Biomedical subjects

C Conradt

Publications and source records attributed to C Conradt.

At least 37 records · Page 2Linked to original sources

PubMed2001

Increased rectal cell proliferation following alcohol abuse.

BACKGROUND: Epidemiological data indicate an increased risk for rectal cancer following chronic alcohol consumption. As chronic ethanol ingestion leads to rectal hyperregeneration in experimental animals, indicating a state of increased susceptibility to carcinogens, we studied cell proliferation in alcohol abusers. METHODS: Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell proliferation, including proliferative compartment size, was measured by immunohistological staining for proliferative cell nuclear antigen (PCNA) and Ki67, and by in situ hybridisation for histone H3. Quantification of cell proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12 controls. In addition, immunohistology was performed for cytokeratins and gene products of Rb1, bcl-2, and p53. RESULTS: Heavy drinking resulted in increased cell proliferation of the rectal mucosa, as shown by increased detection of different proliferation markers. However, cell differentiation regarding cytokeratin expression patterns was unchanged as well as regulatory factors involved in carcinogenesis and/or apoptosis. CONCLUSION: Chronic alcohol abuse leads to rectal mucosal hyperproliferation in humans, a condition associated with an increased cancer risk.

Adult↗

PubMed2001

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.

Adolescent↗

PubMed2001

Overexpression of p53 in tumor-distant epithelia of head and neck cancer patients is associated with an increased incidence of second primary carcinoma.

Second primary carcinoma is a peculiar feature of head and neck cancer and represents a form of treatment failure distinct from the recurrence of the primary tumor. Whether altered p53 expression in tumor-distant epithelia at the time of diagnosis is of clinical value as a biomarker for second primary carcinoma development has not been rigorously answered because of the lack of long-term follow-up studies involving a sufficiently large patient cohort. In this prospective study, we have investigated p53 expression in tumor-distant epithelia and in the corresponding primary tumors of 105 head and neck cancer patients by immunohistochemistry on frozen sections. After a median follow-up of 55 months, the clinical course of disease parameters, i.e., local recurrences, lymph node and distant metastasis, incidence of second primary carcinoma, and survival, was evaluated. Overexpression of p53 in tumor-distant epithelia was found in 49 patients (46.7%), and it was independent of the p53 protein status of the primary tumor and of the tumor site, size, stage, and grading. Mucosal p53 overexpression was not associated with local primary recurrences, lymph node or distant metastases, or overall survival. Importantly, mucosal p53 overexpression, but not overexpression in the primary tumors, was significantly associated with an increased incidence of second primary carcinomas (P = 0.0001; Fisher's exact test). When the times to second primary tumor occurrence were analyzed by the Kaplan-Meier method, the difference remained significant (P = 0.005; log rank test). We conclude that IHC staining for p53 overexpression in tumor-distant epithelia provides a simple and rapid tool to identify head and neck cancer patients at increased risk of developing second primary tumors. Because p53 overexpression in these epithelia in our patient cohort was specifically associated with second primary cancer but not with recurrences, at least a fraction of the second primary cancers appears to have resulted from genetic events in the mucosa ("field cancerization").

Carcinoma, Squamous Cell↗

PubMed2000

Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy.

BACKGROUND: The objective of this trial was to analyze the prognostic relevance of the angiogenic peptides basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in the serum of patients with advanced carcinoma of the head and neck treated by primary radiochemotherapy. METHODS: From 1992 to 1995, 26 patients with advanced head and neck cancer (25 stage IV, 1 stage III UICC) were treated according to the protocol of radiochemotherapy with carboplatin. The pretreatment serum levels VEGF, bFGF, and MMP-2 were measured by ELISA, and data were correlated with tumor characteristics and followed up (median time of follow up, 60 months). RESULTS: An increase in bFGF serum level above the upper limit of normal controls showed a significant correlation with shorter time the of locoregional control (p =.036). In covariant analysis bFGF serum concentration proved to be independent of other prognostic factors like tumor site, age, total tumor volume, and response to therapy. No prognostic relevance of VEGF and MMP-2 serum levels could be determined. CONCLUSIONS: The results of this pilot study indicate that the serum concentration of bFGF has prognostic relevance for advanced head and neck cancer.

