tbuckley/cabot-search huggingface dataset:
Accuracy of lung auscultation to detect abnormal respiratory mechanics: A cross-sectional diagnostic study
Authors: Glaciele Xavier, César Melo, Eduardo Gaio, Veronica Amado
Journal: European Respiratory Journal (2014)

Introduction: Lung auscultation is a subjective method used in clinical practice for the evaluation and detection of respiratory system abnormalities. Measuring respiratory mechanics at the bedside is an objective method and helps to guide clinical practice.

Objectives: To correlate the lung sounds with the respiratory system mechanical properties and to analyze the agreement between examiners in assessing this clinical examination in mechanically ventilated patients.

Methods: The respiratory system mechanical properties of 200 mechanically ventilated patients in the immediate postoperative period after cardiac surgery (116 men; 56 ± 11 years) were assessed. Then, 2 independent examiners carried out the lung auscultation. For the correlation analysis, ronchi and wheezes were correlated with increased respiratory system resistance (R,rs) (increased R,rs defined as › 15 cmH2O/L/s), and breath sound and crackles related to decreased respiratory system compliance (C,rs) (decreased C,rs defined as ‹ 50 mL/cmH2O). The interobserver agreement was quantified by the Kappa statistic.

Results: There was a correlation between the presence of ronchi and wheezes with increased R,rs only for 1 examiner (P=0.001) and breath sound and crackles were not associated with decreased C,rs (P=1.0) despite the examiner. The kappa was 0.2 (P=0.3) for sounds related with increased R,rs and 0.6 (P=0.2) for sounds related with decreased C,rs.

Conclusion: Lung auscultation is not associated with decreased C,rs of mechanically ventilated patients in the immediate postoperative period after cardiac surgery and there was not an agreement between examiners.
Dominant determinants in hen eggwhite lysozyme correspond to the cryptic determinants within its self-homologue, mouse lysozyme: implications in shaping of the T cell repertoire and autoimmunity.
Authors: K D Moudgil, E E Sercarz
Journal: The Journal of Experimental Medicine (1993)

We have studied the mouse lysozyme (ML) peptide-specific T cell repertoire in mice of five different major histocompatibility complex (MHC) class II haplotypes. 14 ML peptides were tested in a lymph node T cell proliferation assay. Upon immunization of diverse mouse strains with native ML, there was no response to any of the ML peptides tested. However, nine peptides were immunogenic, although there was no consistent pattern of reactivity toward any peptide among these strains. Thus, an autoreactive T cell repertoire directed against cryptic self(ML)-determinants exists, and it is different in mice of different MHC haplotypes. Moreover, our results demonstrate that crypticity is MHC associated and not merely a structural attribute of the determinant. On comparison of the pattern of response of various peptides of ML and that of its foreign homologue, hen eggwhite lysozyme (HEL) in H-2k, H-2b, and H-2d strains of mice, a striking correlation was evident. The stretches of amino acid sequences of determinants within HEL that were dominant in each of these three strains, almost exactly overlapped in position with those of the cryptic ML determinants against which self-reactivity was demonstrated in the same strain. These results demonstrate that the dominance-crypticity relationship between HEL and ML resulting from differential processing of these two proteins is critical in determining the response to HEL rather than the degree of sequence difference between them. These observations have important implications in the shaping of the T cell repertoire for foreign proteins and in the pathogenesis of autoimmunity.
Neural networks in the analysis of episodic growth hormone release
Authors: K Prank
Journal: Human Reproduction Update (1997)

