tbuckley/cabot-search huggingface dataset:
The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.
Authors: J T Willerson, J T Watson, I Hutton, D E Fixler, G C Curry, G H Templeton
Journal: Journal of Clinical Investigation (1975)

The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling.
Head and Neck Cancer
Authors: Philip Rubin
Journal: JAMA (1971)

<h3>To the Editor.—</h3> I was surprised at Leonard's conclusion that the CURRENT CONCEPTS IN CANCER series on Cancer of the Head and Neck has been prejudicial and inaccurate as to the current status of treatment of head and neck cancer, since one of our primary aims in this series was to present a multidisciplinary approach to the diagnosis and treatment of cancer. Examination of the entire eight sections of articles on head and neck cancer reveals the following number of specialists as contributors: surgeons, 17; radiotherapists and diagnostic radiologists, 17; chemotherapists, 2; pathologists, 5; and specialists in etiology and epidemiology, 2. In addition, many of the surgeons who have contributed could not be categorized as being pro radiation therapy since they advocate radical and aggressive surgery in preference. Kramer at the Thomas Jefferson University Hospital is an advocate of the interdisciplinary approach to cancer treatment. In his preliminary data, he
A Controlled Trial of Valganciclovir as Induction Therapy for Cytomegalovirus Retinitis
Authors: Daniel F. Martin, Juan Sierra-Madero, Sharon Walmsley, Richard A. Wolitz, Katherine Macey, Panos Georgiou, Charles A. Robinson, Mary Jean Stempien
Journal: New England Journal of Medicine (2002)

Valganciclovir is an orally administered prodrug that is rapidly hydrolyzed to ganciclovir. We compared the effects of oral valganciclovir with those of intravenous ganciclovir as induction therapy for newly diagnosed cytomegalovirus retinitis in 160 patients with the acquired immunodeficiency syndrome (AIDS).
Recombinant human interferon alfa-2b treatment for acute non-A, non-B hepatitis.
Authors: N C Tassopoulos, M G Koutelou, G Papatheodoridis, H Polychronaki, I Delladetsima, T Giannikakis, A Todoulos, A Toliopoulos, A Hatzakis
Journal: Gut (1993)

To assess the safety and possible efficacy of recombinant human interferon alfa-2b in preventing the development of chronic hepatitis, 24 adults (eight men, 16 women) with acute non-A, non-B (NANB) hepatitis were recruited to a pilot study. Half of the cases were parenterally transmitted and half were community acquired. Twelve patients received 3 million units (MU) interferon three times weekly subcutaneously for six weeks and the remaining 12 patients received no treatment. Anti-hepatitis C virus (HCV) was detected in 14 (58.3%) of the 24 patients. The alanine aminotransferase activity returned to normal in nine of 12 interferon alfa-2b treated patients and six of 12 controls by week 52. Interferon alfa-2b was well tolerated, even in jaundiced patients, who only complained of mild flu like syndrome during the first week of treatment. These data are consistent with the hypothesis that interferon alfa-2b may help prevent progression to chronic hepatitis (interferon alfa-2b 25% v controls 50%), particularly in anti-HCV negative cases (interferon alfa-2b none of six v controls two of four). A randomised, double blind placebo-controlled trial is required, however, to substantiate these results further.
Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin
Authors: Rayko Evstatiev, Adam Bukaty, Kristine Jimenez, Stefanie Kulnigg‐Dabsch, Lidia Surman, Werner Schmid, Robert Eferl, Kathrin Lippert, Barbara Scheiber‐Mojdehkar, Hans Michael Kvasnicka, Vineeta Khare, Christoph Gasche
Journal: American Journal of Hematology (2014)

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding.
Characterization of mixed syngeneic-allogeneic and syngeneic-xenogeneic islet-graft rejections in mice. Evidence of functional impairment of the remaining syngeneic islets in xenograft rejections.
Authors: O Korsgren, L Jansson
Journal: Journal of Clinical Investigation (1994)

