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Biomedical subjects

R V Perez

Publications and source records attributed to R V Perez.

At least 19 recordsLinked to original sources
PubMed2005

Predictive value of pretransplant inflammatory markers in renal allograft survival and rejection in children.

Pretransplant (pre-Tx) inflammation has been associated with acute rejection (AR) in adult Tx recipients. Our study was performed to determine whether a single pre-Tx serum C-reactive protein (CRP), Neopterin (Neo), and IL-12 determination could predict outcome in pediatric renal Tx recipients. Pre-Tx sera from 51 children transplanted between 1985 and 2000 were analyzed for serum CRP, Neo, and IL-12 for correlation with Tx-related variables. Endpoints were graft loss and AR. Kaplan-Meier and log-rank statistics were used to compare rejection-free and overall graft survival at different quartiles for each marker. Cox regression analysis was performed to determine the independent effects of various pre-Tx variables on the endpoints. The mean age of the children at Tx was 11 years. The mean CRP, Neo, and IL-12 were 1.3 mg/L, 1.78 ng/mL and 123 pg/mL, respectively. At last-follow-up (mean 4.9 years after Tx), 50% of the children had experienced AR and 29% had lost their grafts. The mean CRP, Neo, and IL-12 were not different between the patients with versus without AR or graft loss (P > .4 for all). Neither rejection-free survival nor graft survival was affected by CRP, Neo, or IL-12 quartiles (log-rank test). Cox regression analysis demonstrated no predictive value of any marker on the outcomes. Unlike adults, a single pre-Tx determination of inflammatory markers was not predictive of AR or graft loss in children. The pathogenesis of AR may be different in children with a lesser contribution of alloantigen-independent factors such as chronic infections.

Analysis of Variance↗
PubMed2001

Factors affecting choice of surgical residency training program.

BACKGROUND: A significant problem facing American surgery today is the lack of participation from women and minorities. In 1995 and 1996, 15.1 and 15.8% of United States general surgical residency graduates were women. Of our 71 graduates in the last 12 years, 38% were women. The aim of this study was to identify the factors influencing our residents' choice of training program and the reasons why our program has a high percentage of female graduates. METHODS: Between 1989 and 2000, 27 women and 44 men completed general surgical training at our university and 44/71 (59%) responded to our survey. The age at residency completion was 34 +/- 2.2 years for men and 33.9 +/- 2.8 years for women. Fifty-five percent of men and 30% of women went on to fellowship training; and 36% of men and 20% of women are in academia. RESULTS: Factors influencing our graduates' selection of training program are: Only 23% of men had a female faculty as their mentor, whereas 90% of women had a male faculty as their mentor during training. Only 59% of men but 80% of women (P < 0.05) agreed that female medical students need role models of successful female faculty members. Fifty-five percent of men and 45% of women would encourage a female medical student to choose surgery as a career, but 82% of men and 50% of women would encourage a male medical student to do so. Ninety-one percent of men and 85% of women would choose surgery as a career again. CONCLUSIONS: A surgical residency training program with strong leadership, good clinical experience, and high resident morale will equally attract both genders. Women may pay more attention to the program's gender mix and geographic location.

Adult↗
PubMed2001

Increased transplantation of kidneys with multiple renal arteries in the laparoscopic live donor nephrectomy era: surgical technique and surgical and nonsurgical donor and recipient outcomes.

BACKGROUND: For anatomical and technical reasons, many transplant centers restrict laparoscopic live donor nephrectomy (in contrast with open live donor nephrectomy) to left kidneys. HYPOTHESIS: This change in surgical practice increases procurement and transplantation rates of live donor kidneys with multiple renal arteries (RAs), without affecting donor and recipient outcomes. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center comparing laparoscopically procured single vs multiple-RA kidney grafts (April 1997 to October 2000). PATIENTS: Seventy-nine consecutive left laparoscopic live kidney donors and 78 transplant recipients. MAIN OUTCOME MEASURES: Donor and recipient complications and postoperative length of stay; cold and warm ischemia time; operating time; short-term and long-term graft function; and survival. RESULTS: We noted multiple RAs in 21 (27%) of all kidneys. The proportion of donors with 1 or more perioperative complications was 19% in the single-RA group vs 10% in the multiple-RA group (P was not significant). For the recipients, we noted no significant differences between groups with respect to surgical complications, quality of early and late graft function, rejection rates, graft losses (all immunologic), and graft survival. Cold and warm ischemia time and length of stay were similar for donors and recipients in both groups. Median operating times were significantly longer for the multiple-RA vs single-RA group (difference, 41 minutes for donors and 45 minutes for recipients; P<.02). CONCLUSIONS: While the introduction of laparoscopic live donor nephrectomy has significantly increased the number of grafts with multiple RAs (compared with historical open controls), this change in practice is safe for both donors and recipients from a patient outcome-based perspective. However, from an economic perspective, the longer operating time associated with multiple-RA grafts provides strong added rationale for optimization of surgical instruments and techniques to make right-sided laparoscopic nephrectomy a routine intervention.

Adult↗
PubMed2000

Dose response to a single intramuscular injection of recombinant adeno-associated virus-erythropoietin in monkeys.

BACKGROUND: Anemia is a significant problem in many disease states. Erythropoietin (Epo) has been used in the treatment of anemia associated with numerous chronic diseases. This study investigates the dose-response profiles of a single intramuscular (im) injection of a recombinant adeno-associated virus vector (rAAV) containing the Epo gene with the goal of achieving a sustained elevation of hematocrit (Hct). METHODS: Cynomolgus (cm) monkeys were given single injections of different doses of rAAV-cm-Epo. The biological effect of Epo gene expression was monitored by determining the Hct levels and circulating hormone levels by ELISA. Antibody to the rAAV capsid protein was also measured over the 41-week period of the experiment. RESULTS: Epo expression was noted only when 2 x 10(11) or more particles were injected. Epo was noted to be increased as soon as 1 week postinjection and was maximum in 6 to 8 weeks. This level of expression remained constant for nearly 20 weeks. Animals given the highest dose of rAAV developed a higher Hct over the first 8 weeks postinjection than those given an intermediate dose. However, the maximum levels of hemoglobin were the same. There was a weak correlation between amount of rAAV injected and capsid antibody response. CONCLUSIONS: AAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single im administration. Dose responses to rAAV-Epo are achievable, although a threshold inoculum of virus is necessary to produce an effect and the therapeutic window is narrow.

Anemia↗
PubMed2000

Pretransplant systemic inflammation and acute rejection after renal transplantation.

BACKGROUND: There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS: Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS: Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS: Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.

Acute Disease↗
PubMed2000

The role of percutaneous biopsy in detection of pancreatic transplant rejection.

The purpose of this study was to investigate the effectiveness and safety of percutaneous pancreatic transplant biopsy guided by ultrasound alone or with a combination of computerized tomography (CT) for pancreas localization and ultrasound for needle placement. We also compare our finding on the use of 18-gauge and 20-gauge needles for percutaneous pancreatic transplant biopsy. In 42 attempted biopsies performed on 21 patients, two different imaging modalities were used. Twenty-seven attempted biopsies were performed under the guidance of ultrasound alone, and 15 used a combination of ultrasound and CT. Of the 27 ultrasound-guided biopsies. 24 produced at least one sample adequate for histopathological analysis for an 89% biopsy success rate. Of the 15 biopsies guided by combined ultrasound and CT, 11 produced adequate samples for a 73% success rate. For all biopsies, an 83% success rate was found. In assessing the use of 18-gauge versus 20-gauge needles, 86 out of 110 tissue cores were adequate for histopathological analysis for a 78% yield. In 27 biopsy attempts using the 18-gauge needle, 75 tissue cores were obtained, for an average of 2.8 cores per biopsy. Fifty-seven pancreas samples collected using the 18-gauge needle were adequate for pathological evaluation for a 76% yield. With 15 biopsy attempts using the 20-gauge needle, 35 tissue cores were collected, for an average of 2.3 cores per biopsy. Twenty-nine pancreas specimens obtained from using the 20-gauge needle were adequate for analysis for an 83% yield. No major complications occurred. Only one incidence of minor complication was reported for a 2% complication rate. The only complication was local, mild bleeding at the biopsy site in one case. Air within the transplant pancreas as revealed by post-biopsy scans and streaky density appearing adjacent to the biopsy site occurred in a total of four cases and were not included. No complications were reported that required any invasive intervention. We conclude that percutaneous biopsy guided by ultrasound is a safe, simple, and effective method to detect pancreatic transplant rejection. Our results for biopsies compare favorably with other reported techniques in terms of effectiveness, complication rates, and ease of use. With its high success rate and low complications, ultrasound-guided percutaneous biopsy is an excellent method to sample pancreatic transplant.

Adult↗
PubMed2000

Effect of intravascular volume expansion on renal function during prolonged CO2 pneumoperitoneum.

