tbuckley/cabot-search huggingface dataset:
Mouse spleen lymphoblasts generated in vitro. Their replication and differentiation in vitro
Authors: RM Steinman, BG Machtinger, J Fried, ZA Cohn
Journal: The Journal of Experimental Medicine (1978)

Mouse spleen lymphoblasts induced with lipopolysaccharide and fetal calf serum were obtained in high yield and purity in their first proliferative cell cycle by floatation in dense bovine plasma albumin columns (3). The blasts were maintained in vitro for 3 more days. The cultures were examined in bulk on each day, and in addition, those cells in S phase initially were tagged with [(3)H]thymidine and followed continuously in vitro. Grain count dilution data indicated that most blasts divided but twice over a 2- to 3-day interval in vitro. [(3)H]Thymidine pulse radiolabeling and flow microfluorometry suggested that at least 50-70 percent of the proliferating blasts withdrew from proliferative activity after 2-3 days of culture. Morphologic studies demonstrated that lymphoblasts persisted as such for 1-2 days in vitro and then matured into typical plasma cells. Many of the blastprogeny had small nuclei and considerable basophilic cytoplasm on Giemsa-stained cell smears; abundant rough endoplasmic reticulum by electron microscopy; and readily detectable cytoplasmic Ig by immunocytochemistry. Reversion of blasts to small lymphocytes could not be detected; however, some blasts persisted even after 3 days of culture. The viability of the cultured lymphoblast was followed by initially tagging the cells with [(3)H]thymidine as well as several other techniques. Little cell death was documented during the first day of culture. The number of labeled progeny increased twofold whereas the grain count halved. But 40- 50 percent of the cell-associated label was lost during each of the second and third days, and fewer labeled progeny than predicted by grain count dilution were identified. The culture medium could not be implicated in this loss of lymphoblast progeny, and we suggest that the maturation of the lymphoblast to a short-lived plasma cell was responsible. Therefore mitogen-stimulated B blasts seem to mature into typical plasma cells after just two cycles of cell division. The plasma cells resemble those produced in situ during an immune response in their cytologic features, withdrawal from active proliferative activity, and short life-span.
Pathophysiological Interactions of Ventilation, Arousals, and Blood Pressure Oscillations during Cheyne–Stokes Respiration in Patients with Heart Failure
Authors: JOHN TRINDER, ROBERT MERSON, JOSEPH I. ROSENBERG, FABIA FITZGERALD, JAN KLEIMAN, T. DOUGLAS BRADLEY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Arousals from sleep can be associated with increases in blood pressure (BP). However, it is uncertain whether this is due to a direct effect of arousals on BP, or is secondary to respiratory stimuli present at the time of the arousal. Cheyne–Stokes respiration (CSR) in patients with congestive heart failure (CHF) provides unique conditions that may allow these two possibilities to be distinguished. In CSR, the apnea–hyperpnea cycle can be dissociated from arousals because when CSR occurs during wakefulness, it does so in the absence of arousals, and when it occurs during sleep, arousals occur either at the termination of apnea (early arousals) or several breaths after the onset of hyperpnea (late arousals). We therefore measured BP during wakefulness and non-rapid eye movement (NREM) sleep in eight patients with CHF and CSR. During wakefulness, CSR was associated with wide fluctuations in systolic BP (mean ± SD, 11.3 ± 6.0 mm Hg) synchronous with the apnea–hyperpnea cycle, in the absence of arousals. Similar fluctuations in BP were observed during CSR with early arousals (13.7 ± 7.0 mm Hg) in NREM sleep. However, late arousals during CSR were associated with a small, but significant additional effect on systolic BP (14.2 ± 7.1 mm Hg, p < 0.05). Furthermore, the degree of BP increase following arousals was directly related to the associated increase in ventilation (r = 0.70, p < 0.05). We conclude that BP fluctuations during CSR in patients with CHF are primarily related to oscillations in ventilation during the CSR cycle and can occur in the absence of arousals. Arousals augment these BP oscillations, but only when they occur late in hyperpnea.
Effects of chronic treatment with adrenaline or propranolol on platelet function and c-AMP levels in the rat
Authors: W. TERRES, B. F BECKER, W. SCHRODL, E. GERLACH
Journal: Cardiovascular Research (1989)

