RESUMO
CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.
Assuntos
DNA Mitocondrial/genética , Surdez/genética , Diabetes Mellitus/genética , Leucócitos/metabolismo , Doenças Mitocondriais/genética , Mutação Puntual , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Caracteres SexuaisRESUMO
INTRODUCTION: Interferon-alpha (IFN alpha) used to treat chronic hepatitis C can be responsible for some side effects. We report two cases of sarcoidosis which appeared in patients treated with IFN alpha and ribavirin for chronic hepatitis C. EXEGESIS: A first patient, treated for 5 months with IFN alpha and ribavirin because of chronic hepatitis C, after the failure of a first treatment with IFN alpha alone, was hospitalized for dyspnea. The chest X-ray and scanner revealed an interstitial syndrome and mediastinal adenopathies. Biopsies of bronchial spurs revealed epithelioid and giganto-cellular granuloma. After discontinuation of antiviral treatment and starting corticosteroid therapy, the evolution was favourable but viremia reappeared. A second patient with IFN alpha and ribavirin for 4 months because of chronic hepatitis C (after the failure of a first treatment with IFN alpha alone) was hospitalized for fever, arthralgias, erythema nodosa and modification of previous skin scars. The biopsy of a scar showed an epithelioid and giganto-cellular granuloma. After discontinuation of antiviral therapy and starting corticosteroid treatment, the evolution was favourable. CONCLUSION: Some publications mention occurrence of sarcoidosis during IFN alpha therapy, occasionally associated with ribavirin, disappearing after discontinuation of the treatment, though sometimes corticotherapy is necessary. The roles of IFN alpha and ribavirin are discussed.
Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Pneumopatias/induzido quimicamente , Ribavirina/efeitos adversos , Sarcoidose/induzido quimicamente , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Sarcoidose/diagnóstico , Fatores de TempoRESUMO
The respective roles of general practitioners and of consultants, for the care of patients treated for polycythemia vera, deserve to be defined in order to improve the detection of late therapeutic complications. The involvement of the general practitioner in the care of patients can only reinforce his knowledge of a rare disease and his interest in its detection. Three factors can influence the methods of supervision and the respective roles of specialists and general practitioners: the easy access to the reference centre, the evolution of policy of medical Insurance Authorities refunding travelling expenses, the quality of contacts between the specialist and the practitioner in charge.
Assuntos
Medicina de Família e Comunidade , Medicina Interna , Papel do Médico , Policitemia Vera/terapia , França , HumanosRESUMO
Diabetes insipidus is the most common endocrine disturbance associated with chronic multifocal form of histiocytosis X. Involvement of the hypothalamus can lead to growth hormone deficiency and short stature in children. Two cases with hypogonadism, growth hormone deficiency and diabetes insipidus are reported. In a 22-year-old man plasma testosterone was low and increased after administration of human chorionic gonadotrophin. Cutaneous and lytic bone lesions disappeared after treatment with Vinblastin. Partial diabetes insipidus was treated with clofibrate. A 59-year-old woman was found to have low pituitary gonadotrophins that failed to rise after administration of gonadotropin-releasing hormone and hyperprolactinemia. Fatal outcome was associated with polyuria, bone, cutaneous, gut and hypothalamic infiltration by histiocytes. There was no direct involvement of the anterior pituitary gland.
Assuntos
Histiocitose de Células de Langerhans/complicações , Doenças da Hipófise/etiologia , Dermatopatias/complicações , Adulto , Diabetes Insípido/etiologia , Feminino , Gonadotropinas Hipofisárias/sangue , Histiocitose de Células de Langerhans/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Adeno-Hipófise/fisiopatologia , Prolactina/sangueRESUMO
To determine whether abnormalities of the perisinusoidal space of Disse are present in the liver of diabetic patients with microangiopathy, an ultrastructural stereologic study of the space of Disse was performed in six insulin-treated diabetics with severe performed in six insulin-treated diabetics with severe proliferative retinopathy and six insulin-treated diabetics with normal fluorescein angiography, six patients with familial unconjugated hyperbilirubinemia were studied as controls. No patient had clinical and/or biochemical hepatic abnormalities and none suffered from any of the pathologic conditions known to be associated with collagenization of the perisinusoidal space. In control patients, the space of Disse of liver sinusoids contained occasional small deposits of collagen fibers. The relative volume of these fibers per unit of sinusoid represented 2.63 +/- 0.82%. In all diabetic patients with retinopathy, marked deposition of collagen fibers within the perisinusoidal space was constantly observed, a finding confirmed by ultrastructural stereologic analysis which showed that the relative volume of collagen fibers per unit of sinusoid represented 7.33 +/- 1.44% and differed significantly from control patient values (P less than 0.001). On the contrary, the relative volume of collagen fibers within the space of Disse in diabetic patients without retinopathy (3.95 +/- 2.96%) did not differ significantly from control patient values. These findings demonstrate that collagenization of the space of Disse is positively correlated with the presence of diabetic microangiopathy. Ultrastructural examination of the liver sinusoids might constitute a sensitive and useful approach for detecting the early changes of the microcirculation in diabetic patients.