tbuckley/cabot-search huggingface dataset:
Vibrio cholerae non-O1 bacteraemia: description of three cases in the Netherlands and a literature review
Authors: Madelon F Engel, Mariette A Muijsken, Esther Mooi-Kokenberg, Ed J Kuijper, David J van Westerloo
Journal: Eurosurveillance (2016)

Vibrio cholerae non-O1 serogroup (VCNO) bacteraemia is a severe condition with a high case–fatality rate. We report three cases diagnosed in the Netherlands, identified during a national microbiological congress, and provide a literature review on VCNO bacteraemia. A search strategy including synonyms for 'VCNO' and ‘bacteraemia' was applied to PubMed, Medline, Web of Science and Embase databases. The three cases were reported in elderly male patients after fish consumption and/or surface water contact. The literature search yielded 82 case reports on 90 cases and six case series. Thirty case reports were from Asia (30/90; 33%), concerned males (67/90; 74%), and around one third (38/90; 42%) involved a history of alcohol abuse and/or liver cirrhosis The presenting symptom often was gastroenteritis (47/90; 52%) which occurred after seafood consumption in 32% of the cases (15/47).Aside from the most frequent symptom being fever, results of case series concurred with these findings. Published cases also included rare presentations e.g. endophthalmitis and neonatal meningitis. Based on the limited data available, cephalosporins seemed the most effective treatment. Although mainly reported in Asia, VCNO bacteraemia occurs worldwide. While some risk factors for VCNO were identified in this study, the source of infection remains often unclear. Clinical presentation may vary greatly and therefore a quick microbiological diagnosis is indispensable.
Uncertainty in Treatment Rankings: Reanalysis of Network Meta-analyses of Randomized Trials
Authors: Ludovic Trinquart, Nassima Attiche, Aïida Bafeta, Raphaël Porcher, Philippe Ravaud
Journal: Annals of Internal Medicine (2016)

Ranking of interventions is one of the most appealing elements of network meta-analysis. There is, however, little evidence about the reliability of these rankings.To empirically evaluate the extent of uncertainty in intervention rankings from network meta-analysis.Two previous systematic reviews that involved searches of the Cochrane Library, MEDLINE, and Embase up to July 2012 for articles that included networks of at least 3 interventions.58 network meta-analyses involving 1308 randomized trials and 404 interventions with available aggregated outcome data.Each network was analyzed with a Bayesian approach. For each intervention, the surface under the cumulative ranking curve (SUCRA) and its 95% credible interval (95% CrI) were estimated. Through use of the SUCRA values, the interventions were then rank-ordered between 0% (worst) and 100% (best).The median width of the 95% CrIs of the SUCRA was 65% (first to third quartile, 38% to 80%). In 28% of networks, there was a 50% or greater probability that the best-ranked treatment was actually not the best. No evidence showed a difference between the best-ranked intervention and the second and third best-ranked interventions in 90% and 71% of comparisons, respectively. In 39 networks with 6 or more interventions, the median probability that 1 of the top 2 interventions was among the bottom 2 was 35% (first to third quartile, 14% to 59%).This analysis did not consider such factors as the risk of bias within trials or small-study effects that may affect the reliability of rankings.Treatment rankings derived from network meta-analyses have a substantial degree of imprecision. Authors and readers should interpret such rankings with great caution.Cochrane France.
Abstract 1479: Investigation of the permeation and retention of biocompatible low-retention superparamagnetic iron oxide nanoclusters in tumors with magnetic resonance imaging
Authors: Yushuang Wei, Liang Shan, Paul Wang, Qibing Zhou
Journal: Cancer Research (2015)