Pulsatile secretion of growth hormone (GH) has been observed in healthy controls as well as acromegalic patients. In healthy adults, highly regulated secretory pulses of GH occur 4-8 times within 24 h. This episodic pattern of secretion seems to be related to the optimal induction of physiological effects at the peripheral level. In contrast to normal subjects, acromegalic patients demonstrate an irregular pattern of excessive GH release. This pattern of secretion is responsible for many systemic effects, such as the stimulation of connective tissue growth, cardiovascular and cerebrovascular disease, diabetes mellitus and arthritis. Standard methods for the analysis of pulsatile patterns of hormone secretion did not consistently separate the temporal dynamics of GH release in healthy controls and acromegalic patients under various study conditions. Using the cutting edge technology of artificial neural networks for time series prediction, we were able to achieve significant separation of both groups under various conditions by means of the predictability of their GH secretory dynamics. Improving the predictive results by using a more refined system of multiple neural networks acting in parallel (adaptive mixtures of local experts), we found that this system performed a self-organized segmentation of hormone pulsatility. It separated phases of secretory bursts and quiescence without any prior knowledge of the form of a GH pulse or a model of secretion. Comparing the predictive results for the GH dynamics with those for computer-simulated stochastic processes, we were able to define the irregular pattern of GH secretion in acromegaly as a random autonomous process. The introduction of neural networks to the analysis of dynamic endocrine systems might help to expand the existing analytical approaches beyond counting frequency and amplitude of hormone pulses.
FURTHER OBSERVATIONS ON THE RELATION OF THE EYE TO IMMUNITY IN EXPERIMENTAL SYPHILIS
Authors: Alan M. Chesney, Alan C. Woods
Journal: The Journal of Experimental Medicine (1944)

Two experiments are reported in which an attempt was made to determine the extent to which a primary syphilitic infection of the cornea in rabbits is followed by the development of a local corneal immunity, by the generalization of the virus, and by the development of a general immunity to the infection. Female rabbits were inoculated intracorneally with a virulent strain of T. pallidum and the disease was allowed to run its course until the lesions which had developed at the site of inoculation had healed spontaneously. Popliteal lymph nodes were transferred from about one-half of these animals (in the second experiment only) to normal male rabbits and in almost every instance the nodes were proved by this method to contain virulent treponemes, showing that generalization of the syphilitic infection is the rule after intracorneal inoculation. All animals were treated with arsphenamine after the local lesion had subsided (160 and 275 days after the original inoculation). The rabbits were then reinoculated with the homologous strain of treponemes, injections being made into the cornea originally inoculated and also into the skin of the back. In one experiment both corneas were reinoculated. The incidence of lesions developing in either cornea after reinoculation was higher than the incidence of lesions developing in the skin. The lesions developing in the corneas of the "immune" animals had a longer incubation period and were of shorter duration on the average than the lesions in the control group. As far as intensity of reaction was concerned no difference was observed. Inoculation of the cornea of rabbits with syphilitic virus is often followed by the development of immunity to the homologous strain of organisms. This immunity is imparted to the skin to a greater extent than to either the cornea inoculated originally or to the opposite uninoculated cornea. It persists after treatment with arsphenamine. It appears to be more marked the longer treatment is postponed. It is apparent from Table IV that in one-half of all the test animals both cornea and skin were immune to a second inoculation of homologous syphilitic virus. In addition to these there were 5 animals in which the cornea was immune and the skin nearly so, for the lesions which developed in the skin of these animals were minimal in extent and duration and were in no way comparable to those which were observed in the controls. Thus in two-thirds of our animals there developed in both the skin and the cornea, after a primary intracorneal inoculation, a high degree of resistance toward a second inoculation with homologous syphilitic virus, but syphilitic disease of the cornea does not always impart to the cornea itself an absolute immunity to reinoculated homologous virus.
Epidemiologic studies of fatal and nonfatal cardiovascular disease and ETS exposure from spousal smoking.
Authors: M Thun, J Henley, L Apicella
Journal: Environmental Health Perspectives (1999)

This article reviews the epidemiologic studies of the association of ischemic heart disease risk and environmental tobacco smoke (ETS) exposure from a spouse who smokes. Seventeen studies (nine cohort, eight case-control) comprising more than 485,000 lifelong nonsmokers and 7,345 coronary heart disease (CHD) events were included in a meta-analysis. Together, these studies include 36% more CHD events and 58% more study subjects than were available for review by the U. S. Occupational Safety and Health Administration (OSHA) in 1994. The relative risk (RR) for fatal or nonfatal coronary events among never smokers married to smokers, compared to those whose spouses did not smoke, was RR = 1.25 (95% confidence interval [95% CI], 1.17-1.33) across the combined studies. This association was statistically similar in men (RR = 1.24; 95% CI, 1.15-1.32) and women (RR = 1.23; 95% CI, 1.15-1.32); in studies of cohort (RR = 1.23; 95% CI, 1.15-1. 31) and case-control (RR = 1.47; 95% CI, 1.19-1.81) design; in the United States (RR =1.22; 95% CI, 1.13-1.30) and other countries (RR = 1.41; 95% CI, 1.21-1.65); and in studies of fatal (RR = 1.22; 95% CI, 1.14-1.30) and nonfatal (RR = 1.32; 95% CI, 1.04-1.67) heart disease. In three studies that presented data separately for nonsmokers married to current or former smokers, the association was stronger when the spouses continued to smoke (RR = 1.16, 1.06-1.28) than with former smokers (RR = 0.98; 95% CI, 0.89-1.08). The aggregate data are unlikely to be attributable to chance, publication bias, confounding, or misclassification of exposure. The evidence linking heart disease and ETS exposure from a spouse has become substantially stronger since OSHA first proposed including heart disease in its risk assessment of ETS in 1994.
Viral hepatitis B and C in children
Authors: D. Kelly
Journal: Journal of the Royal Society of Medicine (2006)

