tbuckley/cabot-search huggingface dataset:
Transversus abdominis and core stability: has the pendulum swung?
Authors: G T Allison, S L Morris
Journal: British Journal of Sports Medicine (2008)

In the past decade there has been a focus on isolated transversus abdominis activation and how it contributes to lumbo-pelvic stability. This rationale has not only influenced the management of chronic low back pain (LBP); it has also been included in exercises for many other pathologies of the lower and upper limb and also for prophylaxis in pain-free subjects.
Phase I and pharmacologic study of topotecan in patients with impaired renal function.
Authors: S O'Reilly, E K Rowinsky, W Slichenmyer, R C Donehower, A A Forastiere, D S Ettinger, T L Chen, S Sartorius, L B Grochow
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the toxicities, pharmacokinetics, and recommended doses of the topoisomerase I inhibitor, topotecan, in patients with varying degrees of renal excretory dysfunction. PATIENTS AND METHODS Fourteen patients with normal renal function [creatinine clearance (CrCl) &gt; or = 60 mL/min] and 28 patients with varying degrees of renal dysfunction were treated with topotecan 0.4 to 2.0 mg/m2/d as a 30-minute infusion for 5 consecutive days every 3 weeks. Plasma and urine samples were obtained to determine the disposition of topotecan. RESULTS In patients with mild renal dysfunction (CrCl = 40 to 59 mL/min), dose-limiting hematologic toxicity was observed in three of eight patients receiving topotecan 1.0 mg/m2/d and in two of five patients receiving topotecan 1.5 mg/m2/d. In patients with moderate renal dysfunction (CrCl = 20 to 39 mL/min), dose-limiting hematologic toxicity was observed in three of eight patients who received topotecan 0.5 mg/m2/d, and in two of four patients receiving topotecan 1.0 mg/m2/d; these events were more frequently observed in extensively pretreated patients. Pharmacokinetic analyses showed significant correlations between CrCl and the plasma clearance of both total topotecan [Spearman's correlation coefficient (r2) = 0.65, P = .00001] and topotecan lactone (r2 = 0.65, P = .00003). Mean systemic plasma clearance of total topotecan was significantly reduced in patients with mild (P = .04) and moderate (P = .00006) renal dysfunction. There was no evidence of changes in the pharmacodynamic relationship between topotecan exposure (AUC) and myelotoxicity. CONCLUSION Dose adjustments are required in patients with moderate, but not mild, renal impairment. For patients with moderate renal dysfunction, the recommended starting dose of topotecan is 0.75 mg/m2/d for 5 days every 3 weeks. Moreover, extensively pretreated patients need further dose reductions.
Time and day of admission does not predict outcome of appendicectomy
Authors: Stephen Chapman, Abdul Hakeem, Nicholas Smith, K. Raj Prasad
Journal: International Journal of Surgery (2013)

