tbuckley/cabot-search huggingface dataset:
Pivotal Role of Dendritic Cell–derived CXCL10 in the Retention of T Helper Cell 1 Lymphocytes in Secondary Lymph Nodes
Authors: Hiroyuki Yoneyama, Shosaku Narumi, Yanyun Zhang, Masako Murai, Marco Baggiolini, Antonio Lanzavecchia, Takafumi Ichida, Hitoshi Asakura, Kouji Matsushima
Journal: The Journal of Experimental Medicine (2002)

Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5′-bromo-2′-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-γ–producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-γ leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.
Effects of ischemic-like insult on myocardial thallium-201 accumulation.
Authors: S Z Goldhaber, J B Newell, N M Alpert, E Andrews, G M Pohost, J S Ingwall
Journal: Circulation (1983)

Despite extensive clinical use of thallium-201 (201TI) for myocardial imaging, the effect of ischemia on myocardial accumulation and release of 201TI independent of flow has not been fully defined. Therefore, myocardial accumulation of 201TI in response to ischemic-like myocardial injury was assessed in vitro using the cultured fetal mouse heart preparation. Cultured fetal mouse hearts (n = 311) were subjected to injury simulating ischemia by deprivation of oxygen and oxidizable substrates for periods ranging from 15 minutes to 10 hours. The extent of irreversible injury was determined by the percentage of lactic dehydrogenase (LDH) lost from the hearts to the culture medium during recovery from injury. Injury was essentially reversible at 1 hour of insult. The fraction of 201TI content in injured compared with control hearts was not significantly lower after 1 hour of insult. By 3 hours of insult, irreversible injury as assessed by loss of LDH was detectable and the extent of injury increased progressively through 10 hours. During the 3-10-hour period of irreversible injury, 201TI accumulation within injured hearts compared with controls was related in a monotonically decreasing fashion to the loss of LDH as described by a mathematical kinetic model that fit the observations closely (R2 greater than 0.99). These results indicate that in this organ culture preparation, in which there is effectively an unlimited reservoir of 201TI and no confounding effects of perfusion, the time-dependent 201TI accumulation is determined by the extent of irreversible injury.
Education of adult patients at an "asthma school": effects on quality of life, knowledge and need for nursing
Authors: KC Ringsberg, I Wiklund, L Wilhelmsen
Journal: European Respiratory Journal (1990)

The effect of education of adult asthma patients at a special "asthma school" was studied with regard to knowledge of the disease and its treatment and quality of life measured by leisure activities, social interaction and psychological well being. We also studied if there were any differences in number of days in hospital and emergency visits before and one year after the asthma-school. Patients were randomised to an intervention group (7 men and 13 women) and a control group (7 men and 11 women). The age-range was 22-66 yrs. Both groups answered the same standardized and quantified questionnaires on three occasions, before the start of the asthma school, after five months and after twelve months. Both groups increased their knowledge of the disease and how to treat it, with slightly better results in the intervention group. The self-assessments all showed that patients in the intervention group felt better than those in the control group. The number of days in hospital as well as acute visits to out patients clinics were reduced significantly after the asthma school. The intervention did not influence spirometric variables.
Increased left ventricular dysfunction in elderly patients despite successful thrombolysis: The GUSTO-I angiographic experience
Authors: Edward J. Lesnefsky, Conor F. Lundergan, John McB. Hodgson, Ravi Nair, Jonathan S. Reiner, Samuel W. Greenhouse, Robert M. Califf, Allan M. Ross
Journal: Journal of the American College of Cardiology (1996)
Structural and functional origins of suppressed acetylcholine vasodilation in diabetic rat intestinal arterioles.
Authors: J M Lash, H G Bohlen
Journal: Circulation Research (1991)

