tbuckley/cabot-search huggingface dataset:
Health costs of a reduced energy supply.
Authors: J R McCarroll
Journal: Environmental Health Perspectives (1983)

Health effects associated with electricity production, especially air pollution from fossil fuel combustion, have received much attention in the past 30 years. Virtually no attention has been paid to the health costs of a reduced or overpriced energy supply although these are real and formidable. Stringent regulations mandating control technology on stack emissions and/or burning of low sulfur fuels have been promulgated which cost the American public billions of dollars. These have indeed alleviated some health problems, but pressures to further tighten regulations offer little chance of further health benefits commensurate with their cost and are most likely to produce a new series of problems.
ABC of arterial and venous disease: Non-invasive methods of arterial and venous assessment
Authors: Richard Donnelly, David Hinwood, Nick J M London
Journal: BMJ (2000)

Although diagnostic and therapeutic decisions in patients with vascular disease are guided primarily by the history and physical examination, the use of non-invasive investigations has increased significantly in recent years, mainly as a result of technological advances in ultrasonography. This article describes the main investigative techniques.



Handheld pencil Doppler being used to measure ankle brachial pressure index



In the simplest form of ultrasonography, ultrasound is transmitted as a continuous beam from a probe that contains two piezoelectric crystals. The transmitting crystal produces ultrasound at a fixed frequency (set by the operator according to the depth of the vessel being examined), and the receiving crystal vibrates in response to reflected waves and produces an output voltage. Conventional B mode (brightness mode) ultrasonography records the ultrasound waves reflected from tissue interfaces, and a two dimensional picture is built up according to the reflective properties of the tissues.

### Doppler ultrasonography

Ultrasound signals reflected off stationary surfaces retain the same frequency with which they were transmitted, but the principle underlying Doppler ultrasonography is that the frequency of signals reflected from moving objects such as red blood cells shifts in proportion to the velocity of the target. The output from a continuous wave Doppler ultrasonograph is usually presented as an audible signal, so that a sound is heard whenever there is movement of blood in the vessel being examined.



Left: Doppler velocity waveforms:( a ) triphasic waveform in normal artery; ( b ) biphasic waveform, with increased velocity, through a mild stenosis;( c ) monophasic waveform, with greatly increased velocity, through tight stenosis; and ( d ) dampened monophasic waveform, with reduced velocity, recorded distal to tight stenosis. Right:Anatomical chart used to record position of stenoses, showing three stenoses with velocity increases of 7×, 4×, and 3× compared with adjacent unaffected arteries



### Pulsed ultrasonography

Continuous wave ultrasonography provides little scope for restricting the area of …
Significance of the Weight Wave of Menstruation.
Authors: William T. Belfield
Journal: JAMA (1904)

Chicago, Feb. 24, 1904. <h3>To the Editor:</h3> —As supplemental to my article on this subject inThe Journal, June 13, 1903, allow me to report: 1. The increase in weight preceding the menstrual flow— which may exceed one pound per hour for several hours, the total increment being sometimes seven to nine pounds in 24 hours—is due to (<i>a</i>) increased absorption of oxygen, and (<i>b</i>) decreased excretion, notably of carbon dioxid and water. (Increased pressure of oxygen in the blood has been shown by Paul Bert, Hill and Macleod to retard metabolism and to decrease the excretion of CO<sub>2</sub>and water.) 2. The essential phenomena of the menstrual weight wave are therefore (1) the rapid absorption of oxygen with coin coincident retardation of metabolism and excretion, and consequent increase in weight; and (2) rapid excretion, especially of carbon dioxid (the exhalation of which may exceed two pounds in one hour)
HPV vaccine prices in Italy
Authors: L. Garattini, K. v. d. Vooren, G. Casadei
Journal: BMJ (2011)

In contrast to what was reported in the editorial,1 both the bivalent (Cervarix) and the quadrivalent (Gardasil) vaccines are used in Italy for the campaign against cervical cancer. Most of the 20 Italian regions, which fund and implement vaccination programmes on their territory, ran single tenders to exploit potential competition between the two …
Hypoxia-Inducible Factor-2α Correlates to Distant Recurrence and Poor Outcome in Invasive Breast Cancer
Authors: Karolina Helczynska, Anna-Maria Larsson, Linda Holmquist Mengelbier, Esther Bridges, Erik Fredlund, Signe Borgquist, Göran Landberg, Sven Påhlman, Karin Jirström
Journal: Cancer Research (2008)