s / International Journal of Surgery 11 (2013) 589e685 655 ABSTRACTS 1249: SEPSIS WEEK e A PILOT STUDY Timur Navruzov, Dexter Perry, Natalie Chand. Royal Bournemouth Hospital,
Metabolism of Cisplatin to a Nephrotoxin in Proximal Tubule Cells
Authors: Danyelle M. Townsend, Mei Deng, Lei Zhang, Maia G. Lapus, Marie H. Hanigan
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Cisplatin, a commonly used chemotherapeutic agent, is nephrotoxic. The mechanism by which cisplatin selectively kills the proximal tubule cells was heretofore unknown. Recent studies in mice and rats have shown that the nephrotoxicity of cisplatin can be blocked by acivicin or (aminooxy)acetic acid, the same enzyme inhibitors that block the metabolic activation of a series of nephrotoxic halogenated alkenes. In this study, it was hypothesized that cisplatin is activated in the kidney to a toxic metabolite through the same pathway that has been shown to activate the halogenated alkenes. This activation begins with the formation of a glutathione-conjugate that is metabolized to a cysteinyl-glycine-conjugate, to a cysteine-conjugate, and finally to a reactive thiol. In this study, a protocol was developed in which confluent monolayers of LLC-PK<sub>1</sub> cells were exposed to clinically relevant concentrations of cisplatin or cisplatin-conjugate for 3 h. Cell viability was assayed at 72 h. The role of gamma-glutamyl transpeptidase (GGT) and cysteine-S-conjugate beta-lyase in the metabolism of each of the cisplatin-conjugates was investigated. Pre-incubation of cisplatin with glutathione, cysteinyl-glycine, or n-acetyl-cysteine to allow for the spontaneous formation of cisplatin-conjugates increased the toxicity of cisplatin toward LLC-PK<sub>1</sub> cells. Inhibition of GGT activity showed that GGT was necessary only for the toxicity of the cisplatin-glutathione-conjugate. Inhibition of cysteine-S-conjugate beta-lyase reduced the toxicity of each of the cisplatin-conjugates. These data demonstrate that metabolism of cisplatin in proximal tubule cells is required for its nephrotoxicity. The elucidation of this pathway provides new targets for the inhibition of cisplatin nephrotoxicity. E-mail: marie-hanigan@ouhsc.edu
Development and validation of database indexes of asthma severity and control
Authors: F. Firoozi, C. Lemiere, M.-F. Beauchesne, A. Forget, L. Blais
Journal: Thorax (2007)

The use of administrative databases to perform epidemiological studies in asthma has increased in recent years. The absence of clinical parameters to measure the level of asthma severity and control is a major limitation of database studies. A study was undertaken to develop and validate two database indexes to measure the control and severity of asthma.Database indexes of asthma severity and control were derived from definitions in the Canadian Asthma Consensus Guidelines based on dispensed prescriptions and on medical services recorded in two large administrative databases from the Canadian province of Québec (Régie de l'Assurance Maladie du Québec (RAMQ) and MED-ECHO) over 12 months. The database indexes of asthma severity and control were validated against the pulmonary function test results of 71 patients with asthma randomly selected from two asthma clinics, and they were also applied to a cohort of patients with asthma followed up for 139 283 person-years selected from the RAMQ and MED-ECHO databases between 1 January 1997 and 31 December 2004.According to the database indexes, 49.3%, 29.6% and 21.1% of patients recruited at the asthma clinics were found to have mild, moderate and severe asthma, respectively, while 53.5% were found to have controlled asthma. The mean predicted value of the forced expiratory volume in 1 s (FEV(1)) ranged from 89.8% for mild asthma to 61.5% for severe asthma (p<0.001), whereas the range from controlled to uncontrolled asthma was 89.5% to 67.3% (p<0.001). The ratio of the FEV(1) to the forced vital capacity (FEV(1)/FVC ratio) measured in 56 patients ranged from 75.8% for mild asthma to 61.8% for severe asthma (p = 0.030), whereas the range from controlled to uncontrolled asthma was 75.3% to 65.7% (p<0.001).In the absence of clinical data, these database indexes could be used in epidemiological studies to assess the severity and control of asthma.
Involvement of tumor necrosis factor-α in development of hepatic injury in galactosamine-sensitized mice
Authors: Ieharu Hishinuma, Jun-Ichi Nagakawa, Kazuo Hirota, Kaname Miyamoto, Kazuo Tsukidate, Takashi Yamanaka, Kou-Ichi Katayama, Isao Yamatsu
Journal: Hepatology (1990)