This study evaluated the possible impairments to endothelium-mediated vasodilation by structural and functional properties of the intestinal arterioles in adult (20-21-week-old) rats after 8-11 days or 7-8 weeks of streptozotocin-induced diabetes. Arteriolar intravascular pressures and luminal diameters were simultaneously measured during iontophoretic application of acetylcholine, bradykinin, and nitroprusside to the outer vessel wall, and passive diameter-pressure relations were obtained during maximal vasodilation. Microvascular pressures and circumference-passive wall tension relations were similar between all diabetic and normal rats and did not appear to significantly influence vasodilation. Both acute and chronic hyperglycemia were associated with near complete suppression of acetylcholine-induced vasodilation in large arterioles, and the threshold dose for vasodilation of intermediate arterioles was approximately 10-fold higher in diabetic rats. In both diabetic groups, dilatory responses to nitroprusside were normal, and in chronically diabetic rats, the relative vasodilation in response to various doses of bradykinin was equivalent to that found in normal rats. These observations indicate that a very specific deficit of acetylcholine-induced endothelium-derived relaxing factor action rapidly develops in intestinal arterioles of diabetic rats, but the arteriolar wall mechanical properties, cGMP-mediated muscle relaxation, and endothelial release of the bradykinin-stimulated relaxing factor are not compromised after 7-8 weeks of chronic hyperglycemia.
Screening the general population for cirrhosis using transient elastography: finding a needle in a haystack?
Authors: L. Castera
Journal: Gut (2011)

Screening the general population for cirrhosis is an important public heath issue. However, it has remained thus far an impossible challenge, like ‘finding a needle in a haystack’, because of the lack of appropriate tools.

In order for health authorities to justify the application of a generalised screening policy, a disease should meet a list of criteria that were established by the WHO more than 40 years ago.1 The first criterion is that the disease should be an important public health problem because of its prevalence and severity. Undoubtedly, chronic liver diseases (CLDs), with a worldwide mortality attributable to cirrhosis of around 800 000 deaths per year, meet this criterion. Although the exact prevalence of cirrhosis is currently unknown, it was recently estimated at 76.3 per 100 000 population aged over 25 in the UK (corresponding to 30 000 people) with an increasing incidence between 1993 and 2001.2 Given the high prevalence of undiagnosed cirrhosis in patients with non alcoholic fatty liver disease (NAFLD) and chronic hepatitis C, these numbers are likely an underestimation. Since compensated cirrhosis often goes undetected for extended periods, a reasonable estimate is that up to 1% of the general population could have histological cirrhosis.3

The second and third criteria are that there should be a recognisable latent stage and an accepted treatment for patients with recognised disease. In the case of cirrhosis, early diagnosis triggers specific monitoring of complications related to portal hypertension and to the increased risk of developing hepatocellular carcinoma. It also enables initiation of specific measures or treatment to prevent disease progression and improve survival (antiviral therapy for viral hepatitis; abstinence from alcohol; lifestyle changes in NAFLD; steroid …
A national early warning score for acutely ill patients
Authors: A. McGinley, R. M. Pearse
Journal: BMJ (2012)

A new standard to help identify patients in need of critical care 

The critical care unit, which clusters patients with life threatening illness in a single geographical area, is now a familiar concept. It offers patients the best chance of survival through optimum technology and the concentration of clinical skills and experience. Critical care medicine is a specialty that depends largely on a resource intensive environment. Until recently, for both economic and practical reasons, critical care could not be provided for every hospital inpatient. As the specialty has developed, it has repeatedly been noted that poor outcomes commonly result from a failure to promptly recognise and treat patients who become acutely ill on a standard hospital ward. As part of a long term strategy to tackle this problem, the Royal College of Physicians has launched a national early warning score.1 This is a welcome development that may be good news for patients. However, it is worth highlighting some potential pitfalls.

Patients die not from their disease but from the disordered physiology caused by the disease. The early warning score is an established tool that uses this concept …
NOSA in HCV infection: markers or makers of disease?
Authors: D VERGANI
Journal: Gut (1999)

See article on page 435 

In this issue Lenzi et al (see page435) provide convincing evidence that non-organ specific autoantibodies (NOSA) are highly prevalent in subjects exposed to hepatitis C virus (HCV), and their presence is associated with clinical and biochemical signs of liver disease. The observation that autoimmunity and HCV infection are associated is not new: several hundred hits are returned when Medline is interrogated using HCV and autoimmune, including autoantibodies, as coordinates. Invariably, however, the infected individuals are patients referred to hospital and who have undergone some form of selection, primarily dictated by the severity of their underlying disease. The population studied by Lenzi et al makes their paper unique.

