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Biomedical subjects

E Benedetti

Publications and source records attributed to E Benedetti.

At least 73 records · Page 4Linked to original sources
PubMed1999

Successful living related simultaneous pancreas-kidney transplant between identical twins.

Simultaneous pancreas-kidney transplant from living donors has been recently proposed as an effective therapeutic option in selected uremic patients with type I diabetes. We report the first simultaneous pancreas-kidney transplant performed between identical twins. Posttransplant, the recipient has been maintained on low dose cyclosporine to avoid recurrent auto-immune insulitis. At the 1-year follow-up, both donor and recipient are well with normal renal function and excellent glucose control. Simultaneous pancreas-kidney transplant between identical twins can be performed successfully using cyclosporine to prevent recurrent auto-immune insulitis.

Adult↗
PubMed1999

Activation and repression of the 2-5A synthetase and p21 gene promoters by IRF-1 and IRF-2.

The Interferon Regulatory Factors-1 and -2 (IRF-1 and IRF-2) were originally identified as transcriptional regulators of the interferon (IFN) and IFN-stimulated genes. These factors also modulate immune response and play a role in cell growth regulation. In this study we analysed the effect of the ectopic expression of IRF-1 and IRF-2 on the regulation of two potential IRF target genes involved in cell growth regulation, 2-5A synthetase and p21 (WAF/CP1), both of which contain consensus binding sites for IRF family members within their promoters. Following ectopic expression, IRF-1 transactivated 2-5A synthetase and p21 genes, an effect that was counterbalanced by concomitant ectopic expression of IRF-2. These effects were mediated by direct binding of IRF to the gene promoters. A construct expressing an IRF-2 antisense (FRI-2) was able to revert the inhibitory effect of IRF-2 on the IRF-1 transactivation. IRF-1 also induced expression of its homologous repressor IRF-2 as indicated by EMSA analysis using an IRF-E probe from the IRF-2 promoter; and by cotransfection of IRF-1 together with an IRF-2 promoter CAT construct. Therefore, the induction of IRF-1 by IFNs or other stimuli acts as a transactivator of genes involved in cell growth regulation, as well as of its own repressor IRF-2, thus providing autoinhibitory regulation of IRF-1 activated genes.

2',5'-Oligoadenylate Synthetase↗
PubMed1999

A prospective randomized trial comparing the efficacy of tacrolimus versus cyclosporine in black recipients of primary cadaveric renal transplants.

BACKGROUND: We performed a prospective randomized trial to compare the efficacy and safety of tacrolimus (FK506) versus cyclosporine (CSA) in black primary cadaveric renal transplant (CRT) recipients. METHODS: Between December 1994 and February 1997, 35 black primary CRT recipients were enrolled in this trial. All patients received 7 days of induction therapy with OKT3. Fourteen patients received FK506 and prednisone only. Twenty-one patients received CSA, azathioprine, and prednisone. The two groups were comparable in terms of age, gender, plasma renin activity, human leukocyte antigen mismatches, and cause of renal failure. RESULTS: Patient and graft survival were 12 of 14 (86%) for the FK506 group and 20 of 21 (95%) for the CSA group (P = 0.71). Three patients died owing to cardiac events with functioning grafts. Acute rejection was 2 of 14 (14%) for the FK506 and 8 of 21 (38%) for the CSA group (P = 0.25). Two other patients on CSA were converted to FK506 as rescue for OKT3-resistant rejection. Mean serum cholesterol at 1 year was 198 +/- 45 mg/dL for the FK506 group and 244 +/- 49 mg/dL for the CSA group (P = 0.03). Mean serum creatinine at 1 year was 1.39 +/- 0.38 mg/dL for the FK506 group and 1.94 +/- 0.64 mg/dL for the CSA group (P = 0.02). CONCLUSION: Patient and graft survival were similar in both groups at 1 year posttransplant. Although statistically not significant, the incidence of acute rejection was lower in the FK506 group. Furthermore, FK506-treated patients had significantly lower serum creatinine and cholesterol levels at 1 year posttransplant.

Adult↗
PubMed1999

A new solid-phase synthesis of oligonucleotides 3'-conjugated with peptides.

