastolic area increased over time in both groups (P=0.004, 0.0001 for ATR and HF respectively), but increases were much larger in CHF (80.2%) compared to ATR (24.2%, P=0.0002). Similar findings were obtained for RA. Fractional area shortening (FAS) decreased by 19.4% (ATR) versus 41.8% (HF, P=0.007) in LA and 13.7% (ATR) versus 33.7% (HF, P=0.03) in RA. RA ERP correlated with DAF in ATR dogs (r=-0.79, P<0.001), but not in HF dogs (r=0.20, P=NS). DAF and diastolic areas of RA and LA were highly correlated (r=0.71, 0.77; P<0.01 for each) in HF dogs, but not in ATR dogs (r=-0.18, 0.29; P=NS).Remodeling of atrial size and emptying function is much greater in HF than in ATR. Whereas in ATR, electrophysiological remodeling is of prime importance in AF promotion, structural remodeling (as reflected in changes in atrial size and contraction) appears much more important in HF-induced AF.
LUCADA: a valuable resource but there are questions it cannot answer
Authors: T. Treasure, G. Hillerdal, M. Utley
Journal: Thorax (2011)

Rich and colleagues have recently provided information on lung cancer in England from the National Lung Cancer Audit database (LUCADA). 1The authors concluded that LUCADA accurately describes people in England with lung cancer and can be used to drive healthcare improvements.They found that the socioeconomic status of individual patients does not affect survival and has only limited impact on patients' access to treatment.The question remained as to whether differences in service, at the level of the NHS Trust, might explain regional variation in outcome.In this issue of Thorax, they explore inequalities in outcomes and how these are influenced by clinical characteristics of the patients and the features of local cancer services.In the tables, they also show that survival (but not the proportion operated on) differs between various ethnic groups but do not comment further on this finding in the results or discussion sections.The authors conclude that there is an opportunity to increase access to thoracic surgeons for patients who present and are being cared for in non-surgical centres. 2 Access to care should ideally not be dependent on where people live.There is no doubt that historically it has been and the authors quote evidence in support of the point from Scotland, 3 where population density is low and thoracic units are geographically sparse.In the major cities of England whether patients are seen in a specialist thoracic centre is not determined solely by where they live.Selective routing of patients by general practitioners could contribute to the differences in utilisation of surgery reported.
FoxP3 gets a new gig
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

On page 1141, the one-trick transcription factor FoxP3 reveals a new function. According to Chang and colleagues, FoxP3 does more than just drive regulatory T (T reg) cell development; it also promotes the proliferation of developing thymocytes.






Figure 

FoxP3 (red) is expressed on cortical epithelial cells (green) and drives thymocyte proliferation.




FoxP3 is required for the development of CD4+CD25+ T reg cells, which subdue the activation of conventional T cells and thus protect against chronic inflammation and autoimmunity. Mice and humans that lack FoxP3 develop a spontaneous, multi-organ autoimmune disease that has been primarily attributed to the lack of T reg cells. But one fact suggests that this explanation may be too simple. Irradiated mice that are reconstituted with FoxP3-deficient bone marrow do not develop disease, suggesting that FoxP3 also functions in nonhematopoietic cells.

Chang and colleagues now show that FoxP3 is not exclusive to T cells, but is also expressed in thymic epithelial cells. In mice lacking FoxP3, developing thymocytes were unable to proliferate normally, resulting in thymic atrophy. The proliferation defect was caused by a lack of FoxP3 in thymic stromal cells, rather than in T cells, as normal thymocytes also failed to proliferate in a FoxP3-deficient thymic environment.How FoxP3 expression on thymic epithelial cells helps drive thymocyte proliferation is unknown. Also unclear is how the proliferation defect contributes to autoimmune disease, although there is a long-standing but poorly understood link between thymic atrophy and T cell–driven autoimmune disease.
Elimination of Hepatic Metastases of Colon Cancer Cells via p53-Independent Cross-Talk between Irinotecan and Apo2 Ligand/TRAIL
Authors: Rajani Ravi, Ajay J. Jain, Richard D. Schulick, Vui Pham, Traci S. Prouser, Heather Allen, Elizabeth Garrett Mayer, Hua Yu, Drew M. Pardoll, Avi Ashkenazi, Atul Bedi
Journal: Cancer Research (2004)

