Lipomatosis, proximal myopathy, and the mitochondrial 8344 mutation. A lipid storage myopathy?

Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We report on two families harboring the 8344 mutation. The patients presented with MSL and myopathy, expressed as limb girdle weakness in index cases and as exercise intolerance in the others. All muscle biopsies performed showed lipid storage apart from RRF and respiratory chain complexes deficiency. A possible explanation for both adipose proliferation and lipid storage myopathy in these cases is a disturbance in intermediary lipid metabolism secondary to mitochondrial respiratory chain deficiency that could be related via carnitine deficiency.     

Cosmetic outcome of breast conservative treatment for early stage breast cancer

Purpose To evaluate the cosmetic outcome of breast conservative therapy and to examine the degree of agreement between the patients’ and oncologists’ ratings. We also analyze the influence of several factors on cosmesis. Methods and materials We retrospectively evaluated 145 patients with primary breast cancer treated by local excision and radiotherapy between January 2000 and May 2001. Cosmetic outcome was evaluated by doctors and patients and was scored as excellent, good, fair or poor. Results 73% of patients rated cosmesis as excellent or good while the percentage was 71% when rated by radiation oncologists. The degree of cosmesis concordance evaluated by oncologists and patients was low (kappa=0.3). In our study the variables which significantly influence on the cosmetic outcome were concomitant adjuvant chemotherapy (p=0.04) and radiation therapy boost, either by electron beam or brachytherapy (p=0.013). Conclusion The cosmetic outcome of breast conserving therapy was good. There was a similar rating by the patient and radiation oncologist, but the level of concordance between patients and doctors was low. Factors that significantly influence the cosmesis appear to be concomitant adjuvant chemotherapy and radiation therapy boost.     

Serum levels of coenzyme Q10 in patients with amyotrophic lateral sclerosis

Summary. To elucidate whether serum coenzyme Q₁₀ levels are related with the risk for amyotrophic lateral sclerosis (ALS), we compared serum levels of coenzyme Q₁₀ and the coenzyme Q₁₀/cholesterol ratio, in 30 patients with ALS and 42 matched controls using a high performance liquid chromatography technique. The mean serum coenzyme Q₁₀ levels and the coenzyme Q₁₀/cholesterol ratio did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal vs. bulbar) of ALS, and they did not correlate with age, age at onset, and duration of the disease. These results suggest that serum coenzyme Q₁₀ concentrations are unrelated with the risk for ALS. Received September 1, 1999; accepted January 4, 2000     

Non-hodgkin’s lymphoma of the frontal sinus

Non-Hodgkin’s lymphoma (NHL) of the head and neck area is rare, and constitutes 0.4%–2% of all extranodal lymphomas and 6.4%–13% of extranodal lymphomas of the head and neck area^1–6. The maxillary antrum, nasal cavity and ethmoid sinus are the most common sites for this tumor³. Prognosis of the NHL affecting the paranasal sinuses and nasal cavity is poor with 33% of survival at 5 years^5–7. Failure of the treatment is local and with distant metastasis. Radiotherapy permits disease-free survival at 5 years in T1–T2 of 78% and in T3–T4 of 18%⁷. Only three cases in the literature have been described affecting the frontal sinus, in two cases there was infiltration of the other paranasal sinuses and in one case there was an isolated primary non-Hodgkin’s lymphoma of the frontal sinus^3,4 (Medline from 1966 to 2001). We present the second case reported in the literature of NHL exclusively affecting the frontal sinus showing local control 5 years after diagnosis.     

Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family

BACKGROUND: Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. OBJECTIVE: To characterize a potential mitochondrial dysfunction associated with mutations in the Notch3 gene. METHODS: Biochemical, histochemical, molecular, and genetic analyses were performed on muscle biopsy specimens and fibroblasts obtained from patients of a Spanish family with CADASIL. Additional biochemical and molecular analyses of the N(55e11) mutant of D. melanogaster were performed. RESULTS: In muscle biopsy specimens, a significant decrease was found in the activity of complex I (NADH [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one patient, histochemical analysis showed the presence of ragged-red fibers with abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V (ATP synthase) was found. Supporting data on patients with CADASIL, it was found that the mutation N(55e11) in Drosophila decreases the activity of mitochondrial respiratory complexes I and V. CONCLUSIONS: Mitochondrial respiratory chain activity responds, directly or indirectly, to the Notch signaling pathway. Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation.