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Biomedical subjects

S M Katz

Publications and source records attributed to S M Katz.

At least 19 recordsLinked to original sources
PubMed2006

Fibromuscular dysplasia recurrence after kidney transplantation: case report.

We report the extremely rare recurrence of intimal fibroplasia, a rare form of fibromuscular dysplasia, in a kidney recipient at 6 months after transplantation from a living-related donor. The patient was successfully treated and maintains good kidney function, however, the case raises the question of whether kidneys with fibromuscular dysplasia should be included in the expanded criteria for kidney transplantation.

Adult↗
PubMed2005

Transplantation of single pediatric kidneys into adult recipients.

AIM: To evaluate the outcome of single pediatric kidneys transplanted into adult recipients. METHODS: A retrospective single-center review was performed of transplants from donors less than 5 years of age. Outcomes were compared with recipients of grafts from donors 18 to 45 years transplanted during the same time period. RESULTS: Thirty single renal transplants from pediatric donors and 117 transplants from adult donors between 18 and 45 years of age were performed during the study period. The mean age of the pediatric donors was 2.9 +/- 0.8 years versus 31.5 +/- 8.9 years for adult donors (P < .001). The mean age of the recipients of pediatric donors was 41.9 +/- 13 years versus 48 +/- 12.6 years for recipients of adult grafts (P = .020). The mean recipient weight of pediatric donors was 55.9 +/- 7.8 kg versus 78.0 +/- 17.7 kg for recipients of adult donors (P < .001). Sixty-six percent of pediatric donor recipients were of female gender compared to only 36% of adult donor recipients (P = .005). Death-censored actuarial graft survivals at 1 and 4 years for recipients of pediatric donor grafts were 90% and 85% compared to 93% and 85% for recipients of adult donor grafts (P = NS). The mean calculated creatinine clearances of adult donor graft recipients at 1 and 4 years posttransplantation were 70.8 +/- 26.5 and 73.7 +/- 27.2 mL/min, respectively, compared to 50.3 +/- 20.1 and 56.3 +/- 21.4 mL/min for pediatric donor grafts (P < .01 at 1 and 4 years). CONCLUSION: The use of single pediatric donor kidneys provides an excellent opportunity to safely expand the donor pool.

Actuarial Analysis↗
PubMed2005

Graft survival and immune regulation of pancreas allograft recipients induced with thymoglobulin, sirolimus, and cyclosporine.

BACKGROUND: Our objective was to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimmune response of pancreas-kidney transplant recipients. METHODS: Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. A subset of 10 recipients were also enrolled in a study to measure immune responsiveness. Flow PRA-determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed at various timepoints during the first posttransplant year. RESULTS: One-year patient, kidney, and pancreas survivals were 97%, 94%, and 92%, respectively. There was 1 death due to sepsis, and 1 kidney and 2 pancreas graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study displayed depression of CD3, CD4, and CD8 counts (<80%) until 3 months posttransplant. At transplantation, 9 of 10 patients displayed <10% class I HLA antibody. By 3 months, 7 of 10 showed a transient elevation in class I HLA antibodies, with 2 patients expressing >80% flow PRA. At transplant 1 patient was FCXM-positive, whereas, by 3 months posttransplant, 2 of 10 patients demonstrated a positive FCXM. There were no clinical consequences to either the presence of HLA antibody or the positive FCXMs. By 6 months, 7 of 9 patients expressed immunoregulatory suppressor cell activity. CONCLUSIONS: The absence of acute rejection events was likely due to inhibition of donor-specific immunity. Seventy percent of patients demonstrated an early non-donor-directed HLA antibody response that had no adverse effect on graft function and 78% of the patients displayed immunoregulatory suppressor cell function, probably contributing to the successful clinical outcome.

Anti-Bacterial Agents↗
PubMed2000

The development of sirolimus: The University of Texas-Houston experience.

