tbuckley/cabot-search huggingface dataset:
Toxic threats to neurologic development of children.
Authors: T Schettler
Journal: Environmental Health Perspectives (2001)

Learning disabilities, attention deficit hyperactivity disorder, developmental delays, and emotional and behavioral problems are among childhood disabilities of increasing concern. Interacting genetic, environmental, and social factors are important determinants of childhood brain development and function. For many reasons, however, studying neurodevelopmental vulnerabilities in children is challenging. Moreover, inadequate incidence and trend data interfere with full understanding of the magnitude of the problem. Despite these difficulties, extensive laboratory and clinical studies of several neurodevelopmental toxicants, including lead, mercury, polychlorinated biphenyls, alcohol, and nicotine, demonstrate the unique vulnerability of the developing brain to environmental agents at exposure levels that have no lasting effect in adults. Historically, understanding the effects of these toxicants on the developing brain has emerged slowly while generations of children are exposed to unsafe levels. Unfortunately, with few exceptions, neurodevelopmental toxicity data are missing for most industrial chemicals in widespread use, even when populationwide exposures are documented. The personal, family, and communitywide costs of developmental disabilities are profound. In addition to the need for more research, a preventive public health response requires mitigation of exposures to potential neurodevelopmental toxicants when available evidence establishes the plausibility of harm, despite residual toxicologic uncertainties.
Home sampling versus conventional contact tracing for detecting Chlamydia trachomatis infection in male partners of infected women: randomised study
Authors: B. Andersen, L. Ostergaard, J. K Moller, F. Olesen
Journal: BMJ (1998)

Urogenital infections with Chlamydia trachomatis are widespread and usually asymptomatic. Major complications from infection include ectopic pregnancies and female infertility.1 Although contact tracing reduces the prevalence of chlamydia infection,2 the test rate among partners is often low, partly because male contacts have to have a urethral swab taken by a doctor.

As the polymerase chain reaction can successfully detect infection in urine samples,3 we investigated whether the test rate could be increased by asking the male contacts of infected women to send a urine sample directly from home to a laboratory instead of having a doctor take a urethral swab.

Ninety six women with C trachomati s infection seen in general practices in Aarhus County, Denmark, were randomly divided according to their date of birth into an intervention group (45 patients) and a …
How the media caught Tamiflu
Authors: Michael Day
Journal: BMJ (2005)

<h3>Objective</h3> To quantify the journeys and CO<sub>2</sub> emissions if women with breast cancer are treated with risk-adapted single-dose targeted intraoperative radiotherapy (TARGIT) rather than several weeks9 course of external beam whole breast radiotherapy (EBRT) treatment. <h3>Setting</h3> (1) TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy, (2) 2 additional UK centres offering TARGIT. <h3>Participants</h3> 485 UK patients (249 TARGIT, 236 EBRT) in the prepathology stratum of TARGIT-A trial (where randomisation occurred before lumpectomy and TARGIT was delivered simultaneously with lumpectomy) for whom geographical data were available and 22 patients treated with TARGIT after completion of the TARGIT-A trial in 2 additional UK breast centres. <h3>Outcome measures</h3> The shortest total journey distance, time and CO<sub>2</sub> emissions from home to hospital to receive all the fractions of radiotherapy. <h3>Methods</h3> Distances, time and CO<sub>2</sub> emissions were calculated using Google Maps and assuming a fuel efficiency of 40 mpg. The groups were compared using the Student t test with unequal variance and the non-parametric Wilcoxon rank-sum (Mann-Whitney) test. <h3>Results</h3> TARGIT patients travelled significantly fewer miles: TARGIT 21 681, mean 87.1 (SE 19.1) versus EBRT 92 591, mean 392.3 (SE 30.2); had lower CO<sub>2</sub> emissions 24.7 kg (SE 5.4) vs 111 kg (SE 8.6) and spent less time travelling: 3 h (SE 0.53) vs 14 h (SE 0.76), all p&lt;0.0001. Patients treated with TARGIT in 2 hospitals in semirural locations were spared much longer journeys (753 miles, 30 h, 215 kg CO<sub>2</sub> per patient). <h3>Conclusions</h3> The use of TARGIT intraoperative radiotherapy for eligible patients with breast cancer significantly reduces their journeys for treatment and has environmental benefits. If widely available, 5 million miles (8 000 000 km) of travel, 170 000 woman-hours and 1200 tonnes of CO<sub>2</sub> (a forest of 100 hectares) will be saved annually in the UK. <h3>Trial registration number</h3> ISRCTN34086741; Post-results.
Human Rabies in the United States, 1960 to 1979: Epidemiology, Diagnosis, and Prevention
Authors: LARRY J. ANDERSON
Journal: Annals of Internal Medicine (1984)

