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C Matthias

Publications and source records attributed to C Matthias.

35 records · Page 2Linked to original sources
PubMed1998

Influence of tumour necrosis factor microsatellite polymorphisms on susceptibility to head and neck cancer.

While cigarette smoking and alcohol consumption are recognized covariates for head and neck squamous cell carcinoma (SCC), the role of genetic factors in determining individual susceptibility is unknown. The human tumour necrosis factor (TNF) region on chromosome 6p21 within the major histocompatibility complex (MHC) includes a number of immunologically important genes. Recently, five microsatellite markers have been described in the TNF locus. TNF levels vary with different TNF microsatellite alleles, and associations of these microsatellite markers with autoimmune diseases and different types of cancer have been shown. Therefore, the TNF locus represents candidate susceptibility genes for head and neck cancer. This study describes the influence of TNF a-d microsatellite polymorphisms on susceptibility to head and neck cancer by comparing the allele frequencies of 269 patients suffering from laryngeal cancer and 123 patients suffering from oral cavity pharyngeal cancer and 113 German controls. DNA was extracted from peripheral blood samples, amplified by polymerase chain reaction with fluorescently labelled primers for TNF microsatellite (a-d) and electrophoresed on polyacrylamide gels using an automated DNA sequencer. The data showed no differences in allele frequencies between controls and pharyngeal cancer patients. By contrast, the TNF b3 allele was associated with altered risk for laryngeal cancer (p = 0.0006, odds ratio 2.2). Homozygosity for TNF b3/b3 resulted in an increased risk of developing laryngeal cancer (p = 0.004, odds ratio 5.3). Susceptibility to supraglottic SCC and multiple primary tumours was mediated by the absence of the a11 allele. The data provide the first evidence that allelism at the TNF microsatellite markers alter the risk of developing SCC of the larynx.

Alleles↗
PubMed1998

The glutathione S-transferase GSTP1 polymorphism: effects on susceptibility to oral/pharyngeal and laryngeal carcinomas.

We have examined the hypothesis that the polymorphic, glutathione S-transferase GSTP1 gene is a susceptibility candidate for squamous cell cancer of the oral/pharynx and larynx. We describe GSTP1 genotype frequencies in 380 cases and 180 controls. We found a lower frequency of GSTP1 AA in the oral/pharyngeal cases compared with controls (p = 0.003, odds ratio = 0.47) after correction for age and gender. We used an immunohistochemical approach to show widespread expression of the GSTP1 subunit throughout the pharynx and larynx. In uninfiltrated tissue, strong positivity was found throughout the squamous cell epithelium with the exception of the basal cell layer. The cilia of the respiratory epithelium of the larynx also showed positivity for GSTP1. In tumour tissue, expression of GSTP1 was similar in pharyngeal and laryngeal samples. These data are the first to show that polymorphism at GSTP1 mediates susceptibility to squamous cell cancer of the upper aerodigestive tract. No significant interactions were identified between GSTP1 and GSTM1, GSTM3, GSTT1 and the cytochrome P450 CYP1A1, CYP2D6 and CYP1A1 genotypes.

Alcohol Drinking↗
PubMed1998

Susceptibility and outcome in oral cancer: preliminary data showing an association with polymorphism in cytochrome P450 CYP2D6.

