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Biomedical subjects

S M Greenstein

Publications and source records attributed to S M Greenstein.

At least 19 recordsLinked to original sources
PubMed2000

Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit.

Immune/inflammatory responses of arterial vessel wall constituents to lipid metabolic disturbances have been postulated to contribute to the pathogenesis of atherosclerosis. Mycophenolate mofetil (MMF), an antiproliferative agent used in clinical transplantation, has been shown to inhibit smooth muscle cell (SMC) proliferation and decrease the recruitment of monocytes into sites of chronic inflammation. This study was conducted to determine the effect of MMF on atherosclerotic plaque development after cholesterol-induced injury. New Zealand white rabbits were fed a high-cholesterol diet containing 0.5% cholesterol and 8% peanut oil. The experimental group (n = 10) was given MMF (80 mg/kg/day subcutaneously); the control group (n = 10) received placebo injections. The aortas were harvested at 12 weeks for immunohistochemical analyses. SMCs were identified by reactivity with a monoclonal antibody (mAb) to alpha smooth muscle actin. Monocytes/macrophages were detected with mAb RAM 11. Cross-sectional areas of the media and neointima were measured using computer-assisted image analysis. The density of SMCs and macrophage/foam cells within the neointima was calculated by dividing the number of cells by the area of the plaque. Total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein were significantly increased compared with levels before the initiation of a high-cholesterol diet, but there were no significant differences between the MMF-treated and untreated groups. Neointimal area in aortic tissue sections of the MMF-treated group (0.586 +/- 0.602 mm(2)) was significantly lower when compared with that in control animals (1.082 +/- 0.621 mm(2)) (P < 0.05). The densities of neointimal SMCs and monocytes/macrophages in the control group were 778 +/- 293 and 341 +/- 90 cells/mm(2), respectively. MMF treatment significantly reduced the number of neointimal SMCs (506 +/- 185 cells/mm(2)) (P < 0.05). The number of monocytes/macrophages was also reduced after MMF treatment (260 +/- 124 cells/mm(2)) but not significantly. Our results demonstrate that the administration of MMF significantly reduced neointimal SMC accumulation and plaque development in a hypercholesterolemic model of atherosclerosis.

Animals↗
PubMed2000

Plasmapheresis treatment for recurrent focal sclerosis in pediatric renal allografts.

Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric renal allografts is associated with a poor graft survival. This study reports on plasmapheresis for the treatment of recurrent FSGS in pediatric renal transplant recipients. The records of 100 consecutive pediatric (age <21 years) renal transplants were reviewed. Twenty patients had FSGS as the cause of renal failure. Eight of these (40%) had a recurrence (proteinuria >1 g/m2 per day) within 1 month of transplantation. Five of six patients treated with plasmapheresis went into remission (<0.2 g/m2 per day), receiving a total of 42+/-26 (12-73) sessions, with the mean number of sessions required to achieve a remission being 24+/-17 (8-51). One patient had a second recurrence 1 year following cessation of plasmapheresis and responded to another course of plasmapheresis. The 1 patient who did not respond to plasmapheresis had a delay in initiation of therapy of 42 days. Plasmapheresis initiated within 48 h of recurrence resulted in earlier remissions and improved graft survival among our patients. Plasmapheresis appears to be effective in treating recurrent FSGS following kidney transplantation and should be started as soon as possible. The number of plasmapheresis sessions used to achieve remission should be adjusted according to response rather than adhering to a fixed protocol.

Adolescent↗
PubMed2000

Renal transplantation in patients above 60 years of age in the modern era: a single center experience with a review of the literature.

A retrospective study was conducted of 797 patients receiving renal transplants from January 1985 to March 1997. Patient and graft survival was compared for patients above and below the age of 60. Sixty-nine patients < or =60 years old received 73 kidneys. Race: 73% Caucasian, 26% Black, 1% Other. Sex: 68% M. Hypertension (19) and PCKD (15) were the most common diagnoses. Mean peak panel reactive antibody (PRA) was 37.7%. Donor age was 2 to 66 years. Mean Cold ischemic time was 28.1 hours. Follow-up was until death or until 8/30/97. Patients <60 years included: 62% Caucasian, 34% Black, 4% Other; 60% male, Mean PRA 39.3. Of the 69 study patients, 27 died: 19 with a functioning graft, 8 within one year of transplantation. Cardiovascular causes (19 patients, 72%) and infection (7 patients, 24%) were most common. Common causes of graft loss were death with a functioning graft (19) and chronic rejection (15); other causes were acute rejection and primary non-function. Univariate analysis of 18 risk factors showed CHF and past history of vascular surgery significantly (p < 0.05) affected time of return to dialysis. Multi variate analysis did not show these independent variables to be significant. Abnormal ejection fraction and presence of q waves on EKG significantly affected time to death (p < 0.05) on uni- and multi-variate analysis. After censoring patients that died with functioning grafts, difference in graft survival between > or =60 and <59 years was not significant (p > 0.2). In this study, 68% of older patients had allografts functioning at 1 year. The fact that older patients succumb over time from natural causes should not keep patients from transplantation. Immunosuppressive agents need to be limited to reduce the incidence of infection. Criteria need to be refined to define those who are at prohibitive risk, who may not be candidates for transplantation.