Thirty-eight cases of human rabies occurred in the United States and its territories from 1960 to 1979. The major source of exposure to rabies has changed from indigenous dogs and cats in the 1940s and 1950s to wild carnivores and bats (11 of the 27 cases with known exposures); unusual exposures (3 cases) and exposures in a foreign country (7 cases) have also become more important. No exposure could be identified for 6 of the 38 cases. Two patients received optimal prophylaxis, 14 suboptimal, and 22 no prophylaxis after exposure. Some cases might have been prevented by an increased awareness of the risks and treatment for exposure to rabies, and use of the new rabies vaccines. The diagnosis was often made late in the clinical course including after death in 8 cases. This delay, in part, resulted from the diversity in the clinical presentation. Rabies should be considered in any case of encephalitis or myelitis. Laboratory confirmation of the diagnosis was often delayed. Testing for serum antibodies was the most reliable test in unvaccinated patients, and isolation of virus was the test most likely to be positive early in the illness.
Observations on the Visceral Removal of Plasma Peptidase Activity1
Authors: Theodore B. Schwartz, J. D. Myers
Journal: Journal of Clinical Investigation (1954)

Fluctuation in activity of plasma peptidases has been noted as a concomitant of a wide variety of clinical disorders.These proteolytic enzymes ex- hibit enhanced activity in the plasma of man or ex- perimental animals subjected to any severe tissue damage, and there is convincing evidence, dis- cussed elsewhere (1, 2), that these enzymes gain entrance to the circulation from injured or de- stroyed cellular components.With healing (3) or clinical remission (4, 5), elevated plasma pepti- dase values return to the normal range, but the mechanisms involved in the removal of peptidase activity from the plasma have not been systemati- cally investigated.The present study was under- taken in an attempt to determine the fate of these circulating peptidases. MATERIALS AND METHODSA. Nephrectomy in rats After an 18-hour fast, male rats of the Vanderbilt strain weighing 200 to 250 Gm. were bilaterally nephrecto- mized using pentobarbital anesthesia and a lumbodorsal operative approach.Twenty-four hours later the ani- mals were reanesthetized, and heparinized blood was col- lected from the abdominal aorta.Control blood samples were similarly obtained from rats not subjected to nephrectomy.B. Studies of splanchnic removal of plasma peptidase in man Accepted techniques were employed for collecting simultaneous femoral arterial and hepatic venous blood samples and determining hepatic blood flow, BSP clear- ance, net splanchnic oxygen consumption and net splanchnic glucose production (6-8).Peripheral venous blood was obtained from the antecubital vein.
478 PREOPERATIVE ALPHA-FETOPROTEIN LEVEL AND 18F-FDG PET PREDICT THE TUMOR RECURRENCE AFTER ADULT LIVING DONOR LIVER TRANSPLANTATION FOR HEPATOCELLULAR CARCINOMA BEYOND MILAN CRITERIA
Authors: T. Kim, K.-S. Suh, Y.M. Jeon, W.Y. Shin, N.-J. Yi, K.U. Lee
Journal: Journal of Hepatology (2010)
Effects of intracoronary administration of bradykinin on the impulse activity of afferent sympathetic unmyelinated fibers with left ventricular endings in the cat.
Authors: F Lombardi, P Della Bella, R Casati, A Malliani
Journal: Circulation Research (1981)

