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Biomedical subjects

G Hoffmann

Publications and source records attributed to G Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed1999

Evaluation of severe insomnia in the general population: results of a European multinational survey.

The epidemiology of severe insomnia and its effect on quality of life and healthcare consumption was assessed in a survey of the general population of five northern European countries. Applying established consumer sampling techniques, insomnia sufferers were selected from the general population using a questionnaire, conducted by face-to-face interview, and severity of insomnia was ranked (severe, mild/moderate, no sleep complaint) using a specific algorithm. Population samples were matched according to case control methodology for age, gender and geographical region. A second questionnaire gathered information on sleep problems, quality of life (SF-36 scores) and healthcare consumption. The prevalence of severe insomnia ranged from 4% to 22%, was higher in females than in males, but did not increase significantly with age. Patients with severe insomnia had been experiencing sleeping problems for a median of 2-6 years. In all countries, insomnia had a negative impact on quality of life, and the degree of impairment in quality of life was directly related to the severity of insomnia. Individuals with severe insomnia also showed a higher level of healthcare consumption. Despite this, severe insomnia did not appear to feature prominently in the doctor-patient relationship.

Adult↗
PubMed1999

Urokinase and plasminogen activator-inhibitor (PAI-1) status in primary ovarian carcinomas and ovarian metastases compared to benign ovarian tumors as a function of histopathological parameters.

Ninety-eight patients with histologically confirmed ovarian tumors (77 primary ovarian carcinomas of stages T1 to T3 according to the postoperative histopathological classification pTNM classification, 14 ovarian metastases of various origins and seven benign ovarian tumors) were investigated with regard to the concentration of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) in membrane extracts of tumors. The results were correlated with the clinical course and with histopathological findings. With more advanced stage of primary ovarian carcinomas, there was a highly significant rise in the membrane concentrations of both uPA and PAI-1. However, increasing dedifferentiation of the tumors correlated only with uPA, but not with PAI-1. There was no correlation between the number of steroid receptors for estradiol and progesterone and the content of uPA or PAI-1 in the primary ovarian carcinomas. In the 14 ovarian metastases of different origins incluced in the study, the contents of uPA and PAI-1 were comparable to those of primary ovarian carcinomas. Compared with the malignant ovarian tumors, the median uPA and PAI-1 concentrations in the membrane fraction were 2.5-6 fold lower (highly significant) in the group of seven benign tumors. A cut-off value of 4.8ng/mg pellet protein for a prognostically favorable (< 4.8) or unfavorable course (> 4.8) could be determined for uPA (p = 0.0392) but not for PAI-1 on the basis of the Kaplan and Meier survival curves in the malignant primary ovarian carcinomas.

Adult↗
PubMed1999

[Value of p53, urokinase plasminogen activator, PAI-1 and Ki-67 in vulvar carcinoma].

OBJECTIVE: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors. MATERIAL AND METHODS: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences. RESULTS: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients. CONCLUSIONS: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201.

Adult↗
PubMed1999

Anti-inflammatory and nitric oxide-inhibiting properties of granulocyte colony-stimulating factor.

A proposed scheme between the possible interactions of pro- and anti-inflammatory cytokines, NO and G-CSF during severe inflammation/infection is presented. Taken together, these data indicate that G-CSF exhibits anti-inflammatory properties which may prove to be beneficial in situations associated with an increased activity of the cellular immune system. Since the suppressive effects of G-CSF on the production of pro-inflammatory mediators like TNF-alpha and nitric oxide are most likely neither cell type nor tissue specific, it is conceivable that NO release induced by pro-inflammatory mediators can be reduced by G-CSF in various organ systems and in different forms of shock. In this context, G-CSF might represent a counterregulatory mechanism directed against a downstream oriented inflammatory response to infection. Therefore, the investigation of G-CSF in the prophylaxis of nonneutropenic infections, sepsis, and other severe inflammatory disorders seems reasonable.

Animals↗
PubMed1998

Granulocyte-colony stimulating factor inhibits inducible nitric oxide synthase gene expression in pulmonary epithelial cells in vitro.

