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Biomedical subjects

W Voigt

Publications and source records attributed to W Voigt.

At least 19 recordsLinked to original sources
PubMed2007

A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis.

GOALS OF WORK: Comparing antiemetic efficacy of different 5-HT(3)-receptor antagonists (5-HT(3)RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV). PATIENTS AND METHODS: Comparisons between 5-HT(3)RAs were based on 44 randomized studies (including 12,343 patients) identified by MEDLINE, CANCERLIT or EMBASE searches and subcategorized by chemotherapy type (cisplatin- or non-cisplatin-based). MAIN RESULTS: When all studies were combined, granisetron was equivalent to ondansetron (n = 27), and showed an advantage vs tropisetron (p = 0.018; n = 12). Ondansetron vs tropisetron (n = 11) and ondansetron vs dolasetron (n = 3) revealed equivalence in each comparison. An advantage for 3 mg granisetron vs 8 mg ondansetron was found in non-cisplatin-based studies (p = 0.015; n = 6). Overall equivalence was seen between ondansetron, 24 or 32 mg, and granisetron, 2 or 3 mg, for all studies (n = 13). There was a possible advantage for higher (24 or 32 mg) vs lower (8 mg) ondansetron dose regimens with cisplatin-based trials (n = 6). No differences were seen between 3 and 1 mg granisetron doses (n = 6). CONCLUSIONS: Efficacy of 5-HT(3)RAs for preventing CINV following cisplatin- and non-cisplatin-based chemotherapy is comparable, with the exception of granisetron vs tropisetron. Some differences were noted in dosing subanalyses.

Antiemetics↗
PubMed2006

[Chemotherapy induced-vomiting--a practical guide for prevention and therapy].

Nausea and vomiting are considered as two of the most distressing side effects of chemotherapy. The frequency of nausea and vomiting depends primarily on the emetogenic potential of the chemotherapeutic agents used. With the introduction of the neurokinin-1-receptor-antagonists in combination with 5-HT(3) receptor-antagonists and steroid approximately 70-90 % of patients receiving highly emetogenic chemotherapy can be protected from emesis. Here, the most recent developments in the antiemetic therapy including the latest guidelines for antiemetic prophylaxis are described.

Antiemetics↗
PubMed2006

C-reactive protein is a strong independent predictor of death in type 2 diabetes: association with multiple facets of the metabolic syndrome.

INTRODUCTION: It has been suggested that atherosclerotic vascular disease is a chronic inflammatory process. The aim of this study was to investigate the importance of C-reactive protein (CRP) as a cardiovascular risk marker and predictor of death, as well as its relation to other factors of the metabolic syndrome in a cohort of type 2 diabetic patients at high risk of severe macrovascular complications. MATERIAL AND METHODS: 592 patients, aged 55 to 74 years (311 men, 281 women), with signs and symptoms of circulation deficits were examined by duplex ultrasound for suspected cerebrovascular and peripheral arterial disease and followed over a period of 5 years. At baseline, 292 patients of the total group had type 2 diabetes (49.3%). Ischemic heart disease was present in 40.2%, internal carotid stenosis in 21.9% and peripheral arterial disease in 39.7% of the subjects. RESULTS: During the observation period, 104 patients had died, 72 (69.2%) due to cardiovascular causes. Non-fatal myocardial infarction occurred in 39 patients (7.4%), non-fatal stroke in 70 patients (13.3%) and amputations because of gangrene were unavoidable in 24 patients (4.6%). In Cox regression analysis, CRP was the strongest predictor of death and cardiovascular death in the total cohort (RR 3.7 [95% CI 1.86-7.50] and 5.4 [2.13-13.76]), as well as in the type 2 diabetic subgroup (RR 3.3 [1.27-8.70] and 5.4 [1.44-20.0]). In contrast neither the traditional cardiovascular risk factors nor the data of diabetic metabolic control were able to improve prediction. CRP was correlated positively with plasma levels of triglycerides (r=0.19, p=0.002), C-peptide (r=0.21, p=0.004), postprandial glucose (r=0.17, p=0.009), albuminuria (r=0.16, p=0.020), and inversely with HDL cholesterol (r=-0.20, p=0.002) in type 2 diabetic patients. CONCLUSIONS: CRP seems to be a better predictor of death and cardiovascular events than traditional risk factors or parameters of metabolic control in type 2 diabetic patients at high risk for cardiovascular endpoints. Additionally, CRP is associated with several facets of the metabolic syndrome.

Aged↗
PubMed2006

Enterobacterial autoinducer of growth enhances shiga toxin production by enterohemorrhagic Escherichia coli.

The addition of the enterobacterial autoinducer of growth to nutrient-poor minimal medium markedly accelerated the exponential growth rates of strains of enterohemorrhagic Escherichia coli but had little or no effect on maximal cell densities in stationary phase. Growth in the presence of the autoinducer resulted in an approximately twofold enhancement in Shiga toxin production.

4-Butyrolactone↗
PubMed2005

Potential activity of paclitaxel, vinorelbine and gemcitabine in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) has a rapidly fatal course in the mostly elderly patients with a median survival after diagnosis of 4-12 months. Activity of commonly used chemotherapy (doxorubicin) is low, thus more active compounds need to be introduced into the therapeutic concept of ATC. Recently, based on preclinical data Ain et al. conducted a clinical phase II study with paclitaxel 96 h infusion in ATC achieving a promising response rate of 53%. To further improve therapeutic options in ATC, we evaluated the activity of topotecan, oxaliplatin, vinorelbine, gemcitabine and paclitaxel in comparision to cisplatin and doxorubicin (1 and 96 h drug exposure) alone or in combination in the ATC cell lines SW1736 and 8505C. IC50 values were determined by the sulforhodamine B assay, potential clinical activity was estimated by relative antitumor activity (RAA) and drug interaction was analyzed using a parametric response surface approach (Greco model) of the Loewe additivity. Duration of drug effect was estimated by regrowth kinetics. We found paclitaxel, vinorelbine and gemcitabine active in ATC with RAA (1 h drug exposure) ranging from 86 to 454, 15 to 17 and 31 to 140, respectively. The activity of doxorubicin and cisplatin was moderate with RAA ranging from 1.4 to 2.2 and 0.2 to 0.3, respectively. Combined drug exposure of gemcitabine/paclitaxel and gemcitabine/vinorelbine was synergistic with a Loewe index > 0. However, these results did not reach statistical significance with p > 0.05. At clinically relevant drug concentrations paclitaxel, gemcitabine and vinorelbine but not oxaliplatin exerted a sustained growth inhibition after cessation of drug exposure for the complete assay time of 15 days. In conclusion, paclitaxel, gemcitabine and vinorelbine but not topotecan or oxaliplatin appeared to be active in anaplastic thyroid carcinoma based on RAA or growth delay at clinically relevant drug concentrations. Combinations of vinorelbine/gemcitabine and paclitaxel/gemcitabine exerted a trend to synergy. Thus, further evaluation of paclitaxel, vinorelbine and gemcitabine alone or in combination with ATC seems warranted.

Antineoplastic Agents↗
PubMed2005

Catecholate receptor proteins in Salmonella enterica: role in virulence and implications for vaccine development.

Three outer membrane proteins of Salmonella enterica serovar Typhimurium function as catecholate siderophore receptors. IroN promotes uptake of enterobactin, salmochelins and 2,3-dihydroxybenzoylserine, FepA transports enterobactin and 2,3-dihydroxybenzoylserine, and Cir is a receptor for 2,3-dihydroxybenzoylserine. In addition, all three proteins are required for l-norepinephrine-facilitated iron uptake from transferrin as judged by failure of a fepA iroN cir triple mutant to grow in serum-containing medium in the presence of l-norepinephrine. Moreover, pre-treatment of mice with l-norepinephrine resulted in enhanced systemic spread of the parental strain, but had no effect on the fepA iroN cir mutant. Inoculation of mice with the triple mutant, which is significantly attenuated, elicited a significant protective effect against subsequent challenge with the parental strain.

Animals↗
PubMed2003

Role of receptor proteins for enterobactin and 2,3-dihydroxybenzoylserine in virulence of Salmonella enterica.

Single, double, and triple mutants of an enterobactin-deficient mutant strain of Salmonella enterica serovar Typhimurium were constructed that were defective in the expression of the iron-regulated outer membrane proteins (IROMPs) FepA, IroN, and Cir, which are proposed to function as catecholate receptors. Uptake of naturally occurring and chemically synthesized catecholate molecules by these mutants was assessed in standard growth promotion assays. Unique patterns of uptake were identified for each IROMP; specifically, FepA and IroN were confirmed to be required for transport of enterobactin, and all three proteins were shown to function as receptors for the enterobactin breakdown product 2,3-dihydroxybenzoylserine. The fepA, iroN, and cir alleles were transduced to enterobactin-proficient strains of S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, and the resulting phenotypes were confirmed by analysis of outer membrane protein profiles, by sensitivity to KP-736, a catecholate-cephalosporin conjugate, and by growth promotion tests on egg white agar. Intragastric infections of mice with the S. enterica serovar Typhimurium strains indicated that the parental strain and the fepA iroN double mutant were similarly virulent but that the fepA iroN cir triple mutant was significantly attenuated. Moreover, in mixed infections, the fepA iroN mutant showed similar cecal colonization and invasion of the liver to the parental strain, while the triple mutant showed significantly reduced cecal colonization and no measurable spread to the liver. Infections of 4-day-old chicks with S. enterica serovar Enteritidis strains also indicated that mutation of the fepA iroN genes did not significantly reduce cecal colonization and systemic spread compared with those of the parental strain. The results indicate that, while enterobactin uptake is not essential for the virulence of S. enterica serovars in mouse and chicken infection models, the ability to take up 2,3-dihydroxybenzoylserine via any of the three catecholate siderophore receptors appears to play an important role, since the S. enterica serovar Typhimurium triple mutant was significantly attenuated in the mouse model. Salmochelins appear not to be involved in the virulence of S. enterica.

Animals↗
PubMed2002

Clonal diversity of Shiga toxin-producing Escherichia coli O103:H2/H(-) in Germany.

Shiga toxin producing Escherichia coli O103:H2/H(-) belong to the third most frequently isolated EHEC serotypes in Germany following isolates of O157:H7/H(-) and O26:H11/H(-). A total of 145 respective E. coli 103 isolates from single cases of diarrhoea and haemolytic uremic syndrome (HUS) in 1997-2000 were characterised by a range of molecular subtyping methods (PFGE, P-gene profiling, ribotyping, electrotyping) and phage typing in order to analyse their genetic relatedness and the practicability for new epidemiological tracing back. All isolates cluster into a distinct EHEC subgroup and reveal a high clonal diversity together with a considerable stability. Since strains of this serotype rank up to the third most frequently isolated EHEC in Germany a large population of this serotype, and therefore, a great supply of such strains may exist in this country.

Clone Cells↗
PubMed2002

Brackiella oedipodis gen. nov., sp. nov., gram-negative, oxidase-positive rods that cause endocarditis of cotton-topped tamarin (Saguinus oedipus).

A gram-negative, oxidase-positive, rod-shaped bacterium isolated from the heart of a cotton-topped tamarin was characterized by 16S rDNA sequence analysis, SDS-PAGE of whole-cell proteins, fatty acid analysis and biochemical tests. Outer-membrane proteins, iron-regulated outer-membrane proteins, lipopolysaccharides and siderophore production were studied. On the basis of the results, the organism belongs to the beta-Proteobacteria where it forms a separate line of descent, for which a novel genus and species are proposed, Brackiella oedipodis (LMG 19451T = DSM 13743T = NCIMB 13739T). Nearest phylogenetic neighbours of the new genus are Taylorella, Pelistega, Bordetella, Alcaligenes and Achromobacter.

Animals↗
PubMed2002

A new chemoembolization protocol in refractory liver metastasis of colorectal cancer--a feasibility study.

INTRODUCTION: In patients with advanced colorectal cancer (CRC) refractory to systemic chemotherapy including 5-fluorouracil (5-FU) / folinic acid (FA), oxaliplatin and irinotecan we assessed the feasibility, toxicity and response to hepatic transcatheter arterial chemoembolization (TACE). At the time of treatment, patients had exclusively or dominantly liver metastasis of CRC. PATIENTS AND METHODS: The following protocol was applied via a selective transfemoral hepatic arterial approach: mitomycin C 5 mg/m(2), interferon-alpha2b 4.5 Mio IU, dexamethasone 20 mg mixed with Amilomer DSM 45/25 (Spherex((R))) days 1 and 2 i.a. (bolus), oxaliplatin 50 mg/m(2) (2 h) day 1 i.a., FA 500 mg/m(2) (2 h) day 1 i.v., and 5-FU 1.500 mg/m(2) (24 h) day 1 i.a. Cycles have been repeated at days 15-22. The dose was adjusted according to the pretreatment performance status and elevation of alkaline phosphatase, bilirubin and serum albumin. Treatment was continued until progression or emergence of intolerable toxicity. RESULTS: 11 patients received a total number of 43 TACE, with a range of 2-6 per patient. There was no TACE-related mortality. 4 patients died 5, 8, 10 and 11 months after initiation of treatment due to progression of disease. 7 patients are alive at 4+ (n = 2), 5+ (n = 1), 6+ (n = 1), 7+ (n = 1) and 11+ (n = 2) months after start of treatment. Toxicity (CTC) was mild with grade I-II asthenia (n = 10), grade I-II neurotoxicity (n = 5), grade II nausea and/or vomiting (n = 2) and grade II diarrhea (n = 1). Treatment had to be postponed due to grade I thrombocytopenia in 2 patients. No bleeding episodes or obvious infectious complications occurred during treatment intervals. 1 patient experienced an allergic reaction to oxaliplatin which led to exclusion from further therapy. Arterial catheter dislocation occurred in 3 patients. In 10 patients evaluable for response we observed 3 partial responses, 2 minor responses, and 4 times stable disease. Only 1 patient had further progression of disease under treatment. CONCLUSION: TACE, using a combination of mitomycin C, dexamethasone and interferon-alpha2b mixed with Spherex((R)), followed by oxaliplatin, FA and 5-FU, appears to be an effective and feasible treatment option in the case of liver metastasis of CRC refractory to standard systemic chemotherapy. This treatment is associated with tolerable toxicity, which becomes apparent mainly as asthenia, neurotoxicity or thrombocytopenia. These preliminary data warrant further evaluation for patients with refractory disease and would probably also be of interest for first-line treatment in this patient population.

Adult↗
PubMed2000

Clonal diversity of Shiga toxin-producing Escherichia coli O157:H7/H- in Germany--a ten-year study.

Two hundred and ten E. coli O157:H7/H- strains isolated from single cases and outbreaks of diarrhoea and haemolytic uraemic syndrome (HUS) in Germany between 1988 and 1998 were characterised by a range of molecular subtyping methods and phage typing in order to analyse their clonal nature. A high clonal heterogeneity, together with a considerable clonal stability, has been identified among the bacterial isolates and no single clonal type appeared to be geographically dominant. It is recommended to apply pulsed-field gel electrophoresis (PFGE) together with P gene profile determination (number and genomic positions of lambdoid bacteriophages) as laboratory tools for an extended epidemiological surveillance of E. coli OOFF phage typing will remain helpful as a first line of analysis, particularly in outbreak situations.

