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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 505 records · Page 28Linked to original sources

A simple index relating clinical activity in Crohn's disease with T cell activation: hematocrit, frequency of liquid stools and urinary neopterin as parameters.

Crohn's disease is characterized by alternating acute and quiescent periods. Several indices for activity of the inflammatory process have been proposed to have criteria for prognosis of the clinical course and therapeutic efficacy. Neopterin is specifically released from human monocytes-macrophages after induction by interferon-gamma secreted from activated human T lymphocytes. Thus, urinary neopterin excretion is elevated in diseases involving activation of cellular immunity. Fifteen clinical and laboratory parameters, including urinary neopterin levels, collected from 35 visits of patients with Crohn's disease, were compared using multiple linear regression analysis with a simple clinical activity index as reference. Prediction of clinical activity was best with the combination of hematocrit, weekly number of liquid stools and neopterin. A simple triple-parametric Crohn's disease activity index was established on the basis of this result. Its quality was tested on independent data obtained from 25 repeat visits of 13 of these patients. A comparison with the well-known Crohn's Disease Activity Index (CDAI) was performed. The results obtained with the proposed activity index were slightly better than those with the eight-parametric CDAI for the data from the first as well as from the repeat visits. We conclude that our simple index is a reliable and easily accessible measure for clinical activity in patients with Crohn's disease.

Adolescent↗

Colchicine suppression of local inflammation due to calcinosis in dermatomyositis and progressive systemic sclerosis.

Two girls, one with progressive systemic sclerosis and a second with dermatomyositis, developed calcinosis in the skin of the prepatellar area. Calcinosis was accompanied by local inflammation and skin ulceration. Oral colchicine therapy in a dosage of 1 mg per day was followed within two months by significant regression of local inflammation and healing of the skin ulcers.

Administration, Oral↗

Significance of urinary neopterin in patients with malignant tumors of the genitourinary tract.

The urinary neopterin excretion was measured by high-performance liquid chromatography in 417 healthy subjects and in 76 patients with clinically and pathohistologically verified neoplasias of the urinary tract (bladder tumor, carcinoma of the prostate, and renal cell carcinoma). The patients with early tumor stages both with bladder tumor and carcinoma of the prostate had normal urinary neopterin levels, except one patient with bladder tumor who had a value at the upper confidence limit. Of 40 patients with higher stages of bladder tumor and carcinoma of the prostate, 35 had elevated urinary neopterin levels. Two of 10 patients with bladder tumor in stage T3, 1 of 4 patients with carcinoma of the prostate Stage C, and 2 of 15 patients with prostatic cancer Stage D showed normal neopterin levels. The patients with renal cell carcinoma did not demonstrate any definite correlation between tumor stage and urinary neopterin excretion. The current study suggests that the neopterin assay may supplement laboratory measurements in tumors of the urinary tract, providing helpful information regarding case selection for the most convenient therapeutic management and postoperative follow-up.

Adolescent↗

[1st case of AIDS in Salzburg. Important diagnostic hint by determination of neopterin].

This case report describes the first case of AIDS in Salzburg. The patient belonged to the male homosexual risk group. He presented with opportunistic infections: oral candidiasis, bilateral Pneumocystis carinii pneumonia and cerebral toxoplasmosis. The diagnosis of AIDS was corroborated by highly elevated urinary neopterin levels. Despite treatment with antibiotics the patient died within 5 weeks due to cardiorespiratory insufficiency.

Acquired Immunodeficiency Syndrome↗

Neopterin release in human mixed lymphocyte culture: requirement of HLA-DR disparity.

Recent evidence suggests that immune responses in vivo as well as in vitro are accompanied by release of neopterin [C. H. Huber, et al. (1983) J. Immunol. 130, 1047]. This investigation aimed to elucidate the genetic control of in vitro neopterin release in family mixed lymphocyte culture (MLC) studies. Neopterin levels and responder cell proliferation were assessed in a total of 92 MLCs established from different intrafamilial combinations. Results indicated a strong association between the magnitude of responder cell proliferation and the neopterin levels induced by stimulation with allogeneic cells. This conclusion was based on three findings: first, almost no neopterin release and proliferation was seen in MLCs established between HLA genotypically identical siblings; secondly, very low proliferation and neopterin levels were observed in MLCs between HLA-DR phenotypically identical family members; and thirdly, high neopterin release and strong cellular proliferation were a feature of MLCs established between individuals differing for at least one HLA-DR antigen. We thus conclude that T cell activation subsequent to recognition of HLA-DR disparity represents an essential prerequisite for induction of neopterin release in human MLC.

Biopterins↗

Neopterin levels in long-term renal allograft recipients.

In this paper we present results dealing with neopterin levels in the urine of 21 kidney grafted patients during long-term allograft survival. Data dealing with results of urinary neopterin excretion to predict acute cellular allograft rejection during the immediate post-transplant period have been reported previously. The evaluation of patients included a physical investigation and numerous biochemical parameters as described below. We found that neopterin excretion is normal or elevated, but if elevated levels remain stable the prognosis for the allograft seems to be good.

Biopterins↗

Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis.

