tbuckley/cabot-search huggingface dataset:
Role of outdoor aeroallergens in asthma exacerbations: epidemiological evidence
Authors: R W Atkinson
Journal: Thorax (2004)

Confounding factors complicate the interpretation of time series studies in examining the role of outdoor aeroallergens in asthma exacerbations

Despite historically low levels, outdoor environmental pollutants such as nitrogen dioxide, sulphur dioxide, and particulate matter are thought to play a role in exacerbating asthma. Much of this evidence comes from ecological “time series” studies that use sophisticated statistical methods to examine temporal associations between daily counts of asthma attacks and daily levels of air pollution at the population level. A good example of this type of study is the multi-city European study APHEA (Air Pollution and Health: an European Approach).1,2 Panel studies have also investigated temporal associations between daily outdoor air pollution levels and asthma but use the symptoms, lung function and medication use of individuals as the health status indicators. The multi-city equivalent in panel design is the PEACE study (Pollution Effects in Asthmatic Children in Europe). However, it failed to find statistically significant associations between particle measures, sulphur dioxide and nitrogen dioxide and respiratory symptoms, peak expiratory flow and medication use.3

Only a relatively small number of studies have used the time series approach to investigate the health effects of aeroallergens at the population and individual levels. Some studies of air pollution have included pollens and fungal spores as potential confounders,4–7 while others have been designed specifically to investigate the health effects of aeroallergens.8–16 The conclusions from this latter group are inconsistent—some report significant effects of pollens and spores and others …
Association between Azathioprine Therapy and Lymphoma in Rheumatoid Disease
Authors: P I Pitt, A H Sultan, M Malone, V Andrews, E B D Hamilton
Journal: Journal of the Royal Society of Medicine (1987)

Three out of 41 patients treated with azathioprine and low-dose corticosteroids from 1976 to 1983 developed non-Hodgkin's lymphoma. This strikingly high incidence of lymphoma may be a reflection of long-term use of azathioprine.
Waist-to-Height Ratio Is Independently and Better Associated With Urinary Albumin Excretion Rate Than Waist Circumference or Waist-to-Hip Ratio in Chinese Adult Type 2 Diabetic Women but Not Men
Authors: Chin-Hsiao Tseng
Journal: Diabetes Care (2005)

Extreme obesity has been shown to be associated with focal-segmental glomerulosclerosis and nephrotic syndrome in a report of four cases (1). However, this association has not gained much attention until recently when histologically proven glomerulopathy was demonstrated in animals (2) and humans (3). The study of renal biopsy taken from humans included mostly patients with clinical proteinuria or proteinuria with renal insufficiency (3). Therefore, whether obesity is associated with nephropathy in the early stage of microalbuminuria is not yet proven. This study evaluated the effects of the commonly used indicators for obesity (i.e., BMI, waist circumference, waist-to-hip ratio [WHR], and waist-to-height ratio [WHeiR]) on the urinary albumin excretion rate (UAER) in the early normo- or microalbuminuric stages in type 2 diabetic patients.

A total of 569 (282 men and 286 women) type 2 diabetic patients, aged 63.6 ± 11.0 years, were recruited. Measurements of body height, body weight, waist circumference, and hip circumference were described elsewhere (4). BMI was calculated as body weight (in kilograms) divided by the square of height (in meters). WHR and WHeiR were calculated by dividing the waist circumference by the hip circumference and the body height, respectively.

The patients’ age, sex, diabetes duration, and systolic (sBP) and diastolic blood pressure (dBP) were recorded or measured. Urine specimens and blood samples were collected in …
THE BEHAVIOR OF ABNORMAL HUMAN THYROID TISSUE CULTIVATED IN THE LINDBERGH APPARATUS
Authors: N. Chandler Foot, Lillian E. Baker, Alexis Carrel
Journal: The Journal of Experimental Medicine (1939)

1. Human thyroid tissue may be kept alive and in good condition in the Lindbergh apparatus for at least 3 weeks, in usable condition from 1 to 2 months, provided that the vascular tree remain patent and functioning. 2. Experiments with altered amounts of iodin, adrenalin, hormones, and other substances show constant results only in connection with eschatin and pitressin which, in concentrations of 1:1000 in the perfusate almost invariably cause hyperplasia of the explanted tissue. 3. The original state of the tissue and the character of the symptom complex in the patient from which it was taken appeared to play no part in the subsequent behavior of the tissue explants. 4. In one experiment a most remarkable metaplasia was observed in the explanted thyroid tissue during the 6 to 8 weeks that it remained in two apparatuses. The cause of this is not evident.
The aggressive peripheral T‐cell lymphomas: 2012 update on diagnosis, risk stratification, and management
Authors: James O. Armitage
Journal: American Journal of Hematology (2012)

