PubMed Health⌕ Search

Biomedical subjects

Ron Shapiro

Publications and source records attributed to Ron Shapiro.

At least 55 records · Page 3Linked to original sources
PubMed2004

Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center's experience.

BACKGROUND: Chronic renal failure leads to amenorrhea, and successful pregnancy is rare. The aim of the present report is to examine the outcome of pregnancies under tacrolimus after kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). METHOD: All pregnancies under tacrolimus after KTx or SPKTx from 1993 to April 2002 were retrospectively examined. Renal function and the mother's survival were followed until December 2002. RESULTS: Thirteen mothers after KTx delivered 19 babies, and 2 mothers after SPKTx delivered 3 babies. All mothers survived the pregnancy and retained allograft function. One mother had a stillborn baby from an unrecognized amniotic fluid leak and a small ischemic placenta. The mean gestational period was 34.4 +/- 5.1 weeks. Mean birth weight was 2373 +/- 1001 g. Birth-weight percentile to gestational period was 40 +/- 28. None of the mothers experienced rejection during the pregnancy. Three pregnancies in mothers with KTx experienced toxemia of pregnancy, and one mother with SPKTx developed pre-eclampsia during both pregnancies. Five mothers (6 deliveries, 27.3%) required caesarian section. During the follow-up period, one mother died from a cerebrovascular accident. Another five mothers returned to dialysis 55.6 +/- 32.4 months after the last delivery and 99.4+28.5 months after the last KTx. Both SPKTx mothers have maintained normal renal and pancreatic allograft function 42 and 62 months postdelivery. CONCLUSION: All mothers survived the pregnancy. One baby was stillborn. Forty-one percent of babies were either preterm or premature, and 27% of babies were delivered by caesarean section. Toxemia of pregnancy or pre-eclampsia was observed in 23% of pregnancies postKTx and SPKTx. None of the mothers experienced rejection during their pregnancy.

Birth Weight↗
PubMed2004

Lessons of organ-induced tolerance learned from historical clinical experience.

Although the reductionist approach has served science well for 400 years, the accumulation of details can obscure the truth if the original premise is incorrect. One such premise has been that successful organ transplantation and bone marrow engraftment are fundamentally different outcomes involving separate and distinct mechanisms. Some historical clinical observations pointed to a different conclusion almost from the beginning and included clues about how to induce tolerance with the aid of immunosuppression.

Bone Marrow Transplantation↗
PubMed2004

Retransplantation in patients with graft loss caused by polyoma virus nephropathy.

The characteristics and outcome in 10 patients who underwent retransplantation after losing their renal grafts to BK virus-associated nephropathy (BKAN) are described. The patients underwent retransplantation at a mean of 13.3 months after failure of the first graft. Nephroureterectomy of the first graft was performed in seven patients. Maintenance immunosuppression regimens after the first and second grafts were similar, consisting of a combination of a calcineurin inhibitor, mycophenolate mofetil, and prednisone. BKAN recurred in one patient 8 months after retransplantation, but stabilization of graft function was achieved with a decrease in immunosuppression and treatment with low-dose cidofovir. After a mean follow-up of 34.6 months, all patients were found to have good graft function with a mean creatinine of 1.5 mg/dL. From this collective experience from five transplant centers (although the follow-up after retransplantation was not extensive), it can be concluded that patients with graft loss caused by BKAN can safely undergo retransplantation. The risk of recurrence does not seem to be increased in comparison with the first graft.

Adult↗
PubMed2004

Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial.

Reported are the reduction of anti-HLA antibody levels and improvement of transplant rates by intravenous immunoglobulin (IVIG) in a randomized, double-blind, placebo-controlled clinical trial. Between 1997 and 2000, a total of 101 adult patients with ESRD who were highly sensitized to HLA antigens (panel reactive antibody [PRA] > or =50% monthly for 3 mo) enrolled onto an NIH-sponsored trial (IG02). Patients received IVIG or placebo. Subjects received IVIG 2 g/kg monthly for 4 mo or an equivalent volume of placebo with additional infusions at 12 and 24 mo after entry if not transplanted. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. However, IVIG significantly reduced PRA levels in study subjects compared with placebo. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Seven graft failures occurred (four IVIG, three placebo) among adherent patients with similar 2-yr graft survival rates (80% IVIG, 75% placebo). With a median follow-up of 2 yr after transplant, the viable transplants functioned normally with a mean +/- SEM serum creatinine of 1.68 +/- 0.28 for IVIG versus 1.28 +/- 0.13 mg/dl for placebo. Adverse events rates were similar in both groups. We conclude that IVIG is better than placebo in reducing anti-HLA antibody levels and improving transplantation rates in highly sensitized patients with ESRD. Transplant rates for highly sensitized patients with ESRD awaiting kidney transplants are improved with IVIG therapy.