Abstract Superparamagnetic iron oxide (SPIO) nanoclusters assembled with poly-L-lysine (PLL) and hydroxyl starch show a unique bioclearance property with low retention in the liver and spleen and effective renal excretion. In the orthotopic liver tumor model, the assembled low retention biocompatible SPIO nanoclusters exhibit a high contrast enhancing capability in T2-weighted magnetic resonance imaging (MRI) at a low dose. For the orthotopic liver tumor, the T2-weighted MRI with SPIO nanoclusters is a negative imaging method to reduce the signal intensity of the normal liver tissue, whereas the potential of the retention and permeability of SPIO nanoclusters in tumors was not fully assessed. The latter becomes critically important for diagnosis and prognosis of pancreatic and prostate tumors in the non-reticuloendothelial system. Two approaches of tumor targeting were investigated and compared in this study including the passive targeting via the EPR effect of nanoparticles and the active targeting by the tumor-specific ligands such as TAT, iRGD and pH sensitive peptides. The accumulation of SPIO nanoclusters in tumors was assessed in the subcutaneous pancreatic and prostate tumor models with MRI over times, iron levels and pathological assessment. Our results showed that the retention and permeation of SPIO nanoclusters varied with multiple factors of tumors. For example, well developed tumors with large necrosis core tended to have a high level of SPIO accumulation. In contrast, the early stage solid tumor had minimal retention of SPIOs. Similar effects have been observed in both passive and active tumor targeting by SPIO nanoclusters. Moreover, the accumulation of SPIOs in tumor was achieved over a longer time period over 24 to 48 h with long retention as compared with those in the normal liver, lung, and spleen tissue (between 30 min to 3 h) with rapid clearance. Our data suggested that with well-designed tumor targeting, the biocompatible low-retention SPIO nanoclusters could be an effective MRI contrast agent for MRI of pancreatic and prostate tumors. Citation Format: Yushuang Wei, Liang Shan, Paul Wang, Qibing Zhou. Investigation of the permeation and retention of biocompatible low-retention superparamagnetic iron oxide nanoclusters in tumors with magnetic resonance imaging. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1479. doi:10.1158/1538-7445.AM2015-1479
PTH-281 The colostomy location and radiological progression of trephine size over time: a clue to the development of parastomal hernia?
Authors: KK Ho, T Economou, ES White, NJ Smart, IR Daniels
Journal: Gut (2015)

<h3>Introduction</h3> Parastomal hernias (PH) have been reported to occur at a rate of 4–48% and it is the most frequent complication to occur as a result of stoma formation. This study evaluated the relationship between abdominal wall aperture (AWA) diameter and colostomy site position relative to the rectus abdominis muscle (RAM) to examine the effect on PH development. <h3>Method</h3> A retrospective review of all end colostomies created following abdominoperineal excisions (APE) between February 2006 and November 2014. Those with no post-operative Computed Tomography (CT) imaging were excluded from the analysis. Data including age, sex, curative intent, and colostomy position relative to the RAM and serial AWA diameters on follow up CT imaging were collected retrospectively. The severity of PH was assessed using the Moreno-Matias classification. <h3>Results</h3> One hundred and fourteen elective APEs were performed, of which 85 were the subject of this study. Seventy-three (85.9%) had the colostomy created through the RAM, whilst 12 (14.1%) had it lateral to the RAM (LRAM). Median time to first post-operative CT imaging was at 9.2 (0.1–43.6) months in the RAM group compared to 3.9 (0.2–10.6) months in the LRAM group (p = 0.056). The median AWA diameter on the earliest CT image after surgery was 19 (6–45) mm in the RAM group and 26 (15–46) mm in the LRAM group (p = 0.01). We implemented a linear mixed effect model and found that in the LRAM group the AWA diameter increased on average by 1.5 mm per year (95% CI: 0.5, 2.5), whereas in the RAM group it increased by 1.6 mm per year (95% CI: 0.4, 2.8), after adjusting for age at surgery, gender and other unobserved patient-specific effects. The difference between both groups was 0.013 mm (95% CI: -0.09, 0.11; p &gt; 0.05). The overall difference between the AWA size of the RAM group compared to the LRAM group was 9.6 mm (95% CI: 3.5, 15.6). We found that age increased the AWA size by 0.2 mm per year regardless of colostomy position. An ordinal mixed effect model was fitted for the PH severity index. There was no significant difference in overall severity (p = 0.21) or rate of change of PH severity (p = 0.59) between both groups (RAM and LRAM). <h3>Conclusion</h3> There was a significant difference between median AWA diameter on earliest CT image after surgery in the RAM group compared to LRAM group. AWA diameter increases with time regardless of colostomy position relative to the RAM. There was no significant difference between the rate of AWA progression between colostomies created through the RAM and those created through the LRAM. Furthermore, there was no significant difference between PH severity and colostomy position. <h3>Disclosure of interest</h3> None Declared.
The Virtues and Vices of Single-Payer Health Care
Authors: Jonathan Oberlander
Journal: New England Journal of Medicine (2016)

