Acquired hepatocerebral degeneration: full recovery after liver transplantation.
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Biomedical subjects
Publications and source records attributed to M Guarino.
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BACKGROUND: Liver transplantation (LT) is the sole resolutive therapy for Wilson disease (WD) and is the treatment of choice for patients with WD who have fulminant hepatic failure or end-stage cirrhosis. Although its role in managing the neurological manifestations of WD is not yet conclusive, LT has recently been advocated as a therapy for neurologically affected patients with WD with stable liver function. OBJECTIVE: To evaluate the effect of LT on the neurological manifestations of WD. OBSERVATION: A 44-year-old man with WD with cirrhosis and neurological symptoms (motor dysfunction and cognitive impairment) experienced a dramatic improvement in motor function early after LT, as well as normalization of copper balance and the disappearance of Kayser-Fleischer rings. Abnormalities seen on magnetic resonance imaging scans were reversed 18 months after LT. Cognitive testing 2 years after LT showed a moderate global improvement. CONCLUSIONS: In this case, LT healed the neurological manifestations of WD. To date, this favorable result has been seen in almost 80% of cases. However, the decision to perform LT in patients with WD solely on the basis of neurological impairment must be considered experimental.
We performed the first population-based case-control study on clinical risk factors and drug exposure in Guillain-Barré syndrome (GBS). Sixty patients with GBS were collected through an incidence survey performed in the Emilia-Romagna region of northern Italy. GBS patients were compared with 109 hospital controls (HC) and 59 population controls (PC) as for clinical events and drug exposure during the month preceding the study inclusion. Comparison of HC with PC showed no significant difference in the frequency of clinical events which occurred during the preceding month. This indicated that our HC were well representative of the general population for the risk factors investigated. GBS patients were compared with HC or both HC and PC using both univariate and multivariate analysis. Univariate analysis showed a significant association with fever and upper airway infection symptoms occurring in the preceding month. Furthermore, a significantly higher exposure to antibiotics, antipyretics/analgesics, and gangliosides was observed. However, multivariate analysis showed that only fever was significantly related to GBS onset (OR 28, 95% CI 5.2-313 for GBS vs. HC; OR 29, 95% CI 7.0-256 for GBS vs. HC and PC).
Epithelium and mesenchyme, two tissue types virtually found in every organ, are endowed with fundamentally different functional properties. Active motility, a capability that is limited to the mesenchymal repertoire, is the principal characteristic that distinguishes them. During embryonic development, conversions from epithelium to mesenchyme and from mesenchyme to epithelium normally occur, allowing morphogenetic processes and tissue remodelling to take place. However, there is now increasing evidence that the modulation between the epithelial and the mesenchymal phenotypes is not limited to embryonic life. Indeed, the pathogenesis of some adult diseases seems to implicate an inappropriate activation of this change. On the other hand, failure of normally occurring embryonic epithelial-mesenchymal interconversions could result in the development of some pathologies. It is now possible to study some molecular events underlying these phenotype transitions, since several biological agents implicated in the epithelial-mesenchymal interconversion, such as growth factors, extracellular matrix components and their receptors, transcription factors and oncogenes have been identified. The malignant potential of some oncogenes seems to express itself through the disruption of the mechanisms involved in the maintenance of the epithelial phenotype while, on the other hand, some observations suggest the existence of regulatory genes able to counteract the action of oncogenes by restoring epithelial characteristics. Therefore, the manipulation of the tissue phenotype could represent a novel strategy for the prevention and treatment of diseases in the future.
We report an unusual case of sudden isolated transient amnesia triggered by acute marijuana use. The memory disorder, apart from the long duration, had the characteristics of a transient global amnesia-like episode. Acute marijuana intoxication can affect memory more globally and severely than previously reported.
We performed a case-control study to investigate the association between Campylobacter jejuni (CJ) infection and Guillain-Barr| syndrome (GBS) or Miller-Fisher syndrome. We compared 60 cases with 109 hospital controls matched for age, gender, hospital and geographical location. To diagnose the CJ infection, we considered the association between serologic positivity for CJ and a previous diarrheal illness within 3 months of inclusion in the study. Fifteen percent of cases versus 5% of hospital controls had CJ infection (p < 0.003, OR = 3.96, 95% CI: 1.0817.85). However, CJ infection was related to GBS only if it occurred during the previous month (p< 0.001, OR = 7.29, 95% CI: 1.4371.28). No statistical differences were found between the cases who were positive for CJ infection and those who were negative for CJ infection when studied by stepwise multivariate logistic regression for age, gender, clinical and electrophysiological features and outcome. Recent CJ infection may be a risk factor for GBS.
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A man experienced temporary amnesia for tasks which he was used to performing daily as they were the core of his working activity (bread making). No overt etiology was found. We hypothesized a disorder that is similar to transient global amnesia, but selectively affects procedural memory.
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We examined 199 consecutive patients who underwent 220 liver transplantations, to define the type, frequency and aetiology of posttransplant neurological complications and their prognostic value. We found neurological complications in 63 patients (32%), mostly involving the central nervous system. The most frequent complications were mental status changes ranging from delirium to coma and seizures. The aetiology was multifactorial, cyclosporin A neurotoxicity being the main cause. Patients with neurological complications had a higher mortality rate than those without. In our series, neurological complications represented a major medical problem with increased morbidity and mortality.
