Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte Depletion

Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5-90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 +/- 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.     

The effect of dimethyl sulfoxide (DMSO) on the growth of dermatophytes.

Dimethyl sulfoxide(DMSO) is frequently used as a solvent for antifungal drugs in various studies to determine their MICs. Reports on comparative evaluation of methods for the susceptibility testing of antifungal drugs have shown there is poor agreement among methods. Besides other factors which could cause variability in the results, one important factor might be the effect of DMSO on the growth of fungi. The effect of DMSO on the growth of some species of Candida has been reported in the literature. The present study aimed at determination of the effect of different concentrations of DMSO (0.125 to 10%) on the growth of dermatophytes by agar diffusion method. There was no growth of fungi in 10% DMSO, between 1.25 and 5% there was a rather linear dose-related inhibitory effect on the growth, significantly different from the controls, and below 1% there was a variable effect among the species. DMSO down to 0.25% significantly inhibited the growth of most strains of M. canis. The lower concentrations of DMSO, which apparently do not affect the growth of fungi, may potentiate the effect of antifungal drugs.     

Evaluation of peptone glucose fluconazole agar as a selective medium for rapid and enhanced isolation of Aspergillus fumigatus from the respiratory tract of bronchopulmonary aspergillosis patients colonized by Candida albicans.

We have reported earlier that Aspergillus fumigatus is inhibited in vitro by Candida albicans which also interferes in its isolation from sputum experimentally seeded with predetermined graded inocula of the two fungi. It was further shown that this interference was neutralized by employing peptone glucose agar with incorporation of fluconazole which is more inhibitory to C. albicans than to A. fumigatus. This communication embodies the results of evaluation of peptone glucose fluconazole agar (PGFA) as a selective culture medium for rapid and enhanced isolation of A. fumigatus from sputum of patients clinically suspected of aspergillosis with C. albicans colonization in the respiratory tract. Of the 23 sputum specimens and one broncho-alveolar lavage collected from 15 suspected aspergillosis patients, A. fumigatus was isolated from all (100%) on PGFA as against only 19 specimens (79%) that proved to be positive on the control PGA medium (P<0.05). The greater efficacy of PGFA than that of PGA was further evident from the 2-fold higher A. fumigatus mean colony count (8.2+/-1.87) on the former medium than on the latter (3.7+/-1.00), and this difference was found to be statistically significant (P<0.05). Besides, A. fumigatus colonies were macroscopically recognizable within 2-3 days on PGFA at 28 degrees C in strong contrast to 5-7 days required on PGA. Based upon these observations, PGFA is recommended for wider application as a selective medium for rapid and enhanced recovery of A. fumigatus from sputum of patients clinically suspected of aspergillosis with C. albicans colonization in their respiratory tract.     

Glomerular changes in BK virus nephropathy

This study seeks to define the glomerular changes that are associated with human BK virus nephropathy (BKVN). It is based on histopathologic review of 124 biopsies showing light-microscopic changes of viral nephropathy. The diagnosis of BKVN was confirmed by immunohistochemistry or by in situ hybridization. Histological lesions were scored by the Banff 97 criteria for renal allograft pathology and were correlated with clinical parameters. Viral cytopathic effect in the parietal Bowman's capsular epithelium was seen in 21/124 (17%) biopsies. Immunohistochemistry showed infection of Bowman's capsular epithelium in an additional 15/124 (12%) biopsies. Crescents were found in 15/124 (12%) samples. Glomerulitis exceeding grade Banff g1 was only occasionally shown (4/124=3% biopsies). Other pathologic lesions documented include mild increase in mesangial matrix in 23% biopsies, aneurysmal dilatation of glomerular capillaries in 28%, ischemic glomerulopathy in 62%, and chronic transplant glomerulopathy graded as mild (cg1) in 62% of biopsies and as moderate (cg2) in 2/124 (1.9%) biopsies. These findings show that infection of the glomerular epithelium cells can occur in a subset of patients with BKVN, most often in biopsies with high viral load in the tubular epithelium. Isolated crescents can occur in BKVN biopsies, but rapidly progressive glomerulonephritis is not observed. Two biopsies showed electron-dense deposits on ultrastructural examination, but a cause and effect relationship to BK virus infection could not be established.     

Malassezia furfur in a case of onychomycosis: colonizer or etiologic agent?

The etiologic role of Malassezia furfur in onychomycosis is a contentious diagnostic problem because its keratinolytic ability has never been verified. This case report describes the isolation of M. furfur from the infected nails of a child clinically diagnosed with onychomycosis, and discusses the role of this organism as an etiologic agent/colonizer. The patient presented with subungual hyperkeratosis and onycholysis without associated paronychia. Budding yeast cells compatible with M. furfur were repeatedly demonstrated in KOH wet mounts of damaged nails, histopathology of hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stained sections showed penetration of fungal elements between deeper layers of keratin, and numerous colonies of M. furfur were isolated on three consecutive occasions from nail specimens collected from different areas of hand and toenail lesions. No evidence of nail invasion by dermatophytic or nondermatophytic filamentous fungi were found by direct microscopy or culture. Microscopy and culture were negative following 12 weeks of ketoconazole treatment, which resulted in growth of healthy nail plates with normal beds. We can infer from these observations that M.furfur was an etiologic agent rather than a colonizer in the patient's nails even though direct keratinolytic character of this fungus was not demonstrated.     

Renal cortical neoplasms in long term survivors of solid organ transplantation

BACKGROUND: Renal cortical neoplasms have been reported after organ transplantation, but the level of risk as well as the histological features are poorly defined. METHODS: A retrospective autopsy-based study was performed to evaluate renal neoplasms occurring in patients who underwent solid organ transplantation, died, and received an autopsy from 1981 to 1997 (383 liver, 125 heart, 52 lung, 39 heart/lung, 98 kidney, 4 bowel). Patients were divided into those with short (less than 101 days), medium (101 days to 5 years), and long-term survival (more than 5 years). The control group consisted of hospital autopsies on nontransplanted patients from the odd-numbered years, 1983 through 1997. RESULTS: Renal cortical neoplasms were identified in 32/1325 of nontransplanted patients and 15/701 transplanted patients. In transplanted patients, neoplasms were identified in 14 native and 1 allograft kidney: 2/391 in short-term survivors, 3/234 in medium, and 10/76 in long term survivors. While transplant patients with short and medium length survival had no increased risk for neoplasms, patients with long-term survival showed a 9-fold increase in cortical neoplasms. Transplant patients with neoplasms averaged 47 years of age at death, significantly younger than the average age of 70 for nontransplanted control patients with renal neoplasms. The neoplasms in transplanted patients were all tubulopapillary, except for one clear cell neoplasm and ranged in size from 0.1 to 2 cm. CONCLUSIONS: Long-term survivors of solid organ transplants have an 9-fold increased risk of developing tubulopapillary renal cortical neoplasms.     

Familial nephrotic syndrome: clinical spectrum and linkage to chromosome 19q13

BACKGROUND: Familial nephrotic syndrome (NS) has both autosomal dominant and recessive forms of inheritance. Recent studies in families with an autosomal dominant form of focal segmental glomerulosclerosis (FSGS) have been at odds concerning linkage to chromosome 19q13 (Mathis et al, Kidney Int 53:282-286, 1998; Winn et al, Kidney Int 55:1241-1246, 1999), suggesting genetic heterogeneity. This study examines the clinical features and confirms linkage to chromosome 19q13 in a family with autosomal dominant NS. METHODS: DNA samples were obtained from 16 of 17 family members. Genomic DNA was isolated, and polymerase chain reaction was performed for five markers spanning the area of interest on chromosome 19q13. Data were evaluated using two- and six-point linkage analysis. RESULTS: Clinical features included presentation of NS in childhood, steroid unresponsiveness, and slow progression to renal failure. Renal biopsy in affected family members showed lesions ranging from minimal change to mesangial proliferative glomerulonephritis to FSGS. Linkage was confirmed between the disease state and chromosome 19q13, with a maximum logarithm of odds (LOD) score of 2.41. Linkage was observed for a 7 cM region on chromosome 19q13, defined by markers D19S425 and D19S220. CONCLUSIONS: This study confirms the Mathis et al report of linkage to chromosome 19q13 in a family with autosomal dominant NS. However, there were notable differences in the presenting clinical and histopathologic features of our affected family members compared with those of Mathis et al. This suggests that the gene on chromosome 19q13 may be responsible for considerable phenotypic heterogeneity and variable expression in both clinical presentation and renal histopathology.     

Altruism,gift giving and reciprocity in organ donation: A review of cultural perspectives and challenges of the concepts

Living and deceased organ donation are couched in altruism and gift discourse and this article reviews explores cultural views towards these concepts. Altruism and egoism theories and gift and reciprocity theories are outlined from a social exchange theory perspective to highlight the key differences between altruism and the gift and the wider implications of reciprocation. The notion of altruism as a selfless act without expectation or want for repayment juxtaposed with the Maussian gift where there are the obligations to give, receive and reciprocate. Lay perspectives of altruism and the gift in organ donation are outlined and illustrate that there are differences in motivations to donate in different programmes of living donation and for families who decide to donate their relative's organs. These motivations reflect cultural views of altruism and the gift and perceptions of the body and death.     

B cells mediate chronic allograft rejection independently of antibody production

Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture.