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Biomedical subjects

P Tanganelli

Publications and source records attributed to P Tanganelli.

At least 19 recordsLinked to original sources

The number of pregnancies is a risk factor for Alzheimer's disease.

Epidemiological data show a higher prevalence of late-onset Alzheimer's disease (AD) in women. The estrogenic deficiency in the post-menopausal period is suspected to be the cause of the gender-related risk of the disease, but studies on the estrogenic therapy and occurrence of AD were not consistent and sometimes contradicting. The aim of this study is to investigate whether a higher exposure to endogenous estrogens is associated with lower risk of dementia or not. Two hundred and four AD patients and 201 control women were considered. By interviews, we evaluated different variables, indirectly correlated to estrogenic natural exposure, as well as educational level and head trauma. These data were correlated in the AD group with the disease progression, as well as with the age at onset. Unexpectedly, we found a significant higher number of pregnancies in the AD than in the control group. Within the AD cases, the number of lifetime pregnancies is related to an earlier onset of the disease. As previously reported, we confirmed that the educational level is a protective factor and that major head trauma represents a risk factor in developing AD. The higher number of pregnancies and a less frequency of nulliparous women, indirectly relate the AD group to a higher estro-progestinic exposure. These findings suggest that it is the increase of progesterone or estrogens level--and not the estrogens decrease, as previously indicated by other authors--that could play a role in the Alzheimer's pathology.

Aged↗

The prevalence of multiple sclerosis in the north-west Italian province of Genoa.

UNLABELLED: The objective of this study was to assess the prevalence of multiple sclerosis (MS), calculated as point prevalence on 31 December 1997, in the province of Genoa, North-western Italy. METHODS: The province of Genoa is located in North-western Italy, an area of 1,835 km(2). On the point prevalence day the population consisted of 913,218 inhabitants. MS cases were identified by analysing archives of the hospitals with neurological or rehabilitation wards, neurologists serving the community, files of local chapters of the Italian MS society, all requests for oligoclonal bands analysis on CSF in the studied area. Patients included in the study were MS cases diagnosed before 31 December 1997 according to the Poser criteria resident in the province under study. RESULTS: A total of 857 subjects were alive and residing in the province of Genoa on the prevalence day. The overall crude prevalence rate was 94 per 100,000 (95% CI 88-100); 291 were males (34%) with a crude prevalence of 67 per 100,000 (95 % CI 60-76) and 566 were females (66%) with a prevalence of 118 per 100,000 (95% CI 108-128). The female/male ratio was 1.9. When age and sex were adjusted to the Italian standard population of 1991 prevalence was 85 per 100,000. Five hundred and thirty two out of the 857 patients agreed to be interviewed. The interviewed sample was representative of the prevalence sample: sex and gender distributions were identical in the two samples. The overall mean age was 48 (+/-13) years (48 +/-12 years in males; 48+/-14 years in females). Mean disease duration was 15 (+/-10) years for males and 16 (+/-11) years for females. Two hundred and ninety one (55 %) subjects had a relapsing remitting (RR) clinical course, 150 (28%) were secondary progressive (SP) and 91 (17%) were primary progressive (PP). Mean EDSS score was 5 (+/- 2; median 5). The mean age at time of onset was 33 (+/-10) years for males and 32 (+/- 11) years for females. The disease onset was monosymptomatic in 76% (n=407) patients and polysymptomatic in 24% (n=125). The mean length of time between clinical onset and diagnosis was 5 (+/- 6) years. CONCLUSION: We confirmed that the province of Genoa is a very high risk area for MS. We found a high rate of patients with a PP course; also the proportion of patients with high disability scores is greater compared to previous studies.

Adult↗

Pregnancy, patent foramen ovale and stroke: a case of pseudoperipheral facial palsy.

