tbuckley/cabot-search huggingface dataset:
Clinical and economic consequences of a reimbursement restriction of nebulised respiratory therapy in adults: direct comparison of randomised and observational evaluations
Authors: Sebastian Schneeweiss, Malcolm Maclure, Bruce Carleton, Robert J Glynn, Jerry Avorn
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To compare the results of a randomised and an observational evaluation of the same policy that restricted reimbursement for nebulised respiratory medications in adult patients in a community setting. <b>Designs</b> Cluster randomised controlled trial and observational time series with historical controls. <b>Setting</b> Pharmacare, the government funded drug benefits plan for elderly people and patients receiving social assistance in British Columbia, Canada. <b>Participants</b> In the randomised controlled trial 104 clusters of medical practices, pair matched by geography and approximately by practice size, were randomised to the intervention group (449 patients affected by the policy on 1 March 1999), and the control group (offered a six month exemption, affecting 386 patients). The observational analysis included all Pharmacare beneficiaries (excluding the 386 exempt patients) who had used any nebulised drugs six months before the policy (4624 patients). <b>Intervention</b> Pharmacare restricted reimbursement for nebulised bronchodilators, steroids, and cromoglycate to patients whose doctors applied for an individual patient9s exemption, giving an appropriate clinical reason. <b>Main outcome measures</b> Number of contacts with doctors and services, emergency admissions to hospital, and utilisation of and expenditure for respiratory drugs in databases of British Columbia9s Ministry of Health. <b>Results</b> Contacts with doctors or emergency admissions to hospital did not increase in association with the restriction, regardless of the analytical approach. In the observational analysis, we found a reduction of $C24 per patient month in all nebulised drug use (95% confidence interval 19 to 29) and an increase of $C3 per patient month in all expenditure for inhalers (1.4 to 4.5). The randomised evaluation found savings of $C8 per patient month for nebulisers (P = 0.24) and no increase in spending on inhalers (P = 0.79). Correcting for 60% non-compliance by exempt doctors in a sensitivity analysis yielded similar results as the observational evaluation. <b>Conclusions</b> Observational as well as randomised analyses found moderate net savings and no increase in unintended healthcare outcomes after restricting reimbursement for nebulised respiratory drugs. Randomised policy trials are feasible and, if carefully implemented, likely to be concordant with observational evaluations.
Autologous fascia lata transplantation for heart valve replacement: A two-year experience at the National Heart Hospital, London
Authors: H. Dalichau, L. Gonzalez-Lavin, D. N. Ross
Journal: Thorax (1972)

Between April 1969 and December 1970, 201 patients underwent 262 valve replacements with frame-mounted autologous fascia lata valves in the aortic, mitral, and/or tricuspid positions at the National Heart Hospital. A single fascia lata valve was inserted in 146 patients and multi-valve replacement was performed in 55 instances. Hospital and late mortality are comparable with that following other procedures of heart valve replacement. One hundred and fifty-four patients with 193 fascia lata valves were available for follow-up. A retrospective analysis of this method of valve replacement has been undertaken to assess the suitability of fascia lata as a heart valve substitute as well as the clinical results achieved by this method of valve replacement.
Systemic tolerance and secretory immunity after oral immunization.
Authors: S J Challacombe, T B Tomasi
Journal: The Journal of Experimental Medicine (1980)

Diminished systemic immune reaction after ingestion of antigen has been reported in several animal models. Conversely, it has been reported recently that oral immunization may lead to the production of secretory antibodies. To determine whether these events could occur concurrently, CBA/J mice were immunized intragastrically with varying doses of ovalbumin (OVA) and Streptococcus mutans. After 7 d, the animals were challenged systemically with antigen in complete adjuvant and 8 d later serum and saliva taken, and the draining lymph nodes assayed for a proliferative response. Intragastric doses of 1 mg OVA or 10(9) S. mutans led to significant suppression of the proliferative response, and intragastric doses of 10 mg OVA or 2.5 X 10(9) S. mutans led to the production of detectable salivary antibodies using hemagglutination. Serum antibodies were not detected after intragastric administration of OVA or S. mutans. Suppression of the proliferative response could be detected from 2-60 d after intragastric administration of OVA, and 2-21 d after S. mutans. Prior intragastric immunization with heterologous antigens did not suppress the response to OVA or S. mutans. Transfer of 40 X 10(6) mesenteric lymph node cells from mice given 20 mg OVA or 10(9) S. mutans led to suppression of the proliferative response in syngeneic recipients. Salivary antibodies wer removed by absorption with anti-IgA, but not anti-IgG or IgM, indicating that they were of the IgA class. It appears that intragastric administration of soluble or particulate antigens in mice may lead to the concurrent induction of salivary antibodies and systemic suppression.
Radiation Dose and Breast Cancer Risk in the Childhood Cancer Survivor Study
Authors: Peter D. Inskip, Leslie L. Robison, Marilyn Stovall, Susan A. Smith, Sue Hammond, Ann C. Mertens, John A. Whitton, Lisa Diller, Lisa Kenney, Sarah S. Donaldson, Anna T. Meadows, Joseph P. Neglia
Journal: Journal of Clinical Oncology (2009)

