Stevens-Johnson syndrome and toxic epidermal necrolysis in childhood-onset systemic lupus erythematosus patients: a multicenter study

Objective: To assess Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a large population of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: Multicenter study including 852 cSLE patients followed in Pediatric Rheumatology centers in Sao Paulo, Brazil. SJS was defined as epidermal detachment below 10% of body surface area (BSA), overlap SJS-TEN 10-30% and TEN greater than 30% of BSA. Results: SJS and TEN were observed in 5/852 (0.6%) cSLE female patients, three patients were classified as SJS and two patients were classified as overlap SJS-TENTEN was not observed. The mean duration of SJS and overlap SJS-TEN was 15 days (range 7-22) and antibio tics induced four cases. Regarding extra-cutaneous manifestations, hepatomegaly was observed in two cSLE patients, nephritis in two and neuropsychiatric involvement and conjunctivitis were observed respectively in one patient. Hematological involvement included lymphopenia in four, leucopenia in three and thrombocytopenia in two patients. The mean SLEDAI-2K score was 14.8 (range 6-30). Laboratory analysis showed low C3, C4 and/or CH50 in two patients and the presence of anti-dsDNA autoantibody in two patients. One patient had lupus anticoagulant and another one had anticardiolipin IgG. All patients were treated with steroids and four needed additional treatment such as intravenous immunoglobulin in two patients, hydroxychloroquine and azathioprine in two and intravenous cyclophosphamide in one patient. Sepsis was observed in three cSLE patients. Two patients required intensive care and death was observed in one patient. Conclusion: Our study identified SJS and overlap SJS-TEN as rare manifestations of active cSLE associated with severe multisystemic disease, with potentially lethal outcome.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFederico FoundationNucleo de Apoio a Pesquisa "Saude da Crianca e do Adolescente" of USP (NAP-CriAd)Univ Fed Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, SP, BrazilUniv Sao Paulo, Pediat Rheumatol Unit, Fac Med, Sao Paulo, BrazilUniv Sao Paulo, Div Rheumatol, Fac Med, Sao Paulo, BrazilSao Paulo State Univ UNESP, Fac Med Botucatu, Pediat Rheumatol Div, Botucatu, SP, BrazilHosp Infantil Darcy Vargas, Pediat Rheumatol Unit, Sao Paulo, BrazilUniv Fed Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, SP, BrazilCNPq: 303422/2015-7CNPq: 301805/2013-0CNPq: 305068/2014-8CNPq: 301479/2015CNPq: 303752/2015-7Federico FoundationNAP-CriAd-USPWeb of Scienc

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Planar shock wave generated by uniform irradiation from two overlapped partially coherent laser beams

Copyright 2001 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Journal of Applied Physics, 89(5), 2571-2575, 2001 and may be found at http://dx.doi.org/10.1063/1.134218

Hypertensive patients' perceptions of their physicians' knowledge about them: a cross-sectional study in Japan

<p>Abstract</p> <p>Background</p> <p>In order to evaluate the difference in quality of primary care provided by physicians between the types of medical institutions in Japan, we examined whether the physicians' comprehensive knowledge of their patients is perceived differently by the patients seen at clinics and hospitals.</p> <p>Methods</p> <p>Patients with prescriptions for hypertensive drugs were approached sequentially at 13 pharmacies, and were administered a questionnaire on their perception of their physician's knowledge about them. Data were obtained for 687 patients (362 from clinics and 325 from hospitals). A physician's knowledge of his or her patients was assessed according to six aspects: their medical history, their current medications, history of allergy, what worries patients most about their health, patients' values and beliefs on their health, and patients' roles and responsibilities at work, home, or school. Responses were scored from 1 through 6 (1: knows very well; 6: doesn't know at all).</p> <p>Results</p> <p>Patients treated in clinics were seen more frequently, for a longer period, and had fewer complications than the patients who were treated in hospitals. Among the six aspects of physicians' knowledge assessed, 79.3% of the patients reported that their physicians knew their complete list of medications "very well or well," while 28.3% reported the same about their roles and responsibilities at work, home, or school. Physicians in clinics were considered to know their patients' worries about their health (p = 0.004) and the roles and responsibilities of the patients at work, home, or school (p = 0.028) well. Multiple regression analysis showed that the type of medical institutions remained as a significant variable only for the aspect of patients' worries about their health. The factor that consistently affected the patients' perception of physicians' knowledge about them was the patients' age.</p> <p>Conclusions</p> <p>Hypertensive patients' perceptions of their physicians' knowledge about them did not differ significantly between clinics and hospitals in Japan for most of the aspects. In order to differentiate the roles of physicians in hospitals and clinics better and ensure the quality of primary care, the establishment of a standardized educational system to train primary care physicians better is recommended.</p

Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" for endoscopic resection of colorectal mucosal neoplasms: A prospective multi-center open-label trial

