PubMed Health⌕ Search

Biomedical subjects

S Greenstein

Publications and source records attributed to S Greenstein.

At least 19 recordsLinked to original sources
PubMed2005

No-load sirolimus with tacrolimus and steroids is safe and effective in renal transplantation.

AIM: Basiliximab (BX) induction, tacrolimus (TAC), and steroids have sharply reduced acute cellular rejection at our institution. However, late graft loss has continued, for which sirolimus (SL) was introduced into the protocol. METHODS: From July 1, 2001 to December 31, 2003, 152 live donor (LD) renal transplant recipients received TAC (level 15 to 20 ng/mL) and steroids, with BX induction. One hundred twenty-two patients (Group 1) received SL (3 mg/d African-americans; 2 mg/d for others) starting on days 2 and 3. The SL level was adjusted to 8 to 10 ng/d, usually by weeks 3 to 4 posttransplant. The TAC doses were then progressively reduced. Records were reviewed for demographics, immunosuppressive drug levels, serum cholesterol and blood pressure, and complications. Graft and patient survival rates were calculated. Comparison was made to 53 LD recipients transplanted from July 1, 1998, to June 30, 2001 (Group 2) receiving BX, steroids and TAC, without SL. Recipients of deceased donor kidneys were excluded because of variability in kidney quality, ischemic time, and patient management. RESULTS: Demographics were similar between groups: African Americans, 25% to 35%; mean age 36 years; mean HLA mismatch 3.7. Wound problems and infection were minimal in both groups. Mean serum creatinine and cholesterol and systolic and diastolic blood pressure measured periodically up to 1 year were similar, as was the incidence of rejection. In 25% of patients, SL was discontinued. CONCLUSIONS: Gradual introduction of SL appears to be associated with minimal wound problems. With more aggressive reduction in TAC, better renal function, and better long-term graft survival may be attainable. We currently lower TAC levels to 5 ng/mL by 3 months.

Adult↗
PubMed2003

Primary intestinal posttransplant T-cell lymphoma.

There have been only five reported cases of primary posttransplant T-cell lymphoma. We report the first case associated with the use of sirolimus (Rapamycin, Wyeth-Ayerst, Philadelphia, PA). The patient, receiving prednisone, cyclosporine, and sirolimus treatment, developed ascites, diarrhea, and weight loss 7 months after his second renal transplant. Tissue obtained at laparotomy established the diagnosis of primary T-cell lymphoma. Latent membrane protein-1 for Epstein-Barr virus was negative, but in-site hybridization test for Epstein-Barr-encoded RNA was positive. Despite aggressive chemotherapy, the patient died 8 months posttransplant. This is the sixth reported case of primary intestinal posttransplant T-cell lymphoma, but it is the first case associated with the use of sirolimus. The incidence of posttransplant lymphoproliferative disease in patients receiving sirolimus should be studied.

Fatal Outcome↗
PubMed2001

Basiliximab induction improves the outcome of renal transplants in children and adolescents.

Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with <or=3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels.

Adolescent↗
PubMed2000

Evaluation of a multivariate model predicting noncompliance with medication regimens among renal transplant patients.

BACKGROUND: Because noncompliance with medication regimens is a major cause of renal allograft failure, we evaluated the stability over time of two logistic regression models (sets of variables) that predict noncompliance with immunosuppressive regimens. METHODS: Models were based on questionnaire data from 1402 patients (all over 18, receiving cyclosporine or a cyclosporine-like replacement drug, and with a functioning renal graft). The same questionnaire was completed by a subset of 548 (39.1%) patients approximately 18 months later. The goodness of fit of each model to the new data set was tested. RESULTS: The noncompliance logistic regression model including patient beliefs as well as patient and transplant characteristics was an excellent fit to the second data set. A noncompliance model composed of only patient and transplant characteristics fit the new data set less well. CONCLUSIONS: Clinicians and educators need to take explicit account of renal transplant patients' attitudes when evaluating risks of noncompliance and when developing interventions and educational programs to minimize noncompliance.

Adult↗
PubMed2000

Reversible sensorineural hearing loss following administration of muromonab-CD3 (OKT3) for cadaveric renal transplant immunosuppression.

This prospective study is a follow-up to a case report noting reversible sensorineural hearing loss after administration of OKT3 for immunosuppression in a steroid-resistant renal cadaveric transplant patient who was rejecting his transplant. The objective is to determine the interval estimate for incidence of sensorineural hearing loss following treatment with OKT3. Seven patients were admitted to the Renal Transplant Service at Montefiore Medical Center from July 1996 to July 1997 with steroid-resistant rejection of renal cadaveric transplants and received OKT3 as an immunosuppressant. All 7 patients received 3 audiograms: the first, prior to the administration of the first dose of OKT3, the second, 48 to 72 hours after administration of OKT3, and the third, approximately 2 weeks after administration of OKT3. Five of the 7 patients (71%) demonstrated a sensorineural hearing loss of 15 dB or greater at frequencies of 8 to 12 kHz. Four of the 5 patients with audiographic changes had near-complete to complete recovery of their high-frequency thresholds after discontinuation of the drug regimen. In conclusion, OKT3 can cause sensorineural hearing loss. This side effect is mainly reversible after 2 weeks following discontinuation of the drug. Patients receiving OKT3 should be forewarned of this possible side effect prior to the administration of OKT3.

Audiometry, Pure-Tone↗
PubMed2000

Fas activation reduces neutrophil adhesion to endothelial cells.

Polymorphonuclear neutrophils (PMN) express apoptotic markers and lose effector functions including adhesion, chemotaxis, and phagocytosis when cultured overnight. Although the loss of function correlates with apoptosis, it is not clear if functions are lost before an early marker of apoptosis, the display of phosphatidylserine (PS), targets PMN for removal by phagocytic cells. To address this question, freshly isolated PMN were treated with Fas-activating antibodies to induce apoptosis rapidly. Early markers of apoptosis and PMA-stimulated adhesion to endothelial cells were measured. After 1 h of Fas exposure, only 16% PMN had externalized PS. In contrast, Fas activation reduced PMA-stimulated adhesion between 68 and 27% depending on PMA concentration. The loss of adhesion was accompanied by a reduction in beta2 integrin expression and receptor clustering. These results indicate that the Fas-induced loss of adhesion may precede PS externalization and could limit participation in the inflammatory response before PS externalization targets PMN for removal.

Animals↗
PubMed2000

Fifteen-year experience with pediatric renal transplantation at the Montefiore Medical Center.

At Montefiore Medical Center, 140 pediatric recipients have received 155 renal allografts over a 16-year period with an overall 6% mortality. Graft survival was not significantly different based upon race or sex of recipient. Graft survival was significantly better for first time transplants and the youngest recipients. Graft survival was significantly improved using Tacrolimus immunosuppression.

Academic Medical Centers↗
PubMed1999

MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer.

The products of the MUC1 gene are known to be highly expressed in human breast cancer cells. The best characterized MUC1 protein is a polymorphic, type 1 transmembrane molecule containing a large extracellular domain composed primarily of a variable number of 20 amino acid tandem repeats. We have recently identified a novel protein product of the MUC1 gene, the MUC1/Y protein, that is also a transmembrane protein but is devoid of the tandem repeat array and its immediate flanking sequences. To analyze its expression in tumor cells we generated monoclonal antibodies directed against the MUC1/Y extracellular domain (anti-MUC1/Yex MAbs). Epitope mapping identified the MAb, 6E6, which recognized the MUC1/Y isoform with exquisite specificity- the repeat-array-containing MUC1 isoform could not compete out this immunoreactivity. A 30mer peptide which is unique for MUC1/Y and corresponds to the "join" region generated by the MUC1/Y specific splice, abrogated all 6E6 MAb immunoreactivity towards MUC1/Y. Immunoprecipitation of the MUC1/Y protein with 6E6 MAbs revealed that, in contrast with the proteolytic cleavage of the tandem-repeat-array-containing MUC1 isoform, MUC1/Y is not cleaved. Flow cytometry analyses using the 6E6 MAbs demonstrated that the MUC1/Y isoform is expressed on the cell surface of both MCF-7 breast cancer cells and malignant epithelial cells present in effusions obtained from breast and ovarian cancer patients. Our results unequivocally establish that the MUC1/Y protein is expressed on the surface of breast cancer cells and cells of other epithelial malignancies. The anti-MUC1/Y MAbs described here can target MUC1/Y expressing tumor cells in vivo and are likely to be important reagents both for epithelial tumor diagnosis and immunotherapy.