The pathogenetic role of patent foramen ovale (PFO) in embolic stroke and its prognostic and therapeutic implications have not yet been clearly defined. Nonetheless, recent availability of non-invasive diagnostic techniques, such as the transcranial Doppler (TCD), has increased the frequency with which this anomaly is diagnosed. Here we present the case of a young woman affected by post-partum peripheral facial palsy: further exams disclosed not only its truncal-ischaemic origin, but also, significantly, the presence of PFO, as well as of anticardiolipin antibodies (acL). Given the increased embolic risk in labouring women, this study highlights the importance of searching for PFO in case of a stroke during pregnancy.

Adult↗

Smooth muscle cells of the media in the dilatative pathology of ascending thoracic aorta: morphology, immunoreactivity for osteopontin, matrix metalloproteinases, and their inhibitors.

The etiopathogenesis of thoracic aortic aneurysms is currently an issue of debate. The present study investigated ultrastructural, morphometric, and immunohistochemical aspects of smooth muscle cells (SMCs) in chronic aneurysm of the thoracic aorta (aneurysm group), aortic dilatation associated with valvular disease (valvular group), and dissection of the thoracic aorta (dissection group). Fragments of the ascending aorta that had been taken from the patients during coronary bypass surgery were used as controls. No significant difference was observed in the density of SMCs between the 3 pathologic groups put together and the controls. Only separate analysis of SMC density in each of the pathologic groups showed that the valvular group samples had significantly smaller amounts of SMCs in the internal layer of the media than the dissection group samples and controls. Ultrastructural analysis, in situ end labeling, propidium iodide assay, and DNA laddering did not show apoptosis of SMCs in the samples investigated. Ultrastructure of SMCs characteristic of the synthetic phenotype, together with increased expression of osteopontin in the media of pathologic thoracic aortas indicated the transition of SMCs from the contractile to the synthetic phenotype. Immunohistochemical investigation showed that medial SMCs in the samples taken from aortas of all 3 pathologic groups expressed stronger immunoreactivity for matrix metalloproteinase 1, 2, and 9 and tissue inhibitor of metalloproteinase 1 and 2 than the controls. The present study shows that during the formation of aneurysms, dissection of the thoracic aorta, or aortic dilatation associated with valvular disease, loss of SMCs was not of great importance with respect to their transition from the contractile to the synthetic type in leading to increased production of matrix metalloproteinases.

Adult↗

Early neonatal brain injury in histologic chorioamnionitis.

The relation between clinical or histologic chorioamnionitis and early neonatal adverse neurologic outcome was investigated (n = 483). Histologic, but not clinical, evidence of chorioamnionitis was found to be a significant predictor of periventricular echodensity (odds ratio, 2.4; 95% CI, 1.8-3.2), echolucency (3.3; 1.9-5.6), ventriculomegaly (2.7; 1.8-4.2), intraventricular hemorrhage > or =3 (3.5; 2.4-5.2), and seizures (2.3; 1.4-3.7).

Age Factors↗

A primary intracavitary right atrial neurilemoma.

Primary cardiac neurilemoma, a benign tumor, is extremely uncommon. To our knowledge only eight cases have been reported in the literature. We report a case of a 72-year-old man who presented with complaints of progressive shortness of breath and chest pain, seven years after a right nephrectomy for renal adenocarcinoma. An intra-right atrial tumor was surgically removed; the lesion was found to be a neurilemoma of the right atrium. This case report describes the surgical removal and rarity of neurilemomas, their predisposition to be right-sided in the heart and their coincidental association with other types of cancer.

Adenocarcinoma↗

Old and new anti-epileptic drugs in pregnancy.

