RESUMO
BACKGROUND: Adrenal hypoplasia congenita (AHC) is an X-linked disorder that affects the adrenal cortex and hypothalamus-pituitary-gonadal axis (HPG), leading to primary adrenocortical insufficiency (PAI) and hypogonadotropic hypogonadism. AHC is caused by a mutation in the DAX-1 gene (NR0B1). More commonly, this disease is characterized by early-onset PAI, with symptoms in the first months of life. However, a less severe phenotype termed late-onset AHC has been described, as PAI signs and symptoms may begin in adolescence and adulthood. Here we describe a family report of a novel mutation within NR0B1 gene and variable reproductive phenotypes, including spontaneous fertility, in a very late-onset X-linked AHC kindred. CASE PRESENTATION: Three affected maternal male relatives had confirmed PAI diagnosis between 30 y and at late 64 y. The X-linked pattern has made the endocrinology team to AHC suspicion. Regarding the HPG axis, all males presented a distinct degree of testosterone deficiency and fertility phenotypes, varying from a variable degree of hypogonadism, oligoasthenoteratozoospermia to spontaneous fertility. Interestingly, the other five maternal male relatives unexpectedly died during early adulthood, most likely due to undiagnosed PAI/adrenal crisis as the probable cause of their premature deaths. Sequencing analysis of the NR0B1 gene has shown a novel NR0B1 mutation (p.Tyr378Cys) that segregated in three AHC family members. CONCLUSIONS: NR0B1 p.Tyr378Cys segregates in an AHC family with a variable degree of adrenal and gonadal phenotypes, and its hemizygous trait explains the disease in affected family members. We recommend that NR0B1 mutation carriers, even those that are allegedly asymptomatic, be carefully monitored while reinforcing education to prevent PAI and consider early sperm banking when spermatogenesis still viable.
Assuntos
Insuficiência Adrenal/genética , Insuficiência Adrenal/patologia , Receptor Nuclear Órfão DAX-1/genética , Fertilidade , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Reprodução , Adulto , Idade de Início , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , PrognósticoRESUMO
Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.
Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Mefloquina/uso terapêutico , Adolescente , Adulto , Animais , Antimaláricos/farmacologia , Brasil , Resistência a Medicamentos , Humanos , Masculino , Mefloquina/farmacologia , Pessoa de Meia-Idade , Plasmodium falciparum/efeitos dos fármacos , Resultado do TratamentoRESUMO
The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.
Assuntos
Antimaláricos/administração & dosagem , Malária/tratamento farmacológico , Naftoquinonas/administração & dosagem , Proguanil/administração & dosagem , Adolescente , Adulto , Idoso , Antimaláricos/efeitos adversos , Atovaquona , Brasil , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Naftoquinonas/efeitos adversos , Proguanil/efeitos adversos , Quinina/administração & dosagem , Quinina/efeitos adversos , Tetraciclina/administração & dosagem , Tetraciclina/efeitos adversosRESUMO
This is the first report of serologic evidence of hepatitis E infection in Brazil. During a community-based survey of healthy individuals, six of 97 gold miners in the Amazon region of Mato Grosso had antibody to the virus. The mining camps have poor sanitation with a great potential for fecal-oral transmission of disease. Since levels of hepatitis E antibodies may quickly wane, studies to directly measure the incidence of seroconversion are planned to determine the intensity of transmission in this area.