Adult↗
PubMed2004

Initial experience using histidine-tryptophan-ketoglutarate solution in clinical pancreas transplantation.

BACKGROUND: The colloid-based University of Wisconsin (UW) preservation solution has been used extensively in clinical pancreas transplantation. Experimental studies support the use of the crystalloid-based histidine-tryptophan-ketoglutarate (HTK) preservation solution for this purpose. AIM: We report our initial experience with HTK for pancreas allograft preservation and compare this to a contemporary experience with UW solution in conventional multiorgan deceased donors (<50 yr). MATERIALS AND METHODS: Retrospectively collected information on 33 pancreas transplants between September 2001 and October 2002 were analyzed for early graft function and complications up to 30 d after procurement and storage in either HTK or UW solutions. During multi-organ recovery, either UW solution (4-5 L) or HTK solution (8-10 L) was used for aortic perfusion and subsequent back-table flush and storage. Exocrine drainage of 31 pancreas allografts was enteric, while the bladder was used for drainage in two cases. Patient outcomes were analyzed according to the preservation solution used. Sixteen pancreata were used in combination with a kidney allograft (SPK), seven were used in patients after prior kidney transplantation (PAK), while 10 were used in patients who were not in renal failure (PTA). RESULTS: The UW group consisted of 17 patients (10 SPK, three PAK, four PTA) with a mean donor age of 29.5 +/- 10.7, and a mean cold ischemia time of 15.1 +/- 2.1 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (315 and 99 IU/L), lipase (1727 and 346 IU/L), glucose (121 and 100 mg/dL) and creatinine (5.01 and 1.77 mg/dL). Patient and graft survival was 100% at 1-month post transplant. In the HTK group there were 16 patients (six SPK, four PAK, six PTA) with a mean donor age 21.9 +/- 5.7 and a mean cold ischemia time 14.0 +/- 1.3 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (588 and 126 IU/L), lipase (4711 and 441 IU/L), glucose (97 and 109 mg/dL) and creatinine (5.28 and 2.42 mg/dL). Patient survival was 100% while graft survival was 94% at 1-month post-transplant. CONCLUSIONS: Early graft function and complications are comparable with HTK and UW solutions for pancreas allograft preservation.

Adenosine↗
PubMed2004

Immunosuppression: practice and trends.

Over the past decade, immunosuppression therapy has undergone striking changes in the scale and pace by which new immunosuppressive molecules and antibodies have become incorporated into daily transplant medicine. An organ-by-organ review of data reveals several trends. The highest use of induction therapy (over 70% of patients) was reported for simultaneous pancreas kidney (SPK) and pancreas after kidney (PAK) transplants in 2002; use of induction therapy was less common in liver transplants (only 18%). Corticosteroids served as discharge maintenance immunosuppression in over 87% of the recipients of kidney, SPK, PAK and thoracic transplants, and in over 70% of pancreas transplant alone (PTA) recipients. Corticosteroid use in intestine transplants was reported in 64% of recipients in 2002. A shift in the calcineurin inhibitor used for maintenance immunosuppression from cyclosporine to tacrolimus for the majority of patients had occurred for kidney, PAK, SPK, PTA, liver, lung, and heart-lung by 2001. For heart transplants, cyclosporine remained the calcineurin inhibitor of choice; tacrolimus remained the predominant calcineurin inhibitor agent for intestine (since 1994). Use of antibody treatment for rejection during the first post-transplant year for most organs declined. Short-term outcomes have improved, based on the observation that rates of rejection within the first year post-transplant have diminished.

Graft Rejection↗
PubMed2004

Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients.

BK virus-allograft nephropathy (BKVAN) is an increasingly recognized complication after kidney transplantation. Quantitative tests have been advocated to monitor patients, but data demonstrating their efficacy are relatively limited. We developed a real-time PCR assay to quantitate BK virus loads in the setting of renal transplantation, and we correlated the BK virus load with clinical course and with the presence of BK virus in renal biopsy specimens. BK virus loads were measured in urine, plasma, and kidney biopsy samples in three clinical settings: (i) patients with asymptomatic BK viruria, (ii) patients with active BKVAN, and (iii) patients with resolved BKVAN. Active BKVAN was associated with BK viremia greater than 5 x 103 copies/ml and with BK viruria greater than 107 copies/ml in all cases. Resolution of nephropathy led to resolution of viremia, decreased viruria levels, and disappearance of viral inclusions, but low-level viral DNA persisted in biopsy specimens even for patients whose viruria was cleared. All but one patient in the resolved BKVAN group carried a urinary viral load below 107 copies/ml. Viral loads in patients with asymptomatic viruria were generally lower but in some cases overlapped with levels more typical of BKVAN. One patient with asymptomatic viruria and with a viral load overlapping values seen in BKVAN had developed nephropathy by the time of follow-up. In conclusion, serial measurement of viral loads by quantitative PCR is a useful tool in monitoring the course of BK virus infection. The results should be interpreted in conjunction with the clinical picture and biopsy findings.

BK Virus↗
PubMed2004

Low toxicity immunosuppressive protocols in renal transplantation.

With the development of increasingly potent new immunosuppressive agents, the outcomes after renal transplantation have continued to improve. However, patients continue to require long term chronic immunosuppression. The toxicities associated with cyclosporine, azathioprine, prednisone, and anti-lymphocyte antibodies are well known; those associated with the newer agents, tacrolimus, mycophenolate mofetil, and sirolimus, have also been described. In an attempt to minimize these side effects, a number of low toxicity protocols have been developed. They can be categorized into those that withdraw, minimize, or avoid calcineurin inhibitors, those that withdraw or avoid steroids, and those that withdraw adjunctive (third) agents. This presentation will review the various low toxicity protocols that have been utilized in clinical renal transplantation. While there are a number of combinations that have been tried, it is not yet clear which regimen(s) will prove to be the most efficacious and least toxic. In addition, the presentation will also describe preliminary outcomes with a new tolerogenic protocol developed at the University of Pittsburgh. This regimen combines steroid avoidance with low doses and gradual tapering of calcineurin inhibitors, and has shown considerable promise in kidney, pancreas, liver, and intestine recipients.

Azathioprine↗
PubMed2004

Pancreatic transplantation at the University of Pittsburgh.

Campath-1H preconditioning with tacrolimus monotherapy is an effective immunosuppressive regimen for pancreas transplantation, with acceptable patient and graft survival rates early after transplantation. Rejection rates are low under this protocol if the tacrolimus level is kept consistently >10 ng/ml. This immunosuppressive protocol, combined with recent technical refinements, has resulted in lower rates of thrombosis and overall complications. Pancreatic transplantation en-bloc with visceral grafts has the following unique features: Diabetes is a rare indication, and HLA matching is not required. The gland is immunologically protected by the simultaneously transplanted visceral organs. Disease gravity, surgical complexity and gut alloimmunity influence the overall pancreatic allograft survival. The current UNOS listing criteria and data registry should be modified for obvious logistic and scientific reasons.

Adolescent↗
PubMed2003

Long-term results of pediatric renal transplantation into a dysfunctional lower urinary tract.

BACKGROUND: The authors reviewed their long-term experience with pediatric renal transplantation into a dysfunctional lower urinary tract to evaluate the results of contemporary lower urinary tract evaluation and management on graft survival and function. METHODS: Between 1990 and 1996, 21 renal transplants were performed in 20 children with dysfunctional lower urinary tracts and 61 transplants were performed in 61 patients with normal lower urinary tracts. The minimum follow-up was 36 months (mean, 62.0 +/- 19.6 months). The cause of lower urinary tract dysfunction included posterior urethral valves (n=13), prune belly syndrome (n=4), meningomyelocele (n=2), and urogenital sinus abnormality (n=1). Urodynamics were performed on all children with dysfunctional lower urinary tracts. Using these perioperative assessments, lower tract management strategies were devised, including timed voiding alone (n=6), clean intermittent catheterization (n=8), bladder augmentation (n=4), and supravesical urinary diversion (n=2). RESULTS: Overall 5-year actuarial patient and graft survival rates were 100% versus 95% (P=not significant [NS]) and 83% versus 69% in the dysfunctional and normal urinary tract groups (P=NS), respectively. Mean serum creatinine levels in dysfunctional and normal urinary tract patients with functioning grafts at 3 years were 1.3 +/- 0.5 and 1.3 +/- 0.7 mg/dL, respectively (P=NS). However, 35% of patients with a dysfunctional lower urinary tract experienced urologic complications. CONCLUSIONS: Pediatric renal transplantation into a dysfunctional lower urinary tract yields outcomes comparable to transplantation into the normal lower urinary tract. Because of the high urologic complication rates, careful surveillance of lower urinary tract function by urodynamic evaluation is essential to optimize these outcomes.