3T3 Cells↗
PubMed1999

The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein.

MUC1 proteins, some of which contain a mucin-like domain and others lacking this region, can be generated from the human breast cancer-associated MUC1 gene by alternative splicing. The MUC1/Y isoform is devoid of the mucin domain and is a cell membrane protein that undergoes transphosphorylation on both serine and tyrosine residues. We have identified cognate binding proteins that specifically interact with the extracellular domain of MUC1/Y. Coimmunoprecipitation analyses clearly revealed the presence of complexes composed of MUC1/Y and its cognate binding proteins in primary breast tumor tissue. MUC1/Y-expressing mammary tumor cells can be specifically targeted, in vivo, with the labeled cognate binding protein. The k(D) of MUC1/Y for its binding proteins was estimated as 1.2 nM. The MUC1/Y binding proteins are also derived from the MUC1 gene and represent the secreted mucin-like polymorphic MUC1 proteins MUC1/SEC and MUC1/REP, which contain a tandem repeat array. Whereas nonposttranslationally modified MUC1/Y bound efficiently to MUC1/SEC, the latter mucin-like protein had to be posttranslationally modified in a cell-type specific manner to bind MUC1/Y. The interaction of MUC1/Y with MUC1/SEC has important biological functional correlates: (a) it induces MUC1/Y phosphorylation; and (b) it has a pronounced effect on cell morphology. These findings suggest that MUC1/Y and MUC1/SEC form an active receptor/ cognate binding protein complex that can elicit cellular responses. The proteins comprising this complex are, thus, generated by alternative splicing from one and the same gene, namely the MUC1 gene.

Animals↗
PubMed1999

Safety of Neoral conversion in maintenance renal transplant patients: A one-year, double-blind study. NOVARTIS OLN-353 Study Group.

BACKGROUND: Despite the improved pharmacokinetic characteristics of Neoral, some centers have encountered difficulty with the conversion of some patients from Sandimmune to Neoral and have reported precipitation of toxicity and rejection. METHODS: We conducted a randomized, double-blind, parallel-group, multicenter prospective study of stable maintenance renal transplant patients to compare the safety and tolerability of converting from Sandimmune to Neoral (N = 132) versus continuing Sandimmune (N = 130). Patients were studied for one year. The cyclosporine (CsA) dose was adjusted as necessary to maintain site-specific trough whole blood levels. RESULTS: During the study, dose adjustments were frequent in both groups: 67% Neoral versus 65% Sandimmune patients. At study completion, the mean trough CsA levels were comparable; the dose change-from-baseline did not differ statistically between groups. Fewer Neoral (87.1%) than Sandimmune (95.4%) patients reported adverse events, and serious adverse events were comparable. Adverse events related to CsA were not more common in the Neoral group. Renal function measures also implied comparability of the two treatments. Three Neoral versus five Sandimmune patients experienced acute rejection; two Neoral versus five Sandimmune patients experienced chronic graft dysfunction. Two septic deaths occurred in the Neoral group. No grafts were lost. CONCLUSIONS: With careful monitoring, conversion of maintenance renal transplant patients to Neoral can be safely accomplished.