Adult↗

PubMed2000

[Detection of numerical chromosome aberrations in leukoplakia and squamous epithelial carcinomas of the head-neck area using fluorescence in situ hybridization].

The tumorigenesis of head and neck squamous cell carcinoma (HNSCC) has been proposed to represent a multistep process characterized by an accumulation of genetic alterations. To study numerical chromosomal aberrations and chromosomal imbalances, biopsies of 11 malignant tumours and biopsies of 16 oral premalignant lesions (leukoplakias) were analyzed by fluorescence in situ hybridization (FISH) using centromeric probes for chromosomes, 1, 7, 9, 10 and 17. The comparison of the alterations observed in simple leukoplakias (group 1, n = 8), dysplastic leukoplakias (group 2, n = 8) and malignant tumours (group 3, n = 11) by the Cochran-Armitage Trend Test revealed an increasing number of numerical chromosomal abberations. This difference was statistically highly significant (p < 0.001). The data open up the possibility that FISH analysis might help to better characterize the progression of premalignant oral leukoplakias.

Biopsy↗

PubMed2000

[Prognostic value of hemoglobin level for primary radiochemotherapy of head-neck carcinomas].

The pretherapeutic hemoglobin level (Hb) has been postulated to constitute a prognostic marker for outcome after primary chemoradiation of patients with advanced cancer of the head and neck. However, this hypothesis has not been tested systematically in large study samples. In the years 1992-1997, 125 patients with advanced head and neck cancer (stages III/IV UICC) were treated with primary chemoradiation in two different prospective multicentric trials, 62 patients in trial A (phase II, 1992-1995), and 63 in trial B (phase III, 1995-1997). Beside initial Hb, other pretherapeutic parameters with potential prognostic relevance were assessed and correlated with clinical outcome after 43-months follow-up: total tumor volume (TTV; calculated in initial CT scans), tumor oxygenation (polarographic measurements with Eppendorf histography), TNM, tumor localization, age, and performance status. The evaluation of the clinical end points (progression-free and overall survival and local tumor control) revealed that Hb and TTV were independent parameters with strong predictive character of outcome after primary chemoradiation in both trials (n = 125). Bivariate analysis showed < median (13.5 g/dl) a hazard ratio of 2.1 (P = 0.002) for Hb; and > median (98 ml) a Hazard ratio of 2.0 (P = 0.006) for TTV. Severe anemia (Hb < 10 g/dl) was an adverse factor in three patients. Hypoxia was associated with poorer initial therapeutical response but was not predictive of clinical outcome. Furthermore, tumor oxygenation showed no correlation with Hb. The other parameters examined failed to show prognostic significance. Our results indicate a high prognostic value of initial Hb for outcome after primary chemoradiation in advanced head and neck cancer and imply a therapeutic benefit of Hb substitution or erythropoietin administration. We propose to test this in randomized clinical trials.

Adult↗

PubMed2000

Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study.

PURPOSE: Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain. SUBJECTS AND METHODS: We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study. RESULTS: The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract. CONCLUSION: Willow bark extract may be a useful and safe treatment for low back pain.

Administration, Oral↗

PubMed2000

Oxygenation of advanced head and neck cancer: prognostic marker for the response to primary radiochemotherapy.

