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G Cathomas

Publications and source records attributed to G Cathomas.

At least 55 records · Page 3Linked to original sources

Transplantation-associated malignancies: restriction of human herpes virus 8 to Kaposi's sarcoma.

BACKGROUND: The human herpes virus 8 (HHV8) has been detected in all forms of Kaposi's sarcoma. HHV8 was also reported to be present in epithelial skin tumors of patients after renal transplantation, raising the question of the clinical relevance of HHV8 in transplant-related tumors. METHODS: Using a highly sensitive nested polymerase chain reaction assay, we analyzed for the presence of HHV8-DNA in the tumor tissue of renal transplant recipients with Kaposi's sarcoma (n=2) and non-Hodgkin's lymphomas (n=6), and in 32 tumors from 10 patients with multiple epithelial skin tumors. RESULTS: HHV8-DNA was detected in both cases of Kaposi's sarcoma but not in either the non-Hodgkin's lymphomas or the epithelial skin tumors. CONCLUSIONS: Our data confirm the association of HHV8 with Kaposi's sarcoma but not with other transplant-related tumors. Further studies are needed to analyze the risk for transmission of HHV8 by the donor and the possible exclusion of HHV8-positive patients as organ donors.

Adult↗

[Detection of human herpesvirus 8 (HHV 8) in Kaposi sarcomas of the gastrointestinal tract].

Involvement of Kaposi's sarcoma in the gastrointestinal tract is common in AIDS patients. The disease is, however, usually asymptomatic and, due to the tumor growth primarily in the submucosa, biopsy diagnosis is possible in under 25%. The recently described human herpes virus 8 (HHV8) is closely associated with all forms of Kaposi's sarcoma. Detection of HHV8 in the tissue samples may therefore improve the diagnosis of gastrointestinal Kaposi's sarcoma. In the present study we analyze autopsy samples of tumor and non-tumor tissue from the gastrointestinal tract in patients with and without Kaposi's sarcoma for the presence of HHV8 DNA using a nested polymerase chain reaction (PCR) assay. HHV8 DNA was present in all 15 tissues with Kaposi's sarcoma. In contrast, HHV8 DNA was present only in 3 (18.8%) of 16 gastrointestinal tissues of patients with Kaposi's sarcoma but without histologically detectable tumor. No HHV8 DNA was present in 15 tissue samples of AIDS patients without Kaposi's sarcoma. Our data show that detection of HHV8 DNA using a nested PCR assay is a highly sensitive and specific diagnostic test for Kaposi's sarcoma in autopsy tissue samples from the gastrointestinal tract. It should therefore be possible to use detection of HHV8 DNA in biopsy material as an assay for the diagnosis of Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Celiac disease transmitted by allogeneic non-T cell-depleted bone marrow transplantation.

We observed the occurrence of celiac disease following allogeneic bone marrow transplantation in a patient transplanted for acute leukemia. The marrow donor was his HLA-identical sister, who had suffered from celiac disease since birth. The post-transplant period was characterized by recurrent episodes of diarrhea. Detailed workup showed atrophic intestinal mucosa on histology and anti-gliadin and anti-endomysium antibodies in the serum, features that were not present before transplantation. GVHD was absent at that time. The patient remains free of symptoms on gluten-free diet and slight immunosuppression. This case suggests transmission of celiac disease by bone marrow transplantation and supports the T cell concept in celiac disease.

Acute Disease↗

Mechanisms underlying mismatch repair deficiencies in normal cells.

Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominantly inherited cancer predisposition which is linked to heterozygous mutations in mismatch repair genes. HNPCC tumour cells, in which the remaining wild-type copy of the mismatch repair gene is inactivated, display instability of microsatellite markers reflecting a defect in mismatch repair. Recently, patients carrying either one of two distinct germline mutations in the MLH1 and PMS2 genes were reported to accumulate somatic mutations of microsatellites in untransformed cells. One of the mechanisms that might account for this phenomenon was a dominant negative effect of the mutant allele. To evaluate this possibility, we examined a different family carrying one of the mutations (deletion of codon 618K in the MLH1 gene) which has been suspected to induce genetic instability in untransformed cells. No mutations in dinucleotide repeat markers were observed in a large number of lymphoblast clones derived from a carrier. Evidence for the deletion of the wild-type allele in two different tumours suggested that the inactivation of both gene copies was required for tumour initiation. These results indicate that the MLH1 618K deletion mutation alone does not necessarily cause marked mismatch repair deficiency in the presence of a wild-type allele.

