Distribution of drugs of abuse within specific regions of the human brain.

Since concentration of drugs of abuse found in the brain better reflect drug concentration at their site of action, brain specimens are useful in the determination of the role of drugs of abuse in the cause of death. In order to allow for the routine use of brain specimens in this field, a comprehensive database with reliable reference values is needed and should include both post-mortem data for cases where drugs have been taken in therapeutic doses as well as for cases of overdose. In this study, a semi-automated extraction procedure, in combination with gas chromatography/mass spectrometry (GC-MS) using stable isotope internal standards was applied to yield reproducible, quantitative results which could be used to investigate the distribution patterns of drugs of abuse within specific regions of the brain, by analyzing several segments of both medulla oblongata and cerebellum. A homogenous distribution of unconjugated morphine, dihydrocodeine, and benzoylecgonine within the investigated segments of medulla oblongata or cerebellum could be found. However, when these two brain regions from the same case were compared to each other, significantly higher concentrations of unconjugated morphine, dihydrocodeine, and benzoylecgonine were found in the cerebellum than in the medulla oblongata.

[Biocompatibility testing of different sterilised or disinfected allogenous bone grafts in comparison to the gold standard of autologous bone grafts--an "in vitro" analysis of immunomodulation]. / Biokompatibilitätstestung unterschiedlich sterilisierter bzw. desinfizierter allogener Knochentransplantate im Vergleich zum Goldstandard der autologen Knochenspende--Eine "In-vitro"-Analyse der Immunmodulation.

INTRODUCTION: Repair of large skeletal defects using bone allografts has become a routine procedure in orthopaedic and trauma surgery. Different procedures of sterilisation (82.5 degrees C disinfection; 121 degrees C autoclaving; PES; Tutoplast; 25 kGy gamma irradiation) are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone allografts. The efficiency of these procedures has been proven. However, the effects on the cellular response are rarely investigated. This present in vitro study investigates the immunological answer of human bone marrow cells to human allogenous and autologous bone platelets which were sterilised by different methods. MATERIALS AND METHODS: Human bone marrow cells and the bone platelets were harvested from patients undergoing a total hip replacement. All patients provided informed consent. Human bone platelets, 10 mm in diameter, 3 mm in height, were produced from femoral heads which were removed within the scope of total hip replacements. They were sterilised by different procedures or were disinfected (gamma radiotherapy, PES/ethanol treatment, Tutoplast procedure, 121 degrees C autoclaving, > 82.5 degrees C thermodisinfection). In addition, an autologous in vitro bone donation was simulated and compared with the allogenous bone grafts. Endobon was evaluated as a bovine hydroxyapatite ceramic. As control a human bone marrow cell culture without bone platelets was used. Over a period of four weeks the changes of the immunogenic cell populations were analysed in vitro (FACS analysis). Light and scanning microscopy were done to reveal morphological differences. As a vitality test the trypan-blue staining was performed. RESULTS: Light and scanning microscopy demonstrated large differences between the various sterilisation and disinfection methods. After 4 weeks the autologous bone platelets were completely covered with homogenously distributed human osteoblast like cells. The heat-sterilised/disinfected transplants demonstrated similar effects compared to the autologous bone grafts while the irradiated bone platelets demonstrated less cell coverage. 2/3 of the cells were vital on average after four weeks, with the exception of the irradiated bone platelets. The FACS analysis revealed in comparison to the control group provable differences in the immunological answer for the autologous bone donation as well as for the differently sterilised or disinfected allogenous bone grafts. The heat sterilisation or, respectively, disinfection methods compared to the autologous bone donation demonstrated almost similar in vitro effects. By far the worst results, characterised by an excessively increased portion of cytotoxic T-cells and a decreased amount of viable cells, were seen in the 25 kGy gamma irradiation samples. CONCLUSIONS: The results demonstrate the influence of the different sterilisation and disinfection procedures on the differentiation of human marrow cells (host). Similar in vitro effects were seen for the autologous and heat-treated bone platelets. The treatment of allogenous bone grafts with PES/ethanol and the Tutoplast procedures showed, just as Endobon, only low differences in comparison with the control cultures. The worse results in the case of the irradiated bone platelets may be explained by the production of free radicals which led to an excessive cell death.

Blood stem cell collections after mobilization with combination chemotherapy containing ifosfamide followed by G-CSF in multiple myeloma.

High-dose chemotherapy with autologous peripheral blood stem cell transplantation is the standard treatment of patients with multiple myeloma today. In this study we used a combination mobilizing chemotherapy containing ifosfamide with G-CSF before stem cell collection. The chemotherapy regimen consisted of ifosfamide (2,500 mg/m(2) days 1-3), epirubicin (100 mg/m(2) day 1) and etoposide (150 mg/m(2) days 1-3) followed by G-CSF (5 mug/kg from day 5). In 30 younger patients (median age 51 years; range 41-60 years) who received the IEV regimen in 100% dosage, a median of 11.15 x 10(6) CD34(+) cells/kg (range 0-44.60 x 10(6) CD34(+) cells/kg) was collected. In 22 elder patients (median age 64 years; range 59-72 years) similar collection results were obtained with a median of 10.82 x 10(6) CD34(+) cells/kg (range 0.99-42.22 x 10(6) CD34(+) cells/kg) after the IEV regimen in 75% dosage. The pretreatment chemotherapy cycles before mobilization were fewer in elder patients with a median of 0 cycles (range 0-7 cycles) compared with younger patients with a median of 4 cycles (range 0-7 cycles). These collection results were favorable and allowed to support a tandem transplantation procedure in younger and elder patients in 97 and 95%, respectively. In the majority of patients, the hematological toxicity of IEV was of WHO grade 3/4. The extramedullary toxicity was mild to moderate and there were only few cases (5-10%) of relevant nephrotoxicity or neurotoxicity associated with the application of ifosfamide.

[Congenital, solitary hepatic cyst: Observation of the development from birth upon the intervention in the 5th year of life]. / Kongenitale solitäre Leberzyste - Eine Verlaufsbeobachtung von der Geburt bis zur Intervention im 5. Lebensjahr.

BACKGROUND: Sonographic screening helps to discover pathological findings in asymptomatic patients. In these cases the decision about diagnostic and therapeutic consequences is difficult. CASE REPORT: We describe a girl with a congenital small solitary hepatic cyst with rapidly increasing size after the second year, which was interventionally sclerosed at the age of five years. CONCLUSION: Even in cases of small cysts long term follow up investigations are necessary, because the growth rate of the cyst can change.

[Evaluation of the efforts in prenatal care for the prevention of prematurity]. / Bewertung von Bemühungen in der Schwangerenvorsorge um Prävention der Frühgeburtlichkeit.

A retrospective analysis was done in 341 singleton premature deliveries to assess the practised activities in antenatal care for the prevention of premature delivery. This analysis, expressed in terms of adequacy revealed that 56% were adequate whereas 23% were conditionally adequate and 21% were inadequate. Clinically these activities were reflected in suppression of uterine contractions (80%/57%/40%-effective tocolysis), achieved prolongation of pregnancy (25d/8d/2d) and a lowered rate of premature delivery before the 32nd week of gestation (17%/31%/33%), respectively. A prospective study depending on these results (n = 450) done in 4 centers for antenatal care (under constant supervision to keep the respective recommended activities) showed a significant reduction in the rate of premature delivery compared to a similar control group (n = 458) in the year 1988. Simultaneously, we could demonstrate the influence of patient explanation and the growing patient satisfaction which resulted in reduction of premature delivery.