A convenient 'on line' solid-phase synthesis of oligonucleotides conjugated at the 3'-end with peptides by means of a polymeric support linking the first nucleoside via the base has been developed. A 17-mer designed for antisense experiments against HIV-1, linking at the 3'-terminus the tripeptide Gly-Gly-His, was prepared in good yields and characterized by MALDI-TOF mass spectrometry.

Chemistry↗
PubMed1999

Comparison of rejection rate and functional outcome of small bowel transplantation alone or in conjunction with the ileocecal valve versus combined small and large bowel transplantation.

Preservation of the ileocecal valve improves absorptive function and decreases the amount of small bowel needed for survival in patients with short gut syndrome. We compared the results of small and large bowel transplant (SLBTx), small bowel transplant only (SBTx), and SBTx with the ileocecal valve (ICVTx) in a porcine model. Total enterectomy was performed on 18 Yorkshire-Landrace pigs followed by orthotopic SBLTx (n = 6), SBTx (n = 6), and ICVTx (n = 6). A jejunostomy and an ileostomy were constructed for biopsies. Overall mean survival was 17 d with no statistically significant difference between groups. Rejection was seen in 6/6 SLBTx, 4/6 SBTx, and 4/6 ICVTx recipients. Acute rejection was seen in 84.3% of SLBTx, 52.3% of SBTx, and 42.5% of the ICVTx mucosal biopsy samples. Two cases of intra-abdominal infection were in the ICVTx group only. Weight loss was 147 g/d in the SLBTx group, 643 g/d in the SBTx group, and 393 g/d in the ICVTx group. While the functional outcome after SLBTx and ICVTx was noticeably better than the SBTx group, the increased rejection and intra-abdominal infection rates make transplanting the large bowel or the ileocecal valve a less attractive clinical option.

Acute Disease↗
PubMed1999

Is the presence of surgically treatable coronary artery disease a contraindication to liver transplantation?

Advanced coronary artery disease has been traditionally considered an absolute contraindication to orthotopic liver transplantation where chronic liver failure significantly increases the surgical risk for coronary artery bypass grafting. Performing a simultaneous coronary artery bypass grafting and liver transplant is a theoretically attractive strategy in liver transplant candidates with coronary artery disease in need of revascularization. In the present article, we report a successful simultaneous coronary artery bypass grafting and orthotopic liver transplant with 1-yr post-operative follow-up and we discuss the rationale for this approach. In selected cases, the presence of advanced coronary artery disease should not be considered an absolute contraindication to liver transplantation.

Carcinoma, Hepatocellular↗
PubMed1999

Laparoscopic drainage of giant lymphocele after renal transplantation.

Lymphocele is a relatively frequent complication of kidney transplantation. A 46-year-old man presented 2 years after kidney transplantation with a giant septated lymphocele. The patient underwent successful laparoscopic drainage of the collection and was discharged home on the day of the procedure. Laparoscopic drainage is a safe and effective treatment for complex lymphocele after kidney transplantation.

Drainage↗
PubMed1999

Long-term outcome of a prospective trial of steroid withdrawal after kidney transplantation.

BACKGROUND: Steroid withdrawal (SW) after kidney transplantation is desirable to avoid associated serious side effects. We studied the long-term outcome of a group of kidney transplant recipients who underwent SW. METHODS: Between 1991 and 1993, kidney transplant recipients (N = 12) who had posttransplantation diabetes were entered in a prospective trial of SW. These patients were compared with a demographically similar comparison cohort (N = 66). End points of the study were patient and graft survival, incidence of late acute and chronic rejection, and changes in diabetes management. RESULTS: Previously published data from the SW group at 15 months of follow-up indicated improvement in diabetes control without any adverse effect on patient or graft actuarial survival. At long-term follow-up (mean, 56 months) the improvement in diabetes management was not detectable. The incidence of late acute rejection in SW and cohort groups was 42% and 8%, respectively (P = .006). Likewise, the incidence of chronic rejection in the SW versus cohort group was 42% and 12%, respectively (P = .014). CONCLUSIONS: Although SW appeared to be successful initially, our long-term data indicate that SW significantly increases the risk of late acute rejection and chronic rejection episodes without benefits in posttransplantation diabetes management. Steroid withdrawal in patients with posttransplantation diabetes should be approached with caution.

Acute Disease↗
PubMed1999

[Mucoepidermoid bronchial tumor with an unusual radiologic presentation].

