Serum erythropoietin levels and blood component therapy after autologous bone marrow transplantation: implications for erythropoietin therapy in this setting.

To determine the potential impact of recombinant human erythropoietin (EPO) therapy in patients undergoing autologous bone marrow transplantation (BMT) and colony-stimulating factor therapy, we assayed endogenous serum EPO levels and noted blood transfusion requirements in relapsed non-Hodgkin's lymphoma patients treated with high-dose chemo-radiation therapy and autologous BMT. Hematocrit and reticulocyte counts were determined daily, and hematocrit was maintained in the 25-30% range by transfusion according to criteria established by our hospital transfusion committee. EPO levels were measured by radioimmunoassay and were determined at baseline, throughout therapy, and 2 and 3 months after BMT. Serum EPO levels increased more than 25-fold above baseline in most subjects after initiating chemoradiation therapy. No correlation was noted between serum EPO and hematocrit, reticulocyte count or serum creatinine. Total red blood cell units transfused ranged from 4 to 15 (mean 7.7). Mean total donor exposures (red blood cell plus platelet units transfused) were 83.6 units (range 16-175). Serum EPO levels increased early in the course of preparation for autologous BMT and remained elevated for at least 2-3 weeks thereafter although at a lower level. Red blood cell transfusions were required despite very high EPO levels after BMT. Red cell transfusions, moreover, accounted for only 9.2% (69 of 746) of total donor exposures and only 5.8% (42 of 746) of donor exposures during the interval when pharmacologic doses of erythropoietin might be of benefit. In contrast to the potential benefit of colony-stimulating factors such as G-CSF and GM-CSF in BMT, our study suggests limited value for erythropoietin therapy in this setting.     

T cell activation and thymic tolerance induction require different adhesion intensities of the CD8 co-receptor.

Activation of mature lymphocytes requires in addition to the TCR contact with the corresponding antigen the binding of the CD8 or CD4 co-receptors to MHC class I or class II proteins respectively. To investigate the contribution of the CD8-class I interaction to the elimination of autoreactive T cells during negative selection in the thymus we generated two types of transgenic mice. One set expressed a modified Kb molecule which contained a human HLA-A2 alpha 3 domain, thereby missing the binding residues for the murine CD8 molecules. The second set of mice expressed an anti-Kb specific TCR. Both lines were crossed and in the resulting double transgenic mice the development of Kb-reactive T cells was followed with an anti-clonotypic antibody. Surprisingly, efficient clonal deletion in the thymus was still observed, although the reduced CD8-class I adhesion abrogated effector functions in vivo and in vitro. These results imply that even T cells with intermediate affinity for self are negatively selected in the thymus despite the fact that they are not able to react against self antigens in the periphery. Thus a safety window is created which decreases the risk of autoaggression.     

Food-induced contact urticaria syndrome (CUS) in atopic dermatitis: reproducibility of repeated and duplicate testing with a skin provocation test, the skin application food test (SAFT)

IgE-mediated contact urticaria syndrome (CUS) is one of the manifestations of allergy in childhood atopic dermatitis (AD). Allergens such as foods and animal products penetrate the skin easily. They can then cause urticarial reactions in sensitized individuals. A provocation test system for foods, called the skin application food test (SAFT), has been developed. Over more than 5 years, a group of 175 patients with AD was built-up and investigated in a prospective follow-up study with SAFT. SAFT was more frequently positive in AD children aged 6–2 years than in older children. In several children of this population (Group 1), we repeated SAFT within a period of 1 year. In another unrelated group of children (Group 2–1), we compared the results of 'original' SAFT and SAFT using square chambers (Van der Bend) or Silver patches. In the 3rd group (Group 2–2) we compared'original' SAFT with SAFT using big Finn Chambers. The agreement between the tests was high: in Group 1, we observed 88 to 93% concordant scores, and in Group 2, the scores were 96% to 100%. Statistically, the K coefficient ranged from 0.71–0.87 in Group 1, and from 0.83–1.00 in Group 2. SAFT is therefore highly reproducible. Agreement was at least 88% between the scores (the lowest K value observed was at least 0.71).     

3D reconstruction of the cardiovascular and central nervous system of a human embryo Carnegie-stage 15--case report.

A human embryo at Carnegie stage 15 was serially sectioned and 3D computer aided reconstructions were made to demonstrate the cardiovascular system and cranial structures and to study developmental variations at this stage. The development of the heart and pharyngeal arteries was according to the existing literature. Differences were found in the development of the arterial circle of Willis and the central nervous system. The cranial venous system seemed to show great variability. Whereas the telencephalon was not developed according to the stage, the development of the hypophysis had occurred prior to stage 15. From the results we conclude that there are remarkable individual differences in embryological differentiation of structures which have to be taken into account during staging of human embryos.     

Zur Entstehung und Behandlung der Netzhautablösung

Ohne Zusammenfassung     

Osteonecrosis of the jaws associated with use of risedronate: report of 2 new cases.

Use of various bisphosphonates has been associated with the development of osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these agents have been reported in the English-language literature. Approximately 96% of these published cases were seen with administration of the intravenous agents pamidronate and zoledronate, whereas only 26 cases have been associated with oral bisphosphonates, 25 of them with alendronate. Only a single case of ONJ associated with the oral bisphosphonate risedronate has been previously cited. We report 2 cases of ONJ attributed to risedronate administration. The patients developed osteonecrosis 15 and 24 months after treatment for osteopenia. A regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect in the mandible caused by complete exfoliation of a lingual torus in 1 patient. The other patient required sequestrectomy, repeated courses of antibiotics, surgical debridement, and steroids to promote closure of an oroantral fistula and management of sinusitis after bone grafting and implant placement in the posterior maxilla. A demographic profile of reported oral bisphosphonate users affected by ONJ is also provided. With the millions of patients receiving various oral bisphosphonates for osteopenia and osteoporosis, health care practitioners should be aware of the potential for the onset of osteonecrosis and familiar with its management.     

Beiträge zur Anatomie des miliaren Tuberkels

Ohne Zusammenfassung     

Spread of local anaesthetic solution in epidural space visualisation with ultrasound in single shot caudals

Background: Ultrasonography is becoming an important adjunct in paediatric neuraxial blockade. Ultrasound guidance helps in visualisation of relevant neuraxial structures, predicting depth of epidural space from skin, reduction in bony contact and faster epidural placement. The visibility of neuraxial structures declines in patients as age increases. To date, there are no studies looking at the extent of spread of local anaesthetic solution in the epidural space and its correlation to the volume used, under ultrasound guidance. We report the results of our audit on spread of local anaesthetic solution in the epidural space in single shot caudal blocks. This abstract is based on the first 17 patients, the presentation will be based on all 50 patients. Methods: This audit was approved by the local audit committee. We aimed to follow the extent of the spread of local anaesthetic within the epidural space with real time ultrasonography. Patients were selected when the planned anaesthetic included a single shot caudal block. The anaesthetists performing the anaesthetic and the caudal block consented to our ultrasound visualisation. All patients were below 5 years of age. No attempt was made to standardise the technique, the dose, or the speed of injection. After the placement of the caudal cannula by the primary anaesthetist involved in patient care, a separate anaesthetist, experienced in using ultrasound, visualised the neuraxial structures and subsequent spread of the local anaesthetic solution with real time ultrasound. The spread was followed during the injection and for 10 s after the completion of the injection. A 5 cm 7.5–12 MHz linear array was used longitudinally with either midline or paramedian approach. Results: We are reporting the preliminary results from 17 patients. Patients were aged between 1 day and 1 year 10 months. They weighed between 3.3 kg and 14.6 kg. Either 22 gauge Jelco or Abbocath were used to perform the procedure; 0.25% or 0.20% L‐bupivacaine was used on all occasions. The volume administered per kg ranged between 0.33 and 1.27 ml. The visibility of neuraxial structures was good on all occasions. On calculating the Spearmans correlation coefficient, the extent of spread of local anaesthetic in the epidural space was positively correlated with the volume used by a correlation coefficient of 0.64, with a P value of 0.008. The postoperative pain score in recovery was 0 in 16 out of the 17 cases. The one failure occurred when the observed spread would not have been expected to provide analgesia for the performed operation. Conclusions: Among children below 5 years of age, there seems to be a positive correlation between the volume of local anaesthetic injected into the epidural space and the extent of its spread. This needs to be further investigated by a prospective randomised control trial. The utility of real time ultrasound to allow a reliable achievement of a desired level of sensory block, should be investigated i.e, whether the volume used in achieving a desired level of local anaesthetic spread, as guided by ultrasound, provides superior analgesia and fewer adverse effects compared with the volume calculated using the Armitage regimen. References 1 Rapp HJ, Folger A, Grau T. Ultrasound guided epidural catheter insertion in children. Anesth Analg 2005; 101 : 333–339. 2 Willschke H, Marhofer P, Bosenberg A, et al. Epidural catheter placement in children: comparing a novel approach using ultrasound guidance and a standard loss of resistance technique. Br J Anaesth 2006; 97 : 200–207. 3 Marhofer P, Bosenberg A, Sitzwohl C et al. Pilot study of neuraxial imaging by ultrasound in infants and children. Pediatr Anesth 2005; 15 : 671–676.