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Biomedical subjects

P Petruzzo

Publications and source records attributed to P Petruzzo.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic consequences of pancreatic systemic or portal venous drainage in simultaneous pancreas-kidney transplant recipients.

AIMS: The aim was to investigate pancreatic B-cell function and insulin sensitivity in simultaneous pancreas-kidney (SPK) recipients with systemic or portal venous drained pancreas allograft using simple and easy tests. METHODS: The study included 44 patients with Type 1 diabetes and end-stage renal disease who had undergone SPK transplantation: 20 recipients received a pancreas allograft with systemic venous drainage (S-SPK) and 24 with portal venous drainage (P-SPK). We studied only recipients with functioning grafts, with normal serum glucose, HbA(1c) and serum creatinine values, on a stable drug regimen. The subjects were studied at 6, 12, 24, 36, 48 and 60 months after transplantation. Insulin sensitivity and B-cell function indices were derived from blood samples and oral glucose tolerance tests. RESULTS: All patients from both groups had normal fasting glucose, body mass index and HbA(1c) values by selection. The homeostatic model (HOMA) beta-cell index was significantly lower in P-SPK recipients at several points of the follow-up. HOMA-IR was significantly higher in S-SPK recipients at 6 and 24 months after transplantation and was positively correlated with fasting insulin values, but never exceeded 3.2. There was no significant difference in QUICKI index values between the two groups. Although all patients from both groups always had normal glucose tolerance, the area under the insulin curve was higher in the S-SPK group. Cholesterol, low-density lipoprotein-cholesterol and triglycerides were higher in the P-SPK group. CONCLUSIONS: The results suggest sustained long-term endocrine function in both groups and show that portal venous drainage does not offer major metabolic advantages.

Adult↗
PubMed2006

Bilateral hand transplantation: six years after the first case.

In this study we present our experience concerning bilateral hand transplantation. Two cases were performed: the first in January 2000 and the second in April 2003. Both recipients received the same immunosuppressive treatment, which was similar to those used in solid organ transplantation, including tacrolimus, prednisone and mycophenolate mofetil while antithymocyte globulins were added for induction. Both recipients presented two episodes of acute rejection (maculopapular lesions) in the first 3 months after transplantation; however, these were easily reversed after a few days increasing oral steroid doses and using topical immunosuppressants. The first recipient presented hyperglycemia and serum sickness while the second recipient suffered a thrombosis of the right ulnar artery and an osteomyelitis of left ulna. All the complications were successfully treated. Functional Magnetic Resonance Imaging (fMRI) showed that cortical hand representation progressively shifted from the lateral to the medial region in the motor cortex. After 6 and 2 years respectively, they showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. The first recipient has been working since 2003. They are both satisfied with their grafted hands.

Adolescent↗
PubMed2004

Human hand transplantation: what have we learned?

Hand transplantation may become an important procedure for upper limb functional restoration. To date, 18 patients have been undergone 24 hand operations in the world. Initial results are extremely promising; the functional results are apparently superior to those obtained with prostheses. We report on the combined French and Italian experience of six patients (eight hands), which is based on a jointly devised protocol and represents the largest available clinical series. Six male patients aged 43, 33, 35, 32, 33, and 22 years received either a single right hand-dominant transplantation (four cases) or a simultaneous double hand transplantation (two cases). The time since the amputation ranged from 3 to 22 years. The level of transplantation was at the wrist in five cases (six hands) and at the distal forearm in two cases (two hands). Cold ischemia averaged 11.5 hours. Three patients simultaneously received additional full-thickness skin taken from the donor and transplanted onto their left hip area. This skin served as a source for biopsies and as an additional area to monitor rejection (distant sentinel skin graft). The immunosuppressive protocol included polyclonal antibodies (three patients) or monoclonal anti-CD 25 antibody (three patients), tacrolimus, mycophenolate mofetil, and prednisolone. No surgical complications occurred. Skin rejection occurred at least once in all patients at a mean of 40 days postoperatively. Three patients recovered protective and some discriminative sensation in their palm and fingers. Two patients are recovering sensation, but are still in the early phases of the regenerative process, due to the short time since the transplantation. One patient was not compliant with the immunosuppressive therapy, and underwent uncontrolled rejection and reamputation.

Adolescent↗
PubMed2004

Concerns on clinical application of composite tissue allotransplantation.

Composite tissue allograft has become a clinical reality: hands, vascularized femoral diaphyses, abdominal walls, a larynx have all been transplanted throughout the world. Conventional immunosuppressive protocol has shown to be sufficient and effective. Rejection has been prevented in most cases and when it did occur it was successfully reversed. Skin has been confirmed as the principal target of acute and chronic rejection. There has been no mortality or early graft losses and, particularly in hand transplantation, the survival graft rate is 91% with a follow-up period ranging from 6 months to 61 months. The side effects of immunosuppression are limited and include primarily transient hyperglycemia, an increase in creatinine values and some opportunistic infections (i.e. cytomegalovirus infection). Nerve regeneration and cortical reorganization have been demonstrated in hand transplantation. Functional results have been encouraging particularly for hand and larynx transplantation. Appropriate indications and patient selection, based particularly on patient motivation and compliance, are essential requirements for composite tissue allograft success.

