Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy

Background

The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities.

Methods

Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated.

Results

Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients.

Conclusions

Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.     

Mineral Content in Baltic Herring and Baltic Herring Products

The contents of Fe, Cu, Zn, Mn, K, Mg, Ca, Na, As and Cd in gutted Baltic herring (Clupea harengus membras), in Baltic herring fillets and in two commercial ready-to-eat products made of these were investigated. The fish was caught in 1996–1998 in the northern Baltic. The commercial products were fried fillets and fish burgers. The effects of industrial processing on the mineral composition were studied by collecting samples at several consecutive stages. In the gutted fish the levels of Mn, Ca and Cd were considerably higher than in the fillet mainly due to the bones. Significant differences were also observed in the contents of Mg, Na, Cu and Zn. In the burger process the bones and skin were removed which caused a decrease in the Zn and Ca levels. Ingredients such as salt, spices and flour as part of the formula increased Na and Mn contents in the ready-to-eat products. In the final products the Na content was about 6 times higher than that of the fresh fish.     

Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory and degenerative disease leading to demyelination and axonal damage in the CNS. Autoimmunity plays a central role in MS pathogenesis. Per definition, monoclonal antibodies are recombinant biological compounds with a well defined target, thus carrying the promise of targeting pathogenic cells or molecules with high specificity, avoiding undesired off-target effects. Natalizumab was the first monoclonal antibody to be approved for the treatment of MS. Several other monoclonal antibodies are in development and have demonstrated promising efficacy in phase II studies. They can be categorized according to their mode of action into compounds targeting (i) leukocyte migration into the CNS (natalizumab); (ii) cytolytic antibodies (rituximab, ocrelizumab, ofatumumab, alemtuzumab); or (iii) antibodies and recombinant proteins targeting cytokines and chemokines and their receptors (daclizumab, ustekinumab, atacicept, tabalumab [Ly-2127399], secukinumab [AIN457]). In this review, we discuss the specific molecular targets, clinical efficacy and safety of these compounds and discuss criteria to anticipate the position of monoclonal antibodies in the diversifying armamentarium of MS therapy in the coming years.     

Neurological outcome of childhood brain tumor survivors

We assessed neurological and neurocognitive outcome in childhood brain tumor survivors. Altogether, 75 out of 80 brain tumor survivors diagnosed below 17 years between 1983 and 1997; and treated in Tampere University Hospital, Finland, were invited to participate in this population-based cross-sectional study. Fifty-two (69%) participated [mean age 14.2 (3.8–28.7) years, mean follow-up 7.5 (1.5–15.1) years]. Neurological status was abnormal in 69% cases. All were ambulatory, but only 50% showed normal motor function. Twenty-nine percent showed clumsiness/mild asymmetry and 21% hemiparesis. One suffered from intractable epilepsy. According to structured interview, 87% coped normally in daily living. Median full-scale IQ was 85 (39–110) in 21 6–16 year olds (70%); in 29% IQ was <70. Thirty of the 44 school-aged subjects attended school with normal syllabus and 32% needed special education. Six of the 16 patients over 18 years of age were working. Regarding quality of life, 38% were active without disability, 33% active with mild disability, 21% were partially disabled, but capable of self-care, and 8% had severe disability, being incapable of self-care. Supratentorial/hemispheric tumor location, tumor reoperations, shunt revisions and chemotherapy were associated with neurological, cognitive and social disabilities. In conclusion, of the 52 survivors, neurological status was abnormal in 69%; 71% lived an active life with minor disabilities, 29% had major neurological, cognitive and social disabilities, and 8% of them were incapable of self-care. Predictors of these disabilities included supratentorial/hemispheric tumor location, tumor reoperations, shunt revisions and chemotherapy. Survivors need life-long, tailor-made multiprofessional support and follow-up.