Disappearance of diabetes mellitus after conversion from FK 506 to Neoral in two liver transplanted patients.
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Administration, Oral↗
Biomedical subjects
G C Actis
Publications and source records attributed to G C Actis.
[Cyclosporin for steroid refractory ulcerative colitis. Results of a study conducted at Turin General Hospital between 1990 and 1997].
BACKGROUND: Four every ten patients receiving high-dose parenteral steroids for severe ulcerative colitis fail and may have their colon removed. Intravenous followed by oral cyclosporin has been shown to initially rescue approx. 70% of these non-responder patients, but dosages and long term-efficacy are still debated. We reviewed the clinical outcomes of patients treated with cyclosporin for refractory ulcerative colitis at our Center in the last 7 years. METHODS: Fifty-four patients destined to colectomy because of refractory ulcerative colitis (previous failure to respond to 7 days of 1 mg/kg/day steroids) were enrolled to initially receive a two-week continuous infusion of 2 mg/kg/day cyclosporin. Responders (showing at least a 50% reduction of activity) were meant to be treated with oral drug at 6-8 mg/kg/day for 6 months with the maintenance of remission and the spare of steroids being the end-points. RESULTS: Data are available for 47 patients followed-up for a minimum of 6 months up to 6 years. Of these 47, 14 did not respond to the intravenous drug and were submitted to surgery; of the remaining 33 responders (70%) entering the oral 6-month phase, 17 relapsed before end or on leaving the drug and were considered as failures. The remaining 16 (34% of the 47) left cyclosporin in remission and in need of less than 20 mg steroids daily. Of them, 12 avoided colectomy in a follow-up of 6 months-6 years. CONCLUSIONS: Intravenous cyclosporin may be rapidly effective in 7 every 10 patients whose acute ulcerative colitis fails a full-dose steroid course. However, only 3 of the initial 10 may maintain remission over a 6-month oral course. Further efforts should concentrate on improving the long term efficacy of cyclosporin.
English Abstract↗
Recurrence of hepatitis B in liver transplants treated with antiviral therapy.
BACKGROUND AND AIMS: In patients with terminal Hepatitis B Virus-related liver diseases, liver transplantation carries a consistent risk of Hepatitis B Virus recrudescence in the graft. In the attempt to reduce the reinfection rate with antiviral therapy, we studied a total of 16 viraemic patients. PATIENTS AND METHODS: Twelve patients received Ganciclovir, starting 4-67 days (mean 25 days) before transplantation and prolonged for 10 days after transplantation; four patients were treated with Lactosaminated Arabinoside-Monophosphate 6 hours before surgery and prolonged for 28 days after surgery. All received hepatitis B immunoglobulins. RESULTS: At transplantation, HBV-DNA had decreased to about 10(4) virus/ml (as assessed by the polymerase chain reaction assay) in 10 of the 12 patients treated with Ganciclovir. Of these patients, 4 died perioperatively from causes unrelated to Hepatitis B Virus reinfection. Of the eight survivors, only the patient who maintained a titre of 10(6) virus/ml at the time of transplantation developed viral recurrence 4 months after surgery. Before transplantation, 2 of the patients treated with Lactosaminated Arabinoside-Monophosphate had a viraemic load of 10(6) and 2 of 10(4) virus/ml. In all cases, viraemia became undetectable at the end of therapy. None died and Hepatitis B Virus recurred 2 months after transplantation in one. The overall rate of Hepatitis B Virus recurrence was 16.6%. The recurrence rate decreased to 9% in patients in whom the viraemic load decreased to around 10(4) virus/ml following treatment, compared to an overall recurrence rate of 50% in our historical series of patients transplanted for Hepatitis B Virus-related cirrhosis. CONCLUSION: Antiviral therapy was effective in decreasing the risk of Hepatitis B Virus reinfection of the liver graft by decreasing the viral load before surgery.
Adult↗
Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.
OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.
Adult↗
Recurrent necroinflammatory disease of multiple organs and colon. Systemic presentation of inflammatory bowel disease or gut involvement during systemic disorder.
A 30-year-old man with a recurrent febrile illness resembling infection is described. Because he presented with an acute abdomen, he underwent a laparotomy, which showed the paraaortic and mesenteric lymph nodes to be changed into an abscess-like granulomatous tissue made up of necrotized granulocytes. During further flare-ups, the disease affected the spleen, skin, colon, peripheral nerve, and muscle. Histology on the biopsy materials of both the skin and colon, and on the surgically removed spleen showed the same invading pathologic tissue. Exhaustive investigation disclosed no pathogen, and the flare-ups responded repeatedly to high-dose steroids. This patient's picture has recently been defined as a syndrome of chronic granulomatosis based on several published cases. As a distinctive feature, in our patient the granulomas affected also the colon. For the present, and for another previously described similar case we analyzed the factors that might permit the differential diagnosis between the above-mentioned granulomatous syndrome and Crohn's colitis.
Adult↗
Effect of patient characteristics on hospital costs for cirrhosis: implications for the disease-related group (DRG) reimbursement system.
The Prospective Payment System uses Diagnosis-Related Groups (DRG) as a reimbursement system. DRG 202 is a disease-related group including liver cirrhosis as a whole. Patients referring to the inpatient unit complain of variable severity and complications of cirrhosis, possibly implying different expenditure of resources. Aim of the investigation was to identify factors affecting cost variability in patients with cirrhosis. A total of 73 consecutive, DRG 202-assigned, cirrhotic patients classified according to demographic and clinical variables were evaluated for length and costs of hospitalization calculated on a full-cost basis. Mean length of hospitalization was 10.2 +/- 7 days. Mean cost of hospitalization was Lit. 4.348.000 +/- 2.718.000. Medical, nursing, diagnostic, drug and general charges accounted for 13%, 29%, 37%, 5% and 16% of the cost, respectively. Child-Pugh score significantly correlated with drug consumption (p < 0.005), length (p < 0.01) and costs (p < 0.001) of hospitalization, but not with cost per day. Age, sex, admission status, referral reason, associated diseases and liver transplant susceptibility did not correlate with duration and costs of hospitalization. Disease severity significantly modifies costs of hospital admission in cirrhotic patients mostly on account of longer hospital stay. Surrogate indexes of disease severity, derived from ISTAT/DRG records, cannot identify patients consuming larger resources. In liver cirrhosis, the DRG system could be improved by introducing parameters, such as Child-Pugh score, directly taking into account disease severity.
Adolescent↗
Recurrent Sweet's syndrome in reactivated Crohn's disease.
A 50-year-old woman developed an acute febrile dermatosis on two occasions concurrently with recurrent Crohn's disease of the colon. Based on the presence of painful erythematous plaques on both hands and forearms, on the leukocytosis with excess bands in peripheral blood, on the histology showing dermal infiltration by mature granulocytes, and on the prompt response to steroids, the diagnosis was made of Sweet's syndrome associated with Crohn's disease. Sweet's syndrome is thought to be a hypersensitivity reaction that leads to parainflammatory (e.g., infections, autoimmune disorders, vaccinations) and paraneoplastic (myeloproliferative disorders, solid malignancy) associations, with a frequency of 10-30%. The association of Sweet's syndrome with Crohn's disease is very rare, but the gastroenterologist should readily differentiate it; it is important to be aware that such patients may have a nonspecific elevated activity index owing to the underlying dermatosis.
Biopsy↗
Hepatotoxicity of intravenous cyclosporin A in patients with acute ulcerative colitis on total parenteral nutrition.
A group of 24 patients underwent a 7-14-day course of continuously infused Cyclosporin A (2 mg.kg-1.day-1) to treat a severe attack of ulcerative colitis. In 19 of them, including eight treated with total parenteral nutrition, we retrospectively analyzed the serum aminotransferase (AST/ALT) levels at the beginning and at the end of Cyclosporin infusion. The baseline levels of AST/ALT in the group were 19.9 +/- 3.2 and 31.4 +/- 6.4; on stopping Cyclosporin infusion, they were 43 +/- 15.8 and 119 +/- 56, respectively. Six patients showed an ALT change above 1.5 times the upper limit of reference. They included five of the eight patients treated with total parenteral nutrition (62.5%). In one of six, ALT rose to 1000 U/l and was accompanied by full-blown febrile cholangitis (proven by liver biopsy). This episode was preceded by excessive accumulation of Cyclosporin in blood. The development of liver toxicity was independent of the length of Cyclosporin treatment, nor did it impair drug efficacy. Thus, in these patients total parenteral nutrition and Cyclosporin were synergistic, causing twice the frequency of liver damage (62.5%) reported for ulcerative colitis patients on total parenteral nutrition alone (37%). Total parenteral nutrition should not be used to support patients needing Cyclosporin for autoimmune disease. However, too high a dose of Cyclosporin may cause liver disease per se.
Acute Disease↗
Continuously infused cyclosporine at low dose is sufficient to avoid emergency colectomy in acute attacks of ulcerative colitis without the need for high-dose steroids.
A dosage of 4 mg/kg/day intravenous cyclosporine as an adjunct to high-dosage hydrocortisone has been recommended to avoid colectomy in acute steroid-resistant ulcerative colitis. In treating eight such patients, four of whom presented with toxic megacolon, we immediately tapered the steroid dosage and infused a lower dosage of only 2 mg/kg cyclosporine for 15 days to fit a therapeutic range of 60-240 ng/ml, as previously designed for a kidney transplant program. Seven of the eight (87.5%), including three with megacolon, went into remission and started the chronic phase of treatment; the eighth patient underwent colectomy. Of the seven, one died on day 3 of the chronic phase because of pulmonary embolism while in clinical remission, and another discontinued treatment. The other five (62.5%) remain in remission on 6 mg/kg oral cyclosporine, or have already switched from cyclosporine to azathioprine. Two episodes of reversible nephrotoxicity appeared in the chronic phase only. These results emphasize the efficacy and safety of cyclosporine in acute ulcerative colitis, but there is still a need for further dose-response and drug association relationship studies.
Acute Disease↗
[Combined treatment of colorectal polyps with diathermy and the Nd-YAG laser. Our experience].
Among colorectal polyps, those of the sessile and villous type are said to bear a high frequency cancer degeneration. While surgery is considered the cure, alternative choices are to be offered in the presence of contraindications or lack of an informed consent. We analyzed the results of the "combined therapy" that requires the use of the ND-YAG laser following the ablation of the lesion with diathermic snare. We used an EV laser 132 with double wavelength to allow the ablation of flat lesions and minimize the risk of perforation. We included 12 patients with sessile colorectal polyps. In 9/12 complete eradication was obtained over a follow-up 11 months; of the remaining 3, 2 dropped out, 1 did not respond. Owing to the small series, the relationship between the successful eradication and the size of the polyp cannot be evaluated. We conclude that the treatment of sessile colorectal polyps with this combined approach may be a promising one.
Aged↗
Treating chronic liver disease: lessons from a day hospital.
The relationship between the professional background of the physician requesting the biopsy procedure (whether non-specialist or specialist in hepatology/gastroenterology) and the subsequent decision of treatment of the patients was analyzed. Treatment was divided into two categories named arbitrarily "no therapy" (general supportive measures) or "therapy" (causal treatment based on active drugs or measures aimed at affecting the cause of the disease). Of the 204 cases of outpatient needle biopsies available for study, 157 were made by specialist request and 47 were made by a non-specialist request. Sixty-eight (43%) of the former, but only 3 (2%) of the latter had "therapy" (p = 0.0001). Also, patients in which histology showed chronic active liver disease had "therapy" more frequently (49 of 109, 44.9%) than those without chronic active liver disease (22 of 95, 23%) with p less than 0.01. However, patients with histological active chronic disease were not more frequent among specialist requests (56.6%) than among the non-specialist requests (42.5%). But among patients attended by the specialist, there were more patients (31.8%) with positive serum markers of Hepatitis B virus infection than among those sent by others (12.7%) with p less than 0.01. We conclude that at least in the premises in which this study was carried out, blind liver biopsies will lead to active treatment more often in patients treated by a specialized physician, because these patients are more likely to have a virus identified as the cause of their liver disease and consequently will receive antiviral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Chronic active hepatitis B. Interferon-activated natural killer-like cells against a hepatoma cell line transfected with the hepatitis B virus nucleic acid.
In a rapid 51Cr release assay, peripheral blood mononuclear cells from 12 healthy donors did not lyse the hepatitis B virus deoxyribonucleic-acid-transfected human hepatoma cell line 2.2.15, but under the same experimental conditions they did lyse K562 cells. Peripheral blood mononuclear cells from 10 out of 16 patients with chronic active hepatitis B exhibited cytotoxic activity against 2.2.15 cells in the presence of a relatively reduced natural killer cell activity to the K562 cell target. Enhancement of the cytotoxic activity to 2.2.15 cells was statistically significant in the group of patients being treated with leukocyte alpha-interferon. The activity was not influenced by the degree of human leukocyte antigen type matching between effector and target, and was enhanced by depletion of T-cells and by in vitro interferon treatment. These results therefore support the concept of a natural killer-like cell activated by clinical administration of interferon in chronic active hepatitis B patients. This cell effector was lytic for the virus B negative HEP-G2 cells also. However, T-cells purified from a few patients failed to lyse the HEP-G2 while lysing the 2.2.15 target, thus indicating that a preferential recognition of the virus-infected target may be exerted by certain T-lymphocyte subsets. The use of the human leukocyte antigen type defined, highly differentiated, hepatitis B virus releasing 2.2.15 cell line as target for fresh lymphocytes in this cytolytic assay did not disclose cytolytic T-cells in an obvious way. Further manipulation of this system perhaps using T-cell clones may be the next step to exploit the investigative possibilities offered by the availability of the 2.2.15 cell target.
Adult↗
Pathobiology of chronic hepatitis virus infection and hepatocellular carcinoma (HCC).
Hepatitis viruses may cause liver cancer (HCC) through an indirect mechanism inducing inflammation and cirrhosis. Only hepatitis B virus (HBV) was shown to have a direct oncogenetic potential. Hepatitis D virus (HDV) infection, superimposed on the oncogenetic background provided by chronic HBV infection, appears to provide an additional risk for HCC. Patients with florid infections from both HBV and HDV and active liver inflammation develop HCC at a significantly younger age than those infected by HBV alone or infected by hepatitis C virus (about 10 years earlier). In patients positive for serum HBV-DNA/HDV-RNA and/or IgM anti-HBc/IgM anti-HD it is mandatory to program a more frequent (thrice a year) schedule of screenings (ultrasound scan, alpha-1-phetoprotein, etc.) for prophylaxis of HCC.
Animals↗
Natural killer response to exogenous interferon in delta hepatitis: boost or depression defined within the first week of therapy.
Six patients with hepatitis B surface antigen (HBsAg)-positive chronic active liver disease and superimposed delta virus infection were followed up for changes of natural killer (NK) cell function during a 3-month course with median doses of recombinant leukocyte alpha interferon (rIFN). Careful record of the off-therapy NK function means revealed that 3 subjects were boosted, 2 were depressed, and 1 was unchanged. The NK activity patterns showed that after the start of therapy the maximal shift from the off-therapy mean was concentrated in the first week; then the trend, although confirmed, had a gentler slope on the follow-up. This indicated that the first week reflects the availability of rIFN-sensitive NK cells and characterizes the immunological competence of the patient; whilst later in follow-up, suppressive control mechanisms or loss of receptor affinity tend to blur the response. The serum levels of delta RNA dropped in the NK-boosted patients; persistently negative RNA together with clearance of intrahepatic delta antigen was demonstrated solely in that 1 patient showing 164% NK cell function increment in the first week. This study shows that paradoxical responses to exogenous rIFN are not confined to cancer patients, as indicated so far, but may appear in other subjects as well, and reflect the peculiar response of the individual; whenever an NK-dependent clearance of virus-infected cells is required, recognition of the early pattern of reactivity would be useful.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Natural killer cell function during interferon treatment of delta hepatitis.
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Antigens, Viral↗
Treatment of chronic delta hepatitis with alpha-2 recombinant interferon.
The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are the carriers of HBsAg. Spontaneous resolution of chronic HDV hepatitis has been observed rarely and therapeutic attempts with steroids or azathioprine and levamisole have been discouraging. With the advent of recombinant DNA technologies several human alpha-interferons (IFNs) have been synthesized by genetic engineering and the availability of large amounts of the drug has dramatically altered the therapeutic prospects of viral hepatitis. In view of the wide range of biological activities of IFN, including inhibition of viral nucleic acid replication, we have tested the tolerance and the efficacy of this drug in chronic HDV hepatitis. The preliminary results of this study are reported.
Adult↗
Treatment of patients with delta hepatitis using interferon.
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Hepatitis D↗
Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe.
A biotin-labeled DNA probe specific for hepatitis B virus (HBV) nucleotide sequences was hybridized in situ to liver tissue of 20 patients; 16 were chronic carriers of hepatitis B surface antigen (HBsAg) and 4 had no markers of HBV infection. HBV-DNA was also analyzed in the serum and the liver of these patients by spot and Southern blot hybridization, respectively. Liver specimens from six carriers were positive for HBV-DNA both by in situ and Southern blot hybridization; ten carriers were negative by in situ hybridization, and two of these were positive by Southern blot technique. The staining was granular, mainly cytoplasmic, limited to liver specimens containing replicative forms of HBV-DNA, and associated with detection of HBcAg in hepatocytes by immunofluorescence. The sensitivity of this technique was not sufficient to detect few copies of integrated HBV-DNA. The hybridization procedure was specific, as results were constantly negative in liver specimens of patients without markers of HBV infection, and no reaction was observed using DNA probes lacking HBV-DNA sequences. Detection of HBV-DNA by in situ hybridization, using a biotinylated probe, is a rapid, reproducible, and specific histochemical method. Currently available biotinylated probes are advantageous when absolute sensitivity is not the limiting factor, and they also facilitate studies of the cellular and subcellular distribution of HBV nucleic acids.
Autoradiography↗