Abstract The majority of colorectal cancers have lost/inactivated the p53 tumor suppressor gene. Using isogenic human colon cancer cells that differ only in their p53 status, we demonstrate that loss of p53 renders tumor cells relatively resistant to the topoisomerase I inhibitor, irinotecan. Whereas irinotecan-induced up-regulation of the proapoptotic proteins PUMA and Noxa requires p53, we find that irinotecan inhibits Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 and 5 (STAT3/5) signaling in both p53-proficient and p53-deficient tumor cells. We show that irinotecan inhibits JAK2-STAT3/5-dependent expression of survival proteins (Bcl-xL and XIAP) and cooperates with Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) to facilitate p53-independent apoptosis of colon cancer cells. Whereas xenografts of p53-deficient colon cancer cells are relatively resistant to irinotecan compared with their p53-proficient counterparts, combined treatment with irinotecan and Apo2L/TRAIL eliminates hepatic metastases of both p53-proficient and p53-deficient cancer cells in vivo and significantly improves the survival of animals relative to treatment with either agent alone. Although the synergy between chemotherapy and Apo2L/TRAIL has been ascribed to p53, our data demonstrate that irinotecan enhances Apo2L/TRAIL-induced apoptosis of tumor cells via a distinct p53-independent mechanism involving inhibition of JAK2-STAT3/5 signaling. These findings identify a novel p53-independent channel of cross-talk between topoisomerase I inhibitors and Apo2L/TRAIL and suggest that the addition of Apo2L/TRAIL can improve the therapeutic index of irinotecan against both p53-proficient and p53-deficient colorectal cancers, including those that have metastasized to the liver.
Familial clustering of Helicobacter pylori infection: population based study Commentary: Helicobacter pylori---the story so far
Authors: P. Dominici, S. Bellentani, A. R. Di Biase, G. Saccoccio, A. Le Rose, F. Masutti, L. Viola, F. Balli, C. Tiribelli, R. Grilli, M. Fusillo, E. Grossi, M. Thomson
Journal: BMJ (1999)

To assess the rate of intrafamilial transmission of Helicobacter pylori infection in the general population and the role of a family's social background.Population survey.Campogalliano, a town in northern Italy with about 5000 residents.3289 residents, accounting for 416 families.Prevalence of H pylori infection assessed by presence of IgG antibodies to H pylori.The overall prevalence of H pylori infection was 58%. Children belonging to families with both parents infected had a significantly higher prevalence of H pylori infection (44%) than children from families with only one (30%) or no parents (21%) infected (P<0.001). Multivariate analyses confirmed that children with both parents positive had double the risk of being infected by H pylori than those from families in which both parents were negative. Family social status was independently related to infection in children, with those from blue collar or farming families showing an increased risk of infection compared with children of white collars workers (odds ratio 2.02, 95% confidence interval 1.16 to 3.49).H pylori infection clusters within families belonging to the same population. Social status may also be a risk factor. This suggests either a person to person transmission or a common source of exposure for H pylori infection.
NKG2D-mediated Natural Killer Cell Protection Against Cytomegalovirus Is Impaired by Viral gp40 Modulation of Retinoic Acid Early Inducible 1 Gene Molecules
Authors: Melissa Lodoen, Kouetsu Ogasawara, Jessica A. Hamerman, Hisashi Arase, Jeffrey P. Houchins, Edward S. Mocarski, Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2003)

Natural killer (NK) cells play a critical role in the innate immune response against cytomegalovirus (CMV) infections. Although CMV encodes several gene products committed to evasion of adaptive immunity, viral modulation of NK cell activity is only beginning to be appreciated. A previous study demonstrated that the mouse CMV m152-encoded gp40 glycoprotein diminished expression of ligands for the activating NK cell receptor NKG2D on the surface of virus-infected cells. Here we have defined the precise ligands that are affected and have directly implicated NKG2D in immune responses to CMV infection in vitro and in vivo. Murine CMV (MCMV) infection potently induced transcription of all five known retinoic acid early inducible 1 (RAE-1) genes (RAE-1α, RAE-1β, RAE-1δ, RAE-1ε, and RAE-1γ), but not H-60. gp40 specifically down-regulated the cell surface expression of all RAE-1 proteins, but not H-60, and diminished NK cell interferon γ production against CMV-infected cells. Consistent with previous findings, a m152 deletion mutant virus (Δm152) was less virulent in vivo than the wild-type Smith strain of MCMV. Treatment of BALB/c mice with a neutralizing anti-NKG2D antibody before infection increased titers of Δm152 virus in the spleen and liver to levels seen with wild-type virus. These experiments demonstrate that gp40 impairs NK cell recognition of virus-infected cells through disrupting the RAE-1–NKG2D interaction.
O2.01 * RADIATION THERAPY DOSE PAINTING UTILIZING FET AND FDG PET IN THE MANAGEMENT OF HIGH GRADE GLIOMA
Authors: M. Back, D. Bailey, G. Schembri, M. Kastelan, E. Bailey, H. Wheeler
Journal: Neuro-Oncology (2014)

AIM: Assess the early outcome of patients with favourable subtype anaplastic glioma(AG) managed with an intensity modulated radiation therapy (ib-IMRT) integrated boost technique to minimise the normal brain volume irradiated. METHODS: Patients with AG were subgrouped into a favourable cohort based on presence of oligodendroglial features, 1p19q codeletion or presence of IDH1mutation. Those with favourable features were managed under a protocol utilizing an approach to minimising the volume of normal brain irradiated through the use of an ib-IMRT technique. Combined FET/FDG PET was used with 3T MRI to identify a high risk region, either FDG uptake, MRI gad enhanced region or T1 dense region. A lower risk region was identified by FET uptake or MRI T2 Flair. these regions were then incorporated into RT Plan and dose painted to 59.4Gy ( high risk) or 54 Gy (low risk) in 33 fractions over 6.5 weeks. RESULTS: 124 patients with AG managed with RT between 2008 and 2013 at the Northern Sydney Cancer were identified from a prospective database. 71 patients with favourable subtype received an ib-IMRT approach with 40 based on FET-FDG PET and 31 pts on MRI alone. Median follow-up for survivors was 32 months. 4yOS was 67% for the 124pts and 87% for the ib-IMRT subgroup. There were no infield relapses in the FET- FDG PET ib-IMRT group with the only treatment failure occurring at 12 months at a distant site. CONCLUSION: for patients with favourable AG, ib-IMRT at early followup provides an effective method to potentially minimise late RT morbidity.
Meckel's Diverticulum as an Abdominal Emergency
Authors: E. Christensen
Journal: BMJ (1954)

PSYCHOPATHIC STATES AND ATTEMPTED SUICIDEBRD [IBNSHAL 1347 admitted to a general hospital, have been investigated in detail from psychiatric and social aspects.The sample suggests that at least one-fifth of attempted suicides belong to this group.A family history of psychiatric abnormality was obtained in 67% and of suicide in 14% of the cases.Of the group 74% came from " broken homes."Pre- vious suicidal attempts had been made by 45%.The majority of the patients were in the first half of life, and all had shown persistent social maladjustment; most typically they were impulsive, aggressive, restless, egocentric, and affectionless; many gave histories of unemployment, crime, sexual maladjustment, alcoholism, drug addiction.71 % were in the lowest social class.The physical state was satisfactory in 60%.Nearly one-third had not been complaining of nervous symptoms, and one-half were not under the care of a doctor at the time of their suicidal attempts.Homi- cidal trends were in several cases obvious.The majority of the suicidal attempts were impulsive, precipitated by a personal quarrel or the threat of retribution.Alcohol and fatigue were significant factors.Poisoning was chosen by 91 %.Many were confused about their real intentions.The psychopathology of these acts is described and the following motives are considered most significant: hate, evasion, identification with a dead person, fears, experimentation, the demonstration of omnipotence, and manipulation of the environment.Of the group 86% were discharged home.The difficulty of judging the seriousness of these attempts is discussed, their resemblances to the episodi- cally disturbed behaviour of the epileptic and to the suicidal attempts of children and primitives are briefly considered, and the need for further research and its possible directions are indicated.I am grateful to Professor Sir David Henderson for his criti- cism and advice, and to Dr. J. K. Slater
Drug-induced prolonged cholestasis in adults: A histological semiquantitative study demonstrating progressive ductopenia
Authors: Claude Degott, Gérard Feldmann, Dominique Larrey, Anne-Marie Durand-Schneider, Didier Grange, Jean-Pierre Machayekhi, Alain Moreau, François Potet, Jean-Pierre Benhamou
Journal: Hepatology (1992)

Drug-induced acute hepatitis may be followed by prolonged cholestasis despite the withdrawal of the drug. Eight patients suffering from prolonged cholestasis caused by several drugs were investigated with sequential liver biopsies. At the early stage, lesions of acute cholangitis were observed in most patients; at the chronic phase, ductopenia, defined by the absence of interlobular bile ducts in at least 50% of small portal tracts, was demonstrated in all patients. Ductopenia might be the consequence of acute cholangitis; the degree of ductopenia and the chronicity of the disease might be directly related to the severity of the early acute damage of bile ducts. Consequently, in patients with severe cholestasis related to drugs, research of early morphological signs of acute cholangitis and then of ductopenia seems to be important.