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

Agalsidase Alfa Slows the Decline in Renal Function in Patients with Fabry Disease

The aim of this study was to determine the effects of enzyme replacement therapy with agalsidase α on renal function in patients with Fabry nephropathy. Serum creatinine data were collected from 165 adult patients during 3 years of treatment. Serum creatinine increased in all men whereas it was stable in women, except in stage II renal disease (Kidney Disease Outcomes Quality Initiative). The estimated glomerular filtration rate (eGFR) declined in males with stage I and II (from 115.0 ± 22.2 to 98.3 ± 27.3 and from 76.5 ± 8.1 to 66.3 ±21.6 ml/min/1.73 m2, respectively; both p 2; p = 0.01). The 24-hour proteinuria was <1 g in all patients, and most patients (96%) were treated with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors. Agalsidase α in combination with ACE inhibitors/ARB may be effective in slowing the deterioration in renal function in Fabry nephropathy

Optical spectral transmission to assess glucocorticoid therapy response in patients with arthritis: a longitudinal follow-up comparison with joint ultrasound

Background Optical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up. Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers. Methods 1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses. Results OST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83–0.94) and after GC=0.811(95%CI=0.74–0.881); p<0.001]. Furthermore, OST correlated significantly with all examined sonographic activity scores (all; p<0.001) and with swollen joint counts (p<0.01). Conclusions OST was able to assess response to therapy in a similar way to joint US and correlated significantly with arthritis activity markers. Therefore, OST has proved to be a valuable tool to assist disease activity monitoring in the examined cohort. Trial registration German Registry of Clinical Trials, DRKS0001675

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