Barrett's oesophagus: long-term follow-up after complete ablation with argon plasma coagulation and the factors that determine its recurrence.

BACKGROUND: Argon plasma coagulation seems to be a promising technique for ablation of Barrett's oesophagus, yet few long-term efficacy data are available. AIM: To report on a long-term follow-up and the factors that determine the recurrence of intestinal metaplasia in a cohort of patients with non dysplastic, intestinal type Barrett's oesophagus, after complete ablation of the metaplastic mucosa with argon plasma coagulation. METHODS: Ninety-six patients underwent endoscopic argon plasma coagulation with adequate acid suppression obtained through a continuous omeprazole therapy (50 patients) or through laparoscopic fundoplication (46 patients). Complete ablation was achieved in 94 patients who underwent follow-up. Endoscopic and histological examinations were performed every 12 months. RESULTS: The median follow-up of the patients was 36 months (range 18-98). A recurrence of intestinal metaplasia was found in 17 patients (18%), with an annual recurrence rate of 6.1%. Neither dysplasia, nor adenocarcinoma were found during the follow-up. Through the use of logistic regression analysis, previous laparoscopic fundoplication was associated with a reduced recurrence rate of intestinal metaplasia (odds ratio 0.30, 95% confidence interval 0.10-0.93). CONCLUSIONS: The long-term recurrence of intestinal type Barrett's oesophagus was low after complete ablation with argon plasma coagulation. The control of oesophageal acidity acid exposure with laparoscopic fundoplication seems to reduce the recurrence rate.

First recovery of A/equine/Fontainebleau/1/79 influenza viruses in Italy.

In Italy epizootics of equine influenza often occur, but no virus isolation has been reported since 1971. This paper describes the antigenic and biochemical characterization of two equine influenza viruses isolated in Italy from 1985 to 1989. The virus isolates were shown to differ antigenically from earlier strains of the same subtype, A/equine/Miami/1/63 (H3N8). Monoclonal antibody analysis showed that the haemagglutinins of these strains were serologically indistinguishable from A/equine/Fontainebleau/1/79, a variant of A/equine/Miami, never isolated in Italy before. One of the two virus isolates was obtained from a horse immunized with a bivalent inactivated influenza vaccine, not containing A/equine/Fontainebleau/79 antigens. The vaccine failure underlines the importance of antigenic relatedness between currently circulating viruses and vaccine strains. Therefore, to improve the protection afforded by equine immunization, the vaccine composition should be decided according to the results of a virological surveillance activity, systematically conducted among horses.

Immunohistochemical characterisation of the lymph node reaction in pig post-weaning multisystemic wasting syndrome (PMWS).

The superficial inguinal lymph nodes of 10 piglets which had died spontaneously of post-weaning multisystemic wasting syndrome (PMWS), in which the porcine circovirus type II (PCV-II) genome was revealed by PCR, were submitted to immunohistochemical investigation for CD4, CD8, IgM, MAC387, S-100 protein, vimentin and F-VIII-RA and compared with three normal cases. The lymph node reaction was graded as initial, intermediate and end stage according to histological criteria. In the initial and intermediate stages, absence of follicles and depletion of lymphocytes were evident. Associated with this was a reduction in numbers of interfollicular dendritic cells and interdigitating cells and a reduction/absence of B cells and mainly CD4+ T lymphocytes. In the end stage the reduced expression of high endothelial venules and the prevalence of the stromal component of the lymph node was prominent, as well as the above changes. It is concluded that more than one mechanism is involved in the immunosuppressive ability of PCV-II: reduction of the antigen presenting ability and reduction of B cells and CD4+ T cell function.

Endoscopic ablation of Barrett's esophagus using argon plasma coagulation (APC) following surgical laparoscopic fundoplication.