Excessive release of nitric oxide (NO) is most likely a crucial pathophysiological pathway leading to pulmonary dysfunction. Thus, repression of supranormal NO production might be one beneficial mechanism of granulocyte-colony stimulating factor (G-CSF) in inflammatory processes. The aim of this study was to investigate the influence of G-CSF on inducible nitric oxide synthase gene expression in the alveolar epithelial cell line L2. We show that G-CSF suppresses interferon-gamma/tumor necrosis factor-alpha (TNF-alpha) induced inducible nitric oxide synthase gene expression detected as inducible nitric oxide synthase cDNA (cDNA concentration was 633 +/- 38 amol/microg total RNA following 24 h incubation with 100 U/ml interferon-gamma/500 U/ml TNF-alpha, and 440 +/- 14 amol/microg total RNA following 24 h incubation with 250 U/ml G-CSF +/- 100 U/ml interferon-gamma/500 U/ml TNF-alpha, respectively). In addition, application of G-CSF resulted in a decreased synthesis of inducible nitric oxide synthase protein and diminished NO release mediated by the cytokines. The suppression of inducible nitric oxide synthase gene expression in L2 cells by G-CSF may represent a beneficial counterregulatory effect on excessive NO synthesis induced by proinflammatory cytokines in the lung.

Animals↗
PubMed1998

Nup154, a new Drosophila gene essential for male and female gametogenesis is related to the nup155 vertebrate nucleoporin gene.

The Nup154 gene of Drosophila encodes a protein showing similarity with known nucleoporins: rat Nup155 and yeast Nup170 and Nup157. Hypomorphic mutant alleles of Nup154 affected female and male fertility, allowing investigation of the gene function in various steps of oogenesis and spermatogenesis. Nup154 was required in testes for cyst formation, control of spermatocyte proliferation and meiotic progression. In ovaries, Nup154 was essential for egg chamber development and oocyte growth. In both the male and female germ line, as well as in several other cell types, the Nup154 protein was detected at the nuclear membrane, but was also present inside the nucleus. Intranuclear localization has not previously been described for rat Nup155 or yeast Nup170 and Nup157. In mutant egg chambers the Nup154 protein accumulated in the cytoplasm, while it was only barely detected at the nuclear envelopes. FG repeats containing nucleoporins detected with mAb414 antibody were also mislocalized to a certain extent in Nup154 mutant alleles. This suggests that Nup154 could be required for localizing other nucleoporins within the nuclear pore complex, as previously demonstrated for the yeast Nup170. On the other hand, no evident defects in lamin localization were observed, indicating that Nup155 mutations did not affect the overall integrity of the nuclear envelope. However, ultrastructural analyses revealed that in mutant cells the morphology of the nuclear envelope was altered near the nuclear pore complexes. Finally, the multiplicity of phenotypes observed in Nup154 mutant alleles suggests that this gene plays a crucial role in cell physiology.

Amino Acid Sequence↗
PubMed1998

Granulocyte-colony stimulating factor inhibits TNFalpha production in a human hepatoma cell line.

The syndrome of cachexia associated with malignant diseases can be in part attributed to the effects of tumour necrosis factor alpha (TNFalpha) which itself is produced by a variety of tumour cells. We have recently reported that the human hepatoma cell line HepG2 expresses the TNFalpha gene and releases biologically active TNFalpha protein after stimulation with interleukin-1beta (IL-1beta). Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein necessary for the proliferation and differentiation of neutrophil progenitor cells in the bone marrow. In addition G-CSF has been reported to exert anti-inflammatory effects. In our study we tested the effect of recombinant human G-CSF (rhG-CSF) on TNFalpha production in HepG2 cells. It could be shown that rhG-CSF (250 U/ml) significantly reduced IL-1beta-induced (300 pg/ml) TNFalpha gene expression after 1-h and 3-h incubation periods (TNFalpha mRNA concentrations were: 8.8+/-2.1 amol/ microg total RNA after a 1-h incubation with IL-1beta versus 3.8+/-1.3 amol/ microg total RNA after a 1-h incubation with IL-1beta + rhG-CSF and 13.8+/-2.2 amol/ microg total RNA after a 3-h incubation with IL-1beta versus 8.8+/-2. 1 amol/ microg total RNA after a 3-h incubation with IL-1beta + rhG-CSF). From these data we conclude that rhG-CSF is a potent inhibitor of cytokine-induced TNFalpha production by tumour cells. Therefore, treatment of patients with malignant diseases with rhG-CSF might represent a useful tool to improve the tumour-associated cachexia.

Carcinoma, Hepatocellular↗
PubMed1998

Neopterin induces nitric oxide-dependent apoptosis in rat vascular smooth muscle cells.

Numerous studies indicate that proinflammatory substances like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) as well as macrophage-derived neopterin are increased in atherosclerotic tissue and thus are potentially involved in the process of atherogenesis. Since apoptotic death of vascular smooth muscle cells (VSMC) is reported to occur in atherosclerotic lesions, we investigated the effects of neopterin, TNF-alpha, and IFN-gamma on apoptosis in cultured VSMC. Morphological changes characteristic of apoptosis as well as DNA fragmentation were detected in cells treated with neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma. Simultaneously, neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma led to inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) synthesis. NO generation was significantly reduced when cells were cotreated with the competitive iNOS inhibitor aminoguanidine. This was accompanied by decreased percentual apoptosis as detected by FACS analysis using all kinds of stimuli. We conclude that neopterin as well as TNF-alpha/IFN-gamma are potent mediators of apoptotic death in VSMC which is at least in part triggered by NO synthesis induced by these proinflammatory mediators.

Animals↗
PubMed1998

Diversity among clinical isolates of Proteus penneri detected by random amplified polymorphic DNA analysis.

DNA of thirteen haemolytic Proteus penneri strains of clinical origin, all producing calcium dependent haemolysin and having been derived from four European countries was examined for plasmid profile, and outer membrane protein profile, by random amplified polymorphic DNA-PCR (RAPD-PCR) method, and digestions with restriction endonucleases were performed. All strains contained two large plasmids of approximately 60 and 70 kilobase pairs (kb). In addition, four strains contained a small plasmid of about 6 kb. These four strains produced cell-bound haemolysin only. Outer membrane protein analysis revealed subtle differences between strains. RAPD-PCR with primer I (CCGCAGCCAA) revealed 13 types, whereas primer II (AACGCGCAAC) yielded only two main types of different patterns. Results with primer I suggests a DNA sequence diversity within this species. The RAPD-PCR method provides a fast, economical and reproducible means for the typing of P. penneri. Digestion with restriction endonucleases indicated a high level of DNA methylation in this species.

Bacterial Outer Membrane Proteins↗
PubMed1998

[Rivet-like titanium clamps for refixation of bone covers after craniotomy--radiologic identification, safety and image quality in CT and MR studies].

PURPOSE: The MRI and CT compatibility of a new design of metallic fixation implants for cranial bone flaps was investigated experimentally and following clinical application in craniotomy patients. Is imaging quality impaired through implant-induced artifacts? METHODS: Possible induced movement and heating of the clamp implant as well as the magnitude of susceptibility artifacts were assessed experimentally by MRI at 1.5 T. Additionally, implant-induced artifacts were evaluated under clinical conditions for all relevant MRI-sequences in 100 craniotomy patients whose skull flaps were re-affixed using the new clamp implant. RESULTS: In T1-weighted spin echo and fast spin echo sequences the sizes of implant-induced artifacts were equal to the size of the implant or slightly larger; in T2-weighted gradient echo images artifacts were maximally double the size of the implant itself. Induced movement or heating was not observed. CONCLUSIONS: The safety in radiological imaging of titanium clamp implants for fixation of craniotomy bone flaps was established experimentally as well as under clinical conditions. The clamps can be easily identified by radiological imaging, cause no hazards to the patients, and have little effect on image quality.

Artifacts↗
PubMed1998

Long-term outcome of chronic hepatitis C infection in a low-prevalence area.

BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important causative factor in the development of liver cirrhosis and hepatocellular cancer (HCC), the strength of this correlation has been difficult to confirm in low-prevalence areas. METHODS: Stored serum samples from 987 consecutive (1978-88) patients with chronic liver disease were tested with an enzyme-linked immunosorbent assay for anti-HCV and further confirmed by immunoblot. To evaluate the long-term outcome, the cohort was followed up until 1995, for a median observation time of 10 years. RESULTS: Anti-HCV, confirmed by immunoblot, was found in 9.5% (94 of 987) of the patients, and at inclusion most patients were asymptomatic irrespective of anti-HCV status. Of the 445 patients who died during the study period, 44 were HCV-positive. A liver-related cause of death was far commoner and the age-adjusted survival shorter among HCV-positive patients than among HCV-negative ones. At death 68% (30 of 44) of the HCV-positive subgroup had developed cirrhosis, and 30% (13 of 44) had concurrent HCC, as compared with 36% (142 of 393) (P = 0.001) and 8% (31 of 393) (P = 0.001), respectively, of the HCV-negative subgroup. HCV infection (P < 0.001), alcohol abuse (P < 0.001), and immigrant status (P = 0.045) were independent factors with regard to the development of cirrhosis, whereas HCV infection (P = 0.040) and immigrant status (P = 0.012) were independent factors with regard to HCC. CONCLUSIONS: HCV infection is common among patients with chronic liver disease, even when clinical evidence of viral infection is sparse, and constitutes a significant cause of death even in a low-prevalence area.

