tbuckley/cabot-search huggingface dataset:
Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial
Authors: Marc G. Ghany, Hae-Young Kim, Anne Stoddard, Elizabeth C. Wright, Leonard B. Seeff, Anna S.F. Lok
Journal: Hepatology (2011)

Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (HALT-C) trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C. Patients randomized to no treatment and who had ≥2-year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio, total bilirubin, and albumin) with three categories of change (stable, mild, or severe) over 2 years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome. In all, 470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values. A model that included baseline platelet count, AST/ALT ratio, bilirubin, and severe worsening of platelet count, bilirubin, and albumin was the best predictor of clinical decompensation. A total of 483 patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor of liver-related outcomes. Conclusion: Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C. (Hepatology 2011;)
Transient monoclonal gammopathy in hydralazine-induced lupus erythematosus.
Authors: S Freestone, L E Ramsay
Journal: BMJ (1982)

The diastolic pressure in the hypertensive compared with the normotensive subjects showed a distinctly different pattern of response at maximum exercise: in the patients it rose by 11±2 mm Hg while in the normotensive subjects there was no change.A repeat test in eight hypertensive patients three to six months later yielded nearly identical results.225 200 < 175 JfmmHg) 125 , .,. 100 .B , -' 75mm dfE -,-50 0 3 6 9 -15 Timne(min)'.eO-3000 4500 s 0oo 0 N mlrrin Blood-pressure response to graded exercise in untreated hypertensive subjects (n=35) plotted against nomogram obtained from results in normal individuals (n=28).Unbroken line of nomogram represents mean blood pressures; broken line represents mean + 1-65 SD; and hatched area shows upper boundary of 954, confidence limit.Conversion: SI to traditional units-1 N m 0 1 kp m. CommentAn illness characterised byweight loss, ill health, hepatosplenomegaly, a high erythrocyte sedimentation rate, pancytopenia, low albumin and high globulin concentrations, and a high titre of antinuclear factor occurring in a slow acetylator 18 months after the start of treatment on 19 August
Acute gluten challenge in treated adult coeliac disease: a morphometric and enzymatic study.
Authors: M G Bramble, S Zucoloto, N A Wright, C O Record
Journal: Gut (1985)

Using a Quinton hydraulic biopsy tube, jejunal biopsies were obtained from 10 patients with adult coeliac disease in remission and four healthy volunteers before and after administration of gluten fraction III into the proximal duodenum. The biopsies taken at hourly intervals for four hours, were analysed for changes in brush border enzymes, light microscopic appearances, and villous and crypt population counts. The results indicate that mucosal damage occurs within three to four hours of gluten administration with significant falls in brush border enzyme concentrations and villous population counts. The absence of any change in control biopsies indicates that gluten sensitivity is specific to the mucosa of patients with coeliac disease, the timing of the changes being consistent with a type III immune response or direct toxicity. Some recovery of the brush border enzymes but not the villous population was evident 24 hours after gluten administration while the crypt population showed evidence of a compensatory hyperplastic reaction.
Abstract P4-10-14: Risk of Ipsilateral Breast Events in Patients with Ductal Carcinoma In Situ after Local Excision
Authors: M Yi, HM Kuerer, A Lucci, F Meric-Bernstam, GV Babiera, CL Thomas, MI Ross, KK. Hunt
Journal: Cancer Research (2010)