During the recent years, a significant number of anti-epileptic drugs have been approved for prescription in different countries. In addition, some other promising drugs are in various stages of development. Soon after each drug has found its place in the therapeutic arsenal, pregnancies with exposure occur, with an increased risk of birth defect and developmental disturbances. As regards the possible teratogenic effect of the new anti-epileptic drugs, apart some individual reports we have only the results of pre-clinical toxicological studies which are difficult to extrapolate to the human situation, because of the well-known interspecies differences in pharmacokinetics and pharmacodynamics. Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically while these new drugs are prescribed as add-on medication. So, metabolic interactions between individual components of such drug combinations may induce unexpected teratogenic effects. Also as for the teratogenic effects of the old drugs many questions have still to be defined. The most common and more important are which anti-epileptic drugs or combination of drugs is most safe for a particular woman with epilepsy and if there is an association between single anti-epileptic drugs and specific malformations. The reason is that none of the available reports to date have studied a sufficient number of women with epilepsy exposed to anti-epileptic drug monotherapy during pregnancy. Other questions concern dose-effect relationships, a universally accepted definition of major and minor malformations, and the lack of a thorough, exhaustive evaluation of the other risk factors, apart from the drugs. All these questions need to be ascertained for both the old and the new anti-epileptic drugs. Owing to these considerations, in 1998 an European Register of anti-epileptic drugs and pregnancy was instituted. The primary objective of the study is to evaluate and determine the degree of safety, with respect to the human foetus, of anti-epileptic drugs with reference to both old and new, and to individual drugs and drugs in combination. Secondary objectives are to establish the pattern of abnormalities, if any, associated with anti-epileptic drugs individually and in combination, to delineate drug-specific syndromes, if any, to evaluate dose-effect relationships. Tertiary objectives are to provide references data for use in pre-pregnancy counselling, and for development of guidelines. The evaluation of other etiological risk factors is also considered.

Abnormalities, Drug-Induced↗

Clinical aspects and biological bases of drug-resistant epilepsies.

The definition of drug-resistant epilepsy (DRE) is elusive and still controversial owing to some unresolved questions such as: how many drugs should be tried before a patient is considered intractable; to which extent side-effects may be acceptable; how many years are necessary before establishing drug resistance. In some cases, the view of epilepsy as a progressive disorder constitutes another important issue. Despite the use of new antiepileptic drugs (AEDs), intractable epilepsy represents about 20-30% of all cases, probably due to the multiple pathogenetic mechanisms underlying refractoriness. Several risk factors for pharmacoresistance are well known, even if the list of clinical features and biological factors currently accepted to be associated with difficult-to-treat epilepsy is presumably incomplete and, perhaps, disputable. For some of these factors, the biological basis may be common, mainly represented by mesial temporal sclerosis or by the presence of focal lesions. In other cases, microdysgenesis or dysplastic cortex, with abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons, may be responsible for the severity of seizures. The possible influence of genes in conditioning inadequate intraparenchimal drug concentration, and the role of some cytokines determining an increase in intracellular calcium levels or an excessive growth of distrophic neurites, constitute other possible mechanisms of resistance. Several hypotheses on the mechanisms involved in the generation of DRE have been indicated: (a) ontogenic abnormalities in brain maturation; (b) epilepsy-induced alterations in network, neuronal, and glial properties in seizure-prone regions such as the hippocampus; (c) kindling phenomenon; (d) reorganization of cortical tissue in response to seizure-induced disturbances in oxygen supply. Such hypotheses need to be confirmed with suitable experimental models of intractable epilepsy that are specifically dedicated, which have until now been lacking.

Anticonvulsants↗

Scarring in papillary carcinoma of the thyroid: report of two new cases with exuberant nodular fasciitis-like stroma.

