tbuckley/cabot-search huggingface dataset:
Effect of positive expiratory pressure breathing in patients with cystic fibrosis.
Authors: C P van der Schans, T W van der Mark, G de Vries, D A Piers, H Beekhuis, J E Dankert-Roelse, D S Postma, G H Koeter
Journal: Thorax (1991)

The effect of positive expiratory pressure breathing, alone and in combination with coughing, was investigated in eight patients with cystic fibrosis. Functional residual capacity and total lung capacity was measured with a body plethysmograph before, during, and immediately after breathing with expiratory pressure of 5 and 15 cm H2O, and after a coughing period. The positive expiratory pressure breathing was carried out five times for two minutes with a two minute interval between each period. Mucus transport was measured in a peripheral lung region and over the whole lung by a radioactive aerosol tracer technique. Clearance measurements were carried out continuously during positive expiratory pressure breathing and during a control period. Two minutes' breathing with an expiratory pressure of 5 and 15 cm H2O caused an increase in mean (SEM) functional residual capacity from 2.6 (0.1) to 3.6 (0.3) and 4.4 (0.5) 1 and an increase in total lung capacity from 5.1 (0.2) to 5.9 (0.3) and 6.9 (0.4) 1. Lung volumes were higher during breathing with an expiratory pressure of 15 cm H2O than with 5 cm H2O; both returned to baseline values immediately after positive expiratory pressure breathing. Spontaneous mucus clearance and mucus clearance by coughing were not influenced by positive expiratory pressure breathing at either expiratory pressure. Thus in patients with cystic fibrosis positive expiratory pressure breathing increases lung volumes in relation to the expiratory pressure imposed; these changes in lung volume did not, however, lead to an improvement of mucus transport.
Proteins mediating collagen biosynthesis and accumulation in arterial repair: novel targets for anti-restenosis therapy
Authors: A. B. Osherov, L. Gotha, A. N. Cheema, B. Qiang, B. H. Strauss
Journal: Cardiovascular Research (2011)

Events contributing to restenosis after coronary interventions include platelet aggregation, inflammatory cell infiltration, growth factor release, and accumulation of smooth muscle cells (SMCs) and extracellular matrix (ECM). The ECM is composed of various collagen subtypes and proteoglycans and over time constitutes the major component of the mature restenotic plaque. The pathophysiology of collagen accumulation in the ECM during arterial restenosis is reviewed. Factors regulating collagen synthesis and degradation, including various cytokines and growth factors involved in the process, may be targets for therapies aimed at prevention of in-stent restenosis.
Nevirapine and Zidovudine at Birth to Reduce Perinatal Transmission of HIV in an African Setting
Authors: Taha E Taha, Newton I Kumwenda, Donald R Hoover, Susan A Fiscus, George Kafulafula, Chiwawa Nkhoma, Samah Nour, Shu Chen, George Liomba, Paolo G Miotti, Robin L Broadhead
Journal: JAMA (2004)

ContextAntenatal counseling and human immunodeficiency virus (HIV) testing are not universal in Africa; thus, women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine (NVP) regimen (a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth).ObjectiveTo determine risk of mother-to-child transmission of HIV when either standard use of NVP alone or in combination with zidovudine (ZDV) was administered to infants of women tested at delivery.Design, Setting, and ParticipantsA randomized, open-label, phase 3 trial conducted between April 1, 2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial included all infants born to 894 women who were HIV positive, received NVP intrapartum, and were previously antiretroviral treatment–naive. Infants were randomly assigned to NVP (n = 448) and NVP plus ZDV (n = 446). Infants were enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18 months. The HIV status of 90% of all infants was established at 6 to 8 weeks.InterventionMothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg of ZDV twice per day for a week.Main Outcome MeasuresHIV infection of infant at birth and 6 to 8 weeks, and adverse events.ResultsThe mother-to-child transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only and 10.1% (45/444) in those administered NVP plus ZDV (P = .30). A life table estimate of transmission at 6 to 8 weeks was 14.1% (95% confidence interval [CI], 10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those who received NVP plus ZDV (P = .36). For infants not infected at birth and retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who received NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P = .88). Almost all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks. Grades 3 and 4 adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants receiving NVP only and NVP plus ZDV, respectively (P = .76).ConclusionsThe frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa. The safety of the regimen containing neonatal ZDV was similar to that of a standard NVP regimen.
<b> <i>In Vitro</i> </b> Characterization of Enzymatic Properties and Inhibition of the p53R2 Subunit of Human Ribonucleotide Reductase
Authors: Jimin Shao, Bingsen Zhou, Lijun Zhu, Weihua Qiu, Yate-Ching Yuan, Bixin Xi, Yun Yen
Journal: Cancer Research (2004)