Hand Transplantation↗
PubMed2002

[First transplantation of two hands: results after 18 months].

AIM OF THE STUDY: The previous results achieved in single hand transplantations confirmed the feasibility of this procedure and encouraged us to perform the first human double hand transplantation, which was performed in January 2000. In the present study we reported the results obtained eighteen months after transplantation. PATIENT AND METHODS: The recipient was a 33-year old man suffering from a traumatic amputation of both hands in 1996. Surgery included procurement of the upper extremities from a 18-year old multiorgan cadaveric donor, preparation of the graft and recipient's stumps, transplantation of the hands, which included bone fixation, arterial and venous anastomoses, nerve suture, joining of tendons and muscles, and skin closure. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil. An intensive rehabilitation program was performed. Follow-up included immunological tests, skin biopsies, arteriography, bone scintigraphy, electromyography and brain functional magnetic resonance imaging. RESULTS: No surgical complications, infectious complications and graft-versus-host-disease occurred. Two episodes of acute skin rejection were demonstrated and they were completely reversed increasing steroid dose. Nerve regeneration and cortical reorganization were shown. Sensorimotor recovery was encouraging and life quality improved. CONCLUSION: This double hand transplantation showed that conventional immunosuppressive protocol is effective and safe as well as that functional results are at least as good as those achieved in replanted upper extremities.

Adult↗
PubMed2001

Opposite pattern of MDR1 and caveolin-1 gene expression in human atherosclerotic lesions and proliferating human smooth muscle cells.

Cholesterol esterification and smooth muscle cell (SMC) proliferation are the crucial events in the development of atherosclerotic lesions. The objective of this study was to analyse cholesterol esterification and the expression of MDR1 (multidrug resistance), ACAT (acyl-CoA:cholesterol acyltransferase) and caveolin-1 genes in atherosclerotic and healthy vascular walls, in SMCs obtained from atherosclerotic lesions and saphenous veins. Results demonstrated higher levels of cholesterol esters, ACAT and MDR1 mRNAs and lower levels of caveolin-1 mRNA in atherosclerotic segments compared to adjacent serial sections of the same artery and the corresponding non-atherosclerotic arteries from cadaveric donors. SMCs isolated from atherosclerotic plaques manifested an increased capacity to esterify cholesterol and to grow at a faster rate than SMCs isolated from saphenous veins. In addition, when SMCs from atherosclerotic plaques were cultured in the presence of progesterone, a potent inhibitor of cholesterol esterification, significant growth suppression was observed. An increase in ACAT and MDR1 expression and a concomitant decrease in caveolin-1 expression were also observed in SMCs isolated from atherosclerotic arteries as early as 12 h after serum stimulation. An opposite pattern was found when SMCs were treated with progesterone. These findings support the idea that cholesterol esterification plays a role both in early atherogenesis and in clinical progression of advanced lesions and raise the possibility that the cholesterol ester pathway might directly modulate the proliferation of SMCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Lipid metabolism and molecular changes in normal and atherosclerotic vessels.

OBJECTIVES: a positive correlation between cholesterol esterification, acyl-CoA:cholesterol acyltransferase (ACAT), multidrug resistance (MDR1) gene expression and atherosclerotic lesions has been shown in human arteries. The objective of this study was to map the expression of MDR1, ACAT genes and the cholesteryl ester content in normal, atherosclerotic and varicose human vessels. MATERIALS: vascular segments were obtained from seven cadaveric donors, 27 patients undergoing vascular surgery for severe atherosclerotic disease and 11 patients with saphenous vein varicosities. METHODS: lipid analysis and RT-PCR of MDR1 and ACAT mRNAs were performed. RESULTS: an increase in cholesteryl ester content and in ACAT and MDR1 expression was demonstrated in relation to the age in the arteries prone to atherosclerosis; this expression was maximal in arteries from symptomatic patients. In resistant arteries and in veins cholesteryl ester accumulation was rare and light, while ACAT and MDR1 expression was not related to the age of the subjects. CONCLUSIONS: the results showed that an increase in MDR1 and ACAT expression may be responsible for the accumulation of cholesteryl esters as well as for cell growth rate acceleration in vessel sites prone to atherosclerosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

A primate model of renal ischemia-reperfusion injury for preclinical evaluation of the antileukocyte function associated antigen 1 monoclonal antibody odulimonab.

