Biomedical subjects

P Marchetti

Publications and source records attributed to P Marchetti.

At least 19 recordsLinked to original sources

PubMed2005

Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients.

AIMS/HYPOTHESIS: Little information is available on the insulin release properties of pancreatic islets isolated from type 2 diabetic subjects. Since mitochondria represent the site where important metabolites that regulate insulin secretion are generated, we studied insulin release as well as mitochondrial function and morphology directly in pancreatic islets isolated from type 2 diabetic patients. METHODS: Islets were prepared by collagenase digestion and density gradient purification, and insulin secretion in response to glucose and arginine was assessed by the batch incubation method. Adenine nucleotides, mitochondrial membrane potential, the expression of UCP-2, complex I and complex V of the respiratory chain, and nitrotyrosine levels were evaluated and correlated with insulin secretion. RESULTS: Compared to control islets, diabetic islets showed reduced insulin secretion in response to glucose, and this defect was associated with lower ATP levels, a lower ATP/ADP ratio and impaired hyperpolarization of the mitochondrial membrane. Increased protein expression of UCP-2, complex I and complex V of the respiratory chain, and a higher level of nitrotyrosine were also found in type 2 diabetic islets. Morphology studies showed that control and diabetic beta cells had a similar number of mitochondria; however, mitochondrial density volume was significantly higher in type 2 diabetic beta cells. CONCLUSIONS/INTERPRETATION: In pancreatic beta cells from type 2 diabetic subjects, the impaired secretory response to glucose is associated with a marked alteration of mitochondrial function and morphology. In particular, UCP-2 expression is increased (probably due to a condition of fuel overload), which leads to lower ATP, decreased ATP/ADP ratio, with consequent reduction of insulin release.

Adenine Nucleotides↗

PubMed2004

Timed flat infusion of 5-fluorouracil increases the tolerability of 5-fluorouracil/docetaxel regimen in metastatic breast cancer: a dose-finding study.

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00-10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen.

Adult↗

PubMed2004

Alteration of beta-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of type 2 diabetes.

We have previously obtained a new type 2 diabetic syndrome in adult rats given streptozotocin and nicotinamide, characterized by reduced beta-cell mass, partially preserved insulin response to glucose and tolbutamide and excessive responsiveness to arginine. We have also established that the neuronal isoform of constitutive NO synthase (nNOS) is expressed in beta-cells and modulates insulin secretion. In this study, we explored the kinetics of glucose- and arginine-stimulated insulin release in perifused isolated islets as well as the effect of N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, to get insight into the possible mechanisms responsible for the arginine hypersensitivity observed in vitro in this and other models of type 2 diabetes. A reduced first phase and a blunted second phase of insulin secretion were observed upon glucose stimulation of diabetic islets, confirming previous data in the isolated perfused rat pancreas. Exposure of diabetic islets to 10 mM arginine, in the presence of 2.8 mM glucose, elicited a remarkable monophasic increment in insulin release, which peaked at 639 +/- 31 pg/islet/min as compared to 49 +/- 18 pg/islet/min in control islets (P << 0.01). The addition of L-NAME to control islets markedly enhanced the insulin response to arginine, as expected from the documented inhibitory effect exerted by nNOS activity in normal beta-cells, whereas it did not further modify the insulin secretion in diabetic islets, thus implying the occurrence of a defective nNOS activity in these islets. A reduced expression of nNOS mRNA was found in the majority but not in all diabetic islet preparations and therefore cannot totally account for the absence of L-NAME effect, that might also be ascribed to post-transcriptional mechanisms impairing nNOS catalytic activity. In conclusion, our results provide for the first time evidence that functional abnormalities of type 2 experimental diabetes, such as the insulin hyper-responsiveness to arginine, could be due to an impairment of nNOS expression and/or activity in beta-cells.

Animals↗

PubMed2004

Pancreas transplantation from marginal donors.