Interview with Dr. Jonathan Oberlander on the renewed interest in single-payer health insurance and its prospects in the United States. (08:05)Download Democratic presidential candidate Bernie Sanders has made Medicare for All a centerpiece of his platform, reopening an old debate. What are the virtues and vices of single-payer reform? Is it a realistic option for the United States or a political impossibility?
Effects of Tolazamide and Exogenous Insulin on Insulin Action in Patients with Non-Insulin-Dependent Diabetes Mellitus
Authors: Richard G. Firth, Patrick M. Bell, Robert A. Rizza
Journal: New England Journal of Medicine (1986)

To determine whether sulfonylureas and exogenous insulin have different effects on insulin action, we studied eight patients with non-insulin-dependent diabetes mellitus before and after three months of treatment with tolazamide and exogenous semisynthetic human insulin, using a randomized crossover design. Therapy with tolazamide and therapy with insulin resulted in similar improvement of glycemic control, as measured by a decrease in mean glycosylated hemoglobin (±SEM) from 9.4±0.7 percent to 7.7±0.5 percent with tolazamide and to 7.1±0.2 percent with exogenous insulin (P<0.01 for both comparisons). Therapy with either tolazamide or exogenous insulin resulted in a similar lowering (P<0.05) of postabsorptive glucose-production rates (from 2.3±0.1 to 2.0±0.2 and 1.8±0.1 mg per kilogram of body weight per minute, respectively) but not to normal (1.5±0.1 mg per kilogram per minute). Both tolazamide and exogenous insulin increased (P<0.05) glucose utilization at supraphysiologic insulin concentrations (from 6.2±0.7 to 7.7±0.6 mg per kilogram per minute with tolazamide and to 7.8±0.6 mg per kilogram per minute with exogenous insulin) to nondiabetic rates (7.9±0.5 mg per kilogram per minute). Neither agent altered erythrocyte insulin binding at physiologic insulin concentrations. We conclude that treatment with sulfonylureas or exogenous insulin results in equivalent improvement in insulin action in patients with non-insulin-dependent diabetes mellitus. Therefore, the choice between these agents should be based on considerations other than their ability to ameliorate insulin resistance. (N Engl J Med 1986; 314:1280–6.)
Combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (E) with the insulin like growth factor-1-receptor (IGF-1-R) inhibitor NVP-AEW-541: A mechanistic based anti-tumor strategy
Authors: S. Di Cosimo, J. Seoane, M. Guzman, F. Rojo, J. Jimenez, J. Anido, J. Arribas, F. Cognetti, J. Baselga
Journal: Journal of Clinical Oncology (2005)

3112 Background- Everolimus inhibits mTOR and has anti-tumor activity in vitro and in vivo. Interestingly, E induces up-stream phosphorylated Akt (p-Akt), which could in turn mediate resistance to E. To explore the mechanisms of E-induced p-Akt, we considered that mTOR negatively regulates insulin signaling, and thus p-Akt levels, via degradation of the insulin receptor substrate1 (IRS-1) in differentiated adypocites. Methods- Starved human prostate cancer cells DU-145 were stimulated with IGF-1 after a brief exposure (2 hours) or concomitantly with E. Small interfering RNAs for S6K (Dharmacon) were transfected using LipofectAMINE 2000, cells were treated 48 hours later with NVP-AEW-541. Cell growth inhibition was analysed after 72 hour - exposure to E and NVP-AEW-541 alone or in combination. Results- Treatment with IGF-1 resulted in a strong induction and posterior degradation of IRS-1. Similarly, p-Akt was rapidly induced and then gradually decreased. Conversely, pretreatment with E resulted in a persistent induction of IRS-1 and p-Akt. When E was added after an initial 2 hour IGF-1 stimulation, IGF-1 induced degradation of IRS-1 was inhibited for the rest of 6 hour - exposure to both IGF-1 and E, as if the cells had only been treated with IGF-1 for 2 instead of 8 hours. Experiments with siRNA demonstrated that a 70% knock down of the down-stream effector of mTOR S6K mimics the effect of E increasing the levels of p-Akt in parallel with those of IRS-1 and reducing those of p-S6. These results suggest that the inhibition of S6K by E results in a sustained activation of IGF-1-R signaling which in turn results in the activation of Akt. Accordingly, we demonstrated that NVP-AEW-541, at the dose able to inhibit the IGF-1-R pathway, prevents the activation of Akt induced by either siRNA-S6K or E; and that combined optimal and sub-optimal doses of NVP-AEW-541 and E significantly inhibited cell proliferation more than each drug alone (p<0.001). Conclusion - The IGF-1-R pathway is involved in the activation of Akt by E and dual mTOR and IGF-1-R targeting appears to be a rational and promising anti-tumor strategy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Endre “Andrew” Czeizel
Authors: Ned Stafford
Journal: BMJ (2015)

