Bohr’s radii and strips – a microscopic and a macroscopic view

The Bohr-Bohnenblust-Hille theorem states that the largest possible width $S$ of the strip in the complex plane on which a Dirichlet series $\sum_n a_n 1/n^s$ converges uniformly but not absolutely, equals $1/2$. In fact Bohr in 1913 proved that $S \leq 1/2$, and asked for equality. The general theory of Dirichlet series during this time was one of the most fashionable topics in analysis, and Bohr's so-called \textit{absolute convergence problem} was very much in the focus. In this context Bohr himself discovered several deep connections of Dirichlet series and power series (holomorphic functions) in infinitely many variables, and as a sort of by-product he found his famous power series theorem. Finally, Bohnenblust and Hille in 1931 in a rather ingenious fashion answered the absolute convergence problem in the positive. In recent years many authors revisited the work of Bohr, Bohnenblust and Hille -- improving this work but also extending it to more general settings, for example to Dirichlet series with coefficients in Banach spaces. The aim of this article is to report on parts of this new development

Role of MHC-Linked Susceptibility Genes in the Pathogenesis of Human and Murine Lupus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrum of organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still remain widely unknown. The complex etiology reflects the complex genetic background of the disease, which is also not well understood yet. However, in the past few years advances in lupus genetics have been made, notably with the publication of genome-wide association studies (GWAS) in humans and the identification of susceptibility genes and loci in mice. This paper reviews the role of MHC-linked susceptibility genes in the pathogenesis of systemic lupus erythematosus

Prevalence of Uncontrolled Hypertension in Patients With Fabry Disease

Background: Fabry disease is a rare X-linked disease arising from deficiency of α-galactosidase A. It results in early death related to renal, cardiac, and cerebrovascular disease, which are also important outcomes in patients with elevated blood pressure (BP). The prevalence of uncontrolled hypertension, as well as the effect of enzyme replacement therapy on BP, in patients with Fabry disease is unknown. Methods: We examined uncontrolled hypertension (systolic BP [SBP] ≥130 mm Hg or diastolic BP [DBP] ≥80 mm Hg) among 391 patients with Fabry disease who were participating in the Fabry Outcome Survey (FOS). Results: Uncontrolled hypertension was present in 57% of men and 47% of women. In patients with chronic kidney disease (CKD) stage 1 (n100), median SBP was 120 mm Hg and median DBP was 74 mm Hg. In patients with CKD stage 2 (n172), median SBP was 125 mm Hg and median DBP was 75 mm Hg. In patients with CKD stage 3 (n63), median SBP was 130 mm Hg and median DBP was 75 mm Hg. There was a significant decrease in both SBP and DBP during a 2-year course of enzyme replacement therapy. Conclusions: This study revealed a high prevalence of uncontrolled hypertension among patients with Fabry disease. Thus there is a need to improve BP control and renoprotection in patients with Fabry diseas

P-475: Uncontrolled hypertension in Fabry disease

Fabry disease is a x-linked lysosomal storage disease leading to early death related to renal, cardiac, and cerebrovascular disease. Therefore, proper diagnosis and therapy of elevated blood pressure may improve morbidity and mortality of these patients. However, the prevalence of uncontrolled hypertension in Fabry disease is unknown. We examined blood pressure of patients with Fabry disease using a large international database, the Fabry Outcome Survey (FOS). We defined uncontrolled hypertension as a systolic blood pressure (SBP) ≥130, and/or a diastolic blood pressure (DBP) ≥ 80 mmHg (threshold for blood pressure control in renal disease, JNC7). We used the short MDRD-GFR formula for assessment of renal function, and we classified chronic kidney disease according to K/DOQI. Among 459 patients with Fabry disease, 306 had blood pressure readings entered in the database. Mean SBP was 124.6 ± 16.9 mmHg and mean DBP was 73.6 ± 11.7 mmHg (mean age: 38.4 ± 15.6 years, 142 females, 164 males). Fourty-three percent of men and and 28% of women showed uncontrolled hypertension. In 291 patients both, blood pressure readings and GFR estimates, were available. In patients with normal GFR (>90 ml/min/1.73m2) mean SBP was 119.5 ± 15.6 mmHg and mean DBP was 69.7 ± 11.1 mmHg (n=120). In patients with mild decreased GFR (60-89 ml/min/1.73m2) mean SBP was 126.7 ± 15.9 mmHg and mean DBP was 75.0 ± 11.0 mmHg (n=110). In patients with moderate decreased GFR (30-59 ml/min/1.73m2) mean SBP was 132.7 ± 20.8 mmHg and mean DBP was 79.0 ± 13.3 mmHg (n=41). In 70 patients blood pressure readings were available before start of enzyme replacemen therapy (ERT) with agalsidase alfa (Replagal, TKT 5S Europe, 0.2 mg/kg bodyweight fortnightly i.v.), in 87 at 12 months and in 76 at 24 months of therapy. At baseline, at 12 and at 24 months of ERT, 39%, 30% and 42%of the patients presented with uncontrolled hypertension, respectively. Our study revealed a high prevalence of uncontrolled hypertension among patients with Fabry disease. Thus, there is need for improvement of blood pressure control in these patients. Am J Hypertens (2004) 17, 206A-206A; doi: 10.1016/j.amjhyper.2004.03.54

Position paper on the use of mandibular advancement devices in adults with sleep-related breathing disorders: A position paper of the German Society of Dental Sleep Medicine (Deutsche Gesellschaft Zahnaerztliche Schlafmedizin, DGZS)

Custom-made mandibular advancement devices are an effective treatment option for snoring, upper airway resistance syndrome, and obstructive sleep apnea (OSA). Evidence-based data indicates their efficacy, and international sleep societies recommend oral appliance (OA) therapy for patients with sleep-related breathing disorders. The following position paper by the German Society of Dental Sleep Medicine (DGZS) is to guide the interdisciplinary team (sleep physician and sleep disorder dentist) in detail when to prescribe oral appliances. This position paper supports the responsible use of OA as an effective treatment option for patients with sleep-related breathing disorders. The paper advises of proper indication regarding OSA severity, body mass index (BMI), and dentition. It emphasizes the interdisciplinary approach of oral appliance therapy and suggests treatment under the guidance of dentists trained in dental sleep medicine

Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus

Objectives To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). Methods Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. Results A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. Conclusion Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome

Anti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory

Estimates for vector valued Dirichlet polynomials

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