tbuckley/cabot-search huggingface dataset:
Renal Cortical Pyruvate Depletion during AKI
Authors: Richard A. Zager, Ali C.M. Johnson, Kirsten Becker
Journal: Journal of the American Society of Nephrology (2014)

Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15–60 minutes; 0–18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury.
Improvement in Process of Care and Outcome After a Multicenter Severe Sepsis Educational Program in Spain
Authors: Ricard Ferrer, Antonio Artigas, Mitchell M. Levy, Jesús Blanco, Gumersindo González-Díaz, José Garnacho-Montero, Jordi Ibáñez, Eduardo Palencia, Manuel Quintana, María Victoria de la Torre-Prados
Journal: JAMA (2008)

Concern exists that current guidelines for care of patients with severe sepsis and septic shock are followed variably, possibly due to a lack of adequate education.To determine whether a national educational program based on the Surviving Sepsis Campaign guidelines affected processes of care and hospital mortality for severe sepsis.Before and after design in 59 medical-surgical intensive care units (ICUs) located throughout Spain. All ICU patients were screened daily and enrolled if they fulfilled severe sepsis or septic shock criteria. A total of 854 patients were enrolled in the preintervention period (November-December 2005), 1465 patients during the postintervention period (March-June 2006), and 247 patients during the long-term follow-up period 1 year later (November-December 2006) in a subset of 23 ICUs.The educational program consisted of training physicians and nursing staff from the emergency department, wards, and ICU in the definition, recognition, and treatment of severe sepsis and septic shock as outlined in the guidelines. Treatment was organized in 2 bundles: a resuscitation bundle (6 tasks to begin immediately and be accomplished within 6 hours) and a management bundle (4 tasks to be completed within 24 hours).Hospital mortality, differences in adherence to the bundles' process-of-care variables, ICU mortality, 28-day mortality, hospital length of stay, and ICU length of stay.Patients included before and after the intervention were similar in terms of age, sex, and Acute Physiology and Chronic Health Evaluation II score. At baseline, only 3 process-of-care measurements (blood cultures before antibiotics, early administration of broad-spectrum antibiotics, and mechanical ventilation with adequate inspiratory plateau pressure) we had compliance rates higher than 50%. Patients in the postintervention cohort had a lower risk of hospital mortality (44.0% vs 39.7%; P = .04). The compliance with process-of-care variables also improved after the intervention in the sepsis resuscitation bundle (5.3% [95% confidence interval [CI], 4%-7%] vs 10.0% [95% CI, 8%-12%]; P < .001) and in the sepsis management bundle (10.9% [95% CI, 9%-13%] vs 15.7% [95% CI, 14%-18%]; P = .001). Hospital length of stay and ICU length of stay did not change after the intervention. During long-term follow-up, compliance with the sepsis resuscitation bundle returned to baseline but compliance with the sepsis management bundle and mortality remained stable with respect to the postintervention period.A national educational effort to promote bundles of care for severe sepsis and septic shock was associated with improved guideline compliance and lower hospital mortality. However, compliance rates were still low, and the improvement in the resuscitation bundle lapsed by 1 year.
The Molecular Biology of G6PD Variants and Other Red Cell Enzyme Defects
Authors: Ernest Beutler
Journal: Annual Review of Medicine (1992)

Modern techniques of molecular biology have made it possible to identify mutations in a number of different hereditary red cell enzyme defects. Most of the studies have been performed in glucose-6-phosphate dehydrogenase deficiency, where a large number of point mutations have been identified. The same mutations are encountered repeatedly, even in patients with defects that were thought, on the basis of biochemical properties of the residual enzyme, to be distinct. A beginning has been made in identifying mutations in a few other red cell enzyme defects.
Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial Fibrillation Depends on the Quality of International Normalized Ratio Control Achieved by Centers and Countries as Measured by Time in Therapeutic Range
Authors: Stuart J. Connolly, Janice Pogue, John Eikelboom, Gregory Flaker, Patrick Commerford, Maria Grazia Franzosi, Jeffrey S. Healey, Salim Yusuf
Journal: Circulation (2008)