Most of our knowledge about the modulation of platelet function by catecholamines is based on observations of acute in vitro actions. Little is known about the effects of chronically elevated or reduced adrenergic stimulation of the platelets. We therefore treated rats for 8 weeks with either adrenaline or the beta-blocker propranolol. Adrenaline (0.5 mg.kg-1.d-1) continuously administered from subcutaneously implanted osmotic mini pumps caused an increase in the sensitivity of the platelets towards ADP as stimulating agent. In contrast, chronic application of propranolol (10 mg.kg-1.d-1) via the drinking water led to a reduction in platelet aggregability. For animals treated with adrenaline, in accordance with the results of the aggregation experiments, the levels of c-AMP found in platelet rich plasma were reduced, both basally (by 33%) and after stimulation of platelet adenylate cyclase with prostaglandin E1 (by 39%). For the propranolol treated animals, the basal c-AMP concentrations remained unchanged. The levels of c-AMP attained after stimulation with prostaglandin E1 were diminished to a similar extent as for the adrenaline treated animals (by 38%). Although the in vitro addition of adrenaline to platelet rich plasma causes a beta-adrenoceptor mediated inhibition of platelet aggregation in the rat, the simulation seen after chronic adrenaline exposure in vivo, which is associated with decreases in both basal and stimulated c-AMP levels, suggests a functional preponderance of alpha-adrenoceptors over beta-adrenoceptors on the rat platelets. Although intraplatelet metabolic changes (blockade of stimulated c-AMP formation) after chronic application of propranolol should have resulted in enhancement of platelet aggregability, an inhibition of aggregation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Final results from a phase II evaluation of lapatinib (L) and bevacizumab (B) in HER2-overexpressing metastatic breast cancer (MBC).
Authors: M Dickler, S Franco, A Stopeck, W Ma, B Nulsen, J Lyandres, M Melisko, S Lahiri, M Arbushites, M Koehler, HS Rugo
Journal: Cancer Research (2009)

Abstract Abstract #3133 Background:&amp;#x2028; HER2 overexpression has been shown to upregulate VEGF expression in pre-clinical breast cancer models. Overexpression of both HER2 and VEGF has been associated with worse clinical outcome than overexpression of either receptor alone. In pre-clinical models, combination anti-HER2 and anti-VEGF therapy has been shown to be more effective than either treatment alone. B plus trastuzumab (T) has shown promising activity in patients (pts) with HER2+ MBC, however the cardiac toxicity of this regimen requires further study. L, an oral dual tyrosine kinase inhibitor of EGFR and HER2, is approved in combination with capecitabine after T-based therapy for HER2+ MBC. L may have less cardiac toxicity and may be a safer and more effective alternative to T. This hypothesis was evaluated in a phase 2 trial of L+B in HER2+ MBC pts.&amp;#x2028; Methods: &amp;#x2028; This single-arm study was designed to evaluate L (1500 mg PO daily) plus B (10 mg/kg IV q2wk) in 50 HER2+ MBC patients. The primary endpoint is crude progression-free survival (PFS) rate at 12 weeks with 84% power to detect a clinically significant PFS rate of 60%; secondary endpoints include toxicity and response per RECIST. Efficacy was assessed at Week 6, 12, and q12wks thereafter. HER2-overexpression was defined as local FISH-positive or IHC 3+ results. Serial evaluation of circulating tumor and endothelial cells and HER2 extracellular domain was performed.&amp;#x2028; Results:&amp;#x2028; Enrollment to this study ended in March 2008 (n=52). Data are presently available on 32 of 52 pts enrolled before January 1, 2008. Pts received a median of 5 prior MBC therapies (range 0-15); 88% received prior T (median 19.7 months; range 1.2-56.8 months). The most frequently reported AEs included diarrhea (81%), rash (66%), nausea (56%), fatigue (56%), and emesis (46%). Four asymptomatic LVEF declines were reported (three grade 2 events; one grade 1 event), as were nine cases of hypertension (eight grade 1 or 2 events; one grade 3 event) and one grade 3 GI hemorrhage. 27/32 patients were evaluable for response; five withdrew prior to first radiologic assessment (two due to toxicity, three due to investigator/pt request). The crude 12-week PFS rate was 63% (20/32 did not progress by Week 12); overall response rate (complete/partial response) was 13%, and the clinical benefit rate (complete/partial response or stable disease for ≥ 24 weeks) was 34%.&amp;#x2028; Conclusions:L+ B is well tolerated and has shown promising activity in heavily pretreated HER2+ MBC pts. Final efficacy and safety data will be presented on the full study cohort. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3133.
Numbers alone cannot determine rational treatment
Authors: P. Vallance
Journal: BMJ (1995)

