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Biomedical subjects

P Drings

Publications and source records attributed to P Drings.

At least 19 recordsLinked to original sources
PubMed2005

[The effect of haemoglobin levels on prognosis and quality of life of patients with bronchial carcinoma].

As a consequence of tumour and therapy related effects anaemia is a particularly frequent occurrence in patients with lung cancer. The ensuing symptoms such as dyspnoea, fatigue and decreased general health reduce their quality of life and can impede if not altogether prevent an effective cytostatic therapy. A positive outcome after oxygen-dependent anti-tumour therapy, for example radiation therapy or various cytostatic treatments as well, can be reduced or even put at risk when tumour tissue is hypoxic. In order to treat anaemia, recombinant human erythropoietin can be used beside blood transfusions. Erythropoietins are well tolerated and allow for a long-lasting, gradual increase of Hb-levels, which cannot be achieved via transfusions. Furthermore, transfusion risks such as intolerance reactions or disease transmission can also be avoided. The various studies presented here evaluated the impact of anaemia treatment with erythropoietins on the need for transfusions and quality of life of patients with lung cancer over the last few years. They all agreed in their conclusion that both parameters can be improved with erythropoietin therapy. It turned out that the patients' quality of life improved most when Hb levels reached around 12 g/dl . Studies examining the impact of anaemia treatment on a patient's prognosis also showed positive effects in the majority of cases. In order to investigate this issue, our Heidelberg work group has designed a prospective, randomised phase-III study on NSCLC patients, which will be explained in detail further down.

Anemia↗
PubMed2005

[IALT Trial].

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Data security and protection in cross-institutional electronic patient records.

This paper aims at identifying the specific legal requirements concerning data security and data protection of patient health data that apply to a cross-institutional electronic patient record (EPR) and describes possible solutions for meeting these requirements. In Germany, the legal framework for such records provide that disclosure of patient health information to physicians of third-party institutions is only allowed in case that it is necessary for the joint treatment of the patient, i.e. in case of a "treatment connection". As a first step, the functionality of a remote-access architecture was proven allowing a one-way connection between the EPR systems of two health institutions in Germany, which jointly treat tumor patients. Besides, a signature system model for ensuring the integrity and authenticity of medical documents was developed and implemented in the existing information system architecture of the University Medical Center of Heidelberg. Especially in Germany, the legal framework for cross-institutional EPRs is very complex and has a considerable influence on the development and implementation of cross-institutional EPRs. However, its introduction is thought to be valuable, since a cross-institutional EPR will improve communication within shared care processes, and thus improve the quality of patient care.

Communication↗
PubMed2002

Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking.

Cigarette smokers inhale a broad range of carcinogens derived from tobacco and its pyrolysis products, including free radicals, which induce oxidative stress and subsequent lipid peroxidation (LPO). Miscoding carcinogen-DNA adducts are formed by cigarette smoke constituents and are thought to initiate lung carcinogenesis. The presence of various types of DNA damage was therefore analyzed in tumor adjacent uninvolved lung tissues of 13 smoking and 11 non-smoking operated lung cancer patients. O(4)-ethylthymidine (O(4)etT), 1,N(6)-ethenodeoxyadenosine ( epsilon dA) and 3,N(4)-ethenodeoxycytidine ( epsilon dC) were determined by immuno-enriched (32)P-postlabeling. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were measured as diagonal radioactive zones after nuclease P1 enriched (32)P-postlabeling. Mean O(4)etT and PAH-DNA adduct levels were higher in lung DNA of smokers than of non-smokers (O(4)etT/10(8) thymidine: 3.8 versus 1.6, P < 0.01; PAH-DNA adducts/10(8) nucleotides: 11.2 versus 2.2, P < 0.01). Pulmonary etheno-DNA adduct levels did not differ between smokers and non-smokers, but large inter-individual variations were observed (80- and 250-fold differences for epsilon dA and epsilon dC, respectively). As all smokers (except one) refrained from smoking at least for 1 week before surgery, our results demonstrate the persistence of O(4)etT and PAH-DNA adducts in human lung. A positive correlation obtained between O(4)etT and PAH-DNA adducts (R = 0.65, P < 0.01) suggests that both adducts are formed from cigarette smoke as the main exposure source. We conclude that in addition to the DNA adducts derived from PAH and tobacco-specific nitrosamines, miscoding O(4)etT lesions are formed by cigarette smoke that contribute to the increased genomic instability and increased lung cancer risk in smokers.

