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1.
Dev Neurorehabil ; 24(4): 230-236, 2021 May.
Article de Anglais | MEDLINE | ID: mdl-33416415

RÉSUMÉ

Objective: Evaluate the feasibility of implementing cycling-based exergames for children with cerebral palsy (CP) following lower extremity orthopedic surgery and explore its impact on pain and well-being.Methods: Ten children with CP were recruited; the first five received physiotherapy (comparison) and next five received fifteen exergame sessions over 3 weeks and physiotherapy (case) (NCT0376907). Feasibility indicators evaluated recruitment, questionnaire and exergame completion. Faces Pain Scale-Revised (FPS-R), PROMIS Pediatric Pain Interference Scale (PPIS), and KIDSCREEN-27 were administered. Wilcoxon signed-rank and effect size (r) tests evaluated within-group differences and between-group differences were assessed using Mann-Whitney U tests.Results: All feasibility indicators were met. Large effects for improved case group pain were identified (FPS-R r = 0.60, PPIS r = 0.58), as well as significant improvement in KIDSCREEN-27 total (U = 0.50, p = .05) and psychological well-being (U = 3.00, p = .01) scores, favoring the case group.Conclusions: Incorporating pediatric exergames is feasible and demonstrates potential for improving pain and well-being.


Sujet(s)
Paralysie cérébrale/rééducation et réadaptation , Traitement par les exercices physiques/méthodes , Douleur postopératoire/rééducation et réadaptation , Réalité de synthèse , Adolescent , Paralysie cérébrale/chirurgie , Enfant , Enfant d'âge préscolaire , Études de faisabilité , Femelle , Humains , Membre inférieur/chirurgie , Mâle , Procédures orthopédiques/effets indésirables , Enquêtes et questionnaires
2.
Ann Behav Med ; 52(10): 878-889, 2018 09 13.
Article de Anglais | MEDLINE | ID: mdl-30212848

RÉSUMÉ

Background: Exergames have the potential to significantly increase physical activity in children. Studies to date have shown mixed results and often rely on self-reported data. Multi-player gaming may augment participation. Purpose: The purpose of the study was to examine children's adherence behaviors in multi-player online exergames compared to a single-player condition within a home environment. Methods: Seventy-two children, aged 9-12 years, who were not meeting physical activity guidelines at baseline, were allocated to the multi-player or single-player condition. Six-week cycle-based exergaming trials took place 5 day/week in the early evening with online game supervision. Bike use was objectively recorded via game logs. Results: Adherence was high throughout the trial. Play session duration was M = 37.65 (SD = 15.39) min/day, and overall play duration was M = 133.45 (SD = 81.27) min in Week 1 and M = 77.23 (SD = 84.09) min in Week 6. Total physical activity was significantly higher at 6 weeks compared to baseline (p = .01, ηp2 = .13). There was no significant difference in play duration between conditions (p = .57, ηp2 = .01). Conclusion: This trial objectively demonstrated that exergames can promote high adherence levels. Multi-player capabilities did not augment adherence levels. Introducing new games throughout the trial may have motivated participants to keep playing, regardless of whether play was against real or artificial opponents. Weekly play duration decreased due to a significant drop in play frequency. For children who enjoy exergames, innovative solutions to promote more frequent exergame play are needed. Clinical This Registration: NCT02032667.


Sujet(s)
Cyclisme/psychologie , Comportement de l'enfant/psychologie , Exercice physique/psychologie , Observance par le patient/psychologie , Jeux vidéo/psychologie , Canada , Enfant , Femelle , Humains , Mâle ,
3.
Scand J Med Sci Sports ; 28(10): 2234-2242, 2018 Oct.
Article de Anglais | MEDLINE | ID: mdl-29797588