Mohai Balazs/MTI

Life in Hungary was bleak in 1959 when Endre Czeizel, at the age of 24, began his career as a doctor and medical researcher at Budapest’s National Institute of Hygiene. Czeizel, like millions of others at the time, was working behind the so called iron curtain, the political boundary between democratic western Europe and the Soviet controlled communist countries of eastern Europe. Just three years earlier the Soviet army had crushed an uprising of Hungarians seeking independence and freedom. Thousands of Hungarians were wounded and killed. After defeat, hundreds were executed and thousands imprisoned.

By the early 1960s Czeizel, who had trained in gynaecology and obstetrics, had become fascinated with the emerging specialism of medical genetics. Isolated from the West, Czeizel was hungry for information. He had a good command of the English language and monitored, as best as he could, international research into medical genetics.

He persevered over the next three decades and was able to overcome huge difficulties not faced by medical geneticists in the West. On Christmas Eve 1992 he was rewarded with the publication of his most influential study in the New England Journal of Medicine . The landmark paper confirmed that the risk of neural tube birth defects can be reduced if mothers take folic acid during the periconceptional period—that is, shortly before conception and during early pregnancy.1

Pierpaolo Mastroiacovo, director of the International Clearinghouse for Birth Defects Surveillance and Research in Rome, says of Czeizel: “He will be remembered …
Mosaic‐activating <i>FGFR2</i> mutation in two fetuses with papillomatous pedunculated sebaceous naevus
Authors: P. Kuentz, S. Fraitag, M. Gonzales, F. Dhombres, J. St‐Onge, Y. Duffourd, N. Joyé, J.‐M. Jouannic, A. Picard, N. Marle, J. Thevenon, C. Thauvin‐Robinet, L. Faivre, J.‐B. Rivière, P. Vabres
Journal: British Journal of Dermatology (2016)

Papillomatous pedunculated sebaceous naevus (PPSN) has been described as a subtype of sebaceous naevus (SN), typically affecting the scalp and face. In contrast with Schimmelpenning syndrome, no cerebral, ocular or skeletal anomalies have hitherto been reported. We report two unrelated fetuses with PPSN, one with large pink exophytic tumours, the other with minor features but similar microscopic findings. We performed whole-exome sequencing in affected skin tissue from fetus 1, which identified a postzygotic de novo FGFR2 c.1144T>C (p.Cys382Arg) mutation in 34·6% of reads which was absent in the parents' blood. Targeted deep sequencing of FGFR2 confirmed its mosaic status in additional affected skin from fetus 1, and identified the same substitution in 26% of reads in affected skin from fetus 2. FGFR2 p.Cys382Arg is a known somatic driver mutation in human cancer, previously reported to result in activation of RAS signalling. A similar paralogous missense mutation in the transmembrane domain of FGFR3 (p.Gly380Arg) has been reported in keratinocytic epidermal naevi. Our findings define a distinct clinical and molecular subgroup of SN, beside HRAS or KRAS-related SN, and expand the spectrum of mosaic skin conditions associated with receptor tyrosine kinase mutations.
Chromosomal Translocations in Secondary Acute Myeloid Leukemia
Authors: Janet D. Rowley, Christine Vignon, Susanne M. Gollin, Carol L. Rosenberg, Herman E. Wyandt, Aubrey Milunsky
Journal: New England Journal of Medicine (1996)

To the Editor: Acute myeloid leukemia (AML) occurs in up to 15 percent of patients treated with cytotoxic drugs, radiation, or both.1 In the leukemic cells of these patients, losses of chromosome 5, 7, or both are most common; a balanced translocation involving chromosome band 11q23 and the MLL gene is closely associated with prior treatment with drugs that inhibit topoisomerase II.2–6 The Clinical Investigations Branch of the National Cancer Institute has compiled eight cases of chemotherapy-related AML among the 2548 patients with node-positive breast cancer who were enrolled in Protocol B25 of the National Surgical Adjuvant Breast and . . .
Checkpoints for Autoreactive B Cells in the Peripheral Blood of Lupus Patients Assessed by Flow Cytometry
Authors: Susan Malkiel, Venkatesh Jeganathan, Stacey Wolfson, Nataly Manjarrez Orduño, Emiliano Marasco, Cynthia Aranow, Meggan Mackay, Peter K. Gregersen, Betty Diamond
Journal: Arthritis & Rheumatology (2016)