Adult↗
PubMed1999

Compliance and noncompliance in kidney transplant patients: cues for transplant coordinators.

Maximizing kidney transplant patients' long-term compliance with immunosuppressants is a major challenge to transplant coordinators. Although previous research has found substantial proportions of recipients to be noncompliant, predictors of noncompliance and characteristics of noncompliers remain unclear. In this study of more than 1400 kidney transplant patients, we found noncompliance to be associated with patient and transplant characteristics and with patient beliefs concerning the efficacy of immunosuppressants. Three distinct profiles of noncompliers were identified: accidental noncompliers, invulnerables, and decisive noncompliers. This information can be used by transplant coordinators to recognize cues that predict noncompliance and to work with at-risk patients to forestall or remedy noncompliant behavior.

Adult↗
PubMed1998

Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study.

BACKGROUND: Noncompliance with medication is a major cause of renal allograft failure among adult renal transplant patients. We summarize previous studies of noncompliance and report results of a large, multicenter survey designed to identify variables that (1) affect the likelihood of compliance with immunosuppressive medication regimens and (2) distinguish among noncompliant patients. METHODS: Questionnaires were distributed to 2500 patients at 56 U.S. transplant centers. Compliance was determined by patient responses to questions concerning whether, within the previous 4 weeks, one or more doses of immunosuppressive medications had been missed. Independent variables included patient and transplant characteristics, memories of dialysis, posttransplant symptoms and beliefs, and beliefs concerning the efficacy and importance of immunosuppressants. RESULTS: The incidence of noncompliance reported by the 1402 respondents was 22.4%. A logistic regression model that included age, occupation, time since transplant, and three medication-related beliefs was most predictive of the likelihood of compliance. Donor type and histories of diabetes and of infection entered the multivariate model when belief-related variables were excluded. Cluster analyses identified three distinct profiles of noncompliers: accidental noncompliers, invulnerables, and decisive noncompliers. CONCLUSIONS: Results of this study, which included nearly three times more patients than the largest previously reported study, can be used by clinicians to identify patients likely to become noncompliant, by researchers to develop randomized, prospective clinical trials of interventions designed to increase compliance, and by educators to tailor patient education programs.

Adult↗
PubMed1997

Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function.

The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not polymorphic. Despite their documented importance in signal transduction processes, the relative expression of the 2 isoforms in epithelial tumors is unknown. Using antibody reagents which recognize different MUC1 domains, the expression of these isoforms in malignant epithelial cells has been evaluated. A comparison of the amounts of the 2 isoforms revealed preferential expression of the novel MUC1/Y protein in breast cancer tissue samples. Furthermore, although the MUC1/REP protein is almost undetectable in HeLa cervical adenocarcinoma epithelial cells, the MUC1/Y isoform is extensively expressed in these cells. The presence of the MUC1/Y sequence as well as that of an additional tandem-repeat-array-lacking isoform, designated MUC1/X, were demonstrated by reverse transcriptase PCR amplification of RNA extracted from HeLa and ovarian carcinoma cells. It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation. We present here data demonstrating that MUC1/Y isoform expression increases the tumorigenic potential of DA3 mouse mammary epithelial cells; in contrast, potentiation of tumorigenicity is not observed with MUC1/REP expression. Our studies thus demonstrate that expression of the MUC1 gene in epithelial tumors can give rise to substantial levels of MUC1 proteins devoid of the tandem repeat array, which are generated by alternative splicing mechanisms.

Amino Acid Sequence↗
PubMed1996

The clinical effectiveness and financial impact of utilizing peripheral blood progenitor cells as rescue therapy following autologous bone marrow transplant.

The use of peripheral blood progenitor cell transplant as rescue therapy after high-dose chemotherapy and autologous bone marrow transplant significantly decreases transfusion, laboratory, room, and total charges. An improvement in clinical indicators also points toward decreased patient morbidity. Additional cost reductions may be realized by greater utilization of outpatient care, thereby further reducing room and total charges.

