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R D Bloom

Publications and source records attributed to R D Bloom.

18 recordsLinked to original sources
PubMed2006

Emerging issues in hepatitis C virus-positive liver and kidney transplant recipients.

Hepatitis C virus (HCV) infection is a major health care issue in liver and kidney transplantation. Besides negatively affecting both patient and graft survival, HCV is associated with a heightened risk for new onset diabetes mellitus (NODM). The mechanisms underlying the diabetogenicity of HCV are complex but are likely to involve insulin resistance caused by inhibitory actions of the virus on insulin regulatory pathways in the liver. The resultant glucose dysregulation is an important determinant of increased morbidity and mortality in liver and kidney recipients. This review highlights the concerns for outcomes in HCV-positive liver and kidney transplant patients with particular focus on the interrelationship between hepatitis C and diabetes. Data about the potential role of calcineurin inhibitors, corticosteroids and mycophenolate mofetil in HCV infection and HCV-associated NODM will also be discussed.

Diabetes Mellitus↗
PubMed2006

Treatment of PTLD with rituximab or chemotherapy.

Information regarding treatment of post-transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab and/or chemotherapy for PTLD for response, time to treatment failure (TTF) and overall survival (OS). Thirty-five patients met inclusion criteria. Twenty-two underwent rituximab treatment, with overall response rate (ORR) 68%. Median TTF was not reached at 19 months and estimated OS was 31 months. In univariable analysis, Epstein-Barr virus (EBV) positivity predicted response and TTF. LDH elevation predicted shorter OS. No patient died of rituximab toxicity and all patients who progressed underwent further treatment with chemotherapy. Twenty-three patients received chemotherapy. ORR was 74%, median TTF was 10.5 months and estimated OS was 42 months. Prognostic factors for response included stage, LDH and allograft involvement by tumor. These factors and lack of complete response (CR) predicted poor survival. Twenty-six percent of the patients receiving chemotherapy died of toxicity. Rituximab and chemotherapy are effective in patients with PTLD who fail or do not tolerate RI. While rituximab is well tolerated, toxicity of chemotherapy is marked. PTLD patients requiring therapy beyond RI should be considered for rituximab, especially with EBV-positive disease. Chemotherapy should be reserved for patients who fail rituximab, have EBV-negative tumors or need a rapid response.

Adult↗
PubMed2006

Kidney disease after heart and lung transplantation.

Kidney disease is a commonly recognized complication of heart and lung transplantation and is associated with increased morbidity and mortality. While the spectrum of kidney disease in this population is wide-ranging, studies indicate that between 3% and 10% of these patients will ultimately develop end-stage renal disease (ESRD). This review examines the risk factors for both acute and chronic kidney injury, with a particular emphasis on the role of calcineurin inhibitor-mediated nephrotoxicity in both these settings. Against the background of current National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, we have further considered and recommended appropriate strategies for long-term management of kidney disease-related manifestations in heart and lung transplant recipients. Specific aspects addressed include retarding progressive renal injury and minimizing nephrotoxicity, as well as treatment of hypertension, hyperlipidemia and anemia. Finally, for patients in this population with advanced kidney disease, renal replacement therapy options are discussed. Based on the impact of chronic kidney disease on outcomes in both heart and lung recipients, we advocate early referral to a nephrologist for patients displaying evidence of significant renal dysfunction.

Acute Disease↗
PubMed2006

Kidney and pancreas transplantation in the United States, 1995-2004.

This article examines OPTN/SRTR data on kidney and pancreas transplantation for 2004 and the previous decade, and discusses recent changes in kidney-pancreas (KP) allocation policy and emerging issues in kidney donation after cardiac death (DCD). Although the number of kidney donors continues to increase, new waiting list registrations again outpaced the number of kidney transplants performed, rising by 11% between 2003 and 2004 and contributing to a 1-year increase of 8% in the number of patients active on the waiting list. DCD has increased steadily since 2000; 39% more DCD transplants were performed in 2004 than 2003. Both deceased donor and living donor kidney graft survival rates remain excellent and are improving. The number of people living with a functioning kidney transplant doubled between 1995 and 2004, to 101,440 with a functioning kidney-alone and 7213 with a functioning KP. Health care providers in all settings are more likely to be exposed to these transplant recipients. Patient survival following simultaneous pancreas-kidney (SPK) transplantation is excellent and has improved incrementally since 1995; death rates in the first year fell from 60 per 1000 patient-years at risk in 2001 to 45 in 2003. The number of solitary pancreas transplants increased dramatically in 2004.

Adolescent↗
PubMed2004

Ganciclovir prophylaxis delays but does not prevent cytomegalovirus infection in renal transplant recipients.

Cytomegalovirus (CMV) infection is associated with reduced graft and patient survival among renal transplant recipients. The purpose of this study was to examine the effect of routine prophylaxis with 12 weeks of oral ganciclovir on the incidence of CMV infection in a center that predominantly uses antibody induction together with tacrolimus/mycophenolate mofetil-based maintenance immunosuppressive therapy. The control group consisted of a historical patient cohort transplanted immediately prior to the use of oral ganciclovir prophylaxis. The use of tacrolimus (88% vs 77%, P=.02) and cytolytic therapy (81% vs 46%, P <.0001) was likewise greater among patients who received ganciclovir prophylaxis. CMV infection occurred in 20 (9%) patients in the ganciclovir era and 4 (3%) patients in the preganciclovir era (P=.003). The mean time to CMV infection was longer in patients who received ganciclovir prophylaxis than in patients in the preganciclovir era (23.4 +/- 10.9 weeks vs 9.8 +/- 5.6 weeks, P=.03). We conclude that 12 weeks of ganciclovir prophylaxis delays but does not prevent CMV infection from occurring in renal transplant recipients. These results suggest that with the use of 12 weeks of ganciclovir prophylaxis, vigilance for CMV infection is needed well beyond 24 weeks posttransplant.

Adult↗
PubMed2001

A comparison of the survival of shipped and locally transplanted cadaveric renal allografts.

BACKGROUND: The effect on allograft survival of the shipment of cadaveric renal allografts from one organ-procurement organization to another is uncertain. METHODS: Using data from the Organ Procurement and Transplantation Network of the United Network for Organ Sharing, we identified 5446 pairs of cadaveric kidneys (10,892 allografts) in which one kidney was shipped and the other was transplanted locally. We compared the risk of graft failure using statistical models that accounted for confounding variables, including the degree of HLA mismatching. RESULTS: After adjustment for the degree of HLA mismatching, shipped organs had a significantly higher rate of allograft failure than locally transplanted organs in the first year after transplantation (adjusted hazard ratio, 1.17; 95 percent confidence interval, 1.05 to 1.31; P=0.004), but not thereafter. An association between the shipment of organs with no HLA mismatches and allograft failure was not confirmed. CONCLUSIONS: The shipment of cadaveric renal allografts increases the risk of failure of HLA-mismatched grafts during the first year after transplantation.

Acute Disease↗
PubMed1999

Transforming growth factor-beta levels in human allograft chronic fibrosis correlate with rate of decline in renal function.

BACKGROUND: Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed "chronic rejection, chronic allograft nephropathy, or allograft fibrosis." Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro-sclerotic growth factor, transforming growth factor beta (TGFbeta). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFbeta protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFbeta and whether heightened expression of TGFbeta is clinically significant. METHODS: Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFbeta protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFbeta. RESULTS: Seventy-two percent of patients expressed high levels of intra-allograft TGFbeta. This group of patients lost renal function at an average rate of -19.5+/-17.3 ml/min/year. In contrast, patients with minimal or no TGFbeta expression experienced a decline of only -6.2+/-4.1 ml/min/year (P=0.01). CONCLUSIONS: These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFbeta that correlates with an increased rate of decline in renal function.

