tbuckley/cabot-search huggingface dataset:
Antenatal education and postnatal support strategies for improving rates of exclusive breast feeding: randomised controlled trial
Authors: Lin-Lin Su, Yap-Seng Chong, Yiong-Huak Chan, Yah-Shih Chan, Doris Fok, Kay-Thwe Tun, Faith S P Ng, Mary Rauff
Journal: BMJ (2007)

<b>Objective</b> To investigate whether antenatal breast feeding education alone or postnatal lactation support alone improves rates of exclusive breast feeding compared with routine hospital care. <b>Design</b> Randomised controlled trial. <b>Setting</b> A tertiary hospital in Singapore. <b>Participants</b> 450 women with uncomplicated pregnancies. <b>Main outcome measures</b> Primary outcomes were rates of exclusive breast feeding at discharge from hospital and two weeks, six weeks, three months, and six months after delivery. Secondary outcomes were rates of any breast feeding. <b>Results</b> Compared with women who received routine care, women in the postnatal support group were more likely to breastfeed exclusively at two weeks (relative risk 1.82, 95% confidence interval 1.14 to 2.90), six weeks (1.85, 1.11 to 3.09), three months (1.87, 1.03 to 3.41), and six months (2.12, 1.03 to 4.37) postnatally. Women receiving antenatal education were more likely to breast feed exclusively at six weeks (1.73, 1.04 to 2.90), three months (1.92, 1.07 to 3.48), and six months (2.16, 1.05 to 4.43) postnatally. The numbers needed to treat to achieve one woman exclusively breast feeding at six months were 11 (6 to 80) for postnatal support and 10 (6 to 60) for antenatal education. Women who received postnatal support were more likely to exclusively or predominantly breast feed two weeks after delivery compared with women who received antenatal education (1.53, 1.01 to 2.31). The rate of any breastfeeding six weeks after delivery was also higher in the postnatal support group compared with women who received routine care (1.16, 1.02 to 1.31). <b>Conclusions</b> Antenatal breast feeding education and postnatal lactation support, as single interventions based in hospital both significantly improve rates of exclusive breast feeding up to six months after delivery. Postnatal support was marginally more effective than antenatal education. <b>Trial registration</b> Clinical Trials NCT00270920.
Phenoxodiol, a Novel Isoflavone, Induces G1 Arrest by Specific Loss in Cyclin-Dependent Kinase 2 Activity by p53-Independent Induction of p21WAF1/CIP1
Authors: Martin F. Aguero, Maria M. Facchinetti, Zhanna Sheleg, Adrian M. Senderowicz
Journal: Cancer Research (2005)