We report a case of low-grade malignant mucoepidermoid bronchial tumor in a 21-year-old woman who presented with hemoptysis. There was a striking radiological presentation with a unilateral clear radiograph. Lung scintigraphy demonstrated perturbed ventilation and perfusion of the left lung. Pulmonary angiography only showed diminished peripheral vascularization. The main vessels were clear. These anomalies fit the radiological category of air trapping accompanied by probably hypoxic pulmonary vasoconstriction. Mucoepidermoid tumors account for only 0.5-1% of all primary lung tumors. They are found in adults as well as in children. There are two clear-cut histological forms with very different prognosis. The tumors of high-grade malignancy are considered as undifferentiated carcinomas and should be treated as such. The prognosis is much better for tumors of low-grade malignancy and current treatment is surgical in the absence of recurrence after isolated endoscopic treatment.

Adult↗
PubMed1999

Rejection pattern of simultaneously transplanted cardiac and skeletal muscle grafts in a rat model.

BACKGROUND: We studied the correlation of cardiac and skeletal muscle allograft rejection in a rat model to assess the feasibility of using biopsies from simultaneously transplanted skeletal muscle for surveillance of cardiac graft rejection. METHODS: Thirty Lewis rats (RT1l)) underwent simultaneous heterotopic heart and cutaneous maximus flap (HHCM) allotransplant. Seven recipient rats (control) received syngeneic HHCM grafts from Lewis donors while the remaining 23 (study group) received HHCM grafts from Brown Norway (RT1n) donors. Control rats were sacrificed after 7 days while rats in the study group were serially sacrificed at days 1-7 after transplantation. No immunosuppression was given. The tissue sections from the HHCM grafts were assessed for acute rejection based on the grading system adopted by the International Society for Heart and Lung Transplantation. RESULTS: As expected, all the control rats had no evidence of rejection. One study animal developed an infection in the skeletal muscle allograft and was excluded. Two study animals had no evidence of rejection when sacrificed 1 day after transplant. The remaining 20 rats developed acute cellular rejection in their graft(s). Upon comparison of acute cellular rejection between the heterotopic heart and the cutaneous maximus flap grafts, rejection correlated grade for grade in 75% (15 of 20 rats). All five rats that did not have identical grades of rejection had mild rejection (grades IA, IB and II). Presence or absence of rejection, therefore, correlated in 20/22 rats: 15/20 rats with cardiac rejection and 2/2 rats without cardiac rejection. CONCLUSION: Cardiac and skeletal muscle allografts have similar pattern of rejection with little grade to grade variability. The clinical implications for surveillance of cardiac rejection warrants further investigation.

Animals↗
PubMed1998

A new rat model to study the correlation of cardiac and skeletal muscle allograft rejection.

As a first step to study the correlation of cardiac and skeletal muscle allograft rejection, we describe a new experimental rat model of simultaneous heterotopic heart and cutaneous maximus muscle flap allotransplant. Brown Norway rats were used as donors and Lewis rats as recipients. No immunosuppression was given. The grafts were revascularized with sequential end-to-side anastomosis of each vascular pedicle to the infrarenal aorta and vena cava. Syngeneic heart and cutaneous maximus muscle grafts remained functional and showed no sign of rejection at 7 days after the transplant. In contrast, both allografts developed severe rejection and functional compromise at 7 days after the transplant. Our experimental model is technically feasible and reproducible and may provide important information about the pattern of rejection of cardiac and skeletal muscle allografts.

Animals↗
PubMed1998

X-ray structures of new dipeptide taste ligands.