Members of the cytochrome P450 and glutathione S-transferase supergene families are candidates for susceptibility and outcome in oral squamous cell cancer. We determined GSTM1, GSTM3, GSTT1, CYP1A1 and CYP2D6 genotypes in 100 Caucasian cases and 467 control individuals. The frequency of homozygosity for mutant CYP2D6 alleles was higher in the cases (P = 0.001, OR = 3.2, 95% CI = 1.6-6.5) than control individuals. In the cases, the frequency of homozygosity for mutant alleles was greater and that of homozygosity for wild-type CYP2D6 alleles was lower in those diagnosed at > or = 65 years (P = 0.009) than in those diagnosed at < or = 64 years. The older cases included relatively more women and patients who did not consume tobacco or alcohol. The association of CYP2D6 with outcome was assessed using the Cox's proportional hazards model. The time to first cervical node metastasis was shorter in heterozygotes and homozygotes for mutant CYP2D6 alleles compared with homozygotes for wild-type alleles after correction for age at diagnosis, gender, alcohol and tobacco consumption and tumour differentiation (P = 0.04, hazard ratio 3.6, 95% CI 1.1-12.5). The mechanism for the association of CYP2D6 alleles with susceptibility and outcome is unclear though the data are compatible with the view that homozygosity for mutant alleles confers impaired detoxication of an unknown carcinogen. No associations between GSTM1, GSTM3, GSTT1 or CYP1A1 genotypes and susceptibility or, time to node metastases were identified. We previously showed that CYP2D6 genotypes were not associated with susceptibility to squamous cell cancer in the pharynx or larynx. Therefore, the data presented suggest that susceptibility to squamous cell cancer in the various parts of the upper aerodigestive tract is associated with different genes and allelic variants.

Adult↗
PubMed1998

Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers.

Glutathione S-transferase GSTM1, GSTM3 and GSTT1 and cytochrome P450 CYP2D6, CYP1A1 and CYP2E1 loci are susceptibility candidates for cancers of the upper aerodigestive tract because putatively protective and risk genotypes have been identified from studies in other diseases associated with alcohol and tobacco consumption. We describe genotype frequencies in 398 oral, pharyngeal and laryngeal squamous cell carcinoma patients and 219 control individuals. Of the genotypes presumed to be protective, only GSTM1 A/B influenced susceptibility; the GSTM1 A/B frequency was lower in the patients than the control individuals both before [odds ratio = 0.3, 95% confidence interval (CI) 0.1-0.7] and after correction for imbalances in age, sex, smoking and alcohol consumption (odds ratio = 0.2, 95% CI 0.1-0.5). Of the putatively risk genotypes, GSTM3 AA, previously associated with susceptibility to skin cancer, was higher in the cases (odds ratio = 1.6, 95% CI 1.1-2.4). Dividing cases into oral/pharyngeal and laryngeal squamous cell carcinoma showed the GSTM3 AA frequency was higher in laryngeal squamous cell carcinoma than control individuals (odds ratio = 1.6, 95% CI 1.1-2.5) and the difference between control individuals and oral/pharyngeal squamous cell carcinoma approached significance (odds ratio = 1.7, 95% CI 1.0-2.8). The putatively protective GSTM3 BB genotype was lower in patients with glottic (1.0%) than supraglottic (3.0%) squamous cell carcinoma. We identified no differences between patients and control individuals in the frequencies of presumed risk genotypes (e.g. CYP2D6 EM, CYP1A1 m1/m1, CYP1A1 Ile/Ile, CYP2E1 DD, CYP2E1 c1c1, GSTT1 null) or, interactions between genotypes and smoking or alcohol consumption. We conclude, first, that mu class glutathione S-transferase influence risk of upper aerodigestive tract cancers thereby complementing studies in skin cancer patients showing GSTM1 A/B is protective, while GSTM3 AA moderately increases risk. The influence of GSTM1 A/B, but not GSTM1 A or GSTM1 B (mostly heterozygotes with GSTM1*0) suggests that two expressed alleles may attenuate risk. While we found immunohistochemical evidence of GSTM3 expression in the cilia lining the larynx, the biochemical consequences of the polymorphism are unclear. Indeed, the influence of the gene may reflect linkage disequilibrium with another gene. However, we did not find an association with GSTM1 genotypes. Second, we conclude that the CYP2D6, CYP2E1, CYP1A1 and GSTT1 alleles studied, although putatively good candidates, either do not determine the effectiveness of detoxification of tobacco-derived carcinogens in the upper aerodigestive tract or, that chronic consumption of tobacco and alcohol overwhelms enzyme defences, irrespective of genotype.