Abstract Purpose To determine the risk of ipsilateral breast events (IBE) in patients with ductal carcinoma in situ (DCIS) treated with local excision. Patients and Methods We retrospectively identified 692 patients who had undergone local excision from 1968 through 2007 at our institution with a final diagnosis of DCIS. Factors evaluated included age, race, method of detection, menopausal status, bloody nipple discharge, histological type, final margin status, grade, status at last follow-up and recurrence information. An IBE was defined as the development of breast cancer of invasive histology or DCIS (but not lobular carcinoma in situ) in the treated breast. Results At a median follow-up of 6.1 years, 47 (6.8%) IBEs occurred in the 692 patients. Among 47 IBE, 23 (48.9%) were DCIS and 19 (40%) were invasive cancer and 5 (10.6%) were unknown type of IBE. Patients with IBE were younger (53 Vs 57, P=0.04). Whether patients had final positive margin (4 patients) had no influence on IBE. Use of a Cox proportional hazards model showed that patients with high grade tumors and those who did not receive adjuvant radiation therapy (XRT) were more likely to have an IBE (Hazard ratio: 4.1, 95% CI:1.3-13.4, P=0.019). The 5-year rate of ipsilateral breast events for patients with grade III DCIS who did not undergo adjuvant radiation therapy was significantly higher than all others: 15% vs. 4.6% compared to grade I/II with XRT, 15% vs. 10% compared to grade I/II without XRT, and 15% vs. 9.9% in grade III with XRT (P=0.017). Conclusions Patients with low or intermediate grade DCIS have an acceptably low rate of ipsilateral breast events after local excision with adjuvant radiation therapy. Patients with high-grade lesions treated without irradiation have a rate of IBE of 15% at 6 years, suggesting that excision alone is inadequate treatment in this group. Further follow-up is necessary to document long-term results. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-14.
Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study.
Authors: S Kansal, D Roitman, L T Sheffield
Journal: Circulation (1979)

Septal and left ventricular posterior wall (LVPW) thicknesses and their ratios were studied at the left ventricular outflow tract and left ventricular cavity in 66 patients with echocardiographically diagnosed left ventricular concentric hypertrophy, 20 with idiopathic hypertrophic subaortic stenosis (IHSS), and 34 normal subjects. Concentric hypertrophy was due to hypertension in 41 subjects and to valvular disease in 15 subjects. Septal thickness in normal subjects was related to body surface area (p less than 0.02). In 12% of normal subjects, 39% of patients with concentric hypertrophy and 95% with IHSS, the septal/LVPW ratio was greater than or equal to 1.3. Thirty-two percent of patients with hypertension, 78% with aortic stenosis, and 60% with aortic insufficiency had septal/LVPW ratios greater than or equal to 1.3 at left ventricular midcavity level. In conclusion, a septal/LVPW thickness ratio of greater than or equal to 1.3 is common in patients with concentric left ventricular hypertrophy and may also occur in normal subjects. A ratio greater than or equal to 1.5 may be more specific for genetically determined asymmetric septal hypertrophy.
Abstract 2019: Investigation of cell death mediated by poly(ADP-ribose), Apoptosis-Inducing Factor (AIF) and caspases in breast cancer cells by RNA interference
Authors: Xiaoxing Feng, Alicia Proctor, Mandi Hopkins, Mengwei Liu, David W. Koh
Journal: Cancer Research (2012)

Abstract Apoptosis-Inducing Factor (AIF) was previously characterized as a poly(ADP-ribose) (PAR) dependent, caspase independent cell death effector in a wide spectrum of diseases or conditions that involve cell death. The objective of this study was to determine the role of PAR and AIF in cancer cell death after chemotherapy. We have previously demonstrated the presence of AIF mediated caspase-independent cell death in MDA-MB-231 breast cancer cells following treatment with the DNA alkylating agent N-methyl-N’-nitrosoguanidine (MNNG). To gain further insight into the role of AIF in cell death induced by chemotherapy, we utilized RNA interference (RNAi) to knockdown expression of AIF and PAR glycohydrolase (PARG) in MDA-MB-231 and MCF-7 human breast cancer cells. UV-C irradiated AIF-silenced cells displayed increased cell viability. Moreover FACS analysis showed that AIF knockdown successfully protected cells against apoptosis induced by MNNG and the chemotherapeutic agents epirubicin and cyclophosphamide. Interestingly, the knockdown of PARG led to decreased apoptotic cell death after treatment with MNNG. However, inhibition of caspases using Q-VD-OPh in PARG RNAi treated cells led to an increase in apoptotic cell death, which suggests that caspase dependent cell death after chemotherapy is mediated in part by PARG. However, the knockdown of AIF in these cells led to significant protection, which indicates that cell death in the absence of caspase activity in PARG knockdown cells is mediated by AIF. Taken together, the results provide a paradigm where AIF can substitute as caspase executioner in the absence of PARG and caspases in breast cancer cells. Thus, the activation of AIF mediated cell death is a promising strategy to improve the treatment of breast cancer by providing an alternative pathway for tumor eradiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2019. doi:1538-7445.AM2012-2019
Abstract 1180: Activation of antisense transcription by Top1cc in human colon cancer cells
Authors: Jessica Marinello, Davide Bertozzi, Susana Bueno, Raffaella Iurlaro, Olivier Sordet, Giovanni Chillemi, Giovanni Capranico
Journal: Cancer Research (2011)

