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Biomedical subjects

Antonio Secchi

Publications and source records attributed to Antonio Secchi.

31 records · Page 2Linked to original sources

L-arginine-induced vasodilation of the renal vasculature is preserved in uremic type 1 diabetic patients after kidney and pancreas but not after kidney-alone transplantation.

OBJECTIVE: In uremic type 1 diabetic patients, kidney and pancreas transplantation (KP) and kidney-alone transplantation (KD) provide full restoration of normal renal function; however, only KP, i.e., curing diabetes, is expected to prevent endothelial damages. Our aim was to study L-arginine-induced vasodilation of the renal vasculature in uremic type 1 diabetic patients after KP or KD using magnetic resonance (MR). RESEARCH DESIGN AND METHODS: MR quantitative flow measurements were performed in 15 KP patients (mean age 39.0 +/- 1.7 years, 10 men and 5 women), in 11 KD patients (mean age 47.3 +/- 1.9 years, 7 men and 4 women), and in 8 nondiabetic kidney transplant patients (mean age 44.0 +/- 4.8 years, 7 men and 1 woman), who were used as control subjects, to measure renal blood flow and velocity and renal vascular resistance before and immediately after infusion of L-arginine. RESULTS: Renal blood flow and velocity were not different at baseline in KP, KD, and control subjects. In contrast, during L-arginine administration renal blood flow increased significantly in KP subjects (basal 8.4 +/- 0.6 vs. post 9.6 +/- 0.8 ml/s, Delta 14.3 +/- 4.4%, P < 0.05) and in control subjects (basal 9.3 +/- 0.8 vs. post 9.1 +/- 0.8 ml/s, Delta 17.3 +/- 6.2%, P < 0.01), while it remained unchanged in KD subjects (basal 10.0 +/- 0.8 vs. post 11.6 +/- 0.9 ml/s, Delta -1.36 +/- 6.9%, NS). Parallel results have been achieved for renal blood velocity (KP subjects: 20.1 +/- 4.9%, P < 0.01; control subjects: 23.0 +/- 7.99%, P < 0.01; and KD subjects: -0.3 +/- 6.5%; NS). A reduction in renal vascular resistance in response to L-arginine was evident in KP and control subjects but not in KD patients. CONCLUSIONS: L-Arginine vasodilatory response was successfully assessed with MR quantitative flow measurements. KP patients and control subjects, but not those with KD, showed a preserved L-arginine-induced vasodilation of the renal vasculature.

Adult↗

Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes.

Insulin resistance is a key pathogenic factor of type 2 diabetes (T2DM); in contrast, in type 1 diabetes (T1DM) it is considered a secondary alteration. Increased intramyocellular lipid (IMCL) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM. This study was designed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM. We studied 18 patients with T1DM, 7 older and overweight/obese patients with T2DM, and 15 nondiabetic, insulin-resistant offspring of T2DM parents (OFF) and 15 healthy individuals (NOR) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6-2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles. T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate (MCR: 5.1 +/- 0.6 and 3.2 +/- 0.8 ml x kg(-1) min(-1)) similar to OFF (5.3 +/- 0.4 ml x kg(-1) x min(-1)) compared with NOR (8.5 +/- 0.5 ml x kg(-1) min(-1), P < 0.001). Soleus IMCL content was increased in T1DM (112 +/- 15 AU), T2DM (108 +/- 10 AU) and OFF (82 +/- 13 AU) compared with NOR (52 +/- 7 AU, P < 0.05) and the result was inversely proportional to the MCR (R2 = 0.27, P < 0.001); an association between IMCL content and Hb A1c was found only in T1DM (R2 = 0.57, P < 0.001). Fasting plasma adiponectin was reduced in T2DM (7 +/- 1 microg/ml, P = 0.01) and OFF (11 +/- 1 microg/ml, P = 0.03) but not in T1DM (25 +/- 6 microg/ml), whose plasma level was increased with respect to both OFF (P = 0.03) and NOR (16 +/- 2 microg/ml, P = 0.05). In conclusion, in T1DM, T2DM, and OFF, IMCL content was associated with insulin resistance, demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic (chronic hyperglycemia) alterations. The increased adiponectin levels in insulin-resistant patients with T1DM, in contrast to the reduced levels found in patients with T2DM and in OFF, demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear.

Adiponectin↗

Successful endovascular treatment for gastroduodenal artery pseudoaneurysm with an arteriovenous fistula after pancreas transplantation.

