The road to the discovery of the p53 protein: The Steiner Cancer Prize Award Lecture

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world. In 1983, esophageal balloon cytology screening was performed in 3 communes in northern Linxian. Of the participants, 10,066 with no evidence of cancer were followed prospectively for 71/2 years to evaluate the ability of the initial cytologc diagnoses to identify individuals at increased risk for developing cancer of the esophagus or gastric cardia. A total of 747 incident cases of esophageal or cardia cancer and 322 deaths due to these tumors were identified during the follow-up period and used in this analysis. The risks for esophageal or cardia cancer incidence and mortality increased in parallel with the presumed severity of the 1983 Chinese cytologic diagnoses. After adjusting for potential confounding factors, relative risks for esophageal or cardia cancer incidence, by initial cytologic diagnosis, were normal = 1.00 (reference), hyperplasia = 1.25, dysplasia 1 = 2.20, dysplasia 2 = 4.22 and near-cancer = 5.96. Our results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1983, successfully identified individuals at increased risk for developing cancer of the esophagus or gastric cardia. © 1994 Wiley-Liss, Inc.     

Total anomalous pulmonary venous drainage. Seventeen-year surgical experience

Between 1968 and 1985, 80 children underwent correction of total anomalous pulmonary venous drainage. There were 47 boys and 33 girls whose ages ranged from 3 days to 16 years (median 2 months, interquartile range 5 years). Seventy (87.5%) were less than 1 year of age at operation. Fifty-eight (72.5%) weighed less than 5 kg, the range being 1.6 to 42 kg (median 3.7 kg, interquartile range 2.4 kg). Forty-five (56%) patients had supracardiac, 14 (17.5%) cardiac, 15 (19%) infracardiac, and 6 (7.5%) had mixed total anomalous pulmonary venous drainage. Follow-up was complete in 78 (97.5%) and ranged from 6 to 189 months (median 58 months, interquartile range 59 months). There were 14 (17.5%) early and six (7.5%) late deaths. Analysis by various factors revealed year of operation as the only factor to affect survival at the 5% level of significance. Early mortality was 29% between 1968-1977 and 11% between 1978-1985 (p = 0.04). Postoperative pulmonary venous obstruction occurred in five (6%) patients between 6 weeks and 3 months after operation. All 5 died, three after reoperation. Five (6%) other children had reoperations, four for residual shunts and one for superior vena caval obstruction.     

Fortschritte in der systemischen Therapie des metastasierten Magenkarzinoms

In spite of a reduced rate of new occurrence, gastric cancer is still one of the most common causes of cancer related mortality. Crucial to the value of systemic therapy are the 50% of patients who already have metastasizing or locally advanced stages at first diagnosis which are not surgically curable. In comparison to merely supportive therapy, controlled studies have shown the unmistakable value of chemotherapy. Recently, cisplatin and infused 5-fluorouracil (5-FU) based combination treatments have become the therapeutic standard. The internationally best studied scheme is the “ECF” combination. The taxane and irinotecan group has limited value as monotherapy and is used in combination studies, as are oral fluoropyrimidine and oxaliplatin, with other substances. With the introduction of numerous, new, effective cytostatics, a whole series of combinations are being tested. The main aims of these studies are, on the one hand, lowered toxicity or ease of use with equivalent effectiveness, and on the other hand, higher effectiveness without significantly increased toxicity.     

Editorial

Ohne Zusammenfassung     

Gait analysis in patients with total hip endoprosthesis. Part II: Pre- and postoperative gait analysis]

35 patients have been examined before the implantation of a total hip replacement, about 7 days postoperatively and again after 12 weeks by means of the electro-ichnograph EKIG-3 of the Riga Institute of Orthopaedics and Traumatology. Before the hip-joint substitution the normal values could not approximately be attained. The step duration has postoperatively increased, and it has decreased to pre-operative values by the time of the follow-up examination. The best results were obtained concerning the change of the trunk deviation in the frontal plane. The hip mobility measured passively was remarkably better after the operation and almost reached normal values. Regarding the results it should above all be taken into consideration, that the most important fact for the patient is the alleviation and elimination of pain, respectively.     

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.     

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.     

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.