Translation and application of an obesity behavior change technique training in a Spanish nursing undergraduate setting.

BACKGROUND: The TEnT PEGS framework is a behavior change communication toolkit which has been shown to be useful in increasing health professional trainees' skills and knowledge about obesity-related behavior change techniques. There is no version of the behavioral change intervention toolkit in Spanish. Therefore, the objectives of this study were 1) to translate the TEnT PEGS framework into Spanish and apply it to a Spanish nursing student population; 2) To analyze whether training with the Spanish toolkit (DEPREMIO) had a positive impact on students' skills in encouraging obesi-ty-related behavioral change. METHODS: First year nursing students (n=95) attended two face-to-face (2 hours per session) obesity management training sessions. A specifically designed pre-post test was carried out. Data were collected using an ad-hoc questionnaire of fourteen items, ten of them evaluated the student's knowledge and attitude about behavior change techniques, and four evaluated the student's perception of their skills in developing different strategies. RESULTS: Training significantly increased most students' knowledge and attitudes with a 0.05 level of significance and effect sizes were between 0.36 and 0.77. It also increased students' skills, although not to any significant extent. CONCLUSION: The DEPREMIO toolkit helped nursing students to acquire more knowledge, attitudes and skills in obesity management. It therefore seems that this adaptation is an acceptable and feasible training tool for the Spanish nursing student population.

Cambios en las creencias de control, status emocional y adaptación psicosocial en mujeres con cáncer de mama / Changes in control beliefs, emotional status and psychosocial adaptation among women with breast cancer

Diferentes investigaciones han demostrado que las creencias de control están relacionadas con mejor adaptación psicosocial y ajuste emocional. Nuestros objetivos fueron describir los cambios y la influencia a lo largo del tiempo de las creencias de control sobre el estado emocional y la adaptación psicosocial. Método: se entrevistaron 131 mujeres con cáncer de mama adscritas a un protocolo de seguimiento en la unidad de oncología del hospital general de Alicante. Se utilizaron diferentes cuestionarios estándar y también se diseñaron preguntas específicas para este estudio (creencias de control relacionadas con el protocolo de seguimiento. Resultados: No hubo diferencias significativas a lo largo del tiempo ni en las creencias de control ni en los resultados de salud. Las pacientes puntuaron alto en las creencias de control. El mejor predictor del estado emocional fue la creencia de Competencia Percibida en Salud. Tanto las creencias de control generales como las específicas del protocolo tuvieron capacidad predictiva sobre la adaptación. Conclusión: Las mujeres tuvieron una buena adaptación y estado emocional, además presentaron un perfil de locus externo. Las puntuaciones altas en las creencias de control se mantuvieron a lo largo del tiempo (AU)

Studies using samples with chronic illnesses showed that control beliefs are associated with better psychosocial adjustment and emotional status. Our aims were to describe changes and long term influence of general control beliefs and specific control beliefs over psychosocial and emotional adjustment. Method: We analysed 131 breast cancer patients with unilateral primary breast cancer attending the standard follow-up protocol in the Oncology Unit at the General Hospital of Alicante, Spain. Different standard questionnaires were used included and we also designed specific questions for this study (control beliefs regarding follow-up protocol). Results: There were no significant changes in control beliefs nor on psychosocial and emotional adjustment. Patients had high general and specific control beliefs. Perceived Health Competence was the best predictor of emotional status. Finally, both general control beliefs and specific control beliefs predicted some psychosocial areas equally. Conclusions: Women had a good emotional status and psychosocial adaptation and had an external locus profile. Moreover, control beliefs maintain across time (AU)

Design of short Spanish sentences for measuring reading performance: Radner-Vissum test.

PURPOSE: To develop 24 short Spanish optotype sentences for the construction of a test based on the Radner reading test to simultaneously measure near visual acuity and reading speed. SETTING: Department of Refractive Surgery, Vissum-Instituto de Oftalmológico de Alicante, Alicante, Spain. METHODS: Thirty-one sentences were constructed in Spanish following the procedure defined by Radner to obtain sentence optotypes with comparable structure and the same lexical and grammatical difficulty. Sentences were statistically selected and standardized in 60 patients divided into 2 groups by educational level. Group A (30 patients) had a university education and Group B (30 patients), a primary school education. The interval of reading time was defined as the overall mean +/-1.1 x SD. All sentences with a mean between 3.59 seconds and 4.04 seconds were selected for the reading charts. RESULTS: The mean age was 30.8 years +/- 6.2 (SD) in Group A and 37.3 +/- 10.7 years in Group B. The mean reading time was 3.8 +/- 0.9 seconds in all patients, 3.5 +/- 0.6 seconds in Group A, and 4.1 +/- 1.0 seconds in Group B. CONCLUSION: The 24 short single Spanish sentences were highly comparable in syntactical structure; number, position, and length of words; lexical difficulty; and reading length.