Carcinoma, Hepatocellular↗
PubMed1998

Neopterin-induced tumor necrosis factor-alpha synthesis in vascular smooth muscle cells in vitro.

Synthesis and secretion of proinflammatory mediators like tumor necrosis factor-alpha and neopterin are common events in severe systemic inflammatory disorders, e.g. sepsis and septic shock. Recent data suggest that both substances show similarities with respect to their bioactivities. In the present study we investigated the potential interactions of neopterin and tumor necrosis factor-alpha on inducible nitric oxide synthase gene expression and nitric oxide generation in rat vascular smooth muscle cells. In addition, we studied the influence of neopterin on tumor necrosis factor-alpha synthesis in this cell type. Single stimulation of smooth muscle cells with either neopterin or tumor necrosis factor-alpha caused inducible nitric oxide synthase gene expression and nitric oxide production. Coincubation of cells with both compounds resulted in at least additive effects on nitric oxide synthesis. Quantification of tumor necrosis factor-alpha cDNA revealed a dose-dependent effect of neopterin on tumor necrosis factor-alpha gene expression. Similar results were obtained concerning the detection of tumor necrosis factor-alpha protein and the assessment of tumor necrosis factor-alpha bioactivity. These data suggest that neopterin and tumor necrosis factor-alpha are closely associated with regard to synthesis and effects, respectively. The interactions of both inflammatory mediators in vascular smooth muscle cells might contribute to the excessive release of nitric oxide observed during sepsis, thus triggering cellular destruction and multiple organ failure.

Animals↗
PubMed1998

[Pyrethroids in house dust of the German housing population--results of 2 nationwide cross-sectional studies].

As a part of the German Environmental Surveys performed in 1985/86 (West Germany), 1990/91 (West Germany) and 1991/92 (East Germany), dust samples were collected in the households of about 1600 randomly selected adults (25 to 69 years) and an analysis of these samples was performed in respect of their content of 8 different pyrethroids and of the synergist piperonyl butoxide (PBO). In the 1990-92 survey about 90% of the samples contained permethrin in concentrations above the limit of quantification. This showed permethrin to be the most widespread of the 8 compounds investigated. The geometric mean of the permethrin content in domestic dust was 0.22 mg/kg. Only about 8% of the samples contained one or more of the other investigated substances (cyfluthrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, deltamethrin, empenthrin, d-phenothrin) in quantifiable amounts. About 76% of the samples contained quantifiable amounts of PBO. In East Germany the geometric mean of the PBO content (0.21 mg/kg) was significantly higher than in West Germany (0.07 mg/kg), but no difference for permethrin was found. Significant associations could be shown for the permethrin content and the application of biocides as well as for the PBO content and regional factors (size of community, type of dwelling area). Samples collected in 1985/86 (West Germany) showed a geometric mean for permethrin of 0.06 mg/kg and for PBO of 0.07 mg/kg. Comparing the values of 1985/86 and 1990/91, a significant increase can be observed for permethrin, whereas the PBO concentration remained constant.

Adult↗
PubMed1998

[Analysis of subjective effect, acceptance and costs of conservative treatment of prolapse and incontinence in women].

A renaissance of conservative treatment for urinary incontinence and descensus is taking place presently in the German speaking area for pre-surgical improvement of tissue quality as well as for long-term-treatment replacing or postponing surgery. Modern pessaries (shape and material), a more intense and pathophysiological well-founded physiotherapy as well as the support of treatment by electrostimulation and its completion by adequate hormone substitution lead to a successful conservative treatment. "Gesundheitsstrukturreform" (reformatory measures of the German Public Health System), "Fallpauschalen" (flat-rate tariff of treatment by the case) and "Praxisbudgets" (budgets for out-clinic-treatment by the case, also a form of flat-rate tariff) lead to a restriction in prescribing necessary conservative treatment or preventive measures. Assigning the patient to surgical treatment is therefore in large parts favoured (treatment costs are then charged to clinic budgets). On the basis of the presented exemplary cost analysis completed by data on subjective effectiveness, acceptance and evaluation of efforts for patient and doctor we want to show that it is not either method that has to be considered in the treatment but both. Besides we have to treat the patient sequentially-conservative treatment in most cases first, especially in younger women. Conservative treatment thereby offers the possibility to delay or postpone surgery, a very meaningful option offered regarding the relatively poor results of surgery especially in cases of recurrent disease.

Adult↗