Abstract Phenoxodiol, an isoflavone derivative of genistein with unknown mechanism of action, is currently being evaluated in early human cancer clinical trials. To determine the mechanism of antiproliferative effects of phenoxodiol, we examined its effects in a battery of human cell lines. Although we observed caspase-dependent apoptosis in HN12 cells as early as 24 hours after exposure, clonogenic death occurred only after 48-hour exposure despite caspase blockade by the general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (ZVAD)-fmk. Moreover, clear evidence of cell death as determined by nuclear morphology and plasmatic membrane damage occur despite ZVAD, suggesting that another mechanism besides caspase-dependent apoptosis is required for clonogenic death induced by phenoxodiol. In search for other potential antiproliferative effects, we assessed the effects of phenoxodiol in the cell cycle progression of human carcinoma cell lines. A significant G1-S arrest was observed by 12 hours of exposure in HN12 cell lines at concentrations ≥5 μg/mL. Cell cycle arrest occurred several hours (∼12 hours) before induction of apoptosis. Analysis of in vitro purified cyclin-dependent kinase (cdk) activity showed that phenoxodiol did not inhibit cdk activity. In contrast, cellular cdk2 activity obtained from HN12 cell lines exposed to phenoxodiol for 12 hours decreased by 60%, whereas cdk6 activity remained unaltered, suggesting that the loss of cdk2 activity was specific. Loss in cdk2 activity was preceded by the accumulation of the endogenous cdk inhibitor p21WAF1. To assess the role of p21WAF1 induction by phenoxodiol, we used HCT116 isogenic cell lines and showed that phenoxodiol induced G1 arrest together with p21WAF1 expression in wild-type clones. In contrast, p21−/− variants failed to show G1 arrest. Finally, induction of p21 by phenoxodiol is p53 independent, as phenoxodiol induced p21 in HCT116 lacking p53. These data therefore indicate that phenoxodiol promotes G1-S arrest by the specific loss in cdk2 activity due to p53-independent p21WAF1 induction. This novel feature of phenoxodiol may have clinical implications, as the majority of human malignancies have aberrations in cell cycle progression regulation.
Eight Cycles of Escalated-Dose BEACOPP Compared With Four Cycles of Escalated-Dose BEACOPP Followed by Four Cycles of Baseline-Dose BEACOPP With or Without Radiotherapy in Patients With Advanced-Stage Hodgkin's Lymphoma: Final Analysis of the HD12 Trial of the German Hodgkin Study Group
Authors: Peter Borchmann, Heinz Haverkamp, Volker Diehl, Thomas Cerny, Jana Markova, Anthony D. Ho, Hans-Theodor Eich, Hans Konrad Mueller-Hermelink, Lothar Kanz, Richard Greil, Andreas Rank, Ursula Paulus, Lenka Smardova, Christoph Huber, Bernd Dörken, Christoph Nerl, Stefan W. Krause, Rolf-Peter Mueller, Michael Fuchs, Andreas Engert
Journal: Journal of Clinical Oncology (2011)

Purpose Eight cycles of BEACOPP escalated (escalated dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by radiotherapy (RT) to initial bulk or residual tumor mass is the German Hodgkin Study Group standard of care for advanced-stage Hodgkin's lymphoma (HL). However, treatment-related toxicity is a concern, and the role of RT in this setting is unclear. The HD12 study thus aimed to reduce toxicity while maintaining efficacy. Patients and Methods In this prospectively randomized multicenter trial, eight cycles of BEACOPP escalated was compared with four cycles of BEACOPP escalated followed by four cycles of the baseline dose of BEACOPP (BEACOPP baseline ; 4 + 4), and RT with no RT in the case of initial bulk or residual disease. The study was designed to exclude a difference in 5-year freedom from treatment failure (FFTF) rate of 6%. Results Between January 1999 and January 2003, 1,670 patients age 16 to 65 years were enrolled onto the HD12 study. At 5 years, FFTF was 86.4% in the BEACOPP escalated arm and 84.8% in the 4 + 4 arm (difference, −1.6%; 95% CI, −5.2% to 1.9%), and overall survival was 92% versus 90.3% (difference, −1.7%; 95% CI, −4.6% to 1.1%). Deaths related to acute toxicity of chemotherapy were observed in 2.9% of patients (BEACOPP escalated , n = 19; 4 + 4, n = 27). FFTF was inferior without RT (90.4% v 87%; difference, −3.4%; 95% CI, −6.6% to −0.1%), particularly in patients who had residual disease after chemotherapy (difference, −5.8%; 95% CI, −10.7% to −1.0%), but not in patients with bulk in complete response after chemotherapy (difference, −1.1%; 95% CI, −6.2% to 4%). Conclusion The reduction of BEACOPP to the 4 + 4 regimen did not substantially reduce severe toxicity but might decrease efficacy. Our results do not support the omission of consolidation RT for patients with residual disease. Alternative strategies for improving the risk-to-benefit ratio for patients with advanced HL are needed.
Specific PET Imaging of xC− Transporter Activity Using a 18F-Labeled Glutamate Derivative Reveals a Dominant Pathway in Tumor Metabolism
Authors: Norman Koglin, Andre Mueller, Mathias Berndt, Heribert Schmitt-Willich, Luisella Toschi, Andrew W. Stephens, Volker Gekeler, Matthias Friebe, Ludger M. Dinkelborg
Journal: Clinical Cancer Research (2011)

