Analysis of disease-free survival and overall survival in patients with luminal a breast cancer stratified according to TNM.

BACKGROUND AND AIM: The TNM classification of malignant tumours is the most commonly used system to assess the stage as well as the prognosis of cancer. However, one of the biggest challenges in treatment of breast cancer is the understanding of tumour heterogeneity typical of these carcinomas. The aim of this study was to analyse the disease-free survival and overall survival in patients with luminal A subtype of breast cancer, stratified by TNM staging system. METHODS AND STUDY DESIGN: A total of 363 medical records from January 2001 to May 2006 were evaluated for data collection. There were 136 patients with luminal A breast cancer, selected for the cohort. The main objective was the analysis of disease-free survival (DFS) and overall survival (OS) in patients with luminal A breast cancer, stratified according to the TNM classification. RESULTS: The group of 136 patients with immunohistochemically defined luminal A subtype represented 53% of the 253 patients with breast cancer. There was no significant difference in the number and type of patients as for TNM stage and histological grading among patients treated with chemotherapy and HT in comparison to patients treated with HT alone. CONCLUSION: Our analysis did not prove any significant difference in survival of patients treated with chemotherapy followed by hormone therapy in comparison to patients treated with HT alone. We suggest that the IHC luminal A subtype of breast cancer generally warrants a good prognosis independently on other prognostic factors such as TNM stage. We conclude that patients might not benefit of adding a chemotherapy to hormonal therapy in adjuvant settings.

[Value of postmortem computed tomography in comparison to autopsy]. / Prospektive Untersuchung zur Wertigkeit der postmortalen Computertomographie im Vergleich zur Autopsie.

PURPOSE: To assess the diagnostic value of postmortem computed tomography (CT) in comparison to autopsy. MATERIALS AND METHODS: Twenty-seven cadavers were examined by sequential cranial CT and helical CT through the neck, thorax and abdomen and subsequently underwent an autopsy with histomorphologic examination of the pathologic specimens. The findings of CT, autopsy and histology were registered and compared by three radiologists and one specialist for forensic medicine, using a data entry form. RESULTS: In 19 of 27 cases, the findings explaining the cause of death were concordant for CT and autopsy. Intracranial, intraspinal and intracardiac gas accumulations (n = 12) were registered by CT alone. The detection of skull fractures was equal for both methods (n = 3). CT showed diagnostic problems in the assessment of pneumonic infiltrations (n = 16) and pulmonary edema (n = 21). CONCLUSION: CT is a useful and complementary method to autopsy.

Methadone and its role in drug-related fatalities in Cologne 1989-2000.

All drug-associated deaths from 1989 to 2000 were analysed at the Institute of Forensic Medicine in Cologne. Information concerning sex, gender, drug consumption, time, place and circumstances of death were analysed. A number of 605 cases were recorded; in 518 cases a toxicological analysis was possible and in 171 an autopsy was performed. When it was possible to determine the cause of death form the information available, acute drug intoxication was recorded in 65%. Heroin head the list of identified substances. Sixty-three percent of the specimens showed a combination of several substances, especially a combination of morphine, benzodiazepines, other medications and alcohol. In comparison with other studies the percentage of methadone-positive specimens is low, even though the proportion of specimens positive for methadone increased from 1989 to 2000. This analysis is discussed using background information concerning the management of substitution therapy and the available literature.

Analysis of the co-amplified STR loci D1S1656, D12S391 and D18S51: population data and validation study for a highly discriminating triplex-PCR.

A multiplex-PCR composed of the three highly variable STR loci D1S1656, D12S391 and D18S51 has been established. The non-overlapping fragment sizes allow allele detection using a monochrome automated laser fluorescent sequencer (A.L.F. express, Pharmacia Biotech). The typing results of the triplex-PCR showed no difference to those of singleplex-PCR. Allele frequencies were determined in a Western German population of 228 individuals from Cologne. The heterozygosities and exclusion chances (D1S1656, 0.982; D12S391, 0.979; D18S51, 0.97) are very high compared to other short tandem repeats used for forensic applications. No deviations from the Hardy-Weinberg equilibrium were found. Successful typing of DNA amounts down to 50-100 pg is possible. Mixtures of up to 1:10 can be identified. In conclusion, the high combined exclusion chance due to the well-balanced allelic distribution and its high sensitivity make this triplex-PCR a valuable tool for forensic casework.

Highly sensitive DNA typing for detecting tumors transmitted by transplantation.

DNA typing of a variable number of tandem repeats (VNTRs) and of short tandem repeats (STRs) is a modern forensic method for the identification of biological material. In many cases, amplification by the polymerase chain reaction (PCR), especially of STRs, allows DNA typing of minute amounts of or degraded DNA. Here we describe the successful use of forensic DNA typing to clarify the origin of a malignant tumor. We report two cases of metastatic malignant melanoma of unknown origin that developed a few months after transplantation in two recipients of kidneys from the same donor. Fresh metastatic tissue and blood from the first recipient, reference DNA of the donor, and only paraffin-embedded tissue from the second recipient were available for analysis. To investigate whether the melanoma originated in the donor, DNA analysis of nine polymorphic loci was performed. The results of the analysis showed that, in both cases, the tumors were genetically different from the recipient DNA but matched the donor DNA. One incident of allele loss was attributed to a mutation event. We conclude that the metastatic melanoma in both recipients originated in the donor and was transmitted by renal transplantation.

[Autopsy before cremation--formality without efficacy?]. / Die Kremationsleichenschau--formaler Akt ohne Effizienz?

A multicentre study involving 36 out of 38 German medico-legal Institutes discovered 784 non-natural fatalities among 78,000 external examinations before cremation (1%) in 1995. These included 169 accidents, 16 suicides, 3 homicides and 589 deaths in connection with medical treatment. In the remaining 7 cases, a belated differentiation between homicide and accident was not successful. A linear projection results in 1980 non-natural fatalities among all 197,000 external examinations before cremation. This number includes 8 homicides but due to considerable inhomogeneities, a number of 40 homicides appears to be realistic. Consequently, abolishing the mandatory external examination before cremation would be equivalent to an official renouncement of solving relevant non-natural deaths. In case of a thorough external examination, a total of 18,000 non-natural fatalities including approximately 180 homicides could be detected per year during the first external examinations (n = 885,000).

["Handy-cap" in street traffic. Mobile telephone considerably affects driving-relevant performance]. / "Handy-cap" im Strassenverkehr. Mobiltelefone beeinträchtigen fahrrelevante Leistungen erheblich.

The increasing popularity of mobile telephones prompts the question: are they a danger when used while driving? To date, Germany has no law regulating such use. An international enquiry showed that four European and three non-European countries punish the use of mobile phones by drivers. Analysis of scientific studies on the hazard potential of such devices when used in vehicles unequivocally shows a marked impairment of driving performance. Although this cannot be applied to any particular individual, there is indeed a general potential road traffic hazard. There is thus an urgent need to make users aware of the dangers and for legislature to demand the use of no-hand phones in vehicles. A specific punishment by law (inhibition of mobile phones) must be critically discussed.

Resolution of apolipoprotein B repeat unit position variants on agarose, denaturing, and native polyacrylamide gels.

Utilizing three different electrophoresis systems for the separation of variable number of tandem repeats (VNTR) alleles of the high variable region 3' from the apolipoprotein B (Apo B) locus, it could be shown that apparent allele subtypes on native polyacrylamide gels comigrated with the regular ladder alleles on agarose and denaturing polyacrylamide gels. Two subtypes, one with a shift towards the cathode and one shifted towards the anode, and the corresponding ladder alleles were sequenced in order to determine the molecular basis for this aberrant electrophoretical mobility. Subtype and ladder alleles displayed the same number of repeat units but differed in the number and order of different types of repeats. Depending on the variation in the region of pure AT repeat units, the potential secondary structures of hairpin loop formation differed for subtypes and ladder alleles, which is thought to explain the shift in electrophoretic mobility on native polyacrylamide gel electrophoresis.

Cellular distribution of the mRNA for the kappa-opioid receptor in the human neocortex: a non-isotopic in situ hybridization study.

Opioid receptors (OR) provide primary interaction sites of the human brain with opiates. Presently kappa-OR mRNA expression was studied in different cortical areas (A4, A10, A17) by in situ hybridization using digoxigenin-labeled oligonucleotides and an alkaline phosphatase-mediated color reaction. kappa-OR mRNA was expressed mainly in layers II/III and V pyramidal and layer VI multiform neurons. A4 giant pyramidal and A17 giant stellate neurons stood out labeled. These findings fit in with our data on kappa-OR protein distribution. Combined cellular assessment of protein and mRNA will enable the study kappa-OR expression under physiological and pathological conditions.

Multiple skeletal muscle metastases from malignant pleural mesothelioma.

A 54-year-old male patient (occupational asbestos exposure over 27 years) died 2 years and 4 months after the diagnosis of malignant pleural mesothelioma of the right side, despite twice undergoing pleurectomy and radiotherapy. The autopsy revealed a locally advanced pleural mesothelioma of both sides involving the pericardium, heart, right diaphragm, liver and peritoneum. Disseminated metastases in numerous lymph nodes and a hematogenous metastatic spread into both lungs, the thyroid gland, peritoneum and skeletal musculature were found. The left temporal muscle and proximal limb skeletal muscles of the right upper arm and both thighs exhibited multiple metastases measuring up to 7 cm in diameter. Microscopically, a biphasic type of mesothelioma was detected. To our knowledge this is the first extensive case report on muscle metastases in malignant mesothelioma. Reviewing the literature, it is thought that in the presented case the long survival time of the patient and his protracted preterminal immobility could have contributed to the unusual formation of multiple skeletal muscle metastases.

Individualization of fresh and stored human urine samples by PGM1- and Gc-subtyping.

After 50- to 200-fold concentration by ultrafiltration, 56 fresh urine samples from healthy individuals (26 men, 30 women) and eight samples from corpses were subjected to isoelectrofocusing methods. All the urine samples tested could be correctly typed in both the phosphoglucomatase 1 (PGM1) and Gc system when compared to reference blood samples. The activity of urinary PGM1 revealed intraindividual and interindividual variations. To our knowledge this is the first report of PGM1 detection in urine. A systematic storage experiment over a period of 6 months was carried out at different temperatures (-20 degrees C, 4 degrees C, 20 degrees C); furthermore, aging of urine samples from 4 months to 4 years was investigated. The heterogeneous typing results were as follows. For Gc: after a storage period of 6 months positive results could be obtained in approximately 40% of those samples that were stored frozen (-20 degrees C) or in a refrigerator (4 degrees C). Some samples, however, showed negative analyses already after a 1 month storage period. At room temperature positive results could be achieved up to 3 months. Additional bands can appear in pherograms of urine samples stored at room temperature or in a refrigerator; they may cause misinterpretation, dependent on the original Gc-type. The maximum storage time compatible with successful Gc-typing was 1 year. For PGM1: this polymorphism could be regularly detected up to 1 week, and in some cases up to 1 month, in urine samples stored at 4 degrees C. The PGM1 activity gradually decreased; there were no additional or variant bands.

Immunohistochemical localization of kappa opioid receptors in the human frontal cortex.

The cellular and subcellular kappa opioid receptor distribution in human frontal cortex was studied using the monoclonal antibody (KA8). kappa opioid receptor-like immunoreactivity was mainly localized in pyramidal neurons of layers II/III and V. In addition, some round and ovoid neurons were found immunolabeled mainly in layer VI. At the ultrastructural level the immunoprecipitate was attached to the cell membrane but was not associated with synaptic specializations. Furthermore, labeling was present in the neuronal perikarya associated with free ribosomes and in the dendrites partly decorating microtubular structures. Previous autoradiographic findings remained restricted to the level of laminar distribution. By contrast, the monoclonal antibody KA8 provides a unique tool to study the cerebral kappa opioid receptor distribution on the cellular and subcellular level.

High sensitive DNA typing approaches for the analysis of forensic evidence: comparison of nested variable number of tandem repeats (VNTR) amplification and a short tandem repeats (STR) polymorphism.

The approach of using nested primers for the APO B variable number of tandem repeats (VNTR) increases the sensitivity of the polymerase chain reaction (PCR) to single cell level. Different experiments and a comparison to the short tandem repeats (STR) system VWA were carried out, to determine the applicability of this method to forensic samples. Nested amplification of the Apo B VNTR was affected by a strong tendency towards preferential amplification of the shorter alleles. This phenomenon was observed for DNA quantities as low as 100 pg and impaired, depending on the allele length, the results for mixed samples. As expected, VWA polymorphism showed less preferential amplification. The high sensitivity of both PCR systems is accompanied by an increased susceptibility to contamination. Using artificially contaminated bloodstains, the bloodstain genotype, the contamination or both genotypes could be found on one piece of evidence. Here a single analysis can lead to an incorrect result. Therefore a strategy for obtaining reliable results should consist of multiple stain extractions and the amplification of different stepped dilutions of the DNA solution.

[Possibilities of serologic individual typing of urine]. / Möglichkeiten der serologischen Urinindividualisierung.

Human urine is frequently analysed in cases of doping or drug consumption. In this connection the necessity of an adequate urine identification arises. Apart from DNA-polymorphisms it exists a comprehensive repertoire of classic serological methods for this purpose. Human urine samples have been typed successfully in the following blood group systems: antigens of the erythrocytes' membrane (AB0-, Lewis-system), protein polymorphisms (Gc, transferrin, alpha-2-HS-glycoprotein) and enzyme polymorphisms (GPT). The results of the different studies are presented and completed by our own experiences with the Gc-system. In addition it is reported about our investigations concerning PGM1-subtyping of human urine.

Genetic variation of the amplified VNTR polymorphism COL2A1 in Chinese and German populations.

The amplifiable VNTR polymorphic system COL2A1 has been investigated in Chinese and German population samples. In order to accurately identify COL2A1 alleles, a number of human allele ladders were prepared. A total of 14 different alleles in 23 genotypes was observed in the Chinese population, while in the German population there were 11 alleles in 24 genotypes. Four new alleles were observed. All of them were found in the Chinese and one was also observed in the German population. There was no statistical difference in the allele distribution between two German populations from Münster and Köln, while the allele frequency distribution in the Chinese population differed significantly from the German.

[Empirical studies of automobile driving fitness of patients treated with methadone-substitution]. / Empirische Untersuchungen zur Fahreignung von Methadon-Substitutionspatienten.

The aim of this experimental study was to gain an impression on the driver fitness of heroin addicts which were at the moment substituted by methadone especially within a methadone program sponsored by the government of NRW. 21 out of 34 patients investigated were unfit to drive because they were at the time the tests were conducted under the effect of at least one additional psychotropic substance other than methadone or because at prior blood tests within 3 months they had been found at least twice under the effect of psychotropic drugs or they were known as concomitant drug users. The remaining 13 methadone patients were matched with 13 control subjects of the same sex, education and-within a range of +/- 2 years-also the same age. Testing short term memory, tracking, decision and reaction behavior, perception, sustained attention, speed estimation, peripheral attention with simultaneous central task, reactive loading, personality questionnaires including traffic specific questions and psychopathologic characteristics the patients yielded significant poorer results compared with the control group. When selecting 6 very good patients according to the decision of the physicians the significant differences concerning performance measures vanished but some differences concerning personality traits still remained. The results confirm the expert's opinion-called "disease and motor traffic"-that in general methadone substituted patients are unfit to drive. The driver fitness of the very few optimal patients depends on the amount of the personality disorders.

[Plasma levomethadone level and concomitant use of sedatives in a methadone test program]. / Levomethadon-Plasmaspiegel und Beigebrauch von Sedativa im Methadon-Erprobungsprogramm.

Treatment of heroin addicts with levomethadone as an alternative to the clinically performed withdrawal gains in significance more and more. Just for that reason accompanying scientific programs guided along criterions of therapy research are essential. Results of an evaluation which is to be regarded as preliminary showed no correlation between methadone plasma levels and dosage. Additional consumption of opiates, barbiturates, and benzodiazepines was observed to a high degree. The efficiency of methadone treatment is to be valued only under consideration of criterions of admission to the program as for instance a drug abuse of many years or multiple unsuccessful treatments by withdrawal.

[Life expectancy of the drug addict]. / Lebenserwartung des Drogenkonsumenten.

The exact characterization of the epidemiology of drug-related mortality demands investigations of cross-sectional dates and the pursuit of trends under scientifically correct conditions. At the moment the possibilities of research in this field are limited. This is the reason why conclusions concerning the life expectancy of drug-addicts should be drawn with caution. Although systemic studies are not available and--for different reasons--cannot be expected in the FRG few sample surveys do exist which may be considered indicative of certain trends in mortality. Besides the Netherlands the FRG has become the most important market characterized by a rapid increase in illegal drug traffic. The number of drug-related deaths dramatically rises and the elder age-groups are increasingly concerned with the age-group from 20 top 30 years displaying a significantly increased mortality in connection with drug abuse. The epidemiologic development described so far is supposed even to be aggravated because the i.v.-drug-addicts are at high risk to acquire a hepatitis or HIV-infection.