RESUMO
Although relatively common in children, severe acute lactic acidosis is rare in adults with mitochondrial myopathies. We report here three cases, aged 27, 32 and 32 years, who developed life-threatening metabolic crisis with severe lactic acidosis, requiring hospitalisation in intensive care unit. Plasma lactates were elevated 10 to 15 fold normal values, necessitating extra-renal dialysis. By contrast CK levels were moderately increased (3 to 5N). No triggering factor was identified, but retrospectively all patients reported long-lasting mild muscle fatigability and weakness before their acute metabolic crisis. All of them recovered after prolonged intensive care but resting lactate levels remained elevated. Muscle biopsy showed ragged-red and COX-negative fibers in two patients and mild lipidosis in the third one. Heteroplasmic pathogenic point mutations were detected in MT-TL1 (m.3280G>A;m.3258C>T) and MT-TK (m.8363A>G). Life-threatening lactic acidosis may thus be a major inaugural clinical manifestation in adults with mitochondrial myopathies. Prolonged intensive care may lead to a dramatic and sustained improvement and is mandatory in such cases.
Assuntos
Acidose Láctica/etiologia , Acidose Láctica/terapia , Cuidados Críticos , Doenças Mitocondriais/complicações , Doenças Mitocondriais/terapia , Acidose Láctica/diagnóstico , Adulto , Estado Terminal/terapia , Emergências , Feminino , Humanos , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/patologia , Estudos RetrospectivosRESUMO
Lipoic acid (LA) is the cofactor of the E2 subunit of mitochondrial ketoacid dehydrogenases and plays a major role in oxidative decarboxylation. De novo LA biosynthesis is dependent on LIAS activity together with LIPT1 and LIPT2. LIAS is an ironsulfur (Fe-S) cluster-containing mitochondrial protein, like mitochondrial aconitase (mt-aco) and some subunits of respiratory chain (RC) complexes I, II and III. All of them harbor at least one [Fe-S] cluster and their activity is dependent on the mitochondrial [Fe-S] cluster (ISC) assembly machinery. Disorders in the ISC machinery affect numerous Fe-S proteins and lead to a heterogeneous group of diseases with a wide variety of clinical symptoms and combined enzymatic defects. Here, we present the biochemical profiles of several key mitochondrial [Fe-S]-containing proteins in fibroblasts from 13 patients carrying mutations in genes encoding proteins involved in either the lipoic acid (LIPT1 and LIPT2) or mitochondrial ISC biogenesis (FDX1L, ISCA2, IBA57, NFU1, BOLA3) pathway. Ten of them are new patients described for the first time. We confirm that the fibroblast is a good cellular model to study these deficiencies, except for patients presenting mutations in FDX1L and a muscular clinical phenotype. We find that oxidative phosphorylation can be affected by LA defects in LIPT1 and LIPT2 patients due to excessive oxidative stress or to another mechanism connecting LA and respiratory chain activity. We confirm that NFU1, BOLA3, ISCA2 and IBA57 operate in the maturation of [4Fe-4S] clusters and not in [2Fe-2S] protein maturation. Our work suggests a functional difference between IBA57 and other proteins involved in maturation of [Fe-S] proteins. IBA57 seems to require BOLA3, NFU1 and ISCA2 for its stability and NFU1 requires BOLA3. Finally, our study establishes different biochemical profiles for patients according to their mutated protein.