confounding effect of these factors, it may intro- duce a new bias.If the matching factor is associated with the exposure of interest a crude case-control analysis may lead to a result that is confounded by the matching factor itself.2In such a case the confounding must be eliminated by stratified analysis or multivariate analysis.Another potential problem is overmatching, which results from cases and controls being matched on variables that are highly related to the exposure.For example, suppose one matches on the variable "carrying a cigarette lighter" in a study of smoking and lung cancer.Matched analyses depend on the existence of discordant pairs of cases and controls, but few will exist in this situation because the confounder is closely related to the exposure.Overmatching will not bias the results, but it will make the analysis highly inefficient, which abrogates the main virtue of matching.2In case-control studies investigators must use the technique of matching wisely since it is irrever- sible and its advantages may be limited by the problems we have highlighted.
Phrenic Nerve Pacing in a Tetraplegic Patient via Intramuscular Diaphragm Electrodes
Authors: Anthony F. DiMarco, Raymond P. Onders, Krzysztof E. Kowalski, Michael E. Miller, Sandra Ferek, J. Thomas Mortimer
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

In patients with ventilator-dependent tetraplegia, phrenic nerve pacing (PNP) provides significant clinical advantages compared with mechanical ventilation. This technique however generally requires a thoracotomy with its associated risks and in-patient hospital stay and carries some risk of phrenic nerve injury. We have developed a method by which the phrenic nerves can be activated via intramuscular diaphragm electrodes. In one patient with ventilator-dependent tetraplegia, two intramuscular diaphragm electrodes were implanted into each hemidiaphragm near the phrenic nerve motor points via laparoscopic surgery. The motor points were identified employing a previously devised mapping technique. Because inspired volumes were suboptimal on the right, a second laparoscopic procedure was necessary to position electrodes near the anterior and posterior branches of the right phrenic nerve. During bilateral stimulation, inspired volume was 580 ml. After a reconditioning program of progressively increasing diaphragm pacing, maximum inspired volumes on the left and right hemidiaphragms increased significantly. Maximum combined bilateral stimulation was 1120 ml. Importantly, the patient has been able to comfortably tolerate full-time pacing. If confirmed in additional patients, PNP with intramuscular diaphragm electrodes via laparoscopic surgery may provide a less invasive and less costly alternative to conventional PNP.
Malnutrition and peak expiratory flow rate
Authors: R Primhak, FS Coates
Journal: European Respiratory Journal (1988)

In order to assess the effects of malnutrition on the growth of lung function, 376 Indian schoolchildren aged 6-12 yrs were studied. Peak expiratory flow rate (PEFR) was measured with a Wright peak flow meter, and nutritional status assessed by calculation of the percentage predicted height for age (HFA) and weight for height (WFH) using Harvard standards. After standardizing for height and sex, the PEFR of 30 wasted children (WFH below 80%) was significantly reduced (p less than 0.01), but that of 135 stunted children (HFA below 90%) was higher than average (p less than 0.05). It is concluded that current malnutrition has a negative effect on PEFR, possibly due to impaired muscle function, but that past or chronic malnutrition affects growth of lung function less than it affects somatic growth.
Using a dog's superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study
Authors: M. K. Bomers, M. A. van Agtmael, H. Luik, M. C. van Veen, C. M. J. E. Vandenbroucke-Grauls, Y. M. Smulders
Journal: BMJ (2012)

