tbuckley/cabot-search huggingface dataset:
Effects of Feeding Benzo[a]pyrene on Fertility, Embryos, and Young Mice2
Authors: R. H. Rigdon, Jack Neal
Journal: JNCI Journal of the National Cancer Institute (1965)

Mice fed rations containing 0.25, 0.5, and 1.0 mg of benzo[a]pyrene per g of food absorb this hydrocarbon and develop a blue fluorescence. Benzo[a]pyrene was demonstrated spectrophotometrically in the kidney of some of these mice but not in the embryos. Apparently the maximum amount of benzo[a]pyrene that is absorbed is metabolized. A metabolite is responsible for the blue fluorescence. This blue fluorescence decreases rapidly when the benzopyrene-containing ration is discontinued. Mice do not like rations containing benzo[a]pyrene after they have been fed standard laboratory pellets. Their weight decreases and the weight curve correlates with the amount of food consumed. Mice fed the ration containing 1.0 mg of benzo[a]pyrene from weaning readily eat it and gain at the same rate as mice fed laboratory pellets. In time mice will adjust to eating food containing this hydrocarbon; however, cannibalism frequently occurs when the higher concentrations of benzo[a]pyrene are fed. This hydrocarbon in the concentrations fed these mice had no injurious effect on fertility or on the developing embryos. Mice fed 1.0 mg of benzopyrene per g of food for their entire lives reproduce. No malformations were observed and, if resorption of any embryos did occur, it was not evident.
Use of Laser Doppler Flowmetry and Transcutaneous Oxygen Tension Electrodes to Assess Local Autonomic Dysfunction in Patients with Frozen Shoulder
Authors: R Mani, C Cooper, B L Kidd, J D Cole, M I D Cawley
Journal: Journal of the Royal Society of Medicine (1989)

The laser Doppler flowmeter (LDF), which measures changes in cutaneous blood flow, and the transcutaneous oxygen electrode which measures cutaneous perfusion, were used to study reflex changes in the microcirculation of the shoulder in 38 patients with frozen shoulder and 10 normal controls. In all controls and 22 patients with frozen shoulder, a normal LDF response to inspiration/expiration was observed. In 16 patients with frozen shoulder, LDF responses were either unilaterally or bilaterally absent. Comparison between the two patient groups showed a significant association (chi 2 = 6.43, P less than 0.02) between abnormality of response and the persistence of pain. TcPO2 was in the normal range in all patients and controls. These findings suggest that the LDF together with the TcPO2 may be a useful method of studying the skin microcirculation over the shoulder.
Characterization of the human gut microbiome during travelers' diarrhea
Authors: Bonnie P Youmans, Nadim J Ajami, Zhi-Dong Jiang, Frederick Campbell, W Duncan Wadsworth, Joseph F Petrosino, Herbert L DuPont, Sarah K Highlander
Journal: Gut Microbes (2015)

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.
High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results.
Authors: S N Wolff, R H Herzig, J W Fay, G L Phillips, H M Lazarus, J M Flexner, R S Stein, J P Greer, B Cooper, G P Herzig
Journal: Journal of Clinical Oncology (1989)

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.
Effect of heliox breathing on locomotor and respiratory muscle oxygen delivery during exercise in COPD patients with or without dynamic hyperinflation
Authors: Zafeiris Louvaris, Vasilis Andrianopoulos, Maroula Vasilopoulou, Evgenia Cherouveim, Stauroula Spetsioti, Andrea Aliverti, Helmut Habazettl, Peter Wagner, Spyros Zakynthinos, Ioannis Vogiatzis
Journal: European Respiratory Journal (2011)