Abstract Camptothecin (CPT) and derivatives are effective anti-cancer agents exerting their activity through the inhibition of DNA topoisomerase I (Top1). The cascade of events following the collision of a replication fork with CPT-trapped Top1 (TopIcc) has been deeply studied. Recently, strong evidence demonstrated that Top1cc affects specific transcriptional mechanisms as well. In particular, Top1ccs specifically favor RNA polymerase II escape from promoter-proximal pausing sites, and can alter chromatin structure and accessibility. We have also demonstrated that the CPT-induced transcriptional stress determines a changed balance between sense and antisense transcripts at the human HIF-1α locus in cancer cells [Capranico et al., BBA 2010]. Here, we have further investigated the Top1cc-related antisense transcriptional activation at the single gene locus and genome-wide. CPT treatments promote the transcription, in normal as well as hypoxic conditions, of a novel long non-coding antisense RNA at the 5’ of the human HIF-1α mRNA (5’aHIF1α), which is 5’-capped and polyadenylated, indicating that is transcribed by RNA polymerase II. The 5’aHIF1α RNA localizes preferentially in the nuclear compartment, in particular RNA FISH experiments show that it accumulates mainly in the perinuclear region of human HCT116 cells. Thus, the data may suggest that it may have a regulatory role in membrane RNA/protein trafficking. To investigate whether the described effect at HIF-1α locus is a general event after Top1cc, we have carried out a genome-wide analyses of cellular transcripts. rRNA-depleted total RNA samples from CPT-treated and untreated HCT116 cells were subjected to bisulfite C&amp;gt;T conversion to maintain the information of the strand polarity of transcripts, and then sequenced on the Illumina platform (Solexa). Initial analyses of the ratio between sense and antisense sequence tags indicate that Top1cc induces the activation of antisense transcription at several gene loci. The results thus indicate that activation of antisense transcription may be a general response to the transcriptional stress caused by Top1ccs, possibly contributing to the pharmacological activity of camptothecins. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1180. doi:10.1158/1538-7445.AM2011-1180
953 EARLY LIVER BIOPSY IS CRUCIAL FOR ACCURATE DIAGNOSIS OF ALCOHOLIC HEPATITIS AND PROVIDES INDEPENDENT PROGNOSTIC INFORMATION IN PATIENTS WITH DECOMPENSATED ALCOHOLIC LIVER DISEASE
Authors: R.P. Mookerjee, C. Lackner, V. Stadlabauer, M. Deheragoda, R. Jalan
Journal: Journal of Hepatology (2008)
Abstract MP60: Investigation of Blood Pressure Genetic Loci in African Americans using the Metabochip
Authors: Cara L Carty, Lucia A Hindorff, Steven Buyske, Jeff Haessler, Megan D Fesinmeyer, Chris S Carlson, DC Rao, Aravinda Chakravarti, Myriam Fornage, Kari E North, Charles Kooperberg, Nora Franceschini
Journal: Circulation (2013)