In previous publications we showed that neopterin, a pyrazino-pyrimidin compound, represents a biochemical marker for the assessment of cellular immune responses. We thought that the evaluation of this marker molecule might enable insight into the activity of cellular immune responses underlying ulcerative colitis (UC). Evaluation of urinary neopterin excretion in 25 consecutive untreated UC patients revealed striking correlations between neopterin levels and the severity of disease: elevated levels were observed in 9 out of 9 patients with moderately severe to severe, in 3 of 4 with mild and in none of 12 patients with quiescent disease. Further evidence for a correlation between disease activity and neopterin excretion was obtained on the basis of long-term follow-up studies performed in 4 cases. These studies indicated normalization of neopterin levels when clinical remission was achieved. Thereafter, the relative significance of neopterin excretion for determination of clinical stage was assessed by linear correlation analyses and was compared with conventional clinical parameters such as anemia, number of motions per day, raised temperature, ESR and extent of bowel involvement. The logarithm of neopterin excretion and the extent of bowel involvement were the two single parameters most closely related to the clinical stage of ulcerative colitis. We, therefore, conclude that evaluation of neopterin excretion in ulcerative colitis patients represents a new and useful tool for the clinical monitoring of disease activity.

Adolescent↗

The value of urinary neopterin as an immunological parameter in patients with malignant tumors of the genitourinary tract.

In 153 patients with verified neoplasias of the genitourinary tract, urinary neopterin excretion was monitored under different conditions. As control, urinary neopterin values were taken from 208 male and 209 female volunteers. Neopterin excretion was measured by high performance liquid chromatography. Patients with early tumor stages, both with bladder tumor and carcinoma of the prostate, presented almost normal urinary neopterin levels. The difference of urinary neopterin excretion between low and high stages in bladder tumor (T0-1 versus T2-4) as well in carcinoma of the prostate (stage A-B versus stage C-D) is highly significant (p less than 0.001). In the group of patients with renal cell carcinoma we could not find any correlation between tumor stage and neopterin excretion. The basal urinary neopterin values in patients with testicle tumors were as follows: 1 of 6 patients stage-I seminomatous tumors and 2 of 4 patients with stage-I non-seminomatous tumors demonstrated elevated neopterin levels. In the higher stages all patients, in both groups, exhibited pathologically increased neopterin excretion. During therapy and follow-up: all 24 stage-I (seminomatous and non-seminomatous tumors) patients showed normal neopterin levels: 1 of 3 stage-II (non-seminomatous tumors) patients and all 5 stage-IV (seminomatous and non-seminomatous tumors) patients had elevated urinary neopterin excretion. Our experience suggests that neopterin measurements may supplement laboratory examinations in patients with malignant tumor diseases of the genitourinary tract, providing meaningful information in regard to early detection of tumor progression, tumor recurrence and follow-up.

Adolescent↗

Identification of 3-hydroxyanthranilic acid in mixed lymphocyte cultures.

3-Hydroxyanthranilic acid was identified in lymphocyte cultures during allogeneic stimulation. The metabolite and the synthetic product have identical HPLC retention times, fluorescence spectra, fluorescence intensities as a function of pH value and electrochemical behaviour.

3-Hydroxyanthranilic Acid↗

[NK and K cell activity in children with leukemias and aplastic anemias before and after allogeneic bone marrow transplantation].

Mononuclear leukocytes from the peripheral blood and bone-marrow of children affected with aplastic anemia and leukemia were investigated for K-cell activity (antibody-dependent cellular cytotoxicity) and NK-cell activity before and after allogenous bone-marrow transplantation. 51Cr liberation test against murine Graffi erythroblast leukemic cells covered with xenoantibodies and K-562 cells were used for identification. Strongly lowered NK- and K-cell activities could be found in aplastic anemia prior to bone-marrow transplantation. However, NK-cell activity was only lowered significantly in leukemic patients with indication of bone-marrow transplantation. K-cell and NK-cell activities normalised after bone-marrow transplantation. K-cell and NK-cell activities could be observed to be reconstituted very early after bone-marrow transplantation.

Anemia, Aplastic↗

Neopterin, a biochemical indicator of cellular immune reactions, in the detection and control of patients with neoplastic diseases.

The incidence of elevated neopterin levels is presented for 748 patients with various malignancies. The mean urinary neopterin levels varied directly with stage and in patients with carcinoma of bladder according to histological grade of disease. In 178/208 patients with subsequent treatment for gynecological cancer, neopterin levels returned to normal within 3 weeks when tumor remission was achieved but remained high or even raised when persistent or recurrent cancer was later diagnosed. In 160 patients suffering from cervical carcinoma, significant differences in survival were demonstrated by Cox regression when patients were grouped according to their pretherapeutical neopterin level.

Adolescent↗

Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma.

Neopterin, a compound derived from GTP, represents a precursor molecule of biopterin that is an essential cofactor in neurotransmitter synthesis. We have recently reported that in vivo as well as in vitro immune responses are accompanied by an increased release of neopterin and that this phenomenon can be used for the biochemical monitoring of diseases accompanied by hyperimmune stimulation. This article deals with the cellular origin and the control of this immune response-associated neopterin release in vitro. Using highly purified or monoclonal cellular reagents we demonstrate that macrophages (M phi) stimulated with supernatants from activated T cells release large amounts of neopterin into culture supernatants. Further experiments involving induction of neopterin release from M phi with various human recombinant interferons (IFNs) or neutralization of the effect of T cell supernatants with various monoclonal anti-IFN antibodies revealed immune IFN as the active principle. It thus appears that a metabolic pathway so far exclusively known in context with the generation of an essential cofactor of neurotransmitter-synthesis during immune responses is also activated in M phi under stringent control by immune IFN-like lymphokines.

Biopterins↗