Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.     

Humorale Vaskulitisdiagnostik bei peripherer arterieller Verschlusskrankheit

BACKGROUND: In patients with early manifestation of peripheral arterial occlusive disease (PAOD) and a less classical atherosclerotic risk profile, vasculitis is presumed to be the underlying disease. We performed a prospective study of the importance of determination of autoantibodies used for the diagnosis of vasculitis and collagen diseases in patients with symptomatic PAOD. PATIENTS AND METHOD: 698 consecutive patients (mean age +/- SD: 68 +/- 10 years) were included who were referred from 1998 to 1999 for interventional treatment of PAOD. In 121 PAOD-patients (61 +/- 12 years) with a less pronounced atherosclerotic risk profile, or rarefied distal arteries without sclerosis of the media, or elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) independent from the stage IV of PAOD, the following autoantibodies were investigated: antinuclear antibodies (ANA), antibodies against extractable nuclear antigens (ENA): SCL 70, RNP, SS-A, SS-B, Jo-1, SM), double-stranded DNA antibodies (ds-DNA), antineutrophil cytoplasmatic antibodies (c- and p-ANCA), antiphospholipid antibodies [phosphatidylserine (APSA) and beta(2)-glycoprotein], smooth (SMA) and striated muscle (StrMA). ANA, SMA and StrMA were estimated by indirect immunofluorescence technique, ENA by Western-blot and the others by enzyme linked immunoassay. RESULTS: 38 PAOD-patients (35%) had increased autoantibody concentrations. The rate of different PAOD stages and localization did not differ between the group of patients with increased autoantibody concentrations and the group of patients without. But the group of patients with increased autoantibody concentrations had higher rates of elevated ESR [p-value of 0.0043, odds ratio of 7.1 (95% CI: 1.49-33.81)]. ANA were the most frequent autoantibodies detected in 17 (14%) of the 121 patients followed by APSA and autoantibodies directed against beta(2)-glycoprotein. During follow-up of 24 +/- 6 months no vasculitis or collagen diseases associated with the elevated autoantibody concentrations became clinically manifest in the 38 patients. Two patients died due to coronary heart disease. Four patients had a worsening of their PAOD but no amputation was performed. Out of the 83 patients without elevated concentrations of autoantibodies, eight patients died and three amputations were carried out. CONCLUSION: All in all, increased autoantibody concentrations in patients suffering from peripheral atherosclerosis are not a rare finding. A systematic determination of autoantibodies, especially in patients with a low atherosclerotic risk profile, does not increase the number of manifest or developing vasculitis of collagen disease.     

Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects

OBJECTIVE: Studies to prove a relationship between fatigue and immunological, inflammatory, or other disease characteristics of systemic lupus erythematosus (SLE) have shown no consistent findings. To further elucidate the basis for fatigue in SLE, we examined the affective states, personality traits, and mental health status in an unselected group of patients with SLE. METHODS: Fifty-seven Caucasian patients with SLE were examined. Fatigue was measured by the Fatigue Severity Scale. Personality traits and psychological function were evaluated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the affective states by Beck Depression Inventory, and mental health status by the General Health Questionnaire version 30 (GHQ-30). RESULTS: Fatigue was closely associated with high scores on subscales Depression (D-2) and Hysteria (Hy-3) on MMPI-2 (R2 = 0.31; p = 0.0002), as well as with high scores on BDI (R2 = 0.22; p = 0.0006) and GHQ (R2 = 0.33; p < 0.0001). CONCLUSION: Fatigue does not seem to be caused by any easily recognizable single or multiple factor(s) of an inflammatory or immunological state. Our results point to fatigue being a multifaceted phenomenon where several psychosocial factors are strongly related, and indicate that fatigue is part of a complex response to chronic disease.     

