tbuckley/cabot-search huggingface dataset:
Warfarin STEREOCHEMICAL ASPECTS OF ITS METABOLISM AND THE INTERACTION WITH PHENYLBUTAZONE
Authors: Richard J. Lewis, William F. Trager, Kenneth K. Chan, A. Breckenridge, M. Orme, Malcolm Roland, William Schary
Journal: Journal of Clinical Investigation (1974)

An examination of the metabolic fate of the R and the S isomers of warfarin revealed that the two isomers were metabolized by different routes. R warfarin was oxidized to 6-hydroxywarfarin and was reduced to the (R,S) warfarin alcohol. In contrast, S warfarin was oxidized to 7-hydroxywarfarin and was reduced to the (S,S) warfarin alcohol. S warfarin was also oxidized to 6-hydroxywarfarin. These observations suggested that interactions between warfarin and other drugs might be manifest stereo-specifically, i.e., have a different effect on the isomers of warfarin, so a series of experiments were conducted with each isomer of warfarin, before and after phenylbutazone. The plasma clearance of S warfarin was slowed from 3.1 to 1.1% per h in one subject and from 2.3 to 1.6% per h in another. In contrast, the clearance of R warfarin was increased from 1.5 to 3.0% per h and from 0.9 to 1.6% per h in two subjects after phenylbutazone. The rate of clearance of racemic warfarin was unaffected by phenylbutazone; the depression of the rate of clearance of the S isomer masked the stimulation of the clearance of the R isomer. Since S warfarin is five times more potent an anticoagulant than R warfarin, it is concluded that inhibition of the metabolism of S warfarin provides one mechanism for the augmented anticoagulation which follows phenylbutazone.
Enteric coated microspheres of pancreatin in the treatment of cystic fibrosis: comparison with a standard enteric coated preparation.
Authors: R J Stead, I Skypala, M E Hodson, J C Batten
Journal: Thorax (1987)

In an open, randomised crossover study enteric coated microspheres of pancreatin were compared with a standard preparation of enteric coated pancreatin over two consecutive 28 day treatment periods in 23 adults with steatorrhoea due to cystic fibrosis. Lipase intake was equal to the patients9 previous requirements and was the same during the two months. Patients performed 72 hour faecal collections at the end of each month and completed diary cards daily throughout. Comparison of the month of treatment with enteric coated microspheres with the month of standard enteric coated tablets showed a significant increase in body weight on microsphere capsules (p less than 0.02). There was also a reduced frequency of bowel actions (p less than 0.001) and abdominal pain (p less than 0.05), and improvement in stool character (p less than 0.001) on microsphere capsules. Faecal fat excretion was reduced by 44% with the microsphere capsules (p less than 0.01), and 86% of patients showed an increased coefficient of fat absorption (mean increase 13%, 95% confidence limits 6.5-19.1%; p less than 0.001). Eighty one per cent of patients preferred microsphere capsules of the two treatments. Thus enteric coated microsphere capsules are more effective in treating steatorrhoea in cystic fibrosis than standard enteric coated tablets.
Should herbal medicine-like products be licensed as medicines
Authors: P. A G M De Smet
Journal: BMJ (1995)

Herbal remedies form a potpourri that ranges from plants that people collect themselves and then take for health reasons to approved medicinal products. Many herbal products available in Britain fall between the far ends of this regulatory range: unlicensed preparations are thought to account for over 80% of herbal sales.1 European Union legislation requires herbal products to be authorised for marketing if they are industrially produced2 and if their presentation or their function, or both, bring them inside its definition of a medicinal product.3 Unfortunately, the drawing of sharp borderlines is difficult.