Abstract Differential regulation as well as target gene specificity of the two hypoxia-inducible factor (HIF)-α subunits HIF-1α and HIF-2α in various tumors and cell lines have been suggested. In breast cancer, the prognostic significance of HIF-1α is not clear-cut and that of HIF-2α is largely unknown. Using IHC analyses of HIF-1α, HIF-2α, and vascular endothelial growth factor (VEGF) expression in a tissue microarray of invasive breast cancer specimens from 512 patients, we investigated the expression patterns of the 2 HIF-α subunits in relation to established clinicopathologic variables, VEGF expression, and survival. HIF-1α and HIF-2α protein levels and their effect on survival were additionally analyzed in a second cohort of 179 patients. To evaluate the individual role of each subunit in the hypoxic response and induction of VEGF, HIF-α protein and HIF-α and VEGF mRNA levels were further studied in cultured breast cancer cells after hypoxic induction and/or knockdown of HIF-α subunits by siRNA by Western blot and Quantitative Real-Time PCR techniques. We showed that although HIF-1α and HIF-2α protein levels in breast cancer specimens were not interrelated, high levels of both HIF-1α and HIF-2α associated to high VEGF expression. HIF-2α expression was an independent prognostic factor associated to reduced recurrence-free and breast cancer–specific survival, whereas HIF-1α did not exhibit these correlations. In cultured cells, acute hypoxia induced both HIF-proteins. At prolonged hypoxia, HIF-2α remained accumulated, whereas HIF-1α protein levels decreased, in agreement with the oxygen level and time-dependent induction of HIFs recently reported in neuroblastoma. [Cancer Res 2008;68(22):9212–20]
Diabetes after Transplantation and Sirolimus
Authors: Martha Pavlakis, Alexander S. Goldfarb-Rumyantzev
Journal: Journal of the American Society of Nephrology (2008)

New-onset diabetes is a common complication of renal transplantation. The appearance of this form of diabetes is associated with worsening cardiovascular risk and loss of renal allograft function.[1][1]–[3][2] The most important modifiable risks for its appearance are obesity and the choice of
A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration
Authors: Lindsay Y King, Claudia Canasto-Chibuque, Kara B Johnson, Shun Yip, Xintong Chen, Kensuke Kojima, Manjeet Deshmukh, Anu Venkatesh, Poh Seng Tan, Xiaochen Sun, Augusto Villanueva, Angelo Sangiovanni, Venugopalan Nair, Milind Mahajan, Masahiro Kobayashi, Hiromitsu Kumada, Massimo Iavarone, Massimo Colombo, Maria Isabel Fiel, Scott L Friedman, Josep M Llovet, Raymond T Chung, Yujin Hoshida
Journal: Gut (2014)

<h3>Objective</h3> The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. <h3>Design</h3> We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (&gt;1 mg/dL) and platelet count (&lt;100 000/mm<sup>3</sup>), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years). <h3>Results</h3> In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p&lt;0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child–Turcotte–Pugh class (HR=6.70, p&lt;0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p&lt;0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p&lt;0.001) and all liver-related adverse events (HR=4.98, p&lt;0.001). <h3>Conclusions</h3> A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.
Uterine disorders and pregnancy complications: insights from mouse models
Authors: Hyunjung Jade Lim, Haibin Wang
Journal: Journal of Clinical Investigation (2010)

Much of our knowledge of human uterine physiology and pathology has been extrapolated from the study of diverse animal models, as there is no ideal system for studying human uterine biology in vitro. Although it remains debatable whether mouse models are the most suitable system for investigating human uterine function(s), gene-manipulated mice are considered by many the most useful tool for mechanistic analysis, and numerous studies have identified many similarities in female reproduction between the two species. This Review brings together information from studies using animal models, in particular mouse models, that shed light on normal and pathologic aspects of uterine biology and pregnancy complications.
747-1 Progression of Aortic Regurgitation Assessed by Doppler Echocardiography in 127 Patients: Degree of Regurgitation
Authors: Luis R. Padial, Alvaro Oliver, Alex Sagie, Maria T. Vivaldi, Ming Hui Chen, Nelmacy Freitas, J.A. Vazquez de Prada, Arthur E. Weyman, Robert A. LeVine
Journal: Journal of the American College of Cardiology (1995)
Epigenetic Markers in Rectal Cancer
Authors: Lei Xu, Brian G. Czito, Christopher G. Willett
Journal: Clinical Cancer Research (2010)