(18)F-labeled small molecules targeting adaptations of tumor metabolism possess the potential for early tumor detection with high sensitivity and specificity by positron emission tomography (PET) imaging. Compounds tracing deranged pathways other than glycolysis may have advantages in situations where 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) has limitations. The aim of this study was the generation of a metabolically stable ¹⁸F-labeled glutamate analogue for PET imaging of tumors.Derivatives of l-glutamate were investigated in cell competition assays to characterize the responsible transporter. An automated radiosynthesis was established for the most promising candidate. The resulting ¹⁸F-labeled PET tracer was characterized in a panel of in vitro and in vivo tumor models. Tumor specificity was investigated in the turpentine oil-induced inflammation model in rats.A fluoropropyl substituted glutamate derivative showed strong inhibition in cell uptake assays. The radiosynthesis was established for (4S)-4-(3-[¹⁸F]fluoropropyl)-l-glutamate (BAY 94-9392). Tracer uptake studies and analysis of knockdown cells showed specific transport of BAY 94-9392 via the cystine/glutamate exchanger designated as system x(C)(-). No metabolites were observed in mouse blood and tumor cells. PET imaging with excellent tumor visualization and high tumor to background ratios was achieved in preclinical tumor models. In addition, BAY 94-9392 did not accumulate in inflammatory lesions in contrast to FDG.BAY 94-9392 is a new tumor-specific PET tracer which could be useful to examine system x(C)(-) activity in vivo as a possible hallmark of tumor oxidative stress. Both preclinical and clinical studies are in progress for further characterization.
COX-2: A Target for Colon Cancer Prevention
Authors: Lawrence J. Marnett, Raymond N. DuBois
Journal: The Annual Review of Pharmacology and Toxicology (2002)

▪ Abstract Disease prevention is one area that both public and governmental agencies strongly support owing to its potential for an improved lifestyle and a reduction in health care costs. In this review, we focus on the clinical development of one target for cancer prevention, the COX-2 enzyme. This provides an excellent example of how basic research in biochemistry and pharmacology can lead to translational studies and eventually to approval of a drug by the FDA for use as a chemopreventive agent in humans. It is hoped that, as the genome sequence is understood more clearly, other targets will emerge that will provide even more effective drugs for future cancer prevention.
Effect of CPAP on the metabolic syndrome: a randomised sham-controlled study
Authors: CM Hoyos, DR Sullivan, PY Liu
Journal: Thorax (2013)

A recently published editorial1 concluded that severity of disease, Continuous Positive Airway Pressure (CPAP) compliance and comorbidities might explain discrepancies between a randomised sham-controlled crossover study2 which showed that CPAP reversed metabolic syndrome (metS) and reduced weight, body mass index (BMI) and visceral abdominal fat and our findings from a randomised sham-controlled parallel-group study.3 Whether CPAP might be a novel method to reverse metS in those with Obstructive Sleep Apnea (OSA) is an intriguing possibility, since diagnosing and treating metS is important.1 We omitted to examine the effect of CPAP on metS in our population, a typical OSA cohort with treated long-standing metabolic comorbidites and less than ideal CPAP usage.1 To rectify this, we retrospectively assayed stored blood …
An unexpected response
Authors: A Mark Clarfield
Journal: BMJ (2006)

A recent BMJ article exploring the reasons for doctors to consider leaving UK medicine reminded me of a lunchtime conversation in an Edinburgh hospital cafeteria several decades ago. In 1981 my wife, then a senior medical student, and I were on a month-long study leave from our work at McGill University.