Age Factors↗
PubMed1998

Chronic renal allograft rejection: no response to mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) has been previously shown to prevent functional deterioration in an experimental model of chronic renal allograft rejection. METHODS: In this retrospective case-control study, patients with chronic rejection who were receiving cyclosporine or tacrolimus and who had MMF added to their immunosuppressive regimen were compared with patients with chronic rejection who were not receiving MMF. Patients were matched for serum creatinine levels and transplant duration at the time MMF was begun. RESULTS: In the MMF group, the average dose of MMF was 1482 mg/day with an average duration of 19.3 months. Over 36 months, including 12 months before MMF and up to 24 months on MMF, there was no difference in serum creatinine levels between the two groups. Cyclosporine levels and dose were no different. CONCLUSIONS: In this small, retrospective, preliminary study, adding MMF to maintenance immunosuppression provided no clear benefit to renal allograft recipients with established chronic rejection. Larger prospective randomized studies are needed.

Adult↗
PubMed1998

Renal transplantation in a heterogeneous population: the thirty-year Montefiore Medical Center experience.

Based on more than 30 years of renal transplantation experience at Montefiore Medical Center we conclude: 1. Improved patient and graft survival can be achieved in the cadaveric transplant recipient despite increasing co-morbidities. 2. Patients at the extremes of age (< 10 or > 60) can undergo renal transplantation safely, with patient and graft survival rates approaching those of the general recipient population. 3. Results of transplantation in African-Americans are as good as non African-Americans at 3 years. Beyond that point the graft survival curves diverge. Well matched (0-1 HLA mismatches) kidneys in the African-American patient do as well if not better than other ethnic groups. However, African-Americans do not receive as many well matched kidneys as others.

Adolescent↗
PubMed1997

Prevalence of asymptomatic cholelithiasis and risk of acute cholecystitis after kidney transplantation.

Prophylactic cholecystectomy for asymptomatic cholelithiasis is sometimes required before transplantation. However, there is little indication in the literature that transplant recipients are at any greater risk than individuals in the general population. Between January 1990 and December 1993, 211 renal transplant recipients underwent duplex sonography. All were asymptomatic. Twenty-one had positive findings: gallstones were found in 15 patients (7.11%) and sludge was found in 6 (2.84%). Of gallstone patients, seven (3%) were men and eight (4%) were women. One gallstone patient also had diabetes mellitus. The mean age by gender of the patients with calculi was 54 years for men and 38 years for women. Thirteen of the 15 patients with calculi (87%) have remained asymptomatic. Two patients (one diabetic) developed acute cholecystitis and underwent uncomplicated laparoscopic cholecystectomy. Patients with sludge were similar in gender and age to patients with gallstones; one patient had diabetes. No sludge patients became symptomatic. The incidence and morbidity of gallstones after kidney transplantation are low. Prophylactic cholecystectomy in asymptomatic patients before transplantation is not justified.

Acute Disease↗
PubMed1997

Nifedipine protects small intestine from cyclosporine-induced hemodynamic and functional impairment.

We have previously shown that cyclosporine (CsA) causes intestinal hemodynamic and functional impairments. In this study, we evaluated whether nifedipine protects the small intestine from such toxic side effects. Isogeneic small intestinal transplantation was performed in rats which then received one of the following two-week treatments: olive oil, 0.15 ml/kg/day i.m. as vehicle controls in group 1; nifedipine, 1 mg/kg/day i.m. in group 2; CsA, 15 mg/kg/day i.m. in group 3; and both nifedipine and CsA in group 4. Vascular resistance, whole tissue blood flow and its mucosal and serosal/muscularis distributions in both graft and recipient residual native intestines, and absorptive function were determined. The data showed that two-week treatment with CsA resulted in a marked elevation of vascular resistance from 51.0 +/- 6.8 to 72.4 +/- 11.1 U/g in the native whole tissue and from 53.7 +/- 7.2 to 78.2 +/- 12.1 U/g in the graft whole tissue, and decreases in blood flow from 1.59 +/- 0.26 to 1.11 +/- 0.17 ml/g/min in the native whole tissue and from 1.50 +/- 0.21 to 1.03 +/- 0.18 ml/g/min in the graft whole tissue and absorption from 227 +/- 36 to 166 +/- 26 mg glucose/dl. Mucosa was preferentially affected, while serosal/muscularis layers remained relatively unchanged. When nifedipine was concomitantly used with CsA, vascular resistance and blood flow values in the mucosal layer and whole intestinal tissue as well as absorptive function showed no significant differences from the baseline data. The changes observed in denervated grafts and recipient native intestines were similar. We conclude that nifedipine is effective in protecting both graft and native small intestines from CsA-induced toxicity in the rat.

Animals↗
PubMed1997

Postrenal transplant compliance from the perspective of African-Americans, Hispanic-Americans, and Anglo-Americans.

