tbuckley/cabot-search huggingface dataset:
Determinants of Echocardiographic Aortic Root Size
Authors: Ramachandran S. Vasan, Martin G. Larson, Daniel Levy
Journal: Circulation (1995)

Background Previous studies that evaluated the determinants of aortic root size have not yielded uniform results. We examined the relations of age, height, weight, body surface area, sex, and blood pressure to echocardiographically determined aortic root size in a population-based cohort. Methods and Results The study sample consisted of 1849 men and 2152 women in the Framingham Heart Study and Framingham Offspring Study who were free of clinically apparent cardiac disease when echocardiography was performed. Aortic root measurements were made by M-mode echocardiography using a leading-edge-to-leading-edge technique. The relations of age, height, weight, body surface area, and blood pressure variables (contemporary and those obtained 8 years before) to aortic root dimension were examined by use of sex-specific correlations and linear regression analyses. Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions in adults (cumulative R 2 =.2085 in men and .2327 in women). The additional effect of contemporary or previous blood pressure measures was small and revealed direct associations of aortic root dimension with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures. Previous blood pressure measurements did not contribute significantly to prediction of aortic root size once contemporary blood pressure variables entered the models. Results of regression analyses using a sex-pooled data set showed that on average, the aortic root measurement in women was 2.4 mm smaller than that of men of comparable age, height, and weight. Logistic regression was used to assess the likelihood of aortic root enlargement according to blood pressure levels. After adjustment for age, height, and weight, the odds ratio of aortic dilation for a 1-SD increment in systolic pressure was 0.70 (95% CI, 0.52 to 0.95) in men and 0.79 (95% CI, 0.60 to 1.04) in women; the odds ratio for a 1-SD increment in diastolic pressure was 1.22 (95% CI, 0.91 to 1.63) in men and 1.33 (95% CI, 1.01 to 1.73) in women. Conclusions Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions. The additional influences of blood pressure measurements were small; direct associations of aortic root dimensions with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures were observed. Additional prospective studies are needed to confirm these observations and to assess the impact of aortic root dimensions on the incidence of hypertension.
Negligence of medical experts
Authors: M E Jan Wise
Journal: BMJ (2005)

Reduction in mortality from breast cancerDecrease with screening was marked in younger age group Editor-Based on a complicated statistical model, Olsen et al reported that the breast cancer mortality in Copenhagen dropped by 25% for women aged 50-79 when comparing mortality in the screening period (1991-2001) with a pre-screening period (1981-91) and claimed that this decrease was caused by screening. 1According to Statistics Denmark, 217 breast cancer deaths occurred in Copenhagen in the age group 35-54 years in the period 1981-90 and 196 deaths in 1991-2000. 2By comparing these data with those in the article by Olsen et al we calculate that less than 5% of the breast cancer mortality in this age group is caused by tumours diagnosed after age 50 years when women were invited to screening.The number of exposure years increased from about 484 000 to about 538 000.This gives a significant 19% (age adjusted) reduction in breast cancer mortality in the age group 35-54 years.No reduction at all occurred in the age group 55-79. 2Our estimates are based on raw and complete data.In contrast, the estimates in the paper by Olsen et al are sensitive to exclusion of data and model choice.In Copenhagen a drop in breast cancer mortality may reflect a higher fertility quotient due to non-Western immigration, fewer nulliparous women, and other non-screening related factors.It is therefore strange that no causal note was made by Olsen et al on the marked decrease in the breast cancer mortality in the age group 35-54 years.
Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study
Authors: C. Fotopoulou, I. Vergote, P. Mainwaring, M. Bidzinski, J.B. Vermorken, S.A. Ghamande, P. Harnett, S.A. Del Prete, J.A. Green, M. Spaczynski, S. Blagden, M. Gore, J. Ledermann, S. Kaye, H. Gabra
Journal: Annals of Oncology (2013)
Design of a National Distributed Health Data Network
Authors: Judith C. Maro
Journal: Annals of Internal Medicine (2009)

A distributed health data network is a system that allows secure remote analysis of separate data sets, each comprising a different medical organization's or health plan's records. Distributed health data networks are currently being planned that could cover millions of people, permitting studies of comparative clinical effectiveness, best practices, diffusion of medical technologies, and quality of care. These networks could also support assessment of medical product safety and other public health needs. Distributed network technologies allow data holders to control all uses of their data, which overcomes many practical obstacles related to confidentiality, regulation, and proprietary interests. Some of the challenges and potential methods of operation of a multipurpose, multi-institutional distributed health data network are described.
Raised concentrations of C reactive protein in anabolic steroid using bodybuilders
Authors: F M Grace, B Davies
Journal: British Journal of Sports Medicine (2004)

