Diffusion-weighted imaging study of patients with essential tremor.

The pathophysiology of essential tremor (ET) is unknown. PET and fMRI studies have revealed bilateral activation and (1)H-MRS studies metabolic abnormalities in the cerebellum and other functionally related brain structures in ET. Diffusion-weighted imaging (DWI) was used to search for evidence of tissue integrity abnormalities in these areas in ET patients and 10 matched controls by calculating water apparent diffusion coefficients (ADCs). Regions of interest included the left and right cerebellum, red nucleus, thalamus, caudate, putamen, pallidum, and frontal white matter. Histograms of ADCs were generated for all pixels in the infratentorial compartment and manually segmented areas corresponding to brainstem, vermis, and cerebellar hemispheres. ADC values were similar in all brain areas in patients and controls. Our study did not detect changes affecting the investigated brain regions in ET patients. These findings argue against major structural damage in the ET brain, although more subtle neurodegenerative changes cannot be ruled out.     

Treatment of hepatitis B and C after liver transplantation. Part 1, hepatitis B

Abstract The outcome of OLT for HBV-related liver disease is dependent on the prevention of allograft re-infection. Over the past decade, major advances have been made in the management of HBV transplant candidates. The advent of long-term hepatitis B immune globulin (HBIG) administration as a prophylaxis against HBV recurrence, and the introduction of new antiviral agents against HBV infection, such as lamivudine (LAM), were a major breakthrough in the management of these patients. Results of OLT for HBV infection are similar to those achieved with other indications. Pre-OLT antiviral treatment such as LAM can suppress HBV replication before OLT and thus decrease the risk of re-infection of the graft. Combination prophylaxis with LAM and HBIG after transplantation highly effectively reduces the rate of HBV re-infection, even in HBV replicative cirrhotic, patients. The optimal HBIG protocol in the LAM era is yet to be defined: dosing of HBIG, routes of administration, and possibility of stopping HBIG. Several antiviral drugs have been developed for the management of HBV infection on the graft, so outcome is currently good.     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

CD15 (LeuM1) immunoreactivity: Prognostic factor for sporadic and hereditary medullary thyroid cancer?

Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC) have varying rates of persistent disease, recurrence, and survival. The aim of this study was to correlate the immunoreactivity of the monoclonal antibody CD15 (LeuM1) to initial clinical findings and the outcome of treatment. The primary tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little immunoreactivity (<15% positive cells; score 0) in most tumors. The remaining 13% had surgery for tumors with more than 15% cells with positive staining (score I). There was no correlation between LeuM1 immunoreactivity and sex, age, and type of MTC. There was, however, a significant correlation with the pTNM classification and UICC staging. The prognosis for patients with score 0 was significantly better than score 1 patients. CD15 immunoreactivity appears to be a predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to be more successful in patients with score 0 tumors than in those with score 1 tumors. The question of reoperation in patients with recurrence of disease (especially with biochemical recurrence or persistence) should be discussed on the basis of CD15 immunoreactivity.

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Resumen Los pacientes tratados para carcinoma medular, esporádico y hereditario, de la glándula tiroides (CMT) exhiben grandes variaciones en las tasas de enfermedad persistente, recidiva y sobrevida. El propósito del presente estudio fue establecer la correlación entre la inmunorreactividad del anticuerpo CD15 (LeuM1) y los hallazgos clínicos iniciales, así como con el resultado final del tratamiento.Se estudiaron los tumores primarios de 75 pacientes con CMT esporádico, de siete con enfermedad hereditaria y de 3 miembros de familias con síndrome NEM2A.Setenta y cuatro pacientes (87%) exhibieron ninguna o muy baja inmunorreactividad (menos de 15% de células positivas; puntaje 0) en la mayoría de los tumores. El 13% restante fue sometido a cirugía por tumores con más de 15% de las células con coloración positiva (puntaje 1). No se evidenció correlación entre la inmunorreactividad LeuM1 y el sexo, edad o tipo del CMT. Sin embargo, sí apareció una correlación significativa con la clasificiación pTNM y la estadificación de la UICC. El pronóstico de los pacientes con puntaje 0 resultó significativamento mejor que el de los pacientes con puntaje 1.La inmunorreactividad CD15 parece ser un factor de predicción de pronóstico en el CMT esporádico y familiar. La disección ganglionar parece ser más exitosa en pacientes con tumores de puntaje 0 que en los que portan tumores con puntaje 1.El interrogante en cuanto a reoperación en pacientes con recidiva de la enfermedad (especialmente cuando hay recidiva o persistencia bioquímica) debe ser considerada con base en la inmunorreactividad CD15.