Adult↗
PubMed1997

Long-term pancreas allograft outcome in simultaneous pancreas-kidney transplantation: a comparison of enteric and bladder drainage.

BACKGROUND: The optimal pancreatic exocrine drainage method remains controversial. Bladder drainage (BD) is widely used, but associated with a high incidence of urological complications (acidosis, dehydration, pancreatitis, and urinary tract infection). Enteric drainage (ED) avoids this morbidity, but may be associated with inferior graft survival. METHODS: We conducted a retrospective study comparing BD and ED in 71 simultaneous pancreas-kidney transplant recipients (37 BD; 34 ED) transplanted between February 1988 and June 1996. RESULTS: Five BD and five ED patients experienced early pancreas loss within 3 months after transplantation. The mean follow-up of the remaining 61 patients has been 45.7+/-3.9 and 76.0+/-3.3 months for ED and BD patients, respectively (P<0.005). Both groups had similar pretransplant demographics, co-morbidity, and nutritional and immunological status. The incidence of volume depletion (3.4% vs. 34.3%), acidosis (0% vs. 41.0%), pancreatitis (3.4% vs. 39.7%) and urinary tract infection (26.7% vs. 71%) was lower in ED patients (P<0.005 vs. BD). Of the BD group, 18.7% required conversion to ED for intractable complications. Initial length of stay was equivalent (17.7+/-9 days vs. 18.4+/-10 days) between groups. However, the number of admissions (0.79+/-0.18 vs. 1.38+/-0.14) and in-hospital days/patient/year (6.26+/-1.16 vs. 11.46+/-2.12) was less in ED patients (P<0.05 vs. BD). Actuarial patient and pancreas allograft survival up to 4 years after transplant was similar between groups. CONCLUSIONS: Compared with BD, (a) perioperative morbidity is not increased by ED, (b) ED is associated with fewer complications and hospitalizations, and (c) ED is not associated with increased long-term pancreas graft failure. These data suggest that ED is superior to BD and should be considered as the preferred technique for simultaneous pancreas-kidney transplants.

Acute Disease↗
PubMed1994

Pivotal role of colony stimulating factor-1 in lupus nephritis.

Spontaneous autoimmune renal injury in MRL-lpr mice shares many features of human lupus nephritis. We noted a prominent increase of macrophages (M phi) in the glomerulus of MRL-lpr mice. Since colony stimulating factor-1 (CSF-1) regulates M phi growth and is a potent chemoattractant, we explored the possibility that there was an increase in CSF-1 in MRL-lpr mice. We detected a biphasic increase in circulating CSF-1 in MRL-lpr mice as compared to congenic MRL- ++ mice other strains with the lpr gene, and normal mice. There was an increase in CSF-1 steady state mRNA transcripts in the kidney but not in the liver, lung or bone marrow. By in situ hybridization our studies identified the glomeruli as the predominant source of renal CSF-1. Enhanced CSF-1 is expressed by the mesangial cells at the same time (4 weeks of age) that M phi begin to accumulate in the glomeruli, well in advance of the loss of renal function. We have isolated pure populations of glomerular M phi in culture from MRL-lpr mice. These glomerular M phi require CSF-1 to survive and proliferate. Therefore, these data suggest that CSF-1 is increased in the glomerulus prior to the influx and accumulation of M phi. We propose that CSF-1 expression in the kidney is pivotal in the attraction and accumulation of M phi and in turn responsible for initiating tissue destruction.

Animals↗
PubMed1993

Colony stimulating factor-1 in the induction of lupus nephritis.