DNA, Bacterial↗
PubMed2000

Cisplatin resistance and oncogenes--a review.

Cisplatin is among the most widely used broadly active cytotoxic anticancer drugs; however, its clinical efficacy is often limited by primary or the development of secondary resistance. Several mechanisms have been implicated in cisplatin resistance, including reduced drug uptake, increased cellular thiol/folate levels and increased DNA repair. More recently, additional pathways have been characterized indicating that altered expression of oncogenes that subsequently limit the formation of cisplatin-DNA adducts and activate anti-apoptotic pathways may also contribute to the resistance phenotype. Several lines of evidence suggest that expression of ras oncogenes can confer resistance to cisplatin by reducing drug uptake and increasing DNA repair; however, this is not a uniform finding. Tumor cells, in contrast to normal cells, respond to cisplatin exposure with transient gene expression to protect or repair their chromosomes. The c-fos/AP-1 complex, a master switch for turning on other genes in response to DNA-damaging agents, has been shown to play a major role in cisplatin resistance. In addition, AP-2 transcription factors, modulated by protein kinase A, are also implicated in cisplatin resistance by regulating genes encoding for DNA polymerase beta and metallothionines. Furthermore, considerable evidence indicates that mutated p53 plays a significant role in the development of cisplatin resistance since several genes implicated in drug resistance and apoptosis (e.g. mismatch repair, bcl-2, high mobility group proteins, DNA polymerases alpha and beta, PCNA, and insulin-like growth factor) are known to be regulated by the p53 oncoprotein. Improved understanding of molecular factors for the development of cisplatin resistance may allow the prediction of clinical response to cisplatin-based treatment. Furthermore, the identification of oncogenes involved in cisplatin resistance has already led to in vitro approaches which successfully inactivated these genes using ribozymes or antisense oligodeoxynucleotides, thus restoring cisplatin sensitivity. It is conceivable that these strategies, once transferred to a clinical setting, may have the potential to enhance the efficacy of cisplatin against a great variety of malignancies and thus more fully exploit the antineoplastic and curative potential of this drug.

Antineoplastic Agents↗
PubMed2000

Schedule-dependent antagonism of gemcitabine and cisplatin in human anaplastic thyroid cancer cell lines.

Anaplastic thyroid carcinoma (ATC) affects primarily elderly patients, with a median survival of 4-12 months after diagnosis. Presently, under clinical investigation the combination of cisplatin (CDDP) and gemcitabine (GEM) has promising activity in several of human tumor types. To develop new approaches for therapy of ATC, we evaluated the antineoplastic activity of GEM and CDDP alone (1-h and 24-h drug exposure) or in combination in the ATC cell lines SW1736, 8505C, C643, and HTh74. IC50 values were determined by the sulforhodamine B assay, activity was evaluated by the relative antitumor activity (RAA) and drug interaction assessed by isobologram analysis. GEM seemed to be active in ATC, with RAA ranging from 12-114 and CDDP only modestly active (RAA, 0.24-1.4). In four different drug schedules tested, the drug combination was additive when GEM preceded CDDP exposure (combination index, approximately 1), whereas when CDDP preceded GEM exposure the combination was significantly antagonistic (combination index, >1). In SW1736 and 8505C cells, we observed a strong S phase arrest and DNA synthesis inhibition 24 h after a 1-h exposure to an IC50 of CDDP. On the basis of molecular drug targets, cell cycle arrest points, and DNA synthesis inhibition, a model was developed to explain the interaction observed for the combination of GEM and CDDP. In conclusion, GEM shows promising cytostatic activity in ATC. Interaction of GEM and CDDP was schedule and dose dependent, favoring a regime in which GEM is followed by CDDP. Additionally, our model system suggests that DNA-synthesis inhibition and S phase arrest may be important determinants for the drug interaction between GEM and CDDP.

Antineoplastic Agents↗
PubMed1999

The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors.