T-cell lymphomas make up approximately 10-15% of lymphoid malignancies. The frequency of these lymphomas varies geographically, with the highest incidence in parts of Asia.The diagnosis of aggressive peripheral T-cell lymphoma (PTCL) is usually made using the WHO classification. The ability of hematopathologists to reproducibly diagnose aggressive PTCL is lower than for aggressive B-cell lymphomas, with a range of 72-97% for the aggressive PTCLs.Patients with aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat controversial, positron emission tomography (PET) scans appear to be useful as they are in aggressive B-cell lymphomas. The most commonly used prognostic index is the International Prognostic Index. The specific subtype of aggressive PTCL is an important risk factor, with the best survival seen in anaplastic large-cell lymphoma-particularly young patients with the anaplastic lymphoma kinase positive subtype.Anaplastic large-cell lymphoma is the only subgroup to have a good response to a cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like regimen. Angioimmunoblastic T-cell lymphoma has a prolonged disease-free survival in only ∼20% of patients, but younger patients who have an autotransplant in remission seem to do better. PTCL-not otherwise specified (NOS) is not one disease. Anthracycline containing regimens have disappointing results and a new approach is needed. NK/T-cell lymphoma localized to the nose and nasal sinuses seems to be best treated with radiotherapy containing regimens. Enteropathy associated PTCL and hepatosplenic PTCL are rare disorders with a generally poor response to therapy, although selected patients with enteropathy associated PTCL seem to benefit from intensive therapy.
Childhood Obesity is Associated with Both Atopy and Current Asthma
Authors: C.M. Visness, J.L. Daniels, J.S. Kaufman, K.B. Yeatts, S.J. London, A.M. Siega-Riz, A. Calatroni, D.C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2009)
Preexisting Donor-Specific HLA Antibodies Predict Outcome in Kidney Transplantation
Authors: Carmen Lefaucheur, Alexandre Loupy, Gary S Hill, Joao Andrade, Dominique Nochy, Corinne Antoine, Chantal Gautreau, Dominique Charron, Denis Glotz, Caroline Suberbielle-Boissel
Journal: Journal of the American Society of Nephrology (2010)

The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceased-donor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (<i>P</i> = 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI &gt;6000 had &gt;100-fold higher risk for AMR than patients with MFI &lt;465 (relative risk 113; 95% confidence interval 31 to 414). The presence of HLA-DSA did not associate with patient survival. In conclusion, the risk for both AMR and graft loss directly correlates with peak HLA-DSA strength. Quantification of HLA antibodies allows stratification of immunologic risk, which should help guide selection of acceptable grafts for sensitized patients.
Acceptability of low molecular weight heparin thromboprophylaxis for inpatients receiving palliative care: qualitative study
Authors: S I R Noble, A Nelson, C Turner, I G Finlay
Journal: BMJ (2006)

To find out what inpatients with advanced cancer who are receiving palliative care think about the effect of thromoprophylaxis on overall quality of life.Qualitative study using audiotaping of semistructured interviews.Regional cancer centre in Wales.28 inpatients with advanced metastatic cancer receiving palliative care and low molecular weight heparin.Recurring themes on the effect of thromboprophylaxis on overall quality of life.Major emerging themes showed that patients knew about the risks of venous thromboembolism and the purpose of treatment with heparin. Media coverage had raised awareness about venous thromboembolism, and many had previous experience of thromboprophylaxis. All found low molecular weight heparin an acceptable intervention, and many said that it improved their quality of life by giving them a feeling of safety and reassurance. Antiembolic stockings were considered uncomfortable and had a negative impact on quality of life. Patients were concerned that because they had advanced disease they might not be eligible for thromboprophylaxis.Low molecular weight heparin is acceptable to inpatients with advanced cancer receiving palliative care and has a positive impact on overall quality of life. Antiembolic stockings are an unacceptable intervention in this patient group. Guidelines on thromboprophylaxis are urgently needed for palliative care inpatient units and hospices.
“Underuse” as a cause for musculoskeletal injuries: is it time that we started reframing our message?
Authors: S D Stovitz, R J Johnson
Journal: British Journal of Sports Medicine (2006)

