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D Fuchs

Publications and source records attributed to D Fuchs.

At least 235 records · Page 13Linked to original sources

Generalized likelihood ratio concept and logistic regression analysis for multiple diagnostic categories.

Albert (Clin Chem 1982;28:1113-9) has proposed estimation of likelihood ratios by logistic regression analysis. The usual likelihood-ratio approach for estimation of post-test probability of disease from sensitivity and specificity data of a diagnostic test has been extended by Birkett (J Clin Epidemiol 1988; 41:491-4) for situations with more than two diagnostic categories. We suggest here a combination of these ideas, demonstrating this by a re-evaluation of previously published data on the validity of neopterin as a tool for differential diagnosis between chronic non-A, non-B hepatitis and fatty liver. Analysis of neopterin data in combination with the ratio between serum concentrations of aspartate aminotransferase and of alanine aminotransferase yielded a good discrimination between three mutually exclusive diagnostic categories, namely, fatty liver and chronic persistent and chronic aggressive non-A, non-B hepatitis. The approach is flexibly applicable to situations with different pre-test probabilities. The sum of estimated post-test probabilities deviates slightly from the sum of pre-test probabilities. This deviation is a function of the coefficients obtained in logistic regression, and an analytical expression for the deviation is given. The generalized likelihood-ratio approach appears promising in complex diagnostic situations when multiple diagnostic tests are available.

Alanine Transaminase

Neopterin: a predictive marker of acquired immune deficiency syndrome in human immunodeficiency virus infection.

In 79 homosexual men infected with human immunodeficiency virus (HIV), urinary neopterin was significantly higher as compared with 70 HIV-seronegative men in the same cohort (p less than 0.0001). This highly significant association was found both for naturally occurring oxidized (native) neopterin and for total neopterin (native plus chemically oxidized forms). In prospective follow-up for 18 months, the odds that the acquired immune deficiency syndrome (AIDS) would develop were elevated 25-fold among those whose native neopterin levels were in the highest quartile compared with those with lower neopterin levels, and the corresponding odds ratio for total neopterin was 7.8. Logistic regression analyses indicated that neopterin added useful information to T4-cell count in predicting AIDS onset and that both are statistically significant in the multivariate model. A cross-sectional survey revealed that neopterin levels were correlated with number of receptive anal intercourse partners in the year before HIV seroconversion (r = 0.60, p = 0.0005). Since neopterin may serve as a marker of monocyte/macrophage activation by soluble factors such as gamma-interferon, these data support a growing body of virologic and immunologic evidence that highlights the important role of the monocyte/macrophage in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome

Urinary neopterin concentrations vs total neopterins for clinical utility.

Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV-1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4+ T-cell counts and CD4+/CD8+ T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8-dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8-dihydro derivative.

Acquired Immunodeficiency Syndrome

Effects of interferon-alpha on macrophage activation in patients with ovarian carcinoma and cervical dysplasia.

Patients with progressive ovarian carcinoma and patients with dysplasia of the uterine cervix were studied in order to compare clinical efficacy, hematological toxicity and effects on macrophage activation of administered interferon-alpha for both patient groups. One of three patients with ovarian carcinoma showed a minor response. Four of six patients with cervical dysplasia had slight improvements of PAP-smears. Moderate hematological toxicity was observed in the former patient group while side effects were much more pronounced in the latter patients group. However, changes of hematological parameters were not statistically different. Interestingly, the administered interferon-alpha caused the same activation of macrophages in both patients groups as indicated by raised neopterin levels. This activation does not result in clinical improvement but appears to play a role for the hematological toxicity observed during therapy of patients with ovarian carcinoma. It has been suggested that suppression of hematopoiesis is mediated by interferon-gamma. The present neopterin data propose that this lymphokine is continuously produced through influence of the tumor and enhanced by interferon-alpha.

Adult

Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection.

We assessed the value of urinary neopterin concentrations for prognosis of disease progression in HIV-1-infected patients. Sixty-eight anti-HIV-1 seropositive homosexuals with lymphadenopathy syndrome were tested for urinary neopterin and T-cell subset counts in 1982-83, and the incidence rate at which they developed acquired immunodeficiency syndrome (AIDS) between then and May 1988 was evaluated. Overall, 21 of 68 (30.9%) cases progressed to AIDS, with a yearly progression rate of 4-9%. The predictive value of urinary neopterin concentrations was higher (P = 0.0042) than that of CD4+ T-cell counts (P = 0.015) or the CD4+/CD8+ T-cell ratio (P = 0.022). Counts of CD8+ T-cells failed to show predictive significance (P = 0.29). Similarly, multivariate-regression analysis indicated that neopterin concentrations and CD4+ T-cell numbers were significant copredictors. Produced by human macrophages activated by interferon gamma, neopterin is thus a marker of macrophage activation via T cells. We conclude that these data demonstrate a correlation between the amount of T-cell-macrophage activation, as measured by urinary neopterin concentrations, and the progression of the disease.

AIDS-Related Complex

[Thoracic actinomycosis].

Actinomycosis is an infectious disease distributed all over the world. Males are affected three times more than females; the incidence of the disease is higher in adults than in children. The main causative agent is Actinomyces israelii, which can be found in the oropharynx of healthy persons. Therefore actinomycosis represents always an endogenous infection, often in connection with other bacteriae. The thoracic manifestation amounts to approximately 15 percent of all cases. The main clinical symptoms are pain, fever, cough, fatigue, and weight loss. The blood picture shows an increased number of white blood cells with a left shift in the differential white blood cell count. Furthermore, there is a strongly raised erythrocyte sedimentation rate. Radiographs demonstrate no typical patterns of pulmonary abnormalities. For the diagnosis there is a need of anaerobic cultures, in second line histological examination of tissue specimens. Differential diagnosis of actinomycosis includes chronic pneumonias caused by other rare germs and neoplasms. After early onset antibiotic long term treatment a good prognosis may be expected. Penicillin represents the antibiotic of first choice.

Actinomycosis

[Health cures as a part of the rehabilitation program for children and adolescents following malignant diseases].

Aims of the cures for children and adolescents after malignant diseases consist in the promotion and stabilisation of the physical and psychological welfare. It is reported on the experiences from 108 cures with 65 patients. Under the selected conditions of the cure the physical fitness and psychological situation improved. The objective measurement of results must be progressed.

Adolescent

Predicting AIDS.

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Acquired Immunodeficiency Syndrome

Influence of interferon-gamma and extracellular tryptophan on indoleamine 2,3-dioxygenase activity in T24 cells as determined by a non-radiometric assay.

The indoleamine 2,3-dioxygenase (EC 1.13.11.17) activity in human T24 cells has been investigated in cell extracts by using a non-radioactive assay. It is enhanced in a dose-dependent manner up to 25-fold by interferon-gamma. The maximum reaction velocity is increased rather than the Km, which remains at 4 mumol/l. Induction of activity starts 3 h after stimulation and reaches a plateau at 21-48 h. Decreased stimulation was observed in the presence of high L-tryptophan concentrations.

Cell Line

Urinary neopterin excretion in pulmonary sarcoidosis: correlation to clinical course of the disease.

Urinary neopterin levels were determined by high pressure liquid chromatography in 36 patients with pulmonary sarcoidosis. Values were above normal range in 69.4% of all patients. Neopterin excretion was significantly higher in radiologic types II/III than in type I disease (p = 0.0265, Mann-Whitney U-test). Urinary neopterin showed a weak, but significant inverse correlation to disease duration (r = -0.36; p = 0.034, Spearman's rank correlation). No significant correlation could be found between neopterin and the presence of pulmonary or extrapulmonary symptoms, vital capacity, forced expiratory volume in the first second, steroid treatment, and serum angiotensin converting enzyme. Follow-up studies revealed that worsening or improvement of chest X-ray findings was invariably accompanied by rising or decreasing neopterin excretion, respectively. Patients with normal neopterin at initial evaluation had a higher tendency towards spontaneous healing, and none of them deteriorated during the follow-up period. We conclude that urinary neopterin excretion reflects one aspect of alveolitic "activity" in pulmonary sarcoidosis and that normal values probably indicate a favorable prognosis.

Adult

[Etiology--characteristics of HIV infection].

In this study the structures of the AIDS-virus are presented, furthermore the cross-reactivity of HIV-1 and HIV-2 is described as well as the known genes of both viruses. The mechanism of cell infection, its kinetics and the special role of activated T-cells and macrophages in this process are outlined. This interrelation characterized phenomenologically based on the neopterin data available is now supported by experiments at a molecular level. This should lead to therapeutical and diagnostical consequences.

Acquired Immunodeficiency Syndrome

Immunological status and HIV antibodies in patients with haemophilia--a longitudinal study.

Various immunological parameters were investigated in 12 children suffering from severe haemophilia A or B receiving substitution therapy over a follow-up period of 3 1/2 years. At the beginning of the study, the therapy was changed to heat-treated concentrates of factors VIII or IX. Antibodies to HIV were found in 9 out of these patients. There were no AIDS-related clinical symptoms, but HIV antigen was detectable in one case. Abnormalities of immunological parameters were found independently of HIV infection, but were more pronounced in anti-HIV seropositive patients. Elevated levels of immunoglobulins gave evidence of polyclonal B-cell activation whilst increased levels of neopterin indicated activated T-cells and macrophages. There was no close association between these two types of activation. However, peak activation of both immune compartments was found approximately 1 year after changing the therapy. Thereafter a continuous tendency towards normalization of neopterin levels was observed. At the final visit immunoglobulin levels also tended to decrease. The HIV antigen seropositive child showed the highest neopterin levels during the whole study period. Our data indicate that the primarily high risk of developing AIDS in anti-HIV-seropositive haemophiliacs is declining.

Acquired Immunodeficiency Syndrome