ICESat-2/ATLAS Onboard Flight Science Receiver Algorithms: Purpose, Process, and Performance.

The Advanced Topographic Laser Altimetry System (ATLAS) is the sole instrument on the Ice, Cloud, and land Elevation Satellite 2 (ICESat-2). Without some method of reducing the transmitted data, the volume of ATLAS telemetry would far exceed the normal X-band downlink capability or require many more ground station contacts. The ATLAS Onboard Flight Science Receiver Algorithms (hereinafter Receiver Algorithms or Algorithms) control the amount of science data that is telemetered from the instrument, limiting the data volume by distinguishing surface echoes from background noise, and allowing the instrument to telemeter data from only a small vertical region about the signal. This is accomplished through the transfer of the spacecraft's location and attitude to the instrument every second, use of an onboard Digital Elevation Model, implementation of signal processing techniques, and use of onboard relief and surface type reference maps. Extensive ground testing verified the performance of the Algorithms. On-orbit analysis shows that the Algorithms are working as expected from the ground testing; they are performing well and meeting the mission requirements.

ICRP Publication 140: Radiological Protection in Therapy with Radiopharmaceuticals.

Radiopharmaceuticals are increasingly used for the treatment of various cancers with novel radionuclides, compounds, tracer molecules, and administration techniques. The goal of radiation therapy, including therapy with radiopharmaceuticals, is to optimise the relationship between tumour control probability and potential complications in normal organs and tissues. Essential to this optimisation is the ability to quantify the radiation doses delivered to both tumours and normal tissues. This publication provides an overview of therapeutic procedures and a framework for calculating radiation doses for various treatment approaches. In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by radiopharmaceutical uptake, retention in and clearance from the various organs and tissues of the body, together with radionuclide physical half-life. Biokinetic parameters are determined by direct measurements made using techniques that vary in complexity. For treatment planning, absorbed dose calculations are usually performed prior to therapy using a trace-labelled diagnostic administration, or retrospective dosimetry may be performed on the basis of the activity already administered following each therapeutic administration. Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes; these analyses show the reliability and quality of absorbed dose calculations. Effective dose can provide an approximate measure of lifetime risk of detriment attributable to the stochastic effects of radiation exposure, principally cancer, but effective dose does not predict future cancer incidence for an individual and does not apply to short-term deterministic effects associated with radiopharmaceutical therapy. Accident prevention in radiation therapy should be an integral part of the design of facilities, equipment, and administration procedures. Minimisation of staff exposures includes consideration of equipment design, proper shielding and handling of sources, and personal protective equipment and tools, as well as education and training to promote awareness and engagement in radiological protection. The decision to hold or release a patient after radiopharmaceutical therapy should account for potential radiation dose to members of the public and carers that may result from residual radioactivity in the patient. In these situations, specific radiological protection guidance should be provided to patients and carers.

Radiosensitivity: Gender and Order of Administration of G-CSF, An Experimental Study in Mice.

To elucidate the potential influence of stimulating bone marrow before cell-cycle-dependent irradiation, we sought to determine overall survival in mice receiving total-body irradiation (TBI) when administered granulocyte stimulating factor (G-CSF) at different time points. Gender differences were also studied. C57/BL/6J mice, aged 9-14 weeks, received 8 Gy TBI in a perspex cage using a linear accelerator. In each of five different experiments, three groups were studied: 1. one control group receiving TBI only; 2. one group treated with filgrastim [500 lg/kg subcutaneously/intraperitoneally (s.c./i.p.)] the day before TBI, followed by daily filgrastim injections postirradiation (1-5 days); and 3. one group treated with daily filgrastim injections only post-TBI (1-5 days). Each experimental group included male and female mice. Survival of the mice was monitored daily, and mice were euthanized when their condition deteriorated. A total of 293 mice were monitored for at least 37 days post-TBI. Control mice that received 8 Gy TBI showed a significant gender difference, with a median survival of 22 days in females and 17 days in males. Addition of G-CSF, irrespective of pre- or postirradiation, significantly improved survival, but in males the improvement was significantly better when G-CSF was not given before TBI. Improved survival in females was independent of the order of administration of GCSF. Multiple filgrastim injections were more effective than a single injection, and s.c. administration was not better than i.p. In conclusion, these findings indicate that male mice are more sensitive to TBI than females. Filgrastim improved survival in both genders irrespective of whether given pre- or postirradiation, but in males the improvement was significantly less if an injection was given before irradiation. These results suggest that, to prevent toxicity most effectively, GCSF should not be given before cytotoxic therapy. While a completely different experimental model was used here, these results may also be extrapolated to indicate that endocrine cell-cycle suppression therapy should not be given before or during cytotoxic therapy of hormone-dependent tumors (e.g., breast and prostate cancer), thus a reduction in the efficacy of cell-cycle-dependent therapy can be prevented.