Introduction. African Americans (AA) have a higher burden of hypertension than European descent individuals, thus motivating research on blood pressure (BP) risk factors in AA, including genetic variants. Yet to date, few genome-wide association studies (GWAS) of BP have been conducted in AA and it is unclear whether genetic variants identified in mainly European descent populations are also associated with BP in AA. Furthermore, investigation of established BP loci in diverse race/ethnicity groups such as AA, who tend to have higher levels of genetic diversity, provides opportunities to narrow loci for identifying potential causal variants. Methods. We examined whether systolic BP (SBP) and diastolic BP (DBP) loci on the Illumina Metabochip array were associated with BP traits in 18,832 AA from the PAGE, HyperGen and GenNet studies. Only SNPs with minor allele frequency≥0.001 and passing stringent QC were tested. Using p-value&lt;0.05 as a significance threshold for replication of GWAS SNPs in our AA population, we investigated the original GWAS SNP and all SNPs ±500 kilobases in modest linkage disequilibrium with it (r 2 ≥0.3). To test SNPs in the 16 SBP and 14 DBP loci, we used a Bonferroni corrected p-value of 0.05/total SNPs per locus (the number SNPs at each BP locus ranges from 104 to 2,337). Results. In models adjusted for sex, age, body mass index and global ancestry, 5 prior GWAS SNPs were associated (p&lt;0.05) with DBP: rs13107325/ SLC39A8 (non-synonymous), rs1165196/ SLC17A1 (non-synonymous), rs6495122/ CPLX3 , rs1327235/intergenic and rs6015450/intergenic. At several loci, we identified finely-mapped SNPs more strongly associated with DBP in AA than the original GWAS SNPs. Notably, we identified rs56153133 in the gene-rich 1p26 region harboring the chloride channel-voltage-sensitive-6 ( CLCN6 ) gene, p=6.9E-5. This SNP is highly correlated with the GWAS SNP rs17367504/ MTHFR in European-descent individuals (r 2 =0.98) and less so in AA (r 2 =0.64). For SBP, we replicated two GWAS SNPs: rs16998073/intergenic and rs2681472/ ATP2B1 and at many loci (10q24, 1p26, 15q26 et al .), we identified SNPs more strongly associated with SBP in AA than the original GWAS SNPs. Conclusions. Overall, several BP loci originally reported in individuals of European and East Asian ancestry also generalize to AA, which confirms the relevance of specific BP susceptibility loci across diverse populations. In addition, we identified SNPs more strongly associated with BP traits in AA than the original GWAS SNPs, underlying the importance of leveraging differences in nucleotide diversity and LD patterns among populations to narrow GWAS signal boundaries. Future work will include conditional analysis to further refine GWAS loci, and to identify additional signals and population-specific variation.
Marihuana Smoking and Intraocular Pressure
Authors: Robert S. Hepler
Journal: JAMA (1971)

<h3>To the Editor.—</h3> It is accepted widely that the physiologic effects of smoking marihuana are not well known, despite an acknowledged high incidence of usage. Even the President of the United States has called for a major effort to study drug effects in a scientific manner. In an attempt to investigate the effects of marihuana smoking upon the human visual system, complete ocular examinations were performed in a group of youthful subjects, before and one hour after smoking. Selection of subjects, medical and other safeguards utilized, and details of the protocol will be presented in a later publication. The purpose of this letter is to present preliminary data concerning the most impressive change observed so far, namely, a substantial decrease in intraocular pressure observed in a large percentage of subjects. Applanation tonometry was performed by the same experienced examiner, using the same tonometer for each pair of observations. Marihuana was
Diastolic dysfunction is associatedwith altered myocardial metabolism inasymptomatic normotensive patientswith well-controlled type 2 diabetes mellitus
Authors: Michaela Diamant, Hildo J Lamb, Ymte Groeneveld, Edwin L Endert, Jan W.A Smit, Jeroen J Bax, Johannes A Romijn, Albert de Roos, Jasper K Radder
Journal: Journal of the American College of Cardiology (2003)
Diagnostic picture tests in rheumatology
Authors: Sylvia M. Lachmann
Journal: British Journal of Sports Medicine (1987)

This study was not planned in a double blind fashion, so it is not possible to ascertain the degree of bias in the interpretation of the ultrasound scan.Ultrasound scanning could be used as a readily available, low cost, high safety and high accuracy method in suspected Achilles tendon injuries and in the immediate and late post-operative periods of surgically treated injuries for follow-up purposes.
The Enterococcus: "Putting the Bug in Our Ears"
Authors: STEPHEN A. HOFFMANN
Journal: Annals of Internal Medicine (1987)

