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Biomedical subjects

F Stüber

Publications and source records attributed to F Stüber.

47 records · Page 3Linked to original sources
PubMed1998

Gender differences in human sepsis.

BACKGROUND: In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE: In a prospective study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS: In a prospective study, tumor necrosis factor alpha and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-beta estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital-mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS: In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.

APACHE↗
PubMed1998

[Pentoxifylline as adjuvant therapy of multiple organ failure].

To evaluate the therapeutic effect of pentoxifylline (POF) on cardiopulmonary, renal and hepatic dysfunction, 51 patients with sepsis were randomized to receive POF or saline solution as placebo. Continuous intravenous administration of POF beneficially influenced cardiopulmonary organ function without adverse effects. PO2/FiO2-ratio as parameter of pulmonary dysfunction was significantly improved in the second week after diagnosis while parameter of cardial function were significantly different in the initial phase of sepsis. The clinical efficacy of POF in terms of organ dysfunction, however, did not result in improved survival.

Combined Modality Therapy↗
PubMed1997

Tumour necrosis factor alpha promoter gene polymorphism in sarcoidosis.

Biallelic polymorphisms in the promoter region of the TNF-alpha gene (TNFA) and in the first intron of the TNF-beta gene (TNFB) have been associated with variation in TNF-alpha production and with susceptibility to severe diseases. Among other functions, TNF-alpha plays a pivotal role in regulatory aspects of granuloma formation and sustenance. In sarcoidosis, a systemic granulomatous disorder of unknown aetiology, the clinical course of the disease has been associated with the patient's individual capacity of spontaneous TNF-alpha production by alveolar macrophages. We determined the TNFA and TNFB polymorphisms in 101 patients with pulmonary sarcoidosis and 216 healthy blood donors. A highly significant shift to the more uncommon TNFA2 allele was found in the Löfgren syndrome patient group, which represents the acute form of the disease with frequent spontaneous remission. The results show that gene frequencies of the TNFA gene variation are significantly different within the clinical forms of sarcoidosis, indicating that genetic predisposition for TNF-alpha production may play a role in the pathogenesis of the disease.

Humans↗
PubMed1996

A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis.

OBJECTIVES: To determine the allele frequency and genotype distribution of a bi-allelic tumor necrosis factor (TNF) gene polymorphism and plasma TNF-alpha concentrations in postoperative intensive care unit (ICU) patients suffering from severe sepsis. DESIGN: Prospective, consecutive entry study of patients with severe sepsis in a postoperative ICU. SETTING: University hospital. PATIENTS: Forty patients with diagnosis of severe sepsis, admitted to the ICU between June 1993 and December 1994. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A 782 basepairs fragment of genomic DNA, including the polymorphic site of the restriction enzyme Ncol within the TNF locus, was amplified by means of polymerase chain reaction. The genotype of each patient was determined after Ncol digestion of the amplified product and subsequent agarose gel electrophoresis. Reading the size of the resulting DNA bands from the agarose gel demonstrated the genotype, as defined by the two alleles TNFB1 and TNFB2. Serial blood samples were drawn every sixth hour during the first 48 hrs and every 12th hour thereafter, for < or = 96 hrs after diagnosis. TNF-alpha plasma concentrations were detected by an enzyme-linked immunosorbent assay. Assessment of organ dysfunction was performed by calculating a Multiple Organ Failure score. The overall allele frequency (TNFB1 0.35; TNFB2 0.65) and genotype distribution (TNFB1 homozygotes 10%; TNFB1/TNFB2 heterozygotes 48%; TNFB2 homozygotes 42%) in 40 patients with severe sepsis were comparable with those values found in normal individuals. Development of multiple organ failure occurred in 33 (82.5%) of 40 patients, whereas 23 (57.5%) of 40 patients did not survive. In contrast to the overall allele frequency, nonsurvivors showed a significantly higher prevalence of the allele TNFB2(p < .005). Patients homozygous for the allele TNFB2 demonstrated a higher mortality rate than heterozygous (TNFB1/TNFB2) patients (p = .0022). In addition, patients with TNFB2 homozygotes displayed higher circulating TNF-alpha concentrations as well as higher Multiple Organ Failure scores compared with heterozygous (TNFB1/TNFB2) patients. CONCLUSIONS: The bi-allelic Ncol polymorphism within the TNF locus is a genomic marker for patients with increased TNF-alpha response and poor prognosis in severe sepsis. The amount of TNF released in situations of severe infection and sepsis appears to be influenced genetically. TNFB2 homozygous individuals displaying increased circulating TNF plasma concentrations combined with high mortality rate may be included in future studies testing anti-TNF strategies in severe sepsis.

Acute Disease↗
PubMed1996

Phytohemagglutinin-dependent T-cell proliferation is not impaired by morphine.

Opioids have been reported in the literature to have immunosuppressive properties. Thus, we investigated the influence of morphine, morphine-3-glucuronide and morphine-6-glucuronide in vitro on phytohemagglutinin-stimulated proliferation of peripheral mononuclear cells from healthy humans. Furthermore, the effects of a 1-week treatment with morphine in a range of 30-240 mg/day on proliferation of lymphocytes from patients with chronic pain syndromes were evaluated. In addition, human peripheral mononuclear cell membranes were tested for specific opioid radioligand binding. The results show that i) morphine and its main metabolites do not influence mitogen-induced T-cell proliferation, ii) treatment of patients with sustained release morphine for 1 week did not impair the lymphocyte proliferative response, and iii) no specific binding of mu-, delta- and kappa-radioligands could be demonstrated to membranes of peripheral lymphocytes obtained from healthy humans. These results do not indicate an impairment of phytohemagglutinin-induced T-cell proliferation during pain treatment with sustained release morphine.