Results of an international comparison of 57Co.

As part of a Cooperative Research Project (CRP) aimed at improving the state of radioactivity measurement in nuclear medicine, the International Atomic Energy Agency (IAEA) organized a comparison of (57)Co solutions among the participants of the project. The comparison solutions were prepared from a single master stock solution and distributed to the participating laboratories, who measured the activity concentration of the solution using either the laboratory's radionuclide activity calibrator or primary standardization methods. A total of 9 sets of results were received, with 5 laboratories reporting results of primary measurements, one reporting results of secondary measurements calibrated against primary standards, and three laboratories reporting values based on measurements in commercial re-entrant ionization chambers using manufacturer-recommended calibration figures. Most of the laboratories reporting primary standardizations also provided results from secondary standardizations. The Comparison Reference Value was calculated from the mean of the five primary standardizations and was found to be 35.54 MBq g(-1), with a standard deviation of the mean of 0.17 MBq g(-1). Degrees of equivalence were calculated for each reporting laboratory and demonstrated that equivalence to within about 4% could be achieved, even in the case of those laboratories that used instruments calibrated by third parties.

Panmixia in European eel revisited: no genetic difference between maturing adults from southern and northern Europe.

Previous studies of genetic structure in the European eel have resulted in seemingly conflicting results, ranging from no detectable heterogeneity to small but statistically significant differences and isolation by distance patterns among eels sampled across the continental range. Differences with respect to sampling design and choice of molecular markers, combined with a lack of power estimates, complicate comparisons of existing results. In this study we have used six microsatellite markers and, for the first time, compared maturing silver eels of known age from southern and northern Europe (Italy and Baltic Sea). In comparison with previous studies, our data may give a better representation of potential spawning stocks because eels were sampled when having begun their migration toward the presumed spawning area in the Sargasso Sea. Despite large sample sizes (404 and 806 individuals) we could not observe any signs of genetic differentiation (average F(ST)=-0.00003, P=0.61), and a power analysis showed that the true level of heterogeneity (if existing) must be exceedingly small to have remained undetected (say, F(ST) <0.0004). A tendency for slightly increased genetic differences between cohorts over time could be seen, but the amount of temporal change was minor and not statistically significant. Our findings reiterate the notion that previous reports of continental genetic differentiation in the European eel may be largely explained by uncontrolled temporal variation between juvenile glass eel samples.

[Anesthesia for cesarean section of obese women. Results of a four-year observation]. / Anästhesie zur Sectio caesarea bei Adipositas. Befunde einer vierjährigen Beobachtung.

OBJECTIVE: Regional anaesthesia is recommended for caesarean section in obese women. With regard to this aspect anaesthesia practice in the obstetrics department of the University Hospital Kiel was evaluated retrospectively. METHODS: Data from 1,461 consecutive caesarean sections were evaluated. Pregnant women were subgrouped according to their prepartal body mass index (BMI). Statistics were performed by the chi(2)-test and the Wilcoxon and Mann-Whitney U-test, with a significance threshold of p<0.05. RESULTS: Of the pregnant women who underwent a caesarean section 27% were obese (BMI 30.0-34.9) and 15% were extremely obese (BMI > or =35). Spinal anaesthesia was performed most frequently in 47% with an uptrend in severely obese parturients. All other aspects investigated were independent of BMI. Vasoactive drugs were given less during general anaesthesia than in regional anaesthesia (3 vs. 54%). APGAR values were significantly better with regional anaesthesia, but perioperative complaints of distress were more common. Spinal anaesthesia was favoured by patients and staff in the postoperative survey ( p<0.001). CONCLUSION: Obesity is a common risk factor in caesarean section anaesthesia. Spinal anaesthesia can be recommended even for obese parturients.

Lack of molecular genetic divergence between sea-ranched and wild sea trout (Salmo trutta).

The supportive breeding programme for sea trout (Salmo trutta) in the River Dalälven, Sweden, is based on a sea-ranched hatchery stock of local origin that has been kept 'closed' to the immigration of wild genes since the late 1960s (about seven generations). In spite of an apparent potential for substantial uni directional gene flow from sea-ranched to wild (naturally produced) trout, phenotypic differences with a presumed genetic basis have previously been observed between the two 'stocks'. Likewise, two previous studies of allozyme and mitochondrial DNA variation based on a single year of sampling have indicated genetic differentiation. In the present study we used microsatellite and allozyme data collected over four consecutive years, and tested for the existence of overall genetic stock divergence while accounting for temporal heterogeneity. Statistical analyses of allele frequency variation (F-statistics) and multilocus genotypes (assignment tests) revealed that wild and sea-ranched trout were significantly different in three of four years, whereas no overall genetic divergence could be found when temporal heterogeneity among years within stocks was accounted for. On the basis of estimates of effective population size in the two stocks, and of FST between them, we also assessed the level of gene flow from sea-ranched to wild trout to be approximately 80% per generation (with a lower confidence limit of approximately 20%). The results suggest that the reproductive success of hatchery and naturally produced trout may be quite similar in the wild, and that the genetic characteristics of the wild stock are largely determined by introgressed genes from sea-ranched fish.

[Development of ultrasonography in a radiological university department from 1994 to 2001]. / Entwicklung der sonographischen Diagnostik in einer Radiologischen Universitätsklinik von 1994 bis 2001.

BACKGROUND: In 1994, 5 % of a total of 25 718 examinations and 7 % of all 4630 B-mode sonograms performed in the Radiology Department, University of Cologne was classified as not indicated. In light of these results, the health care policy guidelines for sonographic indications have been amended. PURPOSE: The aim of this study was to establish the current rate of non-indicated sonographic examinations performed in routine diagnostics by radiology departments at university hospitals, to determine the reasons for such over-diagnosis and identify which regulatory mechanisms can be implemented to prevent his. METHOD: We counted the number of 1) B-mode and 2) color-flow Doppler ultrasound imaging procedures carried out in patients who had had no change in symptoms within the previous 4 weeks or who were scheduled without reference to an existing sonogram (double examinations). 3) The reasons for over-diagnosis were analyzed. 4) The 1994 survey was repeated in 2000 with an identical protocol and 5) additionally, a modified survey of the diagnostic questions was conducted. RESULTS: 1) Out of 4,119 patients presenting for the first time to receive a B-mode sonogram, 443 prior sonograms (11 %), 305 CT scans (7 %) and 57 MRI scans (1 %) were documented. 2) Double sonograms were carried out in 6 % of the 1,118 patients presenting for the first time for color-flow Doppler ultrasounds and in 16 % of the 651 patients assigned to receive catheter angiographies with arterial color-flow Doppler. 2) 41 out of 55 (75 %) prior sonograms from non-university settings stated by 94 surgery patients were listed in the medical records. 36 out of 43 (84 %) prior sonograms from the university hospital were repeated in the same patients despite the fact that the medical report with the findings was available. None of the 48 sonograms indicated to confirm a plausible finding yielded any information that was additionally relevant to therapy. 4) In the period April - June, 2000, 12 % of all 15,921 tests and interventions, 26 % of 3,569 B-mode sonograms and 58 % of 1,033 abdominal sonograms performed in adults were classified as having not been indicated. 5) Staging and follow-up were stated as the most common reasons that a sonography was carried out in 46 % of the 1,017 adults who were given B-mode sonograms conducted from Jan - Mar, 2000 and comprised 62 % of the 410 sonograms classified as not or probably not medically indicated. CONCLUSION: The results showed that a multidisciplinary consensus was required to establish the diagnostic value of sonographic procedures. Therefore, this research group drafted a hospital-internal interdisciplinary guideline for "abdominal transcutaneous B-mode sonography in oncological questions".