In anesthetized and artificially ventilated cats, we recorded the impulse activity of 23 afferent sympathetic unmyelinated fibers with left ventricular endings, dissected from the left sympathetic rami T3 and T4. All fibers displayed a spontaneous discharge at a rate of 0.79 +/- 0.2 (mean +/- SE) impulses/sec. During constriction of the thoracic aorta, the discharge increased to 1.92 +/- 0.2 impulses/sec. During myocardial ischemia, produced by interruption of left main coronary artery perfusion, supplied through an extracorporeal pump, the impulse activity increased to 1.73 +/- 0.3 impulses/sec. The mean latency for this excitation was 16.5 +/- 1.5 sec. The intracoronary administration of bradykinin (5 and 10 ng/kg) elicited a marked increase in impulse activity that, following 5 ng/kg, reached 2.06 +/- 0.2 impulses/sec, after a latency of 18 +/- 2 sec and in absence of significant hemodynamic changes. Myocardial ischemia and bradykinin never revealed the existence of silent afferent fibers included in the split nerve strand. The results obtained with this experimental model indicate that the ventricular endings of these afferent sympathetic unmyelinated fibers act as "polymodal" receptors. We hypothesize that the peripheral mechanism for cardiac nociception involves intensive excitation of fibers discharging spontaneously and not recruitment of silent fibers which are purely nociceptive in function.
S49 The diagnostic value of measuring AaG during exercise in patients with pulmonary hypertension
Authors: B Mukherjee, E Chan, K Murphy, H Tighe, R Davies, S Gibbs, L Howard
Journal: Thorax (2013)

<h3></h3> The exercise response in pulmonary hypertension (PH) has characteristic features, including decreased peak oxygen consumption (VO2-peak), increased ventilatory inefficiency (VE/VCO2 slope) and widened alveolar-arterial oxygen-gradient (AaG). We wished to evaluate if the AaG at peak exercise predicted those patients likely to have PH who would subsequently require catheter studies. <h3>Methods</h3> We performed a retrospective analysis of patients referred to Hammersmith Hospital between Feb 2008 and Feb 2012 for investigation of Pulmonary Hypertension (PH) who underwent cardiopulmonary exercise testing (CPX) with testing of AaG using arterial blood gas analysis at peak exercise. Patients found to have alternative cardiac or respiratory diagnoses were excluded. Patients given diagnoses of Pulmonary Arterial Hypertension or Pulmonary Hypertension due to Left Heart Disease and with temporally coincident data from CPX and RHC (within 3 months) were included. Patients without cardiorespiratory diagnoses were healthy controls. The VE/VCO2 slope and AaG were compared to the diagnosis of PH and the trans-pulmonary pressure gradient (TPG), (the difference between mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) where available). <h3>Results</h3> Using logistic regression to predict a diagnosis of PH, AaG had an odds ratios of 2.98 (p &lt; 0.01) and receiver operating characteristic curve for sensitivity and specificity had area under the curve (ROC-AUC) of 0.92. An AaG cut-off of 2.5kPA had 90% sensitivity and 80% specificity. Similarly, VE/VCO2 had an odds ratio of 1.21 (p &lt; 0.01) and ROC-AUC 0.85 for predicting PH. Combining AaG and VE/VCO2 had ROC-AUC of 0.94 for diagnosing PH without significant interaction between AaG and VE/VCO2. For predicting a TPG &gt;12mmHg, AaG had an odds ratios of 4.54 (p &lt; 0.01) and ROC-AUC of 0.95. VE/VCO2 had an odds ratio of 1.10 (p &lt; 0.01) and ROC-AUC 0.74 for predicting TPG&gt;12mmHg. <h3>Conclusion</h3> CPX has become part of the diagnostic workup of patients with PH. AaG measured at peak exercise has a high sensitivity and specificity in predicting patients with PH, which may help determining which patients will require invasive catheter studies. The AaG provides independent information than VE/VCO2 alone in predicting PH and may be useful in the investigation of PH.
Abstract 3416: Genomic alterations of the CDK4-pathway in melanoma and evaluation of the CDK4 Inhibitor PD-0332991.
Authors: Karen E. Sheppard, Allen Foo, Richard Young, Kelly Waldeck, Richard Pearson, Grant McArthur, James Christensen
Journal: Cancer Research (2013)