RÉSUMÉ

The use of exergames may be one viable way to increase child physical activity, but investigation of its effects on motivation over time and prediction of adherence have seen little research attention. The purpose of this study was to compare the effect of two cycling exergame interventions (single-player, multi-player) among children aged 9-12 years on motivational variables (theory of planned behavior) and to explore whether these variables could predict objective assessment of playtime across 6 weeks. Sixty-nine insufficiently active children were recruited through advertisements within the community/schools and randomized to either the single play condition (n = 30) or multi-player condition (n = 39). Exergaming use was recorded objectively via game logs and motivational variables were assessed after a familiarization session, at 2 weeks, and at 4 weeks. Participants played the exergames M = 133.45 (SD = 81.27) minutes in week 1 to M = 77.23 (SD = 84.09) minutes in week 6. The two exergame conditions did not result in differences among theory of planned behavior variables (P > .05). Mean levels of these constructs declined across the first 4 weeks (P < .05), with the exception of injunctive norm. Positive bivariate associations (P < .05) between game play and perceived control (0-6 weeks), and intention (weeks 3-4 and weeks 5-6) were identified, but only affective attitude (assessed at week 2) predicted (P < .05) game play (3-4 weeks) in a multivariate examination of the theory of planned behavior model. The results demonstrate that social cognitive motives wane across time when exposed to repeated exergame play.


Sujet(s)
Exercice physique , Motivation , Comportement social , Jeux vidéo , Attitude , Enfant , Femelle , Promotion de la santé , Humains , Intention , Mâle , Théorie psychologique
4.
Games Health J ; 6(6): 379-385, 2017 Dec.
Article de Anglais | MEDLINE | ID: mdl-29016199

RÉSUMÉ

OBJECTIVE: To test if the gross motor function measure (GMFM) could be used to improve game balancing allowing youth with cerebral palsy (CP) with different physical abilities to play a cycling-based exercise videogame together. Our secondary objective determined if exergaming with the GMFM Ability-Based algorithm was enjoyable. MATERIALS AND METHODS: Eight youth with CP, 8-14 years of age, GMFM scores between 25.2% and 87.4% (evenly distributed between Gross Motor Function Classification System levels II and III), competed against each other in head-to-head races, totaling 28 unique race dyads. Dyads raced three times, each with a different method of minimizing the distance between participants (three balancing algorithms). This was a prospective repeated measures intervention trial with randomized and blinded algorithm assignment. The GMFM Ability-Based algorithm was developed using a least squares linear regression between the players' GMFM score and cycling cadence. Our primary outcome was dyad spread or average distance between players. The GMFM Ability-based algorithm was compared with a control algorithm (No-Balancing), and an idealized algorithm (one-speed-for-all [OSFA]). After each race, participants were asked "Was that game fun?" and "Was that game fair?" using a five-point Likert scale. RESULTS: Participants pedaled quickly enough to elevate their heart rate to an average of 120 ± 8 beats per minute while playing. Dyad spread was lower when using GMFM Ability-Based balancing (4.6 ± 4.2) compared with No-Balancing (11.9 ± 6.8) (P < 0.001). When using OSFA balancing, dyad spread was (1.6 ± 0.9), lower than both GMFM Ability-Based (P = 0.006) and No-Balancing (P < 0.001). Cycling cadence positively correlated to GMFM, equal to 0.58 (GMFM) +33.29 (R2adj= 0.662, P = 0.004). Participants rated the games a median score 4/5 for both questions: "was that game fun?" and "was that game fair?." CONCLUSION: The GMFM Ability-Based balancing decreased dyad spread while requiring participants to pedal quickly, facilitating interaction and physical activity.


Sujet(s)
Paralysie cérébrale/complications , Aptitudes motrices/physiologie , Équilibre postural/physiologie , Jeux vidéo/normes , Adolescent , Analyse de variance , Enfant , Femelle , Humains , Mâle , Études prospectives , Jeux vidéo/psychologie
5.
Games Health J ; 6(2): 104-110, 2017 Apr.
Article de Anglais | MEDLINE | ID: mdl-28263666

RÉSUMÉ

OBJECTIVE: To test how three custom-built balancing algorithms minimize differences in game success, time above 40% heart rate reserve (HRR), and enjoyment between youth with cerebral palsy (CP) who have different gross motor function capabilities. Youth at Gross Motor Function Classification System (GMFCS) level II (unassisted walking) and level III (mobility aids needed for walking) competed in a cycling-based exercise video game that tested three balancing algorithms. MATERIALS AND METHODS: Three algorithms: a control (generic-balancing [GB]), a constant non-person specific (One-Speed-For-All [OSFA]), and a person-specific (Target-Cadence [TC]) algorithms were built. In this prospective repeated measures intervention trial with randomized and blinded algorithm assignment, 10 youth with CP aged 10-16 years (X ± standard deviation = 12.4 ± 1.8 years; GMFCS level II n = 4, III n = 6) played six exergaming sessions using each of the three algorithms. Outcomes included game success as measured by a normalized game score, time above 40% HRR, and enjoyment. RESULTS: The TC algorithm balanced game success between GMFCS levels similarly to GB (P = 0.11) and OSFA (P = 0.41). TC showed poorer balancing in time above 40% HRR compared to GB (P = 0.02) and OSFA (P = 0.02). Enjoyment ratings were high (6.4 ± 0.7/7) and consistent between all algorithms (TC vs. GB: P = 0.80 and TC vs. OSFA: P = 0.19). CONCLUSION: TC shows promise in balancing game success and enjoyment but improvements are needed to balance between GMFCS levels for cardiovascular exercise.


Sujet(s)
Paralysie cérébrale/rééducation et réadaptation , Exercice physique/physiologie , Aptitudes motrices/classification , Jeux vidéo/psychologie , Adolescent , Algorithmes , Paralysie cérébrale/physiopathologie , Paralysie cérébrale/psychologie , Enfant , Femelle , Rythme cardiaque/physiologie , Humains , Mâle , Mobilité réduite , Aptitudes motrices/physiologie , , Études prospectives , Jeux vidéo/classification , Marche à pied/physiologie
6.
Ann Oncol ; 24 Suppl 8: viii69-viii74, 2013 Nov.
Article de Anglais | MEDLINE | ID: mdl-24131974

RÉSUMÉ

BACKGROUND: Sequence-based BRCA testing can identify variants of unknown significance (VUS). Relatively little is known about how well a test outcome of VUS is understood by patients and referring physicians, and whether genetic counselors have an interest in the development of VUS management guidelines. DESIGN: Self-administered questionnaires were completed by 36 VUS counselees, 75 women with a BRCA mutation and 33 with no mutation found (NMF). We also surveyed 24 genetic counselors and 22 referring family physicians. RESULTS: One-third of VUS failed to recall the clinical significance of their result. Incorrect recall was significantly higher among VUS with high-school-only education (70% versus 19%, P = 0.02). Risk perception, cancer worry and uptake of surveillance and risk-reducing surgeries among VUS counselees were more similar to NMF than to mutation carriers. Genetic counselors accurately predicted the difficulties counselees would have with a VUS result and identified the need for VUS management guidelines. Referring physicians unanimously stated that genetic testing was indicated for unaffected siblings of VUS carriers. CONCLUSIONS: While VUS seems to be correctly perceived by counselees as more similar to NMF than to a pathogenic mutation, miscomprehension of VUS is more common, particularly in counselees with lower education. VUS-related educational interventions for both VUS counselees and their referring physicians are needed. We encourage the development of national VUS-related guidelines for genetic counselors.


Sujet(s)
Protéine BRCA1/génétique , Protéine BRCA2/génétique , Tumeurs du sein/épidémiologie , Tumeurs du sein/génétique , Tumeurs du sein/anatomopathologie , Tumeurs du sein/chirurgie , Femelle , Conseil génétique , Prédisposition génétique à une maladie , Variation génétique , Hétérozygote , Humains , Mutation , Analyse de séquence d'ADN , Enquêtes et questionnaires
7.
Reprod Toxicol ; 31(2): 134-43, 2011 Feb.
Article de Anglais | MEDLINE | ID: mdl-20977935

RÉSUMÉ

Reproductive and developmental toxicities of zinc supplementation in F(0) rats and F(1) progeny were examined. Rats were treated by gavaging with zinc chloride (ZnCl(2)) at 0.0, 7.5, 15 and 30 mg/kg-d. ZnCl(2) treatment was associated with deficient energy imbalances, reduced number of live pups/litter, decreased live birth index, increased mortality and increased fetal resorption. Changes in serum clinical chemistry and hematologic parameters were sex-related. In F(0) females, ZnCl(2) was associated with increased liver/body weight ratios, reduced creatinine and reduced alkaline phosphatase concentrations. In F(0) males, ZnCl(2) significantly increased relative liver weight and elevated γ-GGT. In addition, at birth, F(1) males exhibited, a significant (p<0.05) increase in anogenital distance, whereas ZnCl(2) hastened the time of eye opening and incisor eruption in males and females. These results indicate that excess ZnCl(2) supplementation before and during pregnancy and during lactation could pose some health risk concerns to pregnant mothers and their offspring.


Sujet(s)
Chlorures/toxicité , Reproduction/effets des médicaments et des substances chimiques , Composés du zinc/toxicité , Animaux , Poids/effets des médicaments et des substances chimiques , Chlorures/administration et posologie , Compléments alimentaires/toxicité , Développement embryonnaire/effets des médicaments et des substances chimiques , Métabolisme énergétique/effets des médicaments et des substances chimiques , Femelle , Mort foetale/induit chimiquement , Résorption foetale/induit chimiquement , Lactation , Taille de la portée/effets des médicaments et des substances chimiques , Foie/embryologie , Mâle , Taille d'organe/effets des médicaments et des substances chimiques , Grossesse , Rats , Rat Sprague-Dawley , Facteurs de risque , Facteurs sexuels , Composés du zinc/administration et posologie
8.
Phys Rev Lett ; 99(24): 247209, 2007 Dec 14.
Article de Anglais | MEDLINE | ID: mdl-18233484

RÉSUMÉ

We report on the optical spectroscopy of a single InAs/GaAs quantum dot doped with a single Mn atom in a longitudinal magnetic field of a few Tesla. Our findings show that the Mn impurity is a neutral acceptor state A0 whose effective spin J=1 is significantly perturbed by the quantum dot potential and its associated strain field. The spin interaction with photocarriers injected in the quantum dot is shown to be ferromagnetic for holes, with an effective coupling constant of a few hundreds of mueV, but vanishingly small for electrons.

9.
Food Chem Toxicol ; 39(1): 73-84, 2001 Jan.
Article de Anglais | MEDLINE | ID: mdl-11259853

RÉSUMÉ

Effects of mercuric chloride (MC) on the reproductive performance of two successive generations of rats was evaluated. F(0) rats were exposed to 0.0:0.0 (males:females), 0.50:0.75 (males:females), 1.00:1.50 (males:females) and 1.50:2.50 (males:females) mg/kg/day MC. Selected parental F(1) males and females were exposed to the same doses received by their parents (F(0)). Significant differences resulting from exposure of the F(0) generation to MC were found in implantation efficiency, fertility, live births and day 4 survival indices, litter size, and the body weight of F(1) pups. However, the continued exposure of the F(1) generation to MC did not affect fertility index or litter size, but did significantly affect implantation efficiency, live births and day 4 survival indices. In F(0) males, body weight and weights of the kidneys, testes, epididymides, prostate and seminal vesicles were significantly different, while in F(1) males, body weight, kidney weight, brain weight, liver weight and the weights of the testes, prostate and seminal vesicles were significantly different. In F(0) females, body weight and the weights of the kidneys, brain and liver were significantly different, while in F(1,) females, body weight, as well as the weights of the kidneys, liver, adrenals, uterus and ovaries were significantly different. These data showed that exposure to MC resulted in more adverse reproductive effects in the first generation and that these effects moderated in the second generation.


Sujet(s)
Fécondité/effets des médicaments et des substances chimiques , Chlorure de mercure II/toxicité , Reproduction/effets des médicaments et des substances chimiques , Animaux , Poids/effets des médicaments et des substances chimiques , Femelle , Taille de la portée/effets des médicaments et des substances chimiques , Mâle , Taille d'organe/effets des médicaments et des substances chimiques , Spécificité d'organe , Rats , Analyse de survie , Tests de toxicité
10.
Article de Anglais | MEDLINE | ID: mdl-11759913