Intravenous injection of lipopolysaccharide and D-galactosamine, at doses of 0.2 micrograms/kg and 800 mg/kg, respectively, elicited massive hepatic necrosis within 24 hr in C3H/HeN mice. The plasma L-alanine aminotransferase (ALT, E.C. 2.6.1.2) or L-aspartate aminotransferase (AST, E.C. 2.6.1.1) activities at this point reached more than 2,000 IU/L. However, overt hepatic injury as evaluated by the plasma aminotransferase activities did not develop in mice in which only lipopolysaccharide or only D-galactosamine was injected. No tumor necrosis factor-like activities could be detected in the plasma of galactosamine- and lipopolysaccharide-injected mice as determined by the assay of cytotoxicity to highly tumor necrosis factor-sensitive L-P3 cells through the experimental period of 24 hr. However, passive immunization against mouse tumor necrosis factor-alpha with polyvalent rabbit anti-mouse tumor necrosis factor-alpha antiserum, which was able to neutralize the cytotoxic effects of recombinant mouse tumor necrosis factor-alpha on L-P3 cells, could protect the mice from the development of hepatic injury in a dose-dependent manner. Simultaneous injection of recombinant human tumor necrosis factor-alpha, instead of lipopolysaccharide, with 800 mg/kg of D-galactosamine in lipopolysaccharide-resistant C3H/HeJ mice sensitized the animals more than one thousand-fold to the development of hepatic injury. The livers appeared to be morphologically similar to those of galactosamine- and lipopolysaccharide-injected C3H/HeN mice.
Prediagnostic Plasma IgE Levels and Risk of Adult Glioma in Four Prospective Cohort Studies
Authors: F. C. F. Calboli, D. G. Cox, J. E. Buring, J. M. Gaziano, J. Ma, M. Stampfer, W. C. Willett, S. S. Tworoger, D. J. Hunter, C. A. Camargo, D. S. Michaud
Journal: JNCI Journal of the National Cancer Institute (2011)

Results for women are based on the two female cohorts: Nurses' Health Study (NHS) and Women's Health Study (WHS).Results for men are based on the two male cohorts: Health Professionals Follow-up Study (HPFS) and Physicians' Health Study (PHS).Conditional logistic regression was used to analyze the matched nested case-control dataset after stratifying data by sex.CI = confidence interval; OR = odds ratio.† Total IgE levels were measured using the Pharmacia Diagnostics AB UniCAP fluorescent immunoassay; cut points were based on clinically defined cut points.Respiratory allergen-specific IgE was measured using the ImmunoCAP Phadiotop and food allergen-specific IgE was measured using a mixed food allergen assay from Pharmacia Diagnostics AB; recommended cut points were provided by Pharmacia Diagnostics AB. ‡ ORs for continuous variable (for increase by 1 ln total IgE).
Vagal mediation of systemic cardiovascular response to portal hypertension: from experimental studies in animals to treatment of humans
Authors: S. Moller
Journal: Gut (2008)

During the last decades research into complications of portal hypertension have focused on the extrahepatic and systemic manifestations. Apart from splanchnic haemodynamic complications owing to increased portal pressure, such as development of oesophageal varices and ascites due to increased splanchnic hydrostatic pressure, it has become evident that patients with portal hypertension exhibit multi-organ failure leaving few organs unaffected. In 1955, Kowalski and Abelman described elevated stroke volume and cardiac output and low systemic vascular resistance in one third of patients with cirrhosis.1 Since that time, many authors have confirmed the presence of a hyperdynamic circulation affecting the course of the disease and the prognosis in portal hypertensive patients. A considerable number of experimental and human studies have sought to reveal a pathogenetic link between portal hypertension and these extrahepatic alterations. The “peripheral arterial vasodilatation theory” was launched 20 years ago and modifications of this hypothesis have prevailed until today.2 A splanchnic arteriolar vasodilatation owing to increased activity of, for example, nitric oxide, tumour necrosis factor-α (TNF-α), endocannabinoids and other vasodilators, and the succeeding neuro-humoral counter-regulatory mechanisms explain many of the haemodynamic changes in portal hypertension.3 Plasma volume expansion and effective central hypovolaemia activates vasoconstrictor systems and secondary sodium–water retention.2 The vasodilatation precedes renal sodium and water retention and plasma volume expansion which correlates with activated counter-regulatory vasoconstrictor systems such as the sympathetic nervous system, the renin–angiotensin–aldosterone system, the …
Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors
Authors: Emilio Bajetta, Valentina Guadalupi, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2008)