Aged↗
PubMed1998

Polymorphism within the cyclin D1 gene is associated with prognosis in patients with squamous cell carcinoma of the head and neck.

We have examined the correlation of a frequent A/G polymorphism within exon 4 of the cyclin D1 gene (CCND1) with genetic susceptibility and clinical outcome in 384 patients with squamous cell carcinoma (SCC) of the head and neck. CCND1 genotype frequencies were similar in the cases and 191 controls. Furthermore, the CCND1 genotype was not associated with susceptibility to SCC of the larynx, pharynx, or oral cavity. The influence of the CCND1 genotype on clinical outcome was also assessed. We found no correlation between genotype and tumor size (T1-T4), the involvement of nodes at presentation, or patient age and gender. However, the distribution of CCND1 genotypes in cases with poorly differentiated tumors was significantly different to that in patients with well-/moderately differentiated tumors (P = 0.016; chi2(2) = 8.71). Homozygosity for CCND1*G (GG genotype) was associated with poorly differentiated tumors (G3). We used Cox's proportional hazards model to investigate the influence of the CCND1 genotype on disease-free interval. CCND1 GG was associated with reduced disease-free interval [P = 0.001; hazard ratio (HR) = 2.95; 95% confidence interval (CI) = 1.54-5.63]. This remained significant after correction for tumor differentiation (P = 0.013; HR = 2.34; 95% CI = 1.2-4.6) and tumor stage (P = 0.005; HR = 2.64; 95% CI = 1.34-5.19). Analysis of the data from patients with tumors at different sites showed that the CCND1 GG genotype was associated with reduced disease-free interval in laryngeal (P = 0.004; HR = 3.63; 95% CI = 1.44-8.83) and pharyngeal (P = 0.006; HR = 3.48; 95% CI = 1.43-8.46) tumors. This is the first report of an association between CCND1 polymorphism and prognosis in SCC of the head and neck. These data show that the CCND1 GG genotype is an independent prognostic indicator of disease-free interval and supports initial observations in non-small cell lung cancer, that polymorphism within CCND1 influences tumor behavior.

Adult↗
PubMed1997

Electron microscopic and immunomorphological investigations on the mucosa of the human paranasal sinuses.

The morphology of the mucosa from the human paranasal sinuses was investigated by electron microscopy. A total of 27 specimens was taken from 11 patients following midfacial fractures. All tissue samples were biopsied during surgery after informed consent had been given. In accordance with light microscopic investigations, the mucosa represented a highly prismatic epithelium consisting of kinocilia-carrying and mucus-producing (goblet) cells. Other cell types, such as those occurring in the respiratory epithelium of other areas, could not be demonstrated. Electron microscopic and immunomorphological investigations revealed collagen type VII beneath the lamina densa of the basal lamina. According to findings obtained to date, this collagen type accompanies only a multilayered epithelium. Another peculiarity was the small number of basophils and eosinophils. Pronounced acute reactions of the mucosa in this area cannot be expected, which is in contrast to that of the nasal mucosa.

Adult↗
PubMed1997

Glutathione S-transferase and cytochrome P450 genotypes as risk factors for laryngeal carcinoma.

While cigarette smoking and alcohol consumption have been linked to laryngeal squamous cell carcinoma (SCC), the role of genetic factors in determining individual susceptibility is unknown. We describe the role of allelism at the glutathione S-transferase GSTM1, GSTM3, GSTT1 and cytochrome P450 CYP1A1, CYP2E1, CYP2D6 loci in determining individual susceptibility to laryngeal SCC. Enzyme genotypes were determined using polymerase chain reaction and restriction enzyme digestion of leukocyte DNA collected from 269 patients with T1-T4 laryngeal carcinomas and 216 controls. While the frequencies of the heterozygote GSTM1 A/B genotype and the homozygote GSTM3 B/B genotype were statistically significantly lower in the patients with tumors than in controls, the frequency of the GSTT1 null genotype was higher in the patients than in controls. The data suggest that allelism at GST loci mediates susceptibility to SCC of the larynx. GSTM1 A/B and GSTM3 B/B appear to be associated with reduced risk, while GSTT1 null may confer increased risk. These findings are compatible with the view that genetic predisposition is important in determining risk for this cancer.

