tbuckley/cabot-search huggingface dataset:
MLH1 -93G&gt;A Promoter Polymorphism and the Risk of Microsatellite-Unstable Colorectal Cancer
Authors: S. Raptis, M. Mrkonjic, R. C. Green, V. V. Pethe, N. Monga, Y. M. Chan, D. Daftary, E. Dicks, B. H. Younghusband, P. S. Parfrey, S. S. Gallinger, J. R. McLaughlin, J. A. Knight, B. Bapat
Journal: JNCI Journal of the National Cancer Institute (2007)

Although up to 30% of patients with colorectal cancer have a positive family history of colorectal neoplasia, few colorectal cancers can be explained by mutations in high-penetrance genes. We investigated whether polymorphisms in DNA mismatch repair genes are associated with the risk of colorectal cancer. We genotyped 929 case patients and 1098 control subjects from Ontario and 430 case patients and 275 control subjects from Newfoundland and Labrador for five polymorphisms in the mismatch repair genes MLH1 and MSH2 with the fluorogenic 5′ nuclease assay. Tumor microsatellite instability (MSI) was determined with a polymerase chain reaction–based method; MSI status was assigned as high (MSI-H, ≥30% unstable markers among all markers tested), low (MSI-L, <30% markers unstable), or stable (MSS, no unstable markers). We used unconditional logistic regression to evaluate the association between each polymorphism and colorectal cancer after adjusting for age and sex. The associations between polymorphisms and tumor clinicopathologic features were evaluated with a Pearson's chi-square or Fisher's exact test. All statistical tests were two-sided. We observed strong associations between the MLH1 –93G>A polymorphism and MSI-H tumors among case patients from Ontario ( P = .001) and Newfoundland ( P = .003). When compared with the control populations, homozygosity for the MLH1 –93G>A variant allele was associated with MSI-H tumors among case patients in Ontario (adjusted odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.65 to 6.30) and in Newfoundland (OR = 8.88, 95% CI = 2.33 to 33.9), as was heterozygosity among case patients in Ontario (OR = 1.84, 95% CI = 1.20 to 2.83) and in Newfoundland (OR = 2.56, 95% CI = 1.14 to 5.75). Genotype frequencies were similar among case patients with MSS and MSI-L tumors and control subjects, and the majority of homozygous variant carriers had MSS tumors. Among case patients from Ontario, an association between the MLH1 –93G>A polymorphism and a strong family history of colorectal cancer (for Amsterdam criteria I and II, P = .004 and P = .02, respectively) was observed. In two patient populations, the MLH1 –93G>A polymorphism was associated with an increased risk of MSI-H colorectal cancer.
Ginseng and Ginsenoside Re Do Not Improve β-Cell Function or Insulin Sensitivity in Overweight and Obese Subjects With Impaired Glucose Tolerance or Diabetes
Authors: Dominic N. Reeds, Bruce W. Patterson, Adewole Okunade, John O. Holloszy, Kenneth S. Polonsky, Samuel Klein
Journal: Diabetes Care (2011)

OBJECTIVE Ginseng and its active component, ginsenoside Re, are popular herbal products that are advocated for treatment of diabetes. The purpose of this study was to determine whether ginseng or ginsenoside Re improves β-cell function and insulin sensitivity (IS) in insulin-resistant subjects. RESEARCH DESIGN AND METHODS Overweight or obese subjects (BMI = 34 ± 1 kg/m2) with impaired glucose tolerance or newly diagnosed type 2 diabetes were randomized to 30 days of treatment with ginseng root extract (8 g/day), ginsenoside Re (250–500 mg/day), or placebo. β-Cell function was assessed as the disposition index (DI) and measured by a frequently sampled oral glucose tolerance test, and IS was assessed as the relative increase in glucose disposal during a hyperinsulinemic-euglycemic clamp procedure plus stable isotope tracer infusion. RESULTS Values for DI and IS after therapy (Post) were not different from values before therapy (Pre) in the placebo (DI: Pre, 5.8 ± 0.9 × 10−3 and Post, 5.8 ± 0.8 × 10−3, P = 0.99; IS: Pre,165 ± 29% and Post, 185 ± 24%, P = 0.34), ginseng (DI: Pre, 7.7 ± 2.0 × 10−3 and Post, 6.0 ± 0.8 × 10−3, P = 0.29; IS: Pre, 171 ± 72% and Post,137 ± 59%, P = 0.88), and ginsenoside Re (DI: Pre, 7.4 ± 3.0 × 10−3 and Post, 5.9 ± 1.1 × 10−3, P = 0.50; IS: Pre, 117 ± 31% and Post, 134 ± 34%, P = 0.44) groups. Ginsenosides Re, Rb1, and Rb2 were not detectable in plasma after treatment with ginseng root extract or ginsenoside Re. CONCLUSIONS Oral ginseng or ginsenoside Re therapy does not improve β-cell function or IS in overweight/obese subjects with impaired glucose tolerance or newly diagnosed diabetes. Poor systemic bioavailability might be responsible for the absence of a therapeutic effect.
Using infertile patients in epidemiologic studies on subfecundity and embryonal loss
Authors: J. Olsen, J.P. Bonde, N.H. Hjøllund, O. Basso, E. Ernst
Journal: Human Reproduction Update (2005)

