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Biomedical subjects

H Joller

Publications and source records attributed to H Joller.

At least 19 recordsLinked to original sources

Detection of hepatitis C viraemia in Caucasian patients with hepatocellular carcinoma.

Potential risk factors for the development of hepatocellular carcinoma were analysed in 40 Caucasian patients with this malignancy. A higher proportion (14 of 40; 35%) had evidence of hepatitis C virus (HCV) infection than had evidence of either hepatitis B virus (HBV) carriage (17.5%) or alcohol abuse (30%). In all 14 patients whose sera were reactive by HCV ELISA (Ortho second generation test), the presence of antibodies to HCV were confirmed by recombinant immunoblot assay (Ortho RIBA-2). Furthermore, two independent laboratories detected HCV-RNA in 10 of the 14 (71%) anti-HCV positive sera. Two additional sera were shown to contain HCV-RNA when reanalysed by a modified PCR using oligonucleotide primers designed to amplify a shorter fragment of the 5' noncoding region of the genome. Seven of the anti-HCV positive patients also had evidence of prior HBV infection and 2 admitted to alcohol abuse. HCV infection was the only identifiable risk factor in 6 patients. These data confirm the association between HCV infection and hepatocellular carcinoma and suggest that persistent viral replication accompanies tumour development in the majority of patients whose serum contains anti-HCV.

Aged

Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection.

Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.

Animals

[Prevalence and significance of ant-HCV-antibodies in ambulatory patients with raised transaminases].

From November 1989 to April 1990 we analyzed prospectively the prevalence of anti-hepatitis C virus antibodies and the possible mode of infection in 90 outpatients with repeatedly elevated alanine-aminotransferase levels. The clinical and serological course of these patients was evaluated after 1, 3 and 6 months. Initially, 24 patients (26.6%) were positive for anti-HCV antibodies, but subsequently only 14 of these patients (15.5%) were positive in the follow-up tests. 9 patients (10%) showed no antibodies against HCV in control evaluations and one patient dropped out of the investigation. The 9 patients with a negative result in the control tests had median relative anti-HCV concentrations of 2.0 (range 1.2-4.1) in contrast to 5.5 (range 1.6-256.5) in the 14 patients with a confirmed anti-HCV test (p less than 0.001). None of those 9 patients had received blood transfusions, 7 had consumed drugs intravenously and only 2 had no specific risk for HCV infection. The consistently anti-HCV positive patients had median alanine-aminotransferase levels between 115 and 200 U/l, whereas the levels in initially anti-HCV positive and subsequently negative patients ranged from 75-90 U/l. The initial prevalence of anti-HCV antibodies in 26.6% of our patients is related to the high rate of either false positive results or sero-conversion in 38% of this group. We recommend cautious interpretation of anti-HCV test results with relative anti-HCV concentrations less than or equal to 2 in equivocal clinical situations.

Adult

[Prevalence of cytomegalovirus, hepatitis B and HIV-1 antibodies in healthy blood donors, hospital patients, kidney transplant recipients, i.v. drug addicts and homosexuals].

Between 1987 and 1988 592 serum samples were analyzed in order to determine the prevalence of cytomegalovirus (CMV), hepatitis-B and HIV-1 antibodies among healthy blood donors and different risk groups in the region of Zurich, Switzerland. Samples from 100 healthy blood donors, 100 hospital patients, 100 renal transplant recipients, 142 iv drug addicts and 150 homosexuals were analyzed. Among 111 (74%) of the 150 homosexuals studied, antibodies against CMV were identified. On the other hand, only a third of the remaining probands proved to be anti-CMV positive (26-37%). All the groups aged between 20 and 39 years showed an increase in anti-CMV frequency with advancing age. Among the 47 homosexuals aged between 20 and 29 years, 30 (64%) were already anti-CMV positive. The relevance of CMV as a sexually transmissible disease is discussed.

Adult

[The tumor markers CA 19.9, Ca 50 and CEA in the differential diagnosis of pancreatic carcinoma].