Many medicine-like products on the British herbal market remain unregistered for two reasons: acceptable data on efficacy, safety, and quality may not be available, and the licensing fee is high. Diluting requirements for registration would introduce double standards, which would be highly controversial. On the one hand, a single regimen for medicinal products offers undeniable advantages including equal treatment for all kinds of remedies and …
Access to Pediatric Cancer Care by Age, Race, and Diagnosis, and Outcomes of Cancer Treatment in Pediatric and Adolescent Patients in the State of Georgia
Authors: Della L. Howell, Kevin C. Ward, Harland D. Austin, John L. Young, William G. Woods
Journal: Journal of Clinical Oncology (2007)

There have been concerns among pediatric oncologists that adolescent and minority patients are not getting adequate access to care. This study examines access to cancer care and survival outcomes based on age, race, and type of cancer in patients in Georgia.We performed a retrospective review of 1,751 cancer patients aged 0 to 19 years, diagnosed between 1998 and 2002, in the Georgia Comprehensive Cancer Registry, which identified patients who were treated at one of five Georgia pediatric cancer centers (Children's Oncology Group [COG] members) at any point in their treatment. Data were further analyzed for age at diagnosis, race, county of residence, and 5-year survival.Eighty-seven percent of patients aged 0 to 14 years and 36% of those aged 15 to 19 years were treated at a COG institution. Twenty-five percent of all patients were of African descent, with 75.4% of black versus 70.3% of white patients (age 0 to 19 years) treated at a COG institution (P < .01); 97.1% of other minorities were treated at a COG institution (P < .05). The 5-year actuarial survival rates for more pediatric-specific cancers were significantly lower in all leukemias (75.1% v 46.4%; P = .0015), and acute lymphoblastic leukemia specifically (86.3% v 53.3%; P < .05) for patients not treated at a COG institution. Actuarial survival rates were much lower for blacks than whites in all cancers as a whole (70% v 82%; P < .001) and for many specific subtypes.Adolescent-aged patients are less likely to be referred to a COG institution, potentially exposing them to worse outcomes in some cancer subtypes. Reassuringly, minority populations are receiving adequate access to pediatric cancer care; unfortunately their survival rates are lower.
Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN
Authors: H. Yu, Yili Li, Chuanyun Gao, L. Fabien, Y. Jia, Junjie Lu, Leslie E. Silberstein, Geraldine Sowinski Pinkus, K. Ye, Li Chai, Hongbo Luo
Journal: Leukemia (2010)
No Association between Atopy/Asthma and the Ile50val Polymorphism of IL-4 Receptor
Authors: EMIKO NOGUCHI, MASANAO SHIBASAKI, TADAO ARINAMI, KAZUNORI TAKEDA, YUKAKO YOKOUCHI, KIMIKO KOBAYASHI, NATSUKI IMOTO, SATOKO NAKAHARA, AKIRA MATSUI, HIDEO HAMAGUCHI
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Susceptibility to atopic diseases is known to involve genetic factors. The interleukin-4 (IL-4) receptor- α gene (IL4R) reportedly is involved in the development of atopy. A recent study has shown the Ile50 allele of a polymorphism (Ile50Val) of IL4R to be associated with atopy. The objective of this study was to replicate this association and confirm the possible role of the Ile50Val polymorphism of IL4R in the etiology of atopic asthma in a Japanese population. We conducted a transmission disequilibrium test in 86 families identified through asthmatic children. A case-control study was also carried out using both atopic and control subjects. The IL4R Ile50Val polymorphism was genotyped by a PCR-restriction fragment length polymorphism method using an intronic upstream primer. The IL4R Ile50 allele was not preferentially transmitted to atopy- or to asthma-affected children. Neither the Ile50 allele nor the Ile50/Ile50 genotype was more prevalent in the atopic subjects than in the control subjects. Our findings indicate that the Ile50Val polymorphism of IL4R does not play a substantial role in genetic predisposition for the etiology of atopy or asthma in this Japanese population.
Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation
Authors: J. Edlmayr, K. Niespodziana, T. Popow-Kraupp, V. Krzyzanek, M. Focke-Tejkl, D. Blaas, M. Grote, R. Valenta
Journal: European Respiratory Journal (2010)