Adaptor Proteins, Signal Transducing↗

Molecular detection and characterization of yellow fever virus in blood and liver specimens of a non-vaccinated fatal human case.

A yellow fever virus of a South American genotype was identified in the liver and blood samples of a non-vaccinated European patient after his return from Brazil. ELISA tests were negative for IgG and positive for IgM against yellow fever. Yellow fever proteins in the formalin-fixed and paraffin-embedded liver biopsy were detected by immunohistochemical procedures. Viral RNA extracted from the liver tissue was also detected using an RT-semi-nested PCR procedure and molecular hybridization. Alignment of the sequence obtained from a gene fragment amplified by RT-semi-nested PCR directly from a blood sample with those of African and South American yellow fever virus strains identified a Brazilian topotype as being responsible for the disease. RT-semi-nested PCR may be used advantageously for clinical specimens for rapid and specific diagnosis, and with archival biopsy material for retrospective studies.

Aedes↗

Detection and typing of hepatitis C RNA in liver biopsies and its relation to histopathology.

This paper describes the correlation of hepatitis C genotypes detected in liver tissue with histological grading (inflammatory activity) and staging (degree of fibrosis/cirrhosis). The viral genotype was analysed by type-specific polymerase chain reaction (PCR) and correlated with histology and age of patients. In 69 patients with chronic hepatitis C (HCV) infection, genotypes 1a and 1b were detected in 13 (18.8%) and 31 (44.9%) liver biopsies, respectively. Genotypes 2a and 2b were each detected once (1.5%) and 12 (17.4%) tissue samples showed a mixed infection with two genotypes. In 11 (15.9%) biopsies, no genotype could be established. The liver specimens were grouped according to the presence or absence of genotype 1b: group A consisted of specimens infected with genotypes 1a, 2a, and 2b (n = 16), Group B contained biopsies infected with genotype 1b (n = 42), and group C were biopsies with no detectable genotype (n = 11). Activity (grade) of chronic hepatitis was not different in these three groups. However, advanced fibrosis/cirrhosis was observed in 16 (38.1%) biopsies in group B (containing genotype 1b), compared with none in group A (P = 0.01). The mean age of patients in group B was significantly higher than that in group A (P = 0.038), and the mean age of patients with advanced fibrosis was higher than that of patients with low fibrosis scores within these two groups (P = 0.004). Stepwise logistic regression revealed an independent association of age and genotype 1b (group B) with advanced fibrosis/cirrhosis. These data indicate that patients infected with genotype 1b have an higher risk of developing cirrhosis than do patients with other genotypes.

Adolescent↗

Detection of herpesvirus-like DNA by nested PCR on archival skin biopsy specimens of various forms of Kaposi sarcoma.

AIMS: To detect herpesvirus-like DNA sequences, defining a new herpesvirus, human herpesvirus 8 (HHV8), in paraffin wax embedded skin biopsy specimens of the various forms of Kaposi sarcoma. METHODS: DNA was extracted from archival skin biopsy specimens of Kaposi sarcoma, other mesenchymal skin tumours and various inflammatory skin lesions of HIV seropositive and negative patients. HHV8 DNA was detected by using a nested PCR assay. Human beta-globin DNA served as an internal control. RESULTS: Twenty two samples of Kaposi sarcoma were analysed, comprising 12 of the endemic type, nine HIV associated and one transplantation related. HHV8 DNA was detected by nested PCR in all forms of Kaposi sarcoma. By contrast, no HHV8 DNA was detected in five mesenchymal skin tumours or nine biopsy specimens of unspecific inflammatory skin lesions of HIV seropositive and negative patients. CONCLUSIONS: Detection of HHV8 DNA in paraffin wax embedded tissue can be used to confirm a diagnosis of Kaposi sarcoma.