At lunch one day with various house officers, senior registrars, and junior faculty, the conversation drifted on to the subject of what we would all do “when we grew up.” The fellow from China …
Fibrillary Glomerulonephritis and Immunotactoid Glomerulopathy
Authors: Charles E. Alpers, Jolanta Kowalewska
Journal: Journal of the American Society of Nephrology (2007)

Fibrillary glomerulonephritis is a now widely recognized diagnostic entity, occurring in approximately 1% of native kidney biopsies in several large biopsy series obtained from Western countries. The distinctive features are infiltration of glomerular structures by randomly arranged fibrils similar in appearance but larger than amyloid fibrils and the lack of staining with histochemical dyes typically reactive with amyloid. It is widely but not universally recognized to be distinct from immunotactoid glomerulopathy, an entity characterized by glomerular deposits of immunoglobulin with substructural organization as microtubules and with clinical associations with lymphoplasmacytic disorders. The pathophysiologic basis for organization of the glomerular deposits as fibrils or microtubules in these entities remains obscure.
Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy
Authors: C. Linassier, C. Barin, G. Calais, S. Letortorec, J.-L. Brémond, M. Delain, A. Petit, M.-T. Georget, G. Cartron, N. Raban, L. Benboubker, R. Leloup, C. Binet, J.-P. Lamagnère, P. Colombat
Journal: Annals of Oncology (2000)
Surface-Mediated Bone Tissue Morphogenesis from Tunable Nanolayered Implant Coatings
Authors: Nisarg J. Shah, Md. Nasim Hyder, Joshua S. Moskowitz, Mohiuddin A. Quadir, Stephen W. Morton, Howard J. Seeherman, Robert F. Padera, Myron Spector, Paula T. Hammond
Journal: Science Translational Medicine (2013)

A multilayered implant coating promotes bone formation and prevents implant loosening and failure.
Evolution of the Globin Gene Family in Deuterostomes: Lineage-Specific Patterns of Diversification and Attrition
Authors: F. G. Hoffmann, J. C. Opazo, D. Hoogewijs, T. Hankeln, B. Ebner, S. N. Vinogradov, X. Bailly, J. F. Storz
Journal: Molecular Biology and Evolution (2012)

In the Metazoa, globin proteins display an underlying unity in tertiary structure that belies an extraordinary diversity in primary structures, biochemical properties, and physiological functions. Phylogenetic reconstructions can reveal which of these functions represent novel, lineage-specific innovations, and which represent ancestral functions that are shared with homologous globin proteins in other eukaryotes and even prokaryotes. To date, our understanding of globin diversity in deuterostomes has been hindered by a dearth of genomic sequence data from the Ambulacraria (echinoderms + hemichordates), the sister group of chordates, and the phylum Xenacoelomorpha, which includes xenoturbellids, acoelomorphs, and nemertodermatids. Here, we report the results of a phylogenetic and comparative genomic analysis of the globin gene repertoire of deuterostomes. We first characterized the globin genes of the acorn worm, Saccoglossus kowalevskii, a representative of the phylum Hemichordata. We then integrated genomic sequence data from the acorn worm into a comprehensive analysis of conserved synteny and phylogenetic relationships among globin genes from representatives of the eight lineages that comprise the superphylum Deuterostomia. The primary aims were 1) to unravel the evolutionary history of the globin gene superfamily in deuterostomes and 2) to use the estimated phylogeny to gain insights into the functional evolution of deuterostome globins. Results of our analyses indicate that the deuterostome common ancestor possessed a repertoire of at least four distinct globin paralogs and that different subsets of these ancestral genes have been retained in each of the descendant organismal lineages. In each major deuterostome group, a different subset of ancestral precursor genes underwent lineage-specific expansions of functional diversity through repeated rounds of gene duplication and divergence. By integrating results of the phylogenetic analysis with available functional data, we discovered that circulating oxygen-transport hemoglobins evolved independently in several deuterostome lineages and that intracellular nerve globins evolved independently in chordates and acoelomorph worms.
Copeptin, a Surrogate Marker for Arginine Vasopressin, Is Associated With Cardiovascular and All-Cause Mortality in Patients With Type 2 Diabetes (ZODIAC-31)
Authors: Ineke J. Riphagen, Wendy E. Boertien, Alaa Alkhalaf, Nanne Kleefstra, Ron T. Gansevoort, Klaas H. Groenier, Kornelis J.J. van Hateren, Joachim Struck, Gerjan Navis, Henk J.G. Bilo, Stephan J.L. Bakker
Journal: Diabetes Care (2013)

Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care.Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality.We included 1,195 patients (age 67±12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1-9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2-10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log2 copeptin was associated with CV (hazard ratio 1.17 [95% CI 0.99-1.39]; P=0.068) and all-cause mortality (1.22 [1.09-1.36]; P=0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR -0.27 to 0.55%]) and all-cause mortality (0.77% [0.17-1.37%]) beyond currently used clinical markers.We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake.
Uninsured Children and National Health Reform
Authors: M. Susan Marquis
Journal: JAMA (1992)

THE HEALTH of the nation's children and their access to care has received renewed public policy attention in recent years. A special policy focus on children derives in part from evidence of the cost-effectiveness of preventive and primary care for children.<sup>1</sup>However, lack of health insurance poses a significant financial barrier to the receipt of the recommended levels of preventive care, especially for poor children. An increase in the share of the cost of health care the family has to pay out-of-pocket is associated with a decrease in immunizations for all children less than age 7 years and a decrease in the likelihood of having a general medical examination and a vision examination among poor children.<sup>2,3</sup>Increased patient cost-sharing also deters poor families from seeking ambulatory care for children for acute problems for which medical advice is highly effective, such as otitis media, "strep throat," lacerations, and fractures.<sup>3</sup>
Acute hepatitis B in a healthcare worker: A lesson in awareness of failure of hepatitis B vaccination
Authors: Hein J. Boot, Laurens A. Van der Waaij, Jurjen Schirm, Cees G.M. Kallenberg, Jim van Steenbergen, Bert Wolters
Journal: Journal of Hepatology (2009)

To the Editor: In response to our case report of an acute HBV infection in a vaccinated male nurse [[1]Boot H.J. van der Waaij L.A. Schirm J. Kallenberg C.G.M. van Steenbergen J. Wolters B. Acute hepatitis B in a healthcare worker: A case report of genuine vaccination failure.J Hepatol. 2009; 50: 426-431Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar], Dr. S. Wiersma of the WHO [[2]Wiersma ST. Hepatitis B vaccine continues to provide long-term protection to healthcare workers. J Hepatol 2009. doi:10.1016/j.jhep.2009.05.018.Google Scholar] argues that our patient had multiple HBV exposure risks, and that HBV acquisition via the hospital setting is less likely than acquisition via sexual exposure in this particular case. We agree with his view that unsafe homosexual contacts in the months preceding the acute HBV infection are the most likely source of infection. However, it is not the source of infection that is the important issue here, but the fact that a fully vaccinated person, registered as being HBV protected, can be a source of HBV transmission to others, and, if the person is a healthcare worker, a source within a hospital. We agree that, at the moment, there is no need to revise the policy for healthcare-specific HB vaccination. However, as also stated by Dr. Wiersma [[2]Wiersma ST. Hepatitis B vaccine continues to provide long-term protection to healthcare workers. J Hepatol 2009. doi:10.1016/j.jhep.2009.05.018.Google Scholar], we must be aware of the fact that vaccinees, including healthcare workers, might become infected with HBV despite a documented adequate response to an HB vaccine in the past. This might become a more prominent feature when individuals who were vaccinated against HBV as neonates start working in the healthcare setting. If and why this specific patient was predisposed to become HBV infected remains unclear. Were his poor-to-moderate responses to the successive HB-plasma vaccines the reason for his vulnerability, or is his unbalanced immune response involved, or is it a combination of both? As we have stressed in the Discussion section of our paper [[1]Boot H.J. van der Waaij L.A. Schirm J. Kallenberg C.G.M. van Steenbergen J. Wolters B. Acute hepatitis B in a healthcare worker: A case report of genuine vaccination failure.J Hepatol. 2009; 50: 426-431Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar], it is not easy to recognize secondary HB vaccination failures because primary HB-vaccination failures occur in over 5% of adult vaccinees. Not only awareness that vaccine-induced immunity against HBV can wane over time, but also awareness of which factors are associated with waning immunity is important for preventing HBV infection in general and in the healthcare setting in particular.