Presentations to the Emergency Department Following Cannabis use—a Multi-Centre Case Series from Ten European Countries

Cannabis is the most commonly used illicit drug in Europe, and is generally regarded as having low acute toxicity. We present the findings of the first 6 months of data collection from the Euro-DEN project on presentations related to cannabis use to further understand the acute toxicity related to the use of cannabis. Data was extracted on clinical features, treatment and outcome from the Euro-DEN minimum dataset for all cases of acute recreational drug toxicity reported 1st October 2013 to 31st March 2014 for all cannabis-related presentations. Of 2198 presentations reported by 14 of the 16 Euro-DEN centres, 356 (16.2 %) involved cannabis either alone or together with other drugs/alcohol. There were 36 that involved lone use of cannabis (1.6 % of all presentations). Of the 35 non-fatal lone cannabis presentations, the most commonly reported features were neuro-behavioural (agitation/aggression 8 (22.9 %), psychosis 7 (20.0 %), anxiety 7 (20.0 %)) and vomiting 6 (17.1 %). Most patients (25, 71.4 %) received no treatment and 30 (85.7 %) were discharged/self-discharged from the ED. There was one fatality amongst these lone-cannabis cases: an 18-year-old male collapsed with an asystolic cardiac arrest whilst smoking cannabis and suffered hypoxic brain injury related to prolonged cardiac arrest. THC was detected in a urine sample taken at ED arrival; no other drugs were detected. Lone acute cannabis toxicity was typically associated with neuro-behavioural symptoms and vomiting. Although uncommon, severe toxicity including cardiovascular toxicity and death may be under-recognised, and it is important that Emergency Physicians are aware of this.     

Impact of age, height, and body mass index on arterial diameters in infants and children: a model for predicting femoral artery diameters prior to cardiovascular procedures.

PURPOSE: To measure common femoral artery (CFA) diameters in infants and children referred for cardiac catheterization and investigate if CFA diameters can be predicted upon the basis of age, body mass index (BMI), and height. METHODS: CFA diameters were measured in 84 infants and children (50 boys; age range 1- 220 months) referred for diagnostic or therapeutic cardiac interventions. Sonographic measurements were made in a supine position utilizing a 7.5-MHz linear transducer; diameters were defined as the intima to intima distance. Age was described in months and height in centimeters. The Spearman correlation coefficient (rho) was used to test the similarity of diameters between sides; the Pearson correlation coefficient (r) was used to analyze the influence of age, height, and BMI on CFA diameter. RESULTS: Diameters of the right and left CFA were similar (rho=0.951). Age and height were highly correlated (rho=0.956), but not BMI and height (rho=0.279). The best model was CFA diameter = -0.838 + 0.031 height + 0.046 BMI. Height was the most relevant determinant for CFA diameter (p<0.0001, 90% CI 0.027 to 0.036; BMI: p=0.093, 90% CI 0.001 to 0.090, and the intercept: p=0.032, 90% CI-1.475 to-0.200). CONCLUSIONS: Common femoral artery diameter can be sufficiently predicted from height and BMI of infants and children prior to femoral catheterization or surgical reconstruction.     

Global epidemiology of tuberculosis: prospects for control

The burden of tuberculosis (TB) is now very slowly decreasing globally. However, the rate of decline is too slow to reach all the epidemiological impact targets set for 2015. The prospects for reaching the TB elimination target set for 2050 are even bleaker. Implementation of the World Health Organization's Stop TB Strategy is currently lagging behind the envisioned scale-up pace, particularly with regard to TB/HIV collaborative activities and management of drug resistant TB. To ensure long-term TB control there is, first, a need to ensure that all components of the Stop TB Strategy are scaled up according to plans, with special attention to improved access for the poor. However, this may not be enough. Recent analyses suggest that the impact of current efforts to reduce TB incidence is less than expected and that improved diagnostic and curative efforts need to be combined with additional preventive efforts. New and more effective vaccines and drugs for preventive treatment would revolutionize TB control. A stronger focus on prevention would also entail more concerted actions to limit the impact of TB risk factors, including HIV/AIDS, smoking, malnutrition, alcoholism, diabetes, crowded living conditions, and indoor air pollution, which may all contribute a considerable proportion of the global TB burden.