To examine levels of C reactive protein in users of anabolic androgenic steroids (AAS) compared with age matched control groups consisting of AAS using (but abstinent)/resistance trained and non-drug using/sedentary controls.Subjects included AAS using bodybuilders (n = 10); bodybuilders who denied AAS use (n = 10); sedentary controls (n = 8). Venous blood was sampled, from which serum concentrations of C reactive protein, male sex hormones, and cardiac troponin T were determined.A significantly altered hormonal profile in the AAS using group provided indirect confirmation of AAS use. C reactive protein concentrations were significantly (p<0.05) higher in the AAS using bodybuilders. There was no relation between C reactive protein and cardiac troponin T.AAS using bodybuilders had significantly higher C reactive protein concentrations, indicating a greater propensity to develop peripheral arterial disease.
A single institution experience on minimally invasive repair of pectus deformities
Authors: Korkut Bostanci, Adamu Issaka, Onur Ermerak, Volkan Kara, Mustafa Yuksel
Journal: European Respiratory Journal (2013)

Minimally invasive repair of pectus excavatum (MIRPE) and minimally invasive repair of pectus carinatum (MIRPC) have become the standard treatment in many centers in recent years due to successful surgical outcomes. The aim of this study was to investigate the results of MIRPE and MIRPC at our institute.  435 patients who had had minimally invasive repair of pectus deformity between August 2005 – February 2013 were evaluated retrospectively, according to the demographics, form of the deformity, number of placed bars, operation duration, perioperative and postoperative complications, length of hospital stay, reoperations, bar removal recurrence and patient satisfaction.  type of deformity, number of bars, operation duration, length of hospital stay, recurrence and patient satisfaction.  375 of the patients were male, 60 were female and the median age was 16.5 (range: 6-46). 343 patients had MIRPE while 92 had MIRPC. The deformity was symmetric in 324 and asymmetric in 111 cases. One pectus bar was placed in 328 cases, two in 100, three in 7 cases for the correction of the deformity. The median operation duration was 60 minutes (range: 20-180) and the median duration of hospital stay was 5 days (range: 2-10). Bars of the 125 patients were removed on planned date. According to the evaluation of the quality-of-life questionnaires 96% of the patients were satisfied with surgical outcome.  Both MIRPE and MIRPC are successful surgical techniques and they can be preferred for the short operating time, low morbidity and high levels of patient satisfaction.
NRH:Quinone Oxidoreductase 2 and NAD(P)H:Quinone Oxidoreductase 1 Protect Tumor Suppressor p53 against 20S Proteasomal Degradation Leading to Stabilization and Activation of p53
Authors: Xing Gong, Labanyamoy Kole, Karim Iskander, Anil K. Jaiswal
Journal: Cancer Research (2007)

Abstract Tumor suppressor p53 is either lost or mutated in several types of cancer. MDM2 interaction with p53 results in ubiquitination and 26S proteasomal degradation of p53. Chronic DNA damage leads to inactivation of MDM2, stabilization of p53, and apoptotic cell death. Here, we present a novel MDM2/ubiquitination-independent mechanism of stabilization and transient activation of p53. The present studies show that 20S proteasomes degrade p53. The 20S degradation of p53 was observed in ubiquitin-efficient and -deficient cells, indicating that this pathway of degradation did not require ubiquitination of p53. The cytosolic quinone oxidoreductases [NRH:quinone oxidoreductase 2 (NQO2) and NAD(P)H:quinone oxidoreductase 1 (NQO1)] interacted with p53 and protected p53 against 20S proteasomal degradation. Further studies revealed that acute exposure to radiation or chemical leads to induction of NQO1 and NQO2 that stabilizes and transiently activates p53 and downstream genes. These results suggest that stress-induced NQO1 and NQO2 transiently stabilize p53, which leads to protection against adverse effects of stressors. [Cancer Res 2007;67(11):5380–8]
Radiation-Enhanced Lung Cancer Progression in a Transgenic Mouse Model of Lung Cancer Is Predictive of Outcomes in Human Lung and Breast Cancer
Authors: Oliver Delgado, Kimberly G. Batten, James A. Richardson, Xian-Jin Xie, Adi F. Gazdar, Aadil A. Kaisani, Luc Girard, Carmen Behrens, Milind Suraokar, Gail Fasciani, Woodring E. Wright, Michael D. Story, Ignacio I. Wistuba, John D. Minna, Jerry W. Shay
Journal: Clinical Cancer Research (2014)

Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment, including the modification of inflammatory responses from antitumorigenic to protumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis.K-ras(LA1) mice were irradiated with various doses and dose regimens and then monitored until death. Microarray analyses were performed using Illumina BeadChips on whole lung tissue 70 days after irradiation with a fractionated or acute dose of radiation and compared with age-matched unirradiated controls. Unique group classifiers were derived by comparative genomic analysis of three experimental cohorts. Survival analyses were performed using principal component analysis and k-means clustering on three lung adenocarcinoma, three breast adenocarcinoma, and two lung squamous carcinoma annotated microarray datasets.Radiation exposure accelerates lung cancer progression in the K-ras(LA1) lung cancer mouse model with dose fractionation being more permissive for cancer progression. A nonrandom inflammatory signature associated with this progression was elicited from whole lung tissue containing only benign lesions and predicts human lung and breast cancer patient survival across multiple datasets. Immunohistochemical analyses suggest that tumor cells drive predictive signature.These results demonstrate that radiation exposure can cooperate with benign lesions in a transgenic model of cancer by affecting inflammatory pathways, and that clinically relevant similarities exist between human lung and breast carcinogenesis.
Randomized Crossover Study Evaluating the Effect of Gemcitabine Infusion Dose Rate: Evidence of Auto-Induction of Gemcitabine Accumulation
Authors: Peter Grimison, Peter Galettis, Susan Manners, Maria Jelinek, Ekkaphon Metharom, Paul L. de Souza, Winston Liauw, Matthew J. Links
Journal: Journal of Clinical Oncology (2007)

Purpose Controversy exists over the optimal dose rate for administration of gemcitabine. There is a strong pharmacologic rationale for increased intracellular accumulation with prolonged infusions, but this failed to translate into a significant benefit in a large randomized study. The purpose of this study was to compare the intracellular pharmacokinetics of gemcitabine given for 30 minutes or for 100 minutes in a crossover design. Patients and Methods We randomly assigned 33 patients to a standard dose of 1,000 mg/m 2 over either 30 minutes or 100 minutes. At the second week, they were transferred to the alternate schedule. Blood samples were collected at various times after the gemcitabine infusion. Gemcitabine and difluorodeoxyuridine were measured in plasma by high-performance liquid chromatography (HPLC), and gemcitabine-triphosphate was measured by HPLC in leukocytes. Results Intracellular accumulation was greater during the 100-minute infusion, which was consistent with previous data. This effect was confounded by an increase in gemcitabine-triphosphate accumulation between weeks 1 and 2, which was consistent with self-induction of gemcitabine accumulation. There was significant heterogeneity: 27% of patients had greater WBC accumulation during the 30-minute infusion (regardless of treatment order). Patients with relatively greater levels of gemcitabine-triphosphate in WBCs tended to have less under-dosing and a greater reduction in midcycle neutrophils. However, this observation did not correlate with plasma gemcitabine levels. Conclusion This work identifies significant variations in intracellular gemcitabine-triphosphate accumulation between and within individuals, and it provides evidence that this variation has potential clinical significance. The observed self-induction of gemcitabine metabolism has broad implications for the dosing of nucleoside analogs.
The rate of the molecular clock and the cost of gratuitous protein synthesis
Authors: Germán Plata, Max E Gottesman, Dennis Vitkup
Journal: Genome biology (2010)

The nature of the protein molecular clock, the protein-specific rate of amino acid substitutions, is among the central questions of molecular evolution. Protein expression level is the dominant determinant of the clock rate in a number of organisms. It has been suggested that highly expressed proteins evolve slowly in all species mainly to maintain robustness to translation errors that generate toxic misfolded proteins. Here we investigate this hypothesis experimentally by comparing the growth rate of Escherichia coli expressing wild type and misfolding-prone variants of the LacZ protein.We show that the cost of toxic protein misfolding is small compared to other costs associated with protein synthesis. Complementary computational analyses demonstrate that there is also a relatively weaker, but statistically significant, selection for increasing solubility and polarity in highly expressed E. coli proteins.Although we cannot rule out the possibility that selection against misfolding toxicity significantly affects the protein clock in species other than E. coli, our results suggest that it is unlikely to be the dominant and universal factor determining the clock rate in all organisms. We find that in this bacterium other costs associated with protein synthesis are likely to play an important role. Interestingly, our experiments also suggest significant costs associated with volume effects, such as jamming of the cellular environment with unnecessary proteins.
Geographical and socioeconomic inequalities in women and children's nutritional status in Pakistan in 2011: an analysis of data from a nationally representative survey
Authors: Mariachiara Di Cesare, Zaid Bhatti, Sajid B Soofi, Lea Fortunato, Majid Ezzati, Zulfiqar A Bhutta
Journal: The Lancet Global Health (2015)