Aged↗
PubMed2002

Networking in shared care--first steps towards a shared electronic patient record for cancer patients.

OBJECTIVES: This paper aims at identifying the data protection and security requirements for a cross-institutional EPR. Three possible models and the first steps towards a cross-institutional EPR for the Thoraxklinik Heidelberg and the Department of Clinical Radiology of the University Medical Center of Heidelberg shall be discussed. METHODS: A comprehensive analysis of literature and legal documents supplied information for determining the data protection and security requirements. By means of information system analysis, the technical preconditions in both institutions as well as three possible models towards a cross-institutional EPR were identified. RESULTS: According to the German penal code it is only allowed to reveal patient information to external physicians in cases of so-called "treatment connection". An extension of the written consent, signed by the patient, verifying the patient agreement that his/her patient data will be stored in a cross-institutional EPR is needed. Among the three models that we identified, the model that constitutes of a virtual EPR with distributed data capture in both institutions was favored. By means of SecuRemote software a secure connection between the Thoraxklinik Heidelberg and the Department of Clinical Radiology was established, allowing the physicians to view the complete cross-institutional health information of a jointly treated patient during the weekly consultation on radiotherapy. CONCLUSIONS: Many requirements listed in this paper are requirements for electronic patient records in general. Besides these general requirements there are specific requirements for a cross-institutional EPR. The legal situation in Germany complicates the development and implementation of a cross-institutional EPR. However, we think that the efforts are reasonable, because a cross-institutional EPR will be able to improve the communication between health institutions, medical disciplines and persons involved in shared care processes. It provides them with more complete health information about the jointly treated patients. A cross-institutional EPR is, therefore, expected to improve the quality of patient care.

Ambulatory Care Facilities↗
PubMed2001

Sensitive detection of rare cancer cells in sputum and peripheral blood samples of patients with lung cancer by preproGRP-specific RT-PCR.

RT-PCR-based amplification of transcripts expressed in cancer but not in normal non-neoplastic cells is increasingly used for the sensitive detection of rare disseminated or exfoliated cancer cells to improve cancer staging and early detection protocols. However, these assays are frequently hampered by false-positive test results due to low-level transcription of the marker genes in normal cells. To overcome these limitations, target transcripts have to be identified that are tightly suppressed in normal non-neoplastic tissues, whereas they should be actively transcribed in the respective cancer cells. Here, we tested RT-PCR assays for 7 neuroendocrine marker transcripts including NCAM, PGP 9.5, gastrin, gastrin receptor, synaptophysin, preprogastrin-releasing peptide (preproGRP) and GRP-receptor to detect rare exfoliated tumor cells in peripheral venous blood and sputum samples from patients with lung cancer. Among these preproGRP RT-PCR was the only assay with which illegitimate transcription in blood or sputum samples from healthy donors or patients with unrelated diseases did not interfere. However, it reproducibly detected up to 10 small-cell lung cancer cells diluted in either 10 ml blood or 5 ml sputum samples. Single blood and sputum samples were collected directly before diagnostic bronchoscopy from 175 patients suspected to have lung cancer. Twenty-six of these had small-cell lung cancer (SCLC). Thereof, 13 patients (50%) tested positive in the blood sample and 5 of 23 patients (22%) tested positive in the sputum sample. Moreover, among 92 patients with non-small-cell lung cancer (NSCLC) 25 patients (27%) had disseminated cancer cells in peripheral blood. Amplification of preproGRP transcripts from clinical samples is a sensitive and specific assay to detect disseminated or exfoliated lung cancer cells either in peripheral blood or sputum samples.

Biomarkers, Tumor↗
PubMed2001

Altered DNA repair capacity and bleomycin sensitivity as risk markers for non-small cell lung cancer.

DNA repair capacity in human peripheral blood lymphocytes was monitored by the repair rate of bleomycin-induced DNA damage using an alkaline single-cell gel electrophoresis assay (comet assay). DNA repair capacity, after 15 min repair time, in lymphocytes of non-small cell lung cancer patients (n = 160) and controls (n = 180) was 67% and 79.3%, respectively (p < 0.0004). Bleomycin sensitivity defined as the tail moment of bleomycin-treated peripheral blood lymphocytes, without allowing time for DNA repair, was significantly higher in lung cancer patients than in tumor-free hospital controls (p < 0.0001). There was no correlation, in either patient or control group, between the bleomycin sensitivity and DNA repair capacity with age or gender. The median values of DNA repair capacity and sensitivity in controls were used as the cut-off points for calculating odds ratios (OR). After adjustment for age, gender and smoking status, the cases vs. controls had reduced DNA repair capacity (OR = 2.1; 95% confidence limit [CL] 1.1-4.0) and increased bleomycin sensitivity (OR = 4; 95% CL 2.2-7.4). For current smokers, the adjusted risk associated with bleomycin sensitivity was 2.3 (95% CL 1.1-4.9). We conclude that our standard comet assay as a phenotypical repair test has sufficient sensitivity and rapidity allowing application to both native and cryopreserved lymphocytes. Bleomycin sensitivity and DNA repair capacity were found to be 2 independent susceptibility markers for non-small cell lung cancer, confirming similar investigations with different marker end points. The latter were much more time consuming than the method used in our study. Thus, the comet assay is more suitable for screening large numbers of individuals in epidemiological studies. Validation of this assay in large prospective studies for the identification of subjects at high risk for non-small cell lung cancer is now warranted.

Adult↗
PubMed2001

Rapid screening assay for mutagen sensitivity and DNA repair capacity in human peripheral blood lymphocytes.

Individual susceptibility to carcinogens, an important determinant of disease risk, is influenced by host factors such as the ability to repair DNA lesions. In order to identify subjects who are at high risk, we have developed a microgel electrophoresis assay for use in molecular epidemiological studies. The assay was validated in a pilot case-control study: Peripheral blood lymphocytes were collected from 100 patients with lung cancer and 110 control patients without cancer and from the same hospital, and stored at -80 degrees C. After thawing, phytohaemagglutinin-stimulated cells were treated with bleomycin at 20 microg/ml for 30 min and the extent of DNA damage and DNA repair capacity were determined by microgel electrophoresis. Peripheral blood lymphocytes from patients with lung cancer were significantly more sensitive to mutagens than those from controls and showed reduced DNA repair capacity (both P < 0.001). Both endpoints were independent risk factors for smoking-related lung cancer. Repeated analysis of peripheral blood lymphocytes from the same individual demonstrated good reproducibility of the assay. Cryopreservation of the lymphocytes for less than or = 12 months did not significantly affect their sensitivity. Our standardized microgel electrophoresis assay is suitable for determining individual sensitivity to mutagens and DNA repair capacity: it is sensitive and faster than cytogenetic assays, and can be applied to native and cryopreserved peripheral blood lymphocytes.

Adult↗
PubMed2001

Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility.

The highly polymorphic N-acetyltransferases (NAT1 and NAT2) are involved in both activation and inactivation reactions of numerous carcinogens, such as tobacco derived aromatic amines. The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls. In addition to the wild-type allele NAT1*4, seven variant NAT1 alleles (NAT1*3, *10, *11, *14, *15, *17 and *22) were analysed. A new method based on the LightCycler (Roche Diagnostics Inc.) technology was applied for the detection of the polymorphic NAT1 sites at nt 1088 and nt 1095. The NAT2 polymorphic sites at nt 481, 590, 803 and 857 were detected by polymerase chain reaction-restriction fragment length polymorphism or LightCycler. Multivariate logistic regression analyses were performed taking into account levels of smoking, age, gender and occupational exposure. An increased risk for adenocarcinoma among the NAT1 putative fast acetylators [odds ratio (OR) 1.92 (1.16-3.16)] was found but could not be detected for SCC or the total case group. NAT2 genotypes alone appeared not to modify individual lung cancer risk, however, individuals with combined NAT1 fast and NAT2 slow genotype had significantly elevated adenocarcinoma risk [OR 2.22 (1.03-4.81)] compared to persons with other genotype combinations. These data clearly show the importance of separating different histological lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma.

Aged↗
PubMed2001

Glutathione-S-transferase M1, M3, T1 and P1 polymorphisms and susceptibility to non-small-cell lung cancer subtypes and hamartomas.

Polymorphic glutathione-S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to lung cancer. In this case-control study (consisting of 389 Caucasian lung cancer patients, including 151 adenocarcinomas (ACs) and 172 squamous cell carcinomas (SCCs), and 353 hospital control subjects without malignant disease, genotype frequencies for GSTM1, GSTM3, GSTP1 and GSTT1 were determined by polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP)-based methods. While adjusted odds ratios (ORs) indicated no significantly increased risk for lung cancer overall due to any single GST genotype, the risk alleles for GSTM1, GSTM3 and GSTP1 conferring reduced enzyme activity were present at higher frequency in SCC than in AC patients. This is consistent with a reduced detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from cigarette smoke that are more important for the development of SCC than for AC. An explorative data analysis also identified statistically significantly increased ORs for the combinations GSTT1 non-null and GSTP1 GG or AG for lung cancer overall (OR 2.23, CI 1.11-4.45), and for SCC (OR 2.69, CI 1.03-6.99). For lung cancer overall, and especially among SCC patients, the GSTT1 null genotype was underrepresented (SCC 11.2% v. control subjects 19%, P = 0.026, OR 0.57, CI 0.30-1.06). Additionally, in 28 patients with hamartomas, the GSTT1 null genotype was also protective (P = 0.013), while GSTP1 variant allele carriers were overrepresented (OR 2.48, CI 1.06-6.51). In conclusion, GST genotypes may act differently, either by detoxifying harmful tobacco carcinogens and/or by eliminating lung cancer chemopreventive agents. The latter role for GSTT1 would explain the observed lower risk of SCC and hamartoma associated with GSTT1 null. Further confirmatory studies are required.

Adenocarcinoma↗
PubMed2001

Endobronchial ultrasound (EBUS)--assessment of a new diagnostic tool in bronchoscopy for staging of lung cancer.

BACKGROUND AND OBJECTIVE: Conventional imaging procedures proved to be insufficient for staging of lung cancer, especially with respect to N-stage, infiltration of mediastinal structures, and early lung cancer. As also the view of the endoscopist is restricted, we developed the new method of endobronchial ultrasonography (EBUS) as an adjunct to conventional bronchoscopy. The initial technical problems were solved by development of a balloon catheter for application of miniaturized 20-MHz probes. PATIENTS AND METHODS: Between January and December, 1999 all patients with an indication for bronchoscopy and additional EBUS were documented prospectively. RESULTS: In 648 patients we used additional EBUS. Of these, 242 (37%) were female and 406 (63%) were male. The mean age was 49.2 (range 0-83) years. The mean procedure time for the bronchoscopies was 18.9 (range 5.7-38.9) min, and the mean time for EBUS was 6.3 (range 3.1-14.4) min. Side effects were comparatively rare. 34 patients (5%) needed supplementary oxygen during the examination, the others tolerated EBUS without any desaturation. CONCLUSION: EBUS is a new technology that can be easily applied and is well tolerated. It improves the results of bronchoscopy in addition to conventional diagnostic procedures. Further developments will be made in future to improve the application of ultrasound in chest medicine.

Adolescent↗
PubMed2001

Integration of clinical practice guidelines into a distributed regional electronic patient record for tumour-patients using XML: a means for standardization of the treatment processes.

With the rising efforts to guarantee a high quality treatment in medicine and to reduce the costs in the health care system, Clinical Practice Guidelines (CPG) have developed into a very important reference in medicine. CPGs are especially useful for the standardization of multi-professional treatment processes like the care for patients with malignant diseases. The Tumour-Centre Heidelberg/Mannheim (Germany) leads a project to build up a regional, virtual distributed Electronic Patient Record (EPR) for patients with malignant diseases in the Rhein-Neckar-Area. Aims of the first stages of the project are the introduction of the distributed EPR to two co-operating pilot-clinics. In this context we intend to provide access for medical professionals not only to the data of the jointly treated patients, but also to relevant existing CPGs and other medical knowledge sources like Medline and Cochrane-Library. Knowledge and Patient data should be interlinked to offer patient-specific views on the CPG-information. As all professions have different information needs, this views should be presented individualized according to the demands of the users. We analysed three relevant CPGs and defined a meta-structure that will be refined to a common meta-structure for CPGs in Oncology. CPGs as well as structured patient-documents will be implemented in the Extensible Markup Language (XML), as this platform-independent technology seems to suit our needs for data exchange and presentation purposes best. The implementation process will be accompanied tightly with evaluations to gain experience for further expansions of the EPR. The vision of the project is, that by integrating CPGs in a shared distributed EPR, the way towards standardized treatment processes in a local, but multi-professional setting, and the efforts to guarantee a high quality treatment in Oncology can sufficiently be supported.

Computer Communication Networks↗
PubMed2001

Using the eXtensible Markup Language (XML) in a regional electronic patient record for patients with malignant diseases.