Recent clinical studies suggest that the degree of tumor oxygenation may be predictive of the response of radiation therapy for cancer. In an exploratory investigation of cervical lymph node metastases in 27 patients with advanced squamous cell carcinoma of the oropharynx and hypopharynx, this relationship was investigated by means of oxygen measurements with an Eppendorf PO (2) histograph. The measurements were made before the start of radiation therapy and after the first week of therapy. Clinical response was evaluated 6 weeks after the completion of therapy. Before therapy, marked hypoxia was observed in the lymph node metastases, with a mean PO (2) value of 16.1 +/- 8.2 mm Hg and a hypoxic fraction (PO (2) < 10 mm Hg) of 56.4% +/- 20.0%. After the first week of radiation (9 Gy) there was a general reoxygenation (DeltaPO (2) = 5.0 +/- 10.1 mm Hg, P < 0.05; Deltahypoxic fraction = -11.3% +/- 31.3%, P = 0.11). A relationship between the degree of reoxygenation and tumor response was not observed. Patients without at least partial lymph node response (n = 8) showed poorer pretherapeutic oxygenation (PO (2) mean = 11.1 +/- 2.9 mm Hg) than those who responded to the therapy (n = 19, PO (2) mean = 18.2 +/- 8.8 mm Hg). In this investigation of a defined set of patients with advanced carcinoma of the oropharynx and hypopharynx, we found that pretherapeutic oxygenation data are predictive for the therapeutic response to radiation therapy or radiochemotherapy.

Adult↗

PubMed2000

Prognostic assessment of sonography and tumor volumetry in advanced cancer of the head and neck by use of doppler ultrasonography.

OBJECTIVE: The objective of this trial was to examine the degree of tumor vascularity in lymph node metastases as depicted by computer-assisted color Doppler sonography and the tumor volumes associated with prognosis in carcinomas of the oropharynx and hypopharynx after primary radiochemotherapy. PATIENTS AND METHODS: In a prospective trial, 25 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx (stage IV UICC 1997) were treated with radiochemotherapy. The color Doppler findings were quantified with a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD). As important prognostic cofactor, total tumor volume (TTV) was calculated from CT sections and related to the degree of vascularity. RESULTS: Low CPD in neck metastases showed a correlation with better overall survival. A high-CPD group and a high-TTV group (median survival 10.1 months) were determined and were compared with all other CPD/TTV combinations (median survival 28.4 months); the difference in survival was significant (P = 0.002). CONCLUSION: The results indicate that high tumor vascularity in combination with high TTV indicates a particularly bad prognosis in patients treated with primary radiochemotherapy for head and neck cancer.

Adult↗

PubMed2000

[How can "significance" and "relevance" be combined?].

Clinical trials are aimed at providing results which enable improvements in patient care. It is widely criticized, however, that the characterization of results as "significant" or "non-significant" does not allow any assessment of their clinical relevance. To counter this criticism 2 biostatistical concepts are available: the use of confidence intervals and the application of statistical tests with shifted null-hypotheses. Possibilities and limitations of these concepts are discussed in this contribution.

Clinical Trials as Topic↗

PubMed1999

[How can "significance" be combined with "relevance"?].

Clinical Trials as Topic↗

PubMed1999

Heparin inhibits ligand binding to the leukocyte integrin Mac-1 (CD11b/CD18).

BACKGROUND: The clinical benefits of heparin reach beyond its anticoagulative properties. Recently, it has been described that leukocytes adhere on immobilized heparin mediated by the integrin Mac-1 (CD11b/CD18, alphaMbeta2, or CR3). Because inhibition of this versatile adhesion molecule could explain various aspects of the beneficial clinical effects of heparin, we evaluated whether soluble heparin modulates Mac-1 function in vitro and in vivo. METHODS AND RESULTS: Binding of unfractionated heparin to Mac-1 on PMA-stimulated monocytes and granulocytes was directly demonstrated in flow cytometry, whereas no binding of heparin was detected on unstimulated leukocytes. Unfractionated heparin inhibited binding of the soluble ligands fibrinogen, factor X, and iC3b to Mac-1. Adhesion of the monocytic cell line THP-1 and of peripheral monocytes and granulocytes to immobilized ICAM-1 was impaired by unfractionated heparin, to the same extent as with inhibition of Mac-1 by monoclonal antibodies such as c7E3. Low-molecular-weight heparin also inhibits binding of fibrinogen to Mac-1. Additionally, flow cytometry of whole blood preparations of patients treated with unfractionated heparin revealed an inhibitory effect of heparin on the binding of fibrinogen to Mac-1 that correlates (n= 48, r=0.63, P<0.001) to the extent of prolongation of the activated partial thromboplastin time. CONCLUSIONS: We describe a pharmacologically relevant property of heparin that may contribute to its benefits in clinical use. The binding of heparin to Mac-1 and the resulting inhibition in binding of Mac-1 ligands may directly modulate coagulation, inflammation, and cell proliferation.

Animals↗

PubMed1999

[Alcohol drinking and cancer of the upper aerodigestive tract in women].

BACKGROUND AND OBJECTIVE: In Germany every year approximately 2000 women die from squamous cell cancer of the oral cavity, pharynx or larynx. Until recently, excessive alcohol consumption and excessive tobacco consumption were blamed as the predominant risk factors. The present study investigated whether alcohol is an independent risk factor even in case of a moderate consumption in increasing the risk of cancer of the mouth, pharynx and larynx in females. PATIENTS AND METHODS: In a hospital based case control study the smoking and drinking patterns of 62 females with squamous cell cancer of the oral cavity, pharynx or larynx and of 248 randomly selected female control subjects were analysed. RESULTS: A regular consumption of alcohol was reported by 59.7% of the cancer patients and by 18.1% of the control subjects. The alcoholic beverages preferred by the cancer patients were beer and spirits. While only 0.8% of the control subjects reported a daily consumption of more than 30 g alcohol, this was the case in 40.3% of the cancer patients. The alcohol-associated risk increasing was dose-dependent. Compared to a daily consumption of less than 10 g alcohol, a consumption of more than 30 g/day has a relative risk of 29 (P < 0.01; adjusted for tobacco) was estimated. CONCLUSION: Even a moderate alcohol consumption (10-20 g/day) causes a significant increasing of head and neck cancer in women.

Adult↗

PubMed1999

Evaluation of the predictive impact of cephalometric variables. Logistic regression and ROC curves.

In the context of orthodontic treatment planning, the decisions to be made are often affected by the assumption of future growth patterns, especially the direction of mandibular rotation. Using longitudinally available lateral cephalograms from the Belfast Growth Study, it was examined whether, on the basis of the cephalometric variables at the ages of 7, 9 and 11, the direction of mandibular rotation can be predicted in the respective subsequent 4-year intervals. For statistical analysis of this problem, logistic regression models were applied to describe and quantify the influence of potential explanatory variables on the direction of mandibular rotation (dependent variable). In addition, graphical methods taken from the field of medical diagnostics were applied for prediction and for determination of predictive accuracy. The use of logistic regression models revealed no relations between the explanatory variables SN-MeGo and S-Go/N-Me and the subsequent mandibular growth pattern. Only the upper and lower parts of the gonial angle showed a minor predictive impact. A graphical evaluation of their prognostic impact by means of "receiver operating characteristics" (ROC) curves, complemented by determination of the areas under the curves, confirmed the relations discovered. Nevertheless the prognostic limits of the lateral cephalogram emerged clearly for all variables investigated.

Adolescent↗

PubMed1999

[Predictive value of serum levels of basic fibroblast growth factor, vascular endothelial growth factor and matrix metalloproteinase-2 in advanced carcinomas of the head and neck].

The objective of this trial was to analyse the predictive character of the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-2 (MMP-2) in the sera of patients with advanced carcinomas of the head and neck treated by primary radiochemotherapy. From 1992 to 1995, 25 patients with UICC stage cancers and one patient with stage III disease were treated in the departments of otolaryngology and radio-oncology of the University of Heidelberg according to a protocol of accelerated concomitant boost radiochemotherapy with carboplatin. The serum levels of VEGF, bFGF and MMP-2 were measured by enzyme-linked radiosorbent assay and data were correlated with followup findings (median time of follow up: 60 months). Patients with serum levels above normal were detected for VEGF in 4 patients, MMP-2 in 7 patients and for bFGF in 13 patients. An increase in bFGF serum levels above the upper limit of normal controls was significantly associated with a shorter time of locoregional control (P=0.036). In a covariate analysis bFGF proved to be independent of other prognostic factors, such as age, site, total tumor volume and response to therapy. No prognostic relevance of VEGF and MMP2 serum levels could be determined. The present suggest that bFGF is an independent prognostic factor for tumor control in advanced head and neck cancer after primary radiochemotherapy.

