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[This corrects the article DOI: 10.7759/cureus.43718.].
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Introduction Wilson's disease (WD) is a rare and underdiagnosed genetic disorder caused by anomalous tissue copper deposition, and for which epidemiological studies, specifically in Portugal, are scarce. Objectives This study aimed to evaluate the prevalence and incidence of WD and provide a description of its main clinical and laboratory features. Methods A retrospective study was carried out, with a search between 1995 and 2015, of all patients with a minimum follow-up of three months and birth confirmed in the northern region of Portugal, with an estimated population of 3,689,682 inhabitants. Database collection was based on the Portuguese National Health Service's clinical coding system, relying on clinical data from 13 northern Portuguese hospitals, liver biopsy histology results, and hospital prescription records. Clinical and biochemical correlations were statistically assessed using chi-square, Mann-Whitney U, Friedman, and Wilcoxon tests. Results Over the 20-year period, a prevalence of 1:37.000 and an incidence of one per million person-year was found. A total of 94 patients were analyzed, with a slight male predominance (53%), the majority with the onset of clinical manifestations in pediatric age (56%), with a median age at diagnosis of 16.6 years (interquartile range of 12.3-20,.8 years). Most patients presented with predominant liver disease (54.8%), with more than a third with cirrhosis; mixed hepatic and neurological manifestations in 17.9%; and mainly neurological symptoms in 10.7% of the patients. Neurological impairment was strongly associated with delayed development of the manifestations of the disease (p = 0.001) and also a higher detection of Kayser-Fleischer rings (p < 0.001), present in 27.0% of the patients. Regarding therapy, penicillamine has been the most widely used, with adverse reactions reported in 24.8%. At six and 12 months after initiation of therapy, a significant decrease in liver enzymes was found (ALT: p = 0.002; AST: p = 0.002, respectively), but no significant reduction was observed in urinary copper excretion. Conclusion This was one of the first studies regarding WD prevalence in a Portuguese population, contributing to a better understanding of the epidemiology, diagnosis, and management of WD in the northern region of Portugal. WD should be considered in any individual with unexplained hepatic or neurological manifestations, and initial symptoms may manifest at an early age, even in children less than five years old. A high percentage of patients were identified in the early stages of the disease by asymptomatic elevation of transaminases. Following copper chelation therapy, cytolysis markers appear to be more sensitive indicators of treatment response.
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The incidence of hepatobiliary malignancies, and especially intrahepatic cholangiocarcinoma (ICC), for patients with Wilsons disease (WD), is very low, even for cirrhotic patients. It has been suggested that hepatobiliary carcinomas are less frequent in Wilsons disease (WD) than in liver diseases of other etiology. However, the protective role of copper against malignancies is debated. Only a few cases of cholangiocarcinoma (CCC) in WD have been published. Here we report a case of a 39-year-old female, WD diagnosed at 19-year-old based on low ceruloplasmin level, low serum copper, and increased urinary copper. She was followed up and treated with chelating agents throughout nineteen years, after this asymptomatic period she reported abdominal pain. MRI showed hepatic lesions not suggestive of hemangiomas and a nodular lesion of 15mm in the right lobe. Liver biopsy was made, with non-specific fibrosis; negative for malignancy. Few months later she was admitted in the hospital because of rapidly development of epigastric/right hypochondrium abdominal pain with four days of evolution, anorexia and asthenia. Biopsy revealed cholangiocarcinoma as the primary tumor confirmed by strong CK7 and CK20 positivity. The curiosity of the presented case is the very rapid development of CCC despite continuous chelating agent therapy. (AU)
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Humans , Hepatolenticular Degeneration , CopperABSTRACT
BACKGROUND: Neurocutaneous melanocytosis (NCM) is a rare congenital disorder that presents with pigmented cell lesions of the brain or leptomeninges in children with large or multiple congenital melanocytic nevi. Although the exact pathological processes involved are currently unclear, NCM appears to arise from an abnormal development of melanoblasts or melanocyte precursors. Currently, it has an extremely poor prognosis due to rapid disease progression and lack of effective treatment modalities. METHODS: In this study, we report on an experimental approach to examining NCM cells by establishing subcutaneous tumors in nude mice, which can be further expanded for conducting molecular and drug sensitivity experiments. RESULTS: Analysis of the NRAS gene-coding sequences of an established NCM cell line (YP-MEL) and NCM patient cells revealed heterogeneity in NRAS Q61K that activated mutation and possibly consequential differential sensitivity to MEK inhibition. Gene expression studies were performed to compare the molecular profiles of NCM cells with normal skin fibroblasts. In vitro cytotoxicity screens of libraries of targeted small-molecule inhibitors revealed prospective agents for further evaluation. CONCLUSIONS: Our studies provide an experimental platform for the generation of NCM cells for preclinical studies and the production of molecular and in vitro data with which to identify druggable targets for the treatment.
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Antineoplastic Agents/administration & dosage , Melanosis/drug therapy , Melanosis/genetics , Neurocutaneous Syndromes/drug therapy , Neurocutaneous Syndromes/genetics , Xenograft Model Antitumor Assays/methods , Animals , Antineoplastic Agents/therapeutic use , Child, Preschool , GTP Phosphohydrolases/genetics , Heterografts/drug effects , Heterografts/pathology , Humans , Male , Melanosis/pathology , Membrane Proteins/genetics , Mice , Mice, Nude , Mutation , Neurocutaneous Syndromes/pathology , Signal Transduction/drug effects , Small Molecule Libraries/administration & dosage , Small Molecule Libraries/therapeutic use , Transcriptome , Tumor Cells, CulturedSubject(s)
Founder Effect , Mutation , Ethnicity/genetics , Female , Genotype , Humans , Infant, Newborn , Male , North America , Protestantism , White People/geneticsABSTRACT
ABSTRACT A mesenchymal hamartoma of the liver (MHL) from a 20-month-old girl was studied cytogenetically. The karyotype was 46,XX,inv(19)(p13q13.4)[38], and fluorescence in situ hybridization using bacterial artificial chromosome probes refined the breakpoints to 19p13.11 and the subtelomeric region of 19q. This is the first report of inversion (19) in MHL, and the q-arm breakpoint is different from that reported previously in other rearrangements.
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Chromosome Inversion/genetics , Chromosomes, Human, Pair 19 , Hamartoma/pathology , Liver Diseases/pathology , Mesoderm/pathology , Abnormal Karyotype , Chromosome Breakpoints , DNA/analysis , Female , Hamartoma/genetics , Humans , In Situ Hybridization, Fluorescence , Infant , Liver Diseases/geneticsABSTRACT
Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT. In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development.
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O mercado de saúde tem características bem particulares. Apesar do avanço tecnológico ter impactado muito positivamente, também tem deixado os cuidados de saúde cada vez mais caros. Outro ponto que tem influenciado fortemente o crescimento dos gastos com saúde é o envelhecimento da população. Portanto, ser mais eficiente na gestão de custos é fator crítico de sucesso no segmento hospitalar e este livro apresenta ferramentas importantes, que auxiliam o gestor na formulação e implementação de estratégias que possibilitem a conversão do plano estratégico em medidas administrativas e operacionais que vão criar valor para a empresa.
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Humans , Health Expenditures , Health Management , Health Services , Accounting , Decision Making , Inflation, EconomicABSTRACT
Recurrent respiratory papillomatosis is a relatively uncommon disease that presents clinically with symptoms ranging from hoarseness to severe dyspnea. Human papilloma virus types 6 and 11 are important in the etiology of papillomas and are most probably transmitted from mother to child during birth. Although spontaneous remission is frequent, pulmonary spread and/or malignant transformation resulting in death has been reported. CO2 laser evaporation of papillomas and adjuvant drug therapy using lymphoblastoid interferon-alpha are the most common treatments. However, several other treatments have been tried, with varying success. In the present report, a case of laryngeal papillomatosis presenting with chronic stridor and delayed speech is described.