Antinuclear antibodies (ANAs) are diagnostic in several autoimmune disorders, yet the failure to achieve B cell tolerance in these diseases is still poorly understood. Although secreted ANAs detected by an indirect immunofluorescence assay are the gold standard for autoreactivity, there has been no convenient assay with which to measure the frequency of circulating B cells that recognize nuclear antigens (ANA+ B cells) in patients. The aim of this study was to generate an assay to easily identify these B cells and to examine its utility in a study of autoreactive B cells in systemic lupus erythematosus (SLE).We developed and validated a novel flow cytometry-based assay that identifies ANA+ B cells using biotinylated nuclear extracts, and utilized it to examine B cell tolerance checkpoints in peripheral blood mononuclear cells obtained from SLE patients and healthy controls.We observed progressive selection against ANA+ B cells as they matured from transitional to naive to CD27+IgD- and CD27+IgD+ memory cells in both healthy subjects and SLE patients; however, ANA+ naive B cells in SLE patients were not anergized to the same extent as in healthy individuals. We also showed that anergy induction is restored in SLE patients treated with belimumab, an inhibitor of BAFF.This assay will enable studies of large populations to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in healthy subjects and patients with autoimmune disease and permit monitoring of the B cell response to therapeutic interventions.
Immunoglobulins (E, M, G) and Complement in the Connective Tissues of the Thyroid in Graves's Disease
Authors: Sidney C. Werner, Otto Wegelius, Joshua A. Fierer, Konrad C. Hsu
Journal: New England Journal of Medicine (1972)

Abstract When 14 thyroid glands from patients with Graves's disease were studied by immunofluorescence technic, immunofluorescence in focal areas of the stroma was found in all, as well as in the follicular basement membranes in 10. Positive staining was produced by specific antiserums to human immunoglobulins E, M, and G, and complements C1q and C3. Specificity of immunofluorescent staining was confirmed by a series of maneuvers. This includes loss of staining property from sections of thyroid upon elution with acid citrate solution before staining, but not with phosphate-buffered saline elution, and negative staining for fibrinogen (except intravascularly). No staining was found in a variety of control thyroid glands. The connective-tissue localization of complement and immunoglobulins suggests that Graves's disease may be an immune disorder, with possible links to other immune disorders such as rheumatoid arthritis, systemic lupus erythematosus, and nephrosis.
Role of the Renin-Angiotensin System in Post-Transplantation Hypertension in Patients with Multiple Kidneys
Authors: Stuart L. Linas, Paul D. Miller, Keith M. McDonald, Derek P. Stables, Fred Katz, Richard Weil, Robert W. Schrier
Journal: New England Journal of Medicine (1978)

To define the role of the renin-angiotensin system in post-transplantation hypertension we studied 12 hypertensive recipients of renal transplants. The patients received saralasin acetate, an angiotensin II antagonist, while on a normal sodium diet and again after seven days of sodium restriction. In six patients with only one kidney, saralasin did not lower blood pressure on either diet; salt depletion did not lower systolic or diastolic blood pressures. In six patients with more than one kidney, salt depletion also did not lower blood pressure; however, salt depletion plus saralasin lowered their systolic pressures from a mean (± S.E.M.) of 146±9 to 128±8 mm Hg, and mean diastolic pressures fell from 103±5 to 89±5 (P<0.001). In four of five patients renal-vein renin activity was greater in one or more host kidneys than in the transplant kidney (or kidneys). Although pre-transplant blood pressure was the same in both groups, post-transplantation hypertension is more likely to be angiotensin II-dependent in patients with more than one kidney. (N Engl J Med 298:1440–1444, 1978)
The growth of investor-owned psychiatric hospitals
Authors: A I Levenson
Journal: American Journal of Psychiatry (1982)

The number of investor-owned (proprietary) psychiatric hospitals in the United States has increased substantially in the past decade: these facilities now account for well over half of the nation's nongovernmental psychiatric hospitals. One of the reasons for this development has been the growth of multihospital chains, and another factor has been the economic advantages enjoyed by all investor-owned hospitals. These factors are likely to bring about further growth among investor-owned psychiatric hospitals in the future. Investor-owned hospitals in general, however, have become a subject of considerable controversy. Investor-owned psychiatric hospitals warrant specific consideration with respect to this controversy, particularly with respect to questions about quality of care.