BACKGROUND: Barrett's esopagus (BE) is considered a risk factor for the development of esophageal carcinoma. Recently, partial restoration of squamous mucosa after ablation of BE with endoscopic techniques has been described. METHODS: From November 1996 to November 1999, 23 patients with histologically proven BE have been treated by endoscopic argon plasma coagulation (APC) following suppression of gastro-esophageal reflux by laparoscopic fundoplication. Histological follow-up after completed ablation ranged from 16 to 45 months (mean, 31.9 months). RESULTS: Histologically, complete squamous reepithelialization was observed in 20/23 patients, whereas a regrowth of a mixed squamous and gastric type mucosa was observed in 1 patient. Small islands of intestinal metaplasia were observed under the neosquamous epithelium in two patients (9%) during follow-up. CONCLUSION: The success rate of APC ablation following laparoscopic antireflux surgery in our series may be as high as 91%. Nevertheless, small islands of intestinal metaplasia under the new squamous epithelium may persist in some patients. In these circumstances, the authors recommend that endoscopic ablation of BE should be confined to controlled clinical trials.

Ultrastructural study of experimental myocarditis induced by cardiovirus (EMCV-M) in swine.

Eight 6-week-old piglets were inoculated with a strain of encephalomyocarditis virus (EMCV) isolated from an outbreak which occurred naturally in the Po Valley in 1988. Two non-infected animals, kept in the same cage, were used as controls. Out of the eight inoculated piglets, two died and two were suppressed on the 2nd post infection day (PID), the four remaining were killed on the 5th, 7th, 11th and 15th PIDs. Control animals were killed at the end of the experiment. The pathogenesis of myocarditis has been studied using routine methods (Alcian-PAS, Masson's trichrome, Gomori's for reticulin and Mallory's stain), histochemical techniques (ATPase and NADH-TR reactions) and ultrastructural observations (TEM). All the inoculated piglets showed macro and/or microscopic lesions of lymphocytic myocarditis, only in one case associated with fibrinous exudation. One control piglet also showed myocarditic lesions, probably due to a contact infection. An early myocardial fibrosis was already present on the 5th PID. Ultrastructurally the cardiac muscle cells showed severe myofibrillar losses and other regressive alterations. Only on the 15th PID did we observe calcification of the degenerating myocytes, while ultrastructurally we detected needle-like calcium deposits in the mitochondria from the 5th PID. From the 5th PID in the areas of myocarditis the myocytes showed a reduction and/or absence of ATPase and NADH-TR reactions. On TEM, one or more aggregates of viral particles in crystalline array were detected in the cytoplasm of many endothelial cells.

[Wilson's disease: physiopathology, therapeutic approach and case report]. / Morbo di Wilson. Fisiopatologia, approccio terapeutico e contributo alla casistica.

Wilson's disease is an hereditary recessive autosomal disorder which affects around five people per million inhabitants. The primary defect is localized in the liver and the disease is manifested by the accumulation of copper in tissues. The diminution of ceruloplasmin, which until a few years ago was mistakenly thought to be the pathogenetic cause of Wilson's disease, is an epiphenomenon of the underlying metabolic defect characterized by defective copper biliary excretion. There are four stages in the natural history of the disease: 1) an asymptomatic stage of hepatic copper accumulation; 2) dismission and redistribution of copper leading to hepatocellular necrosis and hemolysis; 3) extrahepatic accumulation of copper leading to the onset of cirrhosis and neurological damage; 4) stage of homeostasis following treatment but with possible irreversible neurological damage. Treatment of Wilson's disease takes the form of pharmacological, dietary and surgical therapy. Through the formation of copper and protein metal complexes D-penicillamine impoverishes copper deposits causing the reduction or disappearance of hepatic and neurological symptoms; a small percentage of patients treated develops a nephrotic syndrome requiring the compulsory suspension of the drug. In this case a valid alternative is triethylenetetramine dichlorohydrate (TETA) which provokes increased blood copper during copper diuresis. The response to pharmacological treatment is better the earlier treatment is started and the more regular its administration. Dietary intake of copper must be reduced in parallel avoiding foods with a high copper content. Liver transplant obviously leads to the "resolution" of the underlying metabolic problem in patients who develop fulminating hepatitis with hypercupremia and hemolysis and, of course, in cases of uncompensated cirrhosis which do not respond to chelating therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic reassortment between avian and human influenza A viruses in Italian pigs.