Assuntos
Fibroblastos/metabolismo , Proteínas Ferro-Enxofre/genética , Proteínas Mitocondriais/genética , Mutação , Ácido Tióctico/biossíntese , Aciltransferases/genética , Adolescente , Vias Biossintéticas/genética , Proteínas de Transporte/genética , Criança , Pré-Escolar , Feminino , Fibroblastos/química , Humanos , Lactente , Masculino , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Estresse Oxidativo , Fenótipo , Proteínas/genética , Ácido Tióctico/genéticaRESUMO
We addressed uncertainties regarding hereditary leiomyomatosis and renal cell carcinoma (HLRCC) by exploring all French cases, representing the largest series to date. Fumarate hydratase (FH) germline testing was performed with Sanger sequencing and qPCR/MLPA. Enzyme activity was measured when necessary. We carried out whenever possible a pathology review of RCC and S-(2-succino)-cysteine (2SC)/fumarate hydratase immunohistochemistry. We estimated survival using non-parametric Kaplan-Meier. There were 182 cases from 114 families. Thirty-seven RCC were diagnosed in 34 carriers (19%) at a median age of 40. Among the 23 RCC with pathology review, 13 were papillary type 2. There were 4 papillary RCC of unspecified type, 3 unclassified, 2 tubulocystic, and 1 collecting duct (CD) RCC, all 2SC+ and most (8/10) FH-. Of the remaining 14, papillary type 2, papillary unspecified, CD, and clear cell histologies were reported. The vast majority of RCC (82%) were metastatic at diagnosis or rapidly became metastatic. Median survival for metastatic disease was 18 months (95%CI: 11-29). 133 cases (73%) had a history of cutaneous leiomyomas, 3 developed skin leiomyosarcoma. Uterine leiomyomas were frequent in women (77%), but no sarcomas were observed. Only 2 cases had pheochromocytomas/paraganglioma. CONCLUSION: Our findings have direct implications regarding the identification and management of HLRCC patients.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma de Células Renais/genética , Fumarato Hidratase/genética , Leiomiomatose/genética , Leiomiossarcoma/genética , Síndromes Neoplásicas Hereditárias/genética , Feocromocitoma/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Criança , Feminino , França , Expressão Gênica , Predisposição Genética para Doença , Heterozigoto , Humanos , Leiomiomatose/diagnóstico , Leiomiomatose/mortalidade , Leiomiomatose/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Metástase Linfática , Pessoa de Meia-Idade , Mutação , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/mortalidade , Síndromes Neoplásicas Hereditárias/patologia , Feocromocitoma/diagnóstico , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: To compare the perception of benign prostatic hypertrophy (BPH) between patients and general practitioners (GPs) in terms of severity and evolution of symptoms and medication adherence. METHODOLOGY: A cross-sectional observational study was performed in France in a sample of GPs who included patients for whom a BPH treatment was prescribed. Data were collected on patient and GP characteristics, diagnosis, BPH management, severity and evolution of symptoms and medication adherence. RESULTS: One thousand and ninety-eight patients were recruited by 247 GPs. In 87.4% of cases, diagnosis was performed by GPs. Among them, 82.7% of patients were treated by monotherapy. The choice of a treatment was mainly based on treatment efficacy and the patient's opinion was taken into account by 5% of GPs. The patient's evaluation of symptoms severity was consistent with the GP's in 53.9% of cases. A worsening of symptoms was reported significantly more frequently by patients (18.5%) than by GPs (8.8%). Among 94 patients who reported poor adherence, GPs estimated that the level of medication adherence was good for 72 of these (77%). CONCLUSION: There was discordance between the evaluation made by GPs and by patients on the perception of BPH symptoms and medication adherence. The patient's opinion was rarely taken into account in the therapeutic decision, reflecting a lack of shared medical decision-making, which would be helpful for the physician in order to optimize BPH management.
Assuntos
Atitude Frente a Saúde , Clínicos Gerais/psicologia , Adesão à Medicação/psicologia , Pacientes/psicologia , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/psicologia , Antagonistas Adrenérgicos alfa/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , França , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Hiperplasia Prostática/tratamento farmacológico , Qualidade de Vida , Fatores de Risco , Estudos de Amostragem , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Ex vivo lung perfusion (EVLP) provides the ability to evaluate donor lungs before transplantation. Yet, limited prospective clinical data exist with regard to its potential to recondition unacceptable donor lungs. This paper summarizes the results of a prospective study of lung transplantation using only initially unacceptable donor lungs, which were improved by EVLP for 2-4 h. From March 2010-June 2011, 13 lungs were evaluated ex vivo. Median donor PaO(2) at FiO(2) 1.0/PEEP5 was 216 mmHg (range 133-271). Four lungs, all with trauma history, showed no improvement and were discarded. Nine lungs improved to a ΔPO(2) higher than 350 mmHg. Median PvO(2) at final assessment in these lungs was 466 mmHg (range 434-525). These lungs were transplanted with a median total ischemic time of 577 min (range 486-678). None of the patients developed primary graft dysfunction grades 2 or 3 within 72 h after transplantation. One patient with secondary pulmonary hypertension was left on a planned prolonged extracorporeal membrane oxygenation postoperatively. Median intubation time was 2 days. Thirty-day mortality was 0%. During the observation period, 119 patients received standard lung transplantation with comparable perioperative outcome. EVLP has a significant potential to improve the quality of otherwise unacceptable donor lungs.
Assuntos
Transplante de Pulmão , Perfusão , Adolescente , Adulto , Idoso , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis. Age at presentation may vary, but is generally within the first year of life. The most prevalent symptoms include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs, dystonia, psychomotor retardation or regression, failure to thrive, and feeding problems. Characteristic symptoms include brainstem involvement, optic atrophy and Leigh syndrome on MRI, either or not in combination with internal organ involvement and lactic acidemia. Virtually all children ultimately develop Leigh syndrome or leukoencephalopathy. Twenty-five percent of the patients died before the age of six months, more than half before the age of two and 75 % before the age of ten years. Some patients showed recovery of certain skills or are still alive in their thirties . No clinical, biochemical, or genetic parameters indicating longer survival were found. No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions.
Assuntos
Núcleo Celular/genética , Doenças Mitocondriais/genética , Mutação , Complexo I de Transporte de Elétrons/deficiência , Complexo I de Transporte de Elétrons/genética , Estudos de Associação Genética , Humanos , Mitocôndrias/genéticaRESUMO
OBJECTIVE: To identify a consistent pattern of brain MRI imaging in primary complex I deficiency. Complex I deficiency, a major cause of respiratory chain dysfunction, accounts for various clinical presentations, including Leigh syndrome. Human complex I comprises seven core subunits encoded by mitochondrial DNA (mtDNA) and 38 core subunits encoded by nuclear DNA (nDNA). Moreover, its assembly requires six known and many unknown assembly factors. To date, no correlation between genotypes and brain MRI phenotypes has been found in complex I deficiencies. DESIGN AND SUBJECTS: The brain MRIs of 30 patients carrying known mutation(s) in genes involved in complex I were retrospectively collected and compared with the brain MRIs of 11 patients carrying known mutations in genes involved in the pyruvate dehydrogenase (PDH) complex as well as 10 patients with MT-TL1 mutations. RESULTS: All complex I deficient patients showed bilateral brainstem lesions (30/30) and 77% (23/30) showed anomalies of the putamen. Supratentorial stroke-like lesions were only observed in complex I deficient patients carrying mtDNA mutations (8/19) and necrotising leucoencephalopathy in patients with nDNA mutations (4/5). Conversely, the isolated stroke-like images observed in patients with MT-TL1 mutations, or the corpus callosum malformations observed in PDH deficient patients, were never observed in complex I deficient patients. CONCLUSION: A common pattern of brain MRI imaging was identified with abnormal signal intensities in brainstem and subtentorial nuclei with lactate peak as a clue of complex I deficiency. Combining clinico-biochemical data with brain imaging may therefore help orient genetic studies in complex I deficiency.
Assuntos
Encéfalo/enzimologia , Encéfalo/patologia , Complexo I de Transporte de Elétrons/deficiência , Imageamento por Ressonância Magnética/métodos , Doenças Mitocondriais/enzimologia , Doenças Mitocondriais/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Complexo I de Transporte de Elétrons/genética , Feminino , Humanos , Lactente , Leucoencefalopatias/complicações , Leucoencefalopatias/patologia , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico por imagem , Doenças Mitocondriais/genética , Mutação/genética , Complexo Piruvato Desidrogenase/genética , Radiografia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Adulto JovemAssuntos
Neoplasias Faciais/genética , Fumarato Hidratase/genética , Mutação em Linhagem Germinativa/genética , Leiomiossarcoma/genética , Neoplasias Cutâneas/genética , Idoso , Bochecha , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Ultrassonografia , Neoplasias Uterinas/diagnóstico por imagemRESUMO
INTRODUCTION: Ghost cell odontogenic carcinoma is a rare malignant tumor that occurs both in the mandible and maxilla. It has a variable non-specific clinical and radiological appearance. The authors report a mandibular case. CASE REPORT: A 89-year-old man consulted for swelling of the left lower mandible and gums having developed over the previous 8 months. The lesion was 6cm long, ulcerative and budding, bleeding on contact. Radiological assessment revealed blurred contour osteolysis with extension to the mouth floor and sub-mandibular compartment. Histological examination of the surgical piece supported the diagnosis of ghost cell odontogenic carcinoma. The tumor recurred 2 months later and the patient died 6 months after surgery. DISCUSSION: Ghost cell odontogenic carcinoma is a rare lesion. The patient was very old. Clinical and radiographic signs were unspecific. Histopathology proved the diagnosis. Evolution was unpredictable due to the wide spectrum of growth patterns. Extensive radical surgery is mandatory due to the high risk of recurrence.
Assuntos
Neoplasias Mandibulares/diagnóstico , Tumores Odontogênicos/diagnóstico , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Evolução Fatal , Seguimentos , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Úlceras Orais/diagnóstico , Osteólise/diagnósticoRESUMO
GOAL OF THE STUDY: Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolic events (TEE) during outbreaks, increasing morbidity and mortality. The aim of our study was to specify the prevalence of TEE in IBD patients and to determine their epidemiological, clinical and evolutionary characteristics. MATERIEL AND METHODS: This is a retrospective study collecting all patients with IBD, who had a thromboembolic complication confirmed by imagery, between January 2012 and December 2018. RESULTS: One hundred patients with IBD were diagnosed during the study period. A TEE occurred in 6 patients (5.9%). These patients had an average age of 41 years, divided into 4 women and 2 men. Five patients had Crohn's disease and one patient had ulcerative colitis. The IBD was active in all patients. Five patients were already hospitalized and under preventive heparin therapy. Patients had deep venous thrombosis of the lower limbs in 3 cases, associated with pulmonary embolism in 1 case, cerebral venous thrombosis in 2 cases and pulmonary embolism isolated in 1 case. Thrombophilia investigations were negative in all patients. Evolution under medical treatment was favorable in 4 patients and fatal in 2 patients. CONCLUSION: In our study, the prevalence of TEE in patients with IBD was 5.9%. Thrombosis occurred during the active phase of IBD in all cases.
Assuntos
Doença de Crohn/epidemiologia , Trombose Intracraniana/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/mortalidade , Colite Ulcerativa/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/mortalidade , Doença de Crohn/terapia , Feminino , Heparina/uso terapêutico , Humanos , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/tratamento farmacológico , Trombose Intracraniana/mortalidade , Masculino , Prevalência , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/diagnóstico por imagem , Tromboembolia/tratamento farmacológico , Tromboembolia/mortalidade , Fatores de Tempo , Tunísia/epidemiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Trombose Venosa/mortalidadeRESUMO
Acute liver failure (ALF) in childhood is a life-threatening emergency. ALF is often caused by drug toxicity, autoimmune hepatitis, inherited metabolic diseases, and infections. However, despite thorough investigations, a cause cannot be determined in approximately 50% of cases. Here, we report three cases with recurrent ALF caused by NBAS and SCYL1 pathogenic variants. These patients did not present with any other phenotypic sign usually associated with NBAS and SCYL1 pathogenic variants. Two of them underwent liver transplantation and are healthy without recurrence of ALF. We propose NBAS and SCYL1 genetic analysis in children with unexplained fever-triggered recurrent ALF even without a typical phenotype.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas de Ligação a DNA/genética , Falência Hepática Aguda/genética , Mutação , Proteínas de Neoplasias/genética , Criança , Pré-Escolar , Feminino , Marcadores Genéticos , Testes Genéticos , Humanos , Lactente , Falência Hepática Aguda/diagnóstico , Masculino , RecidivaRESUMO
Deoxyguanosine kinase (dGK) deficiency is a frequent cause of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this study, we describe a new splice site mutation in the DGUOK gene and the clinical, radiologic, and genetic features of these DGUOK patients. This new DGUOK homozygous mutation (c.444-62C>A) was identified in three patients from two North-African consanguineous families with combined respiratory chain deficiencies and mitochondrial DNA depletion in the liver. Brain MRIs are normal in DGUOK patients in the literature. Interestingly, we found subtentorial abnormal myelination and moderate hyperintensity in the bilateral pallidi in our patients. This new mutation creates a cryptic splice site in intron 3 (in position -62) and is predicted to result in a larger protein with an in-frame insertion of 20 amino acids. In silico analysis of the putative impact of the insertion shows serious clashes in protein conformation: this insertion disrupts the alpha5 helix of the dGK kinase domain, rendering the protein unable to bind purine deoxyribonucleosides. In addition, a common haplotype that segregated with the disease in both families was detected by haplotype reconstruction with 10 markers (microsatellites and SNPs), which span 4.6 Mb of DNA covering the DGUOK locus. In conclusion, we report a new DGUOK splice site mutation that provide insight into a critical protein domain (dGK kinase domain) and the first founder mutation in a North-African population.
Assuntos
DNA Mitocondrial/genética , Efeito Fundador , Predisposição Genética para Doença , Encefalopatia Hepática/enzimologia , Encefalopatia Hepática/genética , Mutação/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Análise Mutacional de DNA , Evolução Fatal , Regulação Enzimológica da Expressão Gênica , Genótipo , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Linhagem , Fosfotransferases (Aceptor do Grupo Álcool)/química , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Estrutura Secundária de Proteína , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SíndromeRESUMO
This study determined the prevalence of inherited factor V Leiden mutation in a group of 128 thrombosis patients (102 with venous thrombosis and 26 with arterial thrombosis) attending a hospital in Sousse, Tunisia, and a control group of 100 with no history of thrombosis. Using an allele-specific PCR amplification technique, factor V Leiden was found in significantly more patients (20.3%) than controls (6.0%). The higher prevalence was significant in the subgroup of venous thrombosis patients but not in arterial thrombosis patients. The allele frequency was 3.5% in the normal Tunisian population. Screening Tunisian patients with venous thrombosis and their relatives for factor V Leiden may be justified.
Assuntos
Fator V/genética , Predisposição Genética para Doença , Trombose , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Frequência do Gene/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Lactente , Pacientes Internados/estatística & dados numéricos , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Trombose/epidemiologia , Trombose/genética , Tunísia/epidemiologiaRESUMO
AIMS: To report on a family with five members who carry the A3243G mutation in mitochondrial tRNA for leucine 1 (MTTL1) and present with diabetes, chronic intestinal pseudo-obstruction (CIPO) and recurrent pancreatitis, and to screen for this mutation in a cohort of 36 unrelated patients with recurrent pancreatitis. METHODS: The mutation was quantified in several tissue samples from patients. Respiratory chain activity was studied in muscle biopsies and fibroblast cultures. In addition, the thymidine phosphorylase gene (TP) involved in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and three genes involved in chronic pancreatitis - PRSS1, SPINK1 and CFTR - were sequenced in affected patients. Finally, the MTTL1 gene was examined in 36 unrelated patients who had recurrent pancreatitis, but no mutations in the PRSS1 and SPINK1 genes. RESULTS: Heteroplasmy for the mtDNA A3243G mutation was found in all tissue samples from these patients, but no mutations were found in the genes coding for thymidine phosphorylase, PRSS1, SPINK1 and CFTR. Also, none of the 36 unrelated patients with recurrent pancreatitis were carrying any MTTL1 mutations. CONCLUSION: The mtDNA A3243G mutation associated with the gastrointestinal manifestations observed in the affected family should be regarded as a possible cause of CIPO and unexplained recurrent pancreatitis. However, the mutation is probably only weakly involved in cases of isolated recurrent pancreatitis.
Assuntos
DNA Mitocondrial/genética , Complicações do Diabetes/genética , Diabetes Mellitus/genética , Pseudo-Obstrução Intestinal/genética , Pancreatite/genética , Polimorfismo de Nucleotídeo Único , Surdez/genética , Complicações do Diabetes/patologia , Diabetes Mellitus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Mutação , Linhagem , RecidivaRESUMO
This paper describes MRI aspects of a leukodystrophy due to the Mitochondrial Neurogastrointestinal Encephalomyopathy syndrome in an adolescent girl investigated for nocturnal recurrent emesis leading to major cachexia.
Assuntos
Gastroenteropatias/diagnóstico , Imageamento por Ressonância Magnética , Encefalomiopatias Mitocondriais/diagnóstico , Adolescente , Caquexia/etiologia , Diagnóstico Diferencial , Feminino , Gastroenteropatias/complicações , Humanos , Encefalomiopatias Mitocondriais/complicações , Vômito/etiologiaRESUMO
OBJECTIVE: To define the clinical, laboratory and morphological features of emphysematous pyelonephritis, as well as the treatment modalities, with particular emphasis on the need for urgent treatment. MATERIAL AND METHODS: Between 1987 and 2004, 21 patients were treated for emphysematous pyelonephritis. Epidemiological, clinical, laboratory and radiological data, treatments and clinical outcome were retrospectively collected for all patients. RESULTS: This series comprised 15 women and six men with a mean age of 54.6 years. All were diabetic. Upper urinary tract obstruction was demonstrated in 47.6% of cases. The left kidney was affected in 14 patients and the right kidney was affected in six patients. Only one patient had bilateral pyelonephritis. The diagnosis was established by CT in every case. All patients received appropriate intensive care. Treatment was purely medical in one case. Emergency nephrectomy was performed in 12 patients, emergency surgical drainage was performed in three patients, percutaneous drainage was performed in two cases and ureteric catheter drainage was performed in three patients. The mortality rate in this series was 23.8%. CONCLUSION: Emphysematous pyelonephritis is a serious infection. Early diagnosis is essential, particularly in diabetic patients. The positive diagnosis is based on computed tomography and treatment is now increasingly conservative.
Assuntos
Enfisema/complicações , Pielonefrite/complicações , Adulto , Idoso , Complicações do Diabetes/epidemiologia , Enfisema/diagnóstico por imagem , Enfisema/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pielonefrite/diagnóstico por imagem , Pielonefrite/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To evaluate the results of one-stage bilateral rigid ureteroscopy for the treatment of bilateral ureteric stones and to identify predictive factors of failure. MATERIALS AND METHODS: From January 1995 to June 2006, 61 patients were hospitalised for bilateral ureteric stones. Fifty patients, that is, 100 renal units were treated by first-line one-stage bilateral rigid ureteroscopy using an 8 F rigid ureteroscope and a ballistic lithotriptor. A complete statistical analysis (bivariate analysis completed by multivariate analysis) was performed to identify predictive factors of intraoperative failure. RESULTS: The overall success rate per patient (success on at least one side) was 92% (with bilateral success in 70% of cases). Statistical analysis revealed a statistically significant difference between the two failure/success groups for mean stone diameter (p < 0.1%), site (p = 0.6%) and degree of cavity dilatation (p = 4%). Similarly, a strong statistical correlation was observed between these variables and intraoperative failure. The intraoperative complication rate was 4% (two patients) and the postoperative complication rate was 16%, corresponding to minor complications in every case (low back pain, fever) not requiring a supplementary procedure. CONCLUSION: One-stage bilateral rigid ureteroscopy achieved satisfactory results similar to those of unilateral ureteroscopy. Predictive factors of failure were: stone diameter (greater than 15 mm), stones in the lumbar ureter and marked cavity dilatation.
Assuntos
Cálculos Ureterais/terapia , Ureteroscópios , Ureteroscopia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Adulto JovemRESUMO
Steroids are neuroprotective and a growing body of evidence indicates that mitochondria are a potential target of their effects. The mitochondria are the site of cellular energy synthesis, regulate oxidative stress and play a key role in cell death after brain injury and neurodegenerative diseases. After providing a summary of the literature on the general functions of mitochondria and the effects of sex steroid administrations on mitochondrial metabolism, we summarise and discuss our recent findings concerning sex differences in brain mitochondrial function under physiological and pathological conditions. To analyse the influence of endogenous sex steroids, the oxidative phosphorylation system, mitochondrial oxidative stress and brain steroid levels were compared between male and female mice, either intact or gonadectomised. The results obtained show that females have higher a mitochondrial respiration and lower oxidative stress compared to males and also that these differences were suppressed by ovariectomy but not orchidectomy. We have also shown that the decrease in brain mitochondrial respiration induced by ischaemia/reperfusion is different according to sex. In both sexes, treatment with progesterone reduced the ischaemia/reperfusion-induced mitochondrial alterations. Our findings indicate sex differences in brain mitochondrial function under physiological conditions, as well as after stroke, and identify mitochondria as a target of the neuroprotective properties of progesterone. Thus, it is necessary to investigate sex specificity in brain physiopathological mechanisms, especially when mitochondria impairment is involved.
Assuntos
Encéfalo/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Caracteres Sexuais , Acidente Vascular Cerebral/metabolismo , Animais , Feminino , Masculino , Camundongos , Fosforilação Oxidativa , Consumo de Oxigênio/fisiologiaRESUMO
Deficiency of the enzymes of mitochondrial fatty acid oxidation and related carnitine dependent steps have been shown to be one of the causes of the fasting-induced hypoketotic hypoglycemia. We describe here carnitine-acylcarnitine translocase deficiency in a neonate who died eight days after birth. The proband showed severe fasting-induced hypoketotic hypoglycemia, high plasma creatine kinase, heartbeat disorder, hypothermia, and hyperammonemia. The plasma-free carnitine on day three was only 3 microM, and 92% of the total carnitine (37 microM) was present as acylcarnitine. Treatments with intravenous glucose, carnitine, and medium-chain triglycerides had been tried without improvements. Measurements in fibroblasts confirmed deficient oxidation of palmitate and showed normal activities of the carnitine palmitoyltransferases I and II and of the three acyl-CoA dehydrogenases. A total deficiency of the carnitine-acyl-carnitine translocase was found in fibroblasts using the carnitine acetylation assay (1986. Biochem. J. 236:143-148). This assay has been further simplified by seeking conditions permitting application to permeabilized fibroblasts and lymphocytes.
Assuntos
Carnitina Aciltransferases/deficiência , Bloqueio Cardíaco/enzimologia , Hipoglicemia/enzimologia , Carnitina/sangue , Carnitina O-Palmitoiltransferase/metabolismo , Permeabilidade da Membrana Celular , Células Cultivadas , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/metabolismo , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Bloqueio Cardíaco/genética , Humanos , Hipoglicemia/genética , Recém-Nascido , Isoenzimas/metabolismo , Masculino , Valores de Referência , Pele/enzimologia , Pele/metabolismoRESUMO
To determine if blunt or sharp expansion of the uterus at caesarean delivery is associated with increased maternal peripartum haemorrhage as estimated by the drop in hematocrit. Prospective randomised intention to treat clinical trial of women undergoing elective or urgent caesarean delivery at at least 36 weeks gestation. Two study groups were formed; after an initial hysterotomy which consisted in a transverse uterine incision of the lower segment, in the blunt group, the surgeon's indexes expanded the initial incision bilaterally and cephalad; in the sharp group, expansion of the initial incision was made using scissors. The primary outcome measure was the mean drop in hematocrit and p < 0.05 was considered significant. Three hundred women were randomised: 153 to the sharp group and 147 to the blunt group. The demographic and clinical characteristics of the two populations were similar. There were no statistically significant differences between the groups in estimated blood loss as assessed by the mean drop in hematocrit (%) (respectively 1.71 +/- 3.18 versus blunt group 1.91 +/- 3.28 p = 0.58 non significant). Our findings support that sharp or blunt expansion of hysterotomy during caesarean section equally affect blood loss as estimated by drop in hematocrit.