Abstract p53R2 is a newly identified subunit of ribonucleotide reductase (RR) and plays a crucial role in supplying precursors for DNA repair in a p53-dependent manner. In our current work, all three human RR subunit proteins (p53R2, hRRM2, and hRRM1) were prokaryotically expressed and highly purified. Using an in vitro [3H]CDP reduction assay, the activity of RR reconstituted with either p53R2 or hRRM2 was found to be time, concentration, and hRRM1 dependent. The kinetic activity of p53R2-containing RR was about 20–50% lower than that of hRRM2-containing RR. Using a synthetic heptapeptide to inhibit RR activity, it was shown that p53R2 bound to hRRM1 through the same COOH-terminal heptapeptide as hRRM2. However, hRRM2 had a 4.76-fold higher binding affinity for hRRM1 than p53R2, which may explain the reduced RR activity of p53R2 relative to hRRM2. Of interest, p53R2 was 158-fold more susceptible to the iron chelator deferoxamine mesylate than hRRM2, although the iron content of the two proteins determined by atomic absorption spectrometer was almost the same. To the contrary, p53R2 was 2.50-fold less sensitive than hRRM2 to the radical scavenger hydroxyurea, whereas EPR showed similar spectra of the tyrosyl radical in two proteins. Triapine, a new RR inhibitor, was equally potent for p53R2 and hRRM2. These inhibition studies showed that the iron center and tyrosyl radical are involved in RR activity for both p53R2 and hRRM2. The susceptibility differences to RR inhibitors between p53R2 and hRRM2 may lead to a new direction in drug design for human cancer treatment.
Meeting the Challenge of Nursing and the Nation's Health
Authors: Edward O'Neil
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Gaining consent for publication in difficult cases involving children
Authors: D. Isaacs, H A Kilham, S Jacobe, M. M Ryan, B. Tobin
Journal: BMJ (2008)

Problem substance use makes a significant contribution to the burden of injuries and noncommunicable diseases in South Africa. In 2012, the Western Cape Department of Health funded a randomised controlled trial of substance use SBIRT in emergency centres (ECs). Based on the promising results, the programme was implemented in 2016 in three ECs, offering motivational interviewing-based counselling delivered at the acute EC visit by lay counsellors. This study utilised data from a novel EC SBIRT service (1 August 2016 – 31 July 2017) and compared the characteristics, process and substance use outcome data for injured and non-injured patients. A screening questionnaire was administered to less seriously ill or injured adult patients, and those scoring at moderate-high risk on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were eligible and received a motivational-interviewing-based session. Data collected included sociodemographics, presenting complaint, substance use days and the ASSIST. A three-month follow-up phone call was conducted to evaluate substance use in a small sample of service users. Process data was collected on the numbers of: patients screened, eligible patients, and sessions given. In total, 13 136 patients were screened. Over half were male, the mean age was 37 years and 43% presented with an injury. Of the non-injured patients, 23% met criteria for problem substance use, compared to 56% of injured patients. Of the eligible patients, 74% were male and 83% received a counselling session. At three-month follow-up there was a significant reduction in substance use days for all patients and injured patients' alcohol use scores decreased by 6.4 points, compared to 4.7 in the non-injured patients. This EC SBIRT service delivered a substance use intervention to over 80% of eligible patients. Injured patients were more likely to report problem substance use, and showed a greater decrease in substance use scores.
Major morphological effects of a regulatory gene: Pgm1-t in rainbow trout.
Authors: R F Leary, F W Allendorf, K L Knudsen
Journal: Molecular Biology and Evolution (1984)