Communication between different institutions which are responsible for the treatment of the same patient is of outstanding significance, especially in the field of tumor diseases. Regional electronic patient records could support the co-operation of different institutions by providing ac-cess to all necessary information whether it belongs to the own institution or to a partner. The Department of Medical Informatics, University of Heidelberg is performing a project in co-operation with the Thoraxclinic-Heidelberg and the Department of Clinical Radiology, University of Heidelberg with the goal: to define an architectural concept for interlinking the electronic patient record of the two clinical institutions to build a common virtual electronic patient record and carry out an exemplary implementation, to examine composition, structure and content of medical documents for tumor patients with the aim of defining an XML-based markup language allowing summarizing overviews and suitable granularities, and to integrate clinical practice guidelines and other external knowledge with the electronic patient record using XML-technologies to support the physician in the daily decision process. This paper will show, how a regional electronic patient record could be built on an architectural level and describe elementary steps towards a on content-oriented structuring of medical records.

Computer Security↗
PubMed2000

hOGG1 polymorphism and loss of heterozygosity (LOH): significance for lung cancer susceptibility in a caucasian population.

Oxidative damage is implicated in several chronic diseases including cancer. 8-Hydroxyguanine (8-oxoG) is one of the major promutagenic DNA lesions, which is produced by reactive oxygen species, causes G:C to T:A transversions and is excised by OGG1, an 8-oxoG specific DNA glycosylase/AP-Lyase. In a nested case-control study, gDNA from 105 Caucasian primary non-small cell lung cancer cases and 105 matched controls was screened for 6 possible new polymorphic sites in the human OGG1 gene, detected previously mainly in tumour tissue. The previously described Ser(326)Cys polymorphism was found to be common (allele frequency 0.22) in Caucasians. However, no major difference in Ser(326)Cys genotype distribution could be detected between cases and controls. Two 5;-end polymorphisms previously found in Japanese as well as Arg(131)Gln could not be detected in this population. An Ala(85)Ser polymorphism was found in 2 controls, whereas Arg(46)Gln was detected in only 1 case. As the hOGG1 gene is mapped (3p26.2) to a region frequently lost in primary lung tumours, the frequency of loss of heterozygosity (LOH) was investigated. Forty-three percent of the studied lung tumours exhibited loss of one of the hOGG1 alleles. The wt Ser(326) allele was not predominantly lost in our sample set, which suggests a minor role of this polymorphism in tumourgenesis. Our results show that LOH at the hOGG1 gene locus is a very common occurrence in lung tumourgenesis, possibly leading to increased mutational damage due to ROS in smokers. However, the hOGG1 polymorphisms studied are probably not major contributors to individual lung cancer susceptibility in Caucasians.

Adenocarcinoma↗
PubMed2000

Long-term survival in small cell lung cancer patients is correlated with high interleukin-2 secretion at diagnosis.

PURPOSE: We have previously reported significant impairment of IL-2 secretion in patients with small cell lung cancer (SCLC) at the time of diagnosis. Impairment of IL-2 secretion correlated with reduced survival in SCLC. This new prognostic factor was independent of other factors of prognostic relevance in SCLC. The prognostic value of IL-2 secretion was comparable to the most predominant prognostic factors for survival in SCLC identified so far. We now report long-term survival data from these patients. METHODS: The significance of correlations between single parameters in the test groups was calculated by using linear regression analysis, the Wilcoxon rank sum test, and Fisher's exact test. Using the Kaplan-Meier method, the log-rank test and the Cox regression model, we analyzed the relation of IL-2 secretion in whole blood cell cultures from 52 patients with SCLC at the time of diagnosis to established prognostic factors relevant for survival in SCLC. RESULTS: IL-2 secretion correlates with survival in SCLC. In addition, survival analysis according to tumor response and level of IL-2 secretion at the time of diagnosis demonstrates that long-term survival can only be observed after complete response to chemotherapy and high initial IL-2 secretion. CONCLUSIONS: IL-2 secretion at the time of diagnosis represents an independent prognostic factor for survival in SCLC. Moreover, long-term survival is only observed in patients with complete response upon chemotherapy that showed high IL-2 secretion at diagnosis. Therefore, IL-2 secretion may partially define long-term survival in this disease. These results have to be confirmed in a larger patient population.

Adult↗
PubMed2000

[Differential indications for induction therapy of non-small-cell lung tumors].

Induction chemotherapy and induction chemo-radiotherapy have shown their efficiency and feasibility in many phase-II studies and have profen superior to operation alone in stage IIIa of NSCLC in several phase-III studies. Therefore it is justified to recommend this multimodal therapy in stage IIIa N2 disease within clinical studies. However, it is currently not justified to present this multimodal treatment modality as a generally agreed standard.

Carcinoma, Non-Small-Cell Lung↗