Promoting physical activity S ports medicine clinicians need to be leaders in the field of physical activity promotion.As such, we must avoid language that inappropriately discourages exercise.Articles on musculoskeletal injuries typically divide the causes into either ''acute'' or ''overuse''.Both of these terms implicate activity as the basis for the musculoskeletal pain.However, as we learn more about the epidemiology, pathophysiology, treatment, and prevention of these injuries, it is clear that, in fact, inactivity may be the underlying cause of many of these conditions.''Underuse injuries'' may be a more appropriate term to explain the aetiology of many conditions seen by those in the field of sports medicine.. . . . . . . .
Central nervous system metastases of a pulmonary epitheloid haemangioendothelioma
Authors: R. Díaz, Á. Segura, V. Calderero, I. Cervera, J. Aparicio, M.V. Jordá, L. Pellín
Journal: European Respiratory Journal (2004)

The case of a 55-yr-old male with a right pleural effusion and multiple bilateral nodules is reported. A diagnostic thoracothomy was necessary to obtain a definitive histological diagnosis. During the postoperative course, the subject's neurological condition deteriorated and multiple cerebral mass lesions were discovered. The pathological analysis of both lung and cerebral tumours revealed an atypical endothelial cell proliferation; vascular immunohistochemical markers, such as factor VIII and CD34, were strongly positive. His general condition remained poor and the patient died 18 months after the initial diagnosis. The final diagnosis was pulmonary epitheloid haemangioendothelioma with synchronous central nervous system dissemination, the first time the authors believe that association has been reported. Little is known of the prognosis and treatment of these tumours, due to their rarity. Negative prognostic factors appear to be the presence of symptoms, pleural effusion or multifocal presentations. Treatment should include surgical resection if possible; chemotherapy appears to have little effect. Watchful waiting is an acceptable option, especially in asymptomatic patients.
Abstract B12: Predictibility of response to anti-EGFR treatment with respect to assessment of receptor status in different geographical population with lung cancer (NSCLC)
Authors: Veerendra Kumar K V
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer affecting populations in different geographical areas varies with respect to incidence, smoking history, histology and response to treatment with monoclonal antibodies inhibiting EGFR. Assessment of EGFR status in lung cancer varies with respect to methodology, type of antibody etc, resulting in wide variation in reported incidence of positivity. In addition EGFR receptor is a polyclonal antigen (eg: EGFR1, EGFR2) and standardization of antigen methodology of assessment and interpretation of the test results is not yet uniformly accepted worldwide. Response to treatment with monoclonal antibodies to EGFR in lung cancer patients vis a vis receptor status is varied in different geographical areas. Study in Erlotinib has shown response in selected sample of patients in western population whereas there are no well established clinical trials in Asian population establishing relevance of receptor status with respect to clinical response to EFGR antibodies. It is well known fact from different clinical trials that Asian especially Southeast Asian populations with lung cancer respond differently in comparison to European population (cacuasions). But receptor status and response to treatment not known. Hence it is opinioned that Asian and especially Southeast Asians population's treatment with monoclonal antibodies should be given a clinical trial irrespective of receptor status or unknown receptor status. However clinical trials with respect to response v/s receptor status should be conducted. Till then these populations should not be denied treatment with monoclonal antibodies in lung cancer (NSCLC).
Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products
Authors: Young-Woong Kim, Valentin P. Yakubenko, Xiaoxia Z. West, Gabriel B. Gugiu, Kutralanathan Renganathan, Sudipta Biswas, Detao Gao, John W. Crabb, Robert G. Salomon, Eugene A. Podrez, Tatiana V. Byzova
Journal: Circulation Research (2015)

Oxidative stress is an important contributing factor in several human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty acid docosahexaenoic acid, results in the accumulation of an end product, 2-(ω-carboxyethyl)pyrrole (CEP), which was shown to have proangiogenic and proinflammatory functions. Although CEP is continuously accumulated during chronic processes, such as tumor progression and atherosclerosis, its level during wound healing return to normal when the wound is healed, suggesting the existence of a specific clearance mechanism.To identify the cellular and molecular mechanism for CEP clearance.Here, we show that macrophages are able to bind, scavenge, and metabolize carboxyethylpyrrole derivatives of proteins but not structurally similar ethylpyrrole derivatives, demonstrating the high specificity of the process. F4/80(hi) and M2-skewed macrophages are much more efficient at CEP binding and scavenging compared with F4/80(lo) and M1-skewed macrophages. Depletion of macrophages leads to increased CEP accumulation in vivo. CEP binding and clearance are dependent on 2 receptors expressed by macrophages, CD36 and toll-like receptor 2. Although knockout of each individual receptor results in diminished CEP clearance, the lack of both receptors almost completely abrogates macrophages' ability to scavenge CEP derivatives of proteins.Our study demonstrates the mechanisms of recognition, scavenging, and clearance of pathophysiologically active products of lipid oxidation in vivo, thereby contributing to tissue protection against products of oxidative stress.
Partial Sleep Restriction Decreases Insulin Sensitivity in Type 1 Diabetes
Authors: Esther Donga, Marieke van Dijk, J. Gert van Dijk, Nienke R. Biermasz, Gert-Jan Lammers, Klaas van Kralingen, Roel P.L.M. Hoogma, Eleonora P.M. Corssmit, Johannes A. Romijn
Journal: Diabetes Care (2010)