Abstract Activation of CDK4 by amplification, increased expression of Cyclin D1 (CCND1) or reduced expression of the CDK inhibitor p16 (CDKN2A) can contribute to melanocyte transformation, indicating that CDK4 can act as an oncogene in melanoma. We have analyzed the frequency of gene copy number variations (CNV) in the CDK4 pathway and looked for associations of these alterations with patient survival to assess if CDK4 is a viable target for the treatment of human melanoma. In addition, we screened a panel of melanoma cells with a highly selective CDK4/6 inhibitor PD-0332991 (PD-991) and performed gene expression and mutation analysis on these cells to explore possible genomic predictors of sensitivity. Genomic analysis revealed that 75% of primary melanomas had at least one CNV in the CDK4 pathway, with 55% showing a loss of CDKN2A. 28% of melanomas had two or more CNVs and melanomas with two or more CNVs involving CCND1 had worse overall survival (HR 5.56, P=0.02). From the cell line studies low CDKN2A mRNA expression, mutation or loss predicted sensitivity to PD-991 with 23 out of 27 mutant/loss cell lines being sensitive compared to only 3/7 wild type lines (p&amp;lt;0.03). Expression of CDK4, CCND1 or other cyclins or CDK-inhibitors did not predict sensitivity to PD-991. PD-991 induced an increase in both cell size and SA-ß-galactosidase activity that is indicative of a senescent phenotype, and this was associated with cells having wild type p53. In summary, genomic alterations in the CDK4 pathway are frequent in melanoma and are associated with worse survival, particularly when melanomas harbor two or more CNVs involving CCND1. CDK4 inhibition induces a senescent phenotype in melanoma cells that is associated with loss of CDKN2A and wild type TP53. Taken together these data support evaluation of CDK4 inhibitors in melanoma and suggest that CDKN2A and TP53 maybe genomic predictors of sensitivity. Citation Format: Karen E. Sheppard, Allen Foo, Richard Young, Kelly Waldeck, Richard Pearson, Grant McArthur, James Christensen. Genomic alterations of the CDK4-pathway in melanoma and evaluation of the CDK4 Inhibitor PD-0332991. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3416. doi:10.1158/1538-7445.AM2013-3416
Acute cholecystitis: a case for early surgery?
Authors: P F Jones
Journal: BMJ (1982)

splenectomy in a laparotomy performed for another purpose appear to be particularly hazardous.26Four of 12 hyposplenic patients submitted to colectomy for inflammatory bowel disease developed clinical features of the overwhelming post- splenectomy infection syndrome with disseminated intra- vascular coagulation,27 and subcutaneous heparin may have a role in prophylaxis perioperatively in such patients.Can severe infection after splenectomy be prevented?Penicillin prophylaxis seems reasonable in children to reduce the risk of pneumococcal infection.Active immunisation with pneumococcal vaccines should certainly be considered.Unfortunately, antibody responses are impaired in asplenia.2829Furthermore, not all serotypes which may cause disease have been included in current vaccines.The vaccine com- mercially available in Britain did not contain the antigen type that produced fatal pneumococcal septicaemia in a 22-year-old English woman with ulcerative colitis and splenic atrophy.30Nevertheless, asplenic patients should be sought out and immunised with existing vaccines, and pneumococcal vaccination should be performed before an elective splenectomy.Patients who have had a splenectomy or who have developed hyposplenism must be identified as being at special risk.Their general practitioners should be advised that if they develop an unexplained illness with shock, blood should be taken immediately for culture, and empirical treatment of the presumptive pneumococcal or haemophilus septicaemia should be started without delay-a suitable regimen is the combination of benzylpenicillin with amoxy- cillin.
STUDIES ON THE DISEASE OF GUINEA PIGS DUE TO BACILLUS ABORTUS
Authors: William A. Hagan
Journal: The Journal of Experimental Medicine (1922)