Child↗
PubMed2003

Tolerogenic immunosuppression for organ transplantation.

BACKGROUND: Insight into the mechanisms of organ engraftment and acquired tolerance has made it possible to facilitate these mechanisms, by tailoring the timing and dosage of immunosuppression in accordance with two therapeutic principles: recipient pretreatment, and minimum use of post-transplant immunosuppression. We aimed to apply these principles in recipients of renal and extrarenal organ transplants. METHODS: 82 patients awaiting kidney, liver, pancreas, or intestinal transplantation were pretreated with about 5 mg/kg of a broadly reacting rabbit antithymocyte globulin during several hours. Post-transplant immunosuppression was restricted to tacrolimus unless additional drugs were needed to treat breakthrough rejection. After 4 months, patients on tacrolimus monotherapy were considered for dose-spacing to every other day or longer intervals. FINDINGS: We frequently saw evidence of immune activation in graft biopsy samples, but unless this was associated with graft dysfunction or serious immune destruction, treatment usually was not intensified. Immunosuppression-related morbidity was virtually eliminated. 78 (95%) of 82 patients survived at 1 year and at 13-18 months. Graft survival was 73 (89%) of 82 at 1 year and 72 (88%) of 82 at 13-18 months. Of the 72 recipients with surviving grafts, 43 are on spaced doses of tacrolimus monotherapy: every other day (n=6), three times per week (11), twice per week (15), or once per week (11). INTERPRETATION: The striking ability to wean immunosuppression in these recipients indicates variable induction of tolerance. The simple therapeutic principles are neither drug-specific nor organ-specific. Systematic application of these principles should allow improvements in quality of life and long-term survival after organ transplantation.

Antilymphocyte Serum↗
PubMed2003

Longitudinal study of cryptococcosis in adult solid-organ transplant recipients.

While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.

Adult↗
PubMed2003

Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults.

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) has been increasingly recognized as an important cause of renal transplant dysfunction. We report the role of quantitative viral load monitoring in the management of BKVAN. METHODS: We developed a real-time quantitative polymerase chain reaction (PCR) assay for BKV detection in urine and plasma. Four renal allograft recipients, including two children, with BKVAN were treated with low-dose cidofovir and followed prospectively. RESULTS: The PCR assay showed a detection limit of 10 viral copies with an intra-assay coefficient of variation of 19%. All four patients with BKVAN demonstrated intranuclear inclusions on allograft biopsy and a progressive rise in serum creatinine; three patients underwent multiple biopsies before the diagnosis of BKVAN was made. Three of the patients experienced a "viral syndrome" before the onset of renal dysfunction. One child also demonstrated an echogenic renal mass. All of the patients demonstrated strongly positive urinary PCR values (>100,000 copies/microL). BKV DNA was also detected in the plasma of three patients. All the patients were treated with intravenous low-dose cidofovir (0.25-1 mg/kg per dose, every 2-3 weeks, without probenecid). BK viruria resolved within 4 to 12 weeks (after 1-4 doses) of the cidofovir therapy, and all patients remain with stable renal function 6 to 26 months posttherapy. CONCLUSIONS: Quantitative PCR for BKV is a sensitive and reliable method for following the course of the infection in renal transplant patients. In addition, cidofovir therapy may be useful in the treatment of some of these patients, and its role needs to be investigated further.

Adult↗
PubMed2003

Four-color flow cytometric analysis of peripheral blood donor cell chimerism.

Passenger leukocytes have been demonstrated to play significant roles in initiating and also regulating immune reactions after organ transplantation. Reliable techniques to detect donor leukocytes in recipients after organ transplantation are essential to analyze the role, function, and behavior of these leukocytes. In this report we describe a simple, reliable method to detect donor cells with low frequencies using peripheral blood samples. Detection of small numbers of major histocompatibility complex (MHC) mismatched cells was first studied using four-color flow cytometry in artificially created cell mixtures. By selecting the CD45(+) population and simultaneous staining with several leukocyte lineage markers (CD3, CD4, CD8, CD56, and CD19), MHC-mismatched leukocytes were consistently detected in cell suspensions prepared from directly stained whole blood samples with a threshold sensitivity as low as 0.1%-0.2%. When the fresh peripheral blood mononuclear cells were separated by conventional Ficoll gradient purification, similar, but slightly lower levels of donor cells were detected. Blood samples obtained 1-5 months after liver, kidney, and intestine transplants revealed that the kind of organ allograft influenced levels and lineage pattern of the circulating donor cells. This procedure provided a simple and reliable method in determining early chimerism in transplant recipients. However, the detection of MHC-mismatched leukocytes of all lineages was much lower when frozen peripheral blood mononuclear cells were used.