The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer.We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records.The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine.Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones.
Plasma Concentration of Asymmetric Dimethylarginine (ADMA) Predicts Cardiovascular Morbidity and Mortality in Type 1 Diabetic Patients With Diabetic Nephropathy
Authors: Maria Lajer, Lise Tarnow, Anders Jorsal, Tom Teerlink, Hans-Henrik Parving, Peter Rossing
Journal: Diabetes Care (2008)

To investigate whether circulating asymmetric dimethylarginine (ADMA) levels are predictive of cardiovascular events, decline in glomerular filtration rate (GFR), end-stage renal disease (ESRD), and all-cause mortality in type 1 diabetic patients.We performed a prospective observational follow-up study including 397 type 1 diabetic patients with overt diabetic nephropathy (243 men aged 42.1 +/- 10.5 years, GFR 76 +/- 34 ml/min per 1.73 m(2)) and a control group of 175 patients with longstanding type 1 diabetes and persistent normoalbuminuria (104 men aged 42.7 +/- 9.7 years, duration of diabetes 27.7 +/- 8.3 years). Patients were followed for a median 11.3 years (range 0.0-12.9) with yearly measurements of GFR ((51)Cr-EDTA plasma clearance) in patients with diabetic nephropathy. Endpoints were fatal and nonfatal cardiovascular disease (CVD), decline in GFR, ESRD, and all-cause mortality.Among patients with diabetic nephropathy, 37 patients (19.4%) with ADMA levels below the median, compared with 79 patients (43.4%) above the median, suffered a major cardiovascular event during the follow-up period (P < 0.001). This effect persisted after adjustment for conventional CVD risk factors including baseline GFR (adjusted hazard ratio [HR] for elevated ADMA 2.05 [95% CI 1.31-3.20], P = 0.002). Furthermore, elevated ADMA levels predicted an increased rate of decline in GFR, development of ESRD, and all-cause mortality (P < 0.001). After adjustment for well-known progression promoters, including baseline GFR, the HR (adjusted) was 1.85 (95% CI 0.99-3.46, P = 0.055) for ESRD comparing upper and lower median ADMA levels.Plasma ADMA levels predict fatal and nonfatal cardiovascular events in patients with type 1 diabetic nephropathy. Furthermore, increased ADMA levels tend to contribute to increased risk of progressive diabetic kidney disease.
Relation between response to exercise and diurnal variability of peak expiratory flow in primary school children.
Authors: T Frischer, J Kuhr, R Meinert, W Karmaus, J Forster, R Urbanek
Journal: Thorax (1993)

BACKGROUND: Variability in peak expiratory flow (PEF) has been proposed as a simple method of screening for asthma in epidemiological studies. This study was designed to assess whether the bronchial response to exercise and the diurnal variation in PEF identified the same subjects. METHODS: Bronchial response to a free running exercise test was assessed in a cohort of 918 seven year old children and was compared with variability of PEF as assessed by twice daily recordings for a one week period. Mini Wright peak flow meters were used throughout the study. RESULTS: Baseline PEFs of both tests were highly correlated but there was no significant correlation between a response to exercise and variability of PEF. Of 33 children with a physician9s diagnosis of asthma, 18 had at least one abnormal test, but only five children were abnormal in both tests, showing that the tests did not identify the same subjects. CONCLUSION: Increased variability of PEF, as well as a response to exercise, was associated with respiratory symptoms, but only a response to exercise was closely associated with atopy (defined as a positive skin test to any of seven aero-allergens).
Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives.
Authors: C Cellier, T Sahmoud, E Froguel, A Adenis, J Belaiche, J F Bretagne, C Florent, M Bouvry, J Y Mary, R Modigliani
Journal: Gut (1994)