Human rhinoviruses (HRVs) are the major cause of the common cold and account for 30–50% of all acute respiratory illnesses. Although HRV infections are usually harmless and invade only the upper respiratory tract, several studies demonstrate that HRV is involved in the exacerbation of asthma. VP1 is one of the surface-exposed proteins of the viral capsid that is important for the binding of rhinoviruses to the corresponding receptors on human cells. Here we investigated its potential usefulness for vaccination against the common cold. We expressed VP1 proteins from two distantly related HRV strains, HRV89 and HRV14, in Escherichia coli . Mice and rabbits were immunised with the purified recombinant proteins. The induced antibodies reacted with natural VP1 and with whole virus particles as shown by immunoblotting and immunogold electron microscopy. They exhibited strong cross-neutralising activity for different HRV strains. Therefore, recombinant VP1 may be considered a candidate HRV vaccine to prevent HRV-induced asthma exacerbations.
The clinical utility of screening of biochemical parameters in elite athletes: analysis of 100 cases
Authors: K E Fallon
Journal: British Journal of Sports Medicine (2007)

To determine the clinical utility of screening for biochemical parameters in elite athletes.A prospective sequential case series.The Department of Sports Medicine at the Australian Institute of Sport.100 elite athletes from 11 sports (56 male and 44 female athletes, mean age 19 years, range 16-27), undergoing routine medical screening.Initial and follow-up assessment of the following biochemical parameters in association with clinical assessment; serum iron, ferritin, transferrin, percent transferrin saturation, sodium, potassium, chloride, calcium, magnesium, phosphate, urate, urea and creatinine, total protein, albumin, creatine kinase (CK), lactate dehydrogenase, aspartate aminotransaminase (AST), alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin, cholesterol and triglycerides (non-fasting), and random glucose.18 athletes showed no abnormalities on biochemical screening. 194 abnormal results were found in 82 athletes. 115 abnormalities were noted in 46 male and 79 in 36 female athletes. In 43 individual tests, the results did not return to normal on repeat testing. The most common abnormalities were increases in AST (27%), phosphate (13%), CK (13%), urea (12%) and bilirubin (12%). Three cases of hypercholesterolaemia and one case of haemochromatosis were identified, and one athlete, who was asymptomatic, was diagnosed with Epstein-Barr virus infection, which was suspected because of an abnormal liver function test. The other abnormalities found appeared not to be of clinical significance.Most abnormalities found on routine biochemical screening in elite athletes are of no clinical significance, therefore such testing should, if used only for clinical purposes, be abandoned. When athletes are tested for iron status it would be prudent to include assessment of serum cholesterol in those with a family history of hyperlipidaemia.
Phase III Randomized Trial of Doxorubicin and Docetaxel Versus Doxorubicin and Cyclophosphamide As Primary Medical Therapy in Women With Breast Cancer: An Anglo-Celtic Cooperative Oncology Group Study
Authors: T.R. Jeffry Evans, Ann Yellowlees, Elizabeth Foster, Helena Earl, David A. Cameron, Andrew W. Hutcheon, Robert E. Coleman, Timothy Perren, Christopher J. Gallagher, Mary Quigley, John Crown, Alison L. Jones, Martin Highley, Robert C.F. Leonard, Janine L. Mansi
Journal: Journal of Clinical Oncology (2005)

Purpose To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. Patients and Methods Eligible patients with histologically proven breast cancer with primary tumors ≥ 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m 2 ) plus cyclophosphamide (600 mg/m 2 ) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m 2 ) plus docetaxel (75 mg/m 2 ) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. Conclusion In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.
C2238 Atrial Natriuretic Peptide Molecular Variant Is Associated With Endothelial Damage and Dysfunction Through Natriuretic Peptide Receptor C Signaling
Authors: Sebastiano Sciarretta, Simona Marchitti, Franca Bianchi, Amie Moyes, Emanuele Barbato, Sara Di Castro, Rosita Stanzione, Maria Cotugno, Lorenzo Castello, Camilla Calvieri, Ivano Eberini, Junichi Sadoshima, Adrian J. Hobbs, Massimo Volpe, Speranza Rubattu
Journal: Circulation Research (2013)