During the screening of an unselected population of 7000 (the Dionysos study1) for indicators of liver disease, 226 were positive for HCV markers. Lenzi and colleagues found NOSA in 25% of these subjects, a prevalence much higher than that of the 226 demographically matched uninfected individuals and of the 78 HBsAg positive subjects from the Dionysos study. Within the HCV positive group, the presence of NOSA was significantly associated with clinical and biochemical evidence …
Molecular Alterations at 9q33.1 and Polyploidy in Asbestos-Related Lung Cancer
Authors: Penny Nymark, Eeva Kettunen, Mervi Aavikko, Salla Ruosaari, Eeva Kuosma, Esa Vanhala, Kaisa Salmenkivi, Risto Pirinen, Antti Karjalainen, Sakari Knuutila, Harriet Wikman, Sisko Anttila
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Asbestos causes DNA damage and the fibers, together with tobacco smoke, have a synergistic effect on lung cancer risk. We recently identified 18 chromosomal regions that showed differences in DNA copy number between the lung tumors of asbestos-exposed and nonexposed patients. One of the previously identified asbestos-associated chromosomal regions at 9q was further analyzed for allelic imbalance and DNA copy number alterations (CNA) in the lung tumors of asbestos-exposed and nonexposed patients. In addition, the ploidy level of the tumors was studied. Experimental Design: Allelic imbalance was analyzed at 9q31.3-34.3 with 15 microsatellite markers in 52 lung tumor samples from asbestos-exposed and nonexposed patients. CNA at 9q32-34.3 were characterized by fluorescent in situ hybridization (FISH) with six bacterial artificial chromosome probes in 95 lung tumors. The ploidy level was analyzed in 100 lung tumors with FISH using three to five centromere probes. Results: Allelic imbalance at 9q31.3-q34.3 was found in all asbestos-exposed patient tumors (100%, 17 of 17) compared with 64% (14 of 22) in the nonexposed cases (P = 0.005). The most significant difference was detected at 9q33.1 (P = 0.002). FISH results showed that also CNA were more frequent at 9q33.1 in the three major histologic types of non–small-cell lung tumors of exposed patients, and the association showed a dose-dependent trend (P = 0.03). Furthermore, we detected more frequent polyploidy among the exposed (48%, 28 of 58) than among the nonexposed (29%, 12 of 42) patient tumors (P &amp;lt; 0.05). Conclusions: These results provide a basis for the development of a method to identify asbestos-related lung cancer on a molecular level.
Newly diagnosed diabetes mellitus after acute pancreatitis: a systematic review and meta-analysis
Authors: Stephanie L M Das, Primal P Singh, Anthony R J Phillips, Rinki Murphy, John A Windsor, Maxim S Petrov
Journal: Gut (2013)

<h3>Background</h3> Diabetes mellitus (DM) is common in the general population and it poses a heavy burden to society in the form of long-term disability, healthcare use and costs. The pancreas is a key player in glucose homeostasis, but the occurrence of newly diagnosed DM after acute pancreatitis (AP), the most frequent disease of the pancreas, has never been assessed systematically. The aim of this study was to conduct a systematic literature review to determine the prevalence and time course of DM and related conditions after the first attack of AP as well as the impact of covariates. <h3>Methods</h3> Relevant literature cited in three electronic databases (Scopus, EMBASE and MEDLINE) was reviewed independently by two authors. The main outcome measures studied were newly diagnosed prediabetes, DM, or DM treated with insulin. Pooled prevalence and 95% CIs were calculated for all outcomes. <h3>Results</h3> A total of 24 prospective clinical studies, involving 1102 patients with first episode of AP, met all the eligibility criteria. Prediabetes and/or DM was observed in 37% (95% CI 30% to 45%) individuals after AP. The pooled prevalence of prediabetes, DM and treatment with insulin after AP was 16% (95% CI 9% to 24%), 23% (95% CI 16% to 31%), and 15% (95% CI 9% to 21%), respectively. Newly diagnosed DM developed in 15% of individuals within 12 months after first episode of AP and the risk increased significantly at 5 years (relative risk 2.7 (95% CI 1.9 to 3.8)). A similar trend was observed with regard to treatment with insulin. The severity of AP, its aetiology, individuals’ age and gender had minimal effect on the studied outcomes. <h3>Conclusions</h3> Patients with AP often develop prediabetes and/or DM after discharge from hospital, and have a greater than twofold increased risk of DM over 5 years. Further studies are warranted to determine the optimal strategy for its detection and whether the risk of developing DM after AP can be reduced.
Role of radiation therapy in the treatment of stage I/II mucosa-associated lymphoid tissue lymphoma
Authors: H.K. Tsai, S. Li, A.K. Ng, B. Silver, M.A. Stevenson, P.M. Mauch
Journal: Annals of Oncology (2007)