The aim of this study was to demonstrate the usefulness of endovascular treatment for gastroduodenal artery pseudoaneurysm with an arteriovenous fistula after simultaneous pancreas-kidney transplantation. We describe the case of a 38-year-old man who underwent successful simultaneous pancreas-kidney transplantation. An asymptomatic pseudoaneurysm of the donor gastroduodenal artery with an arteriovenous fistula was incidentally diagnosed by routine color flow Doppler ultrasound (CDU) examination and confirmed by 3-D gadolinium-enhanced magnetic resonance angiography (MRA) 15 days after transplantation. Selective arteriography (via the right femoral artery) confirmed an arteriovenous fistula and a pseudoaneurysm of the donor gastroduodenal artery. The patient underwent successful endovascular embolization. At 11 months of follow-up, normal pancreatic function was reported. Endovascular treatment for gastroduodenal artery pseudoaneurysm with an arteriovenous fistula after pancreas transplantation obviates the need for surgical intervention.

Adult↗

Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation.

BACKGROUND: The aim of this study was to evaluate the effects of islet transplantation on patient survival and diabetic vascular complications. METHODS: Thirty-seven type 1 uremic diabetic kidney transplant patients underwent islet transplantation (KI group). Uremic type 1 diabetic kidney-pancreas (KP group, n=162), kidney-alone (KD group, n=42) transplant patients, and uremic type 1 diabetic patients still on hemodialysis (HD+DM group, n=196) constituted the control groups for survival and endothelial morphology. RESULTS: Patient survival was similar in the KI and KP groups and higher than in the HD+DM group (P<0.05). Patients experiencing long-term islet function (KI-successful [KI-s], n=24) showed a better survival (100%, 100%, and 90%) than those in the KI group who lost islet function (KI-unsuccessful [KI-u], n=13) (84%, 75%, and 45%) at 1, 4 and 7 years, respectively (P=0.02). The cardiovascular death rate for the KI group (18%) was similar to the KD group (19%) but lower when the KI-s group is considered alone (5%), and showed a cardiovascular death rate similar to the KP group (8%). The KI-s group showed a good metabolic profile, with reduction of exogenous insulin requirement and persistent C-peptide secretion, as compared with the KI-u group. The endothelial morphology was evaluated with a skin biopsy obtained in all groups. The KI-s and the KP groups demonstrated decreased signs of endothelial injury compared with the KI-u and HD+DM groups. The KI group showed a better atherothrombotic profile than the HD+DM group, with higher levels of natural anticoagulant protein. CONCLUSIONS: Successful islet transplantation improves survival, atherothrombotic profile, and endothelial morphology in uremic type 1 diabetic kidney transplant patients.

Adult↗

Successful surgical salvage of pancreas allograft.

BACKGROUND: Early and late complications related to the pancreas after simultaneous kidney-pancreas transplantation (SKPT) frequently result in graft loss. The authors describe a surgical rescue technique that allows salvage of the pancreatic graft when surgical complications appear after the transplant. METHODS: Of 158 patients who underwent SKPT, 7 were identified with posttransplant complications that required surgical salvage of the pancreas allograft. The surgical salvage technique consisted of the following: pancreatoduodenectomy with conversion from whole-pancreas transplant with bladder or enteric diversion to segmental graft with duct injection (three cases) and conversion from whole-pancreas transplant with duct injection (four cases). RESULTS: Five of seven pancreas allografts are still functioning, with a mean follow-up of 28 months (range, 6-42 months). CONCLUSION: The described surgical treatment may be useful for surgical salvage of the pancreatic allograft, without major impairment of endocrine function.

Humans↗

Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants.

The potential effects of islet transplantation on the renal function of 36 patients with type I diabetes mellitus and kidney transplants were studied with 4 yr of follow-up monitoring. Kidney-islet recipients were divided into two groups, i.e., patients with successful islet transplants (SI-K group) (n = 24, fasting C-peptide levels of >0.5 ng/ml for >1 yr) and patients with unsuccessful islet transplants (UI-K group) (n = 12, fasting C-peptide levels of <0.5 ng/ml). Kidney graft survival rates and function, urinary albumin excretion rates, and sodium handling were compared. Na(+)/K(+)-ATPase activity in protocol kidney biopsies and in red blood cells was cross-sectionally analyzed. The SI-K group demonstrated better kidney graft survival rates (100, 83, and 83% at 1, 4, and 7 yr, respectively) than did the UI-K group (83, 72, and 51% at 1, 4, and 7 yr, respectively; P = 0.02). The SI-K group demonstrated reductions in exogenous insulin requirements and higher C-peptide levels, compared with the UI-K group, whereas GFR values were similar. Microalbuminuria (urinary albumin index) increased significantly in the UI-K group only (UI-K, from 92.0 +/- 64.9 to 183.8 +/- 83.8, P = 0.05; SI-K, from 108.5 +/- 53.6 to 85.0 +/- 39.0, NS). In the SI-K group, but not in the UI-K group, natriuresis decreased at 2 and 4 yr (P < 0.01). The SI-K group demonstrated greater Na(+)/K(+)-ATPase immunoreactivity in renal tubular cells (P = 0.05) and higher activity in red blood cells (P = 0.03), compared with the UI-K group. The Na(+)/K(+)-ATPase activity in red blood cells was positively correlated with circulating C-peptide levels but not with glycated hemoglobin levels. Successful islet transplantation was associated with improvements in kidney graft survival rates and function among uremic patients with type I diabetes mellitus and kidney grafts.