The relationships between clinical activity, endoscopic severity, and biological parameters in Crohn9s disease have not been thoroughly investigated and a link was therefore sought between these three elements. The following parameters were determined simultaneously in 121 consecutive patients with colonic or ileocolonic Crohn9s disease: Crohn9s disease activity index, Crohn9s disease endoscopic index of severity, and serum albumin, alpha 2-globulin, alpha 1-antitrypsin, orosomucoid, C reactive protein, erythrocyte sedimentation rate, platelets, lymphocyte and polymorphonuclear cell counts, haematocrit, and faecal alpha 1-antitrypsin concentration. The distribution of these parameters was studied and transformation was used so that data matched the normal distribution closely. A weak but significant correlation (r = 0.32; p &lt; 0.001) was found between clinical and endoscopic indices in the whole group of patients and this correlation seemed to be homogenous in various patient subgroups (clinically quiescent or active disease, pure colonic disease, untreated patients). Endoscopic or clinical indices were also found to be weakly linked with biological parameters (r &lt; 0.50). Stepwise linear regression identified C reactive protein as predictive of the clinical index, and, successively, alpha 2-globulin, erythrocyte sedimentation rate, faecal alpha 1-antitrypsin, serum orosomucoid, and alpha 1-antitrypsin as predictive of the endoscopic index. Both predictions were poor--the biological variables accounting for only 22 and 44% respectively of the clinical and endoscopic index variations. In conclusion, Crohn9s disease clinical activity seems to be virtually independent of the severity of the mucosal lesions and biological activity.
Different electrical responses to vasoactive agonists in morphologically distinct smooth muscle cell types.
Authors: C B Neylon, P V Avdonin, R J Dilley, M A Larsen, V A Tkachuk, A Bobik
Journal: Circulation Research (1994)

Vascular smooth muscle cells (SMCs) in the blood vessel wall are frequently heterogeneous in nature, differing in their gross morphology, size, and shape, subcellular organelles, cytoskeleton, and contractile protein composition. In adult rat arterial vessels, two populations of SMCs have been shown to predominate: elongated bipolar cells, representing the majority of cells, and epithelial-like SMCs. We examined the ionic responses of these two types of SMCs, isolated by multiple subculture, to vasoactive stimuli. Elevations in intracellular Na+ and Ca2+ were measured with SBFI and fura 2, respectively, and changes in membrane potential were measured using the potential-sensitive fluorescent probe bis-oxonol. The resting membrane potential of the elongated bipolar cells was less negative than that of the epithelial-like SMCs. Exposure of the elongated SMCs to endothelin 1, alpha-thrombin, or arginine vasopressin induced elevations in [Ca2+]i and [Na+]i and membrane depolarization. Depolarization occurred because of entry of both Na+ and Ca2+, and pharmacological blockade of Cl- or K+ channels did not attenuate the depolarization. In contrast, when [Ca2+]i was elevated by the same agonists in the epithelial-like SMCs there was a pronounced hyperpolarization that appeared to be the consequence of enhanced activity of charybdotoxin-sensitive Ca(2+)-activated K+ channels because it was abolished by charybdotoxin (20 nmol/L), partially attenuated by tetraethylammonium chloride (10 mmol/L), and unaffected by apamin (1 mumol/L), glibenclamide (1 mumol/L), or 4-aminopyridine (5 mmol/L). Chelation of [Ca2+]i also abolished the hyperpolarization; instead, a small depolarization was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of coronavirus on human nasal ciliated respiratory epithelium
Authors: M.A. Chilvers, M. McKean, A. Rutman, B.S. Myint, M. Silverman, C. O'Callaghan
Journal: European Respiratory Journal (2001)

Human coronavirus (HCoV) accounts for 15–30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6–14.0) and day 3 (9.4 Hz (95% CI 7.2–11.6)), there was a significant increase (p&lt;0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0–0.5)) and day 3 (1.1 (95% CI 0.5–1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.
Population Genomics Reveals Chromosome-Scale Heterogeneous Evolution in a Protoploid Yeast
Authors: Anne Friedrich, Paul Jung, Cyrielle Reisser, Gilles Fischer, Joseph Schacherer
Journal: Molecular Biology and Evolution (2014)

Yeast species represent an ideal model system for population genomic studies but large-scale polymorphism surveys have only been reported for species of the Saccharomyces genus so far. Hence, little is known about intraspecific diversity and evolution in yeast. To obtain a new insight into the evolutionary forces shaping natural populations, we sequenced the genomes of an expansive worldwide collection of isolates from a species distantly related to Saccharomyces cerevisiae: Lachancea kluyveri (formerly S. kluyveri). We identified 6.5 million single nucleotide polymorphisms and showed that a large introgression event of 1 Mb of GC-rich sequence in the chromosomal arm probably occurred in the last common ancestor of all L. kluyveri strains. Our population genomic data clearly revealed that this 1-Mb region underwent a molecular evolution pattern very different from the rest of the genome. It is characterized by a higher recombination rate, with a dramatically elevated A:T → G:C substitution rate, which is the signature of an increased GC-biased gene conversion. In addition, the predicted base composition at equilibrium demonstrates that the chromosome-scale compositional heterogeneity will persist after the genome has reached mutational equilibrium. Altogether, the data presented herein clearly show that distinct recombination and substitution regimes can coexist and lead to different evolutionary patterns within a single genome.
Plant Expansins in Bacteria and Fungi: Evolution by Horizontal Gene Transfer and Independent Domain Fusion
Authors: Nikolas Nikolaidis, Nicole Doran, Daniel J. Cosgrove
Journal: Molecular Biology and Evolution (2013)