BACKGROUND: Marginal donor organs are a supplementary source of grafts that has not been fully exploited for pancreas transplantation (PTx). METHODS: A total of 100 PTx were performed with grafts procured from either 48 nonmarginal donors (NMD) or 52 marginal donors (MD), namely age greater than 45 years and/or severe hemodynamic instability at the time of procurement. PTx outcome was evaluated as the incidence of delayed endocrine pancreas function (DEPF), the complication rate, and the patient and graft survivals. RESULTS: The DEPF rate was 6.2% for NMD as compared to 0 for MD (P >.05). Relaparotomy rate was 12.5% for NMD and 9.6% for MD (P >.05). Actuarial 1-year graft survival was 91.7% and 94.2% for NMD and MD, respectively (P >.05). Equivalent figures for patients were 97.9% and 98.1%, respectively (P >.05). CONCLUSIONS: Pancreas from MD may be safely employed and significantly expand the donor pool for PTx.

Cadaver↗

PubMed2004

Pancreas transplant alone.

Pancreas transplant alone (PTA) represents a growing proportion of overall pancreas transplantations, with 1-year patient and graft survivals of almost 100% and higher than 80%, respectively. PTA can restore normoglycemia without exogenous insulin administration and eliminate acute diabetic complications. In our series of 28 PTA, performed with portal-enteric drainage, 2-year patient and pancreas survivals were 100% and 87%, respectively. In patients with successful transplantation, rapid normalization of blood glucose level and HbA1c concentration was observed, due to restored endogenous insulin secretion. Several classical cardiovascular risk factors were measured before and after transplant, with significant improvements shortly after transplantation. Diabetic retinopathy improved in 58.8% of examined eyes, stabilized in 35.3%, and worsened in 5.9%. In conclusion, PTA represents a clinically relevant option for patients with type 1 diabetes without advanced renal disease. It restores normoglycemia in the vast majority of patients and seems to have a positive impact on late diabetic complications.

Blood Glucose↗

PubMed2004

Retroperitoneal pancreas transplantation with portal-enteric drainage.

BACKGROUND: Portal-enteric drainage (PED) is the latest refinement in the surgical technique for pancreas transplantation (PTx). We herein describe the results of a modified technique for PED that places the pancreas in a totally retroperitoneal position. METHODS: Between April 2001 and June 2003, 79 PTx were performed using a retroperitoneal PED technique. RESULTS: No graft was lost due to surgical complications and the relaparotomy rate was 11.4%. Mean hospital stay averaged 25.9 days (+/-14.4 days) with a 30-day readmission rate of 12.7%. One graft was lost due to delayed (6 months) arterial thrombosis and three to acute rejection. The overall 1-year patient and graft survivals were 98.7% and 93.7%, respectively. CONCLUSIONS: Our data confirm that PED of pancreas grafts is associated with low morbidity and mortality rates. Whether retroperitoneal graft placement has actual advantages over the "classical" intraperitoneal position remains to be ascertained.

Adult↗

PubMed2004

Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study.

Type I diabetes mellitus (IDDM) is associated with an increased cardiovascular risk, and eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) are consequently accurate for preoperative cardiovascular assessment. According to our algorithm, coronary angiography in SPKT candidates is indicated for patients not only experiencing previous cardiac events or symptoms, but also those with long-standing diabetes (more than 25 years) and/or age over 45 years. Furthermore, a basal transthoracic echocardiographic exam (TTE) is performed to assess cardiac volumes, left ventricular mass, systolic function, and kinesis. The aims of this study were to evaluate perioperative cardiac morbidity and mortality in 18 SPKT-eligible patients, divided into two groups on the basis of the presence/absence of angiographically evident coronary artery disease (CAD), as well as to assess the impact of left ventricular hypertrophy (LVH) on cardiac complications. Cardiac intraoperative morbidity and mortality and postoperative mortality and major morbidity were absent; minor cardiac morbidity consisted only of silent ischemic ECG alterations, without significant differences between groups, although the incidence seemed to be higher in the CAD-positive population. LVH detected preoperatively by TTE exam also failed to correlate with the incidence of such complications. Selection of SPKT candidates by coronary angiography may have positive effects on perioperative cardiac morbidity and mortality. A larger sample size is needed to give the study statistical power. Medium- and long-term follow-up studies are warranted to evaluate the effects of preoperative selection on survival rates.