The transplant team at The University of Texas-Houston has studied sirolimus from preclinical through pivotal Phase III trials to single-center Phase IV trials as we continue to refine algorithms for sirolimus therapy. The sirolimus/CsA combination produces a marked reduction in the occurrence and severity of acute allograft rejection episodes. A recently completed post hoc median effect analysis of drug blood concentrations displayed by patients in the 2 pivotal Phase III trials documented that the combination displays synergistic interactions. Patients in the sirolimus/CsA arms did not display an increased incidence of infectious or malignant complications. However, they did experience a range of nonimmune toxicities, including potentiation of putatively CsA-related adverse reactions, such as renal dysfunction and hypercholesterolemia, which appear to be mitigated by reduction or elimination of CsA. However, thrombocytopenia and to a lesser extent leukopenia and anemia appear to be sirolimus-related side effects. The occurrence and severity of these adverse reactions seem to be avoided or ameliorated in most patients by optimizing sirolimus exposure at concentrations (15 ng/mL or by dose reduction. Sirolimus thus appears to be a potent and unique agent for developing new immunosuppressive strategies in organ transplantation.

Animals↗
PubMed1998

Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation.

BACKGROUND: Sirolimus, a novel immunosuppressant that inhibits cytokine-driven cell proliferation and maturation, prolongs allograft survival in animal models. After a phase I trial in stable renal transplant recipients documented that cyclosporine and sirolimus have few overlapping toxicities, we conducted an open-label, single-center, phase I/II dose-escalation trial to examine the safety and efficacy of this drug combination. METHODS: Forty mismatched living-donor renal transplant recipients were sequentially assigned to receive escalating initial doses of sirolimus (0.5-7.0 mg/m2/day), in addition to courses of prednisone and a concentration-controlled regimen of cyclosporine. We conducted surveillance for drug-induced side effects among sirolimus-treated patients and compared their incidence of acute rejection episodes as well as mean laboratory values with those of a historical cohort of 65 consecutive, immediately precedent, demographically similar recipients treated with the same concentration-controlled regimen of cyclosporine and tapering doses of prednisone. RESULTS: The addition of sirolimus reduced the overall incidence of acute allograft rejection episodes to 7.5% from 32% in the immediately precedent cyclosporine/prednisone-treated patients. At 18- to 47-month follow-up periods, both treatment groups displayed similar rates of patient and graft survival, as well as morbid complications. Although sirolimus-treated patients displayed comparatively lower platelet and white blood cell counts and higher levels of serum cholesterol and triglycerides, sirolimus did not augment the nephrotoxic or hypertensive proclivities of cyclosporine. The degree of change in the laboratory values was more directly associated with whole blood trough drug concentrations than with doses of sirolimus. CONCLUSIONS: Sirolimus potentiates the immunosuppressive effects of a cyclosporine-based regimen by reducing the rate of acute rejection episodes.

Adult↗
PubMed1998

Decreased protein binding of mycophenolic acid associated with leukopenia in a pancreas transplant recipient with renal failure.

BACKGROUND: Mycophenolate mofetil (MMF) is rapidly hydrolyzed to its active metabolite mycophenolic acid (MPA), which is excreted by the kidney after undergoing glucuronidation to MPAG. MPAG has been shown to accumulate in patients with renal failure. MPA is extensively and avidly bound to human serum albumin. In vitro inhibition of the pharmacologic target, inosine monophosphate dehydrogenase, is dependent on free MPA. It has been demonstrated that high MPAG concentrations decrease MPA protein binding in vitro. In addition, the uremic state is associated with altered protein binding of many drugs. METHODS: We assessed free MPA, total MPA, and MPAG kinetics in a patient with renal failure receiving MMF for a pancreas transplant, who presented with signs of MMF toxicity. MPA, MPAG, and free MPA were measured by high performance liquid chromatography and a validated 14C-MPA ultrafiltration methodology. RESULTS: The MPAG area under the concentration curve (AUC) in this patient was extremely high (5899 microg x hr/ml). The total MPA AUC of 36.8 microg x hr/ml was within the range usually obtained in stable renal patients. The free fraction of MPA and the free MPA AUC were markedly elevated (13.8% and 5.07 microg x hr/ml, respectively). CONCLUSIONS: Patients with severe renal insufficiency may have markedly increased free MPA levels that may not be reflected in total MPA concentrations. These patients may be at increased risk for MMF-related toxicity.

Adult↗
PubMed1998

Long-term function and survival of elderly donor kidneys transplanted into young adults.