Horizontal gene transfer (HGT) has been described as a common mechanism of transferring genetic material between prokaryotes, whereas genetic transfers from eukaryotes to prokaryotes have been rarely documented. Here we report a rare case of HGT in which plant expansin genes that code for plant cell-wall loosening proteins were transferred from plants to bacteria, fungi, and amoebozoa. In several cases, the species in which the expansin gene was found is either in intimate association with plants or is a known plant pathogen. Our analyses suggest that at least two independent genetic transfers occurred from plants to bacteria and fungi. These events were followed by multiple HGT events within bacteria and fungi. We have also observed that in bacteria expansin genes have been independently fused to DNA fragments that code for an endoglucanase domain or for a carbohydrate binding module, pointing to functional convergence at the molecular level. Furthermore, the functional similarities between microbial expansins and their plant xenologs suggest that these proteins mediate microbial–plant interactions by altering the plant cell wall and therefore may provide adaptive advantages to these species. The evolution of these nonplant expansins represents a unique case in which bacteria and fungi have found innovative and adaptive ways to interact with and infect plants by acquiring genes from their host. This evolutionary paradigm suggests that despite their low frequency such HGT events may have significantly contributed to the evolution of prokaryotic and eukaryotic species.
Equilibrative Nucleoside Transporter 1 Expression Is Downregulated by Hypoxia in Human Umbilical Vein Endothelium
Authors: Paola Casanello, Alberto Torres, Felipe Sanhueza, Marcelo González, Marcelo Farías, Victoria Gallardo, Marçal Pastor-Anglada, Rody San Martín, Luis Sobrevia
Journal: Circulation Research (2005)

Reduced oxygen level (hypoxia) induces endothelial dysfunction and release of the endogenous nucleoside adenosine. Human umbilical vein endothelium (HUVEC) function in an environment with 3% to 5% O 2 and exhibit efficient adenosine membrane transport via human equilibrative nucleoside transporters 1 (hENT1). We studied whether adenosine transport and hENT1 expression are altered by hypoxia in HUVEC. Hypoxia (0 to 24 hours, 2% and 1% O 2 ) reduced maximal hENT1-adenosine transport velocity ( V max ) and maximal nitrobenzylthionosine (NBMPR, a high-affinity hENT1 protein ligand) binding, but increased extracellular adenosine concentration. Hypoxia also reduced hENT1 protein and mRNA levels, effects unaltered by N ω -nitro- l -arginine methyl ester ( l -NAME, nitric oxide synthase [NOS] inhibitor) or PD-98059 (inhibitor of mitogen-activated protein kinase kinase 1 and 2 [MEK1/2]). Hypoxia reduced endothelial NOS (eNOS) activity and eNOS phosphorylation at Ser 1177 , but increased eNOS protein level. Hypoxia increased (1 to 3 hours), but reduced (24 hours) p42/44 mapk phosphorylation. Thus, hypoxia-increased extracellular adenosine may result from reduced hENT1-adenosine transport in HUVEC. Hypoxia effect seems not to involve NO, but p42/44 mapk may be required for the relatively rapid effect (1 to 3 hours) of hypoxia. These results could be important in diseases where the fetus is exposed to intrauterine environments poor in oxygen, such as intrauterine growth restriction, or where adenosine transport is altered, such as gestational diabetes.
Performance enhancing drug abuse and cardiovascular risk in athletes: implications for the clinician
Authors: Peter J Angell, Neil Chester, Nick Sculthorpe, Greg Whyte, Keith George, John Somauroo
Journal: British Journal of Sports Medicine (2012)

The use of performance-enhancing and social drugs by athletes raises a number of ethical and health concerns. The World Anti-Doping Agency was constituted to address both of these issues as well as publishing a list of, and testing for, banned substances in athletes. Despite continuing methodological developments to detect drug use and associated punishments for positive dope tests, there are still many athletes who choose to use performance and image enhancing drugs. Of primary concern to this review are the health consequences of drug use by athletes. For such a large topic we must put in place delimitations. Specifically, we will address current knowledge, controversies and emerging evidence in relation to cardiovascular (CV) health of athletes taking drugs. Further, we delimit our discussion to the CV consequences of anabolic steroids and stimulant (including amphetamines and cocaine) use. These drugs are reported in the majority of adverse findings in athlete drug screenings and thus are more likely to be relevant to the healthcare professionals responsible for the well-being of athletes. In detailing CV health issues related to anabolic steroid and stimulant abuse by athletes we critique current research evidence, present exemplar case studies and suggest important avenues for on-going research. Specifically we prompt the need for awareness of clinical staff when assessing the potential CV consequences of drug use in athletes.