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.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

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.     

Interstitial deletion of 10q: Clinical features and literature review

We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dysplastic” pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. © 1992 Wiley-Liss, Inc.     

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).