<b>Objective</b> To investigate whether a dog’s superior olfactory sensitivity can be used to detect <i>Clostridium difficile</i> in stool samples and hospital patients. <b>Design</b> Proof of principle study, using a case-control design. <b>Setting</b> Two large Dutch teaching hospitals. <b>Participants</b> A 2 year old beagle trained to identify the smell of <i>C difficile</i> and tested on 300 patients (30 with <i>C difficile</i> infection and 270 controls). <b>Intervention</b> The dog was guided along the wards by its trainer, who was blinded to the participants’ infection status. Each detection round concerned 10 patients (one case and nine controls). The dog was trained to sit or lie down when <i>C difficile</i> was detected. <b>Main outcome measures</b> Sensitivity and specificity for detection of <i>C difficile</i> in stool samples and in patients. <b>Results</b> The dog’s sensitivity and specificity for identifying <i>C difficile</i> in stool samples were both 100% (95% confidence interval 91% to 100%). During the detection rounds, the dog correctly identified 25 of the 30 cases (sensitivity 83%, 65% to 94%) and 265 of the 270 controls (specificity 98%, 95% to 99%). <b>Conclusion</b> A trained dog was able to detect <i>C difficile</i> with high estimated sensitivity and specificity, both in stool samples and in hospital patients infected with <i>C difficile</i>.
Maternal nutrition during pregnancy and risk of asthma, wheeze, and atopic diseases during childhood: a systematic review and meta‐analysis
Authors: A. A. Beckhaus, L. Garcia‐Marcos, E. Forno, R. M. Pacheco‐Gonzalez, J. C. Celedón, J. A. Castro‐Rodriguez
Journal: Allergy (2015)

Abstract Background Epidemiologic studies suggest a relationship between maternal nutrition during pregnancy and the occurrence of asthma and atopic conditions during childhood. However, individual study results are conflicting. The objective of this meta‐analysis was to critically examine the current evidence for an association between nutrition (dietary patterns, food groups, vitamins, or oligo‐elements) ingestion during pregnancy and asthma, wheeze, or atopic conditions in childhood. Methods The inclusion criteria were as follows: (i) systematic recording of diet during the gestational period and (ii) documentation of asthma, wheezing, eczema, or other atopic disease in the offspring. The primary outcomes were prevalence of asthma or wheeze among the offspring during childhood; and secondary outcomes were prevalence of eczema, allergic rhinitis, or other atopic conditions. Results We found 120 titles, abstracts, and citations, and 32 studies (29 cohorts) were included in this analysis. Data on vitamins, oligo‐elements, food groups, and dietary patterns during pregnancy were collected. A meta‐analysis revealed that higher maternal intake of vitamin D [odds ratio (OR) = 0.58, 95% confidence interval (CI) = 0.38–0.88], vitamin E (OR = 0.6, 95% CI = 0.46–0.78), and zinc (OR = 0.62, 95% CI = 0.40–0.97) was associated with lower odds of wheeze during childhood. However, none of these or other nutrients was consistently associated with asthma per se or other atopic conditions. Conclusions Current evidence suggests a protective effect of maternal intake of each of three vitamins or nutrients (vitamin D, vitamin E, and zinc) against childhood wheeze but is inconclusive for an effect on asthma or other atopic conditions.
Asthma at 8 years of age in children born by caesarean section
Authors: C Roduit, S Scholtens, J C de Jongste, A H Wijga, J Gerritsen, D S Postma, B Brunekreef, M O Hoekstra, R Aalberse, H A Smit
Journal: Thorax (2008)

<h3>Background:</h3> Caesarean section might be a risk factor for asthma because of delayed microbial colonisation, but the association remains controversial. A study was undertaken to investigate prospectively whether children born by caesarean section are more at risk of having asthma in childhood and sensitisation at the age of 8 years, taking into account the allergic status of the parents. <h3>Methods:</h3> 2917 children who participated in a birth cohort study were followed for 8 years. The definition of asthma included wheeze, dyspnoea and prescription of inhaled steroids. In a subgroup (n = 1454), serum IgE antibodies for inhalant and food allergens were measured at 8 years. <h3>Results:</h3> In the total study population, 12.4% (n = 362) of the children had asthma at the age of 8 years. Caesarean section, with a total prevalence of 8.5%, was associated with an increased risk of asthma (OR 1.79; 95% CI 1.27 to 2.51). This association was stronger among predisposed children (with two allergic parents: OR 2.91; 95% CI 1.20 to 7.05; with only one: OR 1.86; 95% CI 1.12 to 3.09) than in children with non-allergic parents (OR 1.36; 95% CI 0.77 to 2.42). The association between caesarean section and sensitisation at the age of 8 years was significant only in children of non-allergic parents (OR 2.14; 95% CI 1.16 to 3.98). <h3>Conclusions:</h3> Children born by caesarean section have a higher risk of asthma than those born by vaginal delivery, particularly children of allergic parents. Caesarean section increases the risk for sensitisation to common allergens in children with non-allergic parents only.
Hedgehog Signaling Restrains Bladder Cancer Progression by Eliciting Stromal Production of Urothelial Differentiation Factors
Authors: Kunyoo Shin, Agnes Lim, Chen Zhao, Debashis Sahoo, Ying Pan, Edda Spiekerkoetter, Joseph C. Liao, Philip A. Beachy
Journal: Cancer Cell (2014)
Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset
Authors: H. Blons, J.F. Emile, K. Le Malicot, C. Julié, A. Zaanan, J. Tabernero, E. Mini, G. Folprecht, J.L. Van Laethem, J. Thaler, J. Bridgewater, L. Nørgård-Petersen, E. Van Cutsem, C. Lepage, M.A. Zawadi, R. Salazar, P. Laurent-Puig, J. Taieb
Journal: Annals of Oncology (2014)
The Role of Organized Medicine in Correctional Health Care
Authors: B. Jaye Anno
Journal: JAMA (1982)