Abstract DNA methylation changes in rectal cancer may serve as a new screening marker and a tool for monitoring recurrence. Importantly, these changes may also function as a predictive marker to allow appropriate exclusion of (neo)adjuvant therapies in patients at low risk for disease recurrence, sparing them from potential treatment-related morbidities. Clin Cancer Res; 16(10); 2699–701. ©2010 AACR.
Treatment of Seizure Disorders (Epilepsy)
Authors: Mary Louise Scholl
Journal: New England Journal of Medicine (1963)

WITH the presently available anticonvulsant drugs patients with seizure disorders can anticipate marked relief of symptoms. Seventy-five to 80 per cent of patients with epilepsy either obtain complete seizure control or are markedly improved on drug therapy. Another 15 per cent show moderate improvement; the remaining 5 to 10 per cent either are unimproved or appear to have their spells aggravated by medication.Seizures are only symptoms of underlying cerebral dysrhythmia. The pathology associated with these abnormal neuronal discharges is frequently obscure. However, it is unwise to undertake the treatment of the symptom without establishing, if possible, its cause. Occasionally, . . .
Anemia, Transfusion, and Mortality
Authors: Lawrence Tim Goodnough, Richard G. Bach
Journal: New England Journal of Medicine (2001)

Questions surrounding the risks and costs associated with blood transfusion have led to a reevaluation of clinical transfusion practices during the past 15 years.1 Guidelines for blood transfusion have been issued by several organizations, including a consensus conference of the National Institutes of Health,2 the American College of Physicians,3 the American Society of Anesthesiology,4 and the Canadian Medical Association.5 The guidelines recommend that among patients without known risk factors, the threshold for transfusion should be a hemoglobin level in the range of 6.0 to 8.0 g per deciliter. They also indicate that patients with hemoglobin levels higher than 10.0 g . . .
Well-defined biomimetic surfaces to characterize glycosaminoglycan-mediated interactions on the molecular, supramolecular and cellular levels
Authors: Elisa Migliorini, Dhruv Thakar, Rabia Sadir, Tino Pleiner, Françoise Baleux, Hugues Lortat-Jacob, Liliane Coche-Guerente, Ralf P. Richter
Journal: Biomaterials (2014)
Estimates of Gestational Age-Reply
Authors: Michael S. Kramer
Journal: JAMA (1989)

<h3>In Reply.—</h3> Drs Knoke and Sokol provide a clear and heuristic explanation of how regression to the mean can produce bias in estimates of gestational age when those estimates are based on the mother's recollection of the LNMP and are associated with appreciable random error. We in fact mentioned the phenomenon (on page 3308 of our article) in discussing possible reasons for our results, but dismissed it as insufficient to account for either the magnitude of the biases we observed or the differences between apparent (ie, LNMP-based) preterm and postterm births. As we stated in our article, "Regression toward the mean due to random errors in recall at the two extremes of menstrual dates can explain only a small part of the phenomenon, since random errors in menstrual dating have been shown to be much smaller in magnitude than those demonstrated herein. Nor does it explain the larger errors postterm
A CASE OF RENAL GLYCOSURIA
Authors: William Allan
Journal: JAMA (1923)

In defining renal glycosuria, Strouse<sup>1</sup>gives four points of differentiation from diabetes mellitus: (1) glycosuria without hyperglycemia; (2) glycosuria almost entirely independent of carbohydrate intake; (3) absence of diabetic symptoms, and (4) no subsequent development of diabetes mellitus. Paullin<sup>2</sup>has added a fifth characteristic in this condition, that sugar shall be constantly present in the urine. That renal glycosuria shall not later become diabetes mellitus necessitates a prolonged observation of such patients, and this is the reason for reporting a case in which glycosuria was discovered eighteen years ago, the patient having been employed in a hospital for the sake of supervision for the last nine years. Bailey<sup>3</sup>has reported a case in which glycosuria has been known for ten years, and says, "The patient's history points strongly to this being a congenital condition." Strouse has observed a case for eight years, Garrod<sup>4</sup>and Bonninger<sup>5</sup>
CPNE7, a preameloblast-derived factor, regulates odontoblastic differentiation of mesenchymal stem cells
Authors: Hyun-Jung Oh, Han-Wool Choung, Hye-Kyung Lee, Su-Jin Park, Ji-Hyun Lee, Dong-Seol Lee, Byoung-Moo Seo, Joo-Cheol Park
Journal: Biomaterials (2014)
Starting date of house officer posts
Authors: D. R Tooth
Journal: BMJ (1992)