Allogeneic mouse islets or xenogeneic rat islets, or fetal porcine islets were implanted under the renal capsule of C57BL/6 mice either alone or carefully mixed with syngeneic islets. With this experimental model the syngeneic islets, although not rejected themselves, are exposed to cytokines and inflammatory mediators released during either allograft or xenograft rejection. No differences in insulin content could be observed between mixed islet grafts and pure syngeneic islet grafts 6 wk after transplantation. Neither was there any morphological evidence of a non-specific destruction of syngeneic islets. These findings suggest that the mechanisms of both allograft and xenograft rejections are highly specific. The hormone release from the mixed syngeneic-allogeneic grafts was similar to that from pure syngeneic islet grafts. In contrast, a pronounced impairment of both the first and second phases of insulin release was observed 2 wk after implantation in mixed syngeneic-xenogeneic islet grafts. When perfusing the mixed islet graft after completed rejection of the concordant xenogeneic rat islets (6 wk after implantation), the insulin release from the remaining syngeneic mouse islets was identical to that of control grafts. However, syngeneic mouse islets exposed to the rejection mechanism of the discordant xenogenic pig islet-like cell clusters did not attain a complete functional recovery.
Effects of caerulein on the apical cytoskeleton of the pancreatic acinar cell.
Authors: M S O'Konski, S J Pandol
Journal: Journal of Clinical Investigation (1990)

In this study experiments were performed to correlate the rate of digestive enzyme secretion to morphologic observations of the apical cytoskeleton using dispersed rat pancreatic acini with various concentrations of caerulein. Caerulein at concentrations of 10 pM to 0.1 nM stimulated increasing rates of secretion of amylase, a digestive enzyme. Greater concentrations of caerulein caused progressively less amylase secretion. Transmission electron microscopy demonstrated several characteristics of the apical cytoskeleton in untreated acini that were altered with the "inhibitory" concentrations of caerulein. In control acini and acini stimulated with concentrations of caerulein up to 0.1 nM, the micrographs reveal an apical actin network extending into microvilli, an intermediate filament band, and electron-dense structures contained in both the actin filament network and the intermediate filament band. With concentrations of caerulein greater than 0.1 nM, these structures were progressively ablated. The findings with respect to the actin filament network were confirmed with light microscopic observations of dispersed acini stained with rhodamine-phalloidin. These results indicate that caerulein has marked morphologic effects on the pancreatic acinar cell cytoskeleton and that the cytoskeletal changes may modulate the secretory response.
Central Venous Catheter Care for the Patient With Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Charles A. Schiffer, Pamela B. Mangu, James C. Wade, Dawn Camp-Sorrell, Diane G. Cope, Bassel F. El-Rayes, Mark Gorman, Jennifer Ligibel, Paul Mansfield, Mark Levine
Journal: Journal of Clinical Oncology (2013)

Purpose To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer that addresses catheter type, insertion site, and placement as well as prophylaxis and management of both catheter-related infection and thrombosis. Methods A systematic search of MEDLINE and the Cochrane Library (1980 to July 2012) identified relevant articles published in English. Results The overall quality of the randomized controlled trial evidence was rated as good. There is consistency among meta-analyses and guidelines compiled by other groups as well. Recommendations There is insufficient evidence to recommend one CVC type or insertion site; femoral catheterization should be avoided. CVC should be placed by well-trained providers, and the use of a CVC clinical care bundle is recommended. The use of antimicrobial/antiseptic-impregnated and/or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs, particularly in high-risk groups; more research is needed. The prophylactic use of systemic antibiotics is not recommended before insertion. Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy; more research is needed. Before starting antibiotic therapy, cultures should be obtained. Some life-threatening infections require immediate catheter removal, but most can be treated with antimicrobial therapy while the CVC remains in place. Routine flushing with saline is recommended. Prophylactic use of warfarin or low–molecular weight heparin is not recommended, although a tissue plasminogen activator (t-PA) is recommended to restore patency to occluded catheters. CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy.
Mortality study of 18 000 patients treated with omeprazole
Authors: D N Bateman
Journal: Gut (2003)