High-level resistance to gentamicin among clinical isolates of enterococci has been found with increasing frequency in recent years. In this issue, Zervos and colleagues report findings from a prospective study in which they assessed the frequency of colonization and infection with such organisms at a university medical center, demonstrating probable person-to-person spread. Their findings suggest that hospitals should conduct systematic screening for enterococci with high-level resistance to gentamicin, that antimicrobial treatment habits be modified to limit the emergence of such organisms, and that rigorous infection control be practiced to minimize their spread. These observations are particularly timely because it has become clear that enterococci are extremely versatile pathogens which are both well suited for survival and capable of causing serious illness, especially in hospitalized patients treated with some of the newer broad-spectrum antibiotic agents. Enterococci with high-level resistance to gentamicin are also of growing concern because their resistance to many antibiotic agents severely limits the clinician's options for treatment.
Management strategies using pharmacogenomics in patients with severe HCV-1b infection: A decision analysis
Authors: Hisashi Moriguchi, Takamoto Uemura, Makoto Kobayashi, Raymond T. Chung, Chifumi Sato
Journal: Hepatology (2002)

The management of interferon (IFN) therapy for histologically severe chronic hepatitis C virus genotype 1b (HCV-1b [F3]) is controversial. A decision analysis using the Markov decision analysis model was performed for 6 disease management strategies by using clinical data from a Japanese teaching hospital and available published data. The results of base case analyses showed that IFN monotherapy was considered favorable for patients aged 40 to 60 years with HCV-1b (F3). For the sensitivity analyses, to support the results of base case analyses, HCV-1b (F3) patient quality-of-life (QOL) score must be 0.5 or greater for those 40 to 50 years old and 0.4 to 0.5 or greater for those 60 years old. When patients with HCV-1b (F3) were judged as nonresponsive (NR) after IFN monotherapy, the transition probabilities of liver diseases at 40, 50, and 60 years of age had to be such that the progression of liver diseases was controlled at an annual rate of 7.51% to 8.82% or lower, 7.77% to 8.27% or lower, and 6.39% to 6.60% or lower, respectively, and the sustained virologic response (SVR) rate for IFN monotherapy must be 3.0% to 5.51% or greater, 5.57% to 5.93% or greater, and 10.6% to 11.21% or greater, respectively. It is likely that IFN monotherapy could be applied to patients with HCV-1b (F3) aged 40 years at a dose of at least 432 MU. However, IFN monotherapy did not appear useful for patients with HCV-1b (F3) aged 50 and 60 years if they had no amino acid mutation in NS5A 2209 to 2248 and HCV RNA levels exceeded 1.0 mEq/mL. In conclusion, use of decision analysis models can help in therapeutic decisions for patients with HCV-1b.
Children in Third World slums
Authors: W. A M Cutting, G. Kothari
Journal: BMJ (1988)

As an example of the miserable conditions for children in third world slums the Dharavi area northwest of Bombay is described.  India has the 3rd largest urban population in the world after the U.S. and the U.S.S.R. and is expected to be 45% urban by 2000.  Dharavi covers 4.5 square km possibly the largest slum in Asia with 800000 people.  Most of the dwellings are single-story huts home 3-8 people about 3 m square with no sanitation paved roads or windows.  About 1/4 of the mothers were born there but 1/3 arrived in the past 5 years.  Most children are without benefit of traditional extended family care and live in culturally heterogeneous neighborhoods.  99% were breast-fed however the majority received sweetened water for the 1st 3 days and 11% were exclusively breast-fed at 11 months of age.  The 25% who were supplemented at 8 months received inadequate amounts of contaminated food.  Severe malnutrition was observed in 1% of boys and 5% of girls less than 6 months of age.  After 6 months girls were 10 times as likely to be malnourished as boys but no difference was found in malnutrition between all breast-fed or supplemented children.  The prospect for slum dwellers here is bleak.  Possibly application of practical technology immunizations and education to stimulate community participation and self-reliance in health will be advantageous.