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Laryngeal Neoplasms/complications , Papilloma/complications , Respiratory Sounds/etiology , Speech Disorders/etiology , Bronchoscopy , Chronic Disease , Combined Modality Therapy , Humans , Infant , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/therapy , Laser Therapy , Male , Neoplasm Recurrence, Local , Papilloma/diagnosis , Papilloma/therapy , RetreatmentABSTRACT
Malignant rhabdoid tumor (MRT) is a rare tumor occurring mostly in kidneys and central nervous system (CNS). Its prognosis is not good. Occasionally, MRTs are diagnosed at or immediately after birth. A female neonate presented with MRT in the chest wall, axilla, right elbow, and bone marrow. Chest wall lesion was resected completely. Although the masses in axilla and bone marrow responded rapidly to chemotherapy, the elbow lesion increased in size. Despite intense treatment, the tumor relapsed in lungs and the patient died 12 months after diagnosis. Review of the literature showed twenty additional congenital MRTs arising from sites outside of the kidney and central nervous system were published in the literature. Eighteen patients had disseminated disease at diagnosis. The median overall survival time for all (n = 21) patients was 2.0 months (0-24 months). The only patient who survived had a localized tumor at initial diagnosis. Congenital, extrarenal, non-CNS MRTs are aggressive tumors with poor outcome.
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Brain Neoplasms/pathology , Rhabdoid Tumor/pathology , Axilla/pathology , Bone Marrow/pathology , Brain Neoplasms/therapy , Elbow/pathology , Fatal Outcome , Female , Hematopoietic Stem Cell Transplantation , Humans , Infant, Newborn , Male , Microscopy, Electron , Rhabdoid Tumor/congenital , Rhabdoid Tumor/therapy , Survival Rate , Thorax/pathologyABSTRACT
Male siblings developed acute hemorrhagic leukoencephalitis (AHL) at age five months and eight months, respectively. This rare condition has not been reported in individuals less than two years of age or with a recurrence in the family. The diagnosis was based on neuropathologic features after ruling out potentially mimicking conditions. Genetic counseling of early onset AHL should include the possibility of recurrence in siblings.
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Leukoencephalitis, Acute Hemorrhagic/genetics , Female , Humans , Infant , Italy , Leukoencephalitis, Acute Hemorrhagic/pathology , Male , Nuclear Family , RecurrenceABSTRACT
Em um estudo aberto näo compartivo, 40 pacientes portadoras de processo inflamatório pélvico leve ou moderado foram tratados com Kelfiprim cápsulas (TMP 250 mg e SMP 200 mg) na posologia de duas cápsulas no 1º dia e uma cápsula diária nos 13 dias subsequentes. A eficácia do tratamento foi considerada excelente ou boa em 37 (92,5 por cento) pacientes, regular em duas (5 por cento) e má em uma única paciente. A exceçäo de duas pacientes, a primeira apresentando efeitos colaterais a nível gastroentérico e a segunda com reaçäo cutânea, a tolerabilidade foi boa em todos os casos. As concentraçöes plasmáticas de TMP e SMP, foram determinadas em 10 pacientes, 12 horas após a administraçäo da cápsula de kelfiprim correspondente ao 7º e ao 14º dias de tratamento. Os níveis de TMP e SMP, foram bacteriologicamente ativos e com uma relaçäo TMP: SMP, que garante elevados graus de sinergismo
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Humans , Adult , Female , Pelvic Inflammatory Disease/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
Contiene: Novela social, nos muestra la vida de los mineros y las minas en distintos centros mineros como: Catavi, Llallagua, Siglo XX y la Chojlla