Succinate in dystrophic white matter: A proton magnetic resonance spectroscopy finding characteristic for complex II deficiency

A deficiency of succinate dehydrogenase is a rare cause of mitochondrial encephalomyopathy. Three patients, 2 sisters and I boy from an unrelated family, presented with symptoms and magnetic resonance imaging signs of leukoencephalopathy. Localized proton magnetic resonance spectroscopy indicated a prominent singlet at 2.40ppm in cerebral and cerebellar white matter not present in gray matter or basal ganglia. The signal was also elevated in cerebrospinal fluid and could be identified as originating from the two equivalent methylene groups of succinate. Subsequently, an isolated deficiency of complex II (succinate:ubiquinone oxidoreductase) was demonstrated in 2 patients in muscle and fibroblasts. One of the sisters died at the age of 18 months. Postmortem examination showed the neuropathological characteristics of Leigh syndrome. Her younger sister, now 12 months old, is also severely affected; the boy, now 6 years old, follows a Milder, fluctuating clinical course. Magnetic resonance spectroscopy provides a characteristic pattern in succinate dehydrogenase deficiency

Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis

BACKGROUND: The developing zebrafish is an emerging tool in nanomedicine, allowing non-invasive live imaging of the whole animal at higher resolution than is possible in the more commonly used mouse models. In addition, several transgenic fish lines are available endowed with selected cell types expressing fluorescent proteins; this allows nanoparticles to be visualized together with host cells. METHODS: Here, we introduce the zebrafish neural tube as a robust injection site for cancer cells, excellently suited for high resolution imaging. We use light and electron microscopy to evaluate cancer growth and to follow the fate of intravenously injected nanoparticles. FINDINGS: Fluorescently labelled mouse melanoma B16 cells, when injected into this structure proliferated rapidly and stimulated angiogenesis of new vessels. In addition, macrophages, but not neutrophils, selectively accumulated in the tumour region. When injected intravenously, nanoparticles made of Cy5-labelled poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-PDPA) selectively accumulated in the neural tube cancer region and were seen in individual cancer cells and tumour associated macrophages. Moreover, when doxorubicin was released from PEG-PDPA, in a pH dependant manner, these nanoparticles could strongly reduce toxicity and improve the treatment outcome compared to the free drug in zebrafish xenotransplanted with mouse melanoma B16 or human derived melanoma cells. INTERPRETATION: The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells. FUNDING: We received funding from the Norwegian research council and the Norwegian cancer society

Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

<p>Abstract</p> <p>Introduction</p> <p>Refsum disease is a potentially lethal and disabling condition associated with retinitis pigmentosa in which early treatment can prevent some of the systemic manifestations.</p> <p>Case presentation</p> <p>We present the cases of two brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum disease was subsequently diagnosed midlife, after routine enquiry into hand and feet abnormalities. Subsequent treatment through dietary modification stabilised visual impairment and has prevented development of neurological complications to date.</p> <p>Conclusion</p> <p>It is therefore important to consider the diagnosis of Refsum disease in any patient with autosomal recessive or simplex retinitis pigmentosa, and to enquire about the presence of "unusual" feet or hands in such patients.</p

Immigrants from conflict-zone countries: an observational comparison study of obstetric outcomes in a low-risk maternity ward in Norway

Background Immigrants have higher risks for some adverse obstetric outcomes. Furthermore, refugees are reported to be the most vulnerable group. This study compared obstetric outcomes between immigrant women originating from conflict-zone countries and ethnic Norwegians who gave birth in a low-risk setting. Methods This was a population-based study linking the Medical Birth Registry of Norway to Statistics Norway. The study included the first registered birth during the study period of women from Somalia (n = 278), Iraq (n = 166), Afghanistan (n = 71), and Kosovo (n = 67) and ethnic Norwegians (n = 6826) at Baerum Hospital from 2006–2010. Background characteristics and obstetric outcomes of each immigrant group were compared with ethnic Norwegians with respect to proportions and risks calculated by logistic regression models. Results In total, 7408 women and their births were analyzed. Women from Somalia were most at risk for adverse obstetric outcomes. Compared with ethnic Norwegians, they had increased odds ratios (OR) for emergency cesarean section (OR 1.81, CI 1.17–2.80), postterm birth (OR 1.93, CI 1.29–2.90), meconium-stained liquor (OR 2.39, CI 1.76–3.25), and having a small-for-gestational-age infant (OR 3.97, CI 2.73–5.77). They had a reduced OR for having epidural analgesia (OR 0.40, CI 0.28–0.56) and a large-for-gestational-age infant (OR 0.32, CI 0.16–0.64). Women from Iraq and Afghanistan had increased risk of having a small-for-gestational-age infant with OR of 2.21 (CI 1.36–3.60) and 2.77 (CI 1.42–5.39), respectively. Iraqi women also had reduced odds ratio of having a large-for-gestational-age infant (OR 0.35, CI 0.15–0.83). Women from Kosovo did not differ from ethnic Norwegians in any of the outcomes we tested. Conclusions Even in our low-risk maternity ward, women originating from Somalia were at the greatest risk for adverse obstetric outcomes in the compared groups. We could not find the same risk among the other immigrant women, also originating from conflict-zone countries. Several factors may influence these findings, and this study suggests that immigrant women from Somalia need more targeted care during pregnancy and childbirth

Radiotherapy for spinal metastases from breast cancer with emphasis on local disease control and pain response using repeated MRI

Aims To evaluate metastatic lesions within the radiation field using repeated magnetic resonance imaging (MRI) and to compare the imaging findings with pain response following radiotherapy (RT) in patients with spinal metastases (SM) from breast cancer. Material and methods 32 Patients with SM from breast cancer admitted for fractionated RT were included in this study. MRI examinations of the spine were scored for the extent of bone metastases, epidural disease and the presence and severity of vertebral fractures. Clinical response was defined according to the updated international consensus on palliative RT endpoints. Results At 2 and 6 months after RT, 38% and 44% of the patients were classified as responders. None of the patients developed motor deficits. Importantly, a decrease in the intraspinal tumor volume after RT was reported in all patients. Only 6% of the patients showed bone metastases progression within the RT field, whereas 60% of the patients showed disease progression outside the RT portals. 5 Patients developed new fractures after RT, and fracture progression was observed in 21 of the 38 lesions (55%). The pain response to RT did not correlate with the presence of vertebral body fracture before RT, fracture progression or other recorded MRI features of metastatic lesions. Conclusion RT provided excellent local tumor control in patients with SM. Most patients benefit from RT even in cases of progressive vertebral fracture. Pain response was not associated with imaging findings and MRI cannot be used to select patients at risk of not responding to RT