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PubMed1995

[Chronic hepatitis].

Chronic hepatitis is defined as primary necroinflammatory liver disease with a duration of at least 6 months. It is etiologically heterogeneous and may be caused by hepatitis viruses (B, C, D, others?), autoimmune processes, drug reactions and metabolic disorders. A certain percentage of chronic hepatitides is etiologically still uncertain (cryptogenic). Nomenclature and classification of chronic hepatitis proposed in 1968 on the basis of morphologic appearance is still widely used. However, in view of the recent advances in our knowledge of etiology, pathogenesis, course of the disease, and, particularly, progress in therapy a classification based on morphology alone is unsatisfactory. A modern classification of chronic hepatitis should be easy to apply and reproducible, and based on etiology, grading of necro-inflammation and staging of the disease. Grading should consider portal, periportal and lobular inflammation and type and extent of liver cell alterations and necrosis. Fibrosis and cirrhosis are histological features of staging. Alterations may be semi-quantified particularly to facilitate comparison of results in clinical trials.

Autoimmune Diseases↗
PubMed1999

In patients with cirrhosis, serum albumin determination should be carried out by immunonephelometry rather than by protein electrophoresis.

OBJECTIVE: Serum albumin is a key parameter for prognosis in cirrhosis. We compared levels of serum albumin determined by both protein electrophoresis and immunonephelometry, with special reference to the Child-Pugh classification. DESIGN AND METHODS: One hundred and thirty-one patients, including 39 with cirrhosis, were included prospectively during 2 months. The aetiology of cirrhosis was mainly alcoholism (67%) and hepatitis C virus (HCV) (18%). Serum albumin was determined simultaneously by electrophoresis (Hydrasys SEBIA following protein determination by the biuret reaction) and by immunonephelometry (BECKMAN Nephelometer). Values were compared by non-parametric tests. RESULTS: For the whole population, electrophoretic and immunonephelometric values correlated (p = 0.85; P < 0.0001), but electrophoresis significantly overestimated serum albumin by a median 1.6 g/l (P < 0.0001) with a large spread in values (range, -3.9 to 12.7). Median overestimation in cirrhosis was 2.6 g/l (P < 0.0001; range, -2.0 to 10.2) and 1.0 g/l (P < 0.0001; range, -3.9 to 12.7) in patients without cirrhosis (difference, P < 0.02). For 6/39 (15.4%) patients with cirrhosis, this overestimation led to an underestimation in the Child-Pugh classification. CONCLUSION: In our experience, electrophoresis can lead to serum albumin values which are significantly different compared to those obtained by immunonephelometry. This discrepancy may lead to an incorrect Child-Pugh classification. Therefore, in the follow-up of cirrhotic patients, serum albumin should be determined by immunonephelometry.

Adult↗
PubMed1977

Genetic complementation of propionyl-CoA carboxylase deficiency in cultured human fibroblasts.

Propionyl-CoA carboxylase (PCC) deficiency is an inherited metabolic disorder showing considerable variability of expression. We have investigated the possibility that there is a genetic basis for the clinical heterogeneity in this disorder by examining complementation in Sendai virus mediated heterokaryons of mutant fibroblast strains. Restoration of PCC activity was monitored in individual multinucleate cells in situ using a radioautographic procedure which detects the incorporation of 14C-propionate into trichloracetic acid precipitable material. Each mutant strain incorporated negligible amounts of radioactivity compared to control strains. Activity was not restored when different mutants were mixed without virus or when homokaryons were produced by self-fusion. Seven mutant strains were fused in all pairwise combinations and examined for increased 14C-propionate incorporation in heterokaryons. Two main complementation groups were revealed. One group was composed of three mutants. The other was a complex group composed of four mutants in which intragroup complementation was demonstrated. Two mutants showing excellent complementation by radioautography were examined for complementation by the direct assay of PCC ACTIVITY. The enzyme activity of virus-treated preparations with 23% multinucleate cells was 183 U (pmol/min/mg protein) compared to 16 U for the untreated mixture (normal range 450-850 u). We conclude that PCC deficiency resulted from mutations of heterogeneous origin, although the classification of mutants into complementation groups did not correlate with patterns of clinical heterogeneity.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Vitamin B12 and folate status in human immunodeficiency virus infection.