Oral anticoagulation (OAC) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range. This report examines how differences in time in therapeutic range (TTR) between centers and between countries affect the outcomes of OAC therapy.In a posthoc analysis, the TTRs of patients on OAC in a randomized trial of OAC versus clopidogrel plus aspirin (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ACTIVE W]) were used to calculate the mean TTR for each of 526 centers and 15 countries. Proportional-hazards analysis, with and without adjustment for baseline variables, was performed, with patients stratified by TTR quartile and country. A wide variation in TTRs was found between centers, with mean TTRs for centers in the 4 quartiles of 44%, 60%, 69%, and 78%. For patients at centers below the median TTR (65%), no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC (relative risk, 0.93; 95% confidence interval, 0.70 to 1.24; P=0.61). However, for patients at centers with a TTR above the study median, OAC had a marked benefit, reducing vascular events by >2-fold (relative risk, 2.14; 95% confidence interval, 1.61 to 2.85; P<0.0001). Mean TTR also varied between countries from 46% to 78%; relative risk (clopidogrel plus aspirin versus OAC) varied from 0.6 to 3.6 (a 5-fold difference). A population-average model predicted that a TTR of 58% would be needed to be confident that patients would benefit from being on OAC.A wide variation exists in international normalized ratio control, as measured by TTR, between clinical centers and between countries, which has a major impact on the treatment benefit of OAC therapy. For centers and countries, a target threshold TTR exists (estimated between 58% and 65%) below which there appears to be little benefit of OAC over antiplatelet therapy.
Protein Concentration of Oedema Fluid in Rheumatoid Arthritis : Part I
Authors: R. H. Gandy, B. M. Ansell, E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1965)

M.R.C.Rheumatism Research Unit, Canadian RedCrossMemorial Hospital, Taplow Theprotein content ofoedemafluid depends on several factors, including vascular permeability, serumprotein level, lymphatic clearance, venous pressure, andtissue tension. Recently, Parkand Swinburne (1964) reported thatoedemafluid obtained fromthefeetandankles ofpatients with rheumatoid arthritis contained less than1g.percent. protein, andtheysuggested thatitwasatransudate. Thiswasatvariance withtheexperience ofBywaters (1948), whofounda highprotein content inthe neighbourhood oftheswollen andinflamed joints of rheumatoid arthritis; thetissue fluid clotted and contained over2g.percent.protein compared with less than1g.percent. incardiac orrenal oedema. Someofhiscasesshowed aninflammatory oedema forsomemonths before thejoints becameobviously involved. Thepresent investigation was,therefore, undertaken withparticular reference tocasesshowing an active arthritis asjudged bylocal heatandsoft tissue swelling. Inferences about thenatureofthe oedema inactive arthritis maybedrawnmoreeasily inthehandthaninthefoot, because ofthehigher hydrostatic pressure present inthelatter: fluid from bothhands andfeet wastherefore studied. Material andMethods
Breathlessness in a teenager
Authors: IB Dahlen, GN Hillerdal, GA Wegenius, AC Henze
Journal: European Respiratory Journal (1993)

Case historyAn 18 yr old woman was referred for investigation of therapy-resistant asthma.As a baby, she had had considerable nutritional problems.These problems decreased during infancy, but she was never able to swallow large mouthfuls.As a young child, she was slightly troubled by breathlessness and this became more evident after the age of about 8 yrs.It was most apparent in connection with exercise and during episodes of upper respiratory infection.A chest roentgenogram from this period was interpreted as normal.Asthma medication gave no relief.Her' physical capacity was poor and she was never able to run as fast as her peers.She developed the habit of sleeping with her mouth open and snored loudly.
Biology of Hematopoietic Stem Cells and Progenitors: Implications for Clinical Application
Authors: Motonari Kondo, Amy J. Wagers, Markus G. Manz, Susan S. Prohaska, David C. Scherer, Georg F. Beilhack, Judith A. Shizuru, Irving L. Weissman
Journal: Annual Review of Immunology (2003)

▪ Abstract Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases.
Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster.
Authors: M J Sole, C M Lo, C W Laird, E H Sonnenblick, R J Wurtman
Journal: Circulation Research (1975)

Although a reduction in myocardial norepinephrine stores in cardiac hypertrophy and congestive failure is well documented, norepinephrine turnover has been inadequately studied in such hearts. We compared norepinephrine turnover in control and cardiomyopathic hamsters by following the decline in specific activity of myocardial norepinephrine after labelling with an intraperitoneal tracer dose of 3H-norepinephrine. Adult myocardial norepinephrine concentrations were not attained until 4 weeks of age in both strains. There was no difference in the rate of constant (K) for myocardial norepinephrine turnover (0.107+/-0.004 hours-1 vs. 0.100+/-0.005 hours-1) in the two strains of hamsters during the neonatal period. In young control hamsters, K fell to 0.064+/-0.004 hours-1, but that for age-matched hamsters with mild cardiac hypertrophy was 0.102+/-0.001 hours-1 (P less than 0.001). There was little change in K as control hamsters aged. With the development of more severe hypertrophy in cardiomyopathic hamsters, cardiac norepinephrine decreased and resting K rapidly increased to approach the value obtained when hamsters were subjected to immobilization stress (0.302+/-0.013 hours-1). The maximum achievable K remained the same for both control and dystrophic hamsters even during terminal disease. Prolonged immobilization led to a reduction in cardiac norepinephrine in both strains. Ganglionic blockade of failing hamsters completely restored the levels of both cardiac norepinephrine and K to control values. Splenic noradrenergic nerves showed no change in K, norepinephrine content, or maximum K during cardiac decompensation. We conclude that, in the late stages of hamster cardiomyopathy, there is a progressive and possibly specific increase in cardiac sympathetic tone which leads to a concomitant decrease in cardiac norepinephrine. With the loss of sympathetic reserve, congestive failure supervenes.
Letter: Irresponsible poisoning.
Authors: R H Jackson
Journal: BMJ (1974)

this risk-and at the least avoid prolonged pregnancy.The second item concerns our doubleblind trial of chlorpropamide 100 mg a day in the treatment of gestational chemical diab_tes in women of average body weight.We do know that such a dose of ohlorpropamide is effective in reversing chemical diabetes in the mother in pregnancy-without apparent harm to the fetus4-though we do not recommend this form of treatmenit for diabetes of a more severe degree, wh-ich seems to require more delicate oDntrol during pregnancy.5-Weare, etc.,
The Avandia Debate
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2007)

Perspectives on the News commentaries are now part of a new, free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, is designating this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians .

This is the first in a series of articles based on presentations at the American Diabetes Association's (ADA's) 67th Scientific Sessions in June 2007, in Chicago, reviewing aspects of thiazolidinediones (TZDs) treatment, with focus on the controversy over possible adverse effects of rosiglitazone.

On 21 May 2007, an article appeared on the New England Journal of Medicine Web site giving a meta-analysis of 42 trials comparing rosiglitazone with placebo or other agents. Steven Nissen and Kathy Wolski reported a significant 43% increase in myocardial infarction and a trend almost achieving statistical significance of a 64% increase in cardiovascular mortality (1). In an accompanying editorial, Bruce Psaty and Carl Furberg strongly questioned the wisdom of choosing treatments for diabetes based on “the single dimension of glycemic control,” suggesting that although “high levels of glycated hemoglobin increase risk,” one must “require proof of health benefits” before accepting that an agent lowering blood glucose benefits individuals with diabetes (2).

These articles were accompanied by tremendous publicity. On 22 May 2007, an article in the New York Times entitled “Heart Attack Risk Seen in Drug for Diabetes” summarized the public concern. The article questioned whether GlaxoSmithKline (GSK), the manufacturer of rosiglitazone, and the Food and Drug Administration (FDA) should have released similar data earlier, mentioned investigations being started in Congress, and quoted Nissen …
Is compressive load a factor in the development of tendinopathy?
Authors: JL Cook, C Purdam
Journal: British Journal of Sports Medicine (2011)

Tendons are designed to take tensile load, but excessive load can cause overuse tendinopathy. Overuse tendinopathy results in extensive changes to the cells and extracellular matrix, resulting in activated cells, increase in large proteoglycans and a breakdown of the collagen structure. Within these pathological changes, there are areas of fibrocartilaginous metaplasia, and mechanotransduction models suggest that this response could be due to compressive load. As load management is a cornerstone of treating overuse tendinopathy, defining the effect of tensile and compressive loads is important in optimising the clinical management of tendinopathy. This paper examines the potential role of compressive loads in the onset and perpetuation of tendinopathy, and reviews the anatomical, epidemiological and clinical evidence that supports consideration of compressive loads in overuse tendinopathy.
Expression Level of Valosin-Containing Protein Is Strongly Associated With Progression and Prognosis of Gastric Carcinoma
Authors: Shinji Yamamoto, Yasuhiko Tomita, Yoshihiko Hoshida, Shuji Takiguchi, Yoshiyuki Fujiwara, Takushi Yasuda, Masahiko Yano, Shoji Nakamori, Masato Sakon, Morito Monden, Katsuyuki Aozasa
Journal: Journal of Clinical Oncology (2003)

Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined.VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells.Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification.The prognostic significance of VCP expression level in GC was demonstrated.
The percutaneous rotary lithotrite: a new approach to the treatment of symptomatic cholecystolithiasis.
Authors: A Gillams, J J Donald, R C Russell, A R Hatfield, W R Lees
Journal: Gut (1993)

This report evaluates the use of a new device for destruction of gall stones, the Kensey-Nash Lithotrite (Baxter Corporation, California, USA). The principle of the instrument is that of a liquidiser with an impeller that emulsifies stones. Twenty five patients were treated; 13 patients were considered unfit for conventional treatment (complex group) and 12 elected to have the procedure (non-complex group). In the complex group nine patients were treated under local anaesthesia. Only six of the 13 patients had a clear gall bladder at the end of the first procedure, but after further treatments that included cholecystoscopy, endoscopic sphincterotomy, and percutaneous cholecystolithotomy 11 patients had a gall bladder free of stones. The morbidity was high, mainly due to pain and bile leaks, causing prolonged stays in hospital (median 18 days). In the non-complex group six patients had the procedure performed under local anaesthesia. Ten patients had a successful clearance of the gall bladder, and the remaining two patients had the stones removed at cholecystoscopy. Despite good clearance, the morbidity was high, with eight emergency admissions on account of complications and a prolonged duration of stay (median 13 days). In conclusion the technique is effective, but the morbidity is high. Further development is required if this technique is to be included in the alternative treatments for the management of gall stones.
Rare diseases bullet 9: Adult pulmonary Langerhans' cell histiocytosis
Authors: A. Tazi
Journal: Thorax (2000)

In the early 1950s Lichtenstein introduced the term histiocytosis X to describe a group of syndromes with seemingly unrelated clinical features, but whose pathological findings were characterised by the infiltration of involved tissues with large numbers of unusual histiocytes, often organised as granulomas.1 Subsequently it was shown that these histiocytes were similar to Langerhans' cells normally present in the skin and other epithelia, a finding that led to the current designation of Langerhans' cell histiocytosis (LCH) for this group of disorders.2 3 

Although the different forms of LCH are united by a common histopathological finding—the Langerhans' cell granuloma—the clinical spectrum of these disorders is extremely large, extending from an acute disseminated form which usually occurs in infants and carries a poor prognosis, to the presence of lesions localised to a single tissue which follows a more benign clinical course (table1).4-8 Pulmonary involvement is not unusual in systemic forms of LCH.4-8 In this setting prognosis depends on the age of the patients, the number of organs involved, and the extent to which normal function is impaired.4-9 Pulmonary symptoms are rarely prominent, although the presence or absence of lung involvement does appear to have a bearing on the outcome.7 9 The lung can also be the predominant or only site involved in LCH.4-6 8 10 Localised pulmonary LCH, the form most frequently encountered by specialists in pulmonary medicine, occurs most commonly in young adults and has several unique clinical and epidemiological features that justify its classification as a distinct clinicopathological entity.4 6 8 11-17The development of high resolution computed tomographic (HRCT) scanning has proved to be of considerable help in the diagnosis of this disorder.18 19 In contrast, the natural history of localised pulmonary LCH remains poorly defined and no …
The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials
Authors: Jun-Jie Yin, Fang Lao, Peter P. Fu, Wayne G. Wamer, Yuliang Zhao, Paul C. Wang, Yang Qiu, Baoyun Sun, Gengmei Xing, Jinquan Dong, Xing-Jie Liang, Chunying Chen
Journal: Biomaterials (2008)