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Résumé Les taux de maladie persistante, de récidive et de survie chez des patients traités pour cancer médullaire sporadique et héréditaire de la thyroïde (CMT) sont très variables. Le but de cette étude a été de corréler l'immunoréactivité des anticorps monoclonaux CD15 (LeuM1) à des données cliniques initiales et l'évolution finale du traitement des CMT. On a étudié 75 patients ayant un CMT primitif, sept ayant une maladie héréditaire, et trois membres d'une famille MEN 2A. Soixante quatre patients (87%) avaient peu ou pas d'immunoréactivité (moins de 15% de cellules positive: score = 0). Les 13% restants ont eu une chirurgie pour les tumeurs ayant un pourcentage > 15 (score = 1). Il n'y avait aucune corrélation entre l'immunoréactivité LeuM1 et le sexe, l'âge et le type de CMT. Il y avait, en revanche, une corrélation significative entre la classification pTMN et le stage UICC. Le pronostic des patients ayant un score = 0 était significativement meilleur que celui des patients ayant un score = 1. L'immunoréactivité CD15 apparaît comme étant un facteur pronostique des CMT. Le curage lymphatique

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Members and institutions are listed in Table 1.     

Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

The glycine receptor: pharmacological studies and mathematical modeling of the allosteric interaction between the glycine- and strychnine-binding sites

The displacement by glycine of 3H-strychnine binding to rat spinal cord membranes cannot be explained by a simple competitive interaction. Indeed, protein-modifying reagents can completely abolish the inhibition of 3H-strychnine binding by glycine and other agonists, whereas the interaction of strychnine itself and other related compounds with the binding site is unimpaired. Moreover, glycine cannot inhibit completely saturable 3H-strychnine binding, the extent of its maximum inhibitory effect depending on the ionic composition of the medium. Hill coefficients less than 1 (whose magnitude also depends on the assay medium) were obtained from glycine displacement curves. These properties are consistent with a mathematical model of two different, but mutually interacting, binding sites for strychnine and glycine on the glycine receptor. The effect of ions and protein-modifying reagents might be explained in this model as modifications of the mechanisms that mediate the allosteric interaction, and/or the affinity of glycine for the receptor. The agonists beta-alanine and taurine and the new antagonists, THAZ, iso-THAZ, and 4,5-TAZA, also seem to interact with a site different from the strychnine-binding site, probably the glycine-binding site.     

Alteration of Elastin, Collagen and their Cross-links in Abdominal Aortic Aneurysms

OBJECTIVES: although the mechanism of arterial dilation and aneurysm development has not been clarified, the degradation of elastin and collagen plays undoubtedly a critical role. We evaluated the elastin and collagen content through the detection of their cross-links in aneurysmal and non-aneurysmal abdominal aortic walls. MATERIALS AND METHODS: in 26 human abdominal aortic aneurysm specimens obtained during surgery and in 24 autopsy control samples of non-aneurysmal abdominal aorta the tissue content of elastin and collagen cross-links were measured by HPLC. Collagen was also detected by evaluating two characteristic amino acids, 4-hydroxyproline (4-hypro) with a colorimetric method and 5-hydroxylysine (5-hylys) by gas chromatography. RESULTS: significantly fewer elastin cross-links were found in aneurysm samples compared to controls (desmosines and isodesmosines: 90% reduction; p<0.01). The opposite was true for pyridinoline collagen cross-links (350% increase) and deoxypyridinolines (100% increase, p=0.01). Tissue content of 5-hylys, 4-hypro and total amino acids were reduced significantly by 50% in aneurysmal samples. CONCLUSIONS: beside confirming decreased elastin content in aneurysmal walls, these results show a concurrent increase of collagen cross-links. Since total collagen markers were decreased (decreased 4-hypro and 5-hylys) it is reasonable to suggest that in aneurysmal aortic walls old collagen accumulates cross-links while new collagen biosynthesis is somehow defective.