RÉSUMÉ

This investigation was under taken to evaluate the effect of repeated exposure of mercuric chloride (MC) on food consumption, body weight gain and tissue distribution of mercury in rats. After two weeks of acclimation, male and female rats (45-50 days old) were orally gavaged with 0.00, 2.0, 4.0 6.0, 8.0 or 10.0 mg/kg/day of MC for 14 consecutive days. The mortality and food consumption were recorded daily. The body weight gains were recorded on day 0, 4, 7, 10, and at day of termination. At the end of the experiment, all surviving rats were euthanized and tissue samples from their brains, gonads, hearts, kidneys, livers, lungs, pancreases and spleens were collected and analyzed for mercury content. Exposure of male and female rats to 4.0 mg/kg/day of MC showed a significant reduction in body weight gain and food consumption when compared to their controls. However, at 2.0 mg/kg/day dose group showed no change of body gain and food consumption. The mercury contents in brains, gonads, hearts, and spleens of male and female rats at 0.0 and 2.0 mg/kg/day were undetectable. Both male and female rats accumulated significantly more mercury in the kidneys than the other organs. Mercury content in the kidneys of females was 39.9 and 40.9 microg/g at 2.0 and 4.0 mg/kg/day, respectively and of males was 34.9 and 41.0 microg/g at 2.0 and 4.0 mg/kg/day, respectively. However, mercury content in the kidneys and livers of males and females did not show any significant difference. Mercury content in the kidneys of both of sexes was significantly higher than the other organs.


Sujet(s)
Désinfectants/pharmacocinétique , Consommation alimentaire , Chlorure de mercure II/pharmacocinétique , Mercure/pharmacocinétique , Administration par voie orale , Animaux , Poids , Désinfectants/effets indésirables , Femelle , Rein/composition chimique , Foie/composition chimique , Mâle , Chlorure de mercure II/effets indésirables , Rats , Rat Sprague-Dawley , Facteurs sexuels , Distribution tissulaire
11.
Exp Hematol ; 25(12): 1240-5, 1997 Nov.
Article de Anglais | MEDLINE | ID: mdl-9357967

RÉSUMÉ

We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).


Sujet(s)
Transplantation de moelle osseuse/médecine vétérinaire , Hématopoïèse/effets des médicaments et des substances chimiques , Facteur de croissance des cellules souches/pharmacologie , Animaux , Transplantation de moelle osseuse/immunologie , Chiens , Femelle , Survie du greffon , Maladie du greffon contre l'hôte/étiologie , Facteur de stimulation des colonies de granulocytes/pharmacologie , Histocompatibilité , Mâle , Protéines recombinantes/pharmacologie , Facteurs temps
13.
Bone Marrow Transplant ; 17(4): 649-53, 1996 Apr.
Article de Anglais | MEDLINE | ID: mdl-8722370

RÉSUMÉ

We previously reported an synergism between methotrexate and tacrolimus (FK506) in preventing graft-versus-host disease (GVHD) in dogs given DLA-nonidentical unrelated marrow grafts after 9.2 Gy of total body irradiation (TBI). Methotrexate was given at 0.4 mg/kg i.v. on days 1, 3, 6 and 11 and FK506 at 0.15 mg/kg/day i.m. on days 0-8 and 0.5 mg/kg/day orally on days 9-90. Half of the dogs became long-term survivors. A major toxicity was gastrointestinal, and 25% of dogs died with intussusception. The current study addresses the problem of intussusception by making changes in drug doses used. In one group of dogs, FK506 was reduced to 0.075 mg/kg i.m. on days 1-8, while methotrexate was administered per original schedule. In a second group, methotrexate was reduced to a single dose on day 7, while FK506 was either administered per the original or reduced-dose schedule. None of the 17 current dogs developed intussusception, however, all but two dogs died with GVHD (n = 12) or graft failure (n = 3). Only two dogs survived after transient GVHD. Results show that there is little room for maneuvering FK506 or methotrexate doses, and hopes of reducing gastrointestinal toxicity by dose modifications while retaining the ability to prevent GVHD were not fulfilled.


Sujet(s)
Transplantation de moelle osseuse/effets indésirables , Maladie du greffon contre l'hôte/prévention et contrôle , Antigènes d'histocompatibilité/immunologie , Immunosuppresseurs/usage thérapeutique , Méthotrexate/usage thérapeutique , Tacrolimus/usage thérapeutique , Animaux , Transplantation de moelle osseuse/immunologie , Chiens , Synergie des médicaments , Rejet du greffon , Maladie du greffon contre l'hôte/étiologie , Histocompatibilité , Immunosuppresseurs/administration et posologie , Immunosuppresseurs/pharmacologie , Immunosuppresseurs/toxicité , Intussusception/induit chimiquement , Intussusception/prévention et contrôle , Méthotrexate/administration et posologie , Méthotrexate/pharmacologie , Méthotrexate/toxicité , Chimère post-radique , Tacrolimus/administration et posologie , Tacrolimus/pharmacologie , Tacrolimus/toxicité , Conditionnement pour greffe
14.
Blood ; 86(11): 4376-81, 1995 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-7492799

RÉSUMÉ

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.


Sujet(s)
Hormones corticosurrénaliennes/administration et posologie , Transplantation de moelle osseuse/immunologie , Transplantation de moelle osseuse/méthodes , Ciclosporine/administration et posologie , Antigènes d'histocompatibilité de classe I , Irradiation corporelle totale/méthodes , Animaux , Chiens , Femelle , Facilitation immunitaire de la prise du greffon/méthodes , Survie du greffon/effets des médicaments et des substances chimiques , Survie du greffon/effets des radiations , Mâle , Méthylprednisolone/administration et posologie , Modèles biologiques , Prednisone/administration et posologie , Transplantation homologue
17.
Blood ; 84(10): 3558-66, 1994 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-7524741

RÉSUMÉ

Previous studies found that bone marrow (BM) allografts from DLA-identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.


Sujet(s)
Transplantation de moelle osseuse , Survie du greffon/physiologie , Facteur de stimulation des colonies de granulocytes/usage thérapeutique , Facteurs de croissance hématopoïétique/usage thérapeutique , Antigènes d'histocompatibilité de classe I , Antigènes d'histocompatibilité/immunologie , Irradiation corporelle totale , Animaux , Chiens , Survie du greffon/effets des médicaments et des substances chimiques , Protéines recombinantes/usage thérapeutique , Analyse de régression , Facteur de croissance des cellules souches , Facteurs temps , Transplantation homologue
18.
Gene Ther ; 1(5): 317-22, 1994 Sep.
Article de Anglais | MEDLINE | ID: mdl-7584097

RÉSUMÉ

We studied transplantation of retrovirus vector transduced canine keratinocytes to determine whether keratinocytes could persist and express the transferred gene after superficial transplantation to full-thickness wounds of dogs, a large random-bred model for gene transfer studies. Canine keratinocytes were transduced by co-cultivation with PA317 retrovirus packaging cells which produced helper-free amphotropic retroviral vectors (LZSN and LNPOZ) encoding the genes for beta-galactosidase (beta-gal) and neomycin phosphotransferase (neo). Efficient transfer and expression of the two genes could be demonstrated in confluent keratinocyte cultures for both vectors. When transduced keratinocytes were grown in organotypic cultures on a collagen matrix containing autologous dermal fibroblasts at the air-liquid interface, the cultures showed well-organized and defined epidermal cell layers and several markers of terminal differentiation, including the presence of keratohyalin granules and a multilayered stratum corneum. To determine whether the transferred beta-gal gene was also expressed in vivo, we performed autologous transplantation of transduced keratinocytes onto full-thickness wounds of dogs. beta-Gal expressing keratinocytes could be demonstrated in situ in the regenerating epidermis 2 weeks after transplantation. We conclude that keratinocytes can be efficiently transduced by retroviral vectors, that retroviral transduction does not interfere with proliferation or differentiation, and that transduced keratinocytes express the transferred gene after transplantation to full-thickness skin wounds of dogs. Keratinocytes thus seem to be good target cells for gene therapy.