Pakistan has one of the highest levels of child and maternal undernutrition worldwide, but little information about geographical and socioeconomic inequalities is available. We aimed to analyse anthropometric indicators for childhood and maternal nutrition at a district level in Pakistan and assess the association of nutritional status with food security and maternal and household socioeconomic factors.We used data from the 2011 Pakistan National Nutrition Survey, which included anthropometric measurements for 33 638 children younger than 5 years and 24 826 women of childbearing age. We estimated the prevalences of stunting, wasting, and underweight among children and of underweight, overweight, and obesity in women for all 143 districts of Pakistan using a Bayesian spatial technique. We used a mixed-effect linear model to analyse the association of nutritional status with individual and household sociodemographic factors and food security.Stunting prevalence in Pakistan's districts ranged between 22% (95% credible interval 19-26) and 76% (69-83); the lowest figures for wasting and underweight were both less than 2·5% and the highest were 42% (34-50) for wasting and 54% (49-59) for underweight. In 106 districts, more women were overweight than were underweight; in 49 of these districts more women were obese than were underweight. Children were better nourished if their mothers were taller or had higher weight, if they lived in wealthier households, and if their mothers had 10 or more years of education. Severe food insecurity was associated with worse nutritional outcomes for both children and women.We noted large social and geographical inequalities in child and maternal nutrition in Pakistan, masked by national and provincial averages. Pakistan is also beginning to face the concurrent challenge of high burden of childhood undernutrition and overweight and obesity among women of reproductive age. Planning, implementation, and evaluation of programmes for food and nutrition should be based on district-level needs and outcomes.Bill & Melinda Gates Foundation, Grand Challenges Canada, UK Medical Research Council.
Lumbar Spinal Stenosis
Authors: Jeffrey N. Katz, Mitchel B. Harris
Journal: New England Journal of Medicine (2008)

A 72-year-old woman with hypertension presents with a 4-month history of lower back discomfort that radiates to both buttocks and lateral thighs. Previously, she walked 2 miles (3.2 km) a day; now she has difficulty walking two blocks and standing up for more than 15 minutes at a time. Her physical examination is notable only for a slightly stooped posture and a reduction of vibratory sensibility in both great toes. How should she be evaluated and treated?
Prevalence of night-time dyspnoea in COPD and its implications for prognosis
Authors: P. Lange, J. L. Marott, J. Vestbo, B. G. Nordestgaard
Journal: European Respiratory Journal (2014)

The information on night-time symptoms in chronic obstructive pulmonary disease (COPD) is sparse. We investigated the prevalence of night-time dyspnoea in 6616 individuals with COPD recruited from the general population in the Copenhagen area, Denmark, and described characteristics and prognosis of subjects with this symptom. The prevalence of night-time dyspnoea was 4.3%: 2.1% in Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A, 12.9% in GOLD B, 2.6% in GOLD C and 16.3% in GOLD D. Compared with individuals without night-time dyspnoea, those with night time dyspnoea had lower forced expiratory volume in 1 s, higher daytime dyspnoea scores (modified Medical Research Council scale) and more wheezing, more often had chronic mucus hypersecretion, ischaemic heart disease and atrial fibrillation, and more often reported stress, nervousness and tiredness. After adjustment for age and sex, the presence of night-time dyspnoea was associated with future COPD exacerbations (hazard ratio (HR) 2.3, 95% CI 1.7–3.0), hospital admissions due to COPD (HR 3.2, 95% CI 2.3–4.4) and mortality (HR 1.7, 95% CI 1.2–2.3). Prevalence of night-time dyspnoea in COPD increases with disease severity according to both spirometric and clinical GOLD classification, and is associated with presence of daytime respiratory symptoms and cardiac comorbidities. Night-time dyspnoea is a significant predictor of poor prognosis in individuals with COPD.
Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019
Authors: William A. Bower, Jarad Schiffer, Robert L. Atmar, Wendy A. Keitel, Arthur M. Friedlander, Lindy Liu, Yon Yu, David S. Stephens, Conrad P. Quinn, Katherine Hendricks
Journal: MMWR Recommendations and Reports (2019)

These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.