Sen's editorial,' may well be due to tuberculosis; rates there now are comparable with those in the United Kingdom during part of the last century.Tuberculosis is, to a great extent, a disease of social deprivation, and thus Sen's point is valid.For some reason, however, young females have a higher mortality from tuberculosis than their male peers; this phenomenon is not yet understood and may account for at least some of Sen's missing women.
Reactive ring-opened aldehyde metabolites in benzene hematotoxicity.
Authors: G Witz, Z Zhang, B D Goldstein
Journal: Environmental Health Perspectives (1996)

The hematotoxicity of benzene is mediated by reactive benzene metabolites and possibly by other intermediates including reactive oxygen species. We previously hypothesized that ring-opened metabolites may significantly contribute to benzene hematotoxicity. Consistent with this hypothesis, our studies initially demonstrated that benzene is metabolized in vitro to trans-trans-muconaldehyde (MUC), a reactive six-carbon diene dialdehyde, and that MUC is toxic to the bone marrow in a manner similar to benzene. Benzene toxicity most likely involves interactions among several metabolites that operate by different mechanisms to produce more than one biological effect. Our studies indicate that MUC coadministered with hydroquinone is a particularly potent metabolite combination that causes bone marrow damage, suggesting that the involvement of ring-opened metabolites in benzene toxicity may be related to their biological effects in combination with other benzene metabolites. Studies in our laboratory and by others indicate that MUC is metabolized to a variety of compounds by oxidation or reduction of the aldehyde groups. The aldehydic MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienal (CHO-M-OH), similar to MUC but to a lesser extent, is reactive toward glutathione, mutagenic in V79 cells, and hematotoxic in mice. It is formed by monoreduction of MUC, a process that is reversible and could be of biological significance in benzene bone marrow toxicity. The MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienoic (COOH-M-OH) is an end product of MUC metabolism in vitro. Our studies indicate that COOH-M-OH is a urinary metabolite of benzene in mice, a finding that provides further indirect evidence for the in vivo formation of MUC from benzene. Mechanistic studies showed the formation of cis-trans-muconaldehyde in addition to MUC from benzene incubated in a hydroxyl radical-generating Fenton system. These results suggest that the benzene ring is initially opened to cis,cis-muconaldehyde, an unstable isomer that rearranges to cis-trans-muconaldehyde, which further rearranges to trans-trans-muconaldehyde. The latter is not formed from benzene dihydrodiol by reactive oxygen species in a Fenton system that contains reactive oxygen species.
Deficient human β-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection
Authors: Ruiying Diao, Kin Lam Fok, Hao Chen, Mei Kuen Yu, Yonggang Duan, Chin Man Chung, Zhao Li, Hanwei Wu, Zesong Li, Hu Zhang, Ziliang Ji, Wanhua Zhen, Chi Fai Ng, Yaoting Gui, Zhiming Cai, Hsiao Chang Chan
Journal: Science Translational Medicine (2014)

Human β-defensin 1 plays a dual role in defending male fertility by promoting both the motility of sperm and its bactericidal activity.
Folate Depletion and Increased Glutamation in Juvenile Idiopathic Arthritis Patients Treated With Methotrexate
Authors: Ryan S. Funk, Leon van Haandel, J. Steven Leeder, Mara L. Becker
Journal: Arthritis & Rheumatology (2014)