Adult↗

PubMed2004

Complete reversal of the nephrotic syndrome after preemptive pancreas-kidney transplantation: a case report.

BACKGROUND: Nephrotic syndrome due to diabetic nephropathy is presently considered an indication for pancreas-kidney transplantation even in the absence of severe renal failure. Reversal of the nephrotic syndrome has been reported, but the mechanisms of this effect are unclear. AIM: To describe the renal morphofunctional pattern and the pattern of proteinuria before and after preemptive pancreas-kidney transplantation. METHODS: Methods included quantitative and qualitative assessment of proteinuria as well as renal ultrasound and scintiscan. CASE REPORT: A 42-year-old woman with type 1 diabetes since age 24 had widespread end-organ damage. Renal biopsy (2001) showed a mainly nodular pattern of diabetic nephropathy. Following referral (1999), her serum creatinine ranged from 1.6 to 2.2 mg/dL, with nephrotic range proteinuria (glomerular nonselective, tubular complete). Renal scintiscan revealed bilateral, symmetric, well-perfused kidneys. The functional data before pancreas-kidney graft (February 2003) were: serum creatinine 1.6 mg/dL, creatinine clearance 58 mL/min, serum albumin 2.6 g/dL, proteinuria 9.1 g/d. At hospital discharge (March 2003), the creatinine was 1.2 mg/dL, the creatinine clearance 97 mL/min, the proteinuria 0.676 g/d. Two months later, the creatinine was 1.2 mg/dL and proteinuria 0.421 g/d. A renal scintiscan demonstrated the functional prevalence of the grafted kidney (77% of total function), with vital, almost completely excluded native kidneys (functional contribution, 11.5% each). Proteinuria, ranging from 0.3 to 0.6 g/d, showed a physiological pattern. CONCLUSIONS: Functional exclusion of the native kidneys by renal scintiscan gives morphological support to reversal of the nephrotic syndrome.

Adult↗

PubMed2004

Solitary pancreas transplantation: preliminary findings about early reduction of proteinuria in incipient or evident diabetic type I nephropathy.

OBJECTIVE: Our work was aimed to evaluate the precocious reduction of proteinuria in patients suffering from diabetes mellitus type 1 with incipient and evident nephropathy after isolated pancreas transplantation (PTA). MATERIALS AND METHODS: From December 2000 to March 2003, we followed 24 PTA grafts in 24 patients with diabetes mellitus type 1 (mean age 37.8 years; mean duration of diabetes 24.8 years). The pancreas was transplanted with portal-enteric drainage in 23 patients and systemic-enteric in 1 patient. The immunosuppressive therapy used basilixmab induction and tacrolimus, mycophenolate mophetil (MMF), and low dose steroid maintenance therapy. The renal function, proteinuria, and the glucose metabolic parameters were evaluated before and during the following months after transplant. RESULTS: All patients are alive and twenty-one have a well-functioning pancreas with three grafts lost. All patients had persistence of normal renal function. Before transplantation 12 patients displayed proteinuria that was clearly reduced in 11 and gone in three patients, all of whom were insulin-independent. CONCLUSIONS: TPA seems to reduce, and in some cases to regress, the proteinuria associated with early diabetic nephropathy.

Adult↗

PubMed2004

Kidney and pancreas transplants in Jehovah's witnesses: ethical and practical implications.

