Worldwide epidemiology and modes of transmission of delta hepatitis

Conclusions Since the discovery of HDV in 1977 byRizzetto and collegues (10), several studies regarding the pathogenesis, natural history and epidemiology of this infection have been accumulated. It emerges that HDV is an agent with unusual biologic properties which requires HBV replication for its expression. Given the obligatory association between HDV and HBV, transmission of HDV follows the same routes of HBV transmission. This implies that one expects HDV infection to be much more prevalent in countries with high HBsAg carrier rates. This is true in most areas of the world but not in Far East Asia. Endemicity of HDV is maintained in the community through the network of HBsAg carriers. HDV can be transmitted to HBV positive and negative individuals, but survives only after encountering the carrier. Recent outbreaks of severe epidemics of fulminant hepatitis due to HDV among the Yucpa Indians in Northern Venezuela, pointed out very clearly that HDV superinfection is an ominous risk for all populations where HBV is endemic.     

A Case of Hypopigmented Mycosis Fungoides in a Young Caucasian Boy

Abstract: Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described aimost always in young black or dark-skinned patients. The only white patient described was a 64-year-oid woman who not oniy had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunoiogic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder, Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.     

Infections with the hepatitis B virus associated delta agent in an isolated West-African community

The occurrence of delta agent (delta) infection in the native population of the isolated Gbawein and Wroughbarh Clan region of Grand Bassa County, Liberia was studied. Sera of 97 patients with epilepsy, 73 non-epileptic relatives, and 31 non-epileptic control subjects were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs) and antibody to delta antigen (anti-delta). Of the 201 individuals tested 76 (37.8%) were HBsAg positive; the overall infection rate (HBsAg and anti-HBs positives) was 68.7%. No correlation with clinical disease could be established. Markers of delta infection were detected in seven index cases. All subjects with anti-delta were HBsAg positive except one, who was anti-HBs positive with a low titre of anti-delta (less than 1:10(2)), which is indicative of a recent delta infection. Mothers of six delta infected index cases were available for testing, one was found HBsAg and anti-delta positive, while the other five were anti-HBs positive and anti-delta negative. No delta infections occurred in children of HBV negative mothers. Presence of delta markers varied significantly (P less than 0.02) among HBsAg carriers of the Kpelle (18%) and the Bassa (2%) language group. A comparable difference in delta markers was observed among HBsAg carriers of the Gbawein (17%) and the Wroughbarh (4%) clans.     

HLA-DR antigens in HBsAg-positive chronic active liver disease with and without associated delta infection

The A, B, C and DR locus specificities of the human leukocyte antigens system (HLA) were determined in 45 delta-positive and 44 delta-negative Italian patients, all with HBsAg-positive chronic active liver disease; controls were 526 healthy Italian blood donors matched for age, sex and geographical origin. HLA-A, B, C gene frequencies were not significantly changed. In delta-positive patients, the frequencies of the DR locus specificities were: DR2, 37.8%; DR3, 20%; DR4, 11.1%. In the delta-negative patients, the frequencies were: DR2, 13.6%; DR3, 36.4%; DR4, 0%. Control frequencies were: DR2, 19.4%; DR3, 17.1%; DR4, 18.5%. The corrected p values of the differences between controls and delta-positive patients were: DR2, pc = 0.046; DR3, pc = NS (not significant); DR4, pc = NS. The corrected p values of the differences between controls and delta-negative patients were: DR2, pc = NS; DR3, pc = 0.03; DR4, pc = 0.002. These findings show that: (a) DR3, a genetic marker of autoimmunity, might assist the establishment of chronic HBsAg liver disease in the absence of delta superinfection; (b) DR2 is linked with failure to clear the delta agent, and (c) DR4 may protect from virus B persistence. Identification of adventitious factors such as delta may help uncover a subgroup of HBsAg carriers who are genetically predisposed to develop chronic liver disease.     

Predictive significance for sudden death of microvolt-level T wave alternans in New York Heart Association class II congestive heart failure patients: a prospective study

BACKGROUND: Sudden cardiac death (SDC) is responsible for approximately 60-70% of deaths in New York Heart Association (NYHA) class II congestive heart failure (CHF) patients. Recently, microvolt-level T wave alternans has been proposed as a new noninvasive tool to identify CHF patients at risk for SCD and ventricular tachycardia/fibrillation (VT/VF). OBJECTIVES: To determine the prognostic value of MTWA in NYHA class II patients. METHODS: Among 181 consecutive CHF patients with ischemic and nonischemic cardiomyopathy, 73 patients in NYHA class II with left ventricular ejection fraction <45% were selected and prospectively investigated. MTWA was determined during bicycle exercise testing. The study end point was defined as SCD, documented sustained VT/VF and appropriate implantable cardioverter defibrillator (ICD) shock. RESULTS: MTWA was positive in 30 (41%) patients, negative in 26(36%) patients and indeterminate in 17 (23%) patients. During an average follow-up of 17.1+/-7.4 months, seven patients had an arrhythmic event in the MTWA positive group, whereas one and no events occurred in the indeterminate and negative group, respectively. From Kaplan-Meier univariate analysis and multivariate Cox analysis, MTWA was a significant arrhythmic risk stratifier (p=0.01 and p=0.03, respectively). Sensitivity, specificity, negative and positive predictive values of MTWA were 100%, 53%, 100% and 24%, respectively. CONCLUSION: Our data suggest that MTWA is a promising predictor of arrhythmic events in NYHA class II CHF patients.     

