A typical case of myoclonic epilepsy with ragged red fibers (MERRF) and the lessons learned

Mitochondrial diseases have a special predilection to involve the brain in view of its high metabolic demand and the tendency for the formation of excitatory neurotransmitters when there is deficiency of intracellular ATP. These diseases have a great phenotypic variation and need a high degree of suspicion. However, some specific syndromes are well defined, both genotypically and phenotypically. Some of the drugs are potentially fatal mitochondrial poisons and an insight into that may be lifesaving as well as prevent serious morbidities. We report a typical case of myoclonic epilepsy with ragged red fibers (MERRF) with classical phenotype and genotype. There was rapid multiaxial deterioration with the introduction of sodium valproate which partly reversed on introducing mitochondrial cocktail and withdrawal of the offending drug. Sodium valproate, phenobarbitone, chloramphenicol and many anti-viral agents are mitochondrial poisons that increase the morbidity and mortality in patients with mitochondrial disease. More harm to the patient can be avoided with insight into this information.KEY WORDS: Midline lipoma, mitochondrial disease, sodium valproate     

Resistance of <Emphasis Type="Italic">Leishmania (Leishmania) amazonensis</Emphasis> and <Emphasis Type="Italic">Leishmania (Viannia) braziliensis</Emphasis>to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

Background  

Nitric oxide (NO^•) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO^• resistant Escherichia coli and Mycobacterium tuberculosis have been associated with a severe outcome of these diseases.     

The impact of HLA-DRB1*0405 on disease severity in Korean patients with seropositive rheumatoid arthritis

Many reports have described HLA-DRB1 genes as having an influence on disease severity and susceptibility in rheumatoid arthritis (RA). Studies were undertaken to define the effect of RA-associated alleles on disease severity in Korean patients with seropositive RA. The results indicate that the most common RA susceptibility allele, HLA- DRB1*0405, is significantly associated with bony erosion, joint deformity and extra-articular manifestations. However, RA-associated alleles in Koreans have less effect on nodular disease than in Caucasians. This suggests that the presence of RA-associated alleles, especially HLA-DRB1*0405, seems to be a prognostic marker for severe erosive disease in Koreans.      

Severe congenital neutropenia: abnormal growth and differentiation of myeloid progenitors to granulocyte colony-stimulating factor (G-CSF) but normal response to G-CSF plus stem cell factor

Several mechanisms have been proposed to explain the pathogenesis of severe congenital neutropenia (SCN); however, the mechanism(s) still remains unknown. In particular, clinical observations suggest that abnormal responsiveness of myeloid progenitors to hematopoietic growth factors (HGFs) is a possible mechanism. Therefore, to better define the status of hematopoietic progenitors in the bone marrow (BM) of patients with SCN, the responsiveness of myeloid progenitors to HGFs from two SCN patients was compared with the responsiveness of progenitors from healthy individuals. BM cells (BMCs) from the first SCN patient required higher (10- to 100-fold) concentrations of granulocyte colony- stimulating factor (G-CSF) to achieve maximal and half-maximal colony growth in vitro compared with BMCs from controls. In contrast, the dose- response of interleukin-3 (IL-3) and granulocyte-macrophage-CSF (GM- CSF) in colony formation was normal. Interestingly, IL-3, GM-CSF, and G- CSF at optimal doses showed reduced ability to induce neutrophil differentiation of BMCs from a SCN patient compared with BMCs from controls. Despite an abnormal responsiveness of mature myeloid progenitors to G-CSF in this SCN patient, myeloid progenitors responsive to the combination of stem cell factor (SCF) and G-CSF showed normal dose-response. In contrast to G-CSF alone, the combination of G-CSF and SCF induced the formation of neutrophils almost to the same extent compared with cultures of normal BMCs. Furthermore, also on BM progenitor cells obtained from the second patient with SCN, SCF highly synergized with G-CSF to promote neutrophil progenitor cell growth and differentiation in vitro. Thus, these results indicate that one mechanism of the pathogenesis in SCN patients is reduced responsiveness of neutrophil progenitor cells to G- CSF and that SCF can enhance the responsiveness of these cells to G-CSF.