Few large studies exist on the outcome of patients treated for stage I/II mucosa-associated lymphoid tissue (MALT) lymphoma.We retrospectively reviewed the records of 77 patients consecutively treated for stage I (n = 66) or II (n = 11) MALT lymphoma at our institution. Progression-free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS) were calculated using the Kaplan-Meier method.The median follow-up time was 61 months (range 2-177 months). Fifty-two patients (68%) received local radiation therapy (RT) alone, 17 (22%) had surgery followed by adjuvant RT, five (6%) had surgery alone, two (3%) had surgery and chemotherapy, and one patient had chemotherapy alone. The median RT dose was 30 Gy (range 18-40 Gy). The 5-year PFS, FFTF, and OS rates were 76%, 78%, and 91%, respectively. The 5-year PFS (79% versus 50%; P = 0.002) and FFTF (81% versus 50%; P = 0.0004) rates were higher for patients who received RT as compared with patients who did not.The prognosis following treatment of stage I/II MALT lymphoma is excellent. RT improves PFS and FFTF and has an important role in the curative treatment of patients with localized disease.
A long hard look at Dukes' B
Authors: G T Williams
Journal: Gut (2002)

Identification of prognostic pathological factors in Dukes' B colon cancer

Carcinoma of the colon is somewhat of a Cinderella among colorectal cancers, and during the last few years its ugly sister, carcinoma of the rectum, has hogged the limelight. This has been largely due to the (deserved) attention that has been paid to reducing local recurrence in rectal cancer through better preoperative imaging, surgical technique, and adjuvant chemoradiotherapy. However, cancer of the colon remains a highly lethal tumour. There is little controversy that it is best treated initially by surgical resection, that patients with completely resected Dukes' A tumours of usual histological type require no more treatment, and that patients found to have Dukes' C tumours after histological examination of the resection specimen should be offered adjuvant chemotherapy.1 For the 40% or so of colonic cancers that are Dukes' B, however, there is great uncertainty surrounding the place of such chemotherapy, as has been highlighted in the recently published revised Guidelines for the management of colorectal cancer (2001) from the Association of Coloproctology of Great Britain and Ireland (ACP).2 Part of the reason for this is that the Dukes' B category encompasses a wide range of tumours, from those that have just penetrated the muscular coat of the bowel wall to widely infiltrative neoplasms that show extensive extramural local spread, and it would not be surprising that the benefit of postoperative chemotherapy might vary in parallel with this. …
The Association Between Patient-Reported Self-management Behavior, Intermediate Clinical Outcomes, and Mortality in Patients With Type 2 Diabetes: Results From the KORA-A Study
Authors: Michael Laxy, Andreas Mielck, Matthias Hunger, Michaela Schunk, Christa Meisinger, Ina-Maria Rückert, Wolfgang Rathmann, Rolf Holle
Journal: Diabetes Care (2014)