AIMS: To describe two new cases of papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma, one of which was characterized by previously unreported transformation into a poorly differentiated lesion. Moreover, we explore the presence of TGF-beta to help to clarify the pathogenesis of the collagen formation. METHODS AND RESULTS: The case characterized by an aggressive behaviour exhibited areas of transformation into a poorly differentiated (insular) carcinoma of the thyroid. In both cases, as revealed by immunohistochemistry, neoplastic cells produced and secreted high amounts of TGF-beta. On the contrary, TGF-beta immunoreaction was never present in the normal thyroid or in papillary carcinomas without collagen bundles, while a weak, exclusively intracellular reaction was present in a patchy manner in cases showing intratumoral fibrous bundles. CONCLUSIONS: The rare variant of papillary thyroid carcinoma characterized by exuberant stroma may give rise to more aggressive lesions, as do other histotypes of differentiated thyroid carcinomas. TGF-beta, the fundamental cytokine which mediates scarring and activation of myofibroblasts, most probably induces the exuberant stroma.

Adult↗

World Health Organization (WHO) and the World Heart Federation (WHF) Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Study. Histomorphometric investigation of the aorta and coronary arteries in young people from different geographical locations.

BACKGROUND AND AIM: At the Morphometric Reference Center of the World Health Organization (WHO) and the World Heart Federation (WHF) for the Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Project, histomorphometric studies were carried out on aortic and coronary artery walls of 590 people ranging from 5 to 34 yr of age, who were of European, American, Asian and African origin (6 countries) and died of trauma. The aim was to evaluate the mean intimal and medial thickness of arterial tissues. METHODS AND RESULTS: Computerized operator-assisted morphometry with a semiautomatic image analyzer was carried out on 2,893 histological slides (prepared at the WHO Reference Center in Malmö, Sweden). Our data show that age-dependent trends for prevalence of fatty streaks and atherosclerotic plaques in arteries are different: prevalence of fatty streaks increases until a plateau is reached, while exponential growth characterizes atherosclerotic plaque prevalence. Age is statistically associated with an increase in mean intimal and medial thickness in all specimens. CONCLUSIONS: Mean intimal and medial thickness differs in arterial wall specimens of individuals from various geographic locations: persons from countries with high mortality rates from cardiovascular disease tend to have greater mean intimal thickness in youth. Men with hypertension and those who smoke have significantly greater combined means of intimal thickness than normotensives and non-smokers respectively. The also have significantly greater combined means of medial thickness than normotensive men. Histomorphometric data provide evidence of the development of atherosclerotic lesions at an early age and relate their progression to ethnic and lifestyle factors and to major coronary heart disease risk factors.

Adolescent↗

World Health Organization (WHO) and the World Heart Federation (WHF) Pathobiological Determinants of Atherosclerosis in Youth (PBDAY) Study. Lipid and raised lesion distribution in the right coronary artery of young people.

BACKGROUND AND AIM: As part of the WHO-WHF PBDAY Study, we examined the proximal segment of the right coronary artery (RCA) (n = 469) of 5-34 yr-old otherwise healthy trauma victims from 15 countries to establish the topographical relation of atherosclerotic lesions to age, sex and geographical location. METHODS AND RESULTS: Topography and extent of lesions were analyzed by image processing and probability-of-occurrence maps of lipid lesions (mostly fatty streaks) and raised lesions on the intimal surface of the RCA were produced. Extension of lesions varied considerably between the groups and between individuals in the same group. The prevalence of lipid lesions was 68% (319/469) compared with 100% in the aorta. The prevalence of raised lesions was 22% (102/469) compared with 7% and 26% in the thoracic and abdominal aorta. Females had more lipid lesions, whereas raised lesions prevailed in males. Lipid lesion extent increased with age in both sexes. CONCLUSIONS: High probability-of-occurrence areas for lipid and raised lesions prevailed in the proximal 5 cm of the intimal surface of the RCA (myocardial side) and were greatly overlapping. Regression analysis between lipid and raised lesion extent in the thoracic or abdominal aorta and the RCA showed no correlations between the lipid lesion extent, whereas significant correlations were found between the raised lesion extent in the RCA and the thoracic aorta only, showing that the two types of lesion behave differently in different anatomical locations.

Adolescent↗

Bronchopulmonary dysplasia of the premature baby: an immunohistochemical study.