Subfecundity is a frequent and serious problem that may sometimes be preventable, but we need to know more about its determinants. Different epidemiologic designs are available. The best of these use prospectively collected data from the population, but they are time consuming, expensive and often hampered by low-participation rates. Most patients undergoing infertility treatment are closely monitored for clinical reasons, making it feasible to use secondary data to study the period from conception to implantation and pregnancy. In spite that infertility patients are highly selected, there are specific exposure-effect relations that can be studied in cohorts of infertility patients. These patients offer a potentially useful setting for studying exposures that operate late in fertilization, whereas the designs may be inadequate to identify exposures that cause reduced sperm counts, anovulation and total occlusion. The clinical sampling and the treatment set limitations for what can be studied. In certain situations, infertile patients can, however, provide useful epidemiologic evidence for learning about the causes of subfecundity.
PARENTERAL ACYCLOVIR THERAPY FOR HERPESVIRUS INFECTIONS IN MAN
Authors: P.J. Selby, Beryl Jameson, J.G. Watson, G. Morgenstern, R.L. Powles, H.E.M. Kay, R. Thornton, H.M. Clink, T.J. Mcelwain, H.G. Prentice, M.G. Ross, R. Corringham, A.V. Hoffbrand, D. Brigden
Journal: The Lancet (1979)
The primary defect in experimental ileitis originates from a nonhematopoietic source
Authors: Timothy S. Olson, Brian K. Reuter, Kevin G-E. Scott, Margaret A. Morris, Xiao-Ming Wang, Leslie N. Hancock, Tracy L. Burcin, Steven M. Cohn, Peter B. Ernst, Fabio Cominelli, Jonathan B. Meddings, Klaus Ley, Theresa T. Pizarro
Journal: The Journal of Experimental Medicine (2006)

The initiating etiologic factor in Crohn's disease (CD) remains unclear. SAMP1/YitFc (SAMP) mice develop chronic ileitis similar to human CD. We used bone marrow chimeras to determine if SAMP ileitis results from a primary immunological defect or from dysregulated mucosal immunity secondary to intrinsic, nonhematopoietic (e.g., epithelial) dysfunction. SAMP mice receiving wild-type (AKR) BM developed severe ileitis, whereas SAMP BM did not confer ileitis to WT recipients. WT lymphocytes from reconstituted SAMP mice resembled native SAMP populations in regard to surface phenotype and cytokine production. Ilea from native SAMP mice and SAMP recipients of wild-type BM displayed decreased epithelial barrier resistance ex vivo and increased epithelial permeability in vivo compared to native WT mice and AKR recipients of SAMP BM. This permeability defect preceded the development of ileal inflammation, was present in the absence of commensal bacteria, and was accompanied by altered ileal mRNA expression of the tight junction proteins claudin-2 and occludin. Our results provide evidence that the primary defect conferring ileitis in SAMP mice originates from a nonhematopoietic source. Generation of pathogenic lymphocytes is a consequence of this defect and does not reflect intrinsic proinflammatory leukocyte properties. Decreased barrier function suggests that defects in the epithelium may represent the primary source of SAMP ileitis susceptibility.
Interventions with Family Caregivers of Cancer Patients: Meta-Analysis of Randomized Trials
Authors: Laurel L. Northouse, Maria C. Katapodi, Lixin Song, Lingling Zhang, Darlene W. Mood
Journal: CA A Cancer Journal for Clinicians (2010)

Family caregivers of cancer patients receive little preparation, information, or support to perform their caregiving role. However, their psychosocial needs must be addressed so they can maintain their own health and provide the best possible care to the patient. The purpose of this article is to analyze the types of interventions offered to family caregivers of cancer patients, and to determine the effect of these interventions on various caregiver outcomes. Meta-analysis was used to analyze data obtained from 29 randomized clinical trials published from 1983 through March 2009. Three types of interventions were offered to caregivers: psychoeducational, skills training, and therapeutic counseling. Most interventions were delivered jointly to patients and caregivers, but they varied considerably with regard to dose and duration. The majority of caregivers were female (64%) and Caucasian (84%), and ranged in age from 18 to 92 years (mean age, 55 years). Meta-analysis indicated that although these interventions had small to medium effects, they significantly reduced caregiver burden, improved caregivers' ability to cope, increased their self-efficacy, and improved aspects of their quality of life. Various intervention characteristics were also examined as potential moderators. Clinicians need to deliver research-tested interventions to help caregivers and patients cope effectively and maintain their quality of life.
Ocular toxicity and hydroxychloroquine: guidelines for screening
Authors: None JONES
Journal: British Journal of Dermatology (1999)

Chloroquine and hydroxychloroquine (4-aminoquinolones) are used by dermatologists for the treatment of a wide range of disorders. It is widely recognized that their use may lead to ocular complications, but policies for ophthalmological screening and follow-up vary widely. In this article, the current literature on the ocular complications of antimalarials is reviewed, together with the results of a recent survey of dermatological practice on screening. New recommendations for ophthalmological screening recently produced by the Royal College of Ophthalmologists, the British Association of Dermatologists and the British Association of Rheumatologists are presented. It is recommended that baseline screening should include an assessment of renal and liver function, an enquiry about visual impairment and the recording of near visual acuity. Follow-up should comprise an enquiry about visual problems at each clinic visit and assessment of visual acuity once yearly. The multidisciplinary nature of the committee producing the new guidelines will hopefully mean that they will be acceptable to and useable by all those who routinely prescribe antimalarial drugs.
Knocking Down Ca<sub>v</sub>1 Calcium Channels Implicated in Th2 Cell Activation Prevents Experimental Asthma
Authors: Marilena Djata Cabral, Pierre-Emmanuel Paulet, Virginie Robert, Bruno Gomes, Marie-Laure Renoud, Magali Savignac, Catherine Leclerc, Marc Moreau, David Lair, Marie Langelot, Antoine Magnan, Hans Yssel, Bernard Mariamé, Jean-Charles Guéry, Lucette Pelletier
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Th2 cells orchestrate allergic asthma and the cytokines they produce (IL-4, IL-5, and IL-13) are deleterious in allergy. Therefore, it is important to identify key signaling molecules expressed by Th2 cells that are essential for their function. We have previously shown that dihydropyridines selectively modulate Th2 cell functions.Because dihydropyridines bind to and modulate voltage-dependent calcium (Ca(v)1) channel in excitable cells, we aimed at showing that Th2 cells selectively express functional Ca(v)1-related channels, the inhibition of which may prevent asthma.We looked for Ca(v)1 channel expression in Th2 and Th1 cells by real-time polymerase chain reaction and Western blotting. We sequenced the isoforms expressed by Th2 cells and tested whether Ca(v)1 antisense oligodeoxynucleotides (Ca(v)1AS) affected Ca(2+) signaling and cytokine production. Finally, we tested the effect of Ca(v)1AS in the passive asthma model by injection of ovalbumin-specific Th2 cells transfected with Ca(v)1AS into BALB/c mice challenged with intranasal ovalbumin and in the active model of asthma by intranasal delivery of Ca(v)1AS together with soluble ovalbumin in BALB/c mice previously immunized with ovalbumin in alum.We show that mouse Th2 but not Th1 cells expressed Ca(v)1.2 and Ca(v)1.3 channels. Th2 cells transfected with Ca(v)1AS had impaired Ca(2+) signaling and cytokine production, and lost their ability to induce airway inflammation on adoptive transfer. Furthermore, intranasal administration of Ca(v)1AS suppressed airway inflammation and hyperreactivity in an active model of asthma.These results indicate that Th2 cells selectively express Ca(v)1 channels that may be efficiently targeted in T lymphocytes to prevent experimental asthma.
Standards of Care in Geriatric Practice
Authors: Robert J. Luchi, Julie K. Gammack, Victor J. Narcisse, C. Porter Storey
Journal: Annual Review of Medicine (2003)

We propose a set of standards to aid the physician in the care of older patients. These standards are based on the practical experiences of our own group and of others with years of clinical practice in geriatric medicine. The standards also reflect the guidelines, position papers, and deliberations of various organizations concerned with the care of older people. This article does not discuss specific illnesses or the common geriatric syndromes. The proposed standards cover comprehensive care and assessment, especially of vulnerable elders and prevention of disease and disability. We also propose standards for facilitation of care across the health service continuum, care of the nursing home resident, and palliative and hospice care.
Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice
Authors: Jinlu Dai, Dinlii Lin, Jian Zhang, Paula Habib, Peter Smith, Jill Murtha, Zheng Fu, Zhi Yao, Yinghua Qi, Evan T. Keller
Journal: Journal of Clinical Investigation (2000)

To investigate the role of IL-6 in alcohol-mediated osteoporosis, we measured a variety of bone remodeling parameters in wild-type (il6+/+) or IL-6 gene knockout (il6–/–) mice that were fed either control or ethanol liquid diets for 4 months. In the il6+/+ mice, ethanol ingestion decreased bone mineral density, as determined by dual-energy densitometry; decreased cancellous bone volume and trabecular width and increased trabecular spacing and osteoclast surface, as determined by histomorphometry of the femur; increased urinary deoxypyridinolines, as determined by ELISA; and increased CFU-GM formation and osteoclastogenesis as determined ex vivo in bone marrow cell cultures. In contrast, ethanol ingestion did not alter any of these parameters in the il6–/– mice. Ethanol increased receptor activator of NF-κB ligand (RANKL) mRNA expression in the bone marrow of il6+/+ but not il6–/– mice. Additionally, ethanol decreased several osteoblastic parameters including osteoblast perimeter and osteoblast culture calcium retention in both il6+/+ and il6–/– mice. These findings demonstrate that ethanol induces bone loss through IL-6. Furthermore, they suggest that IL-6 achieves this effect by inducing RANKL and promoting CFU-GM formation and osteoclastogenesis.
Intraluminal flow-initiated hyperpolarization and depolarization shift the membrane potential of arterial smooth muscle toward an intermediate level.
Authors: J A Bevan, G C Wellman
Journal: Circulation Research (1993)

We examined the effect of intraluminal flow of physiological saline on the membrane potential of vascular smooth muscle cells in isolated rabbit cerebral arteries. Intraluminal flow (20 microL/min) caused a depolarization of 4.8 +/- 0.7 mV in muscle cells with a resting membrane potential of -62.5 +/- 1.2 mV (n = 19). However, when cells were depolarized to -48.7 +/- 1.8 mV using histamine and serotonin, the response to intraluminal flow was the opposite, a hyperpolarization of 5.6 +/- 1.0 mV (n = 9). These opposing effects of flow on membrane potential appear to balance at -57.8 +/- 1.1 mV (n = 31). Our results suggest that intraluminal flow may affect the level of basal tone present in arteries in vivo through modulating the membrane potential of vascular smooth muscle cells by concurrently activated depolarization and hyperpolarization.
CpG Island Methylator Phenotype Involving Chromosome 3p Confers an Increased Risk of Non-small Cell Lung Cancer
Authors: Zeyi Liu, Wenwen Li, Zhe Lei, Jun Zhao, Xiao-Feng Chen, Rengyun Liu, Xiaobei Peng, Zhi-hao Wu, Jun Chen, Hongyu Liu, Qing-Hua Zhou, Hong-Tao Zhang
Journal: Journal of Thoracic Oncology (2010)
Catatonia in Psychiatric Classification: A Home of Its Own
Authors: Michael Alan Taylor, Max Fink
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors assess the present position of catatonia in diagnostic classification systems and consider the merits of designating catatonia as a separate diagnostic category with defined criteria. METHOD: Following the logical steps to establish diagnostic validity when the etiology of a syndrome is unknown, the authors review the literature on the features that delineate catatonia as a syndrome, the prevalence and response to treatment of catatonia, and the conditions that are associated with catatonia. RESULTS: Catatonia is a well-defined syndrome that can be reliably ascertained. Although more than 40 motor signs of catatonia are known, the presence of two prominent features for 24 hours or longer is sufficient to identify the syndrome. Catatonia is found in about 10% of acutely ill psychiatric inpatients and is more commonly observed in persons with mood disorder than in those with schizophrenia. It is found in many conditions and presents mainly as retarded-stuporous or excited-delirious forms. Catatonia responds to specific treatments, including sedative anticonvulsants (barbiturates and benzodiazepines) and ECT. CONCLUSIONS: Catatonia can be distinguished from other behavioral syndromes by a recognizable cluster of clinical features. Catatonia is sufficiently common to warrant classification as an independent syndrome. It can be reliably identified, has a typical course when appropriately treated, responds to specific treatments, and is worsened by other treatments. It is associated with many pathophysiologic processes and most often with mood disorder. These findings, which are consistent with established methods of defining distinct diagnostic groupings, support consideration of catatonia as an individual category in psychiatric diagnostic systems.
Exhaled Ethane, a Marker of Lipid Peroxidation, Is Elevated in Chronic Obstructive Pulmonary Disease
Authors: PAOLO PAREDI, SERGEI A. KHARITONOV, DAVID LEAK, SIMON WARD, DAVID CRAMER, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Ethane is a product of lipid peroxidation and can be measured in the exhaled air as an index of oxidative stress. Oxidant/antioxidant imbalance is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, we measured exhaled ethane in 22 patients with COPD (mean age ± SEM, 59 ± 8 yr; 19 male) and compared it with other noninvasive markers of oxidative stress and inflammation such as carbon monoxide (CO), measured electrochemically, and nitric oxide (NO), measured by chemiluminescence. Exhaled ethane was collected during a flow and pressure-controlled exhalation into a reservoir, discarding dead space air contaminated with ambient air. A sample of the collected expired air was analyzed by chromatography. Compared with normal subjects (n = 14; eight men; age, 33 ± 2.8 yr), patients with COPD not on steroid treatment (n = 12; FEV1, 58 ± 6%) had elevated levels of exhaled ethane (2.77 ± 0.25 and 0.88 ± 0.09 ppb, respectively, p < 0.05), CO (5.96 ± 0.50 and 2.8 ± 0.25 ppm, p < 0.05) and NO (11.86 ± 0.53 and 6.77 ± 0.50 ppb, p < 0.05) levels. Ethane was correlated to FEV1 (r = − 0.67, p < 0.05). Patients receiving steroid treatment (n = 10; FEV1, 56 ± 2%) had lower levels of ethane (0.48 ± 0.05 ppb) than did steroid-treated patients, whereas CO (5.99 ± 0.63 ppm) and NO (9.11 ± 0.53 ppb) levels were similar in the two treatment groups. Exhaled ethane is elevated, correlates with FEV1, and is significantly lower in patients treated with steroids, so it may be complementary to the use of NO and CO in assessing and monitoring oxidative stress in COPD.
A doubling of admissions due to diverticular disease in Scottish hospitals, in the last 14 years
Authors: I. Arnott, H. Paterson, R. J. Nicholls, A. Crowe, A. Knight, D. Clark, J. Bauer, L. Yen, P. Hodgkins, M. Dunlop
Journal: Gut (2011)