Insulin-like growth factor I (IGF-I) exerts pleiotropic effects on mammalian cells via stimulation of its receptor (IGF-IR), a receptor tyrosine kinase. In vivo, IGF-I acts both as a local tissue growth factor and as a circulating hormone. In oncological research, IGF-I has received increased attention as the activated IGF-I/IGF-IR system displays mitogeneic, transforming, and anti-apoptotic properties in various cell types by stimulating distinct intracellular signaling pathways. Recent data suggest that the anti-apoptotic effect of IGF-I may mediate decreased sensitivity to chemotherapeutic drugs in vitro and in vivo. Thus, targeting the IGF-I/IGF-IR system could serve as an approach to overcome clinical drug resistance in certain tumors.

Animals↗
PubMed1999

Clonal relationship of Salmonella enterica serovar typhimurium phage type DT104 in Germany and Austria.

A new epidemic clone of Salmonella enterica serovar Typhimurium designated definitive phage type (DT) 104 has been emerging since 1990 to become most common type among S. Typhimurium isolates in Germany and Austria. Molecular fingerprinting (PFGE-pattern, plasmid profiles, IS200 pattern, ribotype, ERIC-type, OMP and MLE patterns) revealed the majority of the DT104 isolates to have clonal identity; they were designated as type 1 (about 95%). Moreover, clonal type 1 of DT104 was found to occur in sensitive as well as in a range of multiply drug-resistant variants and in a variety of plasmid profile types (in particular with small cryptic plasmids in the range of 1.0 to 5.0 Md). Since the clonal type 1 of DT104 has been identified among isolates from other countries, too, including such from the United Kingdom, the United Arab Emirates, the Philippines, and the Netherlands, its pandemic spread in man indicates that the import/export of this pathogen continues. About 5% of the DT104 isolates have been identified as genetically diverse indicating the independent appearance of the same multiple drug resistance and phage pattern phenotype among different Salmonella ancestor strains.

Animals↗
PubMed1999

Preferential repair of the N-ras gene in K 562 cells after exposure to cisplatin.

Cisplatin is one of the most active and widely used anticancer drugs; however, its clinical efficiacy is often limited by the development of resistance. Since several studies indicated that ras oncogenes may modulate the cellular response to cisplatin or radiation, we investigated the gene-specific repair of the N-ras gene in the human K 562 cell line after exposure to cisplatin using a novel nonradioactive polymerase chain reaction inhibition assay. This assay is based on the fact that DNA lesions can block the Taq polymerase and thereby result in a decreased amplification of a damaged segment compared to the amplification of the same segment in a non-damaged template. The overall genomic repair rate was measured by atomic absorption spectroscopy. Immediately after cisplatin exposure no amplification segment was observed. However, a complete restoration of the N-ras gene (2.4 kb) was seen after 8 h posttreatment incubation. In contrast, only 60% of the overall genome was repaired at this time. Our results clearly indicate that cisplatin-induced DNA lesions are more efficiently removed from transcribed regions within the DNA, suggesting that the efficiency of DNA repair in a given gene may be correlated to its transcriptional activity. Since ras oncogenes control several cellular signal transduction pathways, known to be involved in DNA damage response, preferential repair of the N-ras gene could therefore be an important step to prevent inactivation of cellular defense mechanisms after exposure to genotoxic agents.

Antineoplastic Agents↗
PubMed1999

Salmonella typhimurium IroN and FepA proteins mediate uptake of enterobactin but differ in their specificity for other siderophores.

Salmonella typhimurium possesses two outer membrane receptor proteins, IroN and FepA, which have been implicated in the uptake of enterobactin. To determine whether both receptors have identical substrate specificities, fepA and iroN mutants and a double mutant were characterized. While both receptors transported enterobactin, the uptake of corynebactin and myxochelin C was selectively mediated by IroN and FepA, respectively.

Bacterial Outer Membrane Proteins↗