tbuckley/cabot-search huggingface dataset:
The Effect of a Lower Target Blood Pressure on the Progression of Kidney Disease: Long-Term Follow-up of the Modification of Diet in Renal Disease Study
Authors: Mark J. Sarnak, Tom Greene, Xuelei Wang, Gerald Beck, John W. Kusek, Allan J. Collins, Andrew S. Levey
Journal: Annals of Internal Medicine (2005)

Background: Hypertension is a risk factor for progression of chronic kidney disease. The optimal blood pressure to slow progression is unknown. Objective: To evaluate the effects of a low target blood pressure on kidney failure and all-cause mortality. Design: Long-term follow-up of the Modification of Diet in Renal Disease Study, a randomized, controlled trial conducted from 1989 to 1993. Setting: 15 outpatient nephrology practices. Participants: 840 persons with predominantly nondiabetic kidney disease and a glomerular filtration rate of 13 to 55 mL/min per 1.73 m2. Intervention: A low target blood pressure (mean arterial pressure < 92 mm Hg) or a usual target blood pressure (mean arterial pressure < 107 mm Hg). Measurements: After the randomized trial was completed, kidney failure (defined as initiation of dialysis or kidney transplantation) and a composite outcome of kidney failure or all-cause mortality were ascertained through 31 December 2000. Results: Kidney failure occurred in 554 participants (66%), and the composite outcome occurred in 624 participants (74%). After Cox proportional hazards modeling and intention-to-treat analysis, the adjusted hazard ratios were 0.68 (95% CI, 0.57 to 0.82; P < 0.001) for kidney failure and 0.77 (CI, 0.65 to 0.91; P = 0.0024) for the composite outcome in the low target blood pressure group compared with the usual target blood pressure group. Evidence was insufficient to conclude that the benefit of a low target blood pressure differed according to the cause of kidney disease, baseline glomerular filtration rate, or degree of proteinuria. Limitations: The exact mechanism underlying the benefit of a low target blood pressure is unknown. Conclusions: Assignment to a low target blood pressure slowed the progression of nondiabetic kidney disease in patients with a moderately to severely decreased glomerular filtration rate.
Pyk2 Signaling Events Mediate Eosinophil Chemotaxis Along Chemoattractant Gradients In The Lung
Authors: C.A. Lipinski, R. Schubert, Z. Yang, R.S. Pero, M. Russ, S. Muller, H. Kohler, J.J. Lee
Journal: Journal of Allergy and Clinical Immunology (2007)
Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement of the American Diabetes Association and the European Association for the Study of Diabetes
Authors: Decio L. Eizirik
Journal: Diabetes Care (2009)

I read with great interest the consensus statement by Nathan et al. (1) on behalf of the American Diabetes Association and the European Association for the Study of Diabetes, suggesting a consensus algorithm for initiation and adjustment of therapy for the medical management of hyperglycemia in type 2 diabetes. Describing the process used to develop the algorithm, the authors mentioned two sources: clinical trials that address the effectiveness and safety of different modalities of therapy and clinical judgment, that is, the collective knowledge and clinical experience of the authors, which takes into account benefits, risks, and costs in the treatment of diabetes (1). Because the authors point to the “paucity of high-quality evidence in the form of well-controlled clinical trials that directly compare different diabetes treatment regimens,” they propose that the scarce evidence-based information should be supplemented by “value judgments, where the benefits of treatment are weighed against risks and costs in a subjective fashion” …
Childhood cancer and power lines: Study had important omissions
Authors: Roger W Coghill
Journal: BMJ (2005)