Alcohol Drinking↗
PubMed1997

Magnification of tributyl tin toxicity to oyster larvae by bioconcentration in biofilms of Shewanella colwelliana.

The toxic effects of dissolved versus bioconcentrated tributyl tin (TBT) on oyster larvae were compared. Water column TBT levels, which had no effect in solution, inhibited natural attachment and metamorphosis of oyster larvae on bottom surfaces due to bioconcentration by biofilms. This mechanism should be considered when evaluating heavy metal toxicity in the environment.

Animals↗
PubMed1996

Glutathione S-transferase and cytochrome-P-450 polymorphism as risk factors for squamous cell carcinoma of the larynx.

PURPOSE: While cigarette smoking and alcohol consumption are recognized covariates for laryngeal carcinoma, the role of genetic factors in determining individual susceptibility is unknown. We describe the influence of polymorphism in carcinogen-metabolizing enzymes on susceptibility to squamous cell carcinoma of the larynx. MATERIAL AND METHODS: We investigated 269 patients with T1-T4 laryngeal carcinoma and 216 controls. Enzyme genotypes at the glutathione-S-transferase GSTM1 (A, B, A/B, null), GSTM3 (A, B), GSTT1 (null and expressors), and cytochrome P-450, CYP2D6 (intron 3/exon 4 boundary mutation and exon 5 deletion), CYP1A1 (3'-mutation and exon 7 mutation), and CYP2E1 (mutation at the 5' flanking region) loci were determined using polymerase chain reaction and restriction-based approaches. RESULTS: While the frequencies of the heterozygote GSTM1 A/B and homocygote GSTM3 B/ B were statistically significantly lower in cases than controls, the frequency of the GSTT1 null genotype was higher in the cases than controls. Genotype frequencies of 123 patients suffering squamous cell carcinomas located at different sites within the upper aerodigestive tract showed no differences between cases and controls. CONCLUSIONS: The data provide evidence that susceptibility to laryngeal carcinoma, but not pharyngeal carcinoma, is mediated by allelism at a number of loci encoding enzymes involved in the detoxification of electrophils derived from environmental pollution including cigarette smoke.

Carcinoma, Squamous Cell↗
PubMed1995

[Olfactory evoked potentials and contingent negative variation in expert assessment of disordered sense of smell].

Normally, the sense of smell is assessed by means of traditional subjective tests (sniff test, gustatory smell test, and trigeminus test). When results are inconclusive, an objective smell test is indicated. Simultaneously registering olfactory evoked potentials (OEP) and contingent negative variation (CNV) permits evaluation of both odor perception and odor discrimination. We can even objectively assess the false olfactory sensations in parosmia patients who are unable to discriminate between different odors. In this study, the results of 59 patients with olfactory disorders are presented. Head trauma and upper respiratory infections were the most common causes of the patients' complaints. In twelve cases, lack of cooperation and patient unrest prevented us from evaluating the data. In anosmia, the objective results agreed completely with the patient's subjective assessment. In hyposmia and parosmia, the results agreed with the patient's subjective assessment in most cases; here we were able to arrive at a more specific diagnosis in several cases. The objective smell test can be used to supplement subjective methods and thus provide more reliable assessment of olfactory disorders.

Attention↗
PubMed1995

[Initial results of glutathione-S-transferase GSTM1 and GSTT1 genotypes and genetic predisposition for laryngeal carcinoma].