Adult↗

PubMed1999

[Construction workers as an extreme risk group for head and neck cancer?].

BACKGROUND: Workers in the construction industry carry an increased risk for head and neck cancer due to the high consumption of alcohol and tobacco plus exposure to occupational carcinogenic or co-carcinogenic agents. These latter substances include asbestos, tar products, metal dust, wood dust, cement dust and paints. RESULTS: The Heidelberg case-control studies showed a statistically increased risk of pharyngeal cancer (RR=2.5 adjusted for tobacco and alcohol) and laryngeal cancer (RR=2.3 adjusted for tobacco and alcohol) in the construction workers (23.3%) when compared to controls (8.2%). A random sample analysis of patients with head and neck cancer referred by the largest health assurance company in Heidelberg (AOK), revealed that 21.2% were employed in the construction industry. Similar results have been obtained in a number of international epidemiological studies. CONCLUSIONS: Our findings show that male construction workers who regularly consume alcohol and tobacco represent an extreme risk group for head and neck cancer. Measures for early detection are important and must be implemented carefully.

Adult↗

PubMed1999

[Prognostic significance of cell-cycle regulatory proteins for outcome after primary radiochemotherapy in patients with advanced head and neck cancer].

BACKGROUND: Primary radiochemotherapy is gaining increasing importance for the treatment of advanced head and neck squamous cell carcinomas. However, there is a lack of clinical factors concerning prognostic information in relation to treatment. In this pilot study, we examined whether molecular factors can provide such information. PATIENTS AND METHODS: The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p53, p21(WAF/CIP1), Rb, p16(INK4A), CDK4 and Cyclin D1, MIB1 (Ki-67) and BCL-2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx (n = 26), hypopharynx (n = 10) and larynx (n = 7) by applying immunohistochemistry to paraffin sections of tumor specimens. All patients were treated by the same method of an accelerated "concomitant boost" radiochemotherapy with carboplatin in a phase II study. Median followup time was 56 months. RESULTS: No correlation was found between any of the markers and the remission rate, T-stage, N-stage, rate of loco-regional recurrences and distant metastases. However, independent of the tumor stage, patients with CDK4/cyclin-D1 overexpressing tumors had a significantly shortened overall survival (P = 0.014 and 0.026, respectively). CONCLUSION: The results of this pilot study indicate that CDK4 and cyclin D1 over-expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients.

Adult↗

PubMed1999

[The role of oncogenic human papillomaviruses in tonsillar squamous cell carcinomas with functional inactivation of the retinoblastoma protein].

In order to identify squamous cell carcinomas of the head and neck (HNSCC) with common biological and clinical features, we investigated the incidence and properties of carcinomas lacking retinoblastoma protein (pR6) cell cycle control. Of 208 HNSCC investigated, 23 (11%) showed a lack of pRb expression. The majority of these tumors (65%) were tonsillar carcinomas. The pRb-negative tonsillar tumors were all stage IV, had metastasized to lymph nodes at the time of diagnosis and were in general poorly differentiated or undifferentiated. Very significantly, the pRb-negative phenotype was strongly associated with the presence of oncogenic human papilloma viruses, implying a viral etiology and functional inactivation of pRb by the viral E7 oncoprotein. Despite the very adverse histopathological factors, patients with pRb-negative tonsillar carcinomas had a better clinical outcome, which was consistent with a uniform favorable responsiveness of these tumors to postoperative radiation therapy.

Carcinoma, Squamous Cell↗