Background:  Dynamic hyperinflation and large intrathoracic pressure swings induce negative hemodynamic effects during exercise in COPD. Heliox breathing reduces the degree of dynamic hyperinflation thereby improving peripheral muscle oxygen delivery. Whether this effect also applies to patients who do not hyperinflate during exercise, is unknown.   Methods:  17 COPD patients (n=8 hyperinflators [FEV 1 =37±4% pred] and n=9 non-hyperinflators [FEV 1 =48±4% pred]) performed two constant-load exercise tests to the limit of tolerance in air and whilst breathing heliox.   Results:  The improvement in exercise tolerance by heliox was not different between hyperinflators and non-hyperinflators (by 3.8±1.9 and 4.2±2.0 min, respectively).This is probably due to the finding that systemic oxygen delivery significantly improved in both hyperinflators (from 1.48±0.10 to 1.70±0.13 l/min) and non-hyperinflators (from 1.68±0.12 to 1.93±0.15 l/min); however, the mechanism of improvement was different as heliox improved cardiac output in non-hyperinflators (from 9.3±0.5 to 10.4±0.5 l/min) whilst arterial oxygen content increased only in hyperinflators (from 160±3 to 177±4 mlO 2 /l). Nonetheless, quadriceps and intercostal muscle oxygen delivery (measured by NIRO+ICG method with arterial sampling) improved significantly and by the same magnitude in both hyperinflators (by 16.6±7.4 and 4.0±1.1 mlO 2 /min/100g, respectively) and non-hyperinflators (by 17.6±8.2 and 4.5±1.2 mlO 2 /min/100g, respectively).   Conclusion:  Heliox improves peripheral and respiratory muscle oxygen delivery in all COPD patients regardless of the occurrence of exercise-induced dynamic hyperinflation.
The psychological status in COPD patients - The influence of the complex psychology rehabilitation
Authors: Larysa Botvinikova, Anna Garagulya, Yulia Guba
Journal: European Respiratory Journal (2013)

Aim: to study the peculiarities of the psychological status in COPD patients and to asses their changes after the course of the long-term treatment and pulmonary rehabilitation (PR).  Study population: we examined 127 patients (103 – men, middle age 57,7 ±3,4) COPD patients, who were divided into 2 groups: 1-st – 63 patients who’s complex treatment involved medicine and long –term pulmonary rehabilitation course (pulmonary rehabilitation, psychotherapy treatment and antismoking program; 2-nd group – 64 COPD patients, who received conventional therapy (GOLD,2011) at the ordinary out-patient department.  Methods: the psychology status was assessed by Zung test (level of depression) and Spilberger-Hanin scale (the level of personal and situate anxiety). All measurements were carried out before and after 1-year course.  Results: the increasing level of the depression in patients of both group – 53,21± 1,97 and 55, 12 ± 2,12 accordingly (normative index – 31,7 ± 0,97); the level of the personal anxiety was 44,56 ± 0,97 in patients of the 1-st group and 43,7 ± 0,87 in patients of the 2-nd group (normative index – 26,6 ± 0,84). After the regular monitoring, long-term complex treatment and pulmonary rehabilitation course we revealed the significant changes of the psychological status in the patients of the 1-st group: the decreasing of depression (43,7± 1,78 p   Conclusions: the COPD significantly changes the patient’s psychological status; 2) the regular monitoring, complex treatment and course of pulmonary rehabilitation allows to reach the positive psychological changes in COPD patients.
In Vitro and In Vivo DNA Damage of Male and Female Rat Liver Nuclei by Oncogenic and Nononcogenic Beta Blockers&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M Presta, C Mazzocchi, S Ziliani, G Ragnotti
Journal: JNCI Journal of the National Cancer Institute (1983)

The beta blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305), hepatocarcinogenic to the female rat, and the nononcogenic beta blockers DL-1-(2-nitro-5-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1327), DL-propranolol, and DL-atenolol were tested for their capacity to damage liver DNA in vitro and in vivo. As revealed by alkaline sucrose gradient analysis, all the beta blockers tested, with the exception of DL-atenolol, caused a dose-dependent DNA fragmentation when they were added in vitro to nuclei isolated from livers of both male and female Wistar rats. Analysis of the DNA sedimentation patterns in neutral sucrose gradients demonstrated the absence of DNA fragmentation, thus indicating that the drugs did not induce double-strand DNA breaks. When the beta blockers were administered in vivo, liver DNA damage was observed only in female Wistar rats treated with ZAMI 1305. A single injection of ZAMI 1305 caused the onset of two distinct episodes of DNA damage. The first episode occurred within 5 minutes, and the damage was repaired within 1 hour after the injection; the second, apparently spontaneous, episode occurred 14 hours after the injection, and the damage was more pronounced than that seen in the first episode and took a much longer time to subside. However, a second injection of ZAMI 1305 into female Wistar rats 8 hours after the first injection did not induce the immediate short-lived episode of DNA damage but, like the first injection, it caused late DNA damage that peaked about 16 hours after drug administration.
Long-term effects of biomass burning exposure on nasal mucociliary clearance in Brazilian sugarcane cutters
Authors: Aline Duarte Ferreira-Ceccato, Ercy Mara Cipulo Ramos, Luiz Carlos Soares de Carvalho Junior, Rafaela Campos Cuissi, Paula Roberta da Silva Pestana, Marceli Rocha Leite, Renata Marques David, Paulo Augusto Raymundo Pereira, Camila dos Anjos Proença, Marcos Fernando de Souza Teixeira, Sérgio Oikawa, Alessandra Choqueta de Toledo, Dionei Ramos
Journal: European Respiratory Journal (2013)