Biopsy↗

Detection of herpesvirus-like DNA in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma.

Pulmonary involvement is a clinically important form of visceral Kaposi's sarcoma in immunocompromised patients. Recently, herpesvirus-like deoxyribonucleic acid (DNA) sequences, defining a new herpesvirus termed "human herpesvirus 8" (HHV8) or "Kaposi's sarcoma-associated herpesvirus" (KSHV), were detected in Kaposi's sarcoma of acquired immune deficiency syndrome (AIDS) and non-AIDS patients. We describe the successful detection of HHV8 DNA in the bronchoalveolar lavage (BAL) fluid of patients with pulmonary Kaposi's sarcoma. Three immunocompromised patients, two HIV seropositive and one after kidney transplantation, suffered from respiratory symptoms and showed pulmonary infiltrates on chest radiography after development of biopsy proven Kaposi's sarcoma of the skin. Bronchoscopy revealed the typical Kaposi like livid endobronchial lesions. BAL fluid was analysed for the presence of HHV8 DNA using a nested polymerase chain reaction (PCR) assay. HHV8 DNA was detected in the BAL fluid of all three patients. In addition, HHV8 DNA could be detected in the skin biopsy tissue, lymph node, and peripheral blood mononuclear cells of these patients. Our data show that human herpesvirus 8 deoxyribonucleic acid can be detected in the bronchoalveolar lavage fluid of patients with pulmonary Kaposi's sarcoma. If further studies reveal a high specificity for human herpesvirus 8 deoxyribonucleic acid detection, this test will improve the tools for the diagnosis of pulmonary Kaposi's sarcoma without further need of biopsies.

Adult↗

Concomitant active Crohn's disease and the acquired immunodeficiency syndrome.

Symptomatic human immunodeficiency virus (HIV) infection is accompanied by depressed CD4+ T-lymphocyte counts. These cells seem to play a role in the inflammatory processes in Crohn's disease. It has even been speculated that depression of CD4+ T-lymphocytes in HIV infection may cure Crohn's disease. Here we describe a 41-year-old drug-addicted man with a 9-year history of Crohn's disease. HIV infection was diagnosed 8 years ago. At present he has stage-C3 HIV infection. He was admitted because of weight loss and chronic diarrhea with rectal blood and mucus discharge. Crohn's disease was confirmed endoscopically and histologically. Infectious diarrhea known to mimic Crohn's disease in patients with acquired immunodeficiency syndrome (AIDS) was excluded. In summary, we describe a patient with AIDS (CD4 count, 84/microliter) and active Crohn's disease, showing that both illnesses can occur simultaneously.

Acquired Immunodeficiency Syndrome↗

[Detection of herpes virus-like DNA in various forms of Kaposi's sarcoma but not in other mesenchymal tumors or inflammatory changes in skin].

Recently, herpes-virus like DNA sequences defining a new herpes virus termed human herpes virus 8 (HHV8), were detected in Kaposi's sarcoma of AIDS and non-AIDS patients. We describe the successful detection of HHV8 DNA in archival skin biopsies of the various forms of Kaposi's sarcoma. DNA was extracted from archival skin biopsies of Kaposi's sarcoma, other mesenchymal skin tumors and various inflammatory skin lesion of HIV seropositive and negative patients. The extracted DNA was analyzed for the presence of HHV8 DNA using a nested PCR assay. All samples were tested for the presence of appropriate DNA using a internal cellular control PCR-reaction. A total of 23 Kaposi's sarcoma were analyzed, including 12 of the endemic type, 9 HIV-associated and 2 transplant related. HHV8 DNA was detected by nested PCR in all forms of Kaposi's sarcoma. In contrast, no HHV8 DNA could be found in 17 mesenchymal, especially vascular skin tumors or in 7 biopsies with unspecific inflammatory skin lesions of HIV seropositive and negative patients. HHV8 DNA was present in all forms of Kaposi's sarcoma tested but not in other mesenchymal tumors or unspecific inflammatory lesions of the skin. This data support the idea of a strong association of HHV8 and Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

[Dysphagia, cavernous changes of the lungs and subarachnoid hemorrhage following kidney transplantation].