We have investigated the morphological effects of a genetic locus, Pgm1-t, that affects the expression of a phosphoglucomutase locus (Pgm1) in liver of rainbow trout (Salmo gairdneri). We have previously shown that embryos with liver Pgm1 expression hatch earlier than those without liver Pgm1 expression. We predicted that this difference in developmental rate should cause a reduction in meristic counts in the more rapidly developing fish with liver Pgm1 expression. Eight meristic (countable) characters in nine full-sib groups segregating for the presence or absence of liver Pgm1 expression are in agreement with this prediction. In eight of the nine families, there is a significant difference in the multivariate distribution of the eight meristic counts between full sibs with and without liver Pgm1 expression. This separation in multivariate space is based on a tendency for lower meristic counts in fish with liver Pgm1 expression. The magnitude of these morphological differences is similar to that between two subspecies of cutthroat trout (Salmo clarki) that show substantial genetic divergence at structural loci encoding enzymes (Nei's D = 0.34). These data support the view that small changes in the developmental process caused by genetic differences at regulatory genes can have large effects on morphology.
Is it time to drop the ‘knowledge translation’ metaphor? A critical literature review
Authors: Trisha Greenhalgh, Sietse Wieringa
Journal: Journal of the Royal Society of Medicine (2011)

The literature on ‘knowledge translation’ presents challenges for the reviewer because different terms have been used to describe the generation, sharing and application of knowledge and different research approaches embrace different philosophical positions on what knowledge is. We present a narrative review of this literature which deliberately sought to highlight rather than resolve tensions between these different framings. Our findings suggest that while ‘translation’ is a widely used metaphor in medicine, it constrains how we conceptualise and study the link between knowledge and practice. The ‘translation’ metaphor has, arguably, led to particular difficulties in the fields of ‘evidence-based management’ and ‘evidence-based policymaking’ – where it seems that knowledge obstinately refuses to be driven unproblematically into practice. Many non-medical disciplines such as philosophy, sociology and organization science conceptualise knowledge very differently, as being (for example) ‘created’, ‘constructed’, ‘embodied’, ‘performed’ and ‘collectively negotiated’ – and also as being value-laden and tending to serve the vested interests of dominant élites. We propose that applying this wider range of metaphors and models would allow us to research the link between knowledge and practice in more creative and critical ways. We conclude that research should move beyond a narrow focus on the ‘know–do gap’ to cover a richer agenda, including: (a) the situation-specific practical wisdom (phronesis) that underpins clinical judgement; (b) the tacit knowledge that is built and shared among practitioners (‘mindlines’); (c) the complex links between power and knowledge; and (d) approaches to facilitating macro-level knowledge partnerships between researchers, practitioners, policymakers and commercial interests.
Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk
Authors: F. L. Wong
Journal: JAMA (1997)

There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy.To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development.Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas.A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984.Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05).Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood.
Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection
Authors: R A M Breen, R F Miller, T Gorsuch, C J Smith, A Schwenk, W Holmes, J Ballinger, L Swaden, M A Johnson, I Cropley, M C I Lipman
Journal: Thorax (2006)

<b>Background:</b> Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co-infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti-TB treatment in the era of effective antiretroviral therapy. <b>Methods:</b> The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co-infected with HIV. <b>Results:</b> 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti-TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co-infected patients (p&lt;0.001; p = 0.006), although all cause interruption of anti-TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re-treatment. <b>Conclusion:</b> Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti-TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals.
Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells
Authors: Michael G. Kharas, Matthew R. Janes, Vanessa M. Scarfone, Michael B. Lilly, Zachary A. Knight, Kevan M. Shokat, David A. Fruman
Journal: Journal of Clinical Investigation (2008)

Some cases of pre-B cell acute lymphoblastic leukemia (pre-B-ALL) are caused by the Philadelphia (Ph) chromosome-encoded BCR-ABL oncogene, and these tend to have a poor prognosis. Inhibitors of the PI3K/AKT pathway reduce BCR-ABL-mediated transformation in vitro; however, the specific PI3K isoforms involved are poorly defined. Using a murine model of Ph+ pre-B-ALL, we found that deletion of both Pik3r1 and Pik3r2, genes encoding class IA PI3K regulatory isoforms, severely impaired transformation. BCR-ABL-dependent pre/pro-B cell lines could be established at low frequency from progenitors that lacked these genes, but the cells were smaller, proliferated more slowly, and failed to cause leukemia in vivo. These cell lines displayed nearly undetectable PI3K signaling function and were resistant to the PI3K inhibitor wortmannin. However, they maintained activation of mammalian target of rapamycin (mTOR) and were more sensitive to rapamycin. Treatment with rapamycin caused feedback activation of AKT in WT cell lines but not PI3K-deficient lines. A dual inhibitor of PI3K and mTOR, PI-103, was more effective than rapamycin at suppressing proliferation of mouse pre-B-ALL and human CD19+CD34+)Ph+ ALL leukemia cells treated with the ABL kinase inhibitor imatinib. Our findings provide mechanistic insights into PI3K dependency in oncogenic networks and provide a rationale for targeting class IA PI3K, alone or together with mTOR, in the treatment of Ph+ ALL.
Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-γ
Authors: Beate Kampmann, Cheryl Hemingway, Alick Stephens, Robert Davidson, Anna Goodsall, Suzanne Anderson, Mark Nicol, Elisabeth Schölvinck, David Relman, Simon Waddell, Paul Langford, Brian Sheehan, Lynn Semple, Katalin A. Wilkinson, Robert J. Wilkinson, Stanley Ress, Martin Hibberd, Michael Levin
Journal: Journal of Clinical Investigation (2005)