Nasal mucociliary clearance (NMC) is the main defense mechanism respiratory against inhaled particles and there is evidence that exposure to biomass burning particles cause adverse effects on this system. This study aimed to evaluate the long-term effects of sugarcane biomass burning exposure on NMC in sugarcane cutters during a harvest. Fourteen non-smokers sugarcane cutters (mean age 25±4 years old, BMI 24±2 kg/m2) were evaluated. The NMC was measured by Saccharin Transit Time (STT) test in pre-harvest, three and six months of harvest. Air quality was evaluated at harvest, in which occurs biomass burning, by the passive sampler in the third and sixth month being measured heavy elements cadmium (Cd2+), copper (Cu2+) and lead (Pb2+). Shapiro-Wilk test was used to assess the normality of the data and the ANOVA test was used for STT measures and Bonferroni's post-test to detect the differences. The test t was used to compare the values of trace of heavy elements at moments. Statistical significance was determined at 5%. The STT test decreased significantly at three (4±2 minutes) and six months (3±1 minutes) of harvest compared to pre-harvest (8±3 minutes, p<0.001). Among trace metals, Pb2+ was predominant (0,3 ppm/cm2 - three month and 3,4 ppm/cm2 - six month) while Cu2+ presented the lowest concentration (0,05 ppm/cm2 - three month and 1,5 ppm/cm2 – six month). The Cd2+ concentrations were 0,04 ppm/cm2 (three months) and 2,1 ppm/cm2 (six months). Our study demonstrated which long-term exposure to biomass burning from sugarcane accelerated the nasal mucociliary clearance.
Control of Solid Tumor Metastases With a High-Molecular-Weight Derivative of Methotrexate&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: B C Chu, J M Whiteley
Journal: JNCI Journal of the National Cancer Institute (1979)

Methotrexate (MTX) covalently bound to bovine serum albumin (MTX-BSA), injected ip (10 mg/kg) once every 4 days for a total of 4 doses, was more effective than an equivalent dose of free MTX in reducing the number of metastases observed in female (C57BL/6 X DBA/2)F1 mice bearing the sc implanted Lewis lung carcinoma. Treatment with the high-molecular-weight derivative of MTX in addition caused a decreased rate of growth of the primary tumor and a modest increase in the life-span of the tumor-bearing animal. When tumor-bearing mice were killed after receiving injections of [3H]MTX or [3H]MTX-BSA, no difference in the amount of drug was found at the tumor site after 1 hour; however, after 8 or 24 hours, twice as much radioactivity was found in the tumors of mice treated with carrier-bound drug. Analysis of this radioactivity indicated a ratio of 60--80% carrier-bound to 20--40% free MTX.
The Imperative for a New Approach to Toxicity Analysis in Oncology Clinical Trials
Authors: Gita Thanarajasingam, Joleen M. Hubbard, Jeff A. Sloan, Axel Grothey
Journal: JNCI Journal of the National Cancer Institute (2015)

A consistent system for reporting adverse events (AEs) is paramount in cancer clinical trials and is crucial to ensure the safety and tolerability of chemotherapy. The shift towards individualized medicine in oncology over the last decade has brought with it an impressive array of novel, targeted therapies and increasingly complex clinical trials to investigate them. Many of the newer drugs are oral agents that are taken continuously over protracted periods of time. They stand sharply in contrast to conventional cytotoxic intravenous chemotherapy given over a prefixed number of cycles. With its narrow emphasis on high-grade events, the consensus method for reporting of AEs in current cancer trials has not evolved to reflect the longitudinal toxicity profiles of the newer agents. Current methods do not incorporate patient-reported outcomes, which are of rising importance when therapy lasts for months or even years in a patient's life. Additionally, tables focusing on worst-grade events do not depict evolution of toxicity over time and therefore cannot offer patients and clinicians information about the onset or duration of a given AE. Most importantly, current methods do not capture lower-grade but longer-lasting toxicity that may have important ramifications on patients' quality of life. The failure to include any time-related information in our current methods of toxicity reporting provides an incomplete and even inaccurate depiction of AEs. To remain in step with the advancing science of cancer and the vast array of new therapies with extended treatment durations, our consensus method of AE analysis in oncology clinical trials must modernize to include the dimension of time.
Effects of Metoclopramide and Bromocriptine on the Renin-Angiotensin-Aldosterone System in Man
Authors: Robert M. Carey, Michael O. Thorner, Elizabeth M. Ortt
Journal: Journal of Clinical Investigation (1979)

