Exacerbation of erythropoietic protoporphyria by hyperthyroidism

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. The majority of EPP patients present with a clinical symptom of painful phototoxicity. Liver damage, the most serious complication of EPP, occurs in <5% of the patients. This report describes a case of an EPP patient who complained of worsening cutaneous symptoms, nervousness, and insomnia. Laboratory tests showed highly increased protoporphyrin concentration in erythrocytes and elevated serum transaminases that are indicative of EPP-related liver damage. The subsequent finding of decreased serum thyroid-stimulating hormone (TSH) and increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations, as well antibodies against both thyroid peroxidase (TPO) and TSH receptors, led to the diagnosis of Graves' disease. The patient received 500MBq of radioiodine (I131). Three months after the radioactive iodine therapy, the thyroid volume was reduced to 30% of pretherapeutic volume. Although the patient was slightly hypothyroidic, his liver enzymes returned to normal, his erythrocytic protoporphyrin concentration dropped fivefold, and his skin symptoms improved dramatically. The coexistence of Graves' disease and EPP is a statistically rare event as, besides our patient, there was one additional case reported in the literature. Although the exact mechanism whereby Graves' disease interacts with EPP is yet to be explored, we recommend testing thyroid function in EPP patients with liver complication to exclude hyperthyroidism as a potential caus

Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine

Background: Extensive application of measurement of urinary iodine concentration (UIC) in several benign and malignant thyroid diseases could profit by the availability of rapid and inexpensive measuring techniques. Aim of this study was to apply a simple and inexpensive commercially available potentiometric method for the quantification of UIC based on iodine-specific ion-selective electrodes (ISE) in patients with thyroid diseases. Methods: This retrospective study included patients with differentiated thyroid cancer (n=286) and patients with hyperthyroidism of different etiologies (n=203). Within the whole sample (n=489) 20 patients had previously (1 week-6 months) been exposed to iodine overload, either from contrast media (n=8) or amiodarone (n=12). Results: In patients not exposed to iodine, the histogram showed that the distribution of UIC violated normality. The peak of the curve occurred between 5.0 μmol/L and 6.0 μmol/L. Variability was sizeable (percent coefficient of variation, %CV: 66%, 95% confidence interval: 1.48-18.72 μmol/L). The group of exposed patients could be easily distinguished from not exposed patients (median UIC: 47.5 μmol/L vs. 5.42 μmol/L). UIC was significantly correlated to urinary creatinine concentration, but normalization to urinary creatinine increased the inter-subject variability of UIC (%CV=96% vs. 66%). In test-retest studies (n=25) the intra-class correlation coefficient was 0.73 for UIC, 0.82 for creatinine and 0.64 for the UIC: creatinine ratio. Conclusions: Iodine-specific ISE-based potentiometric methods can be successfully applied as an alternative to existing methods in patients with thyroid diseases. The promising characteristics of the method need to be confirmed in future larger prospective studies

A Next-Generation Sequencing Approach Uncovers Viral Transcripts Incorporated in Poxvirus Virions

Transcripts are known to be incorporated in particles of DNA viruses belonging to the families of Herpesviridae and Mimiviridae, but the presence of transcripts in other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we first established a next-generation-sequencing (NGS)-based protocol, enabling the unbiased identification of transcripts in virus particles. Subsequently, we applied our protocol to analyze RNA in an emerging zoonotic member of the Poxviridae family, namely Cowpox virus. Our results revealed the incorporation of 19 viral transcripts, while host identifications were restricted to ribosomal and mitochondrial RNA. Most viral transcripts had an unknown and immunomodulatory function, suggesting that transcript incorporation may be beneficial for poxvirus immune evasion. Notably, the most abundant transcript originated from the D5L/I1R gene that encodes a viral inhibitor of the host cytoplasmic DNA sensing machinery

Exacerbation of erythropoietic protoporphyria by hyperthyroidism

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. The majority of EPP patients present with a clinical symptom of painful phototoxicity. Liver damage, the most serious complication of EPP, occurs in <5% of the patients. This report describes a case of an EPP patient who complained of worsening cutaneous symptoms, nervousness, and insomnia. Laboratory tests showed highly increased protoporphyrin concentration in erythrocytes and elevated serum transaminases that are indicative of EPP-related liver damage. The subsequent finding of decreased serum thyroid-stimulating hormone (TSH) and increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations, as well antibodies against both thyroid peroxidase (TPO) and TSH receptors, led to the diagnosis of Graves' disease. The patient received 500MBq of radioiodine (I131). Three months after the radioactive iodine therapy, the thyroid volume was reduced to 30% of pretherapeutic volume. Although the patient was slightly hypothyroidic, his liver enzymes returned to normal, his erythrocytic protoporphyrin concentration dropped fivefold, and his skin symptoms improved dramatically. The coexistence of Graves' disease and EPP is a statistically rare event as, besides our patient, there was one additional case reported in the literature. Although the exact mechanism whereby Graves' disease interacts with EPP is yet to be explored, we recommend testing thyroid function in EPP patients with liver complication to exclude hyperthyroidism as a potential caus

Prognostic value of stress-gated 99m-technetium SPECT myocardial perfusion imaging: Risk stratification of patients with multivessel coronary artery disease and prior coronary revascularization