Most pediatric solid tumor protocols include daily cisplatin for 3 to 5 days with higher cumulative doses of cisplatin.Furthermore, such protocols do not generally use a 6-hour infusion of cisplatin.Both these considerations are important in addressing the second question appropriately raised by Freyer et al: What is the therapeutic burden associated with giving amifostine?The reported study is a multiinstitutional, international study that was conducted at six centers in the United States and Australia and has recently expanded to eight centers including Canada.Although the supportive care guidelines are extensive, they have been implemented successfully in these institutions with the provision of appropriate education and clear guidelines.Although we did not capture the incidence of grades 1 and 2 toxicities in this protocol, we do not have concerns regarding the ability to export this therapy to other institutions.However, we concur with Freyer et al that administering multiple daily doses of amifostine to patients with other solid tumors receiving cisplatin daily for 3 to 5 days may require new supportive guidelines and close monitoring.A previous study has shown that amifostine leads to rapid, transient suppression of parathyroid hormone, and hence, transient hypocalcaemia. 3 In that study, amifostine was administered at 600 mg/m 2 /dose twice daily for 3 days with ifosfamide, carboplatin and etoposide to six patients.Grade 3 hypocalcemia was documented in two patients. 3Thus, administration of amifostine twice daily with each cisplatin dose for 3 to 5 days will likely lead to more profound hypocalcemia, requiring prolonged prophylactic calcium infusions and modifications of our supportive guidelines.In addition, although the prescribing information for amifostine recommends administration over 15 minutes, 15 to 30 minutes before radiotherapy or chemotherapy, Wagner et al 4 reported the significantly lower incidents of toxicities such as hypotension with bolus administration of amifostine, a strategy which we adopted in the reported study.Finally, we concur with Freyer et al that other otoprotectants such as sodium thiosulfate also deserve investigation.It is important to point out that both sodium thiosulfate and amifostine are thiol drugs that have similar mechanisms of action, in part acting as scavengers of oxygen-free radicals and binding to the active species of platinum agents. 5However, we believe that given the extensive experience with amifostine, this agent may deserve further study in children with other solid tumors with more careful attention to dosing and scheduling issues.
Maternal Efficacy and Safety Outcomes in a Randomized, Controlled Trial Comparing Insulin Detemir With NPH Insulin in 310 Pregnant Women With Type 1 Diabetes
Authors: Elisabeth R. Mathiesen, Moshe Hod, Marina Ivanisevic, Santiago Duran Garcia, Lise Brøndsted, Lois Jovanovič, Peter Damm, David R. McCance
Journal: Diabetes Care (2012)

This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account.A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups.Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.
Down-regulation of CXCR4 and CD62L in Chronic Lymphocytic Leukemia Cells Is Triggered by B-Cell Receptor Ligation and Associated with Progressive Disease
Authors: Amalia Vlad, Pierre-Antoine Deglesne, Rémi Letestu, Stéphane Saint-Georges, Nathalie Chevallier, Fanny Baran-Marszak, Nadine Varin-Blank, Florence Ajchenbaum-Cymbalista, Dominique Ledoux
Journal: Cancer Research (2009)

Progressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in the accumulation of malignant B cells. We investigated on CLL cells from 30 untreated patients the consequence of B-cell receptor (BCR) triggering on the membrane expression of CXCR4 and CD62L, two surface molecules involved in trafficking and exit of B-lymphocytes from lymph nodes. BCR stimulation promoted a strictly simultaneous down-regulation of CXCR4 and CD62L membrane expression to a variable extent. The variable BCR-dependent decrease of the two proteins was strikingly representative of the heterogeneous capacity of the CLL cells to respond to BCR engagement in a given patient. Functionally, cells down-regulating CXCR4 and CD62L in response to BCR engagement displayed a reduction in both migration toward CXCL12 and adhesion to lymphatic endothelial cells. Remarkably, the ability of CLL cells to respond to BCR ligation was correlated with unfavorable prognostic markers and short progression-free survival. In conclusion, BCR signaling promotes decrease of CXCR4 and CD62L membrane expression in progressive cases only. These results are consistent with the hypothesis that BCR-mediated signaling pathways favor accumulation of a proliferative pool within the lymph nodes of progressive CLL cases.
No audible wheezing
Authors: Joshua A. Boyce, K. Frank Austen
Journal: The Journal of Experimental Medicine (2005)