Analysis of Variance↗
PubMed1996

The effect of donor gender on renal allograft survival.

Donor gender plays a role in the outcome of renal transplantation, but the mechanisms responsible for this effect are unclear. In this study, actuarial graft survival in 1049 recipients transplanted at Montefiore Medical Center between 1979 and 1994 was examined. It was found that donor gender had no influence on graft survival in recipients treated with precyclosporine immunosuppressive agents. In contrast, graft survival time was greater in cyclosporine-treated recipients of male donor kidneys compared with female kidneys (p < 0.05). This survival time difference was evident in the early post-transplant period and was entirely accounted for by the survival advantage of kidneys from white male donors. There was no gender-related difference in graft survival time among recipients of African-American donor kidneys. Recent attention has focused on the hypothesis that a mismatch between female donor kidney nephron supply and male recipient functional demand results in hyperfiltration-mediated glomerular injury and that this is responsible for reduced survival time of female allografts. Any hypothesis purporting to explain gender-related differences in graft survival time must take into account this study's observations that the donor-gender effect was observed only in cyclosporine-treated recipients, was not seen in African-American donors, appeared soon after renal transplantation, and did not increase progressively with time. These observations are most consistent with the hypothesis that gender-related differences in graft survival time may reflect differences in susceptibility to cyclosporine nephrotoxicity or differences in the therapeutic response to cyclosporine.

Black People↗
PubMed1994

Once daily loratadine versus astemizole once daily.

This study was designed to compare the efficacy and safety of loratadine and astemizole for the treatment of seasonal allergic rhinitis. A total of 167 adult patients with seasonal allergic rhinitis was enrolled in a randomized double-blind, parallel group study. Patients were treated once daily for 2 months during a spring allergy season. Both treatment groups showed significant reduction of symptoms (P < .01) from baseline. The physicians' and patients' evaluations of response to treatment were generally higher for loratadine than astemizole but only reached statistical significance (P < .05) at the 1-week evaluation. Astemizole-treated patients showed statistically significantly more weight gain than did loratadine-treated patients. Loratadine and astemizole were comparable in reducing the signs and symptoms of seasonal allergic rhinitis. Both treatments were well tolerated, although less weight gain was observed in patients treated with loratadine.

Administration, Oral↗
PubMed1989

Late failure of reversed vein bypass grafts.

Late failure of reversed vein bypass grafts is preceded by the appearance of stenotic lesions, which progress to total occlusion. These lesions appear either as intrinsic graft lesions or as new arteriosclerotic lesions in contiguous arteries. The present study summarizes the University of Pennsylvania experience with these lesions in 521 vein grafts inserted from 1979 to 1985. The grafts were grouped according to the site of the distal anastomosis; 231 above-knee popliteal (FP AK), 171 below-knee popliteal (FP BK), and 119 tibial (FT). The overall incidence of stenotic lesions was essentially identical with the three grafts (21%), but the relative incidence of intrinsic graft to arterial lesions was higher with the more distal grafts. The most common graft lesions developed adjacent to the proximal anastomosis, which is the narrowest part of a reversed vein graft. The popliteal artery was the most common site of outflow stenosis. There was negligible incidence of tibial lesions. The most common inflow arterial lesion was located in the common femoral and iliac arteries. The superficial femoral artery (SFA) was a rare site of inflow stenosis, even though it was at risk because 96 grafts originated from the SFA or popliteal artery. Sixty-seven per cent of the graft and 52% of the arterial lesions were treated successfully by percutaneous transluminal angioplasty; the rest had minor surgical revisions. This resulted in a 19%, 10%, and 9% improvement in 5-year patency for the FT, FP BK, and FP AK bypasses. These results justify an aggressive policy of graft surveillance to identify and treat stenotic graft lesions before graft occlusion.

Graft Occlusion, Vascular↗