This study was designed to investigate the possible role of dopaminergic mechanisms in the control of the renin-angiotensin-aldosterone system in normal man. Six normal male subjects in metabolic balance at 150 meq sodium, 60 meq potassium constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. or placebo followed by angiotensin II infusion 1 h later on 2 consecutive days. Metoclopramide increased plasma aldosterone concentration from 8.2+/-2.2 to 21.0+/-3.3 ng/100 ml (P < 0.005) and plasma prolactin concentration from 18.0+/-4.0 to 91.7+/-4.0 ng/ml (P < 0.001) within 15 min of its administration. At 1 h, plasma aldosterone and prolactin concentrations remained elevated at 16.8+/-2.1 ng/100 ml (P < 0.01) and 86.8+/-15.9 ng/ml (P < 0.005), respectively. Angiotensin II at 2, 4, and 6 pmol/kg per min further increased plasma aldosterone concentration to 27.2+/-3.4, 31.9+/-5.7, and 36.0+/-6.7 ng/100 ml (P < 0.02), respectively. Placebo did not alter plasma aldosterone or prolactin concentrations, but angiotensin II increased plasma aldosterone concentration to 13.7+/-2.4, 19.0+/-1.9, and 23.3+/-3.2 ng/100 ml (P < 0.005). The increment of plasma aldosterone concentration in response to angiotensin II was similar after metoclopramide or placebo. The six subjects also received the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. followed by angiotensin II infusion on 2 consecutive d. Bromocriptine suppressed prolactin to <3 ng/ml. After placebo, plasma aldosterone concentration increased from 5.2+/-1.4 to 12.3+/-1.7, 17.2+/-2.2, and 21.8+/-3.5 ng/100 ml (P < 0.01) and after bromocriptine from 7.2+/-1.0 to 14.7+/-3.0, 19.8+/-3.2, and 23.4+/-1.6 ng/100 ml (P < 0.001) with each respective angiotensin II dose. No difference in the response to angiotensin II after bromocriptine or placebo was observed. Plasma renin activity, free 11-hydroxycorticoid concentration, and serum potassium concentration were unchanged by metoclopramide or bromocriptine. The results suggest that aldosterone production is under maximum tonic dopaminergic inhibition which can be overridden with stimulation by angiotensin II in normal man.
Doctors will call for review body to return to original remit Staff grade doctors will have new contract BUPA plans to set up partnerships with consultants NHS Executive issues guide on GP pilots BMA Notices
Authors: E M Armstrong
Journal: BMJ (1997)

# Doctors will call for review body to return to original remit {#article-title-2}

As soon as the new government is announced the BMA will ask for a meeting to emphasise the need to retain an independent review body for the medical profession and to insist that the remit of the doctors' review body should be that agreed by the 1960 royal commission. This stated that doctors' pay should be compared with those in comparable professions.

This request will be accompanied by a demand from GPs for an independent review of their contracts and pay, which should take into account the problems of staffing, recruitment, and workload. The BMA also wants more say in the choice of review body members.

At a meeting with the review body chairman, Mr Brandon Gough, last week, which was also attended by the chairman of the BMA council, the GMSC's chairman, Dr Ian Bogle, re-emphasised GPs' concerns, particularly about recruitment and low morale. He told the GMSC that he found the review body chairman “sympathetic” but Mr Gough had said that he would find it difficult to implement the kind of increases that the profession had called for under current financial arrangements. He denied …
Growth of a Heterologous Tumor Cell Line in Neonatal Rats With Graft-Versus-Host Disease2
Authors: J. Clancy, A. L. Chapman, R. Holt
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Growth of a Heterologous Tumor Cell Line in Neonatal Rats With Graft-Versus-Host Disease Get access J. Clancy, Jr., J. Clancy, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. L. Chapman, A. L. Chapman Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Holt R. Holt Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 5, May 1977, Pages 1279–1285, https://doi.org/10.1093/jnci/58.5.1279 Published: 01 May 1977 Article history Received: 30 December 1975 Revision received: 27 October 1976 Accepted: 06 November 1976 Published: 01 May 1977
Endogenous Lung Regeneration
Authors: Jason Rock, Melanie Königshoff
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenance and repair, which is highly regulated by developmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease.