Huntington disease: clinical, genetic, and social aspects

Sexual assaults on girls occur at an alarming rate representing a significant public health problem, but difficulties in correctly identifying the problem, managing the child and reporting for legal purposes have been recognized. We describe data obtained on 154 recent cases of child and adolescent sexual assault. Results indicate that those at highest risk of sexual assault are girls at age of 11-15 years having a stepfather, although the most girls at age of > 15 were assaulted by strange men with higher incidence of cross-race assault. Over a quarter of girls showed signs of physical trauma with face and neck as most common site of contact. A total of 17.5% reported threat of violence or with weapons and 9.7% had alcoholic influence. Pattern and incidence of genital injuries were described.     

Gaucher's disease: molecular, genetic and enzymological aspects

The molecular, genetic and enzymological abnormalities in Gaucher's disease have been delineated during the past decade. Although our understanding of the primary predisposition to the Gaucher's disease phenotypes has improved, the relationships remain poorly understood between the mutant alleles, the resultant enzyme variants, the saposin C (activator protein) locus and phenotypes. Of the more than 100-disease associated alleles, about 8 to 10 have significant frequencies in various ethnic and demographic groups. The N370S(1226G) allele is very frequent in Caucasian populations, but absent in Asian groups. In the Ashkenazi Jewish population, the N370S homozygosity predisposes to Gaucher's disease, but over 50% of such patients escape medical detection because of their mild to absent involvement, i.e. N370S may be a prediposing polymorphic variant. Clarification of genotype/phenotype relationships and the identification of modifier loci that impact on Gaucher's disease phenotypes remain a critical area for research. Greater understanding of these issues will facilitate genetic counselling and appropriate interventive therapy to prevent the morbid long-term manifestations of Gaucher's disease.     

The kidney in hepatic disease and in gout: clinical and pathologic aspects

The role of the kidney in hepatic disease and in gout has been surveyed. Kidney involvement is more common but less severe in hepatic disease, whereas it is less common but more severe in gout. The underlying pathology of the kidney lesions in both diseases (including studies by electron microscopy and immunofluorescence) is presented, with emphasis on the role this pathologic substratum plays in the renal insufficiency. The clinical aspects, including the diagnostic approach and therapeutic management of the "hepatorenal syndrome" and "gouty kidney" are discussed, as are the prognostic implications of the natural history of these "complications" and measures aimed at their prevention.     

Bronchial asthma: pathogenetic mechanisms and genetic aspects

At present there is a general consensus on the inflammatory nature of bronchial asthma. The main immunological features of the atopic state are represented by the ongoing expansion of Th2-like cells and production of IgE antibodies. IL-4 seems to represent the key factor for the differentiation of Th2-like cells, even though other cytokines have been recently proposed to play a some role. The possible genetic alterations which lead to the deregulated overexpression of IL-4 gene and of other genes of the same family in atopics are under active investigation. The existence of a polymorphism at level of IL-4 gene distal and proximal promoter has directly been shown. Even though IL-4 is required for the development and maintenance of atopic state, IL-5 certainly plays an essential role in the pathogenesis of bronchial inflammation in atopic, intrinsic and occupational asthma. On the basis of the findings emerged from new experimental models, it appears that there are different pathways by which T cell responses can develop bronchial eosinophilic inflammation but all the pathways have to lead to obligatory ongoing production of IL-5. The future research can be also addressed either to clarify the cytokines and/or other factors able to induce the differentiation and ongoing expansion of T cells prevalently producing IL-5, possibly involved in the pathogenesis of intrinsic asthma, either to understanding the nature of stimuli acting as etiologic factors. On the basis of the present acquisitions, IL-5 could represent the most important target of the new approaches to asthma therapy.     

Acne: physiopathology and clinical aspects

Acne is easy to diagnose, but its physiopathology is complex and not yet fully elucidated. However, the three factors that are necessary to the genesis of acne are well defined, being seborrhoea, obstruction of the hair follicle and the sebaceous gland, and inflammation of the follicle. To this must be added a genetic predisposition. While the skin lesions leave little doubt about the diagnosis, a thorough examination is needed to evaluate the part due to sebum retention (comedos, microcysts) and that due to inflammatory elements (papules, pustules, nodules), for the lesions are so polymorphous that it would be better to speak of acnes rather than acne. A good knowledge of clinical and physiopathological data leads to the appropriate treatment, since almost all therapeutic failures result from a misappreciation of acne.     