BACKGROUND: While cigarette smoking and alcohol consumption have been linked to laryngeal carcinoma, the role of genetic factors in determining individual susceptibility is unknown. We describe the role of allelism at glutathione-S-transferase GSTM1, GSTT1, and cytochrome P 450 CYP2D6 loci in determining individual susceptibility to laryngeal squamous cell carcinoma. METHODS: Enzyme genotypes were determined using the polymerase chain reaction in 169 patients suffering T1-T4 laryngeal carcinoma and in 145 controls. RESULTS: While the frequency of the heterozygote GSTM1 A/B genotype was statistically significantly lower in the cases than controls, the frequency of the GSTT1 null genotype was higher in cases than controls. CONCLUSION: These initial data suggest that allelism at GST loci mediates susceptibility to squamous cell carcinoma of the larynx. Thus, GSTM1 A/B appears to be associated with a reduced risk while GSTT1 null confers increased risk. The findings are compatible with the view that genetic predisposition is important in determining risk of this cancer.

Adult↗
PubMed1995

Otorhinolaryngological complications of progressive facial hemiatrophy (Romberg's disease).

Progressive facial hemiatrophy (PFH) is characterized by slowly progressive atrophy of subcutaneous tissue. Bone, muscles, nerves, the eye, and the brain may be affected by atrophy. Four patients suffering from various otorhinolaryngological complications of PFH or Romberg's disease are reported. Unilateral hearing loss could be located in the inner ear of one patient by audiologic examination. Localized bone destruction and disintegration of a portion of the anterior wall of the frontal sinus were observed in a patient after more than three decades. Marked shrinking of the homolateral parotid gland and homolateral masticatory spasm are reported as further otorhinolaryngological manifestations. The various complications of PFH call for close interdisciplinary cooperation.

Child↗
PubMed1977

Elimination of cardiac glycosides through hemofiltration.

Elimination of three different cardiac glycosides by hemofiltration was investigated using the flat bed RP-6 (Rhône-Poulenc, Paris). At a filtration rate of 59 +/- 9 ml/min the mean clearance of 3-H-g-strophanthin was 54.9 +/- 10.4, that of a 3-H-digoxin and unlabelled digoxin 36.7 +/- 6.6 and that of digitoxin 4.6 +/- 2.8 ml/min. It is concluded from these results that hemofiltration is able to eliminate more than 50% of the amount excreted during the same period of time by normal kidneys. Elimination of cardiac glycosides by continuous hemofiltration is high enough to justify its use in digitalis intoxication, particularly because of the excellent control of electrolyte balance with this new method of detoxification.

Cardiac Glycosides↗
PubMedDate not supplied

Selection of antibiotics for treatment and prophylaxis of staphylococcal infections in cystic fibrosis patients.

Susceptibility in vitro of 179 staphylococcal strains from 107 cystic fibrosis patients against 31 antibiotics indicates that only teicoplanin, vancomycin and netilmicin were active against all strains. The use of betalactam antibiotics is impaired by 11.7% of methicillin-resistant strains. The bactericidal kinetics of cephalexin and flucloxacillin as determined in a pharmacodynamic model demonstrates the killing of strains resistant to cephalexin (MIC 8 mg/l to 32 mg/l) by flucloxacillin. For the rational selection of antistaphylococcal antibiotics for cystic fibrosis patients, both the MIC of the isolates and the concentration of the antibiotics in cystic fibrosis patients have to be considered.

Adolescent↗
PubMedDate not supplied

Cefpodoxime proxetil concentrations in head and neck tissues.

Three to six hours prior to surgery in the head and neck a single dose of 200 mg cefpodoxime proxetil was administered orally to 30 patients. During surgery serum and tissue samples (concha, mocosa, cartilage, bone, parotis and tonsil) were taken and the concentrations of cefpodoxime were determined by bioassay. The serum concentrations ranged from 0.72 mg/l (determined after 6 h 22 min) to 3.34 mg/l (3 h 15 min). The tissue concentrations were between 0.15 mg/l (determined in bone after 5 h 18 min) and 1.94 mg/l (concha 4 h 13 min). Analogously to recent in vitro data the concentrations reached in head and neck tissue were higher than the MIC90 values for most pathogens of upper respiratory tract infections.

Administration, Oral↗