<b>Background:</b> The long term safety of potent gastric acid suppressive therapy has yet to be established. <b>Method:</b> General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993–1995. Death rates were compared with general population rates. <b>Results:</b> Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34–1.55); p&lt;0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58–2.08); p&lt;0.0001), circulatory diseases (1.27 (95% CI 1.13–1.43); p&lt;0.0001), and respiratory diseases (1.37 (95% CI 1.12–1.64); p&lt;0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87–3.43); p&lt;0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60–6.04); p&lt;0.0001), colon and rectum (1.40 (95% CI 0.84–2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19–2.19); p&lt;0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20–10.09) (p&lt;0.0001) in year 1; 2.88 (95% CI 1.62–4.79) (p&lt;0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett’s disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17–4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37–2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25–1.80)). No relationships were detected with numbers of omeprazole scripts received. <b>Conclusions:</b> Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.
Mould exposure at home relates to inflammatory markers in blood
Authors: L. Beijer, J. Thorn, R. Rylander
Journal: European Respiratory Journal (2003)

Living in damp buildings has been associated with airway symptoms, suspected to be due to inflammatory reactions. The relationship between home exposure to mould and signs of inflammation was, therefore, studied. Nonsmoking subjects with a high (G-high, &gt;4.0 ng·m −3 , n=17) or low (G-low, &lt;2.0 ng·m −3 , n=18) amount of airborne β(1→3)-d-glucan, an indicator of mould biomass, in the home were recruited. Blood samples were analysed for granulocytic enzymes, T-cell subsets and the secretion of cytokines from in vitro incubated peripheral blood mononuclear cells (PBMCs). In the G-high group, the proportion of cytotoxic T-cells (CD8+S6F1+) was lower and secretion of tumour necrosis factor-α from PBMCs higher than in the G-low group. There were no significant differences in secretion of interferon gamma and interleukin (IL)-4 from PBMCs between the two groups. Among nonatopic subjects, the ratio between interferon gamma and IL-4 was significantly higher in the G-high group than in the G-low group and was related to the amount of β(1→3)-d-glucan in the home. No significant differences were found regarding secretion of IL-10 or IL-1β from PBMCs, eosinophil cationic protein or myeloperoxidase in serum, or differential cell counts in blood. The effects found on inflammatory markers in relation to β(1→3)-d-glucan in the home suggest upregulation of some parts of the inflammatory/immunological system due to mould exposure.
Viruses and lymphocytes in rheumatoid arthritis. I. Studies on cultured rheumatoid lymphocytes.
Authors: M Norval, H Hart, B P Marmion
Journal: Annals of the Rheumatic Diseases (1979)

Synovial fluid lymphocytes from patients with rheumatoid arthritis have been examined for evidence of a productive infection with retroviruses by electron microscopy, labelling with 3H-uredine, growth in soft agar, and culturing in conditioned medium. No such viruses were detected. In addition, the synovial lymphocytes were activated before fusion and cocultivation with several cell lines which have proved permissive for primate retroviruses. Monitoring these cultures subsequently by reverse transcriptase assay, labelling with 3H-uridine, and membrane immunofluorescence gave no indication that retroviruses were present.
Long-term Risk of Incident Vertebral Fractures
Authors: Jane A. Cauley, Marc C. Hochberg, Li-Yung Lui, Lisa Palermo, Kristine E. Ensrud, Teresa A. Hillier, Michael C. Nevitt, Steven R. Cummings
Journal: JAMA (2007)