Perfectionism: conceptual and clinical aspects

OBJECTIVE: Study of the concept of perfectionism and its phenomenology, etiology, and treatment. METHODS: Review of the literature, phenomenological, and-clinical analyses. RESULTS: The International Classification of Diseases introduced the notion of perfectionism into psychiatric discourse in 1977. In DSM-III, DSM-III-R, and DSM-IV, perfectionism is a diagnostic criterion of obsessive-compulsive disorder, but has never been defined in the psychiatric literature. We differentiate normal perfectionism and pathological perfectionism, which is of some psychiatric interest: normal perfectionism is manifested according to the aptness of the target and its sociocultural value, and is therefore selective and flexible, whereas pathological perfectionism is the compulsive pursuit of a performance level not required by the circumstances and idiosyncratic in nature. Its symptomatology may resemble that of obsessive-compulsive disorder, but is actually quite different: whereas obsessive-compulsive symptoms are absurd and the product of ego-dystonic compulsion, pathological perfectionism is experienced as a personal obligation, and retain an identifiable cultural objective. CONCLUSIONS: The phenomenology of the normal and abnormal manifestations of perfectionism is well defined. While pathological perfectionism and obsessive-compulsive disorder are similar and may even share a common etiology, they should be considered 2 distinct clinical entities. The therapeutic approaches to pathological perfectionism remain empirical.     

Hereditary spherocytosis: a review of the clinical and molecular aspects of the disease

Hereditary spherocytosis is a common and very heterogeneous hemolytic anemia caused by defects of the red cell membrane proteins. In recent years, major advances in our understanding of the red cell membrane skeleton and a better characterization of its individual components have allowed a brighter insight into the pathogenesis of the disease. In this article, we present an overview of the erythrocyte skeleton and its individual constituents. We also review the clinical aspects of the disease and describe the currently known molecular defects involving the membrane proteins which have been shown to play an essential role in the underlying mechanism of hereditary spherocytosis. Finally we examine several models that have been proposed in an attempt to clarify the mechanism leading from the initial molecular insult to the clinical phenotype.     

Diabetic neuropathy: clinical aspects

The importance of diabetic neuropathy derives from its remarkable frequency and its clinical impact. In view of the varying underlying pathogenetic mechanisms and the resulting diversity of clinical representations, it becomes apparent that there are diabetic neuropathies, rather than a single entity of diabetic neuropathy. The scope of involvement is widespread with virtually every system at risk. Although peripheral neuropathy is by far the most common expression, visceral neuropathy is also highly significant. It may affect every part of the gastrointestinal tract, the genitourinary tract, and sexual function, as well as direct autonomic nerve pathology. Clearly, neuropathy in diabetes offers a specific and important diagnostic challenge to the clinician and plays a definitive role in differential diagnosis. The problem is heightened by the fact that any and all of the diabetic neuropathic syndromes may be the initial clinical manifestation of diabetes in the absence of covert manifestations of carbohydrate metabolic disorder. It is to be stressed that the diagnosis is more than an academic exercise, since each diabetic neuropathic syndrome carries with it some beneficial therapeutic modality to aid the patient.     

Lissencephaly syndromes: clinical aspects

We report clinical and neurophysiological findings in six children (three female, three male) with type I lissencephaly and three children (all female) with type II lissencephaly (Walker-Warburg syndrome). In type I lissencephaly the diagnosis is based only on electroencephalographic (EEG) signs, whereas in type II lissencephaly the diagnosis rests on clinical signs. In type I lissencephaly the EEG typically shows high alpha-beta activity, which is not seen in type II lissencephaly.     

Xenoislet transplantation: experimental and clinical aspects

Ten diabetic renal transplant patients had porcine fetal islet-like cell clusters (ICC) injected intraportally or placed under the kidney capsule. In some patients, temporary graft survival was achieved, as evidenced by the urinary excretion of small amounts of porcine C-peptide (4 patients) and the identification of some intact insulin-staining cells in a biopsy specimen (1 patient). Glucose metabolism remained unaffected. To improve the results, better islets and better immunosuppressive protocols are required. We found that, while fetal porcine ICC produced insulin only after several weeks, adult islets gave immediate insulin production. The search for an optimal immunosuppression was conducted in the pig-to-rat islet transplant model. A clear inhibitory effect on the xenograft rejection was observed when using some of the new drugs. The best results were achieved with a triple drug regimen consisting of cyclosporine, mycophenolate mofetil and leflunomide.     

Retinoblastoma: clinical and molecular diagnostic aspects

Retinoblastoma, a tumor of the immature retina concerns babies and young infants in particular. They make up for 14% of malignomas in the first years of life. There are two types of retinoblastoma: In the first two alleles of the gene Rb1 must be inactivated sequentially in the same retinoblast cell until this may escape control. In this case the retinoblastoma is always unilateral and unifocal. This is explained by the lower frequency of two mutations in one retinoblast. The other type, however, is inherited: One allele Rb1 is inactivated in all cells of the organism by mutation. The probability that a second mutation arrives in different retinoblasts is thus high. In this case bilateral multifocal tumors develop. Characterization of the Rb1 gene has permitted identification or at least determination of a haplotype in persons at risk. This knowledge is decisive for early recognition of babies at risk and for genetic counselling.