C2238 atrial natriuretic peptide (ANP) minor allele (substitution of thymidine with cytosine in position 2238) associates with increased risk of cardiovascular events.We investigated the mechanisms underlying the vascular effects of C2238-αANP.In vitro, human umbilical vein endothelial cell were exposed to either wild-type (T2238)- or mutant (C2238)-αANP. Cell survival and apoptosis were tested by Trypan blue, annexin V, and cleaved caspase-3 assays. C2238-αANP significantly reduced human umbilical vein endothelial cell survival and increased apoptosis. In addition, C2238-αANP reduced endothelial tube formation, as assessed by matrigel. C2238-αANP did not differentially modulate natriuretic peptide receptor (NPR)-A/B activity with respect to T2238-αANP, as evaluated by intracellular cGMP levels. In contrast, C2238-αANP, but not T2238-αANP, markedly reduced intracellular cAMP levels in an NPR-C-dependent manner. Accordingly, C2238-αANP showed higher affinity binding to NPR-C, than T2238-αANP. Either NPR-C inhibition by antisense oligonucleotide or NPR-C gene silencing by small interfering RNA rescued survival and tube formation of human umbilical vein endothelial cell exposed to C2238-αANP. Similar data were obtained in human aortic endothelial cell with NPR-C knockdown. NPR-C activation by C2238-αANP inhibited the protein kinase A/Akt1 pathway and increased reactive oxygen species. Adenovirus-mediated Akt1 reactivation rescued the detrimental effects of C2238-αANP. Overall, these data indicate that C2238-αANP affects endothelial cell integrity through NPR-C-dependent inhibition of the cAMP/protein kinase A/Akt1 pathway and increased reactive oxygen species production. Accordingly, C2238-αANP caused impairment of acetylcholine-dependent vasorelaxation ex vivo, which was rescued by NPR-C pharmacological inhibition. Finally, subjects carrying C2238 minor allele showed early endothelial dysfunction, which highlights the clinical relevance of our results.C2238-αANP reduces endothelial cell survival and impairs endothelial function through NPR-C signaling. NPR-C targeting represents a potential strategy to reduce cardiovascular risk in C2238 minor-allele carriers.
Association of Coffee and Caffeine Intake With the Risk of Parkinson Disease
Authors: G. Webster Ross
Journal: JAMA (2000)

The projected expansion in the next several decades of the elderly population at highest risk for Parkinson disease (PD) makes identification of factors that promote or prevent the disease an important goal.To explore the association of coffee and dietary caffeine intake with risk of PD.Data were analyzed from 30 years of follow-up of 8004 Japanese-American men (aged 45-68 years) enrolled in the prospective longitudinal Honolulu Heart Program between 1965 and 1968.Incident PD, by amount of coffee intake (measured at study enrollment and 6-year follow-up) and by total dietary caffeine intake (measured at enrollment).During follow-up, 102 men were identified as having PD. Age-adjusted incidence of PD declined consistently with increased amounts of coffee intake, from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d (P<.001 for trend). Similar relationships were observed with total caffeine intake (P<.001 for trend) and caffeine from non-coffee sources (P=.03 for trend). Consumption of increasing amounts of coffee was also associated with lower risk of PD in men who were never, past, and current smokers at baseline (P=.049, P=.22, and P=.02, respectively, for trend). Other nutrients in coffee, including niacin, were unrelated to PD incidence. The relationship between caffeine and PD was unaltered by intake of milk and sugar.Our findings indicate that higher coffee and caffeine intake is associated with a significantly lower incidence of PD. This effect appears to be independent of smoking. The data suggest that the mechanism is related to caffeine intake and not to other nutrients contained in coffee. JAMA. 2000;283:2674-2679.
The effects of different inhaler devices on asthma control in patients with persistent asthma in Turkey
Authors: Füsun Yildiz, Serap Akcali, Nese Dursunoglu
Journal: European Respiratory Journal (2012)

AIM

Persistent asthma is a chronic condition treated with continuous use of inhaler devices and stringent courses of follow-up as inhalers requires compliance and close follow-up. We aimed to investigate the effective use of inhaler devices in persistent asthma patients through patient and physician questionnaires.