Jehovah's Witnesses refuse blood transfusions but accept solid organ transplants. Six Jehovah's Witnesses received a kidney and/or a pancreas transplant in our center. After a mean follow-up of 31.4 months (range: 18 to 39) all the recipients are alive and well with functioning grafts. However, 1 month after grafting, one recipient required blood transfusions. Hemorrhage was ruled out and the anemia was attributed to drug-related toxicity. Thus, Jehovah's Witnesses can receive a kidney and/or a pancreas transplant without blood transfusions at the time of surgery. However, lifesaving transfusions may be needed later on, which raises additional and unique medical and ethical issues.

Adult↗

PubMed2004

An alternative and simple method to consistently prepare viable isolated human islets for clinical transplantation.

We describe a method to consistently prepare human islets for transplantation. By combining a simple collagenase digestion method and a density gradient purification system, we were able to obtain successful isolations (>/=200,000 islet equivalents, >/=50% purity) in 69% of processed glands. No reagent of animal source was used. Isolated islets were morphologically well maintained and functionally competent, with sterility confirmed in 97% of cases. Two patients were transplanted with islets prepared by this method; graft function was demonstrated for a few months. Improved simplicity and consistency, together with adequate quality of the preparations, are the main features of this isolation method.

Adult↗

PubMed2004

To give or to receive? Opinions of teenagers on kidney donation.

BACKGROUND: The attitude toward living donation varies widely in the world, for economic and cultural reasons. In Italy, as in other Mediterranean settings, the role of living kidney donation is minor. AIM: To analyze the reasons for this attitude, we gathered data in a general population sample of high school students in a large northern Italian industrial city (Torino, about 900,000 inhabitants). METHODS: Semistructured questionnaires (n = 1676), gathered in 2001 to 2002 in 14 high schools, in the context of an educational program on dialysis, renal transplantation, and organ donation, were analyzed presumably reflecting opinions gathered before the educational intervention. RESULTS: Most students, in the case of a close relative or partner needing dialysis, answer that they would donate a kidney (yes: 78.2%, no: 2.9%, uncertain-blank: 18.9%); receiving a living donor kidney is felt as disturbing: only 57.5% of the students would accept it (no: 5.9%, uncertain-blank: 36.6%), mainly because of fear of long-term problems for the donor. Donation from an older to a younger person is seen more positively than vice versa. CONCLUSION: In our settings, the attitude of the teenagers on living donation is positive; however, while "giving" is positively seen, the presence of unresolved fears is witnessed by the lower acceptance of the idea of "taking." These data suggest to focus on the risks of kidney donation in educational campaigns and in patient-physician information. The positive attitude shared by the teenagers supports the working hypothesis that lack of information is one of the determinants of the low living donor transplantation rate in our area.

Adolescent↗

PubMed2004

Echocardiographic evaluation in type 1 diabetic patients on waiting list for isolated pancreas or kidney-pancreas transplantation.

Type 1 diabetic patients may display abnormalities of left ventricular geometry and systolic and diastolic function. Patients on the waiting list for solitary pancreas or kidney-pancreas transplantation were evaluated by Doppler echocardiography to assess left ventricular geometry and systolic and diastolic function, and correlate these parameters with clinical characteristics. We evaluated 78 patients including 45 men with an overall mean age of 39.5 +/- 7.2 years and a disease duration of 24 +/- 9.8 years. Among these 78 patients, 13 showed isolated retinopathy, 9 isolated arterial hypertension, 45 concomitant retinopathy and hypertension and overt nephropathy, while 11 were free of complications. The results of our study showed an increased left ventricular mass and abnormal diastolic function among patients with simultaneous target organ complications and with hypertension, as has been reported in many previous studies. In contrast study patients with no complications showed normal left ventricular structure and function. This finding conflicts with data from several reports in the medical literature in which diastolic impairment was present in type 1 diabetic patients at an early stage of disease and with no evident microvascular and macrovascular complications.

Adult↗

PubMed2004

Simultaneous cadaver pancreas-living donor kidney transplantation.