Pandemic strains of influenza A virus arise by genetic reassortment between avian and human viruses. To examine the possibility that pigs serve as "mixing vessels" for such reassortment events (Scholtissek et al., Virology 147, 287-294, 1985), we phylogenetically analyzed the internal protein genes of classic H1N1, avian-like H1N1, and human-like H3N2 viruses circulating among Italian pigs. The results show that human-like H3N2 strains isolated from 1985 to 1989 contained the internal protein genes of avian-like H1N1 viruses, whereas those isolated in 1977 and 1983 did not. Thus, at some time between 1983 and 1985, genetic reassortment took place between avian- and human-like viruses in Italian pigs. This study provides the first evidence supporting genetic reassortment between human and avian viruses in a natural swine environment.

Human influenza A viruses in pigs: isolation of a H3N2 strain antigenically related to A/England/42/72 and evidence for continuous circulation of human viruses in the pig population.

An influenza virus strain isolated in Northern Italy in 1977 was identified as belonging to the H3N2 subtype (A/swine/Italy/1850/77). A close antigenic relationship to the human strain A/England/42/72 was demonstrated. Serologic surveys of 548 pig sera from 53 farms in two provinces in Northern Italy demonstrated the existence of antibodies to the swine/Italy/1850/77 strain and to A/Hong Kong/1/68, A/Victoria/3/75 and H 1 N 1 (Hsw 1 N 1) strains in the pig population.

Detection of two antigenic subpopulations of A(H1N1) influenza viruses from pigs: antigenic drift or interspecies transmission?

Serological analysis of a group of 63 influenza H1N1 viruses isolated from pigs in Italy in the period 1976-1988 revealed the presence of two distinct antigenic subpopulations: some viruses possessed a haemagglutinin indistinguishable from that of viruses typically associated with pigs, i.e., A/New Jersey/8/76 (H1N1), whereas others showed a close antigenic relatedness with the haemagglutinin of avian-like H1 viruses. These findings represent further evidence that influenza A viruses from avian species may be transmitted to mammals. The surface and internal proteins of some of these viruses were also analyzed biochemically to evaluate the molecular relatedness among viruses circulating in non-human hosts.

Antigenic and sequence analysis of H3 influenza virus haemagglutinins from pigs in Italy.

To investigate the possible mechanism of maintenance of old human influenza A (H3N2) viruses in pigs, the haemagglutinins (HAs) of seven isolates from swine were studied by analysis of nucleotide and deduced primary amino acid sequences, as well as reactivity of the HA molecule to chicken antisera and monoclonal antibodies. The swine HAs were closely similar to the HA of the A/Victoria/3/75 human variant as regards antigenic and molecular characteristics. These findings are consistent with the hypothesis that the swine HA genes were transmitted from an early human H3 virus to pigs, where they survived with limited mutations over a period of 5 years. The sequence data were also compared with swine H3 sequences to investigate genetic relationships between the H3 genes from swine viruses isolated in different geographical areas. An evolutionary tree, constructed from the nucleotide sequences of viruses isolated from pigs in China and in Italy, illustrated that, depending on the country of their isolation, the HA genes of swine influenza A (H3N2) viruses have different origins, e.g. human and avian, and evolved independently in different lineages. The study provides direct support for the hypothesis that pigs might serve as a 'mixing vessel' for the generation of pandemic strains of human influenza viruses.

Experimental encephalomyocarditis virus infection in pigs.

A field isolate of Encephalomyocarditis (EMC) virus was inoculated intravenously into 8 pigs. Four animals died at post inoculation day (PID) 2, the remaining being sacrificed at PID 5, 7, 11 and 15. Two control, in-contact pigs were sacrificed at PID 19. Virus was isolated from leucocytes and nasal swabs until PID 4, from rectal swabs until PID 2 and, in the pigs found dead at PID 2, from several organs. EMC virus was further isolated from brain and spleen of the pig sacrificed at PID 7. One of the 2 control pigs became infected: virus was isolated from nasal swabs at days 6 and 7 and from leucocytes at day 4 of the experiment. Serum-neutralizing (SN) antibody was detected in the injected pigs starting from PID 4; two days later, it was also revealed in the infected, in-contact control. To our knowledge, this is the first report of an experimental transmission of EMC virus infection in pigs by contact exposure.