Analgesics, Opioid↗
PubMed1992

A rheumatoid factor from a normal individual encoded by VH2 and V kappa II gene segments.

OBJECTIVE: To gain insight into the immunoglobulin variable-region repertoire of anti-IgG antibodies (rheumatoid factors [RF]), we characterized the VH and V kappa gene segments utilized in an IgM-RF-secreting lymphoblastoid cell line (SSH23) isolated from a normal individual. METHODS: The cell line SSH23 was established by Epstein-Barr virus transformation of peripheral blood non-T mononuclear cells. First-strand complementary DNA (cDNA) was generated and used for polymerase chain reaction amplification of the heavy and light chain variable domains. The amplified variable domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be identical to a previously described fetal VH2 incomplete cDNA and to differ by only 3 nucleotides from a JH proximal germline VH2 gene segment. To our knowledge, this is the first example of a VH2 rheumatoid factor. The V kappa 2-J kappa 4 light chain contains an uncommon 10-amino acid third complementarity-determining region (CDR 3). CONCLUSION: Utilization of preimmune fetal VH gene segments and unusual light chain junctional diversity appear to be features shared by many physiologic and pathologic rheumatoid factors.

Amino Acid Sequence↗
PubMed1989

Interleukin 2 as an inducer of proliferation in Klebsiella-stimulated human B cells.

Klebsiella membranes (KLEBS M), a membrane preparation from Klebsiella pneumoniae, acts as a T-cell independent polyclonal B-cell activator (PBA), stimulating B cells to mature into Ig-secreting cells without prior proliferation. The KLEBS M-activated B cells express Tac antigen. Recombinant interleukin 2, used in costimulation with KLEBS M, induces proliferation and increases the Ig secretion of B cells. On the other hand, KLEBS M-activated B cells do not respond to human BCGF. The lack of proliferation in KLEBS M-stimulated mononuclear cells is shown to be due to the inability of this PBA to induce the production of interleukin 2 in T cells.

B-Lymphocytes↗
PubMedDate not supplied

Pattern of soluble TNF receptors I and II in sepsis.

The serum levels of soluble TNF receptors I (sTNFR I) and sTNFR II were measured frequently in 14 patients with sepsis to evaluate the pattern of these TNF antagonists in relation to TNF alpha, Soluble TNFR I and II could be detected in all samples with significantly higher levels (p < 0.001) compared to healthy controls. The concentration of sTNFR I as well as sTNFR II was significantly higher in nonsurvivors compared to survivors during the first 36 h of sepsis (p < 0.001). Levels remained elevated throughout the evaluation with maximal values in patients who died. A positive correlation exists between both receptors and between soluble receptors and simultaneously obtained sepsis score (p < 0.01) while TNF immunoreactivity detected in 80% of all samples did not correlate to soluble receptor levels or sepsis score. Soluble receptors were constantly found in the circulation representing the inflammatory state throughout the evaluation even when TNF activity was undetectable.

Adult↗
PubMedDate not supplied

Pilot study assessing TNF gene polymorphism as a prognostic marker for disease progression in neonates with sepsis.

In adult postoperative intensive care patients, the biallelic Ncol polymorphism within the tumor necrosis factor (TNF) locus has been shown to be a genomic marker for individuals with increased TNF-alpha response and poor prognosis in severe sepsis. We characterized the genomic distribution and allele frequency of the Ncol polymorphism in 23 preterm and term neonatal intensive care unit (NICU) patients with culture-proven sepsis and compared it with clinical and laboratory characteristics to assess its prognostic value for disease progression. Genotype analysis demonstrated the following absolute (relative) frequencies: 7 (0.31) infants were homozygous for the allele TNFB2 (Group A). 12 (0.52) infants were heterozygous (TNFB1/TNFB2) and four (0.17) infants homozygous for the allele TNFB1 (Group B). There was no significant difference compared to adult intensive care patients with severe sepsis (p = 0.31). The median gestational age of all infants (13 female and ten male) as well as for either group was 28 weeks (range 23-37) with a median birth weight of 845 g (range 560-2,720). The study population included a total of 16 very low birth weight (VLBW) infants, four in Group A and 12 in Group B. However, there was no significant difference for gestational age and birth weight in both groups (p = 0.82 and 0.71, respectively). Laboratory parameters as maximum and minimum leukocyte and thrombocyte counts, maximum immature to total neutrophil ratios (ITR), maximum C-reactive protein (CRP) levels, days of CRP levels > 5 mg/l and total days of antibiotic treatment, were not statistically different in both groups. In total, three infants (13%) died in consequence of their underlying disease. Two infants belonged to Group A and one to Group B. The statistical analysis of outcome variables (mortality, neurological impairment, failure to thrive) was not possible, because the study population was small and the reasons for poor outcome and death in these high-risk patients had to be considered multifactorial. In conclusion, in this pilot study the biallelic Ncol polymorphism within the TNF locus was not a prognostic marker for disease progression in high-risk NICU-admitted term and preterm infants with culture-proven sepsis. In order to detect differences in outcome similar to adult postsurgical patients with severe sepsis, an unfeasibly high number of NICU patients with culture-proven sepsis would need to be included for a similar study.

Adult↗