Objective Folates exist as a fluctuating pool of polyglutamated metabolites that may serve as a clinical marker of methotrexate (MTX) activity. This study was undertaken to evaluate circulating folate content and folate polyglutamate distribution in juvenile idiopathic arthritis (JIA) patients and in a cell culture model based on MTX exposure and folate supply. Methods Blood, plasma, and red blood cell (RBC) measurements of MTX and folates were obtained from previously published data sets and an additional analysis of JIA patients receiving MTX (n = 98) and those not receiving MTX (n = 78). Erythroblastoid cells maintained in culture were exposed to MTX and grown under varying levels of folic acid supplementation. Samples were analyzed for cellular folate and MTX content. Results Circulating folate levels were lower in JIA patients receiving MTX, with reduced levels of blood, plasma, and RBC 5‐methyl‐tetrahydrofolate (5mTHF) ( P &lt; 0.0001). Average polyglutamate chain length (Glu avg ) of RBC 5mTHF was elevated in JIA patients receiving MTX (median ± interquartile range 5.63 ± 0.15 versus 5.54 ± 0.11 in those not receiving MTX; P &lt; 0.001) and correlated with both RBC MTX accumulation ( P = 0.02) and reduced plasma 5mTHF levels ( P = 0.008). MTX exposure and folate deprivation in erythroblastoid cells resulted in a depletion of bioactive folate species that was associated with a shift to higher Glu avg values for several species, most notably tetrahydrofolate (THF) and 5,10‐methylene‐tetrahydrofolate (CH 2 THF). Increased Glu avg resulted from the depletion of short‐chain and the accumulation of long‐chain glutamate species. Conclusion Our findings indicate that folate content and polyglutamate distribution are responsive markers of MTX activity and folate supply in vivo and in vitro, and may provide novel clinical markers of pharmacologic activity of MTX.
Prevention of Exercise-induced Bronchoconstriction by Inhaled Low-molecular-weight Heparin
Authors: TAHIR AHMED, BRENDA J. GONZALEZ, IGNACIO DANTA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Because many biological actions of heparin including the antiallergic activity are molecular weight dependent, we hypothesized that low-molecular-weight heparin (LMWH) may have greater potency in attenuating exercise-induced bronchoconstriction (EIB). Therefore, in the present investigation we studied the effects of inhaled LMWH, enoxaparin, and unfractionated heparin on EIB in subjects with asthma. Thirteen asthmatic subjects performed a standardized exercise challenge on a treadmill to document the presence of EIB. The workload was increased until 85% of predicted maximal heart rate was achieved, and the exercise was sustained at that workload for 10 min. EIB was assessed by measuring FEV1 before and immediately after the exercise. On five different experiment days the subjects were pretreated with 4 ml of aerosolized heparin (80,000 units = 7.5 mg/kg), placebo, or 3 different doses of enoxaparin (0.5 mg/kg, 1 mg/kg, 2 mg/kg) in a double-blind, randomized, crossover design, and exercise challenge was performed 45 min later. Bronchial provocation with methacholine was also performed in five subjects on two additional days after pretreatment with either placebo or inhaled enoxaparin (2 mg/kg), and venous blood was obtained for analysis of plasma antifactor Xa. Postexercise, the maximal decreases in FEV1 (mean ± SE) were 30 ± 4% and 29 ± 5% on control and placebo days. The exercise-induced decreases in FEV1 were inhibited by 31% with heparin ( Δ FEV1 = 20 ± 4%); and by 28%, 38%, and 48% by enoxaparin at doses of 0.5 mg/kg ( Δ FEV1 = 21 ± 5%), 1 mg/kg ( Δ FEV1 = 18 ± 5%), and 2 mg/kg ( Δ FEV1 = 15 ± 3%), respectively (p < 0.05). The inhibitory effect of 0.5 mg/kg dose of enoxaparin was comparable to heparin (7.5 mg/kg), whereas 2 mg/ kg dose of enoxaparin was the most potent. Inhaled enoxaparin failed to modify the bronchoconstrictor response to methacholine, and did not change the plasma antifactor Xa activity. These data demonstrate that inhaled enoxaparin prevents EIB in a dose-dependent manner; and its antiasthmatic activity is independent of its effect on plasma antifactor Xa activity.
Science writer is refused permission to appeal against libel ruling over comments on chiropractors
Authors: Z. Kmietowicz
Journal: BMJ (2009)

The science broadcaster and writer Simon Singh has been refused permission to appeal against a ruling in the libel case brought against him by the British Chiropractic Association. His case has aroused the anger of many in the science community, who describe the libel laws as encouraging the law courts to silence critics.

The ruling, made in May by Mr Justice Eady, said that an article by Dr Singh for the Guardian newspaper, published on 19 April 2008, was defamatory and alleged that the association was happy to promote bogus treatments ( BMJ 2009;338:b2127, 26 May, doi:10.1136/bmj.b2127).

In the article (which has been removed from the Guardian ’s website) Dr Singh criticised the British …