Enhancement of Viability of Fat Grafts in Nude Mice by Endothelial Progenitor Cells

BACKGROUND: A recent discovery showed that endothelial progenitor cells (EPCs) could augment collateral vessel growth to ischemic tissues. OBJECTIVE: The objective was to demonstrate the effects of EPCs on the vasculogenesis and survival of free transplanted fat tissues in nude mice. METHODS: EPCs from human donors were cultured in vitro for 7 days. Human fat tissues were injected subcutaneously into the scalps of 20 6-week-old nude male mice. EPCs stained with CM-DiI were mixed with the transplanted fat tissues and injected into the mice. EBM-2 medium was used as control group. The animals were euthanized 15 weeks after the procedure. Graft volume were measured, and histologic evaluation was performed. The central part of fat tissues was histologically evaluated 15 weeks after the fat injection. RESULTS: The survival volume of the experimental group was significantly greater than that of the control group (p< .05). Less cyst formation and fibrosis was obtained in the experimental group. Histologic evaluation of the central part of fat tissues 15 weeks after the fat injection showed that capillary densities increased markedly in the experimental group mice. CONCLUSION: The results indicate that EPCs have the ability to enhance the survival and the quality of the transplanted fat tissues.     

The Impact of Dopamine on Hemodynamics,Oxygen Metabolism,and Cerebral Resuscitation After Restoration of Spontaneous Circulation in Pigs

Background: Restoration of spontaneous circulation after cardiopulmonary resuscitation in cardiac arrest patients does not always signal a completely successful outcome. Functional deficiencies of the nervous system are found in many survivors of cardiac arrest. Objectives: To study the effects of dopamine-induced elevated blood pressure on the hemodynamics, oxygen metabolism, and cerebral resuscitation in different perfusion conditions in a resuscitated animal model. Methods: There were 18 pigs included in the study. Ventricular fibrillation (VF) was induced with a programmed electrical stimulation device. After 4 min of untreated ventricular fibrillation followed by 9 min of CPR, 12 animals were resuscitated successfully, and were then randomly assigned to either the study group (dopamine group) or the control group (normal perfusion group). All animals in the two groups received normal saline through continuous intravenous guttae for 4 h at a rate of 15 mL/kg/h. In the study group, dopamine was added to raise the animals' blood pressure. Four hours of intensive monitoring was performed for all study animals. Finally, 24-h evaluation of neurological function was conducted in surviving animals in accordance with the standard of the Cerebral Performance Category Score. Results: In animals in the dopamine group, the cardiac output, mean aortic pressure, coronary perfusion pressure, oxygen delivery, and oxygen consumption were higher than those found in the animals in the normal perfusion group (p < 0.05). Oxygen metabolism was remarkably improved in animals in the dopamine group. Furthermore, cerebral perfusion was better in the dopamine group than in the control group and thus, results of the evaluation of nervous system function were better in animals treated with dopamine (p < 0.05). Conclusions: Dopamine improved systemic perfusion, cerebral blood supply, and oxygen metabolism after successful resuscitation from VF in a porcine model. All of these factors have profound effects on the cerebral resuscitation.     

Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

The evaluation of gastrointestinal function in diabetic patients

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