Infiltrates in protocol biopsies from renal allografts.

In renal transplantation, clinical decisions are based primarily on the Banff classification of biopsies. However, the incorporation of 'minor or nonspecific' cellular infiltrates into the Banff classification and their interpretation is uncertain. We analyzed 833 protocol and 306 indicated biopsies to test whether such infiltrates are harmless or whether they have a bearing on outcomes. We characterized morphology, localization and cellular composition of infiltrates, and correlated these findings to the Banff classification and allograft outcome. We found that protocol biopsies had the same prevalence of infiltrates as indication biopsies (87% vs. 87%). Diffuse cortical infiltrates, the hallmark of cellular rejection were more common in indication biopsies and related to tubulitis and a rise in serum creatinine. However, in biopsies with cellular rejection according to Banff criteria, we observed an increase in all infiltrate types (specific and nonspecific) and all cell types (T cells, B cells, histiocytes). The only predictor of allograft function outcome was persistent inflammation in sequential biopsies, irrespective of type, localization and composition of the cellular infiltrates. As detected by sequential biopsies, persistence of any inflammation including those infiltrates currently not considered by the Banff classification should be regarded as a morphological correlate of ongoing allograft damage.

Superior long-term graft function and better growth of grafts in children receiving kidneys from paediatric compared with adult donors.

BACKGROUND: Organs from paediatric donors are often not accepted for paediatric recipients because previous reports suggested inferior graft function for small kidneys transplanted in children. On the other hand, studies have shown that kidneys of adult donors transplanted into children down-regulate filtration after transplantation and may not increase their function to the need of the growing child. METHODS: We assessed 64 male and 35 female (total n = 99) white children aged <10 years (male: mean 5.1 years, SD 2.8; female: mean 5.8 years, SD 3.4) who had received cadaveric kidney transplants at our centre between 1990 and 2005. Mean observation time was 5.9 years, SD 4.0. The children were divided into two groups depending on the kidney donor age: 63 children (mean age 5.0 years, SD 2.9) received an organ of an adult, and 39 (mean age 6.4 years, SD 3.4) of a paediatric donor. Immunosuppression was performed with prednisolone, cyclosporin A microemulsion+/-mycophenolate mofetil. RESULTS: Three to five years after transplantation the calculated glomerular filtration rate corrected to body surface was significantly higher in recipients of paediatric organs. The size of paediatric grafts doubled in the first years after transplantation while adult grafts had a stable size. Graft survival was comparable in both groups during observation time. CONCLUSIONS: We conclude that paediatric donor kidneys should be given preferentially to paediatric recipients due to better long-term function.

Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract.

BACKGROUND AND AIMS: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear. METHODS: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining. RESULTS: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls. CONCLUSIONS: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases.

[Living kidney transplantation. A comparison of Scandinavian countries and Germany]. / Lebendnierenspende. Ein Vergleich zwischen den skandinavischen Ländern und Deutschland.

The discussion of compensating for shortages of cadaveric donation with increased living donation often reveals differences between the Scandinavian countries and Germany. Possible adoption of Scandinavian structures to improve the rate of living donations in Germany warrants analysis of the actual differences between these two regions. Close examination reveals that significantly higher rates of living donation are achieved only in Sweden and Norway. In Norway, a frequently postulated negative effect on cadaveric donation due to very high rates of living donation could not be confirmed. In contrast to Germany and as a consequence of Norwegian geography, kidney transplantation has been regarded in Norway as the first-line therapy for endstage renal disease for more than 35 years. Living donation has since been actively pursued and is traditionally the transplantation of first choice. In Germany, living donation is still regarded as the second choice after cadaveric donation, due to legal regulations. Significant improvements in living donation frequencies could be achieved there by adopting the active Norwegian approach to living donor identification.

Morbidity and mortality associated with pancreatogastrostomy and pancreatojejunostomy following partial pancreatoduodenectomy.