BACKGROUND: Traditionally, elderly donor kidneys have not been widely accepted for transplantation on the assumption of inferior performance. However, the United Network for Organ Sharing reports an increase in the number of elderly donors from less than 2% in 1982 to 24% in 1995. This trend is commensurate with the increase of older dialysis patients and an overall increase in the elderly population in the United States (1). Optimal utilization of these kidneys is essential to overcome the acute organ shortage. METHODS: In this study, we transplanted 25 kidneys from elderly donors (ages 56-72 years) into young adult recipients (ages 20-50 years) (group 1) over a 4-year period. We compared the results with matched recipients of young adult donor kidneys (group 2) with regard to long-term kidney function and graft survival. A pretransplant biopsy of elderly donor kidneys was carried out and a frozen section report was obtained. Only those kidneys showing glomerulosclerosis of less than 20% were accepted for transplantation. All cadaveric kidneys were preserved in University of Wisconsin solution. RESULTS: Pretransplant biopsies of elderly donor kidneys showed structural deficits, which included glomerulosclerosis in 85%, arteriolar and/or mesangial thickening in 75%, and interstitial lymphocyte infiltration in 30%. The mean serum creatinine was 2.4+/-0.74, 2.2+/-0.56, and 2.9+/-0.76 mg/100 ml in group 1 and 1.5+/-0.55, 2.3+/-2.24, and 1.7+/-0.62 in group 2 at 1, 3, and 5 years, respectively. The patient survival was 92%, 92%, and 88% in group 1, and 100%, 100%, and 100% in group 2 at 1, 3, and 5 years, respectively. The graft survival was 80%, 64%, and 56% in group 1 and 100%, 96%, and 88% in group 2 at similar time intervals. The differences in the serum creatinine and graft survival between the two groups were statistically significant (P < 0.05). CONCLUSIONS: Most of the elderly donor kidneys with structural deficits transplanted into young adults provided suboptimal function and inferior long-term graft survival. To maximize the utilization and optimize the survival of elderly donor kidneys, we propose transplantation of these kidneys into age-matched recipients with similar physiological requirements as those of donors, with regard to kidney function.

Adult↗
PubMed1998

Feature asymmetries in visual search: effects of display duration, target eccentricity, orientation and spatial frequency.

In Experiments 1-3, we monitored search performance as a function of target eccentricity under display durations that either allowed or precluded eye movements. The display was present either until observers responded, for 104 msec, or for 62 msec. In all three experiments an orientation asymmetry emerged: observers detected a tilted target among vertical distracters more efficiently than a vertical target among vertical distracters. As target eccentricity increased, reaction times and errors augmented, and the set size effect became more pronounced, more so for vertical than tilted targets. In Experiments 4-7, the stimulus spatial properties were manipulated: spatial frequency; size; and orientation. The eccentricity effect was more pronounced for vertical than tilted targets and for high- than low-spatial frequency targets. This effect was eliminated when either the size, the size and orientation, or the size and spatial frequency were magnified (M-cortical factor). By increasing the signal-to-noise ratio, magnification reduced the extent of both asymmetries; it aided more the detection of tilted than vertical and of high- than low-spatial frequency targets. Experiments 4-7 indicate that performance improvement in the magnified conditions was due to the specific pairing of stimulus size with retinal eccentricity and not to the larger stimulus size of the magnified conditions. We conclude that stimulus size, orientation and spatial frequency influence the extent of the eccentricity effect and the efficiency of search performance.

Eye Movements↗
PubMed1997

Developing tomorrow's integrated community health systems: a leadership challenge for public health and primary care.

As the nation's health system moves away from earlier models to one grounded in population health and market-based systems of care, new challenges arise for public health professionals, primary care practitioners, health plan and institutional managers, and community leaders. Among the challenges are the need to develop creative concepts of organization and accountability and to assure that dynamic, system-oriented structures support the new kind of leadership that is required. Developing tomorrow's integrated community health systems will challenge the leadership skills and integrative abilities of public health professionals, primary care practitioners, and managers. These leaders and their new organizations must, in turn, assume increased accountability for improving community health.

Community Health Services↗
PubMed1996

Variable oral absorption of cyclosporine. A biopharmaceutical risk factor for chronic renal allograft rejection.