The molecular basis of sweet taste was investigated by carrying out the crystal state conformational analysis by X-ray diffraction of the following dipeptide taste ligands: N-3,3-dimethylbutyl-aspartylphenylalanine methyl ester, I (N-DMB-Asp-Phe-OMe), its sodium salt (N-DMB-Asp-Phe-ONa), II, aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide, III (Asp-D-Abu-(S)-alpha-ethylbenzylamide), aspartyl-N'-((2,2,5,5-tetramethylcyclopentanyl)-carbonyl)-(R)- 1,1-diamino-ethane, IV (Asp-(R)-gAla-TMCP), and aspartyl-D-valine-(R)-alpha-methoxymethylbenzyl amide, V (Asp-D-Val-(R)-alpha-methoxymethylbenzylamide). With the exception of the sodium salt II, all compounds are sweet-tasting, showing in some cases considerable potency enhancement with respect to sucrose. The results of this study confirm the earlier model that an 'L-shape' molecular array is essential for eliciting sweet taste for dipeptide-like ligands. In addition, it was established that (i) substitution of the N-terminal group does not inhibit sweet taste, if its zwitterionic character is maintained; (ii) a hydrophobic group located between the stem and the base of the L-shape could be responsible for sweetness potency enhancement, as found in I, III and IV; in fact, the extraordinary potency of the N-alkylated analogue I would support a model with an additional hydrophobic binding domain above the base of the 'L'; (iii) removal of the methyl ester at the C-terminus of compound I with the salt formation gives rise to the tasteless compound II; (iv) for the first time all possible side-chain conformers (g-, g+ and t) for the N-substituted aspartyl residue were observed; and (v) a retro-inverso modification, incorporated at position 2 of the dipeptide chain, confers greater flexibility to the molecule, as demonstrated by the contemporary presence of six conformationally distinct independent molecules in the unit cell and yet sweet taste properties are maintained, as found in IV.

Computer Simulation↗
PubMed1998

The crystal state conformation of Aib-rich segments of peptaibol antibiotics.

Ac-(Aib-Ala)3-OH (a protected segment of the peptaibols gliodeliquescin and paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of [Leu]7-gliodeliquescin), Z-Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsin, and hypelcin), and Ac-Aib-Pro-(Aib-Ala)2-OMe and Z-Aib-Pro-(Aib-Ala)2-OMe, which represent differently N(alpha)-protected 1-6 segments of alamethicin and hypelcin, have been synthesized by solution methods. The crystal-state conformations of these five Aib-containing peptides have been determined by X-ray diffraction analysis. We have confirmed that the 3(10)-helical structure is preferentially adopted by Aib-rich short peptides. An experimentally unambiguous proof for the 3(10)-->alpha-helix conversion has been provided by the two differently N-blocked -Aib-Pro-(Aib-Ala)2-OMe hexapeptides. The beta-bend ribbon conformation, commonly observed in the (Aib-Pro)n sequential oligopeptides, is not found in the -Aib-Pro-Aib-Ala-Aib-Ala-sequence. As expected on the basis of the L-configuration of the C(alpha)-monoalkylated residues, a right-handed helix screw sense was found in all peptides investigated.

Anti-Bacterial Agents↗
PubMed1998

A prospective randomized clinical trial of perioperative treatment with octreotide in pancreas transplantation.

BACKGROUND: Technical failures continue to plague clinical pancreas transplantation. The somastatin analogue octreotide has been shown able to decrease morbidity after pancreatic resection. We studied the effect of perioperative treatment with octreotide on technical complications after pancreas transplant. PATIENTS AND METHODS: Seventeen recipients of bladder-drained transplant were randomized to receive either octreotide, 100 microg TID SQ for 5 days after transplant (n = 10) or no additional treatment (n = 7). We compared the two groups in terms of patient and graft survival and incidence of graft pancreatitis, intra-abdominal infections, and anastomotic leaks. RESULTS: In the untreated group, 1 patient developed a bladder leak and 2 had intra-abdominal infections, while no complications occurred in the octreotide-treated patients (P = 0.05). Six-month patient and pancreas survival was 100% and 90%, respectively, in octreotide-treated patients versus 86% and 86% in the control group (P = NS). CONCLUSION: Perioperative treatment with octreotide seems able to reduce the incidence of technical complications after pancreas transplantation.

Adult↗
PubMed1998

Combined coronary bypass and liver transplantation: technical considerations.

Combined coronary artery bypass grafting and orthotopic liver transplantation was carried out successfully in a 58-year-old man with angina pectoris and end-stage liver disease. To date, only 2 similar cases have been documented worldwide whereby the transplantation was performed either during cardiopulmonary bypass or with femoral-to-axillary venovenous bypass initiated at the termination of cardiopulmonary bypass. In this report we describe our experience with a simplified one-exposure approach for the combined operation using cardiopulmonary bypass in tandem with percutaneous femoral-to-right atrial venovenous bypass.

Angina Pectoris↗