Malignant tumors with a mixed phenotype are a controversial field of pathology. In this article the morphological aspects and the immunohistological characterization of sarcomatoid carcinomas are presented. These uncommon neoplasms show both carcinomatous and sarcomatous features, and have been described in the past under a variety of different names causing great uncertainty about their classification and histogenesis. They can occur in various anatomical sites and exhibit a wide range of microscopic appearances, but some features are quite characteristic and are found in many cases. Morphological "transition" between carcinomatous and sarcomatous tissue, and detection of epithelial characteristics by electron microscopy or immunohistochemistry in the sarcomatous component, are very peculiar features of these neoplasms, providing both helpful clues for pathological diagnosis and important insights into histogenesis. Here a unifying histopathogenetic mechanism based on the phenotypic conversion of carcinoma into sarcomatoid tissue is proposed and supporting literature data from both experimental systems and clinicopathological observations are reviewed and discussed.
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Under some in vitro conditions, such as exposure to collagen, growth factors and related molecules, and agents affecting DNA methylation, a cell phenotype shift can be observed from an epithelial to a mesenchymal state of differentiation. The reverse process, a mesenchymal-to-epithelial conversion can likewise be obtained by certain experimental manipulations. In some instances the change is fully reversible by removing the inducer substances, but in others the conversion appears to be stable and irreversible. Only a partial modulation of the cell phenotype is often seen, but sometimes a complete switch to a new phenotype occurs, and morphological, biochemical and functional characteristics of the parent cells can be abrogated. In some in vivo models development of sarcomatous tumours can be seen in animals transplanted with several types of carcinoma, and it is possible that in some of these experiments an epithelial-to-mesenchymal conversion has occurred too. In normal embryonic development as well as in pathological lesions including tissue repair, tumour invasion, and some malignant biphasic tumours, changes similar to the ones observed in experimental epithelial-mesenchymal interconversion seem to take place. Therefore, it is conceivable that experimentally-induced phenotype conversions reflect an inherent potential of cells, and that under some experimental circumstances normally silent genetic programs for epithelial or mesenchymal differentiation are activated, thus recapitulating a phenomenon that occurs in physiopathological circumstances in vivo.
Orthotopic liver transplantation (OLT) represents the sole etiological treatment for Wilson's disease (WD), but its efficacy in resolving the neurological symptoms is still a matter of debate. We present the case of a young male affected with WD with hepatic and neurological involvement, who underwent OLT for subacute liver failure. Clinical, neuropsychological and neuroradiological assessment were performed before and after OLT. OLT had no effect on neurological symptoms, suggesting that the basal ganglia damage may be irreversible. Nineteen months after OLT, the patient went on to develop new permanent extrapyramidal symptoms. We postulate a sequela of an early post-operative central pontine and extrapontine myelinolysis.
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In embryonic morphogenesis, dramatic changes from one state of differentiation to another take place, and some epithelia transform into mesenchymal cells endowed with the ability to migrate and to form connective tissue. In vitro model systems have been developed which have provided new insights into crucial aspects of this differentiation change. Triggered perhaps by either extracellular matrix or growth factors, this phenotypic conversion involves a reorganization of the cytoskeleton, and changes in both cell-cell and cell-matrix interactions. As embryonic and adult tissues contain the same, albeit differently expressed, genetic information, one could expect, under particular circumstances, conversion to mesenchyme from epithelium to occur in adult tissues too. Indeed, there is evidence that this change really occurs in human diseases: some tissue reactions to injury; the process of tumour invasion and metastasis; and the development of carcinosarcomas, are all pathological conditions in which an epithelial conversion into mesenchyme probably plays a role. Here, recent observations on embryonic and in vitro epithelial-mesenchymal conversion are reviewed, and these data are compared with findings from some pathological situations. Many similarities emerge which further strengthen the belief that this change in differentiation is involved in the pathogenesis, and underlies the pathological pattern of some diseases.
Little attention has been paid to the composition of the extracellular matrix in synovial sarcoma, a tumour showing both epithelial and mesenchymal phenotypes. As extracellular matrix participates actively in interactions between epithelial and mesenchymal tissues, further knowledge of the pathogenesis of this tumour may be provided by the study of extracellular matrix components. Therefore, we have analysed the immunohistochemical distribution of type I, III, and IV collagen, fibronectin, laminin and tenascin in four cases of synovial sarcoma. The pattern of immunoreactivity for these molecules varied according to the tissue phenotype of the tumour. Mesenchymal tissue labelled mainly for type I and III interstitial collagen and fibronectin. The epithelial component was surrounded by a laminin and type IV collagen-positive basement membrane, but punctate pericellular reactivity for laminin and type IV collagen was also detected among some mesenchymal cells. Tenascin was strongly expressed in the mesenchymal tissue immediately around epithelial structures and weakly or not at all expressed in the monophasic tumours and in mesenchymal tissue distant from epithelial elements in the biphasic tumours. These results suggest some resemblances between synovial sarcoma and the embryonic development of epithelia from mesenchymal cells, providing further support for the concept of an epitheliogenesis from the mesenchyme in these tumours.