Viral hepatitis B and C are the cause of significant disease worldwide.Acute infection is more common with hepatitis B than C in childhood; but chronic asymptomatic infection leading to chronic liver disease and hepatocellular carcinoma is a considerable concern.The natural history of hepatitis B is well established in adults but the long-term outcome for children is still under debate.Following an acute infection, 90% will recover spontaneously; but approximately 1% of patients develop acute fulminant hepatitis requiring liver transplantation.The main source of infection in childhood is perinatal transmission, which is effectively prevented using vaccination, antenatal screening and screening of blood products and organ donors.The vaccine is effective in 97% of newborn infants and lasts for 10-15 years.All children with chronic hepatitis B infection should be annually monitored and those with persistent infection should be considered for anti-viral therapy.Treatment options include Interferon (5 M units per m 2 subcutaneously Â3 weekly for 6 months) or Lamivudine (3 mg/kg for 12-24 months), but neither therapy is completely effective.Interferon clears viral infection in 20%-40% and is most effective in children with elevated transaminases or horizontal transmission.Only 23% seroconvert after lamivudine, 26% of whom may develop resistance with YMDD mutant variants of the hapatitis B virus.A number of other drugs, such as Adefovir Dipivoxil, Famciclovir, Entecavair and Pegylated Interferon, are under evaluation.Liver transplantation is an effective treatment for children with acute or chronic liver failure, but recurrence is high without prophylaxis.The main route of transmission for hepatitis C was originally through infected blood products or organs; but now the most common source is vertical transmission which ranges from 2%-12% depending on maternal infectivity.Breast feeding is safe in mothers with low titres of hepatitis C RNA.The natural spontaneous clearance rate for hepatitis C is between 20% and 40% and is higher in children who have been parenterally infected compared to perinatal infection.It is a mild disease in children, but the indication for treatment is based on the future risk of cirrhosis and hepatocellular cancer.Children with persistent infection (hepatitis C RNA positive for 6 months) and evidence of histological disease should be considered for combination treatment with Pegylated Interferon (3 M units/m 2 subcutaneously Â1 weekly) and oral Ribavirin (15 mg/kg) which has a sustained response rate of 80%-100% for genotypes 2 and 3, and 50% for genotype 1. Liver transplantation for hepatitis C in children is rarely required, but 100% recurrence can be expected without prophylaxis.Emerging new therapies include viral enzyme inhibitors, cytokines, antisense oligonucleosides which are at an early stage of development.
Bicalutamide Monotherapy Versus Leuprolide Monotherapy for Prostate Cancer: Effects on Bone Mineral Density and Body Composition
Authors: Matthew R. Smith, Melissa Goode, Anthony L. Zietman, Francis J. McGovern, Hang Lee, Joel S. Finkelstein
Journal: Journal of Clinical Oncology (2004)

Purpose Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition. Patients and Methods In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily). Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography. Results Mean (± standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% ± 0.5% in the leuprolide group and increased by 2.5 ± 0.5 in the bicalutamide group from baseline to 12 months (P &lt; .001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P ≤ .003 for each comparison). Fat mass increased by 11.1% ± 1.3% in the leuprolide group and by 6.4% ± 1.1% in the bicalutamide group (P = .01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group. Conclusion In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist.
European Antimicrobial Resistance Surveillance System (EARSS): susceptibility testing of invasive Staphylococcus aureus
Authors: I Veldhuijzen, S Bronzwaer, J Degener, J Kool, Collective les participants de EARSS / EARSS participants
Journal: Eurosurveillance (2000)