Vitamin B12 and folate status were determined in 35 male HIV seropositive patients. Of these, 16 were asymptomatic (CDC II/III) and 19 were symptomatic (CDC IV) according to the Centre for Disease Control (CDC) Classification. Deviations from normal values for serum B12, serum folate and red cell folate were not a common finding in this sample of patients. No patient had low serum B12. One CDC IV patient and two CDC II/III patients were found to have raised serum B12. Dietary intake of vitamin B12 was well above the Reference Nutrient Intake for all patients. Three patients displayed low folate values (one CDC IV patient had low serum folate, one had low red cell folate and one CDC II/III patient had both). No patient displayed elevated serum or red cell folate. Only 56% of the CDC II/III and 36% of the CDC IV group were meeting the Lower Reference Nutrient Intake for folate. The only significant difference between the CDC II/III group and the CDC IV group was a lower red cell folate (although within the normal laboratory range) in the CDC IV group. There was no significant difference in dietary intake and haematological status between the drug users and the homosexuals.

Diet Records↗
PubMed1986

Genotypic variation among six isolates of lactate dehydrogenase-elevating virus.

In the present study, six lactate dehydrogenase-elevating virus (LDV) isolates obtained independently from inbred mice were compared by RNA oligonucleotide fingerprint analysis. The genome RNAs of four of the isolates gave unique fingerprint patterns. The patterns obtained for the other two isolates were similar, but not identical to one of the four unique patterns. These results indicate that more than one genotype of LDV exists and that virus isolates can be grouped by genotype. We have also demonstrated the presence of a 3'-terminal poly(A) tract by direct sequencing of 3'-32P-labelled LDV genome RNA. The presence of a 3'-terminal poly(A) tract distinguishes LDV from the members of the family Flaviviridae, which lack a 3'-poly(A), and justifies the current classification of LDV within the family Togaviridae.

Animals↗
PubMed2002

[Long PCR amplification of varicella-zoster virus DNA in clinical specimens from the patients with varicella and herpes zoster].

Long PCR amplification of the 7.7 to 33.5 Kbp regions of varicella-zoster virus (VZV) genomic DNA was performed using template DNAs extracted from clinical specimens such as vesicle fluid and crusts which had been obtained from varicella or herpes zoster patients. PCR products of 7.7-14.4 Kbp in length were efficiently amplified from all of the 14 template DNAs of crust specimens. Targets of 18.6-20.0 Kbp DNA could be also amplified from 14 crust samples except one. From all of the 7 samples derived from infected cells, the DNA targets up to 27.2 Kbp in length could be amplified. Whereas, the efficiency of amplification of 27.2 Kbp DNAs from crust samples was somewhat lower (9/14,64%) than that of DNAs from infected cells. In 83% (5/6) of target DNAs from infected cells, amplification of DNA as long as 33.5 Kbp was possible, while only in 40% (2/5) of these from crust specimens. From crust samples, the efficiency of amplification of DNA longer than 20 Kbp tended to decline. We also confirmed that long target DNA was amplifiable directly from vesicle fluid specimens as effective as from crust specimens. Restriction fragment length polymorphism (RFLP) analyses combined with R2-nested PCR of the long PCR products allowed classification of the 14 clinical specimens into 9 groups. Long PCR derived from clinical specimens was demonstrated to be applicable to RFLP analyses and sequencing without laborious test of virus isolation. Furthermore, the long PCR method described here will be useful for studies of the molecular epidemiology of VZV and for investigating variations among VZV isolates.

Chickenpox↗
PubMed2006

Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood.