PURPOSE: We established a primate model to investigate the effects of the antileukocyte function associated antigen 1 (CD 11a) mAb odulimomab (Imtix-Sangstad, Lyon, France) for preventing renal ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 34 Macaca cynomolgus monkeys into groups 1 and 2, which received a renal autograft after 2 hours of cold ischemia, and groups 3 and 4, which received the autograft after 24 hours of cold ischemia. Before cold ischemia all harvested kidneys were subjected to 30 to 45 minutes of warm ischemia. Groups 1 and 3 monkeys were treated with an antileukocyte function associated antigen 1 mAb before cold ischemia and then for 3 days, while groups 2 and 4 monkeys received an IgG1 isotype control. In all groups renal function was investigated before warm ischemia and 72 hours after reperfusion. Serum creatinine and the leukocyte count were determined daily. Histological studies were done and lactoferrin was measured in the autotransplanted kidney 72 hours after reperfusion. RESULTS: A decrease in renal function was shown after 2 hours of cold ischemia with tubular necrosis and mild cell infiltration, while after 24 hours of cold ischemia there was severe renal failure with tubular and glomerular necrosis, and leukocyte infiltration. A significant improvement in renal function and decrease in kidney lactoferrin content was evident in group 1 compared to group 2 at 72 hours, while no significant difference was noted in groups 3 and 4. No difference in histological patterns was evident in treated and untreated animals. CONCLUSIONS: This study provides evidence for the validity of this ischemia-reperfusion injury model in primates. The protective effects of antileukocyte function associated antigen 1 mAb on renal injury was not as dramatic as in rodent models but a significant improvement in renal function was observed in treated animals after 2 hours of cold ischemia.

Animals↗
PubMed2001

Evidence of pituitary adenylate cyclase activating polypeptide (PACAP) in pancreatic islet cells by confocal microscopy.

Several studies have shown that pituitary adenylate cyclase activating polypeptide (PACAP) stimulates at very low concentration insulin release from pancreatic beta cells. In addition, PACAP has been evidenced in pancreatic nervous fibers surrounding the islets, the core of the islet, and the capillaries. The aim of the present study was to demonstrate internalization of PACAP in pancreatic islet cells. Pancreatic islets were obtained from Wistar rat pancreata by modified Lacy's isolation method. The isolated islets were incubated in the presence of Fluo-PACAP 27, a fluorescent ligand specific for PACAP receptors. At the end of incubation the islets were fixed in paraformaldehyde and then observed by confocal microscope. Fluo-PACAP 27 was internalized into pancreatic islet cells, and this process was time- and temperature-dependent (37 degrees C). The fluorescent molecules converged toward the nucleus where an intense fluorescence was evidenced after 60 minutes. Incubation with phenyl arsine oxide as well as with PACAP 6-38, a receptor antagonist, prevented the internalization process. Further studies are required to explain the internalization process of PACAP 27 into the nucleus of pancreatic islet cells.

Animals↗
PubMed2000

Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation.

BACKGROUND: Besides alloimmunity to transplanted pancreatic tissue, recurrent autoimmune beta cell destruction is an additional limitation to successful clinical pancreatic allografts in type 1 diabetic patients. METHODS: We studied the prevalence of autoantibodies to glutamate decarboxylase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diabetic patients receiving pancreatic allografts. Sera from patients were obtained immediately before grafting. A second blood sample was analyzed at the time of graft failure in patients who returned to hyperglycemia and during the same follow-up period in those who experienced a functional pancreatic allograft. Patients were classified according to clinical outcome into chronic graft failure (group A, n=20), acute graft failure and/or arterial thrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoantibodies using an islet cell autoantibody assay, a combi-GAD and IA-2 test, and individual GAD and IA-2 assays. RESULTS: Patients from group A had significantly higher combi-test values than patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher anti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) immediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-2 Ab levels increased from baseline, but only the increase in anti-IA-2 Ab levels reached statistical significance (0.28+/-0.12 vs. 15+/-34, P=0.03). When compared with group C, patients from group A had higher anti-GAD65 Abs (0.29+/-0.35 vs. 0.05+/-0.16, P<0.001) after graft failure. Interestingly, the number of double-Ab-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplants with bladder drainage, the presence of anti-GAD65 and/or anti-IA2 Abs was not associated with a reduction in urinary amylase levels. This suggests that a loss of endocrine function was not associated with exocrine failure in patients from group A. CONCLUSIONS: We can conclude from the present study that peripheral autoimmune markers are useful in diabetic patients receiving pancreatic allografts.

Adult↗
PubMed2000

Effects of portal versus systemic venous drainage in kidney-pancreas recipients.

A randomized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous (PV) and systemic venous (SV) drainage. Fourteen patients (SV) group) received systemically drained and sixteen (PV group) portally drained pancreas allografts. Enteric drainage was performed in both groups. The routine follow-up included documentation of the clinical course and detailed endocrine studies. At 1 year after transplantation, the patient survival rate was 92% for the SV group and 96% for the PV group; the graft survival rate was 78% and 82%, respectively. Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups. In addition, no hyperinsulinemia and lipidic abnormalities were evidenced in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences.

Adult↗