BACKGROUND: The expansion of the donor pool achieved with living kidney donation (LKD) is particularly beneficial for diabetic patients, who have a worse prognosis during dialysis when compared to other kidney recipients. Simultaneous cadaver pancreas-living kidney transplantation (SPLKTx) merges the advantages of LKD with those of cadaver donation, and may be an attractive alternative to simultaneous pancreas kidney transplantation (SPKTx). METHODS: The outcomes of 18 SPLKTx were compared with those of 33 SPKTx. RESULTS: LKD expanded the donor pool from 33 to 51 (P =.004). Median wait time was shorter for SPLKTx (14 days) than for SPKTx (95 days) (P =.006). The risk for surgical complications was not increased by SPLKTx, as witnessed by relaparotomy rates (SPLKTx: 2/18, 11.1%; SPKTx: 2/33, 6.1%; P >.05). Hospital stay averaged 26.1 +/- 11.2 days for SPLKTx and 27.1 +/- 16.3 for SPKTx (P >.05) with equivalent 30-day readmission rates (SPLKTx: 5.5%; SPKTx: 6.1%); (P >.05). One acute kidney rejection occurred in SPLKTx (5.5%) as compared with four in SPKTx (12.1%); (P >.05). Equivalent rates for the pancreas were 5.5% (1/18) for SPLKTx and 3.0% (1/33) for SPKTx (P >.05). Two-year recipient survival rates were 100% for SPLKTx as compared with 96.9% for SPKTx. Equivalent figures for kidney and pancreas were 80.0% and 84.0% for SPLKTx and 96.9% and 96.9% for SPKTx. CONCLUSIONS: SPLKTx is a valuable alternative to SPKTx. Further development of SPLKTX relies on increased rates of living kidney donation.

Adult↗

PubMed2004

Pancreas preservation with University of Wisconsin and Celsior solutions.

BACKGROUND: Although the use of Celsior has been recently described for heart, lung, liver, and kidney transplantation, no data are available on its use for clinical pancreas preservation. METHODS: We herein describe the results of 112 pancreas transplants preserved with either University of Wisconsin (UW; (n = 56) or Celsior (n = 56) solution at two Italian transplant centers. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Mean cold and warm ischemia times were 10.1 +/- 2.2 hours and 37.2 +/- 8.2 minutes for UW compared to 10.8 +/- 2.4 hours and 38.3 +/- 6.7 minutes for Celsior (P = NS). Delayed endocrine pancreas function was recorded in two UW-preserved grafts (3.6%). Actuarial 1-year patient survival was 94.6% for UW as compared with 100% for Celsior (P = NS). Equivalent graft survival figures were 91.0% for UW as compared with 96.4% for Celsior (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and Celsior solutions have similar safety profiles for pancreas transplantation.

Adenosine↗

PubMed2004

Portal enteric-drained solitary pancreas transplantation without surveillance biopsy: is it safe?

BACKGROUND: Most solitary pancreas transplants (SPTx) fail due to unrecognized rejection episodes. Consequently, SPTx are monitored by drainage into the bladder or by surveillance biopsies. METHODS: Between April 2001 and June 2003, a consecutive series of 48 SPTx were performed using portal enteric drainage (PED). Rejection episodes were diagnosed empirically, based on the elevated pancreatic enzymes without a surveillance biopsy. Immunosuppression consisted of basiliximab (n = 42) or ATG (n = 6), low-dose steroids, MMF, and tacrolimus. Donors (mean age 28.9 year; range 9 to 54 year) were selected according to standard criteria irrespective of HLA match, although the best HLA matching was considered at the time of graft allocation. RESULTS: After a mean cold ischemia time of 676 minutes (range 475 to 900 minutes), all but two pancreata (95.8%) functioned immediately. Relaparotomy was required in seven cases (14.6%). Three grafts were lost in the early posttransplant period due to hyperacute rejection. Two additional grafts were lost later due to arterial thrombosis or to chronic rejection. After a median follow-up period of 12.2 months (range 0.2 to 27 months) three further recipients were diagnosed with rejection episodes that were reversed with steroid boluses. Actuarial 1-year patient and graft survival rates were 100% and 93.1% and 2-year figures 100% and 88.7%, respectively. At the longest follow-up no recipient was diagnosed with a malignancy. CONCLUSIONS: With current immunosuppression protocols SPTx achieves high rates of insulin independence even without surveillance biopsy or routine use of T-cell-depleting therapies.

Biopsy↗

PubMed2004

Simultaneous pancreas-kidney transplantation is improved by living kidney donation program.

BACKGROUND: Shortage of suitable donors and current graft allocation priorities reduce the number of cadaveric kidneys available to diabetic recipients. The concurrent excess of solitary cadaveric pancreata and the excellent results of living kidney transplantation make simultaneous cadaveric pancreas-living kidney transplantation (SPLKTx) an attractive alternative to simultaneous pancreas-kidney transplantation (SPKTx). METHODS: Between June 2001 and June 2003, 80 recipients were enrolled in the SPKTx waiting list. Each recipient's family was counseled about living kidney donation (LKD). Twenty-nine (36.2%) candidates were evaluated for LKD and 8 (27.6%) were disqualified. The remaining 21 candidates were scheduled for LKD and 18 actually donated. RESULTS: Thanks to LKD 18 additional recipients were transplanted, thus expanding the donor pool from 33 to 51 (P =.004). The median waiting time for SPLKTx was 14 days as compared with 95 days for SPKTx (P =.006). Without LKD the median waiting time for SPKTx would have been 198 days (P =.02). Similarly, 1 year after the enrollment on the waiting list 60% of recipients had been transplanted, while without LKD only 42% would had been grafted (P =.01). Two-year recipient survival rate was 100% for SPLKTx compared with 96.9% for SPKTx. Equivalent figures for kidney and pancreas were 80.0% and 84.0% for SPLKTx compared with 96.9% and 96.9% for SPKTx. CONCLUSIONS: LKD expanded the kidney donor pool, reduced the waiting time of recipients listed for a totally cadaveric procedure, and increased their chance to get a timely graft. One-year outcome of SPLKTx equaled that of SPKTx.

Cadaver↗

PubMed2004

Single-center, open, prospective, randomized pilot study comparing cyclosporine versus tacrolimus in simultaneous pancreas-kidney transplantation.

BACKGROUND: Although tacrolimus (Prograf) is the calcineurin inhibitor usually employed in simultaneous pancreas-kidney transplantation (SPKTx), no prospective randomized studies have compared its efficacy to cyclosporine (Neoral), when either drug is used in combination with mycophenolate mofetil (MMF) and the pancreas is drained into the portal vein. METHODS: Between May 2001 and June 2003, 16 SPKTx recipients were randomized to be prescribed Neoral and 17 Prograf in addition to basiliximab, steroids, and MMF. All pancreata were drained into the portal vein. RESULTS: After a median follow-up of 15.6 months, six kidney acute rejection episodes were observed with Prograf (36.5%; one steroid-resistant) and one Neoral (n = 1, 6.2%; P =.04). No pancreas rejection episode was recorded. Two infections occurred in two recipients from each group. No major adverse events were noted other than a severe hematological toxicity (Prograf). Metabolic parameters were equivalent in the two groups, save for higher total cholesterol (212 +/- 39 mg/dL vs 173 +/- 23 mg/dL; P =.008), LDL (129 +/- 33 mg/dL vs 101 +/- 21 mg/dL; P =.029), and triglyceride (191 +/- 86 mg/dL vs 126 +/- 40 mg/dL; P =.028), values with Neoral, although the same differences were already present at baseline. One recipient (Neoral) died with functioning grafts. Patient, pancreas, and kidney survival rates were all 94% for Neoral versus 100% for Prograf. CONCLUSIONS: Although a larger series and a longer follow-up are needed, Neoral and Prograf used in combination with MMF seem to achieve equivalent success rates among primary SPKTx when the pancreas is drained into the portal vein.

Cyclosporine↗