BACKGROUND: This study assessed the prognostic value of stress-gated 99mTc-sestamibi myocardial perfusion SPECT (MPS) in patients with multivessel coronary artery disease (CAD) and prior revascularization according to the presence and severity of ischemia. METHODS AND RESULTS: We studied the outcome of 472 patients with multivessel CAD and prior revascularization (coronary angioplasty, 290 patients; bypass surgery, 182 patients), who underwent exercise or dipyridamole 99mTc-sestamibi MPS for evaluation of ischemia. Visual scoring of perfusion images used 20 segments and a 5-point scale. Gated post-stress EF was automatically calculated. Endpoints included hard events: cardiac death (CD) and nonfatal myocardial infarction (MI). During a mean follow-up of 3.0 ± 1.0 years, 37 hard events occurred, including CD in 15 (3%) and MI in 22 (5%) patients. In a risk-adjusted multivariable Cox model, a history of prior MI, diabetes, abnormal MPS, moderate-to-severe ischemia, and post-stress EF <35% were important predictors of cardiac events. Four-year risk-adjusted survival was 97.9% for normal MPS, 87.3% for abnormal MPS with ischemia, and 82.1% for moderate-to-severe ischemia. CONCLUSIONS: Among patients with previous coronary revascularization, stress-gated 99mTc-sestamibi MPS provides prognostic information for the prediction of cardiac events. A normal perfusion scan confers an excellent prognosis and an exceedingly low hard event rate (<1%/year). The presence of moderate-to-severe ischemia or a post-stress EF <35% identifies patients at highest risk of subsequent cardiac events

A Next-Generation Sequencing Approach Uncovers Viral Transcripts Incorporated in Poxvirus Virions

Transcripts are known to be incorporated in particles of DNA viruses belonging to the families of Herpesviridae and Mimiviridae, but the presence of transcripts in other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we first established a next-generation-sequencing (NGS)-based protocol, enabling the unbiased identification of transcripts in virus particles. Subsequently, we applied our protocol to analyze RNA in an emerging zoonotic member of the Poxviridae family, namely Cowpox virus. Our results revealed the incorporation of 19 viral transcripts, while host identifications were restricted to ribosomal and mitochondrial RNA. Most viral transcripts had an unknown and immunomodulatory function, suggesting that transcript incorporation may be beneficial for poxvirus immune evasion. Notably, the most abundant transcript originated from the D5L/I1R gene that encodes a viral inhibitor of the host cytoplasmic DNA sensing machinery

Qualitätskultur. Ein Blick in die gelebte Praxis der Hochschulen. Beiträge zur 4. AQ Austria Jahrestagung 2016

Die Publikation zur AQ Austria Jahrestagung 2016 präsentiert in den einzelnen Beiträgen vielfältige Perspektiven, Ansätze, Beispiele und Erfahrungen mit Qualitätskultur und ermöglicht somit einen Blick in die gelebte Praxis der Qualitätskultur an Hochschulen. Die Frage, ob wir eine Qualitätskultur brauchen und was dafür oder dagegen spricht, [wird] in einleitenden Thesen [bearbeitet]. In fünf Foren wurden Kernfragen in Zusammenhang mit Zweck, Bedingungen und Ausgestaltung der Qualitätskultur diskutiert. Es geht u. a. um das Verständnis und den Stellenwert von Qualitätskultur ,das Wechselspiel mit internen und externen Rahmenbedingungen und um die Frage, wie Einstellungen und Werthaltungen der Mitarbeiterinnen und Mitarbeiter im Sinne einer Qualitätskultur gefördert werden können. Weitere Beiträge befassen sich mit dem Verhältnis von Qualitätskultur und externer Qualitätssicherung und damit, wie wirkungsvoll oder auch wirkungslos Qualitätskultur von Hochschulen eingeschätzt wird. (Autor

Prognostic value of stress-gated 99m-technetium SPECT myocardial perfusion imaging: Risk stratification of patients with multivessel coronary artery disease and prior coronary revascularization

BACKGROUND: This study assessed the prognostic value of stress-gated 99mTc-sestamibi myocardial perfusion SPECT (MPS) in patients with multivessel coronary artery disease (CAD) and prior revascularization according to the presence and severity of ischemia. METHODS AND RESULTS: We studied the outcome of 472 patients with multivessel CAD and prior revascularization (coronary angioplasty, 290 patients; bypass surgery, 182 patients), who underwent exercise or dipyridamole 99mTc-sestamibi MPS for evaluation of ischemia. Visual scoring of perfusion images used 20 segments and a 5-point scale. Gated post-stress EF was automatically calculated. Endpoints included hard events: cardiac death (CD) and nonfatal myocardial infarction (MI). During a mean follow-up of 3.0 ± 1.0 years, 37 hard events occurred, including CD in 15 (3%) and MI in 22 (5%) patients. In a risk-adjusted multivariable Cox model, a history of prior MI, diabetes, abnormal MPS, moderate-to-severe ischemia, and post-stress EF <35% were important predictors of cardiac events. Four-year risk-adjusted survival was 97.9% for normal MPS, 87.3% for abnormal MPS with ischemia, and 82.1% for moderate-to-severe ischemia. CONCLUSIONS: Among patients with previous coronary revascularization, stress-gated 99mTc-sestamibi MPS provides prognostic information for the prediction of cardiac events. A normal perfusion scan confers an excellent prognosis and an exceedingly low hard event rate (<1%/year). The presence of moderate-to-severe ischemia or a post-stress EF <35% identifies patients at highest risk of subsequent cardiac events

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P &lt; 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P &lt; 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis