1/15. Rationale and results of in utero transplants of stem cells in humans.Following 18 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The four fetuses that we treated were 28, 26, 17 and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the two other had thalassemia major. Donor cells were obtained from 7- to 12-week-old fetuses, with conditions approved by the National Committee for bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of three patients and injected intraperitoneally into the other one, under ultrasonic visualization. The first patient, bone in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% then 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989; donor cell engraftment has been proven (y chromosome in this female patient) and immunological reconstitution is in progress, allowing a normal life at home. The third patient has also evidence of donor cell take (y chromosome in a female patient) and a partial effect on thalassemia has been documented (donor haemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
2/15. Autosomal dominant B-cell immunodeficiency, distal limb anomalies and urogenital malformations (BILU syndrome) - report of a second family.A family with an unusual combination of B-cell immunodeficiency, distal limb abnormalities, genitourinary malformations, and mild dysmorphic features has recently been described. Here, we report a second family with similar features, which also shows autosomal dominant inheritance. In affected individuals from both families, sequence analysis of candidate gene HOXA13 did not identify a mutation, and there was no evidence of a microdeletion involving either HOXA13 or the HOXA cluster as a whole. We further delineate the phenotype of this condition in females and add weight to the observation that this is a true syndromic association.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
3/15. In utero transplantation of fetal liver stem cells in humans.Following 15 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The three fetuses that we treated were 28, 26, and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the third one had thalassemia major. Donor cells were obtained from 7- to 10-week-old fetuses, with conditions approved by the National Committee for bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% than 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989 and it is too early for a thorough evaluation of the immunological effects of the transplant, although donor cell engraftment has been proven (y chromosome in this female patient). The third patient has also evidence of donor cell take (y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
4/15. Polyfungal systemic infections in pediatric oncology patients.Three cases of two fungal agents causing simultaneous systemic infection in immunocompromised pediatric patients are presented and the literature is reviewed. All three patients had several underlying factors that predispose to systemic fungal infections. A species of candida was identified initially as an etiologic agent in all of the three patients causing subcutaneous abscesses, urinary tract infections, fungemia, catheter exit site infection, or pneumonia. However, a few days later blood cultures grew aspergillus species in two of the three patients; in the third patient aspergillus was identified on microscopic examination of the spleen. All three patients had an associated bacteremia with either staphylococcus aureus or S. epidermidis requiring vancomycin therapy. Presence of aspergillus infection required treatment with amphotericin. Difficulties in making a definitive diagnosis of systemic fungal disease may explain paucity of reports in the literature with simultaneous polyfungal systemic infection.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
5/15. Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections.Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by dna hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
6/15. Thymus and B cell reconstitution in severe combined immunodeficiency after transplantation of monoclonal antibody depleted parental mismatched bone marrow.Two brothers were transplanted with bone marrow which was depleted of mature T cells with monoclonal antibody CT-2 plus complement. One child died of sepsis due to candida present prior to transplant. The other is alive and well with full T and B cell reconstitution over 36 months after transplant. Thymus biopsy taken after transplant demonstrated normal morphology and cellularity. Portions of the marrow that were radiolabeled permitted an assessment of traffic patterns of aliquots that were injected intravenously and directly into the marrow space. The studies reported here document that a one haplotype mismatch is not a sufficient disparity to preclude both B and T cell reconstitution, and that monoclonal antibody plus complement is an effective method for T cell depletion.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
7/15. Refractory esophageal candidiasis associated with a low molecular weight plasma inhibitor of T-lymphocyte function.In a patient with chronic esophageal candidiasis due to C. tropicalis that was refractory to mycostatin and ketoconazole, a generalized cell-mediated immunodeficiency state was detected. Samples of plasma from this patient inhibited T-lymphocyte function, suppressing both rosette formation and mitogen responsiveness of T-cells derived from the patient and from normal individuals. Following plasma exchange, the patient's immune defect resolved and her candida infection disappeared. On further analysis, the plasma inhibitory factor was found to be of low molecular weight (less than 10,000) and heat labile. Preliminary studies suggested that this inhibitor was candida-derived, since it was removed from plasma by anti-candida antibodies in solid phase. Immunodeficiency in chronic candidiasis may be improved by removal of circulating inhibitory factors through plasma exchange.- - - - - - - - - - ranking = 3keywords = candida (Clic here for more details about this article) |
8/15. candida retinitis in bare lymphocyte syndrome.Bare lymphocyte syndrome (BLS) is a rare, severe combined immunodeficiency characterized by lack of expression of HLA A, B and C antigens and the absence of B2 microglobulins. patients with BLS exhibit functional deficiency of both T and B cells resulting in bacterial as well as viral and fungal infection. Ophthalmic findings in this group of disorders have not been reported. We present a case of candida retinitis in a terminally ill 5-year-old girl with BLS.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
9/15. Correction of severe combined immunodeficiency by fetal liver cells.As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin a by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
10/15. Reconstitution of B and T lymphocyte function in severe combined immunodeficiency disease after transplantation with thymic epithelium.A patient with severe combined immunodeficiency has been given a transplant of thymic epithelium obtained from short-term culture of normal human thymus. 4 wk after transplantation immunoglobulin was detected and the patient now has normal levels of the three main classes. Functional antibodies of four specificities have been detected. An increase in reactivity to allogeneic cells and phytohaemagglutinin has been observed, with an increase in E rosettes; a positive delayed skin test to candida antigen is now present. The patient has shown reversal of wasting and has been free of infection for 7 months since receiving the transplant. It appears that under certain circumstances thymic epithelium reconstitutes both T and B cell functions.- - - - - - - - - - ranking = 1keywords = candida (Clic here for more details about this article) |
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