Sujet(s)
Kératinocytes/enzymologie , Kératinocytes/transplantation , Retroviridae/génétique , Transduction génétique , beta-Galactosidase/génétique , Animaux , Séquence nucléotidique , Cellules cultivées , Amorces ADN/génétique , ADN viral/génétique , Chiens , Femelle , Techniques de transfert de gènes , Vecteurs génétiques , Mâle , Données de séquences moléculaires , Provirus/génétique , Peau/cytologie , Peau/enzymologie
19.
Blood ; 83(11): 3384-9, 1994 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-8193376

RÉSUMÉ

We explored in dogs the immunosuppressive properties of 450 cGy total body irradiation (TBI) delivered from two opposing 60Co sources, as assessed by the criterion of successful engraftment of allogeneic genotypically DLA-identical littermate marrow. Two questions were asked in this study. Firstly, does dose rate affect the immunosuppressive effect of TBI when administered in a single dose? Secondly, does fractionation alter the immunosuppression of TBI when delivered at a very fast dose rate? Dose rates studied included 7 and 70 cGy/min, and fractionation involved four fractions of 112.5 cGy each, with 6-hour minimum interfraction intervals. Six of 7 dogs receiving 450 cGy single-dose TBI at 70 cGy/min showed sustained engraftment of the allogeneic marrow, compared with 1 of 7 dogs receiving single-dose TBI at 7 cGy/min (P = .01). Fractionated TBI at 70 cGy/min resulted in sustained allogeneic engraftment in 3 of 10 dogs, a result that was statistically significantly worse than that with single-dose TBI at 70 cGy/min (P = .03) and not statistically different (P = .24) from that with fractionated TBI delivered at 7 cGy/min (0 of 5 dogs engrafted). A single dose of 450 cGy of TBI delivered at a rate of 70 cGy/min is significantly more immunosuppressive than the same total dose delivered at 7 cGy/min. Fractionated TBI at 70 cGy/min is significantly less immunosuppressive than single-dose TBI at 70 cGy/min and not significantly different from fractionated TBI administered at 7 cGy/min. Results are consistent with the notion that significant DNA repair in lymphoid cells is possible during interfraction intervals at the relatively high dose rate of 70 cGy/min.


Sujet(s)
Transplantation de moelle osseuse , Antigènes d'histocompatibilité de classe I , Antigènes d'histocompatibilité/immunologie , Irradiation corporelle totale , Animaux , Chiens , Dose de rayonnement
20.
Blood ; 83(7): 1963-70, 1994 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-8142662

RÉSUMÉ

Recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) was studied in normal dogs and in dogs receiving otherwise lethal total body irradiation (TBI) without marrow transplant. Five normal dogs receiving 25 micrograms/kg of rcGM-CSF by subcutaneous (SC) injection twice daily (BID) for 14 days showed increases in peripheral blood neutrophil counts of three to five times the baseline. Platelet counts decreased during administration of rcGM-CSF to a mean nadir of 52,800. Ten dogs received 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow graft. Within 2 hours of TBI, rcGM-CSF was begun at a dose of 50 micrograms/kg SC BID for 5 doses and then continued at 25 micrograms/kg SC BID for 21 days. Only 1 of the 10 dogs receiving rcGM-CSF survived with complete and sustained recovery of hematopoiesis. One of 13 historical control dogs survived after 400 cGy with no hematopoietic growth factor or marrow infusion. Results with rcGM-CSF were compared with previous and concurrent data with G-CSF studied in the same model. Of 10 dogs receiving G-CSF, 8 survived with complete and sustained hematopoietic recovery, a significantly better survival than that seen with rcGM-CSF (P = .006). Neutrophil counts were sustained at higher levels after TBI for the first 18 days in the G-CSF group (P < .016) and the neutrophil nadirs were higher. No differences in neutrophil nadirs were noted between the rcGM-CSF and control groups. Dogs treated with rcGM-CSF experienced a more rapid decline of platelet counts than G-CSF-treated or control dogs over the first 18 days (P < .001). The nadir of the platelet count was higher in the control group than in either the G-CSF or rcGM-CSF group and no significant difference was observed between the G-CSF and rcGM-CSF groups. After otherwise lethal TBI (400 cGy) in dogs, rcGM-CSF was not effective in promoting hematopoietic recovery or improving survival.


Sujet(s)
Facteur de stimulation des colonies de granulocytes et de macrophages/pharmacologie , Hématopoïèse/effets des médicaments et des substances chimiques , Irradiation corporelle totale , Animaux , Chiens , Femelle , Mâle , Protéines recombinantes/pharmacologie
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