A 54-year-old patient with polycystic kidney disease developed relapsing urinary-tract infections after renal transplantation. In the post-transplantation period he underwent two rejection episodes. The general condition worsened without obvious reason. Six months after transplantation the patient was hospitalized due to gram-negative sepsis. Despite adequate antimicrobial treatment he continued to lose weight and complained of dysphagia. Chest X-ray and computer tomogram of the thorax showed multiple cavitating infiltrations of the lung. A few days later the patient died from an extended subarachnoidal hemorrhage.

Deglutition Disorders↗

[Xanthogranulomatous pyelonephritis with phlegmonous abdominal wall infiltration. Diagnosis and assessment of extent via computerized tomography].

A 34-year-old woman who 14 years previously had undergone a left nephrotomy for nephrolithiasis complained of pain in the left renal fossa which was reddened and painful on percussion. She had a fever of 38.2 degrees C. C-reactive protein was raised to 80 mg/l, the white cell count to 14,620/microliters (83% neutrophils). Protein and white cells were found in the urine together with a significant number of E. coli on urine culture. Plain film of the abdomen showed a staghorn calculus and ultrasonography demonstrated renal enlargement with a possible paranephritic abscess. The computed tomography diagnosis was xanthogranulomatous pyelonephritis, on the basis of renal enlargement, staghorn calculus, hypodense areas with typical density values (10-15 Hounsfield units), contrast enrichment and extrarenal extension of partly phlegmonous partly fused-together inflammatory changes. The abscessing parts were drained under computed tomography control. Starting 7 days pre-operatively the patient had been receiving ciprofloxacin (0.4 g daily) intravenously. A nephrectomy had to be performed subsequently. Antibiotic treatment was discontinued 2 weeks later and she was discharged symptom-free. The diagnosis of diffuse xanthogranulomatous Pyelonephritis was confirmed by histological examination of the surgical specimen.

Abdominal Abscess↗

[Detection and typing of hepatitis C RNA in liver biopsies in comparison with histopathology].

Total RNA of 55 frozen liver biopsies were extracted and tested for the presence of HCV RNA and the genotype by RT-PCR using primers of the 5' non-coding region and a type specific primer set for HCV genotyping. In paralell, the activity of chronic hepatitis, the stage of fibrosis as well as chracteristic features of chronic hepatitis C were evaluated by conventional histology. HCV RNA was detected in 49 (89.1%) of 55 liver specimen by either primer set and genotyping was successful in 42 (76.4%) of liver biopsies. The samples were divided in 3 groups: Group A consisted of specimens infected with genotypes 1a, 2a and 2b (n = 13), Group B contained biopsies infected with genotype 1b (n = 24) and Group C were biopsies with two or no detectable genotype. The histology showed a significant higher degree of fibrosis/cirrhosis in Group B (genotype 1b) compared to Group A (11/24 vs. 0/13, p = 0.011). In addition, an advanced fibrosis/cirrhosis was found more often in Group C than B, however, this difference was not significant (5/15 vs. 0/13, p = 0.072). No difference was seen between the three groups with respect to the activity of chronic hepatitis, presence of lymphoid follicles, bile duct lesions or steatosis. We conclude that HCV RNA can readily be detected and typed in frozen liver tissue. Patients infected with HCV genotype 1b have an increased risk developing liver fibrosis and cirrhosis.

Biopsy↗

[Early diagnosis of cytomegalovirus infection and disease in patients following kidney transplantation].

For early diagnosis of cytomegalovirus (CMV) infection after renal transplantation, 18 patients were monitored within the first 3 months. Blood leukocytes were assayed weekly for the presence of the CMV matrix protein p65 (antigenemia assay) and CMV DNA by the polymerase chain reaction (PCR). In 12 out of 18 patients, 70 (37.8%) of 185 blood samples were positive by antigenemia assay or by PCR. 49 and 115 samples concurrently were positive and negative by both tests. 8 blood samples were positive only by the antigenemia assay and 13 only by PCR. Therefore, the relative sensitivity of PCR and of antigenemia assay was 88.6% and 81.4% respectively. In 9 of 10 patients who were pre-transplant CMV seropositive and in 4 of 7 patients who were pre-transplant CMV seronegative and received a graft from a seropositive donor, CMV infection was detected by positive antigenemia and/or PCR. Four of these patients developed CMV disease. In all these patients, antigenemia assay and PCR were positive 7 to 16 days prior to onset of clinical symptoms. Antigenemia and PCR are rapid and sensitive methods for the detection of CMV infection 1 to 2 weeks prior to disease. In addition, the semi-quantitative assay of antigenemia enables monitoring of the efficacy of antiviral therapy.