Antibodies, Monoclonal↗
PubMed2003

Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management.

Each year, 55 000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300 000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent over-medication, which may leave the patient susceptible to opportunistic infection and drug toxicity effects, or under-dosing, which may lead to shortened graft survival because of rejection episodes. This paper describes the result of a multicenter study conducted at the Universities of Pittsburgh, Alabama and Maryland to evaluate an in vitro assay (CylexTM Immune Cell Function Assay) for the measurement of global immune response in transplant patients receiving immunosuppressive therapy. The assay uses a whole blood sample to maintain the presence of the drug during incubation. Following overnight incubation of blood with phytohemagglutinin (PHA), CD4 cells are selected using paramagnetic particles coated with a monoclonal antibody to the CD4 epitope. The CD4-positive cells are targeted as major immunosuppressive drugs are designed to specifically inhibit T-cell activation which has been implicated in rejection. The data generated at these three sites were submitted in support of an Food and Drug Association (FDA) application for the use of this assay in the detection of cell-mediated immunity in an immunosuppressed population. The assay was cleared by the FDA on April 2, 2002. This cross-sectional study was designed to establish ranges for reactivity of this bioassay in the assessment of functional immunity for an individual solid organ recipient at any point in time.

Adult↗
PubMed2003

Viral regulatory region sequence variations in kidney tissue obtained from patients with BK virus nephropathy.

BACKGROUND: The polyomavirus genome contains a noncoding control region (NCCR), which is believed to contain the enhancer elements that are important activators of viral transcription. We hypothesized that DNA sequence variations in this region play a role in the pathogenesis of BK virus allograft nephropathy (BKVAN). METHODS: Tissue sections were prepared from 26 paraffin-embedded biopsies with BKVAN obtained from 15 patients. The sections were lysed in a proteinase K buffer and subjected to DNA sequencing using Big Dye cycle sequencing reactions run on an automated DNA sequencer (ABI 310). NCCR anatomy was compared to the genomic sequence of archetype BKV strain WW. RESULTS: Twelve putative transcription factor binding sites showed nucleotide substitutions, deletions, or duplications in at least one of the biopsies studied. Changes were most commonly found in binding sites for granulocyte/macrophage stimulating factor promoter (24/26 biopsies) and nuclear factor-I (NF-I) transcription factor (21/22 biopsies). Less frequent changes were seen at other binding sites, including T antigen (3/22 biopsies) and the cytomegalovirus immediate early (CMV IE-1) promoter (3/22 biopsies). Five biopsies showed complex rearrangements reminiscent of those described in JC virus-associated progressive multifocal leukoencephalopathy. CONCLUSION: The regulatory region of BKV shows sequence heterogeneity in biopsy tissue with viral nephropathy. Sequence variations frequently affect putative transcription factor binding sites, with potential implications for promoter activity related to genes important in viral replication. Architectural rearrangements were found in some cases but did not appear to be a prerequisite for the pathogenesis of BKVAN.

BK Virus↗
PubMed2003

Psychological distress and adherence to the medical regimen among adolescent renal transplant recipients.

This longitudinal pilot study of adolescent renal transplant recipients (a) describes the prevalence of psychological distress, (b) describes the prevalence of nonadherence, and (c) explores the association between the recipient's psychological distress and his/her subsequent medical adherence. Twenty-two adolescents, aged 13-18 years, completed two interviews that were separated by approximately 12 months. Psychological distress was assessed in three domains: symptoms of depression, anxiety, and anger. Adherence was assessed in three domains: medication taking, blood work, and clinic attendance. At the initial interview, 36.4% had symptoms of depression, 36.4% endorsed anxiety, and 18.2% endorsed excessive state anger. Non-adherence rates were 13.6% for medication, 22.7% for blood work, and 50% for missed clinic. At the second interview, nonadherence with medication remained the same and the other domains decreased. Our small pilot sample, however, limited our ability to detect statistically significant changes over time. Predictive analyses demonstrated that adolescents with excessive anger were at greater risk for subsequently missing medications than adolescents without excessive anger. These findings suggest that while symptoms of depression and anxiety are observed among some adolescents with renal transplants, only anger is associated with elevated risk for nonadherence with medication.

Adolescent↗