Eradication of hepatitis C virus RNA after alpha-interferon therapy.
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Adult↗
Biomedical subjects
R Romeo
Publications and source records attributed to R Romeo.
Acute inflammation in foetal and adult sheep: the response to subcutaneous injection of turpentine and carrageenan.
Because of the small number of inflammatory cells found in skin wounds, it has been considered that foetal sheep are incapable of an adequate inflammatory response. The present study shows that subcutaneous injection of turpentine or carrageenan into foetal sheep consistently excites a severe cellular inflammatory reaction. At 75 days gestation the inflammatory cells are all macrophages. As the foetus develops, polymorphs play an increasing role in the early response to turpentine. By 120 days inflammatory cells are almost all polymorphs as in adult sheep. However the response to carrageenan remains macrophage in type. At all stages of gestation the acute cellular response is followed by development of scar tissue, more pronounced with turpentine than carrageenan. Any proposed intrauterine surgery must allow for the pronounced and prolonged inflammatory response and scar tissue formation caused by persistent inflammatory stimuli in foetal animals.
Animals↗
Effects of cold storage on the subsequent structure and function of microvenous autografts.
A study was undertaken to evaluate the structure and patency of cold stored rabbit femoral veins following reinsertion as autografts for 3 weeks. The periods of cold ischaemic storage were 1, 2, 3 and 4 weeks (n = 10/gp) and 6 and 10 weeks (n = 6/gp). All rabbits were subject to 3 operations under general anaesthesia. In the first, a 4 cm segment of left femoral vein was harvested and stored at 4 degrees C for the specified ischaemic interval. Following storage the graft was microsurgically reinserted at a second operation into the right femoral artery of the donor rabbit. Three weeks later, graft patency was assessed by surgical exploration and the graft processed for light and electron microscopy. Patency rates remained over 80% after 3 weeks in all groups except the 10 week storage group where only 1 of 6 (17%) grafts was patent at 3 weeks. In all groups normal vein structure was absent, being replaced by thin walled necrotic areas or by neointimal ingrowth. The excellent patency rates achieved indicate it is possible to cold preserve extra lengths of vein grafts harvested at initial operation for reuse should regrafting be necessary.
Animals↗
A multicenter randomized controlled trial of recombinant interferon-alpha 2b in patients with acute transfusion-associated hepatitis C.
To assess whether interferon-alpha might prevent non-A, non-B hepatitis from becoming chronic, 45 consecutive patients with transfusion-associated hepatitis were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients (22 with HCV) were given 3 MU of recombinant interferon-alpha 2b three times a week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological parameters were monitored at regular intervals during an 18-mo follow-up. At the end of the 3-mo therapy, 16 (73%) patients with hepatitis C had normal serum ALT activity, compared with 7 (44%) who were not treated (NS). Fifty-three percent of the treated patients and none of the untreated patients had normal ALT levels and no HCV RNA (p = 0.0087). At the end of the 18-mo follow-up, 13 (59%) treated patients had normal ALT levels, compared with 6 (37%) untreated controls (NS). Thirty-nine percent had normal ALT and no HCV RNA, compared with none of the controls (p = 0.035). Four patients (22%) had had sustained complete responses to interferon, defined as normal ALT levels and no HCV RNA at the end of the 3-mo treatment period and the 18-mo follow-up period. All seven patients with non-A, non-B, non-C hepatitis, treated and untreated, recovered uneventfully from hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
The functional and structural effects of hypothermic storage on ischaemic arterial grafts.
The effects of hypothermic ischaemia on blood vessels are unknown. This study aimed to determine the 3 week patency rate and the pathology of 9 experimental groups of hypothermically stored ischaemic arteries and one control group in a rabbit femoral artery model. Ischaemia times were 0 h, 24 h, 1, 2, 4, 6, 8 and 10 weeks (Groups 1-8). Patency was over 80% in all groups after 3 weeks reinsertion. Following reinsertion control grafts maintained normal arterial structure, but cellular degeneration had occurred in all ischaemic grafts and appeared complete after 4 weeks ischaemia. The graft connective tissue framework frequently remained intact. Repair was evident in central graft regions after 2 weeks ischaemia and 3 weeks reinsertion, but occurred only adjacent to the anastomosis in 4-10 week ischaemic arteries. Four week ischaemic arteries (Groups 9 and 10) reinserted for 6 and 12 weeks respectively exhibited near complete repair but patency dropped to 60% in the 12 week group.
Animals↗
Hepatitis C virus RNA in anti-HCV positive hemodialyzed patients: significance and therapeutic implications.
About 25% of French hemodialysis patients have antibodies against the hepatitis C virus (HCV), which may reflect either past or active HCV infection. It is important to evaluate the significance of these antibodies, as most hemodialysis patients are candidates for kidney transplantation and have normal transaminase activities despite biopsy-proven chronic hepatitis. We prospectively assayed HCV viremia with the nested polymerase chain reaction in 61 patients on maintenance hemodialysis who had anti-HCV antibodies detectable in second generation tests (ELISA2 or RIBA2). HCV RNA was repeatedly detected in the serum of 52 (85.2%) patients. Liver biopsy, which was performed in 17 cases, revealed chronic hepatitis in 16 cases (including 2 of cirrhosis) and steatosis in one. Hypertransaminasemia was observed in only 31.3% and 30.8% of patients with chronic hepatitis and HCV viremia, respectively. Anti-HCV antibodies are frequently associated with HCV viremia, resulting usually in chronic hepatitis, although hypertransaminasemia is uncommon. HCV viremia reflects both post-transfusional and community-acquired HCV infection. These findings suggest a need for liver biopsy and antiviral treatment before kidney transplantation. The isolation of anti-HCV positive subjects in the dialysis setting should be evaluated to reduce patient-to-patient transmission of HCV.
Base Sequence↗
Hepatitis C virus RNA in serum of blood donors with or without elevated transaminase levels.
The pattern of hepatitis C virus (HCV) viremia in blood donors who are positive for antibody to HCV (anti-HCV) according to the level of transaminase activity is unclear. A polymerase chain reaction-based HCV RNA detection method was used to study two clearly defined groups of anti-HCV-positive blood donors with repeatedly normal (n = 27) and elevated (n = 17) alanine aminotransferase (ALT) levels. HCV RNA was detected in only 4 of 27 blood donors with normal ALT values and 15 of 17 with elevated ALT values. These results indicate that anti-HCV-positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases. Polymerase chain reaction should be useful in the surveillance of anti-HCV-positive blood donors with normal ALT levels, by identifying those who might benefit from further investigation and treatment.
Alanine Transaminase↗
A multicentre randomized clinical trial of recombinant alpha-2a interferon therapy in patients with chronic hepatitis B.
Fifty six previously untreated patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than 1 year with detectable serum levels of hepatitis B virus DNA (HBV-DNA) and a liver biopsy performed in the 6 months before enrollment, were randomized to receive recombinant alpha-2a interferon at doses of 3MU intramuscolarly thrice weekly for 6 months or no treatment. Treated and untreated patients had similar clinical characteristics in terms of ALT elevation, HBV-DNA levels, and degree of liver damage. Twenty one had chronic persistent or lobular hepatitis; 28 had chronic active hepatitis and 7 had cirrhosis. The percentages of patients who lost HBeAg at month 6, 12 and 18 were 22%, 32% and 38% in the treated group, and 16%, 20% and 37% in the controls (differences = ns). At the same time intervals, HBV-DNA detected by dot spot hybridization, cleared off in 39%, 39% and 41% of treated patients as compared to 16%, 36% and 37% of controls (difference = p < 0.05 for HBV-DNA clearance at month 6). At the end of follow-up, 12 treated patients (41%, including 8 antiHBe seroconverters) and 10 untreated controls (42%, including 6 anti-HBe seroconverters) had normal aminotransferase levels. Conclusions show that in patients with chronic hepatitis B, clearance of HBV-DNA but not of HBeAg was hastened by a 6-month treatment with low doses of recombinant alpha-2a interferon.
Adolescent↗
Suboptimal response to hepatitis B vaccine in drug users.