<p>Abstract</p> <p>Background</p> <p>Sodium hyaluronate (SH) solution has been used for submucosal injection in endoscopic resection to create a long-lasting submucosal fluid "cushion". Recently, we proved the usefulness and safety of 0.4% SH solution in endoscopic resection for gastric mucosal tumors. To evaluate the usefulness of 0.4% SH as a submucosal injection solution for colorectal endoscopic resection, we conducted an open-label clinical trial on six referral hospitals in Japan.</p> <p>Methods</p> <p>A prospective multi-center open-label study was designed. A total of 41 patients with 5–20 mm neoplastic lesions localized in the colorectal mucosa at six referral hospitals in Japan in a single year period from December 2002 to November 2003 were enrolled and underwent endoscopic resection with SH. The usefulness of 0.4% SH was assessed by the <it>en bloc </it>complete resection and the formation and maintenance of mucosal lesion-lifting during endoscopic resection. Safety was evaluated by analyzing adverse events during the study period.</p> <p>Results</p> <p>The usefulness rate was high (82.5%; 33/40). The following secondary outcome measures were noted: 1) steepness of mucosal lesion-lifting, 75.0% (30/40); 2) intraoperative complications, 10.0% (4/40); 3) time required for mucosal resection, 6.7 min; 4) volume of submucosal injection, 6.8 mL and 5) ease of mucosal resection, 87.5% (35/40). Two adverse events of bleeding potentially related to 0.4% SH were reported.</p> <p>Conclusion</p> <p>Using 0.4% SH solution enabled sufficient lifting of a colorectal intramucosal lesion during endoscopic resection, reducing the need for additional injections and the risk of perforation. Therefore, 0.4% SH may contribute to the reduction of complications and serve as a promising submucosal injection solution due to its potentially superior safety in comparison to normal saline solution.</p

Evaluation of 18F-2-deoxy-2-fluoro-glucose positron emission tomography for gastric cancer screening in asymptomatic individuals undergoing endoscopy

18F-2-deoxy-2-fluoro-glucose Positron Emission Tomography (FDG-PET) has been recently proposed as a promising cancer-screening test. However, the validity of FDG-PET in cancer screening has not been evaluated. We investigated the sensitivity of FDG-PET compared with upper gastric endoscopy in gastric cancer screening for asymptomatic individuals. A total of 2861 consecutive subjects (1600 men and 1261 women) who were asymptomatic and who underwent both FDG-PET and upper gastrointestinal endoscopy between 1 February 2004 and 31 January 2005 were included in this study. Both endoscopists and a radiologist were unaware of the results of the other diagnostic tests. The FDG-PET images were examined using criteria determined by the pattern of FDG accumulation. Sensitivity and specificity of FDG-PET were calculated compared with endoscopic diagnosis as the gold standard. Among 2861 subjects enrolled in the study, there were 20 subjects with gastric cancer, of whom 18 were T1 in depth of cancer invasion. Positive FDG-PET results were obtained only in 2 of the 20 cancer subjects. The calculated sensitivity and specificity for overall gastric cancers were 10.0% (95% confidence interval (CI): 1.2–31.7%) and 99.2% (95% CI: 98.8–99.5%), respectively. 18F-2-deoxy-2-fluoro-glucose Positron Emission Tomography was poorly sensitive for detection of gastric cancer in the early stages

The distribution and transitions of physicians in Japan: a 1974–2004 retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>In Japan, physicians freely choose their specialty and workplace, because to date there is no management system to ensure a balanced distribution of physicians. Physicians in Japan start their careers in hospitals, then become specialists, and then gradually leave hospitals to work in private clinics and take on primary care roles in their specialty fields. The present study aimed to analyse national trends in the distribution and career transitions of physicians among types of facilities and specialties over a 30-year period.</p> <p>Methods</p> <p>We obtained an electronic file containing physician registration data from the Survey of Physicians, Dentists and Pharmacists. Descriptive statistics and data on movement between facilities (hospitals and clinics) for all physicians from 1974, 1984, 1994 and 2004 were analysed. Descriptive statistics for the groups of physicians who graduated in 1970, 1980 and 1990 were also analysed, and we examined these groups over time to evaluate their changes of occupation and specialty.</p> <p>Results</p> <p>The number of physicians per 100 000 population was 113 in 1974, and rose to 212 by 2004. The number of physicians working in hospitals increased more than threefold. In Japan, while almost all physicians choose hospital-based positions at the beginning of their career, around 20% of physicians withdrew from hospitals within 10 years, and this trend of leaving hospitals was similar among generations. Physicians who graduated in 1980 and registered in general surgery, cardiovascular surgery or paediatric surgery were 10 times more likely to change their specialty, compared with those who registered in internal medicine. More than half of the physicians who registered in 1970 had changed their specialties within a period of 30 years.</p> <p>Conclusion</p> <p>The government should focus primarily on changing the physician fee schedule, with careful consideration of the balance between office-based physicians and hospital-based physicians and among specialties. To implement effective policies in managing health care human resources, policy-makers should also pay attention to continuously monitoring physicians' practising status and career motivations; and national consensus is needed regarding the number of physicians required in each type of facility and specialty as well as region.</p

Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer

Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies