RESUMO
RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in DKC1, NOP10, or NHP2 cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin-NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin-NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish dkc1 mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.
Assuntos
Catarata/genética , Proteínas de Ciclo Celular/genética , Enterocolite/genética , Perda Auditiva Neurossensorial/genética , Síndrome Nefrótica/genética , Proteínas Nucleares/genética , Ribonucleoproteínas Nucleolares Pequenas/genética , Animais , Criança , Feminino , Predisposição Genética para Doença , Humanos , Longevidade , Masculino , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutação , Linhagem , Conformação Proteica , RNA Ribossômico/genética , Peixe-ZebraRESUMO
Hypnosis is well known for its modulatory effects on immune and inflammatory processes, and it is a therapeutic option for certain diseases of such pathogenesis. The authors report treatment of an adult patient with extensive atopic dermatitis, who was only minimally responsive to conservative treatment. In a 15 session hypnotherapy the authors combined the use of direct, symptom-oriented suggestive techniques with hypnotic procedures to identify and modify comorbid psychological issues. To monitor the effect of the treatment, patient diaries (quality and quantity of sleep, intensity of pain and itch) and repeated psychometric tests were used. At the end of treatment there were improvements in all measured dimensions (itch, pain, insomnia, activity, anxiety and emotional state) both clinically and psychometrically. The authors conclude, that hypnosis can be an effective adjunctive therapy in atopic dermatitis, and in certain severe cases may constitute a salvage therapy.
Assuntos
Dermatite Atópica/psicologia , Dermatite Atópica/terapia , Hipnose , Corticosteroides/administração & dosagem , Adulto , Anti-Inflamatórios/administração & dosagem , Ansiedade/etiologia , Ansiedade/prevenção & controle , Doença Crônica , Terapia Combinada/métodos , Dermatite Atópica/imunologia , Humanos , Masculino , Dor/etiologia , Dor/prevenção & controle , Prurido/etiologia , Prurido/prevenção & controle , Psicometria , Terapia de Salvação , Autorrelato , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/prevenção & controleRESUMO
UNLABELLED: For the first time in Hungary, a patient with abdominal compartment syndrome after contained aortic aneurysm rupture was treated successfully implementing open abdomen treatment with vacuum-assisted wound closure (V.A.C.) and delayed abdominal wall closure with mesh. CASE REPORT: Contained aortic aneurysm rupture was diagnosed by CT angiography in a 59-year-old patient. After the acute reconstruction of the ruptured aorta (by an open procedure with aorto-aortic Dacron interposition) during the closure of the abdominal cavity the patient could not be effectively ventilated due to high intra-abdominal pressure caused by the severe oedema of the abdominal wall and the hematoma in the retroperitoneal space. In this situation, we decided upon open abdominal treatment using V.A.C. After regular changes of V.A.C. the abdomen was closed with DualMesh and three weeks later the patient was discharged home in good condition. CONCLUSION: In our case, abdominal closure was not implemented after the reconstruction of the ruptured aortic aneurysm due to the extensive oedema. The complications of abdominal compartment syndrome were prevented with the open treatment. Based on our experience and on the results of the international literature we highly recommend open abdominal treatment with V.A.C. in case of abdominal compartment syndrome.
Assuntos
Ruptura Aórtica/complicações , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Hipertensão Intra-Abdominal/etiologia , Telas Cirúrgicas , Feminino , Humanos , Pessoa de Meia-Idade , Tratamento de Ferimentos com Pressão Negativa , Polietilenotereftalatos , Resultado do TratamentoRESUMO
Pudendal neuralgia is a rare and in the absence of somatic, radiological and laboratory abnormalities often unrec-ognizable problem, posing a serious challenge to therapeutic management. Our case study presents the complete diagnostic and therapeutic algorithm of a female patient with chronic pudendal pain. In addition, our paper draws attention to the role of pelvic pain workgroups such as the Pelvic Pain Task Force of the Semmelweis University where cases of chronic pelvic pain with no clear medical reason can be assessed and treated with higher efficiency.