Albumins↗

Long-term beneficial effect of islet transplantation on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients.

OBJECTIVE: Our aim was to evaluate the long-term effects of transplanted islets on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients. RESEARCH DESIGN AND METHODS: A total of 34 type 1 diabetic kidney-transplanted patients underwent islet transplantation and were divided into two groups: successful islet-kidney transplantation (SI-K; 21 patients, fasting C-peptide serum concentration >0.5 ng/ml for >1 year) and unsuccessful islet-kidney transplantation (UI-K; 13 patients, fasting C-peptide serum concentration <0.5 ng/ml). Patients cumulative survival, cardiovascular death rate, and atherosclerosis progression were compared in the two groups. Skin biopsies, endothelial dependent dilation (EDD), nitric oxide (NO) levels, and atherothrombotic risk factors [von Willebrand factor (vWF) and D-dimer fragment (DDF)] were studied cross-sectionally. RESULTS: The SI-K group showed a significant better patient survival rate (SI-K 100, 100, and 90% vs. UI-K 84, 74, and 51% at 1, 4, and 7 years, respectively, P = 0.04), lower cardiovascular death rate (SI-K 1/21 vs. UI-K 4/13, chi(2) = 3.9, P = 0.04), and lower intima-media thickness progression than the UI-K group (SI-K group: delta1-3 years -13 +/- 30 micro m vs. UI-K group: delta1-3 years 245 +/- 20 micro m, P = 0.03) with decreased signs of endothelial injuring at skin biopsy. Furthermore, the SI-K group showed a higher EDD than the UI-K group (EDD: SI-K 7.8 +/- 4.5% vs. UI-K 0.5 +/- 2.7%, P = 0.02), higher basal NO (SI-K 42.9 +/- 6.5 vs. UI-K 20.2 +/- 6.8 micro mol/l, P = 0.02), and lower levels of vWF (SI-K 138.6 +/- 15.3 vs. UI-K 180.6 +/- 7.0%, P = 0.02) and DDF (SI-K 0.61 +/- 0.22 vs. UI-K 3.07 +/- 0.68 micro g/ml, P < 0.01). C-peptide-to-creatinine ratio correlated positively with EDD and NO and negatively with vWF and DDF. CONCLUSIONS: Successful islet transplantation improves survival, cardiovascular, and endothelial function in type 1 diabetic kidney-transplanted patients.

Adult↗

Magnetic resonance image (MRI) of an acquired aorto-pulmonary fistula, associated with cerebral and paradoxical embolism.

Aorto-pulmonary fistula has been described in Marfan's syndrome, with severe degeneration of connective tissue, particularly severe at the aortic site. Rarely, the chronic evolution of this condition could determine the formation of a fistula between the aorta and the adjacent anatomic structures [Ann Thorac Surg 59 (1995) 1563; J Cardiovasc Surg 29 (1988) 403; Thorax 28 (1973) 521]. Here, we describe the first case of aorto-pulmonary fistula, with cerebral and paradoxical embolism, described with angio-nuclear magnetic resonance (MRI) of the heart.

Aged↗

Histamine-induced cytokine production and ICAM-1 expression in human conjunctival fibroblasts.

PURPOSE: Conjunctival fibroblasts stimulated with histamine (H) may be directly involved in the inflammatory and remodeling processes of chronic allergic conjunctival diseases. METHODS: Proinflammatory cytokine and growth factor production, and the expression of intercellular adhesion molecule-1 (ICAM-1) were studied in conjunctival fibroblast cultures challenged with different concentrations of H (from 10(-9) M to 10(-) (4) M). Interleukin (IL)-1, IL-4, IL-6, IL-8, tumor necrosis factor-alfa (TNF-alpha), fibroblast growth factor (FGF), epidermal growth factor (EGF) and transforming growth factor-beta (TGFbeta-1) were measured in supernatants. ICAM-1 expression was evaluated by a fluorescence activated cell sorter (FACS). Inhibitory effects of the H-1 antagonists (antiH): emedastine, levocabastine, and azelastine, and of the antiH-2, cimetidine, on H-stimulated fibroblasts were evaluated by measuring both cytokines in supernatants and the cellular expression of ICAM-1. RESULTS: Histamine increased the production of IL-1, IL-6 and IL-8, and ICAM-1 expression. TNF-alpha, IL-4 and growth factor production were not modified by histamine. The antiH-1, emedastine, significantly reduced H-induced production of IL-1, IL-6 and IL-8, while azelastine reduced only IL-1. Levocabastine and cimetidine were less effective. The histamine-induced increase in ICAM-1 expression was inhibited by emedastine but not by azelastine and levocabastine. CONCLUSIONS: Histamine has pro-inflammatory effects on conjunctival fibroblasts, inducing the production of cytokines and the expression of ICAM-1. Emedastine significantly reduced cytokine and ICAM-1 expression from H-stimulated fibroblasts. Conjunctival fibroblasts may contribute to the maintenance of inflammation in chronic allergic diseases.

