Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.     

Proliferation of myeloid progenitor cells in human long-term bone marrow cultures is stimulated by interleukin-1 beta

To study the effect of interleukin-1 (IL-1) beta on the proliferation of hematopoietic progenitor cells (HPC) in long-term bone marrow cultures (LTBMC), stromal cell layers were established from normal human bone marrow. Autologous cryopreserved mononuclear phagocyte- and T-lymphocyte-depleted bone marrow cells were reinoculated on the stromal layers in fresh culture medium, with or without the addition of human IL-1 beta (30 U/mL). Once a week, half of the culture supernatant was replaced with fresh culture medium with or without IL-1, and all nonadherent cells were returned to the flasks. At weekly intervals during a period of 5 weeks, one culture was sacrificed to determine the total number of cells and hematopoietic progenitor cells, present in the adherent and the nonadherent cell fractions. In IL-1-stimulated cultures, the number of cells recovered during a period of 5 weeks exceeded the number of cells in unstimulated control cultures by 1.5 times. This difference was attributed to a twofold increase in the number of adherent cells. The number of HPC recovered from IL-1- stimulated cultures was not different from that recovered from controls. The levels of colony-stimulating activity (CSA) in supernatants from IL-1-stimulated cultures were significantly higher than those in supernatants from control cultures. These results indicate that IL-1 enhances the recovery of cells in LTBMC by stimulating the proliferation of HPC with the concurrent release of CSA from stromal cells, without diminishing the number of HPC.     

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Virtuelle Simulation

Aim

Investigation of options of virtual simulation in patients with localized prostate cancer.

Patients and Methods

Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient’s skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning.

Results

Mean differences of the patient’s mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs.

Conclusion

The precise patient’s mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarity of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning.     

Palliative Strahlentherapie von Knochenmetastasen Eine retrospektive Analyse von 176 Patienten

BACKGROUND: The effect of the palliative irradiation of bone metastases was explored in this retrospective analysis. The spectrum of primary tumor sites, the localization of the bone metastases and the fractionation schedules were analyzed with regard to palliation discriminating total, partial and complete pain response. PATIENTS AND METHODS: One hundred seventy-six patients are included in this retrospective quantitative study from April 1992 to November 1993. Two hundred fifty-eight localizations of painful bone metastases were irradiated. The percentage of bone metastases of the total irradiated localizations in our department of radiotherapy in the Charité-Hospital, the primary tumor sites, the localizations and the different fractionation schedules were explored. The total, partial and complete pain response was analyzed in the most often used fractionation schedules and by primary tumor sites. RESULTS: Eight per cent of all irradiated localizations in the observation period were bone metastases. There were irradiated bone metastases of 21 different tumor sites. Most of the primary tumor sites were breast cancer (49%), lung cancer (6%) and kidney cancer (6%). The most frequent site of metastases was the vertebral column (52%). The most often used fractionation schedules were: 4 x 5 Gy (32%), 10 x 3 Gy (18%), 6 x 5 Gy (9%), 7 x 3 Gy (7%), 10 x 2 Gy (5%) and 2 x 8 Gy. The total response rates in this fractionation schedules were 72%, 79%, 74%, 76%, 75% and 72%, the complete response rates were 35%, 32%, 30%, 35%, 33% and 33%. There were no significant differences between the most often irradiated primary tumor sites, the most frequent localizations and the palliation with regard to total, partial and complete pain response. CONCLUSION: There are no differences between the different fractionation schedules with regard to the pain effect of bone metastases. A palliation is ensured in 75% of all cases with a partial response of 42% and complete response of 33%. With regard to pain response these results do not justify a recommendation for a standard fractionation schedule. Current fractionation schedules such as 10 x 3 Gy for 2 weeks or 5 x 4 Gy for 1 week should be used. Another point is the recalcification in the palliative treatment of bone metastases in patients with better prognosis. The recalcification is the basis for stabilization and prevention of fractures. This aspect should be explored in prospective studies.     

Reduction of sound levels with antinoise in MR imaging

A combination of active and passive techniques was used to reduce the sound levels in magnetic resonance imagers. These techniques were integrated into an existing audio system. Measurements of sound reduction varied with the protocol being used and averaged 9.9 dB with coaxial cabling and 14.2 dB with fiberoptic conduction of the feedback signal to a controller. Patient comfort and communication were improved.     

Interferon-γ: Promising therapeutic target in atherosclerosis

Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease(CVD). CVD is currently the world's leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ(IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.     

腹腔镜在小儿离断性肾盂成形术中的应用与随访

目的 探讨腹腔镜下离断性肾盂成形术的效果及适应证.方法 总结21例经腹腔途径行腹腔镜离断性肾盂成形术治疗肾盂输尿管连接部狭窄(UPJO)所致肾积水的经验,对比同期开放手术治疗的35例患儿术后影像学.结果 第一例腹腔镜肾盂成形术历时4 h 50 min,随后的20例为1 h 40 min～2 h 30 min,术中出血量5～10 ml.20例术后3～5 d出院,恢复好.1例术后7 d因患儿外伤性肾盂内出血,血块堵塞双J管,致肾盂漏尿、形成尿腹,遂行开放探查术;术中见吻合口良好,清除肾盂内血块,冲洗双J管,放置.肾造瘘管,7 d后拔除肾造瘘管出院.21例患儿术后4～6周拔除双J管.2组患儿均分别在术后1个月、3个月、6个月行B超或CTU检查.腔镜组吻合口通畅率为95.2%(20/21),开放组为100%(35/35),二者差异无显著性意义.结论 熟练掌握腹腔镜缝合技术,是圆满完成经腹腔镜离断性肾盂成形术的基础.腹腔镜下手术创伤轻微,手术效果与传统的开放手术无差别;在应用腹腔镜肾盂成形术的初期,宜选择中度以下肾盂扩张的病例,待熟练后,逐步应用于重度积水病例,确保手术效果.