Persistent fetal vasculature and severe protein C deficiency

Persistent fetal vasculature (PFV) is most often a condition of unknown cause. It represents persisting elements of fetal ocular vessels including the hyaloid arterial network. Protein C is a vitamin K-dependent serine protease, which regulates coagulation. Deficiency of protein C leads to a prothrombotic state. We report the case of a male infant born at 34 weeks gestation to non-consanguineous parents. Ophthalmic examination found bilateral PFV, microphthalmia and vitreoretinal dysplasia. He also suffered bilateral renal vein thrombosis and purpura fulminans and was diagnosed with severe protein C deficiency. Genetic analysis of the PROC gene revealed two separate pathogenic mutations, confirming compound heterozygote status. Both parents were found to be heterozygous. While ocular manifestations (commonly haemorrhages) are often seen in protein C-deficient patients, a search of the literature reveals very few recorded cases of PFV in severe protein C deficiency. We hypothesise that protein C deficiency was the cause of PFV in this patient. Intraocular thrombotic events in utero could affect the normal development of ocular vessels and lead to persistent elements of fetal vasculature in the eye. Consideration should be given to the possibility of protein C deficiency in patients presenting with PFV, particularly if bilatera

New NBIA subtype: Genetic, clinical, pathologic, and radiographic features of MPAN

Objective: to assess the frequency of mutations in C19orf12 in the greater neurodegeneration with brain iron accumulation (NBIA) population and further characterize the associated phenotype.Methods: samples from 161 individuals with idiopathic NBIA were screened, and C19orf12 mutations were identified in 23 subjects. Direct examinations were completed on 8 of these individuals, and medical records were reviewed on all 23. Histochemical and immunohistochemical studies were performed on brain tissue from one deceased subject.Results: a variety of mutations were detected in this cohort, in addition to the Eastern European founder mutation described previously. The characteristic clinical features of mitochondrial membrane protein-associated neurodegeneration (MPAN) across all age groups include cognitive decline progressing to dementia, prominent neuropsychiatric abnormalities, and a motor neuronopathy. A distinctive pattern of brain iron accumulation is universal. Neuropathologic studies revealed neuronal loss, widespread iron deposits, and eosinophilic spheroidal structures in the basal ganglia. Lewy neurites were present in the globus pallidus, and Lewy bodies and neurites were widespread in other areas of the corpus striatum and midbrain structures.Conclusions: MPAN is caused by mutations in C19orf12 leading to NBIA and prominent, widespread Lewy body pathology. The clinical phenotype is recognizable and distinctive, and joins pantothenate kinase-associated neurodegeneration and PLA2G6-associated neurodegeneration as one of the major forms of NBI

Low efficacy of azithromycin to treat cutaneous leishmaniasis in Manaus, AM, Brazil Azitromicina para tratamento de leishmaniose cutânea em Manaus, AM, Brasil

An open trial to evaluate the azithromycin efficacy in cutaneous leishmaniasis patients was carried out in Manaus (AM), where Leishmania (Viannia) guyanensis is the main etiologic agent. Forty-one patients with skin lesions of less than 12 weeks duration, without specific treatment for the last three months and a positive imprint to Leishmania sp. were included. From these, 31 (75.6%) were male with median age of 30.2. All of them received a daily-single oral dose of 500 mg of azithromycin for ten days. At 25th day, 16 (39%) presented therapeutic failure and received intramuscular pentavalent antimonial, four were considered lost, 21, that had improved or were inaltered received another ten-day series of azithromycin and were monthly followed, but nine (21.9%) of them presented a poor clinical response and switched to intramuscular pentavalent antimonial on day 55. Of the 12 remaining cases evaluated on day 55, despite of clinical improvement, three asked for antimony therapy and 9 (21.9%) continued the follow-up but, only three were cured on 55th, 85th and 115th days, and six did not come back for final evaluation. The intention-treatment overall response rate was 22% and whole cure was seen in three (7.3%) of cases. Thus, azithromycin showed a low efficacy to treat cutaneous leishmaniasis in Manaus.<br>Para avaliar a eficácia da azitromicina na leishmaniose cutânea, foi realizado ensaio clínico em Manaus, Amazonas, onde o agente etiológico predominante é a Leishmania (Viannia) guyanensis. Incluídos 41 pacientes com lesões de menos de 12 semanas, sem história de tratamento específico nos últimos três meses e com esfregaço positivo para Leishmania sp. Destes, 31 (75,6%) eram masculinos, idade média 30,2 anos. Todos receberam azitromicina 500 mg em dose única oral, diária, por 10 dias. No dia 25º, 16 (39%) pioraram e receberam antimonial pentavalente via intramuscular por 20 dias e, 21 (61%) que apresentaram melhora da lesão ou esta permanecia inalterada no 25º dia, receberam outro ciclo de 10 dias de azitromicina e foram acompanhados mensalmente. Destes, nove (21,9%) apresentaram piora das lesões na avaliação do dia 55 e iniciaram tratamento com antimonial neste dia. Dos 12 que permaneceram no estudo, porque tinham melhorado clinicamente, três optaram por tratamento com antimonial pentavalente no 55º dia e três apresentaram reepitelização completa das lesões nos dias 55º, 65º e 115º. Seis pacientes não retornaram para avaliação final. Análise por tentativa de tratamento foi 22% e cura confirmada em três (7,3%) casos. Estes resultados mostraram que azitromicina tem baixa eficácia para tratar leishmaniose em área onde a Leishmania (Viannia) guyanensis é o agente etiológico predominante