Cytomegalovirus↗

[Detection of bcr-abl transcripts in "minimal residual disease" in chronic myelogenous leukemia by nested polymerase chain reaction (PCR)].

We compared two non-radioactive PCR methods, a single step PCR and a nested PCR, for detecting bcr-abl transcripts in patients with chronic myelogenous leukemia (CML). The nested PCR assay was about thousand times more sensitive than the single step PCR. In 75 clinical samples tested in parallel, the sensitivity for the single step PCR and the nested PCR was 43.2% and 91.9%, respectively. In all 17 samples of 9 patients before bone marrow transplantation (BMT), bcr-abl transcripts were detected by the single step PCR. After BMT, 5 (9.8%) of 51 samples of 4 patients were positive by the single step PCR and 17 (33.3%) of 7 patients by the nested PCR. These data indicate that single step PCR may miss minimal residual disease whereas nested PCR is a sensitive alternative to the use of radioactive probes.

Bone Marrow Transplantation↗

Rapid diagnosis of cytomegalovirus pneumonia in marrow transplant recipients by bronchoalveolar lavage using the polymerase chain reaction, virus culture, and the direct immunostaining of alveolar cells.

The objective was to compare the use of the polymerase chain reaction (PCR), virus culture, and immunostaining of alveolar cells used alone and in combination as diagnostic methods for the rapid diagnosis of cytomegalovirus (CMV) pneumonia in marrow transplant recipients. Seventy-five marrow transplant recipients with clinical and radiological evidence of pneumonitis were used as subjects. Bronchoalveolar lavage was performed on all patients to obtain material for conventional and/or rapid CMV culture, immunostaining of alveolar cells with monoclonal antibodies (MoAbs), and amplification of CMV-DNA by PCR. Assay results were then prospectively correlated with clinical outcome. Seven of the 75 patients (9.3%) had CMV pneumonitis and 6 patients (8%) had CMV infection without pneumonia. PCR is the most sensitive assay for the detection of CMV in bronchoalveolar lavage fluid. For the diagnosis of CMV pneumonitis, the sensitivity of alveolar cell immunostaining and PCR were both 100%. The sensitivity of virus culture was 85.7%. The positive predictive value for each test, used alone, for the identification of CMV pneumonitis was low. However, when the result of the PCR assay was assessed in combination with CMV immunostaining of alveolar cells, the sensitivity, specificity, positive, and negative predictive value of this strategy was 100%. The concomitant use of PCR and the rapid immunostaining of alveolar cells for CMV has facilitated the development of a sensitive and specific diagnostic algorithm for the detection and early treatment of CMV pneumonitis in transplant recipients.

Animals↗

Prenatal diagnosis of fetal cytomegalovirus infection.

Twelve fetuses were evaluated with a combination of ultrasonography, amniocentesis, and blood sampling for possible cytomegalovirus infection. In seven the mother had a documented primary cytomegalovirus infection. All seven women had normal ultrasonographic findings and one fetus was found to be infected. In the other five cases fetal cytomegalovirus infection was diagnosed in association with abnormal ultrasonographic findings. There was no history of maternal infection in the latter group. All positive and negative diagnoses were confirmed and none of the six infected fetuses survived. In this series, the most reliable parameters of infection were the isolation of the virus from amniotic fluid and elevations of total immunoglobulin M and gamma-glutamyl transpeptidase in fetal blood. In the majority of infected fetuses cytomegalovirus-specific immunoglobulin M was not detected in blood. Prenatal diagnosis of fetal cytomegalovirus infection is possible with a combination of amniocentesis and fetal blood sampling.

Amniocentesis↗