The tumour markers CA 19.9, CA 50 and CEA were measured preoperatively in 178 patients with symptoms of the upper abdomen and in 30 healthy individuals. Raising the cutoff of CA 19.9 and CA 50 and combining the three markers resulted in a sensitivity of 81.5% and a specificity of 86.7%. With increasing local tumour size and tumour spread, a non-significant tendency to greater tumour marker concentrations was observed. The tumour markers tested proved of great value in differentiating between pancreatic cancer and chronic pancreatitis. Sensitivity and specificity in this context were 81.5% and 100% respectively. In postoperative follow-up and in evaluation of new therapy regimens we recommend CA 19.9 as the marker most closely related to tumour progression or recurrence.

Adenocarcinoma

[Kaposi's sarcoma following kidney transplantation: remission following reduction of immunosuppression and consequent HIV infection].

Kaposi's sarcoma (KS) in renal allograft recipients is a rare though serious complication of immunosuppressive treatment. Therapeutic procedures such as surgical excision and local irradiation are inappropriate, since the endothelial-originated tumor is often multicentric. However, systemic treatment such as chemotherapy entails further immunosuppression. We observed a patient with renal allograft who developed disseminated KS of legs and trunk while receiving azathioprine, cyclosporin and prednisone after intensive rejection therapy with high dose corticosteroids, antithymocyte globulin and transplant irradiation. At that time the immunological status was similar to that of an AIDS patient, though HIV serology was negative. Azathioprine was withdrawn while cyclosporin and prednisone were continued. KS disappeared shortly after without a decrease in allograft function, and immunological parameters tended to normalize. When KS had disappeared almost completely the patient became infected with HIV. Complete remission was not hampered, nor was there recurrence of KS. The late appearance of HIV-antigenemia with seroconversion in the course of the tumor makes HIV unlikely as a causative factor. The predisposing factors for KS after renal transplantation are discussed: 1. Amplification of immunosuppression due to rejection therapy, 2. Genetic predisposition such as HLA DR5 antigen, 3. Cytomegalovirus infections. For therapy of iatrogenic KS we propose reduction of immunosuppressive therapy before additional chemotherapy is initiated.

Acquired Immunodeficiency Syndrome

[Essential cryoglobulinemia with glomerulonephritis as a variant of the purpura-arthralgia-nephritis syndrome].

The syndrome of mixed cryoglobulinemia is clinically characterized by the findings of purpura, arthralgia and glomerulonephritis, the latter developing in up to 50% of the cases. The cryoglobulins have rheumatoid factor activity and serum levels of complement factor C4 are significantly reduced. A report is presented on seven patients with a typical purpura-arthralgia-nephritis syndrome and two patients with essential cryoglobulinemia, rheumatoid factor activity and glomerulonephritis without extrarenal manifestations of vasculitis. Based on these observations, measurement of rheumatoid factor activity is recommended in serum of patients with unclassified glomerulonephritis.

Complement C3

[Transfusion-associated LAV/HTLV-III infections in Switzerland. Report of 2 cases].

Two patients developed signs of LAV/HTLV-III infection one and two years respectively after a blood transfusion. The leading symptom in one patient was generalized lymphadenopathy, while the other patient presented with Candida stomatitis. In both cases, blood transfusions administered in 1983 were found to be the only possible source of infection; one blood donor of each patient was anti-LAV/HTLV-III positive. Family members and sexual partners of the two were negative for antibodies against LAV/HTLV-III. Our findings document the first two cases of LAV/HTLV-III associated disease most probably related to blood transfusions in Switzerland.

Acquired Immunodeficiency Syndrome

[Circulating interferon in patients with systemic lupus erythematosus. A prospective study].