OBJECTIVE: To evaluate whether intravascular volume expansion would improve renal blood flow and function during prolonged CO2 pneumoperitoneum. SUMMARY BACKGROUND DATA: Although laparoscopic living donor nephrectomies have a considerably reduced risk of complications for the donors, significant concerns exist regarding procurement of a kidney in the altered physiologic environment of CO2 pneumoperitoneum. Recent studies have documented adverse effects of CO2 pneumoperitoneum on renal hemodynamics. METHODS: Renal and systemic hemodynamics and renal histology were studied in a porcine CO2 pneumoperitoneum model. After placement of a pulmonary artery catheter, carotid arterial line, Foley catheter, and renal artery ultrasonic flow probe, CO2 pneumoperitoneum (15 mmHg) was maintained for 4 hours. Pigs were randomized into three intravascular fluid protocol groups: euvolemic (3 mLkg/hour isotonic crystalloid), hypervolemic (15 mL/kg/hour isotonic crystalloid), or hypertonic (3 mL/kg/hour isotonic crystalloid plus 1.2 mL/kg/hour 7.5% NaCl). RESULTS: In the euvolemic group, prolonged CO2 pneumoperitoneum caused decreased renal blood flow, oliguria, and impaired creatinine clearance. Both isotonic and hypertonic volume expansions reversed the changes in renal blood flow and urine output, but impaired creatinine clearance persisted. CONCLUSIONS: Intravascular volume expansion alleviates the effects of CO2 pneumoperitoneum on renal hemodynamics in a porcine model. Hypertonic saline (7.5% NaCl) solution may maximize renal blood flow in prolonged pneumoperitoneum, but it does not completely prevent renal dysfunction in this setting. This study suggests that routine intraoperative volume expansion is important during laparoscopic live donor nephrectomy.

Animals↗
PubMed1999

Improvements in diabetic microangiopathy after successful simultaneous pancreas-kidney transplantation: a computer-assisted intravital microscopy study on the conjunctival microcirculation.

A computer-assisted intravital microscopy technology has been developed to noninvasively and objectively study diabetic microangiopathy in the conjunctival microcirculation of type-1 diabetics. Quantitative characterization of the conjunctival microcirculation was performed on 12 patients pre- and 18 months postsimultaneous pancreas-kidney transplantation (SPK). Healthy nondiabetic volunteers (n=12), solitary kidney (K) transplanted type-1 diabetics (n=5), and nontransplanted type-1 diabetics (n=12) served as controls. Pre-SPK diabetics showed abnormal-sized venules (diameter=66+/-7 microm) and reduced presence of arterioles (arteriole length/area=18+/-6 microm(-1)) compared with nondiabetic controls (53+/-4 microm; 31+/-8 microm(-1); P<0.05). The computed vascular perfusion capacity of the conjunctival microvasculature was diminished in the same patients (pre-SPK diabetics=49+/-9%; nondiabetic healthy controls=71+/-6%; P<0.05). Significant improvement in microangiopathy was observed in all post-SPK diabetics (diameter=58+/-6 microm; arteriole length/area=26+/-9 microm(-1); vascular perfusion=63+/-8%; P<0.05) 18 months post-SPK. Blood flow velocities in the conjunctival microcirculation in the same post-SPK patients showed noticeable but not significant improvements (nondiabetic controls=2.94+/-0.57 mm/sec; pre-SPK=1.23+/-0.49 mm/sec; post-SPK=1.65+/-0.42 mm/sec). The solitary kidney transplant controls (post-K) showed no significant improvements in diabetic microangiopathy, confirming the unique role of the pancreas in SPK. In general, significant improvements (P<0.05) in diabetic microangiopathy were observed in all 12 diabetics 18 months post-SPK but not in the controls.

Adult↗
PubMed1999

Dissection of an iliac artery conduit to liver allograft: treatment with an endovascular stent.

Hepatic artery thrombosis remains one of the most serious complications after orthotopic liver transplantation. Sepsis, biliary leakage and strictures, and retransplantation are often the result of this devastating complication. Because retransplantation or reoperation is sometimes not possible or advisable, other means of reestablishing hepatic artery continuity are desirable. We describe a liver transplant recipient who developed a dissection of an iliac artery conduit after retransplantation that was treated with fibrinolytic therapy followed by successful placement of an endovascular stent.

Adult↗
PubMed1998

Selective targeting of Kupffer cells with liposomal butyrate augments portal venous transfusion-induced immunosuppression.