METHODS

Patient and physician questionnaires were implemented for basic application procedures of inhalers, including trainings. Physicians evaluation of asthma control was performed by ACT™.

RESULTS

A total of 572 patients were enrolled at 31 centres. Evaluation of basic inhalation techniques; showed common errors; omitting exhaling before inhalation (10-15 %), mouth rinsing or incorrect inhalation (20 %) and omission of mouth rinsing. Evaluation of asthma control was performed at baseline and following visits, 22 % of asthma patients were under control at baseline, increasing to 43%. Fixed combination inhalers BDP/F solution spray, F/S discus, B/F Turbuhaler significantly reduced the rate of uncontrolled patients by p=0.004, p<0.001, p=0.003 respectively where no significant decrease was seen with B+F Aerolizer for related asthmatic group (p=0.13).

View this table:

Table 1. Asthma treatment with inhalers, % of uncontrolled asthma (n=572 patients)





CONCLUSION

This study collected information on specific use of inhaler devices in persistent asthma patients and a correlation in a balanced perception of use for every device by physicians and patients were shown.
The Role of Oxidative Stress in Carcinogenesis
Authors: James E. Klaunig, Lisa M. Kamendulis
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Chemical carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to carcinogenesis, the unregulated or prolonged production of cellular oxidants has been linked to mutation (induced by oxidant-induced DNA damage), as well as modification of gene expression. In particular, signal transduction pathways, including AP-1 and NFkappaB, are known to be activated by reactive oxygen species, and they lead to the transcription of genes involved in cell growth regulatory pathways. This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT
Authors: Mobin A. Karimi, Jerrod L. Bryson, Lee P. Richman, Andrew D. Fesnak, Theresa M. Leichner, Atsushi Satake, Robert H. Vonderheide, David H. Raulet, Ran Reshef, Taku Kambayashi
Journal: Blood (2015)
Bronchial reactivity indices are determinants of health-related quality of life in patients with stable asthma
Authors: C. Cisneros, F. Garcia-Rio, D. Romera, C. Villasante, R. Giron, J. Ancochea
Journal: Thorax (2010)

<h3>Background</h3> A very weak relationship has been reported between the health-related quality of life (HRQL) of patients with asthma and their degree of airway hyper-responsiveness (AHR), evaluated in terms of sensitivity. However, this relationship still has not been sufficiently explored for bronchial reactivity indices. <h3>Objectives</h3> To analyse the relationship between bronchial reactivity and sensitivity with the HRQL of patients with stable asthma, identifying the functional parameters that determine HRQL. <h3>Methods</h3> In 103 consecutive patients with stable asthma, HRQL was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). Patients underwent spirometry and non-specific bronchial provocation with methacoline. Sensitivity (PD<sub>20</sub>) and reactivity (dose–response slope (DRS), continuous index of responsiveness (CIR) and bronchial reactivity index (BRI)) of the dose–response curve were analysed. <h3>Results</h3> BRI presented significant differences with different degrees of asthma severity. Although patients with AHR showed poorer quality of life than patients without AHR, the AQLQ total score was not related to PD<sub>20</sub> but rather to DRS (r=−0.784), CIR (r=−0.712) and BRI (r=−0.776). The indices of bronchial reactivity reached a negative correlation with all the domains of the AQLQ. In a multiple linear regression model, BRI, DRS, FIV<sub>1</sub> (forced inspiratory volume in 1 s) and VCIN (inspiratory vital capacity) were identified as independent predictors of the AQLQ total score (r<sup>2</sup>=0.742, p&lt;0.001). <h3>Conclusion</h3> In patients with stable asthma, bronchial reactivity is associated with HRQL. This could justify incorporating bronchial reactivity indices in bronchial provocation analyses.