Decreased interleukin 10 and increased interferon-gamma production in patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation.

Ex vivo production of interleukin 10 (IL-10) and interferon-gamma (IFN-gamma) was investigated in patients with (n = 5) or without (n = 5) chronic graft-versus-host disease (cGVHD) after allogeneic BMT. Patients were matched for time after transplantation and type of transplant. Anti-CD3-induced IL-10 production in MNCs isolated from patients with cGVHD (range/median: 26-650 pg/10(6) MNC; 400 pg/10(6) MNC) was significantly reduced compared to patients without cGVHD (646-2662 pg/10(6) MNC; 1314 pg/10(6) MNC; P < 0.05) or healthy controls (679-6361 pg/10(6) MNC; 3054 pg/10(6) MNC, P < 0.01). In vitro inhibition of IL-10 by an anti-IL-10 monoclonal antibody enhanced the release of IFN-gamma by anti-CD3-stimulated MNCs from 354 +/- 34 pg/10(6) MNCs to 899 +/- 61 pg/10(6) MNCs. Thus, low IL-10 production may cause high IFN-gamma release. In anti-CD3-activated MNCs obtained from patients with cGVHD IFN-gamma production was significantly increased (324-3331 pg/10(6) MNC; 1849 pg/10(6) MNC) compared to healthy donors (127-900 pg/10(6) MNC; 305 pg/10(6) MNC P < 0.01). In addition, median IFN-gamma release by anti-CD3-activated MNCs obtained from patients without cGVHD (464 pg/10(6) MNC) was about five-fold lower than in patients with cGVHD. In contrast to cytokine production, the differential leukocyte count (percentages of monocytes, T cells and CD4/CD8 ratio) was essentially the same both in patients with or without cGVHD. Thus, a different activation of Th-1 and Th-2 cells by anti-CD3 may be responsible for the deviant cytokine productions in patients with cGVHD. In conclusion, we observed significantly decreased IL-10 production in patinets with cGVHD and an increased median IFN-gamma secretion, which may contribute to the altered cytokine production after allogeneic BMT leading to cGVHD. Thus, supplementing IL-10 may become a new strategy for preventing cGVHD.

Humoral immunodeficiency in patients after bone marrow transplantation.

Ex vivo IgG production was determined in 17 children and adolescents and in 14 adult patients between 10 months and 6 years after BMT. Twenty-four patients received allogeneic transplants. Seven patients were transplanted with autografts. Seven patients received immunosuppressive therapy. B cells were purified by positive selection with a CD20 antibody. After IL-2 or IL-10 stimulation, IgG production of SAC-preactivated B cells in patients with immunosuppression (median/range: 11/4-15 ng/ml or 14210-29 ng/ml) was significantly reduced compared with patients receiving allogenic (30/3-860 ng/ml or 33/2-3431 ng/ml; P < 0.01) or autologous transplants (75/7-1431 ng/ml or 269-/7-13600 ng/ml, P < 0.01). In 14/31 patients ex vivo IgG production was defective. Investigations of B cell function in patients with defective IgG production was performed significantly earlier after BMT compared with patients with normal IgG production ex vivo (2 +/- 1 years vs 3.3 +/- 1.5 years; P < 0.05). In addition, only patients with a B cell deficiency received immunosuppression. However, patients ex vivo IgG produced by B cells was decreased, but IgG production/sIgG+ B cells was within range of healthy volunteers. The number of IgG-committed B cells in these patients was significantly reduced compared to patients without deficiency (23/19-45/microliter vs 100/14-336/microliter; P < 0.05), indicating an in vivo switching defect. Although IL-10 is known to induce IgG-isotype switching in vitro, production of IL-10 by anti-CD3 activated MNCs obtained from patients with a switching defect did not differ from patients without B cell defects (1699/400-2662 pg/ml vs 724-112-1826 pg/ml). In nine patients IgG production and IgG production/sIgG+ B cells were impaired. The number of sIgG+ B cells was not decreased compared with patients without B cell deficiency (115/18-288/microliter), indicating a defective terminal differentiation of IgG-committed B cells to plasma cells. Although autocrine IL-6 is essential for plasma cell formation of isotype-determined B cells, it was comparable in patients with a terminal deficiency and without deficiency (3838/583-5967 pg/ml vs 2423/1643-6184 pg/ml). However, IL-10 production by anti-CD3 activated MNCs in patients with a terminal B cell defect (426/54-2262 pg/ml, P < 0.05) was significantly lower than in patients without deficiency, indicating a deviant cytokine production by T cells which might in part account for the B cell defect. Defective isotype switching as well as impaired terminal differentiation of B cells were found. Further analysis of factors regulating isotype-switching in vivo as well as cytokine receptor expression or signalling processes of differentiation factors in activated B cells might help to characterize the nature of these B cell deficiencies after BMT.

[Significance of interleukin 10 for acute graft versus host disease in children and adolescents after allogenic bone marrow transplantation]. / Die Bedeutung des Interleukin 10 für die akute Graft versus Host Erkrankung bei Kindern und Jugendlichen nach allogener Knochenmarktransplantation.

BACKGROUND: It has been shown that Interleukin 10 (IL-10) is able to inhibit alloreactivity in a mixed lymphocyte culture. Therefore, here IL-10 production in patients after allogeneic BMT was investigated and correlated with the incidence of acute GvHD. PATIENTS: 14 patients after allogeneic BMT have been investigated. Patients' age ranged from 2.6 to 22 yrs. (median 7 yrs.). Patients were diagnosed with Ewing's sarcoma (1), ALL (4), AML (3), CML (2), Wiskott-Aldrich Syndrome (WAS;1), MDS (1) and SAA (2). GvHD > II degrees occurred in 5/14 patients. As control served 20 healthy volunteers. METHODS: Mononuclear cells (MNC's) isolated from patients and 20 healthy controls were stimulated with an anti-CD3 monoclonal antibody for 72 hr. IL-10 was detected in cell-free supernatants by ELISA. RESULTS: Anti-CD3-induced IL-10 production in MNC's isolated from patients (range/median: 0-1579 pg/10(6) MNC; 221 pg/10(6) MNC) was significantly reduced compared to healthy controls (160-5093 pg/10(6) MNC; 1250 pg/10(6) MNC; p < 0.01). 4/5 patients with low IL-10 production, but only 1/9 with a normal IL-10 production presented with GvHD > II degrees (p < 0.05). CONCLUSION: Ex vivo IL-10 production was decreased in about one third of patients early after allogeneic BMT. The low IL-10 production was associated with a significantly increased risk of severe GvHD. Thus, supplementation of IL-10 might become a useful therapy to prevent GvHD.

When is air medical service faster than ground transportation?

The purpose of this study was to mathematically define a distance or travel-time interval in which air medical evacuation would benefit the patient more than ground transport. The authors derived mathematical formulas from known variables (ground travel, extrication and rendezvous times) and fixed averages (on-scene time, lift-off time, and speeds) and used those formulas to test actual flights for appropriateness. The formulas were: [formula: see text] where Y = ground travel time; R = rendezvous time; Z = extrication time; D = distance to scene (km); and X = air travel time. The formulas provide a guide to prospectively determine the legitimacy of air medical transport. They can also be used retrospectively as a guide for quality assurance purposes. During this study of 123 consecutive scene flights, helicopter benefitted all the entrapped patients but only one-third of non-entrapped patients. Of 44 flights from areas with known ground times, helicopter transport benefitted 14 of 16 entrapped, five of 16 non-entrapped, but only three of 17 rendezvous.

[Postpartum perineal rehabilitation by early electrostimulation at home. Preliminary study]. / Rééducation périnéale du post-partum par électrostimulation précoce à domicile. Etude préliminaire.

The authors report a preliminary trial of post-partum perineal physiotherapy by functional electric stimulation at home starting from Day 15. Fifteen primipara used the technique. Perineal muscle testing and urodynamic investigations took place before Perineal muscle testing and urodynamic investigations took place before and after physiotherapy. Testing of the levators showed complete recovery in 20 p. cent of cases and partial in 80 p. cent. Urodynamic results showed a significant increase in resting urethral pressure. Acceptability of physiotherapy was perfect. The early start offered the twin advantages of better muscular recovery and easier motivation of the patient. Physiotherapy at home enabled these women, already busy, to carry out their perineal physiotherapy with minimum difficulty.

[Urethral instability]. / L'instabilité urétrale.

This study was carried out on 121 sets of records of uretrocystomanometry and 25 records of uretrocystomanometry combined with dynamic sphincterometry. The patients consulted us either for stress incontinenceor urgency incontinence. The mean age was 41 years. The urethra was considered to be unstable when variations in pressure reached 20 cm of water or higher. There are four different types of instability described and these correspond to different urodynamic pictures. The treatments that have been proposed resulted from the different aetiologies that we have been proposed resulted from the different aetiologies that we have worked out. Some of these cases are due to an inadequate perineal floor. This has been shown by changes in striated urethral sphincter behaviour and in the improvement that can be brought about by re-education of the levator and muscles.