BACKGROUND: The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. METHODS: 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested with ELISA for dengue IgG and IgM. 74 serum pairs were tested again in another laboratory with similar methods, after a mean of 252 days. RESULTS: Cases were classified as no dengue (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue. Significant differences between the two laboratories' results were found leading to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper results correlated poorly to serum values, being more variable and lower with a mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37) for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage of frozen serum and dried filter papers, sealed in nylon bags in an air-conditioned room, had no significant effect on the ELISA results. CONCLUSION: Dengue virus IgG antibodies in serum and filter papers was not affected by duration of storage, but was subject to inter-laboratory variability. Dengue virus IgM antibodies measured in serum reconstituted from blood spots on filter papers were lower than in serum, in particular in the acute phase of disease. Therefore this method limits its value for diagnostic confirmation of individual patients with dengue virus infections. However the detection of dengue virus IgG antibodies eluted from filter paper can be used for sero-prevalence cross sectional studies.

Antibodies, Viral↗
PubMed1994

Histological evolution of chronic hepatitis C. Factors related to progression.

We have evaluated the histological progression of liver disease in 29 untreated patients with chronic hepatitis C. All patients were positive to antibodies to hepatitis C virus by ELISA2 and RIBA2. Two liver biopsies were carried out for each patient, with an interval ranging between 12 and 126 months (mean 50.2 +/- 30.7). In all cases the usual histological classification was applied and the histological activity index scoring system according to Knodell et al. was determined. Fifteen cases worsened (51.7%), 12 cases showed no histological changes (41.4%) and two patients improved (6.9%). Cirrhosis was found in five patients (18.5%) in the second liver biopsy. Epidemiological, clinical, biochemical and histological progression and the group with impairment in liver histology. Factors related to histological worsening were: more advanced age (p = 0.002), high levels of aspartate aminotransferase (p = 0.04), high global histological activity index (p = 0.03) and piecemeal necrosis and bridging necrosis scores (p = 0.02) at first biopsy. The histological activity index can be applied to assess the natural history of chronic viral hepatitis, and is a good tool to evaluate the prognosis. Thus chronic hepatitis C virus infection is a histologically progressive disease in at least half the cases.

Adult↗
PubMed1997

The use of cytokine inhibitors. A new therapeutic insight into heart failure.

Cytokines are being increasingly recognized as important factors in the pathogenesis and pathophysiology of heart failure. Elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. We have recently compared the effects on cytokine production of drugs for therapy of heart failure that have different effects on survival. Amrinone, pimobendan and vesnarinone, phosphodiesterase III inhibitors that have been shown to have short term haemodynamic benefits, inhibited TNF-alpha production. Differential modulation of the production of IL-1beta and IL-6 was observed; amrinone and pimobendan enhanced the production of IL-1beta, whereas vesnarinone did not. As inotropic agents differentially modulate cytokine production, these agents may interfere with induction of inducible nitric oxide (NO) synthase through an inhibition of cytokine formation. Although differential modulation of the production of NO by inotropic agents may explain their different effect in patients with heart failure, further study is necessary to reach this conclusion. We have shown that amlodipine increases the survival of mice with viral myocarditis and inhibits expression of inducible NO synthase and production of NO in vivo and in vitro. The therapeutic effect of amlodipine may in part result from inhibition of overproduction of NO. As we learn more about the pathophysiological and pathogenetic role of cytokines in heart failure, it should be possible to design better and more targeted pharmacological agents. Furthermore, the investigation of inotropic agents that are effective against the production of cytokines may help in the classification of these agents.

Animals↗
PubMed1988

DNA probes in diagnostic pathology.

Molecular pathology has become firmly established as a distinctive discipline in medicine. It has introduced radical changes in concepts of disease causation and in classification of disease states affecting humans and other organisms. In addition, molecular pathology represents a "new" diagnostic technology with many potentials that have been heretofore untapped. This overview provides a discussion of the use of DNA probes in the study of human diseases. The role of detectable genetic abnormalities in pathogenesis will be considered, as well as their possible impact on nosology and disease classification.

DNA↗
PubMed1983

Cytochemical reactions in bovine and ovine lymphosarcoma.