Spontaneous release of interleukin 1 beta from human blood monocytes in thyrotoxic osteodystrophy.

Hyperthyroidism is a well documented cause of impaired bone turnover characterized by increased osteoblastic and osteoclastic activity, resulting in predominance of bone resorption and in decreased bone mass. Thyroid hormones can carry out a direct effect on osteoblasts which express specific receptors on their surface membrane; differently effect on osteoclast seems to be mediated by local factors, cytokynes released by activated osteoblasts or by bone monocytes cells. Interleukin 1 beta is the first purified cytokyne shown to have bone resorbing activity. In ten thyrotoxic female patients IL 1 beta in the cellular medium of the monocytes blood cells culture has been measured, compared to PYD/cr urinary excretion, and FT3, BGP serum levels, before and after thyrostatic treatment. Ten normal females were studied as control group. The results before treatment showed osteopenia in 20% (DEXA densitometry), increased values of FT3, BGP, IL 1 beta and PYD/cr in patients versus controls (p < 0.001). The thyrostatic therapy obtained normalization of IL 1 beta, PYD/cr, BGP, and FT3 levels. Our data demonstrate that increased thyroid hormone levels in vivo are associated to increased secretion of monocytes cytokynes in vitro and suggest that alterations in local production of bone acting cytokyne may underlie to thyrotoxic osteodistrophy.

Alcohol abstinence does not offset the strong negative effect of lifetime alcohol consumption on the outcome of interferon therapy.

Heavy alcohol consumption has been reported to negatively affect the outcome of interferon therapy. We studied the impact of lifetime alcohol consumption in patients with chronic hepatitis C treated with interferon after 6 months of alcohol withdrawal. Alcohol intake was measured when patients with chronic hepatitis C were referred to us for the first time, and from that moment complete abstinence was recommended. After 6 months of abstinence, 150 patients with persistent elevated serum alanine aminotransferase (ALT) have been treated with interferon (IFN)-alpha, 3 or 6 microU three times per week for 12 months. Univariate and multivariate analysis were performed to identify the predictors of treatment response. Carbohydrate-deficient transferrin was employed to assess alcoholic abstinence. The sustained response rate felt from 33% in nondrinkers to 20% of mild-drinkers and to only 9% in heavy drinkers. Drinker patients showed a relapse rate twice as high as that of nondrinkers. According to the multivariate analysis, the strongest independent predictors of nonresponse were genotype 1b infection, age of the patients and their lifetime alcohol intake. Carbohydrate-deficient transferrin detected at baseline, at 3 months of therapy and at the end of follow-up gave a positive result only in eight determinations (1.77%), confirming the compliance of patients to our recommendation of alcohol abstinence. Lifetime alcohol consumption has a strong negative effect on the outcome of interferon treatment, mainly in heavy drinkers. A 6-month period of abstinence may not be sufficient to offset this negative effect on treatment outcome.

Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients.

BACKGROUND/AIMS: To evaluate the efficacy and tolerance of amantadine in combination with interferon in the treatment of chronic hepatitis C. METHODS: Multi-centre trial including 180 chronic hepatitis C patients without cirrhosis, randomly enrolled to receive interferon 6 MU every other day for 6 months followed by 3 MU for further 6 months (group A, 90 patients), or the same schedule plus amantadine 200 mg/day (group B, 90 patients). Primary end-point was a sustained virological and biochemical response, secondary end-points were on-treatment (third month) and end-of-treatment response rates. RESULTS: The two groups had similar demographic, biochemical and virological characteristics. A sustained response after 6 months follow-up was observed in 17% of group A and 24% of group B patients (P not significant), an end-of-treatment response was observed in 37% in group A and 47% in group B (P not significant), an on-treatment response was observed in 46% in group A and 61% in group B patients (P < 0.05). No major side effects due to amantadine administration were observed. CONCLUSIONS: Adding amantadine to interferon did not improve the sustained treatment efficacy. However, the rate of early response at the third month of therapy was significantly higher in the combination therapy group.