BACKGROUND: Enhanced Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2 (PGE2) has been shown to be a mechanism of the immunosuppressive effect of portal venous transfusions (PVT). Butyrate, a four-carbon short-chain fatty acid, has received increased attention because of its ability to enhance gene transcription. This study tested the hypothesis that the intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production and thus augments the immunosuppressive effect of PVT. METHODS: Butyrate was incorporated into liposomes and administered intravenously to Lewis rats. Control rats were administered liposomes without butyrate. Twenty-four hours after liposome injection, rats were administered a PVT of 1 ml of Wistar-Furth blood. Kupffer cells were isolated, and PGE2 and tumor necrosis factor-alpha levels were measured in the culture medium after 24 hr. Additionally, Kupffer cells from butyrate-treated and control animals were added to one-way mixed lymphocyte reaction cultures. RESULTS: Intrahepatic delivery of butyrate via liposomes increased Kupffer cell PGE2 (3800+/-1220 vs. 1010+/-119 pg/ml, P<0.05) and decreased tumor necrosis factor-alpha (1670+/-81 vs. 3360+/-415 pg/ml, P<0.01) production as compared with controls. Butyrate also augmented the Kupffer cell-mediated immunosuppression as demonstrated by significant depression of the mixed lymphocyte reaction (690+/-119 vs. 3850+/-148 cpm, P<0.01). CONCLUSION: The results support the hypothesis that intrahepatic delivery of butyrate enhances Kupffer cell PGE2 production, and specific targeting of Kupffer cells with liposomes containing immunomodulating agents such as butyrate may be a useful means of augmenting immunosuppression protocols in organ transplantation.

Animals↗
PubMed1997

Portal venous transfusion up-regulates Kupffer cell cyclooxygenase activity: a mechanism of immunosuppression in organ transplantation.

Portal venous transfusions (PVTs) of blood have been shown to induce significant immunosuppression in animal models of organ transplantation. A proposed mechanism of PVT-induced immunosuppression is via alteration of Kupffer cell arachidonic acid metabolism with increased secretion of the suppressive metabolite prostaglandin E2 (PGE2). This study assessed the hypothesis that PVT increases Kupffer cell PGE2 production via up-regulation of Kupffer cell phospholipase A2 (PLA2) as well as constitutive (COX1) and inducible (COX2) cyclooxygenase. Kupffer cells from Lewis rats were harvested 1 hr after PVT with either 1 ml of Wistar-Furth blood, systemic transfusion (SVT), or saline via portal vein (PVSal). After lipopolysaccharide stimulation, 24-hr Kupffer cell supernatant fractions were assayed for PGE2. PGE2 was increased after SVT (1465+/-234 pg/ml) compared with PVSal (597+/-99; P<0.01). PVT increased Kupffer cell PGE2 (5370+/-533; P<0.001 vs. SVT and vs. PVSal) even more substantially. Kupffer cells from PVT-treated rats were then cultured in the presence of inhibitors of PLA2, COX1, or COX2. When Kupffer cells were treated with mepacrine to inhibit PLA2 (5575+/-453 pg/ml), PGE2 production was not different from that by PVSal-treated controls (6467+/-614 pg/ml), but when Kupffer cells were incubated in the presence of the COX1 inhibitor flurbiprofen (3512+/-407 pg/ml) or the COX2 inhibitor nimesulide (2800+/-830 pg/ml), production was decreased 46.7% and 56.7%, respectively, over control activity without added inhibitor. PVT also increased Kupffer cells COX1 and COX2 mRNA as measured by Northern blot. Heart transplants were then performed from Wistar-Furth donors into Lewis recipients at the time of PVT, SVT, PVSal, or PVT + indomethacin (COX1/2 inhibitor). PVT prolonged allograft survival (12.0+/-0.9 days) compared with PVSal (6.3+/-0.3; P<0.01) or SVT (6.3+/-0.3; P<0.04). Indomethacin shortened graft survival when given with PVT (6.5+/-0.3 days). In summary, PVT increased Kupffer cell PGE2 production, up-regulated transcription of Kupffer cells COX1 and COX2 mRNA, and prolonged cardiac allograft survival. COX1/2 inhibition abrogated the effect of PVT. The results indicated that the immunosuppressive effect of PVT may be mediated by up-regulation of Kupffer cell COX1 and COX2. Manipulation of Kupffer cell arachidonic acid metabolism may be useful in augmentation of PVT-induced immunosuppression.

Animals↗