Genetic defects in the IFN-γ response pathway cause unique susceptibility to intracellular pathogens, particularly mycobacteria, but are rare and do not explain mycobacterial disease in the majority of affected patients. We postulated that acquired defects in macrophage activation by IFN-γ may cause a similar immunological phenotype and thus explain the occurrence of disseminated intracellular infections in some patients without identifiable immune deficiency. Macrophage activation in response to IFN-γ and IFN-γ production were studied in whole blood and PBMCs of 3 patients with severe, unexplained nontuberculous mycobacterial infection. In all 3 patients, IFN-γ was undetectable following mitogen stimulation of whole blood, but significant quantities were detectable in the supernatants of PBMCs when stimulated in the absence of the patients' own plasma. The patients' plasma inhibited the ability of IFN-γ to increase production of TNF-α by both autologous and normal donor PBMCs, and recovery of exogenous IFN-γ from the patients' plasma was greatly reduced. Using affinity chromatography, surface-enhanced laser desorption/ionization mass spectrometry, and sequencing, we isolated an IFN-γ–neutralizing factor from the patients' plasma and showed it to be an autoantibody against IFN-γ. The purified anti–IFN-γ antibody was shown to be functional first in blocking the upregulation of TNF-α production in response to endotoxin; second in blocking induction of IFN-γ–inducible genes (according to results of high-density cDNA microarrays); and third in inhibiting upregulation of HLA class II expression on PBMCs. Acquired defects in the IFN-γ pathway may explain unusual susceptibility to intracellular pathogens in other patients without underlying, genetically determined immunological defects.
Predicting Clinical Outcomes and Response to Thrombolysis in Acute Stroke Patients With Diabetes
Authors: Davar Nikneshan, Roula Raptis, Jitphapa Pongmoragot, Limei Zhou, S. Claiborne Johnston, Gustavo Saposnik
Journal: Diabetes Care (2013)

Few tools are available to evaluate clinical outcomes and response to thrombolysis (tPA) in stroke patients with diabetes. We explored how the iScore (www.sorcan.ca/iscore), a validated risk score, predicts clinical outcomes in stroke patients with and without diabetes.We applied the iScore to stroke patients presenting to stroke centers participating in the Registry of the Canadian Stroke Network. Main outcomes included favorable outcome, defined as a modified Rankin scale (mRS) 0-2 at discharge, and intracerebral hemorrhage (ICH) after tPA.Among 12,686 patients with an acute ischemic stroke, 3,228 (25.5%) had diabetes. Among patients receiving tPA (n = 1,689), those with diabetes had a lower rate of a favorable outcome compared with their counterparts (24.3 vs. 31.1%; RR 0.90 [95% CI 0.82-0.98]). The risk of ICH was not significantly different in patients with or without diabetes (for any type 12.6 vs. 12.5%, RR 1.01 [0.72-1.40]; for symptomatic ICH 7.5 vs. 6.8%, RR 1.11 [0.70-1.72]). The regression analysis revealed a decline in the probability of a favorable outcome after tPA with increments in the iScore (P value for iScore × tPA interaction <0.001). There was no difference in the response to tPA predicted by the iScore between stroke patients with and without diabetes (P value = 0.07).Stroke patients with diabetes have poorer outcomes compared with patients without diabetes, which is not explained by ICH. The iScore similarly predicts response to tPA between stroke patients with and without diabetes.