Over 400 laboratories participate in EARSS (European Antimicrobial Resistance Surveillance System) and send data to the National Institute of Public Health and the Environment (RIVM) in The Netherlands. Data on about 14 000 isolates of Staphylococcus aure
Effectiveness of Radiation Therapy in Older Women With Ductal Carcinoma In Situ
Authors: Benjamin D. Smith, Bruce G. Haffty, Thomas A. Buchholz, Grace L. Smith, Deron H. Galusha, Justin E. Bekelman, Cary P. Gross
Journal: JNCI Journal of the National Cancer Institute (2006)

For women with ductal carcinoma in situ (DCIS), radiation therapy after conservative surgery lowers the risk of recurrence. However, emerging evidence suggests that radiation therapy confers only a marginal absolute benefit for older women with DCIS. In a cohort of older women with DCIS, we sought to determine whether radiation therapy was associated with a clinically significant benefit.Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from January 1, 1992, through December 31, 1999, we identified 3409 women aged 66 years or older treated with conservative surgery for DCIS. A proportional hazards model tested whether radiation therapy was associated with a lower risk of a combined outcome, defined as a subsequent ipsilateral in situ or invasive breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. The 5-year event risk was determined for patients without and with high-risk features, which were defined as at least one of the following: age 66-69 years, tumor larger than 2.5 cm, comedo histology, and/or high grade. All statistical tests were two-sided.Radiation therapy was associated with a lower risk for each component of the combined outcome (hazard ratio = 0.32, 95% confidence interval [CI] = 0.24 to 0.44). For high-risk patients, the 5-year event risk was 13.6% without radiation therapy versus 3.8% with radiation therapy (difference = 9.8%, 95% CI = 6.5 to 13.2; P<.001). For low-risk patients, the 5-year event risk was 8.2% without radiation therapy versus 1.0% with radiation therapy (difference = 7.2%, 95% CI = 3.6 to 10.9; P<.001). Among healthy women aged 66-79 years, the number needed to treat with radiation therapy to prevent one event in 5 years was 11 for high-risk patients and 15-16 for low-risk patients.For older women with DCIS, radiation therapy appears to confer a substantial benefit that remains meaningful even among low-risk patients.
Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Single-Agent Gemcitabine As First-Line Treatment of Patients With Advanced Pancreatic Cancer: The GIP-1 Study
Authors: Giuseppe Colucci, Roberto Labianca, Francesco Di Costanzo, Vittorio Gebbia, Giacomo Cartenì, Bruno Massidda, Elisa Dapretto, Luigi Manzione, Elena Piazza, Mirella Sannicolò, Marco Ciaparrone, Luigi Cavanna, Francesco Giuliani, Evaristo Maiello, Antonio Testa, Paolo Pederzoli, Massimo Falconi, Ciro Gallo, Massimo Di Maio, Francesco Perrone
Journal: Journal of Clinical Oncology (2010)

Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) > or = 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m(2) weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m(2) added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral alpha .05, 355 events were needed and 400 patients planned.Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS > or = 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.
VEGF blockade damages brain vessels
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

A factor that promotes blood vessel growth keeps two types of brain cells alive, say Maharaj et al. (page 491). Their findings might explain why anticancer drugs that block this factor cause neurological side effects.






Figure 1

Mice that express high levels of VEGF-blocking molecules develop brain lesions (arrows).




The drug target in question—vascular endothelial growth factor (VEGF)—binds to receptors on blood vessel endothelial cells. A localized increase in VEGF, which is produced by underlying epithelial cells and other neighboring cells, promotes vessel growth in developing organs and injured tissues.

Lower levels of VEGF might also be necessary for the survival of endothelial cells, which become apoptotic when cultured in the absence of VEGF. VEGF-blocking drugs that limit tumor growth by inhibiting the tumors' blood supply can cause seizures and brain swelling in some cancer patients. To find out whether these symptoms stem from the destruction of brain blood vessels, Maharaj et al. examined the brains of mice that had been engineered to express high levels of proteins that block VEGF and TGFβ—a cytokine that stimulates VEGF production.

Besides damage to brain endothelia, the mice developed brain lesions due to a breakdown of the barrier that prevents cerebral spinal fluid from seeping into the brain. The specialized type of epithelial cells that make up this barrier expressed VEGF receptors and became apoptotic when VEGF was systemically blocked. Why brain complications only occur in a subset of cancer patients on anti-VEGF therapy is unknown.