BACKGROUND: The pancreatic anastomosis is still the Achilles heel in partial pancreatoduodenectomy (PPD). METHODS: This study describes retrospectively a series of 441 patients who underwent standard or extended PPD and reconstruction by either pancreatogastrostomy or pancreatojejunostomy over a period of 13 years (1988-2000). RESULTS: Reconstruction of the pancreatic remnant was achieved by pancreatogastrostomy in 250 patients (56.7 per cent) and by pancreatojejunostomy in 191 patients (43.3 per cent). The leakage rate of the pancreatic anastomosis was 2.8 per cent after pancreatogastrostomy versus 12.6 per cent after pancreatojejunostomy (P < 0.001), whereas other surgical complications (bile leakage, haemorrhage, pancreatitis) were identical in the two groups. The leakage rate after standard PPD with or without vascular reconstruction was 2.0 per cent (four of 205 patients) after pancreatogastrostomy and 11.5 per cent (18 of 156) after pancreatojejunostomy (P < 0.001); following extended PPD it was 6.7 per cent (three of 45) after pancreatogastrostomy and 17.1 per cent (six of 35) after pancreatojejunostomy. The mortality rate due to leakage was 1.6 per cent (four of 250 patients) after pancreatogastrostomy versus 5.2 per cent (ten of 191) after pancreatojejunostomy (P = 0.037). CONCLUSION: Pancreatogastrostomy is a safe and reliable method of reconstruction after PPD that may be associated with a lower leakage and mortality rate than pancreatojejunostomy.

Mixed allogeneic chimerism as a reliable model for composite tissue allograft tolerance induction across major and minor histocompatibility barriers.

BACKGROUND: Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting may be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a major MHC mismatch without the need for long-term immunosuppression. METHODS: Mixed allogeneic chimeras were prepared by using rat strains with strong MHC incompatibility [WF (RT1Au), ACI (RT1Aa)] WF + ACI-->WF, n=23. The bone marrow (BM) of recipient animals was pretreated with low-dose irradiation (500-700 cGy), followed by reconstitution with a mixture of T cell-depleted syngeneic (WF) and allogeneic (ACI) cells. Additionally, the recipient animals received a single dose of anti-lymphocyte serum (10 mg) 5 days before bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day before BMT to 10 days post-BMT. Hindlimb transplants were performed 12 months after BMT. Five animals received a limb allograft irradiated (1000 cGy) just before transplantation. Rat chimeras were characterized (percentage of donor cells present within the bloodstream) by flow cytometry at 3 and 12 months after BM reconstitution and after hindlimb transplantation. RESULTS: Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 18/23 animals. Multi-lineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60% (n=18) no sign of limb rejection was present for the duration of the study. All animals with chimerism <20% (n=5) developed moderate signs of rejection clinically and histologically. Gross motor and sensory reinnervation (weight bearing, toe spread) developed at >60 days in 14/21 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n=10). Five out of five animals with irradiated limb transplants showed no sign of GVHD at >100 days. CONCLUSIONS: Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. Partial functional return should be expected. The BM transplanted as part of the hindlimb allograft plays a role in the etiology of GVHD. Manipulating that BM before transplantation may influence the incidence of GVHD. This represents the first reliable rat hindlimb model demonstrating rejection-free CTA survival in an adult animal across a major MHC mismatch without the long-term need for immunosuppressive agents.

Mouse xenoantigens contribute to rat T-cell Vbeta repertoire generation in mixed xenogeneic bone marrow chimeras.

We previously demonstrated that rat bone-marrow-derived cells in mixed xenogeneic chimeras (rat + mouse --> mouse) contribute to peripheral selection of mouse T-cell receptor (TCR) variable betas (Vbetas) repertoire. In this study, we analysed rat T cells that developed in the chimeras to assess the contribution of mouse xenoantigens to the development of rat TCR repertoire. The expression of rat Vbetas was analysed using flow cytometry and a reverse transcription-polymerase chain reaction (RT-PCR) method that allows for both semiquantitative analysis of rat Vbeta gene expression and size heterogeneity of the complementarity determining region 3 (CDR3) domain. Three distinct patterns of Vbeta expression were detected. Partial deletion was observed for Vbeta5, 7, 12, 14, 16, 17 and 20 that exhibited reduced levels of peripheral expression by 3.4-, 1.8-, 8.7-, 2.0-, 7.8-, 9.5- and 1.8-fold, respectively, compared with the levels of Vbetas in naYve rats. Higher levels of peripheral expression were detected for three rat Vbeta genes; Vbeta6 (2.2-fold), Vbeta8.2 (3.2-fold), and Vbeta9 (1.7-fold). The relative expression of the other 10 known rat Vbeta families in chimeras was unchanged as compared with that of normal rats. We did not observe detectable changes in the pattern of CDR3 expression in chimeras, suggesting that the mouse xenogeneic environment exerted its influence on the development of rat T cells via the Vbeta-encoded CDR1/2 domains. Our data demonstrate that the rat T-cell repertoire in chimeras is shaped by both contractions as well as expansions of selected Vbetas and suggest that mouse xenoantigens and/or superantigens of endogenous mouse retroviruses may contribute as ligands for these selection processes