Cells, Cultured↗

Urological complications after simultaneous renal and pancreatic transplantation.

OBJECTIVE: To report the urological complications after simultaneous renal and pancreatic transplantation. DESIGN: Retrospective study. SETTING: Teaching hospital, Italy. SUBJECTS: 143 consecutive patients having simultaneous renal and pancreatic transplantation by one of three techniques. 33 segmental pancreas with duct occlusion, 77 whole pancreas with bladder diversion, and 33 enteric diversion with systemic (n = 26) or portal venous drainage (n = 7). Urological complications were related to the pancreatic transplant, to the renal transplant, or unrelated to the transplant. MAIN OUTCOME MEASURES: Morbidity. RESULTS: After occlusion of the duct and enteric diversion, there were no urological complications related to the pancreatic transplant. On the other hand, among the 77 patients with pancreatic drainage into the bladder, urological complications were common (56/77; 73%). Complications related to the renal transplant were recorded in 6/33 (18%), 26/77 (34%) and 12/33 (36%), respectively. Complications unrelated to the transplant occurred in 6/77 patients (8%) in the bladder drainage group. Five patients after bladder drainage required cystoenteric conversion. CONCLUSIONS: Enteric diversion is a safe alternative to bladder diversion and results in significantly fewer urological complications.

Adult↗

Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation.

We investigated the capacity of human islets to produce monocyte chemoattractant protein-1 (MCP-1). Primary cultures of pancreatic islets expressed and secreted MCP-1, as determined by Northern blot, immunohistochemistry, in situ hybridization, and enzyme-linked immunosorbent assay. The produced MCP-1 was biologically active as it attracted monocytes in chemotaxis assay, and chemotactic activity was almost abrogated by a neutralizing anti-MCP-1 monoclonal antibody. Expression of MCP-1 was increased by primary inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha) and lipopolysaccharide at both the mRNA and protein levels but not by glucose. However, MCP-1 did not modulate insulin secretion. MCP-1 secreted by pancreatic islets plays a relevant role in the clinical outcome of islet transplant in patients with type 1 diabetes. In fact, low MCP-1 secretion resulted as the most relevant factor for long-lasting insulin independence. This finding opens new approaches in the management of human islet transplantation. Finally, the finding that MCP-1 appears constitutively present in normal human islet beta-cells (immunohistochemistry and in situ hybridization), in the absence of an inflammatory infiltrate, suggests that this chemokine could have functions other than monocyte recruitment and opens a new link between the endocrine and immune systems.

Adult↗

Advantages and disadvantages of enteric versus bladder diversion in simultaneous kidney-pancreas transplantation.

Simultaneous kidney-pancreas transplantation is universally accepted as being the first-choice treatment for insulin-dependent diabetes mellitus in young patients with end stage renal disease. One hundred and fifty-six simultaneous kidney-pancreas transplantations were evaluated, namely, 33 segmental pancreas transplants with duct occlusion using neoprene (group I), 73 whole pancreas transplants with bladder diversion (group II) and 46 whole pancreas transplants with enteric diversion (group III) (37 with systemic venous drainage and 9 with portal diversion). Patient actuarial survival rates at 1, 5 and 10 years were 85%, 78% and 49%, respectively, in group I and 95%, 78% and 65% in group II. In group III the rates were 87% and 72% at 1 and 3 years, respectively. Kidney survival rates at 1, 5 and 10 years were 83%, 72% and 36% in group I and 89%, 78% and 59% in group II. In group III the survival rates were 85% and 72% at 1 and 3 years. Pancreas survival rates at 1, 5 and 10 years were 66%, 37% and 15% in group I and 73%, 67% and 65% in group II. In group III the rates were 87% and 68% at 1 and 3 years. Developments in the fields of organ retrieval technology, clinical immunosuppression and surgical technique have enabled us to improve our success rates, both in terms of organ survival and the quality of life of kidney-pancreas transplant recipients.

Adult↗