Keratoconus staging: a computer-assisted ultrabiomicroscopic method compared with videokeratographic analysis

PURPOSE: The aim of this study was to introduce a new paradigm for keratoconus assessment, the keratoconus index (KI), generated from the ratio of peripheral corneal thickness (PCT) to the thinnest corneal thickness (TCT), and calculated by a computer-assisted procedure after ultrabiomicroscope (UBM) examination. Then we compared KI and the keratoconus severity index (KSI), obtained by videokeratography in patients with different stages of keratoconus. METHODS: We studied 60 eyes with different forms of keratoconus using the TMS-3 autotopographer, provided with a keratoconus screening program (using Smolek-Klyce methods) and the commercial version of the ultrasound biomicroscope (Paradigm UBM Plus Model P45) equipped with a 50-MHz probe, which was provided with our computer-assisted program. The proportion test Z and the correlation coefficient R were applied to the outcomes. RESULTS: The keratoconus severity index, KSI, obtained by color-coded videokeratographic maps, was in the range 95% to 32% (mean 52.22%). By means of UBM examination, we obtained 60 images and found values of TCT 0.278-0.592 mm and PCT 0.475-0.704 mm. Applying the computer-assisted method, we obtained values for KI of 1.112-2.159 (mean 1.428). CONCLUSIONS: KI is correlated as well as KSI with the severity of the keratoconus (R = 0.76, P < 0.0001). It can be used as a similar parameter to measure the evolution of the disease, on the basis of corneal thickness rather than the curvature.     

BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology

Here we show that in myasthenic thymus several cell types, including thymic epithelial cells (TEC) and immune cells, were the source and the target of the neurotrophic factor brain-derived growth factor (BDNF). Interestingly, many actively proliferating medullary thymocytes expressed the receptor TrkB in vivo in involuted thymus, while this population was lost in hyperplastic or neoplastic thymuses. Furthermore, in hyperplastic thymuses the robust coordinated expression of BDNF in the germinal centers together with the receptor p75NTR on all proliferating B cells strongly suggests that this factor regulates germinal center reaction. Finally, all TEC dying of apoptosis expressed BDNF receptors, indicating that this neurotrophin is involved in TEC turnover. In thymomas both BDNF production and receptor expression in TEC were strongly hindered. This may represent an attempt of tumour escape from cell death.     

Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease

This study defined the clinical features and assessed the prognosis of 47 patients (17 males, 30 females, median age 63 years) with primary nodal marginal zone B-cell lymphoma. Forty-five per cent had stage IV disease. Hepatitis C virus serology was positive in 24%. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 33% were classified as low-risk, 34% as intermediate-risk, and 33% as high-risk. The 5-year overall survival (OS) was 69%. In univariate analysis worse OS was associated with: FLIPI (P = 0.02), age > 60 years (P = 0.05) and raised lactate dehydrogenase (P = 0.05). In multivariate analysis, only FLIPI predicted a worse OS (P = 0.02).     

Optic disc drusen, angioid streaks, and mottled fundus in various combinations in a Sicilian family

BACKGROUND: We describe a Sicilian family in which optic disc drusen, angioid streaks, and mottled fundus--without dermatological signs of pseudoxanthoma elasticum (PXE)--are present in various combinations and segregate as an autosomal dominant trait. Since these ocular manifestations can be part of the clinical signs of PXE, we examined the possible involvement of a mutation in the ABCC6 gene, which is known to be responsible for PXE. METHODS: Linkage analysis was performed with both intragenic and flanking markers. We used marker D16B9722 and a single-nucleotide polymorphism located in exon 15 of the ABCC6 gene. LOD score values were calculated on the assumption of a gene frequency of 0.0001 and both complete penetrance and reduced penetrance (90%), with theta values between 0.0 and 0.4. RESULTS: LOD score values excluded the involvement of the ABCC6 gene. CONCLUSIONS: The dominant transmission of optic disc drusen, mottled fundus, and angioid streaks in this family is not due to alterations in the ABCC6 gene.