Diferencias en la calidad de vida: un estudio longitudinal de pacientes de cáncer recibiendo tratamiento de quimioterapia / Differences in quality of life: longitudinal study with cancer patients receiving chemotherapy treatment

El impacto del diagnóstico y tratamiento del cáncer provoca una serie de respuestas psicosociales que afectan a la calidad de vida del paciente. El objetivo de este trabajo es evaluar y comparar la calidad de vida y el Estado emocional, (ansiedad y depresión) de 21 pacientes oncológicos entrevistados en dos momentos de su enfermedad, al inicio y en sus últimos ciclos de quimioterapia. Los resultados mostraron que la calidad de vida global y la condición física percibida se asociaron entre sí y con la depresión. Sólo la Condición Física se diferenciaba significativamente entre las fases de estudio. En ambas fases, los Síntomas de Enfermedad, y el Impacto Económico se asociaron, bien con la ansiedad o con la depresión. El Impacto Social se relacionó con la depresión y la ansiedad en la primera fase, y la Discapacidad funcional con la Calidad de vida global, en la segunda. (AU)

A partial conditioning approach to achieve mixed chimerism in the rat: depletion of host natural killer cells significantly reduces the amount of total body irradiation required for engraftment.

BACKGROUND: Mixed allogeneic bone marrow chimerism induces tolerance to solid organ grafts. Although we previously reported that partially ablative conditioning with 700 cGy of total body irradiation (TBI) is sufficient to allow for bone marrow engraftment in mice, we determined that a minimum of 1000 cGy was required in the rat. Because T cells and NK cells are critical in bone marrow graft rejection, our purpose was to examine whether targeting of radioresistant NK cells and/or T cells in the recipient hematopoietic microenvironment would reduce the TBI dose required for engraftment of allogeneic rat bone marrow. METHODS: Wistar Furth rats received either anti-NK3.2.3 monoclonal antibodies on days -3 and -2, anti-lymphocyte serum on day -5, a combination of both or no pretreatment. TBI was performed on day 0 and rats were reconstituted with 100x10(6) T cell-depleted bone marrow cells from ACI donors. RESULTS: Engraftment of T cell-depleted rat bone marrow was readily achieved in animals conditioned with 1000 cGy TBI alone (12/12) and the level of donor chimerism averaged 89%. At 900 cGy TBI alone only one of eight recipients engrafted. In striking contrast, 11 of 12 animals pretreated with anti-NK monoclonal antibodies and irradiated with 900 cGy showed donor chimerism at a mean level of 41%. No further enhancement of bone marrow engraftment could be achieved when recipients were pretreated with antilymphocyte serum alone or antilymphocyte serum plus anti-NK monoclonal antibodies. Mixed allogeneic chimeras exhibited stable multilineage chimerism and donor-specific tolerance to subsequent cardiac allografts. CONCLUSION: Specific targeting of radioresistant host NK cells allows for a significant reduction of the TBI dose required for allogeneic bone marrow engraftment.

Alpha beta TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice.

BACKGROUND: Although the transplantation of solid organs and cellular grafts is a clinical routine, the morbidity and mortality associated with immunosuppression is significant. This could be avoided by the induction of donor-specific tolerance. To develop targeted antirejection strategies and regimens to induce donor-specific tolerance, cell populations in the recipient-mediating rejection of solid organ and cellular grafts must be defined. In this study we examined the role of alpha beta-TCR+ cells in the rejection of allogeneic heart grafts, by use of knockout (KO) mice deficient in the production of alpha beta-TCR+ T cells. METHODS: C57BL/6-TcrbtmlMom (alpha beta-KO) and C57BL6/J (B6) recipient mice were transplanted with B10.BR/SgSnJ (B10.BR) or BALB/c heart allografts. Animals also received bone marrow from normal B10.BR donors, followed by donor-specific or third-party heart transplants. RESULTS: Naive B6 control mice rejected B10.BR and BALB/c grafts within 16 days. In striking contrast, B10.BR and BALB/c heart allografts were indefinitely accepted in unmanipulated alpha beta-KO mice. The immune responsiveness was restored after bone marrow transplantation from normal donors. After bone marrow transplantation major histocompatibility-disparate BALB/c third-party heart grafts were rejected, whereas donor-specific grafts were still accepted. CONCLUSIONS: alpha beta-TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice. Bone marrow chimerism is associated with donor-specific transplantation tolerance.