Childhood cancer and power linesWhat do the data mean?Editor-Draper et al used distance of mother's home from high voltage overhead transmission lines (predominantly 275 kV and 400 kV) at the time of her child's birth as a proxy for her child's subsequent exposure to power-frequency magnetic fields (reviewed by Ahlbom et al). 1 2 As they acknowledge, this is a crude estimate since, in contrast to other reports, 2 no household measurements were taken, no data on more prevalent low voltage distribution sources were collected, no information from other time points in the child's life was obtained, variations during the 33 years period studied were not considered, and no validatory home visits were carried out.A recent report into residential exposures to magnetic fields in the United Kingdom estimated that proximity to high voltage lines, 275 kV and above, explained only 9% of those with measurements ≥ 0.2 microtesla ( T). 3 National data on the distribution of houses in relation to high voltage lines in the UK were provided (J Swanson, National Grid Transco, personal communication, 2000) to the UK Childhood Cancer Study (UKCCS) Group for its study of power lines and childhood cancer, to assess the representativeness of study subjects. 4 An equivalent comparison using National Grid data spanning the far longer period investigated in the paper by Draper et al was not undertaken.The assessments of distance to power lines in the UKCCS were made for all registered controls, who have been shown to represent the general population. 5plot of the distributions of the leukaemia and non-leukaemia cases and controls in the study by Draper et al, national populations, and UKCCS populations by distance from high voltage lines (figure) seems to show that the leukaemia controls used in the analysis presented by Draper et al are systematically different.Their positive result over 100 m may therefore be explained not by an excess of cases but by a deficit of controls in the early years of the study.
Incidence and clinical significance of lactose malabsorption in ulcerative colitis and Crohn's disease
Authors: E. Gudmand-Hoyer, S. Jarnum
Journal: Gut (1970)

The incidence of lactose malabsorption was investigated in 85 patients with ulcerative colitis and 71 patients with Crohn's disease by means of lactose tolerance tests and disaccharidase determinations in small intestinal mucosa. Eight patients with ulcerative colitis (9%) and four with Crohn's disease (6%) had lactose malabsorption. A control group displayed a similar incidence. It is concluded that lactose malabsorption is not particularly common in ulcerative colitis and Crohn's disease. If it is present, its aetiology seems to be unrelated to the intestinal disease. Transitional lactose malabsorption was detected in two cases during a relapse of ulcerative colitis. Institution of a lactose-free (or lactose-poor) diet was an important supporting measure in seven patients who were unaware of their milk intolerance, in particular in two with ileostomy. Therefore, it is recommended that a lactose tolerance test should always be performed in patients with ulcerative colitis or Crohn's disease.Twenty-one patients with ulcerative colitis and nine with Crohn's disease, none of whom had lactose malabsorption, were placed on milk-free diets. A beneficial effect was noticed in five of the patients with ulcerative colitis, and in three of those with Crohn's disease. The mechanism is unknown. Evidence is presented that milk allergy is not responsible for the beneficial effect of a lactosefree diet in patients with associated lactose malabsorption.
Reversing <i>HOXA9</i> Oncogene Activation by PI3K Inhibition: Epigenetic Mechanism and Prognostic Significance in Human Glioblastoma
Authors: Bruno M. Costa, Justin S. Smith, Ying Chen, Justin Chen, Heidi S. Phillips, Kenneth D. Aldape, Giuseppe Zardo, Janice Nigro, C. David James, Jane Fridlyand, Rui M. Reis, Joseph F. Costello
Journal: Cancer Research (2010)

HOXA genes encode critical transcriptional regulators of embryonic development that have been implicated in cancer. In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using reverse transcription-PCR in primary gliomas and glioblastoma cell lines and was validated in two sets of expression array data. In a subset of GBM, HOXA genes are aberrently activated within confined chromosomal domains. Transcriptional activation of the HOXA cluster was reversible by a phosphoinostide 3-kinase (PI3K) inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation. Functional studies of HOXA9 showed its capacity to decrease apoptosis and increase cellular proliferation along with tumor necrosis factor-related apoptosis-including ligand resistance. Notably, aberrant expression of HOXA9 was independently predictive of shorter overall and progression-free survival in two GBM patient sets and improved survival prediction by MGMT promoter methylation. Thus, HOXA9 activation is a novel, independent, and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism. Our findings suggest a transcriptional pathway through which PI3K activates oncogenic HOXA expression with implications for mTOR or PI3K targeted therapies.
Growth of the Concept of the Paucimolecular Membrane
Authors: HUGH DAVSON
Journal: Circulation (1962)

