Mortality study of asbestos cement workers

The present study describes cause-specific mortality of asbestos cement workers in the Emilia Romagna region of Italy. The cohort included workers in ten factories, most of which started operating between 1955 and 1965. Asbestos, mainly chrysotile, constituted 10%–20% of the dry component of the mixture. Crocidolite range between 5% and 50% of total asbestos. Asbestos concentrations up to 44 ff/cc were reported prior to 1975, while in recent years they have usually been below 0–1 ff/cc. The cohort included 3341 workers who had at some time been employed in the ten factories under study. Their mortality experience was compared with that of the population resident in Emilia Romagna. Vital status was ascertained at 1989. Seventy-three subjects were lost to followup (2.2%). Mortality from all causes and from all types of cancer was increased in the cohort. Malignant neoplasms of the respiratory tract showed a significant increase (SMR: 134; 90% confidence interval: 101–175; 40 observed) due to lung cancer (SMR: 124; 90% confidence interval: 91–166; 33 observed) and neoplasms of the pleura, mediastinum, and other parts of the respiratory tract (SMR: 602; 90% confidence interval 237–1267; 5 observed). The discrepancy between observed and expected mortality mainly concerned subjects with at least 20 years of employment in the factories. Five more cases of histologically confirmed mesothelioma occurred after the end of follow-up.     

Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome

Human herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The virus has been found in the cerebrospinal fluid of many children with aseptic meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA detection in cord blood specimens of apparently healthy newborns and in fetuses following spontaneous abortions. A patient is described with early neonatal afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed by repeated detection of viral genome by polymerase chain reaction (PCR) in cerebrospinal fluid in the first days of life. At follow-up, magnetic resonance imaging (MRI) studies disclosed hyperintensities in the periventricular white matter and basal ganglia, associated with cerebral atrophy. Further follow-up at 18 months revealed poor neurological outcome with mild neurodevelopmental retardation, strabismus and hypertonia of legs. This report provides evidence of neurological involvement after HHV 6 vertical transmission, and the association with neurological sequelae.     

Performance of an in-house genotypic antiretroviral resistance assay in patients pretreated with multiple human immunodeficiency virus type 1 protease and reverse transcriptase inhibitors.

An in-house genotypic antiretroviral resistance assay was evaluated by testing 32 plasma samples obtained from heavily pretreated human immunodeficiency virus type 1 (HIV-1)-infected patients failing multiple antiretroviral regimens. The same samples were also sent to Virco Laboratories for genotypic (VircoGEN) and phenotypic (Antivirogram) resistance analysis. Sequencing results obtained by in-house (HG) and VircoGEN (VG) genotyping were concordant for 387 of 400 (96.75%) drug resistance mutations. Genotype-based prediction of drug susceptibility for 13 currently licensed antiretroviral compounds were in agreement in 336 (80.78%) cases, partially concordant in 73 (17.54%) cases and discordant in only seven (1.68%) cases. VG indicated 'possible resistance' twice as much as HG. When genotype interpretation was compared with the Antivirogram phenotypic data, there were 27 (6.49%) and 23 (5.52%) wrong calls by HG and by VG, respectively. Both assays were more sensitive in detecting drug resistance than drug susceptibility (94.61 vs. 65.19% for HG, 80.84 vs. 56.91% for VG) and more specific in detecting drug susceptibility than drug resistance (93.62 vs. 73.49% for HG, 93.62 vs. 80.32% for VG). Rule-based algorithms can reliably interpret genotypic data obtained from most heavily pretreated patients. However, occasional genotypic patterns may be erroneously interpreted without resistance phenotyping.     

Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis

BACKGROUND: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease. AIMS: To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. PATIENTS AND METHODS: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture. RESULTS: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P < 0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance. CONCLUSIONS: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.     

Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy

Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer.     

Mediastinal large B-cell lymphoma: clinical and immunohistological findings in 18 patients treated with different third-generation regimens

We report on the immunophenotype, clinical findings and response to aggressive chemotherapy of 18 patients with mediastinal large B-cell lymphoma (MLCL). Cases were collected from a series of 286 high-grade non-Hodgkin's lymphomas (HG-NHL) which, in the period September 1988 to August 1991, were enrolled in a prospective multicentre trial designed to compare the MACOP-B and F-MACHOP regimens. Immunostaining on frozen sections revealed a previously unrecognized phenotype, i.e. co-expression of B-cell (CD19, CD20, CD22, Ig-associated dimer) and activation-associated antigens (CD30 and CDw70) in about 60% of MLCL cases; in contrast, the activation-associated antigens CD25 and Ki-27 (unclustered) were consistently negative. This peculiar phenotype may reflect a derivation of the tumour from a subset of thymic activated B cells. Clinically, the patients (median age 31 years; F/M ratio 2.6) presented with bulky mediastinal mass (72%) associated with mediastinal syndrome in >50% cases; disease was stage IIA in most cases. All 18 patients received aggressive chemotherapy (F-MACHOP 11; MACOP-B 7). Complete response (CR) was achieved in 57.1% of cases treated with MACOP-B. In contrast, the response of the 11 MLCL treated with F-MACHOP was poor (CR 18.2%) as compared to that of the 135 HG-NHL treated with the same regimen during the trial (CR 69.6%). This difference was still statistically significant after adjusting for negative prognostic factors (mediastinal mass > 10 cm plus increased LDH) and suggests that F-MACHOP might not be the most appropriate regimen for this kind of lymphoma.     

Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long‐term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4‐Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft‐mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3‐dioxigenase were observed only in CTLA4‐Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long‐term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.