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

T-cell depletion of allogeneic bone marrow using anti-alphabetaTCR monoclonal antibody: prevention of graft-versus-host disease without affecting engraftment potential in rats.

Bone marrow chimerism may solve two major limitations in the transplantation of solid organs and cellular grafts: (1) the requirement for life-long immunosuppressive therapy, and (2) acute and chronic rejection. When untreated bone marrow is transplanted into major histocompatibility complex (MHC)-disparate rats, lethal graft-vs-host disease (GVHD) occurs in the majority of recipients. T-cell depletion using anti-CD3 and anti-CD5 monoclonal antibody (mAb) to avoid GVHD led to an increased occurrence of failure of engraftment. We previously identified a cellular population in mouse bone marrow that facilitates engraftment of highly purified hematopoietic stem cells (HSC) across complete MHC barriers. In light of the fact that facilitating cells have a CD8+/CD3+/TCR- phenotype and mostly coexpress CD5, we evaluated in this study whether T-cell depletion of rat bone marrow using anti-alphabetaTCR mAb would retain engraftment potential yet avoid GVHD. T-cell depletion of bone marrow was performed using anti-alphabetaTCR mAb and immunomagnetic beads. Recipients were conditioned with 1100 or 1000 cGy of total body irradiation and reconstituted with 100 x 10(6) T-cell depleted (TCD) MHC- and minor antigen-disparate bone marrow cells. Animals were monitored clinically and histologically for GVHD. Chimerism was assessed by flow cytometry. Immunomagnetic bead depletion resulted in a reduction of T cells from 1.92%+/-0.21% to 0.10%+/-0.04% of total bone marrow. T-cell depletion did not remove facilitating cells (CD8+/alphabetaTCR-/gammadeltaTCR-/NK3.2.3-) from bone marrow. Further, the engraftment potential of TCD bone marrow was not affected, as 100% of animals engrafted and high levels of donor chimerism were detectable. Animals reconstituted with TCD bone marrow showed no clinical evidence of GVHD and histology revealed none to minimal changes, whereas recipients transplanted with untreated bone marrow succumbed to severe lethal GVHD. T-cell depletion using antialphabetaTCR mAb and immunomagnetic beads selectively removes T cells from the bone marrow graft while sparing facilitating cells that are required for engraftment of allogeneic bone marrow across MHC barriers. Moreover, the cells required for engraftment of HSC do not produce GVHD.

A nonlethal conditioning approach to achieve engraftment of xenogeneic rat bone marrow in mice and to induce donor-specific tolerance.

BACKGROUND: The supply of solid organs for transplantation will never meet the growing demand. Xenotransplantation is considered to be a potential solution for the critical shortage of allografts. However, xenograft rejection is currently not controlled by conventional immunosuppressive agents. Bone marrow chimerism induces donor-specific tolerance without the requirement for chronic immunosuppressive therapy. The aim of this study was to develop a nonlethal recipient-conditioning approach to achieve mixed bone marrow chimerism and donor-specific tolerance. METHODS: C57BL/10SnJ mice were conditioned with total body irradiation followed by a single injection of cyclophosphamide on day +2. On day 0, mice were reconstituted with untreated bone marrow cells from Fischer 344 rats. Recipients were analyzed by flow cytometry for donor bone marrow engraftment and multilineage chimerism. Donor-specific tolerance was tested by skin grafting. RESULTS: One hundred percent of recipients engrafted after irradiation with 600 cGy total body irradiation, transplantation with 80 x 10(6) Fischer 344 bone marrow cells, and injection with 50 mg/kg cyclophosphamide intraperitoneally. Donor chimerism was detectable in all engrafted animals for up to 11 months. This conditioning was nonlethal, because conditioned untransplanted animals survived indefinitely. Mixed xenogeneic chimeras were tolerant to donor-specific skin grafts but rejected third-party (Wistar Furth) grafts as rapidly as naive C57BL/10SnJ mice. In contrast, animals that received less efficacious conditioning regimens and did not exhibit detectable chimerism showed prolonged graft survival, but delayed graft rejection occurred in all animals within 10 weeks. CONCLUSION: The induction of bone marrow chimerism and donor-specific tolerance after nonlethal conditioning might be useful to prevent the vigorous cellular and humoral rejection response to xenografts.