The concept of the paucimolecular membrane derived in the first place from studies, such as those of Gorter and Grendel, on the amount of fatty material that could be extracted from the cell, based on the assumption that this was mainly concentrated at its surface. These studies, and other ones, led to the concept of the bimolecular leaflet of lipid as the fundamental basis of membrane structure. Various considerations demanded, also, the presenee of protein as an intimate part of the structure. The simple structure put forward can account for many of the features of cell permeability, but, where facilitated diffusion is concerned, we must invoke the presence of specialized regions, perhaps pores, that have specific structures into which favored molecules and ionis are able to fit. If this is true, variations in the gross analysis of cell membraines are unlikely to be correlated with gross variations in permeability characteristics; instead we must seek, by indirect methods, to lay bare the chemical features of these specialized regions, which doubtless share many of the characteristics of enzymes.
Tolerogenic function of Blimp-1 in dendritic cells
Authors: Sun Jung Kim, Yong Rui Zou, Jordan Goldstein, Boris Reizis, Betty Diamond
Journal: The Journal of Experimental Medicine (2011)

Blimp-1 has been identified as a key regulator of plasma cell differentiation in B cells and effector/memory function in T cells. We demonstrate that Blimp-1 in dendritic cells (DCs) is required to maintain immune tolerance in female but not male mice. Female mice lacking Blimp-1 expression in DCs (DCBlimp-1ko) or haploid for Blimp-1 expression exhibit normal DC development but an altered DC function and develop lupus-like autoantibodies. Although DCs have been implicated in the pathogenesis of lupus, a defect in DC function has not previously been shown to initiate the disease process. Blimp-1ko DCs display increased production of IL-6 and preferentially induce differentiation of follicular T helper cells (TFH cells) in vitro. In vivo, the expansion of TFH cells is associated with an enhanced germinal center (GC) response and the development of autoreactivity. These studies demonstrate a critical role for Blimp-1 in the tolerogenic function of DCs and show that a diminished expression of Blimp-1 in DCs can result in aberrant activation of the adaptive immune system with the development of a lupus-like serology in a gender-specific manner. This study is of particular interest because a polymorphism of Blimp-1 associates with SLE.
Abstract 344: Oxygen sensors are poor prognosticators for survival in NSCLC
Authors: Sigve Andersen, Tom Donnem, Khalid Al-Shibli, Samer Al-Saad, Helge Stenvold, Lill-Tove Busund, Roy Bremnes
Journal: Cancer Research (2011)

Abstract Background: Most solid tumors are at least partly hypoxic. To survive hypoxia, cancer cells must adapt by hypoxic gene activation. Hypoxia-inducible factors (HIFs) have been recognized as key regulators of this transcriptional control. However, oxygen tension is sensed by three HIF prolyl hydroxylases (PHD1, PHD2 and PHD3) and one asparaginyl hydroxylase, FIH (Foctor inhibiting HIF). This study evaluates the prognostic impact of these four oxygen sensors in the biggest killer in cancer, Non-Small Cell Lung Cancer (NSCLC). Methods: 335 unselected stage I-IIIA NSCLC-patients were included. Duplicate 0.6 mm diameter cores from both the viable neoplastic cell compartment (tumor) and stroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expression. Results: There was only scorable expression in the tumor compartment. In univariate analyses high expression of all the oxygen sensors in tumor were significantly associated with a poor prognosis (PHD1, P = 0.023; PHD2, P = 0.013; PHD3, P = 0.018; FIH, P = 0.033). There were only weak correlations between these markers (strongest between PHD2 and FIH; r = 0.18, P = 0.001). In the multivariate analysis, entering all the significant clinicopathological variables and the oxygen sensors, we found only high expression of PHD2 (HR 2.03; CI 95% 1.20-3.42; P = 0.008) and PHD1 (HR 1.45; CI 95% 1.01-2.10; P = 0.047) of the molecular variables to be independent poor prognosticators. Conclusions: Oxygen sensors were only scorable in tumor. High expression of all the oxygen sensors was associated with a poor prognosis. High expression of PHD1 and PHD2 were also significantly and independently associated with a dismal prognosis. 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 344. doi:10.1158/1538-7445.AM2011-344
SUBACUTE PERINEPHRIC ABSCESS OF NON-RENAL ORIGIN
Authors: Z. Cope
Journal: BMJ (1920)