In this study we examine the role of colony stimulating factor-1 (CSF-1) in the induction of lupus nephritis. The purpose of the study was to establish the relationship of CSF-1 to the prominent influx of macrophages (M phi) in the glomeruli of MRL-lpr mice with autoimmune lupus nephritis. The kidneys of MRL-lpr mice were examined before (< 12 weeks of age) and after (> 12 weeks of age) renal injury for CSF-1 transcripts by in situ hybridization. CSF-1 mRNA was detected at four weeks of age within glomeruli and increased with disease severity. To examine whether glomerular M phi (glom M phi) required CSF-1 we isolated M phi from the kidneys of MRL-lpr mice. Two types of glom M phi (with morphological and growth characteristics which correlated with the presence or absence of proteinuria) were isolated. Under CSF-1-free culture conditions, where the viability of glom M phi from proteinuric mice was maintained, glom M phi from pre-proteinuric mice were unable to survive. Neutralization of CSF-1 in the media reduced viability of pre-proteinuric glom M phi (5 to 6 x), while viability of proteinuric glom M phi was diminished < 1.5 x. Additionally, CSF-1 supplementation induced a 10 x proliferation of pre-proteinuric glom M phi when compared to CSF-1-free medium. In contrast, proteinuric glom M phi did not proliferate in response to CSF-1. These studies suggest that CSF-1 induces macrophage proliferation and differentiation within glomeruli and, in turn, renal injury.

Animals↗
PubMed1993

Stimulated renal tubular epithelial cells induce anergy in CD4+ T cells.

Renal tubular epithelial cells (TEC) can express MHC class II molecules in vitro and in vivo. Their ability to also secrete cytokines and express adhesion molecules suggests a possible immune accessory role for TEC. We have previously documented that TEC process and present antigen to T cell hybridomas. However, engagement of the T cell receptor alone is sufficient to induce IL-2 secretion by T cell hybridomas. We now report that presentation of antigen by TEC to a CD4+ T cell clone results in functional inactivation of the T cells. Despite antigen-specific anergy, these T cells are viable and proliferate in response to IL-2. Furthermore, allogeneic antigen presenting cells were unable to restore the T cell proliferative response, suggesting that the mechanism(s) was not entirely costimulator-dependent.

Animals↗
PubMed1993

The nephritogenic immune response.

An emerging viewpoint states that localization of antibodies, T cells, and macrophages within the kidney occurs through specific receptor-mediated interactions to initiate nephritis. The initial events involve loss of tolerance with activation of autoreactive B cells, autoreactive T cells, or both. Many pathogenic autoantibodies form immune deposits either by binding directly to renal antigens or by complexing with endogenous antigens with affinity for renal antigens. Autoreactive T-cell infiltration requires both the presence of specific antigens and costimulatory factors expressed by cells capable of antigen presentation. It is particularly noteworthy that some of the antigen targets of the nephritogenic immune response involve either cell surface molecules or matrix components with functional properties, raising the possibility that ligation of these components could serve to modulate the local inflammatory response. Furthermore, specific perturbations within endogenous cells, resulting directly from these interactions, probably influence subsequent inflammatory-fibrogenic events. In this review, we focus on recent work relating to the loss of tolerance leading to the emergence of autoreactive B and T lymphocytes; specific autoantibody and T-cell interactions within the kidney; and the active participation of endogenous cells in the initiation of the nephritogenic response.

Animals↗
PubMed1992

Cultured mesangial cells from autoimmune MRL-lpr mice have decreased secreted and surface M-CSF.

M-CSF has been implicated in the pathogenesis of lupus nephritis in MRL-lpr mice. We recently reported persistently high levels of serum M-CSF in MRL-lpr mice as early as one week of age, not present in normal mice including C3H mice. In addition, M-CSF transcripts in MRL-lpr renal cortex increased with an increase in the severity of nephritis. Because glomerular mesangial cells (MC) secrete M-CSF, we investigated whether cultured MRL-lpr MC secrete more M-CSF than C3H MC. Paradoxically, unstimulated MRL-lpr MC secreted substantially less M-CSF than C3H MC [26 +/- 11 vs. 109 +/- 7 colony forming units (CFU)]. We then explored whether MC could express membrane bound M-CSF. We detected a 31 kDa form of membrane M-CSF on both MRL-lpr and C3H MC. Fewer MRL-lpr MC than C3H MC (24 +/- 5% vs. 78 +/- 5%) expressed membrane M-CSF. Furthermore, the increase in the mean channel log fluorescence intensity on MRL-lpr MC was considerably less than in C3H MC, indicating a lower density of M-CSF on MRL-lpr MC. Because our prior studies established that MRL-lpr kidneys have enhanced expression of TNF alpha, we stimulated cultured MC with TNF alpha. TNF alpha increased M-CSF secretion by stimulated MRL-lpr by twofold over unstimulated MRL-lpr MC, but did not increase M-CSF in C3H MC. In addition, M-CSF secretion was modestly greater in stimulated MRL-lpr MC compared to stimulated C3H MC. In conclusion, this is the first report of membrane M-CSF detectable on cultured MC. These studies note that despite higher circulating M-CSF and renal M-CSF transcripts in MRL-lpr mice, cultured MRL-lpr MC have lower basal secreted and membrane bound M-CSF than cultured C3H MC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Anti-HIV antibodies in patients receiving intravenous immunoglobulin.

Until recently, donors of serum for intravenous immunoglobulin (IVIG) were not screened for the presence of antibodies to the human immunodeficiency virus (HIV). We detected anti-HIV antibodies (Ab) in the sera of seven patients following IVIG infusions. In addition, enzyme immunoassay values increased and/or Western blot converted from negative to positive in all patients following infusions and declined again over time confirming passive acquisition. Patients who received IVIG manufactured after the screening of donors was initiated may still test positive for anti-HIV Ab due to antibodies to human T-lymphocyte cell lines in which viral antigen was prepared. Such false positives must be excluded when testing IVIG recipients. Despite the presence of antibodies to HIV, IVIG has never been documented to transmit the virus.

Adolescent↗
PubMed1987

Tetany despite normocalcaemia and normomagnesaemia following parathyroidectomy.

Two patients with long-standing hyperparathyroidism due to a parathyroid adenoma are described. Both had severe osteitis fibrosa cystica and a proximal myopathy. Both were treated with alfacalcidol (2 micrograms/day) prior to and following parathyroidectomy, and infused with calcium gluconate following the operation. Plasma total and ionized calcium and magnesium concentrations were maintained within the normal range. However, both developed tetany in the postoperative period in spite of normal ionized calcium and magnesium concentrations. Tetany continued for 4 weeks in one patient and for longer in the other. Prolonged hypercalcaemia may result in a state of neuromuscular excitability following parathyroidectomy even at high normal concentrations of ionized calcium.

Adenoma↗
PubMed1978

Postnatal development of visually evoked activity within motor cortex of cat.

1. The development of visually evoked activity within motor cortex was studied in chloralose-anesthetized kittens of 3, 4, and 5 mo of age and adult cats. 2. The slow-wave response from motor cortex of the adult cat is a triphasic negative-positive-negative wave. In 3-mo-old kittens the response is only a long-duration negative wave, while at 4 mo the positive and late negative waves emerge, and at 5 mo of age the adult form of the response is present. 3. Single neurons in the adult respond to the light during the positive component of the slow-wave response. When only the negative wave is present in kittens of 3 and 4 mo of age, neurons do not respond to the photic stimulus. At 5 mo of age the correlation between unit activity and the positive component of the response is identical to the adult. 4. The laminar analysis of the positive component of the response suggests that it originates relatively superficially in cortex and migrates down toward the deeper layers. Its correlation with unit activity indicates that the positive component represents excitatory postsynaptic potentials. 5. These results are consistent with an excitatory drive on neurons within motor cortex undergoing development change until the 5th mo of life.

Aging↗