[Prophylaxis of Postoperative Nausea and Vomiting FollowingGynaecological Laparoscopy]. / Mono- und Kombinationsprophylaxe von Ubelkeit und Erbrechen nach gynäkologischen Laparoskopien.

OBJECTIVE: Compared to other procedures, gynaecological laparoscopies are followed rather frequently by postoperative nausea and vomiting (PONV). Therefore, we investigated the prophylactic antiemetic efficacy of metoclopramide and droperidol under general anaesthesia with isoflurane (part 1). Given the rather unsatisfying results of this monoprophylaxis we examined the effects of a quintuple prophylaxis in this setting (part 2). METHODS: Part 1: Following ethical committee approval and written informed consent 120 patients scheduled for elective gynaecological laparoscopy were allocated prospectively, randomly and observer-blinded to the following groups: group P (placebo): 2 ml NaCl 0.9 %, group D: 2.5 mg droperidol, group M: 10 mg metoclopramide. Part 2: Subsequently 50 patients scheduled for elective gynaecological laparoscopy and bearing a minimum risk of 25 % to experience postoperative vomiting were allocated prospectively and blinded to the observers to a quintuple prophylaxis group: group X: 10 mg metoclopramide, 2.5 mg droperidol, 12.5 mg dolasetron, 62.5 mg dimenhydrinate, 8mg dexamethasone. Part 1 and 2: Anaesthesia was induced with fentanyl, etomidate and succinycholine and maintained with isoflurane/N2O, fentanyl and cisatracurium. The antiemetics were applied intravenously 20 min prior to end of surgery. RESULTS: Within the first 24 h postoperatively vomiting occurred more frequently in group P (44 %) compared to group D (21 %, p = 0.046) and group M (33 %, n. s.). Nausea also occurred more frequently in group P (61 %) compared to group D (24 %, p = 0.003) and group M (48 %, n. s.). Intensity of nausea was reduced both in group D and group M compared to group P (p = 0.03). Likewise the requirements for antiemetics as a rescue medication were reduced in group D (p = 0.02) and group M (p = 0.047) compared to group P. In group X no patient suffered from postoperative vomiting, no patient required a rescue antiemetic. CONCLUSIONS: Whereas droperidol provides a reliable antiemetic effect, the prophylactic effect of metoclopramide is rather uncertain. Therefore, further studies regarding a dose response-relationship for metoclopramide are deemed necessary. Since a monoprophylaxis with droperidol or metoclopramide failed to attain a satisfying PONV-prophylaxis in patients at high risk for PONV, the quintuple antiemetic combination might be an effective and safe solution.

Dose-response relationship of propofol on mid-latency auditory evoked potentials (MLAEP) in cardiac surgery.

BACKGROUND: Propofol-sufentanil anaesthesia has become popular during cardiac surgery for its titrability and short recovery time. Avoidance of awareness is a major goal during cardiac surgery. We therefore investigated the dose-response relationship of propofol and cortical responses (mid-latency auditory evoked potentials, MLAEP). METHODS: One hundred patients undergoing cardiac surgery were investigated. Basic anaesthesia was performed with sufentanil (4.5 microg kg(-1) h(-1)) / flunitrazepam (9 microg kg(-1) h(-1)) infusion (control group); the other groups received in addition a loading dose of propofol 2 mg kg(-1) and a maintainance infusion of 1-3.5 mg kg(-1) h(-1). MLAEP were evaluated by using Pa/Nb-amplitudes and Nb-latencies. Haemodynamics were monitored by ECG, arterial blood pressure and cardiac function with pulmonary artery catheterization. RESULTS: In the control group, median amplitude of MLAEP decreased by 50% with a wide range, but were detectable in >90% of patients throughout surgery. Propofol suppressed amplitude Pa/Nb of MLAEP dose dependently. With 3.5 mg kg(-1) h(-1) amplitudes disappeared in >40% of patients throughout cardiac surgery. Median Nb-latencies increased in the control group from 44 to a range from 50 to 60 ms. In groups with propofol >2 mg kg(-1) h(-1), Nb-latencies, detectable in the patients without complete suppression of MLAEP, increased to median 60 ms. Haemodynamic parameters and cardiac function did not differ among the groups. The use of vasopressors was not increased even with the highest propofol dose used. CONCLUSION: The dose-response effect of propofol on auditory evoked potentials reveals that combining a loading dose of 2 mg kg-1 with a consecutive infusion of 3.5 mg kg(-1) h(-1) significantly suppresses MLAEP during cardiac surgery. Thus, auditory information may not be processed and awareness with recall becomes unlikely.

Minimum local analgesic dose of plain ropivacaine vs. ropivacaine combined with sufentanil during epidural analgesia for labour.

We have used the up-and-down allocation technique to assess the relative analgesic potencies of epidural ropivacaine alone and ropivacaine combined with sufentanil 0.75 microg.ml-1 in 42 women requesting epidural analgesia in the first stage of labour. Parturients were randomly allocated to one of the two epidural solutions in a double-blind manner. The concentration of local anaesthetic was determined by the response of the previous parturient: an effective concentration (pain < or = 10 mm on a 10-cm visual analogue pain score within 30 min) resulted in a 0.01% decrease in the concentration of ropivacaine for the next parturient, an ineffective concentration resulted in a 0.01% increase. Minimum local analgesic concentration of ropivacaine alone was 0.13% (95% CI 0.12-0.13%) compared with 0.09% (95% CI 0.08-0.1%) for ropivacaine with sufentanil (p < 0.00001).

Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer.

The purpose of the present study was to compare the therapeutic efficacy of the alpha-emitter Astatine-211 with the beta-emitter Iodine-131 bound to the specific monoclonal antibody MOv18. The measurements were performed in an ovarian cancer cell line (NIH:OVCAR 3) growing intraperitoneally in nude mice. Two weeks after the intraperitoneal inoculation of 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR-3 twenty mice were treated intraperitoneally with the specific monoclonal antibody MOv-18 labelled with either 211At (310-400 kBq) or 131I (5100-6200 kBq). The pharmacokinetics and biodistribution of labelled antibody in tumour-free animals were studied and the resulting bone marrow dose was estimated. When the mice were treated with 211At-labelled antibody 9 out of 10 mice were free of macro- and microscopic tumour compared to 3 out of 10 when Iodine-131 was used. The equivalent dose to the bone marrow was 2.4-3.1 Sv from 211At- and 3.4-4.1 Sv from 131I-irradiation. The therapeutic efficacy of 211At-labelled specific antibody is very good and, at approximately equivalent bone marrow doses, better than that of 131I.

Microsurgical epididymal sperm aspiration: aspirate analysis and straws available after cryopreservation in patients with non-reconstructable obstructive azoospermia. MESA/TESE Group Giessen.

Microsurgical epididymal sperm aspiration (MESA) combined with intracytoplasmic sperm injection (ICSI) represents a great advance in the therapy of non-reconstructable obstructive azoospermia. For procedure synchronization, a great number of organizational facilities are needed. Intentional cryopreservation of the aspirate may reduce these problems, therefore the aim of this study was to analyse the amount and quality of aspirate fluid obtained by means of MESA and the quality of the vials after thawing. Furthermore, the available cryopreserved straws were calculated. A total of 93 consecutive MESA procedures were performed and epididymal spermatozoa were obtained in 88 patients. Mean sperm concentration was 40.9 x 10(6) spermatozoa/ml. Global and progressive motility were 24.8 and 7.5% respectively. In one-third of the aspirates, no progressive motile spermatozoa were found. The mean number of straws available was 7.6. In 33 ICSI cycles with frozen-thawed epididymal spermatozoa, a pregnancy rate of 42.4% was achieved. In conclusion, these data show that enough spermatozoa are available for various ICSI cycles following a single MESA procedure in men with non-reconstructable obstructive azoospermia. Furthermore, ICSI with cryopreserved spermatozoa leads to excellent pregnancy rates

Cell growth kinetics of the human cell line Colo-205 irradiated with photons and astatine-211 alpha-particles.

Cell growth kinetics following Astatine-211 (211At, alpha-particle emitter) and photon irradiation were studied for the human colorectal cell line Colo-205. A growth assay using 96-well plates was chosen. The growth kinetics could be simulated by assuming certain fractions of cells with various proliferative capacities, i.e. from none up to 5 cell doublings, in addition to the defined survivors with remaining unlimited clonogenic capacity. No significant difference in cell growth characteristics was seen between 211At and photon irradiation. The cell doubling time, as calculated from the increment in optical density, was compared with the results from BrdU experiments in the early phases of growth (Tpot = 18.5 +/- 0.6 h for LDR (low dose rate) photon irradiated and 20.3 +/- 0.8 hours for sham-irradiated cells 40-45 hours post-irradiation) confirming the transient accelerated growth of irradiated cells. No statistically significant difference in growth was found between LDR, MDR (medium dose rate) and HDR (high dose rate) photon irradiation.

Acute enlargement and subsequent rupture of an abdominal aortic aneurysm in a patient receiving chemotherapy for pancreatic carcinoma.

We report a case of ruptured abdominal aortic aneurysm (AAA) in a patient receiving chemotherapy for pancreatic cancer. We reviewed the literature on the effects of corticosteroids and chemotherapy on aaa formation and discuss possible mechanisms for drug action to promote aneurysm expansion and rupture. If cancer and AAA coincide and curative chemotherapy is possible, a potential impact of chemotherapy on AAA expansion should be considered.

In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines.

BACKGROUND: The aim of this study was to perform various 211At irradiations of importance for the evaluation of 211At-radioimmunotherapy, and compare the effect with that of low linear energy transfer (LET) radiation. MATERIALS AND METHODS: All irradiations were performed on low-concentration single-cell suspensions. Growth assays using 96-well plates were used to estimate apparent cell survival. Centrifuge tube filters were used to estimate the cell uptake and binding of 211At. RESULTS: A relative biological effect (RBE) of 12 +/- 2 (Colo-205) and 5.3 +/- 0.7 (OVCAR-3) was found from 211At-albumin irradiations. There was a 174 +/- 28 times higher free 211At concentration in the cell fraction than in the surrounding medium. For 211At-MAb, an 8,000-30,000 times higher concentration in the cell fraction was achieved, compared to the medium. Corrected for the uptake, an average of 31 +/- 2 ([211At]-astatine) or 26 +/- 5 ([211At]-MAb) decays per cell were required for 37% survival of Colo-205 cells. An average of 19 +/- 3 decays ([211At]-astatine) were required per OVCAR-3 cell. CONCLUSIONS: Cell uptake and binding of 211At was unexpectedly high, possibly favouring its therapeutic use. The binding is probably to the cell surface. The RBE is 5.3 +/- 0.7 for OVCAR-3 and 12 +/- 2 for Colo-205 cells.

Dural closure with nonpenetrating clips prevents meningoneural adhesions: an experimental study in dogs.

OBJECTIVE: Meningospinal and cranial dural adhesions were compared in a canine model, after duraplasty using nonpenetrating clips or penetrating needles and sutures. METHODS: Fourteen dogs underwent bilateral craniotomies and duraplasties, with implantation of dural prostheses (DuraGuard; Biovascular Corp., Minneapolis, MN), using either 6-0 silk sutures or titanium clips (DuraClose; Surgical Dynamics, Norwalk, CT). Fourteen other dogs underwent L3-L4 laminectomies; three longitudinal dural incisions were closed with 6-0 silk sutures, 6-0 polyglactin 910 (Vicryl) sutures, or clips. Groups of eight dogs (four cranially treated and four spinally treated) were killed 6, 12, 24, and 52 weeks after surgery, and specimens were collected for study after perfusion and fixation (two cranial and two spinal dural reconstructions at 52 wk). Evaluations included assessment of the appearance of approximated dural margins and responses to clips, sutures, and dural prostheses (inflammation, foreign body reaction, fibrosis, and severity of meningospinal/meningocerebral adhesions). Data were evaluated using the Wilcoxon signed-rank and McNemar tests. RESULTS: Duraplasties with clips displayed significantly less extensive acute and chronic inflammation, foreign body reaction, and meningoneural adhesions than did repairs with needles and sutures. CONCLUSION: This report is the first long-term experimental study comparing two fundamentally different methods for dural repair in a relevant animal model.

[In vitro investigations of the effect of morphine and its metabolites on the phagocytosis of peripheral mononuclear cells]. / Effekte von Morphin auf die Phagozytosefähigkeit peripher mononukleärer Zellen.

INTRODUCTION: Reports about an increased incidence of infection with facultative intracellular microorganisms suggest a depression of the macrophage/monocyte system. This explosive increase in oxidative metabolism can be measured by chemiluminescence. The aim of the present study was to investigate the influence of morphine and its metabolites morphine-3 (M-3-G) and 6-glucuronide (M-6-G) on the respiratory burst of the peripheral mononuclear cells (PCM). To explain the mechanism of the effect of morphine the antagonist naloxone was used. Furthermore, the effect was compared with that of bupivacaine and propranolol, known as drugs that stabilize the cell membranes. METHODS: PMC were isolated from the blood of healthy young men by Ficol hypaque centrifugation. Four samples of 2 x 10(5) cells were incubated for at 37 degrees C and 10% CO(2) with either morphine, naloxone, bupivacaine, propranolol, M-3-G or M-6-G. After stimulation with oponised zymosan A, the lucigenin-dependent chemiluminescence was measured (n=8) in a biolumat (Berthold). STATISTICS: Wilcoxon matched pairs (significance level p<0.05). RESULTS: Morphine inhibited the phagocytic activity of PMC only in concentrations >10(-7) mol/l. The metabolites M-3-G and M-6-G were considered to be similar based on tests using n=3. Naloxone itself significantly influences the emission of light solely in the high concentration of 10(-4) mol/l. Naloxone (10(-4) mol/l)+morphine(10(-5) mol/l) caused a greater inhibition than either of the substances alone. In comparison, the decreased chemiluminescence of morphine (10(-6) mol/l) was antagonized by naloxone (10(-5) mol/l). Naloxone in the same concentration was ineffective. The membrane stabilization caused by bupivacaine and propranolol did not change the chemiluminescence activity. CONCLUSION: Morphine had a decreasing effect on the respiratory burst of PCM only in concentrations that the human body reaches where renal clearance is reduced. In this situation the metabolites of morphine accumulate more than morphine itself and seem to have a similar effect. The weakening of phagocytosis might possibly be a direct effect of morphine and its metabolites. These investigations suggest that this phenomenon may be receptor dependent: the effect could be antagonized by naloxone, but naloxone itself caused a depression in high concentrations. In comparison the nonspecific stabilization of the membranes showed no such effect.