Medication compliance by patients is a subject that has attracted attention because it has been identified as the third leading cause of renal graft loss. The purpose of this study was to gather specific information about renal-transplant recipients' cognitions, emotions, and behaviors during the postrenal transplant compliance process. Data from 519 renal transplant patients were collected through mailed surveys; chart audits were conducted for 397 patients in the sample. Findings revealed that 96 (18%) of the transplant recipients had been noncompliant with immunosuppressive medications. Factors related to noncompliance included being away from home, length of time since transplant, age, gender, and ethnicity, as well as patients' beliefs regarding how long posttransplant symptoms would persist and their beliefs about the effectiveness of immunosuppressive medications. Of particular interest were the findings related to compliance by African-American patients, which challenge conventional thinking. Implications for assessing patient compliance, patient education, and further research are discussed.

Adult↗
PubMed1996

Effect of tacrolimus on hemodynamics and absorption of experimental small intestinal transplants.

We have previously reported the adverse effects of cyclosporine on small intestine transplant physiology. In this study, we report for the first time the effect of tacrolimus (FK) on graft intestinal blood flow and intramural distribution, vascular resistance, and absorptive function. Isogeneic small intestine transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedules: no treatment for 1 week in group 1; 0.6 ml/kg/day i.m. polyethylene glycol (PEG) for 1 week in group 2; 2 mg/kg/day i.m. FK for 1 week in group 3; 0.6 ml/kg/day PEG for 1 week and then 0.3 ml/kg/day for 5 weeks in group 4; 2 mg/kg/day FK for 1 week and then 1 mg/kg/day for 5 weeks in group 5. Group 6 was the same as in group 5 but FK was withdrawn for 1 week prior to assessment. Maltose absorption was measured to evaluate graft absorptive function. Blood flow and its intramural distribution to mucosal and serosal/muscularis layers were determined using the radioactive microsphere technique. Perfusion pressure was measured to calculate vascular resistance. One week of FK administration in group 3 did not change graft hemodynamics and absorption significantly. Prolonged FK treatment up to 6 weeks in group 5 resulted in a significant increase in mucosal vascular resistance (71.0 +/- 9.6 versus 47.7 +/- 6.7 U/g, P<0.01) and significant decreases in mucosal blood flow (1.14 +/- O.15 versus 1.69 +/- 0.24 ml/g/min, P<0.01) and maltose absorption (30 min after loading. 155.4 +/- 26.9 versus 216.4 +/- 29.6, P<0.01; 60 min after loading: 172.9 +/- 24.5 versus 229.1 +/- 32.6 glucose mg/dl P<0.01). The serosal/muscularis layer remained relatively unaffected. Withdrawal of FK for 1 week after prolonged treatment in group 6 resulted in restorations of all parameters measured to normal ranges. We conclude that a short course of FK is safe, but prolonged FK administration has harmful effects on the hemodynamics and function of small intestinal transplants. Complete recovery is achieved when FK is discontinued.

Animals↗
PubMed1996

Improved renal allograft survival in children treated with FK 506 (tacrolimus) rescue therapy.

FK 506 has been reported to be effective in reversing acute renal allograft rejection that is resistant to steroids and to OKT3. The contribution of FK 506 "rescue" therapy to long-term graft survival has not been determined. We report 23 children transplanted between January 1993 and December 1994, 10 of whom received FK 506 "rescue" therapy. Acute rejection was reversed in 8 of 10, with 7 of the remaining grafts still functioning after a mean follow-up of 10.9 +/- 7.8 (SD) months (range 1-26 months). The actuarial 1-year graft survival rate was 86% compared with 66% for historical controls (P < 0.05). We conclude that FK 506 may provide long-term benefits to children facing allograft loss due to acute rejection.

Adolescent↗
PubMed1995

Improved small intestinal preservation after lazaroid U74389G treatment and cold storage in University of Wisconsin solution.

The small intestine (SI) is highly sensitive to oxygen free radical-induced injury. The most common preservation solution, University of Wisconsin (UW) solution, does not adequately prevent free radical-induced injury. Lazaroids, and U74389G in particular, are a new class of compound that are potent inhibitors of superoxide-mediated lipid peroxidation. We studied the added influence of U74389G to 18-hr cold preservation of rat SI in UW solution. Three groups of rats were studied. In group 1, SI was excised and reperfused immediately. In group 2, SI was stored in UW solution at 4 degrees C for 18 hr. In group 3, U74389G was given to the SI graft before storage and again before reperfusion. Blood reperfusion of the grafts was achieved via connection to the superior mesenteric artery and portal vein of support rats. Functional recovery was assessed using a maltose tolerance test. Weight changes were calculated and histologic studies done. After 30 and 60 min of reperfusion, maltose uptake in group 3 was significantly better than that of the group 2, and returned to control levels. Significantly more tissue swelling was noted in group 3 over control, but the magnitude was less than that of group 2. Less transmural necrosis and villous blunting were noted in group 3 versus group 2; the appearance of the mucosa in group 3 approached that of group 1. We conclude that the use of U74389G treatment in addition to cold storage in UW solution improves recovery of graft function and minimizes morphologic damage to the small intestinal mucosa.

Adenosine↗