_EIA ORNtwe publislhed durinag the war.I did not mean to suggest tllat a-feeling of distension like that wlich lhe felt before his haematemesis is hysterical, but a feeling of this kind is in many cases the exciting cause of-hysterical aerophlagy.In reply to Dr. Hobhouse, the digestive symptoms which follow exlhaustion or neurastlhenia are entirely distinct and need entirely different treatment from the symptoms resulting from the disordered emotions in psyclhasthenia.Dr. Parsons must have entirely misunderstood me if he tlhouglht I would attempt to treat by psyclhotlherapy a case such as the one lhe related of death from Addison's disease.Psychotherapy is, of course, only indicated in digestive symptoms wlicih result from hysteria and psyclhastlhenia, 'PEIR-INEPHRIC ABSCESS OF NON-REXAL ORIGIN.I'mm Jam ZI MDICAL JOUNASL
The Cost-Effectiveness of Preexposure Prophylaxis for HIV Prevention in the United States in Men Who Have Sex With Men
Authors: Howard A. Fink, Areef Ishani, Brent C. Taylor, Nancy L. Greer, Roderick MacDonald, Dominic Rossini, Sameea Sadiq, Srilakshmi Lankireddy, Robert L. Kane, Timothy J. Wilt
Journal: Annals of Internal Medicine (2012)

Background: A recent randomized, controlled trial showed that daily oral preexposure chemoprophylaxis (PrEP) was effective for HIV prevention in men who have sex with men (MSM). The Centers for Disease Control and Prevention recently provided interim guidance for PrEP in MSM at high risk for HIV. Previous studies did not reach a consistent estimate of its cost-effectiveness. Objective: To estimate the effectiveness and cost-effectiveness of PrEP in MSM in the United States. Design: Dynamic model of HIV transmission and progression combined with a detailed economic analysis. Data Sources: Published literature. Target Population: MSM aged 13 to 64 years in the United States. Time Horizon: Lifetime. Perspective: Societal. Intervention: PrEP was evaluated in both the general MSM population and in high-risk MSM and was assumed to reduce infection risk by 44% on the basis of clinical trial results. Outcome Measures: New HIV infections, discounted quality-adjusted life-years (QALYs) and costs, and incremental cost-effectiveness ratios. Results of Base-Case Analysis: Initiating PrEP in 20% of MSM in the United States would reduce new HIV infections by an estimated 13% and result in a gain of 550 166 QALYs over 20 years at a cost of $172 091 per QALY gained. Initiating PrEP in a larger proportion of MSM would prevent more infections but at an increasing cost per QALY gained (up to $216 480 if all MSM receive PrEP). Preexposure chemoprophylaxis in only high-risk MSM can improve cost-effectiveness. For MSM with an average of 5 partners per year, PrEP costs approximately $50 000 per QALY gained. Providing PrEP to all high-risk MSM for 20 years would cost $75 billion more in health care–related costs than the status quo and $600 000 per HIV infection prevented, compared with incremental costs of $95 billion and $2 million per infection prevented for 20% coverage of all MSM. Results of Sensitivity Analysis: PrEP in the general MSM population would cost less than $100 000 per QALY gained if the daily cost of antiretroviral drugs for PrEP was less than $15 or if PrEP efficacy was greater than 75%. Limitation: When examining PrEP in high-risk MSM, the investigators did not model a mix of low- and high-risk MSM because of lack of data on mixing patterns. Conclusion: PrEP in the general MSM population could prevent a substantial number of HIV infections, but it is expensive. Use in high-risk MSM compares favorably with other interventions that are considered cost-effective but could result in annual PrEP expenditures of more than $4 billion. Primary Funding Source: National Institute on Drug Abuse, Department of Veterans Affairs, and National Institute of Allergy and Infectious Diseases.
Which patients with hepatitis C develop liver complications?
Authors: Mahbub H. Khan, Geoffrey C. Farrell, Karen Byth, Rita Lin, Martin Weltman, Jacob George, Dev Samarasinghe, James Kench, Songal Kaba, Evelyn Crewe, Chris Liddle
Journal: Hepatology (2000)

To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age; birth in Asia, Europe, Mediterranean region, or Egypt; transmission by blood transfusion or sporadic cases; HCV genotypes 1b and 4 (compared with 1/1a); fibrosis stage 3 or 4 (cirrhosis); serum albumin; bilirubin; prothrombin time; and alpha-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P <.001), advanced fibrosis (P =.004), and low albumin (P <.001). The corresponding independent risk factors for HCC were male gender (P =. 07), sporadic transmission (P <.001), and albumin (P <.001); bilirubin (P =.02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. Patients without definite risk factors for HCV (sporadic cases) are at higher risk of complications, possibly because of interaction between older age, duration of infection, country of birth, and HCV genotypes 1b and 4.
760 ENTECAVIR TREATMENT IS EFFECTIVE IN PATIENTS WITH PREVIOUS ADEFOVIR TREATMENT: RESULTS FROM AN INTERNATIONAL MULTICENTER COHORT STUDY
Authors: R. Zoutendijk, J.G.P. Reijnders, A. Brown, F. Zoulim, D. Mutimer, K. Deterding, J. Petersen, W.P. Hofmann, M. Buti, T. Santantonio, F. van Bommel, P. Pradat, T. Berg, B.E. Hansen, H. Wedemeyer, H.L.A. Janssen
Journal: Journal of Hepatology (2011)
Adolescent Hypertension
Authors: MARGARET M. KILCOYNNE
Journal: Circulation (1974)

Two groups of patients were recognized among 27 black and latin adolescents who underwent diagnostic evaluation for hypertension. Group I consisted of ten patients, seven of whom had arterial pressures consistently higher than 1 standard deviation above the pressure means of normal adolescents and three had pressures below this level. Group II consisted of 17 patients, 16 of whom had systolic and diastolic pressures greater than 2 standard deviations above the means for their age-sex group. One patient had solely systolic hypertension. An assignable cause for their hypertension was not apparent. Chemical parameters, including plasma renin activity (radioimmunoassay Angiotensin I), were similar to those observed in adult hypertensive patients of the same community. A difference in response to therapy was noted in adolescents compared to adults which may imply differences in the mechanisms involved at this phase of the disease, as has been reported in patients with labile and early hypertension and spontaneously hypertensive rats. At least three facets of this adolescent hypertension study deserve implementation and investigation: 1) routine blood pressure measurements in high schools, 2) longitudinal evaluation of the indications for and effects of therapy, and 3) intensive inquiry into the hemodynamic and neurohumoral aspects of hyperten- sion in its early unfolding.
Peanut and tree nut consumption during pregnancy and allergic disease in children—should mothers decrease their intake? Longitudinal evidence from the Danish National Birth Cohort
Authors: Ekaterina Maslova, Charlotta Granström, Susanne Hansen, Sesilje B. Petersen, Marin Strøm, Walter C. Willett, Sjurdur F. Olsen
Journal: Journal of Allergy and Clinical Immunology (2012)
1981 United States Pharmacopeia Dispensing Information
Authors: Lawrence Fleckenstein
Journal: JAMA (1982)

<h3>About Your Medicines, Abstracted From the 1981 United States Pharmacopeia Dispensing Information,</h3> Abridged Consumer ed, 594 pp; Complete Reference ed, 398 pp, paper, $4.50, $8.95, Rockville, Md, US Pharmacopeial Convention, 1981. After 160 years of setting standards of purity and potency for medications used in the United States, the US Pharmacopeia no longer rolls along in the old ruts. It has branched in a new direction—providing drug information for physicians, other health workers, and patients. The parent volume of this wellspring is the<i>USP Dispensing Information (USP DI)</i>. A divided book, the first section has prescribing and dispensing information for professionals, and the second part has advice for patients. Monographs for prescribers on many drugs or drug classes can be found in the first section, and corresponding monographs for patients are located in the second section. This latter section on patient information is a unique and noteworthy feature of the