Prematurely born infants who required assisted ventilation may develop chronic lung disease or bronchopulmonary dysplasia (BPD). The cells involved in the reparative process of the premature lung are not well defined. The repair of injured tissues is a highly standardized process and the most important cells are activated (modulated) fibroblasts (myofibroblasts). A key cytokine in controlling repair is transforming growth factor-beta (TGF-beta). To characterize the cells involved in the repair process of the premature lung, we employed immunocytochemical techniques and examined the lungs of 39 autopsied premature babies who had neonatal respiratory distress syndrome (RDS). All were treated in neonatal intensive care units and required mechanical ventilation and supplemental oxygen; all survived for at least 12 hours. Antibodies were employed against vimentin, alpha-smooth muscle (alpha-SM) actin, total muscle actin, desmin, MAC387, and TGF-beta. Our study indicates that myofibroblasts are normally present along terminal airways in the developing lung. These cells increase in number some days after lung injury, form bundles of cells encircling terminal air spaces, and acquire desmin contractile filaments shortly thereafter. Myofibroblasts do not lose their contractile filaments with time, suggesting a conversion to smooth muscle metaplasia. The proliferation and migration of such myofibroblasts at sites of lung injury is associated with the presence of TGF-beta. These findings suggest that myofibroblasts play an important role in premature lung repair. They may point the way to experimental and clinical trials that will identify drugs antagonistic to TGF-beta (or other cytokines). Such antagonists may protect the neonates who are at high risk of developing BPD.

Acute Disease↗

Clinicopathological and genetic studies of two further Italian families with cerebral autosomal dominant arteriopathy.

We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psychiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. Moreover, to confirm the CADASIL gene location to 19p12, we performed a linkage analysis with four microsatellite markers. The results of the genetic study gave positive but not significant lod scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we found extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions consisted of a thickening of the media with deposition of granular eosinophilic material. Ultrastructural examination of the arterial walls showed graded damage to smooth muscle cells, mostly of the longitudinal layer, and an abnormal proliferation of basal lamina components. Immunocytochemical analysis showed strong reactivity using antibodies to collagen IV and smooth myosin proteins. The results suggest a primary involvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue.

Adult↗

Vigabatrin vs. carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study.

The clinical efficacy and safety of vigabatrin (VGB) as add-on therapy for pharmaco-resistant focal epilepsies is well established. However, for an objective evaluation, the effects of the drug in the monotherapy of newly diagnosed subjects should be determined. With this aim, VGB was compared, in a randomized, response conditional cross-over study, with carbamazepine (CBZ), the most widely prescribed drug in focal epilepsies. Fifty-one patients with complex partial (CP) seizures were randomly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period. The cross-over to the alternative drug was carried out, for an analogous period, only in cases with persisting seizures or in the presence of intolerable side effects. Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ. No significant difference was revealed in the efficacies of VGB and CBZ; a complete control of seizures was obtained in 17/37 patients (45.9%) treated with VGB and in 20/39 patients (51.3%) treated with CBZ. The side effects were somewhat more frequent (41%) and severe with CBZ than with VGB (21.6%). The power to detect a 20% difference between the two drugs was 75%. The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases. The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated.

Adolescent↗

Newer antiepileptic drugs as monotherapy: data on vigabatrin.

Studies examining the use of vigabatrin as monotherapy for the treatment of epilepsy are relatively scarce, and of the few that have been reported, only two were of sufficient size to provide definitive data. In both trials, vigabatrin was compared with carbamazepine for efficacy and safety. In one of these studies, carbamasepine was found to be more effective than vigabatrin in reducing seizure frequency, and the two were found to be comparably efficacious in the other study. What differed significantly, however, was vigabatrin's favorable safety profile. Vigabatrin appears to be a reasonable choice for single-drug therapy in the treatment of certain types of seizures. In other patients, it remains useful as an adjunct to other antiepileptic drugs.

Adolescent↗