In the early 1970s, the American Medical Association initiated a program to improve health care in the nation's correctional institutions. The AMA's involvement in such an effort was a surprise to those who viewed organized medicine as one of the "last bastions of conservatism." To them, it was difficult to reconcile the image of the AMA with a program designed to improve the plight of inmates of jails and prisons. After all, prisoners didn't vote, and correctional institutions were at the bottom rung of everybody's ladder. So why should physicians be concerned with the welfare of those who have been charged with transgressing society's laws? In other words, what was in it for physicians? The skepticism of some segments of the public was matched by some members of the Association. There were state societies and individual physicians who wondered whether the image of organized medicine might not be tarnished rather
Transmission of a homogenous hepatitis B virus population of A1896-containing strains leading to mild resolving acute hepatitis and seroconversion to hepatitis B e antigen antibodies in an adult
Authors: M J Mphahlele, A G Shattock, W Boner, J Quinn, P A McCormick, W F Carman
Journal: Hepatology (1997)

The pre-core variant, A 1896 , which switches off hepatitis B e antigen (HBeAg) production, is common in hepatitis B e antigen antibody (anti-HBe)-positive chronic hepatitis patients. It has been observed in occasional case reports of acute hepatitis. However, transmission in the absence of HBeAg-producing strains, leading to acute nonfulminant hepatitis and clearance in adults, has not been reported. Here, we show that this event can occur, further confirming that A 1896 strains are “wild-type” and can lead to all the same outcomes as G 1896 strains. This is in keeping with phylogenetic evidence that A 1896 is transmitted independently on a large scale in the population and explains anti-HBe-positive persons who have not had an HBeAg-positive phase documented.
Childhood Social Environment and Risk of Non–Hodgkin Lymphoma in Adults
Authors: Karin Ekström Smedby, Henrik Hjalgrim, Ellen T. Chang, Klaus Rostgaard, Bengt Glimelius, Hans-Olov Adami, Mads Melbye
Journal: Cancer Research (2007)

Abstract Better hygiene and sanitation and decreasing family size parallel the increasing incidence of non–Hodgkin lymphoma (NHL) in many populations around the world. However, whether sibship size, birth order, and crowding are related to adult NHL risk is not clear. We investigated how family structure and childhood social environment were related to the risk of NHL and NHL subtypes in a large Scandinavian population–based case control study with 6,242 participants aged 18 to 74 years. Detailed exposure information was obtained through telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression, and all statistical tests were two-sided. Having four or more siblings was associated with a moderately increased risk of NHL, compared with having no siblings (OR 1.34, 95% CI 1.11-1.62, Ptrend &amp;lt; 0.001). Having four or more older siblings was associated with a similar risk increase (OR 1.33, 95% CI 1.12-1.59, Ptrend = 0.003) compared with being the oldest, whereas number of younger siblings was unrelated overall. The associations were independent of other environmental exposures and did not vary by country, age, or sex. High household crowding was also positively associated with risk of NHL. Results were slightly stronger for diffuse large B-cell and T-cell lymphomas than for other major NHL subtypes. Our findings add to the evidence that large sibship size, late birth order, and childhood crowding are associated with an elevated risk of NHL. Effect mechanisms may be related to early age at onset and high frequency of specific infections or total microbial exposure in childhood. [Cancer Res 2007;67(22):11074–82]