The inter- and intrapatient variability in cyclosporine (CsA) pharmacokinetics obfuscates the relationship between therapeutic outcome and administered dose, thereby impeding the development of secure algorithms for CsA therapy. In an attempt to understand these variabilities, we previously performed serial pharmacokinetic profiles on 160 renal transplant recipients during the first 3 posttransplant months. Drug exposure was estimated by the average CsA concentration (Cav), which was defined as a time-corrected (tau, hours) expression of the area under the concentration-time curve (AUC), i.e., Cav = (AUC/tau). Low Cav values correlated with an increased occurrence of acute rejection episodes and 1-year rate of renal transplant loss. The present study examines the results of serial pharmacokinetic profiling of a cohort of 204 patients treated for up to 5 years with CsA doses selected to achieve target Cav values. Multivariate analyses correlated demographic factors, laboratory values, clinical parameters, and CsA pharmacokinetic parameters with the occurrence of chronic rejection. The factors that predisposed to chronic rejection included a previous acute rejection episode, initial acute tubular necrosis, diastolic blood pressure above 85 mmHg, and African-American race. Once regression models were adjusted to account for the impact of these factors, we examined the association between the incidence of chronic rejection and individual pharmacokinetic parameters, including the mean values of the absolute and dose-corrected trough, peak, and Cav concentrations, as well as the percent coefficient of variation of each of these values. Receiver operating characteristic curves documented that 27% of the total risk for the occurrence of chronic rejection was attributable to a greater than 20% coefficient of variation of the dose-corrected Cav, namely, AUC/(tau.mg). This study suggests that variable oral bioavailability of CsA represents a biopharmaceutical risk factor for the occurrence of chronic rejection.

Administration, Oral↗
PubMed1996

Correlation of ELISA-detected IgG and IgA anti-HLA antibodies in pretransplant sera with renal allograft rejection.

The present study compared the occurrence of rejection episodes during the first twelve posttransplant (Tx) months and the 1-, 2-, and 3-year graft survivals among recipients stratified by the percent panel reactive antibody (% PRA) of pre-Tx sera as detected using either an antihuman globulin determined PRA (AHG-% PRA) or an ELISA methodology detecting IgG reactive against soluble HLA class I antigens (% PRA-STAT). There was a significant correlation between AHG-PRA greater than or equal to 10% and a PRA-STAT greater than or equal to 10% (P<0.001). However, among 200 sera displaying an AHG-PRA greater than or equal to 10% (mean 57 +/- 2l%), only 69% (138/200) displayed a PRA-STAT greater than or equal to 10%. With further study the discrepant finding, of 62 sera that were AHG-PRA greater than or equal to 10% but PRA-STAT <10%, was due to the presence of IgM and/or IgG non-MHC reactivity. In contrast, among 293 sera displaying an AHG-PRA < 100% (mean 3 +/- 2%), 15% (43/293) displayed a PRA-STAT greater than or equal to 10%. There was no correlation between AHG-% PRA and rejection episodes occurring during the first twelve post Tx months. In contrast, however, there was a highly significant correlation between PRA-STAT greater than or equal to 10% and the occurrence of rejection episodes during the first twelve post-Tx months (P < 0.001). Patients with PRA-STAT greater than of equal to 10% experienced a 70% rejection frequency compared with the 35% rejection frequency for patients with PRA-STAT sera < 10% (P<0.001). A significant correlation was observed between the presence of IgG-1 and rejection (P<0.01) but not IgG-subclasses 2, 3, or 4. Of particular interest was the observation in 11 patients that the presence of ELISA-detected IgA anti-HLA class I antigen (ELISA-IgA PRA greater than or equal to 10%) was associated with a significantly reduced rejection risk compared with sera where only PRA-STAT greater than or equal to 10% was present (27% vs. 70% incidence of rejection episodes, P<0.01). Finally, patients displaying pretransplant PRA-STAT results < 10% experienced significantly improved l-, 2-, and 3- year graft survivals of 85% vs. 74%, 82% vs. 70% and 81% vs. 67%, respectively (P<0.01 for each time point), compared with patients displaying PRA-STAT results greater than or equal to 10%. These data suggest that the use of the ELISA methodology to detect IgG reactivity against soluble HLA class I antigens (PRA-STAT) may allow for the determination of a more clinically informative % PRA than the AHG-% PRA. Moreover, the presence of ELISA-detected IgA anti-HLA may act to inhibit rejection mechanisms associated with ELISA-detected IgG anti-HLA greater than or equal to 10%.

Enzyme-Linked Immunosorbent Assay↗