Biomedical subjects

P Marchetti

Publications and source records attributed to P Marchetti.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2004

Targeting insulin resistance and beta-cell dysfunction: the role of thiazolidinediones.

Insulin resistance and beta-cell dysfunction are fundamental defects that contribute to the development of type 2 diabetes, and as such are targets for primary prevention of disease progression. The two parameters are linked by several factors, including glucotoxicity and lipotoxicity, and recent research has enlightened understanding of the molecular mechanisms underlying the development and progression of the disease. Historically, type 2 diabetes has been managed by controlling hyperglycemia, using agents that increase insulin levels or reduce hepatic glucose production, as exemplified by the United Kingdom Prospective Diabetes Study. The thiazolidinediones control hyperglycemia by targeting the fundamental defects of the disease, and have shown well-documented improvements in insulin sensitivity and beta-cell function, both in monotherapy and in combination with other oral antidiabetic agents. TRoglitazone In the Prevention Of Diabetes (TRIPOD) has demonstrated the potential for thiazolidinediones to delay progression to type 2 diabetes. Prospective studies such as Diabetes REduction Approaches with ramipril and rosiglitazone Medications (DREAM) are currently evaluating the long-term effects of thiazolidinediones on metabolic status and disease progression.

Blood Glucose↗

PubMed2004

An oncologist-based model of cancer genetic counselling for hereditary breast and ovarian cancer.

BACKGROUND: We describe a multistep model of cancer genetic counselling designed to promote awareness, and disease surveillance and preventive measures for hereditary and familial breast and ovarian cancer. PATIENTS AND METHODS: Step T0 of the model entails information giving; this is followed by pedigree analysis and risk estimation (T1), risk communication and genetic testing (T2), and genetic test result communication (T3). User consent was required to proceed from one step to the next. Surveillance and preventive measures are proposed to at-risk users. Of the 311 subjects who requested cancer genetic counselling, consent data to each counselling step were available for 295: 93 were disease-free, 187 had breast cancer, 12 had ovarian cancer and three had breast plus ovarian cancer. RESULTS: Consent was high at T0 (98.39%), T1 (96.40%) and T2 (99.65%). Consent decreased at the crucial points of counselling: T2 (87.71%) and T3 [genetic test result communication (85.08%), and extension of counselling to and testing of relatives (65.36%)]. CONCLUSIONS: The model fosters the user's knowledge about cancer and favours identification of at-risk subjects. Furthermore, by promoting awareness about genetic testing and surveillance measures, the algorithm enables users to make a fully informed choice of action in case of predisposing or familial cancer risk.

Breast Neoplasms↗

PubMed2004

Reducing breast cancer incidence in familial breast cancer: overlooking the present panorama.

Familial breast cancer, whether associated or not with particular other breast cancer features (male, early onset, bilateral breast cancer), determines a wide and variable risk of developing breast cancer in the 'unpatients' (unaffected individuals) of these families, particularly in those harboring a genetic predisposition. The antiestrogen tamoxifen has been proposed in different trials to prevent breast cancer in women at risk. The NSABP-P1 study demonstrated that tamoxifen drastically reduced (by approximately 50%) the incidence of breast cancer in women at risk selected according to the Gail score. The preventive effect was particularly consistent in postmenopausal women and in those showing familial breast cancer (three or more affected patients). BRCA1/BRCA2 (BRCA1/2) gene analysis in women accrued in the NSABP-P1 trial who developed breast cancer showed that tamoxifen chemoprevention reduced breast cancer incidence in BRCA2 carriers. Different chemoprevention trials are ongoing to compare different selective estrogen receptor modulators and aromatase inhibitors with tamoxifen. The Italian Consortium of Hereditary Breast Ovarian Cancer recently developed the Aromasin Prevention Study, a multicenter, double-blind, randomized, placebo-controlled phase III study evaluating the effect of the aromatase inhibitor exemestane for chemoprevention in postmenopausal women carriers of BRCA1/2 genetic predisposition. Women who are postmenopausal unaffected carriers of BRCA1/2 mutations will be selected by participating institutions and randomly assigned to receive either oral exemestane or oral placebo every day for 3 years in order to reduce the incidence of breast cancer. Genetic counseling and the detection of predisposing BRCA1/2 mutations are mandatory before accrual into the study. Signed informed consents for the performing of BRCA1 and BRCA2 genetic analysis and for enrollment into the study are required. Eligible women will be followed thereafter in order to evaluate the efficacy of exemestane in reducing the incidental rate of breast cancer in unaffected postmenopausal carriers of BRCA1/2 mutations.

Anticarcinogenic Agents↗

PubMed2004

Preclinical studies on detection of circulating melanoma cells in patients: telomerase as a recognition marker of malignancy.

Preclinical studies based on a "simulation design", were performed with cultured melanoma cells prelabeled with 51Cr, added to normal blood and subjected to separation and recognition steps. Mononuclear cells (MNC) were isolated on ficollhypaque gradient, and melanoma cells were separated from lymphocytes using anti-CD45 immunomagnetic beads. Malignant cells were then recognized by measuring telomerase activity (TRAP and TRAP-ELISA assays). It was found that: (a)recovery of prelabeled cells present in MNC did not exceed 75%; (b) further recovery of prelabeled cells after separation from lymphocytes did not exceed 68%. Therefore, the overall recovery of prelabeled cells did not exceed 48%; (c) the entire procedure was able to reliably detect as few as 30 malignant cells added to normal blood, providing a telomerase signal significantly higher than that found in absence of melanoma cells. These results furnish the technical bases for developing a tumor detection assay in the blood of melanoma patients.

Biomarkers, Tumor↗

PubMed2004

[New therapeutic approachs in melanoma].

During the last decade, new insights in cellular and molecular biology have opened new avenues in cancer immunotherapy. Two distinct modalities have been developed: adoptive immunotherapy and anti-tumoral vaccination (active immunotherapy). We will first describe the main strategies of adoptive immunotherapy and then elaborate on the protocols of anti-tumoral vaccination against tumor associated antigens (TAA). In that context, we will pay peculiar attention on the pivotal role of dendritic cells (DC) as natural adjuvant.

Cancer Vaccines↗

PubMed2003

Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma2 in the modulation of insulin secretion.

Peroxisome proliferator-activated receptors (PPARs) are a subgroup of the superfamily of nuclear receptors, with three distinct main types: alpha, beta and gamma (subdivided into gamma(1) and gamma(2)). Recently, the presence of PPARgamma has been reported in human islets. Whether other PPAR types can be found in human islets, how islet PPARgamma mRNA expression is regulated by the metabolic milieu, their role in insulin secretion, and the effects of a PPARgamma agonist are not known. In this study, human pancreatic islets were prepared by collagenase digestion and density gradient purification from nonobese adult donors. The presence of PPAR mRNAs was assessed by RT-PCR, and the effect was evaluated of exposure for up to 24 h to either 22.2 mmol/l glucose and/or 0.25, 0.5, or 1.0 mmol/l long-chain fatty acid mixture (oleate to palmitate, 2:1). PPARbeta and, to a greater extent, total PPARgamma and PPARgamma(2) mRNAs were expressed in human islets, whereas PPARalpha mRNA was not detected. Compared with human adipose tissue, PPARgamma mRNA was expressed at lower levels in the islets, and PPARbeta at similar levels. The expression of PPARgamma(2) mRNA was not affected by exposure to 22.2 mmol/l glucose, whereas it decreased markedly and time-dependently after exposure to progressively higher free fatty acids (FFA). This latter effect was not affected by the concomitant presence of high glucose. Exposure to FFA caused inhibition of insulin mRNA expression, glucose-stimulated insulin release, and reduction of islet insulin content. The PPARgamma agonists rosiglitazone and 15-deoxy-Delta-(12,14)prostaglandin J(2) prevented the cytostatic effect of FFA as well as the FFA-induced changes of PPAR and insulin mRNA expression. In conclusion, this study shows that PPARgamma mRNA is expressed in human pancreatic islets, with predominance of PPARgamma(2); exposure to FFA downregulates PPARgamma(2) and insulin mRNA expression and inhibits glucose-stimulated insulin secretion; exposure to PPARgamma agonists can prevent these effects.

Adipose Tissue↗