Fifty-five drug users institutionalized in a community for drug detoxification were vaccinated against hepatitis B virus (HBV) with a recombinant yeast-derived vaccine (Engerix B, Smith Kline Biologicals, Belgium). At 0, 1, and 6 months, 20 micrograms of vaccine was given in the deltoid to these patients, of whom 17 had no serum HBV markers, 15 had only the antibody to core antigen (anti-HBc), and 23 had anti-HBc and antibody to the surface antigen (anti-HBs) values lower than the allegedly "protective" value of 10 mIU/mL. Forty-one healthy controls were vaccinated in parallel. At month 7 (ie, 1 month after the third dose of vaccine), in 76% (13/17) of drug users with no HBV markers, 6% (1/15) of those with isolated anti-HBc, and 69% (16/23) of those with anti-HBc and nonprotective anti-HBs, protective anti-HBs titers (greater than or equal to 10 mIU/mL) developed, compared with 97% (40/41) of controls. At month 24, these rates fell to 43% for drug users with no HBV marker, 0% for those with anti-HBc, 31% for those with anti-HBc and anti-HBs, and 86% for controls. The drug users who did not respond to vaccination were more likely to be those with evidence of prior HBV infection and anergy to skin tests. This indicates that unresponsiveness to hepatitis B vaccine in drug users may be due to altered immunity.
Adult↗
Specificity of the hepatitis C virus antibody ELISA in patients with hepatocellular carcinoma.
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Antibody Specificity↗
Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment.
Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause.
Acute Disease↗
Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients.
The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV.
Adolescent↗
Primary carcinoma of the vagina. Case report.
An unusual case of Primary Carcinoma of the vagina was recently observed. The patient was treated surgically in 1981 for squamous cervical carcinoma in situ (CIN 3); eight years later the same patient was treated for squamous carcinoma of the vagina that involved the upper, median and lower tract. She was treated with radical colpectomy and VBP chemotherapy for three courses. The pathology, natural history and treatment are discussed.
Antineoplastic Combined Chemotherapy Protocols↗
Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children.
Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.
Adolescent↗
Isolation and characterization of human apatite-inducing aortic proteolipid.
A proteolipid, capable of inducing hydroxyapatite in vitro, can be isolated from human aortic calcified lesions, noncalcified lesions, and nonlesion tissue obtained at autopsy. Analysis of the amino acid composition after acid hydrolysis showed all nucleators to be high in the hydrophobic amino acids glycine and alanine. Estimation of the molecular weight of the nucleator, extracted from calcified lesions, by gel filtration and lipid content showed a minimum molecular weight of 469,000 Da. All nucleators were characterized by the presence of acidic phospholipids which may have a role in the mechanism of calcification.
Adult↗
[Compensatory response of the residual lung after exeresis (ultrastructural study)].
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Adaptation, Physiological↗
Emetine identified in urine by HPLC, with fluorescence and ultraviolet/diode array detection, in a patient with cardiomyopathy.
A 15-year-old girl with a four-month history of cardiac failure from undetermined cause was admitted to the hospital with weakness, fatigue, and weight loss. During her hospitalization she was found to have abused diet aids, laxatives, and cathartics. Although an electrocardiogram revealed nonspecific T-wave abnormalities and laboratory studies showed supranormal enzyme test results for creatine kinase and lactate dehydrogenase, no definite explanation of the cardiomyopathy was forthcoming. Ipecac abuse leading to cardiomyopathy was suspected early in the hospitalization. HPLC analysis of a urine sample showed emetine, a principle component of ipecac, the presence of which was later confirmed by more-specific HPLC analysis with photodiode array detection.
Adolescent↗
Lidocaine metabolite and creatinine measurements in the Ektachem 700: steps to minimize its impact on patient care.
The single-slide method used for creatinine in the Kodak "Ektachem" analyzer is far more precise than the two-slide method. We confirm that sera from patients on intravenous therapy with lidocaine exhibit a positive bias in results for creatinine but that lidocaine itself does not interfere. Instead, N-ethylglycine, a metabolite of lidocaine with a structure similar to that of sarcosine, is probably the cause. A method that allows N-ethyglycine to be measured directly is described. We followed the degree of this interference through five generations of the slide. Our investigations include two detailed comparison studies between the Kodak Ektachem 700 and the Beckman Astra analyzers. Creatinine determinations on lidocaine-treated patients when first-generation slides were used averaged 4.6 mg/L higher than determinations on these same specimens performed in the Astra. Serum creatinine results from patients not on lidocaine showed no significant difference between the two instruments. The average difference in generation 2, 3, and 4 slides was 0.24, 0.22, and 2.5 mg/L, respectively. No more than 2% of our creatinine results had a clinically significant lidocaine-related bias. We show how to identify and correct this small proportion of results that are biased because of lidocaine therapy.
Autoanalysis↗