The serum levels of interferon (IFN) were measured in 31 patients with systemic lupus erythematosus (SLE). Among the 31 patients, 8 (25%) showed IFN in the sera: in 4 patients IFN titers of 16 U/ml, and in the other 4 patients titers of greater than or equal to 32 U/ml became detectable. Whereas antibodies to native DNA (nDNA) were present in 6 of the 8 IFN positive patients, anti-nDNA antibodies were only positive in 6 of the 23 IFN negative individuals (p less than 0.002). Eight months after the first search for IFN in the patients' sera, 6 of the 8 IFN positive patients showed reduced IFN serum levels and one each had an increased or stable IFN titer. A good correlation between IFN titers and both the anti-nDNA antibody titers and the disease activity was observed. However, there were patients with active disease, high anti-nDNA titers but no IFN in the serum.

Adult

[Prevalence of antibodies against HTLV-III in various regions in Switzerland].

Acquired immune deficiency syndrome (AIDS) has been etiologically linked with the human T-cell lymphotropic virus HTLV-III. In a study on the prevalence of antibodies to this virus in Switzerland, sera from 941 individuals were collected in 5 major urban areas (Basel, Berne, Geneva, Lausanne and Zurich) in 1983 and 1984. All sera were tested by ELISA and the majority also by Western blot. We found an antibody prevalence of 100% among 22 cases of AIDS, of 94% among 48 cases of AIDS-related complex (ARC), and of 57% among 14 homosexual contacts of AIDS patients. Among 55 sera collected from i.v. drug addicts in 1984, 53% were positive, whereas the rate had been 36% among 103 sera collected in 1983. The rate was 19% among 227 sera collected from asymptomatic active homosexuals in 1984, against 10% among 40 sera collected in 1983. 8% positives were found among 98 patients with various types of viral hepatitis. In addition, 4% of 84 sera of individuals from Equatorial Africa were positive. No positives were found among 15 sera of individuals from other African regions, among 32 sera of persons from various regions of Asia, and among 203 Swiss blood donors. These results demonstrate the high and increasing rate of HTLV-III infection among groups at risk for AIDS, and suggest that HTLV-III-related diseases will be a serious problem in the years ahead.

Acquired Immunodeficiency Syndrome

Antibodies to HTLV-III in Swiss patients with AIDS and pre-AIDS and in groups at risk for AIDS.

We tested serum samples from Swiss subjects by three different assays based on enzyme-linked immunosorbent assay (ELISA) and Western blot techniques for antibodies to proteins associated with the recently discovered human T-cell leukemia/lymphoma virus HTLV-III, the putative etiologic agent for the acquired immunodeficiency syndrome (AIDS). Of 10 patients with AIDS and 10 with pre-AIDS, all were antibody-positive. Furthermore, 37 of 103 intravenous-drug addicts (36 per cent), 4 of 40 healthy homosexual men (10 per cent), 7 of 83 patients with various types of hepatitis (8.4 per cent), but none of 83 healthy blood donors or 10 other controls were antibody-positive. Antibodies to the major viral protein p24 were found consistently and at high titers in the seropositive members of the groups at risk and in those with pre-AIDS but were dramatically reduced in patients with AIDS. In contrast, antibodies to another virus-associated protein, p41, were present in all cases of AIDS and pre-AIDS but were absent in nearly 10 per cent of seropositive persons at risk. Whereas p41 and p24 thus appear to be the targets of choice for future screening tests, the ELISA test that is currently available is a useful screening tool.

Acquired Immunodeficiency Syndrome

[Acquired immune deficiency syndrome in the region of Zurich. Report on 12 cases].

Observations of 12 patients with AIDS at this institution from March 1981 to April 1984 are reported. Ten patients were homosexuals and two were bisexual. The majority had travelled abroad (USA, Haiti) and reported multiple anonymous sexual contracts. Eleven patients reported symptoms and signs, of 2-12 months' duration, frequently seen in pre-AIDS: fatigue (10), weight loss (10), diarrhea (7), night sweats (5), fever (4), and generalized lymphadenopathy (1). Laboratory studies showed anemia (10), lymphopenia (9), leukopenia (7), decreased T-helper/T-suppressor ratio (10) and cutaneous anergy to multiple skin-test antigens (9). P. carinii pneumonia was diagnosed in three patients, P. carinii pneumonia and Kaposi's sarcoma in one patient and Kaposi's sarcoma in six patients. Another patient had a chronic mucocutaneous infection with herpes simplex and another an intestinal cryptosporidiosis and Kaposi's sarcoma. Alpha-A-interferon was used to treat patients with Kaposi's sarcoma and three patients with limited disease showed a favorable response. Six patients with advanced disease died.