<h3>Introduction</h3> Information on the epidemiology and burden of diverticular disease (DD) requiring hospitalisation is limited. The study reviewed DD admissions in Scotland in the last 14 years. <h3>Methods</h3> The Scottish national record linkage database was used to assess day case and inpatient hospital admissions from April1 1996 to 31 March 2010 for DD (ICD10 K57). Cases selected were Scottish residents with coding of DD as primary diagnosis on the Scottish Morbidity Record (SMR01). Continuous inpatient stays (CIS) were assessed to include intra-department and inter-hospital transfers. Age, gender and length of stay (LOS) associated with DD were compared to admissions for other gastrointestinal problems in the same period. <h3>Results</h3> Hospital admissions with a primary DD diagnosis increased by 107% over the 14 years (5284 in 1996–1997 to 10,935 in 2009–2010), compared with a 20% increase in admissions for general primary gastrointestinal diagnoses (excluding DD) during the same period. The proportion of DD admissions by age remained largely consistent, but over the 14 years, more women were admitted than men (61% vs 39%), most notably in those over 50 years (65,571♀ vs 39,558♂). Mean LOS for all cases decreased from 6.4 to 3.2 days and mean inpatient LOS from 10.6 to 8.8 days. The rise in DD admissions was almost entirely due to admissions ≤1 day (2562 in 1996–1997, 7893 in 2009–2010). Of these, 74% related to diagnostic colonoscopy/sigmoidoscopy (2158 in 1996–1997, 6089 in 2009–2010). Patients were most often admitted under General Surgery (71%), Gastroenterology (16%) or General Medicine (10%). Of 7893 admissions ≤1 day in 2009–2010, 6089 were for colonoscopy/sigmoidoscopy, and 91% (7186) had an admission reason recorded. Acute medical care or treatment was coded in 69% (3822) of colonoscopy episodes and 67% (1100) of other episodes, with investigation only coded in 31% (1711) and 33% (553), respectively. Only 2.7% of admissions ≤1 day were emergency, with 15% undergoing colonoscopy. <h3>Conclusion</h3> Admissions for DD in Scotland increased considerably between 1996 and 2010. Most of this rise is attributable to admissions ≤1 day for colonoscopy/sigmoidoscopy, but 26% of the rise in admissions ≤1 day was attributable to non-diagnostic admissions where acute treatment was undertaken, adding to the healthcare burden.