OBJECTIVE Little is known about the impact of diabetes self-management behavior (SMB) on long-term outcomes. We aimed to examine the association among patient-reported SMB, intermediate clinical outcomes, and mortality in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Data were collected from 340 patients with type 2 diabetes of the KORA-A study (1997/1998) who were recruited from two previous population-based surveys (n = 161) and a myocardial infarction registry (n = 179) in southern Germany. Based on previous methodological work, a high level of SMB was defined as being compliant with at least four of six different self-care dimensions, comprising physical exercise, foot care, blood glucose self-monitoring, weight monitoring, having a diet plan, and keeping a diabetes diary. The vital status of the participants was observed until 2009. Multivariable linear, logistic, and Cox regression models were applied to assess the association with intermediate clinical outcomes at baseline and to predict mortality over the follow-up period, adjusted for sociodemographic, behavioral, and disease-related factors. RESULTS In the cross-sectional perspective, a high level of SMB was weakly associated with a lower glycated hemoglobin A1c level (−0.44% [−4.8 mmol/mol] [95% CI −0.88 to 0.00]), but not with low-density lipoprotein cholesterol, systolic blood pressure, or the presence of microalbuminuria, peripheral arterial disease, or polyneuropathy. During a mean follow-up time of 11.6 years, 189 patients died. SMB was a preventive factor for all-cause (hazard ratio 0.61 [95% CI 0.40–0.91]) and cardiovascular mortality (0.65 [95% CI 0.41–1.03]). CONCLUSIONS Although measuring SMB is difficult and the used operationalization might be limited, our results give some indication that a high level of SMB is associated with prolonged life expectancy in patients with type 2 diabetes and highlight the potential impact of the patients’ active contribution on the long-term trajectory of the disease. We assume that the used proxy for SMB is associated with unmeasured, but important, dimensions of health behavior.
P16.34 * BEVACIZUMAB TREATMENT FOR ACOUSTIC NEURINOMA IN NEUROFIBROMATOSIS TYPE 2: A CASE REPORT
Authors: A. Sponghini, D. Rondonotti, F. Platini, M. Giavarra, E. Trevisan, R. Soffietti
Journal: Neuro-Oncology (2014)

Neurofibromatosis type 2 (NF2) is a dominantly inherited genetic condition. Unlike patients with sporadic tumours, NF2 patients often have multiple meningiomas, acoustic neurinomas and ependymomas. The multiplicity of tumours make surgery and radiation therapy for all tumours impracticable. In effect, bilateral acoustic neurinomas are the hallmark of this disease and these tumours cause progressive hearing loss in most patients. Neovascularization is necessary for tumour growth and is driven by tumour produced angiogenic factors such as vascular endothelial growth factor (VEGF). Bevacizumab is a humanized monoclonal antibody that neutralizes the activity of VEGF. Recent data showed that VEGF is produced by schwannoma tumour cells. Also, bevacizumab treatment, in patients with NF2 who were considered poor candidates for surgery and radiation therapy, was followed by clinically meaningful hearing improvement and tumour-volume reduction. We report the case of a 39 years old woman with sudden rightsided hearing loss. Magnetic resonance imaging (MRI) revealed multiple meningiomas and neurinomas (C2 and L5 lesions) and a right side acoustic neurinoma of 26x24 mm, confirming the diagnosis of NF2. Bevacizumab was given as an infusion every 2 weeks at a dose of 5.0 mg/kg body weight. Before the treatment, the patient has a thorough medical evaluation including blood pressure, urine analysis, liver and kidney function tests, coagulation status and history of thrombosis, hemoglobin, leukocyte count and thrombocyte count. Three months after the start of therapy the patient has reported an hearing response with progressive improvement in audiometry, word recognition and face-to-face conversation. Six months after the start of therapy, the right acoustic neurinoma had regressed and, also, mitigation of brain stem compression was clearly visible on the cranial MRI scans. The patient, after 12 months, continued to be treated with bevacizumab. In our experience no toxic effects drug-related has been seen; anyway, the absence of many common toxic effects of bevacizumab in our patient may have reflected her youth and the lack of other medical conditions. The exact mechanism of the action of bevacizumab on acoustic neurinomas remains to be elucidated. The drug may also suppress growth of tumour Schwann cells directly, a possibility that can be tested in vitro in future studies. The encouraging results with bevacizumab suggest consideration of a prospective clinical trial for progressive NF2-related acoustic neurinomas, especially for patients with imminent total hearing loss.