Vertebral fractures are the most common osteoporotic fracture. Women with low bone mineral density (BMD) and prevalent vertebral fractures have a greater risk of incident vertebral fractures over the short-term, but their absolute risk of vertebral fracture over the long-term is uncertain.To examine the absolute risk of incident vertebral fracture by BMD and prevalent vertebral fracture status over 15 years.A total of 9704 white women were recruited at 4 US clinical centers and enrolled in the Study of Osteoporotic Fractures, a longitudinal cohort study. Of these, 2680 attended a clinic visit an average of 14.9 years after baseline; mean age of 68.8 years at entry and 83.8 years at follow-up. Mean Outcome Measure Incident vertebral fractures identified from lateral spinal radiographs defined as a decrease of at least 20% and 4 mm at any vertebral level. Prevalent vertebral fractures were identified on the baseline radiographs using vertebral morphometry. Bone mineral density was measured at the total hip and lumbar spine using dual-energy x-ray absorptiometry.Of the 2680 women, 487 (18.2%) had an incident vertebral fracture including 163 of the 394 (41.4%) with a prevalent vertebral fracture at baseline and 324 of the 2286 (14.2%) without a prevalent vertebral fracture at baseline (odds ratio, 4.21; 95% confidence interval, 3.33-5.34). Low BMD was associated with an increased risk of incident vertebral fracture (odds ratio per 1 SD decrease in total hip BMD, 1.78 [95% confidence interval, 1.58-2.00]). The absolute risk of vertebral fracture ranged from 56% among women with total hip BMD T score of -2.5 or less and a prevalent vertebral fracture to 9% in women with normal BMD and no prevalent vertebral fracture.Low BMD and prevalent vertebral fractures are independently related to new vertebral fractures over 15 years of follow-up. Women with a prevalent vertebral fracture have a substantially increased absolute risk of an incident fracture, especially if they have osteoporosis diagnosed by BMD.
Depression and Type 2 Diabetes Over the Lifespan: A Meta-Analysis
Authors: Briana Mezuk, William W. Eaton, Sherita Hill Golden
Journal: Diabetes Care (2009)

We appreciate the thoughtful comments of Nouwen, Lloyd, and Pouwer (1) on our recent systematic review of the bidirectional relationship between depression and type 2 diabetes (2). They criticize the choice of only including studies that excluded cases of depression at baseline from the analysis of type 2 diabetes as a risk factor for incident depression because depression is a chronic condition and the absence of baseline depression does not rule out prior episodes. We agree with the instinct to measure the lifetime history of …
Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City
Authors: John D. Meeker, Howard Hu, David E. Cantonwine, Hector Lamadrid-Figueroa, Antonia M. Calafat, Adrienne S. Ettinger, Mauricio Hernandez-Avila, Rita Loch-Caruso, Martha María Téllez-Rojo
Journal: Environmental Health Perspectives (2009)

Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role.We investigated the relationship between phthalate exposure and preterm birth.Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (> or = 37 weeks of gestation).Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethyl-hexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found.We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth.
Glucose, Glycation, and RAGE
Authors: Thoralf Wendt, Nozomu Tanji, Jiancheng Guo, Barry I. Hudson, Angelika Bierhaus, Ravichandran Ramasamy, Bernd Arnold, Peter P. Nawroth, Shi Fang Yan, Vivette D’Agati, Ann Marie Schmidt
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Receptor for advanced glycation endproducts (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Driven by rapid accumulation and expression of key ligands such as advanced glycation endproducts (AGE) and S100/calgranulins in diabetic tissues, upregulation and activation of RAGE magnifies cellular perturbation in tissues affected by hyperglycemia, such as the large blood vessels and the kidney. In the diabetic glomerulus, RAGE is expressed principally by glomerular visceral epithelial cells (podocytes). Blockade of RAGE in the hyperglycemic db/db mouse suppresses functional and structural alterations in the kidney, in the absence of alterations in blood glucose. Recent studies in homozygous RAGE null mice support a key role for RAGE in glomerular perturbation in diabetes. Importantly, beyond diabetes, studies in other settings of glomerulopathies support a critical RAGE-dependent pathway in podocytes linked to albuminuria, mesangial expansion, and glomerular sclerosis. A new paradigm is propsed in glomerular injury, and it is suggested that blockade of the RAGE axis may provide a novel means to prevent irreparable glomerular injury in diabetes and other sclerosing glomerulopathies. E-mail: ams11@columbia.edu