20 research outputs found

    Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

    Get PDF
    Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

    Eating at the right time of day: an underappreciated lifestyle therapy for hypertension?

    No full text
    Daily cycles of light and dark due to the rotation of the earth around its axis have dictated how life has evolved on Earth. Organisms have thus developed the ability to predict these 24-h cycles by developing an endogenous circadian clock, which is entrained to external cues. In mammals, circadian rhythms are controlled and generated by the central or master circadian clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain [1]. This master clock consists of multiple single-cell circadian oscillators that are synchronized to 24 h by environmental factors, primarily dark/light and also temperature and food. The retina perceives the dark/light cycle information and transmits this signal to the SCN via the retinohypothalamic tract. The SCN then transmits these inputs to peripheral oscillators located outside the SCN. Such peripheral oscillators exist in nearly all peripheral tissues such as liver, adipose, pancreas, muscle and blood. Therefore, circadian rhythms have been described for virtually all physiological and biochemical processes, including behavioural ones [2]

    Associations Between the Ankle-Brachial Index and Cardiovascular and All-Cause Mortality Are Similar in Individuals Without and With Type 2 Diabetes Nineteen-year follow-up of a population-based cohort study

    Get PDF
    OBJECTIVE: In the general population, a low ankle-brachial index (ABI) (<0.9) is strongly associated with (cardiovascular) mortality. However, the association between the ABI and mortality may be weaker in individuals with diabetes, as ankle pressures may be elevated by medial arterial calcification and arterial stiffening, which occur more frequently in diabetes. Therefore, the aim of this study was to compare the association between ABI and mortality in individuals without and with diabetes. RESEARCH DESIGN AND METHODS: We studied the associations between ABI and cardiovascular and all-cause mortality in 624 individuals from the Hoorn study, a population-based cohort of 50- to 75-year-old individuals (155 with diabetes and 469 without) followed for a median period of 17.2 years. Data were analyzed using Cox proportional hazards models. RESULTS: During the follow-up period, 289 of 624 (46.3%) participants died (97 of 155 with and 192 of 469 without diabetes and 52 of 65 with and 237 of 559 without ABI <0.9): 85 (29.4%) of CVD (30 of 155 with and 55 of 469 without diabetes and 20 of 65 with and 65 of 559 without ABI <0.9). A low ABI was strongly associated with cardiovascular mortality (relative risk 2.57 [95% CI 1.50–4.40]) and all-cause mortality (2.02 [1.47–2.76]), after adjustment for Framingham risk factors. The associations of the ABI with mortality did not differ between individuals without and with diabetes for cardiovascular (P(interaction) = 0.45) or all-cause (P(interaction) = 0.63) mortality. CONCLUSIONS: In the Hoorn Study, associations between ABI and cardiovascular and all-cause mortality were similar in individuals without and with diabetes. Future studies should investigate, in both individuals without and with diabetes, whether measurement of ABI can be used to guide treatment decisions

    F-18 FDG PET/CT scanning in Charcot disease: a brief report

    No full text
    PURPOSE: because of the increasing prevalence of diabetes, complications of diabetes will also become more prevalent. The pathophysiology of Charcot neuro-osteoarthropathy (Charcot disease) as a complication of diabetes is still enigmatic. As a consequence, the optimal diagnostic, follow-up, and therapeutic strategies are unclear. To obtain more insight into the relation between bony abnormalities and the (concurrent) inflammatory response in acute Charcot disease, thereby creating more insight into the pathophysiology of this disease, we performed F-18 FDG PET/CT scanning. RESEARCH DESIGN AND METHODS: We performed F-18 FDG PET/CT and Tc-99m bone scintigraphy in 10 patients with Charcot disease. Bony abnormalities on CT-scan and areas of increased uptake on F-18 FDG PET and Tc-99m bone scintigraphy were assessed independently. Subsequently, fused PET/CT images were evaluated for number and location of PET lesions. RESULTS: nine patients had increased uptake of F-18 FDG, indicating inflammation, in 25 areas of soft tissue and/or bone without concurrent bony abnormalities on CT. CONCLUSIONS: presented F-18 FDG PET/CT data may indicate an inflammatory origin of Charcot disease, with secondary bone resorption, possibly due to decreased inhibitory neurogenic inflammatory responses as a result of small fiber neuropathy. If these findings can be confirmed in future studies, F-18 FDG PET/CT scanning may be added to the diagnostic arsenal in Charcot disease, and anti-inflammatory drugs may be added to the therapeutic arsenal

    Bone turnover and hip bone mineral density in patients with sarcoidosis

    No full text
    Background and aim of the work: Sarcoidosis is a chronic inflammatory T-cell-driven disease can also affect bone. We evaluated bone remodelling and bone mineral density (BMD) in patients with coidosis and their dependency of disease-related and treatment-related factors. Methods: In 124 BMD of the hip (DXA) and markers of bone resorption (ICTP) and formation (PINP) were evaluated. thermore a lateral DXA of the spine for morphometric assessment of vertebral deformities was performed 87 patients. Potential predictors of bone markers, BMD and determinants of prevalent vertebral were assessed using multiple and logistic regression analysis. Results: The population studied comprised treated patients (n = 51), patients that previously used glucocorticoids (n = 31) and patients currently glucocorticoids (n = 42). In all these groups the age- and gender corrected Z-scores of the hip were except in untreated patients, which revealed an increased Z-score at the trochanter (p = 0.004). In all but patients currently on glucocorticoids the Z-scores for PINP and ICTP were increased (p <0.05). In currently on glucocorticoids the Z-ICTP was also increased (p <0.05), but the Z-PINP decreased (p <compared to untreated patients). In 20.6% of patients one or more morphometric vertebral deformities found. Conclusions: Hip BMD is normal in patients with sarcoidosis, despite an increased bone turnover. may imply that in sarcoidosis mechanisms are involved that compensate for the well-known effects of tokines in inflammatory diseases on osteoclastogenesis and bone resorption. Nonetheless, vertebral ties suggestive of fracture were found in a significant number of patients which indicates that patients sarcoidosis still have a relevant fracture risk
    corecore