Mouse models of T helper type 2 (Th2) cell–biased pulmonary inflammation have elucidated mechanisms of sensitization, cell traffic, and induced airway hyperresponsiveness (AHR). Nonetheless, most mice lack intrinsic AHR, a central property of human asthma, and disparities persist regarding the contributions of eosinophils and mast cells and the sensitivity to induced AHR in the commonly used mouse strains. We suggest that these discordances, reflecting methodological and genetic differences, may be informative for understanding heterogeneity of human asthma.
Trophic Factors in Neurologic Disease
Authors: S S Stewart, S H Appel
Journal: Annual Review of Medicine (1988)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Respiratory symptoms and home environment in children: a national survey
Authors: M L Burr, H R Anderson, J B Austin, L S Harkins, B Kaur, D P Strachan, J O Warner
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Respiratory diseases are common in childhood and may lead to chronic disease in adult life; environmental factors probably play an important part in their causation. <h3>METHODS</h3> A survey of respiratory symptoms in children aged 12–14 years was conducted throughout Great Britain as part of the International Study of Asthma and Allergies in Childhood (ISAAC). Information was obtained on certain aspects of the home environment in order to assess their importance as risk factors. <h3>RESULTS</h3> The response rate was 79.3%, and 25 393 children in 93 schools participated. In a multiple regression analysis, wheeze was reported more often in non-metropolitan areas and in association with active smoking, passive smoking, the presence of a furry pet, bottled gas, paraffin, and other unusual heating fuels; small regional differences persisted. Current smoking, previous smoking, and passive smoking accounted for 10.4%, 6.8%, and 6.5%, respectively, of wheezing in the past 12 months, and furry pets accounted for 5.0%. Cough and phlegm were associated with active and passive smoking and with the miscellaneous fuels; similar associations were found for rhinitis, but were less consistent for rhinitis occurring in spring and summer. Gas cooking showed little association with respiratory symptoms. <h3>CONCLUSIONS</h3> Passive as well as active smoking is an important cause of respiratory symptoms in adolescence. Pets seem to increase the risk of wheeze and rhinitis, and fumes from certain unusual heating fuels may have adverse effects. Home environment and geographical location have independent effects on the prevalence of respiratory symptoms.
The emotional shape of our moral life: Anger-related emotions and mutualistic anthropology
Authors: Florian Cova, Julien Deonna, David Sander
Journal: Behavioral and Brain Sciences (2013)

Abstract The evolutionary hypothesis advanced by Baumard et al. makes precise predictions on which emotions should play the main role in our moral lives: morality should be more closely linked to “avoidance” emotions (like contempt and disgust) than to “punitive” emotions (like anger). Here, we argue that these predictions run contrary to most psychological evidence.
Nitric oxide, a double edged sword in cancer biology: Searching for therapeutic opportunities
Authors: Simone Mocellin, Vincenzo Bronte, Donato Nitti
Journal: Medicinal Research Reviews (2006)

Abstract Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological and pathological processes. The last decade has witnessed major advances in dissecting NO biology and its role in cancer pathogenesis. However, the complexity of the interactions between different levels of NO and several aspects of tumor development/progression has led to apparently conflicting findings. Furthermore, both anti‐NO and NO‐based anticancer strategies appear effective in several preclinical models. This paradoxical dichotomy is leaving investigators with a double challenge: to determine the net impact of NO on cancer behavior and to define the therapeutic role of NO‐centered anticancer strategies. Only a comprehensive and dynamic view of the cascade of molecular and cellular events underlying tumor biology and affected by NO will allow investigators to exploit the potential antitumor properties of drugs interfering with NO metabolism. Available data suggest that NO should be considered neither a universal target nor a magic bullet, but rather a signal transducer to be modulated according to the molecular makeup of each individual cancer and the interplay with conventional antineoplastic agents. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 317–352, 2007