Acquired Immunodeficiency Syndrome

[Carcinoembryonic antigen (CEA) in surgically treated cancer of the large intestine].

Preoperative CEA value. Dukes stage and recurrence rate have been evaluated in 112 patients with large bowel cancer. Recurrence rate within 24 months was significantly higher (33% vs. 10%, p = 0.01) for preoperative CEA values of more than 5 ng/ml. In patients with moderately or poorly differentiated adenocarcinoma the recurrence rate was nearly 40% if the preoperative CEA value was elevated. Among 13 CEA-detected early recurrences, 3 (23%) have been cured by resection.

Carcinoembryonic Antigen

[Relevant immunological profiles].

In 1980 more than 200,000 immunological tests were performed in the Section of Clinical Immunology, Department of Medicine, University Hospital, Zurich (Switzerland), a fact which raises the question whether the results warrant the effort involved. To answer this question of clinical relevance, 4 disease complexes have been investigated: lupus erythematodes, systemic affections dominated by arthralgia, hepatitis and thyroiditis. The analysis shows that no single factor but only an optimized set of tests is capable of distinguishing between related diseases. Follow-up studies are of prime importance because the sequence of antigen expression and antibody responses provides valuable additional information. Laboratory results can be evaluated only in conjunction with the clinical picture.

Aged

[IgG-IgM cryoglobulinemia with a purpura-arthralgia-nephritis syndrome].

The clinical and laboratory features in 7 patients with essential mixed cryoglobulinemia are presented. The clinical picture was characterized by arthralgia, purpura and glomerulonephritis (3 patients). The cryoprecipitate consisted of IgM and IgG, the IgM being monoclonal (3 patients) with anti-IgG activity. Depressed C4 and/or C3 values were detected in 5 patients and were not correlated with the presence of nephritis. The IgM levels were elevated in 5 patients. The possibility that the disorder represents an immune complex mediated vasculitis is supported by the ability of the cryoglobulins to activate the complement system and by the detection of immunoglobulins and/or complement in the vasculitic lesions in the glomerula or the skin. Treatment by plasma exchange, steroids and azathioprine or cyclophosphamide was followed by a definite improvement in the purpura and the arthralgia, whereas the proteinuria, microhematuria and hypocomplementemia were not affected by therapy.

Adult

[Serum immunoglobulins during immunosuppressive therapy following kidney transplantation].

Immunoglobulins IgG, IgA and IgM and the complement factor C'3 were measured in the serum of 103 kidney allograft recipients. As compared to those in 50 patients on hemodialysis treatment, 100 hospitalized patients and 100 blood donors, the mean values for IgA, IgG and C'3 were significantly decreased. IgM was higher than in blood donors. The longitudinal profile in 6 transplant patients showed remarkably stable immunoglobulin concentrations. No association between low IgG levels and infections or rejection episodes was observed.

Adult

Immunological abnormalities and HLA antigen frequencies in IgA deficient patients with epilepsy.

Twenty-three epileptics with constitutional factors for seizures and low IgA serum concentrations were studied. Imbalance of the IgG subclasses was often observed, the IgG4 being undetectable in 13 (65%) patients. The percentage of circulating lymphocytes positive for surface immunoglobulins was normal except for slightly increased values for IgA in six (28.5%) patients. Of the epileptics, 48% showed subnormal proportions of lymphocytes forming spontaneous rosettes. There was a distinct trend for HLA-A2 antigen in the patients tested.

Adolescent