OBJECTIVE Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS We studied seven patients (three men, four women) with type 1 diabetes: mean age 44 ± 7 years, BMI 23.5 ± 0.9 kg/m2, and A1C 7.6 ± 0.3%. They were studied once after a night of normal sleep duration and once after a night of only 4 h of sleep. Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with an infusion of [6,6-2H2]glucose. RESULTS Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (469 ± 8.5 vs. 222 ± 7.1 min, P = 0.02). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids (NEFAs), or endogenous glucose production. Endogenous glucose production during the hyperinsulinemic clamp was not altered during the night of sleep restriction compared with the night of unrestricted sleep (6.2 ± 0.8 vs. 6.9 ± 0.6 μmol · kg lean body mass−1 · min−1, NS). In contrast, sleep restriction decreased the glucose disposal rate during the clamp (25.5 ± 2.6 vs. 22.0 ± 2.1 μmol · kg lean body mass−1 · min−1, P = 0.04), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by ∼21% (P = 0.04). Sleep restriction did not alter plasma NEFA levels during the clamp (143 ± 29 vs. 133 ± 29 μmol/l, NS). CONCLUSIONS Partial sleep deprivation during a single night induces peripheral insulin resistance in these seven patients with type 1 diabetes. Therefore, sleep duration is a determinant of insulin sensitivity in patients with type 1 diabetes.
Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism
Authors: Claire Brown, Xiaolei Pan, Aviv Hassid
Journal: Circulation Research (1999)

Abstract —Migration of aortic smooth muscle cells is thought to be of essential importance in vascular restenosis, remodeling, and angiogenesis. Recent studies have shown that NO donors inhibit the migration of subcultured aortic smooth muscle cells. However, there is evidence that NO elicits opposite effects on cell proliferation in primary versus subcultured cells, indicating fundamental differences among different models of aortic smooth muscle cell cultures. The purpose of the current study was to investigate the effect of NO donors on migration of primary cultures of rat aortic smooth muscle cells and to compare and contrast their response with those in subcultured cells. A second purpose was to investigate some of the underlying mechanisms associated with NO-induced effects on cell migration. We report that 2 NO donors, S -nitroso- N -acetylpenicillamine (SNAP) and 2,2-(hydroxynitrosohydrazino)bis-ethanamine, stimulated the migration of primary cells in a wounded-culture model as well as in a transwell migration model. The effect of NO donors was mimicked by 2 cGMP analogues and C-type natriuretic peptide and blocked by a specific inhibitor of guanyl cyclase, 1H-(1,2,4)oxadiazolo[4,3,-a]quinoxalin-1-one, indicating the involvement of cGMP as second messenger. Moreover, neither NO donors nor cGMP analogues altered migration of primary cultures stimulated by either FBS or angiotensin II. In contrast to its effect in primary cultures, SNAP did not alter basal or stimulated migration of subcultured cells, except at a relatively high concentration of 1 mmol/L, at which migration was inhibited. The migration-stimulatory effect of NO donors and cGMP was associated with altered cell morphology and dissociation of actin filaments, consistent with recent studies indicating that cell morphology and cytoskeletal organization influence cell migration. The results suggest the possible involvement of NO-induced cell migration in vascular injury or remodeling, representing conditions in which vascular NO levels would be expected to be elevated.
The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis
Authors: G Schett, J Zwerina, G Firestein
Journal: Annals of the Rheumatic Diseases (2007)

Chronic inflammatory processes are based on a sustained and tightly regulated communication network among different cells types. This network comprises extracellular mediators such as cytokines, chemokines and matrix-degrading proteases, which orchestrate the participation of cells in the chronic inflammatory process. The mirrors of this outside communication world are intracellular transcription factor pathways, which shuttle information about inflammatory stimuli to the cell nucleus. This review examines the function of one key signal transduction pathway of inflammation--the p38 mitogen-activated protein kinases (p38MAPK). The signalling pathway is considered as crucial for the induction and maintenance of chronic inflammation, and its components thus emerge as interesting molecular targets of small molecule inhibitors for controlling inflammation. This review not only summarises the current knowledge of activation, regulation and function of the p38MAPK pathway but also examines the role of this pathway in clinical disease. It gives an overview of current evidence of p38MAPK activation in inflammatory arthritis and elaborates the key molecular determinants which contribute to p38MAPK activation in joint disease.