1. The infectivity of Bacillus abortus for guinea pigs is extremely great. It is computed that somewhat less than 100 organisms are required to infect most animals. 2. Occasional animals are encountered having much more resistance to Bacillus abortus infection than is possessed by the average. The most resistant animal encountered was infected by a number of organisms computed to be less than 10,000. 3. The principal effect on the character of the Bacillus abortus disease, caused by varying the size of the infecting dose, is a change in the time relations. Very small doses produce an infection of slower course than do larger doses, but the eventual results are practically the same. 4. Judging by the agglutination curves, guinea pigs inoculated with large or medium sized doses of Bacillus abortus generally begin to gain mastery over the disease about the 10th week after inoculation. At this time the agglutination curve begins to decline. As was first shown by Smillie, the numbers of bacteria in the body organs begin to decline at about the 4th week but the change is rather slow until about the 10th or 12th week when a rapid decline begins, coincidently with the fall in the agglutinin titer. When the inoculating dose is small the course of the disease may be much prolonged. The defensive forces of the body would appear to be quite inactive until a certain stage in the disease is reached. 5. The virulence of Bacillus abortus cultures for guinea pigs may be raised or lowered by appropriate passage through these animals. 6. Normal guinea pig blood will not agglutinate Bacillus abortus in a dilution of 1:10. Immune agglutinins are easily produced by inoculations with dead or living organisms. Agglutinins for Bacillus abortus are capable of passing the placental filter. 7. There appears to be little or no danger of normal guinea pigs becoming infected by association with diseased animals of their own sex. One instance is reported, however, of the infection of a male animal that had cohabited with infected females. 8. The susceptibility of guinea pigs to infection through ingestion of Bacillus abortus is relatively slight.
Prevention of Venous Thromboembolism in Surgical Patients
Authors: G. Patrick Clagett, Edwin W. Salzman
Journal: New England Journal of Medicine (1974)

DESPITE recent advances in diagnosis, venous thrombosis and pulmonary embolism remain major problems in surgical patients. Evidence of previous pulmonary embolism can be found in more than 60 per cent of routine autopsies.1 Pulmonary embolism is a frequent postoperative complication in general surgical, orthopedic and gynecologic patients and is the most common cause of death in the elderly injured.2 Elevations in the concentration of plasma procoagulants, increased fibrinogen levels, thrombocytosis, increased platelet reactivity and defective fibrinolysis are commonly observed after major surgery.3 Augmented by venous stasis engendered by recumbency or immobilization in a chair, these abnormalities seriously predispose to postoperative . . .
Discovery of Novel Biomarkers by Microarray Analysis of Peripheral Blood Mononuclear Cell Gene Expression in Benzene-Exposed Workers
Authors: Matthew S. Forrest, Qing Lan, Alan E. Hubbard, Luoping Zhang, Roel Vermeulen, Xin Zhao, Guilan Li, Yen-Ying Wu, Min Shen, Songnian Yin, Stephen J. Chanock, Nathaniel Rothman, Martyn T. Smith
Journal: Environmental Health Perspectives (2005)

Benzene is an industrial chemical and component of gasoline that is an established cause of leukemia. To better understand the risk benzene poses, we examined the effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression in a population of shoe-factory workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was stabilized in the field and analyzed using a comprehensive human array, the U133A/B Affymetrix GeneChip set. A matched analysis of six exposed-control pairs was performed. A combination of robust multiarray analysis and ordering of genes using paired t-statistics, along with bootstrapping to control for a 5% familywise error rate, was used to identify differentially expressed genes in a global analysis. This resulted in a set of 29 known genes being identified that were highly likely to be differentially expressed. We also repeated these analyses on a smaller subset of 508 cytokine probe sets and found that the expression of 19 known cytokine genes was significantly different between the exposed and the control subjects. Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects. The altered expression was not caused by changes in the makeup of the PBMC fraction. Thus, microarray analysis along with real-time PCR confirmation reveals that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure.
Assessing Competencies of Knowledge and Process Improvement
Authors: Marvin A. Dewar
Journal: JAMA (2008)

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Screening for Colon Cancer — Can We Afford Colonoscopy?
Authors: Allan S. Detsky
Journal: New England Journal of Medicine (2001)

Over the past 20 years, much has been learned about screening for colon cancer from biologic, epidemiologic, and clinical studies.1 Colorectal cancer is a leading cause of death in the Western world, but survival can be improved if the disease is detected early. Precursor lesions (polyps) almost always precede the development of the neoplasm by several years, and removing polyps may reduce the risk of cancer. A variety of screening techniques can detect premalignant lesions and early-stage cancers.Four large-scale, randomized trials have shown that annual or biennial screening of people without symptoms by means of fecal occult-blood testing reduces . . .