Cytochemical reactions with a panel of special stains were explored in peripheral blood and lymph node cells of animals with the adult, calf, and thymic types of bovine lymphosarcoma as well as lymphosarcoma in sheep induced with the bovine leukosis virus. These results were compared with normal lymphoid cells. Cytochemical methods included Sudan black B, periodic acid-Schiff, acid phosphatase and three esterases. Cells from ovine lymphosarcomas and a thymic type of bovine lymphosarcoma were distinctively positive to the alpha naphthyl acetate esterase reaction. These cytochemical reactions which were obtained with standard cytochemical methods should aid in the characterization and classification of lymphoproliferative disorders in animals, especially when combined with immunologic surface markers.

Animals↗
PubMedDate not supplied

Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes.

OBJECTIVE: To determine whether genotypes from human immunodeficiency virus type 1 (HIV-1) subtypes A, C, or D or intersubtype recombinants have the same probability of being transmitted from mother to child. METHODS: We determined the HIV-1 genetic subtype and maternal risk factors of 51 matched transmitting and nontransmitting mothers from Tanzania. The HIV-1 gag (p24-p7) and env (C2-C5) nucleotide sequences were used for genotype classification, and matched logistic regression analysis was used to assess differences among genotypes. RESULTS: Mothers infected with HIV-1 subtype A (odds ratio, 3.8; 95% CI, 0.8-24.7%), HIV-1 subtype C (odds ratio, 5.1; 95% CI, 1.3-30.8%), or HIV-1 intersubtype recombinant viruses (odds ratio, 5.3; 95% CI, 1.2-33.4%) were more likely to transmit HIV-1 to their infants than mothers infected with HIV-1 subtype D. Lower CD4 cell counts at enrollment were associated with transmission, but CD4 cell counts within each genotype did not explain differences in transmission among HIV-1 genotypes. CONCLUSION: We have shown that HIV-1 genotypes might be associated with differential risk for vertical transmission. These findings provide the first evidence that HIV-1 genetic subtypes may play a role in rates of vertical transmission in an African setting.

Base Sequence↗
PubMed2006

Relationships between BK virus lineages and human populations.

BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney, in which it can cause nephropathy in renal transplant patients. BKV isolates are classified into four subtypes (I-IV) using serological or genotyping methods, and subtype I is further divided into four subgroups, Ia, Ib-1, Ib-2, and Ic, based on DNA sequence variations. To clarify whether there is an association between BK virus lineages and human populations, we examined BKV-positive urine samples collected from immunocompetent individuals at various locations in Europe, Africa, and Asia. Partial BKV DNA sequences (n=299) in these samples were determined and subjected to phylogenetic and single nucleotide polymorphism analysis to classify BKV isolates around the world. The validity of the classification was confirmed by analyses based on complete BKV DNA sequences. Subtype I was the major subtype throughout the studied regions, and subtype IV was prevalent only in Asia and Europe. Subtype-I subgroups showed close relationships to major geographical areas. It has recently been shown that JC virus (a human polyomavirus closely related to BKV) co-evolved with human populations, and the present study thus suggests that host-linked evolution is the general mode of polyomavirus evolution. Additionally, our results indicate certain unique aspects of the relationship between BKV and humans.

Africa↗
PubMed2003

Principles of treatment for feline lymphoma.

Lymphoma is the most commonly diagnosed neoplasm in cats. As feline leukemia virus antigenemia has decreased over the past 15 years, there has been a profound shift in the presence, signalment, and frequency of sites of feline lymphoma in North America. There is variation in anatomic classification systems, but most studies have divided lymphoma into four groups: alimentary, mediastinal, multicentric, or extranodal. Clinical signs and common differential diagnoses for each of the forms are described. Staging allows for evaluation of the extent of disease. As in the dog, lymphoma is a systemic disease in the cat, and chemotherapy is the treatment of choice for most forms. Exceptions are described. In contrast to canine lymphoma, feline lymphoma is generally more challenging and frustrating to treat than canine lymphoma. Response rates are lower, and remission duration is shorter. Fortunately, cats treated with chemotherapy tend to have less toxicity than dogs. Positive prognostic factors are feline leukemia virus-negative, clinically well at time of diagnosis, and response to therapy. Achieving a complete remission is prognostic for survival. Unfortunately, response cannot be predicted before treatment.

Animals↗