Hybrid minimally invasive esophagectomy for cancer: impact on postoperative inflammatory and nutritional status.

The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit.

Raw milk-associated foodborne infections: a scoring system for the risk-based categorisation of raw dairy farms.

A pilot study was implemented in the Veneto Region of Italy, aimed at classifying dairy farms which produce milk to be commercialised unpasteurised on the basis of their risk of faecal contamination of milk, which is directly correlated to the probability of a foodborne pathogen, if present in the herd and eliminated through faecal excretion, to contaminate the raw product. Factors considered to be relevant in the definition of the risk of pathogens potentially present in animal faeces to be transmitted to milk, were hierarchically structured, weighted through the application of experts elicitation methods (Analytic Hierarchy Process, Delphi) and used to categorise farms through the application of a herd questionnaire. The probability of faecal contamination of milk, and thus the risk of pathogens transfer appears to be modulated more by farm management than by the structure of the farm or the health status of the herd. Such a method, combined with the microbiological evaluation of the prevalence of faecal excretion of such pathogens, can be used to implement a risk-based surveillance programme and to apply targeted control measures.

Target gene expression signatures in neutrophils and lymphocytes from cattle administered with dexamethasone at growth promoting purposes.

The glucocorticoid dexamethasone (DEX), when used as a growth promoter, cause morphological and functional alterations in cattle lymphoid organs and cells. In the present experiment, the transcriptional effects of an illicit DEX protocol upon six target genes were investigated in cattle neutrophils (NEU) and lymphocytes (LFC). Blood samples were taken before (T(0)) and 2, 3, 10, 19, 31 and 43 days from the beginning of DEX administration (T(1)-T(6)). Leukocytes were counted and cells isolated by gradient centrifugation; then, glutathione peroxidase 1 and 3 (GPX1 and GPX3), glucocorticoid receptor alpha (GRα), l-selectin, nuclear factor κB, subunit p65 (NFκB) and tumor necrosis factor alpha (TNFα) mRNA amounts were measured through a quantitative Real Time RT-PCR approach. A significant change vs controls in NEU/LFC ratio was noticed from T(3) forward. Compared to T(0), DEX significantly increased to a variable extent all candidate gene mRNAs abundances in NEU; in contrast, only l-selectin, GRα and GPX1 were significantly up-regulated in LFC. Present results suggest that illicit DEX affects transcription in cattle immune cells, that might be considered as a promising surrogate tissue for the screening of DEX abuse in cattle farming.

Evaluation of indirect biomarkers for detecting corticosteroids used as illegal growth promoters in beef cattle.

The histological status of the thymus, blood cortisol concentration and circulating neutrophil:lymphocyte ratio were evaluated in 349 slaughtered beef cattle, to assess the potential of these parameters as indirect biomarkers of the illegal use of corticosteroids in meat production. The livers of 20 of the animals were analysed chemically for residues of corticosteroids. The morphology of the thymus was examined for adipose tissue infiltration, cortical atrophy and 'starry sky' appearance, and on the basis of these characteristics, the animals were considered to be negative, suspected or positive for illegal corticosteroid treatment. The animals considered to be negative had a mean cortisol concentration that was significantly higher (29 ng/ml) than that of the animals suspected for corticosteroid treatment (22 ng/ml). Using the chemical analysis as the gold standard for identifying illegally treated animals, the histological examination of the thymus had a sensitivity of 100 per cent and a specificity of 85 per cent. The samples that were positive by chemical analysis had cortisol concentrations of less than 2.0 ng/ml, whereas the mean cortisol concentration of the negative samples was 10.3 ng/ml.

Administration of dexamethasone per os in finishing bulls. I. Effects on productive traits, meat quality and cattle behaviour as indicator of welfare.

The study investigated the effects of prolonged oral administration of dexamethasone at a low daily dosage of 0.75 mg/head per day (Dexa) on beef cattle productive traits, behaviour and meat quality. In all, 14 finishing Marchigiana bulls were used in a trial that begun 56 days prior to slaughter, of which six bulls received treatment from day 5 to day 53, whereas the remaining animals were used for Control. The animals treated showed an increased average daily gain (1515 v. 1177 g/head per day; P < 0.05; s.e.d. = 48.54) and improved warm carcass dressing percentage (60.8% v. 59.7%; P < 0.05; s.e.d. = 0.32). Behavioural observation did not permit a clear distinction between treated and Control animals since feeding and social behaviour were similar in both groups. The bulls treated spent less time lying (16.5% v. 34.6%; P < 0.05; s.e.d. = 4.38) and grooming (6.7% v. 11.9%; P < 0.05; s.e.d. = 1.23), and this may indicate poorer welfare. No evidence of treatment was observed in other carcass traits, and redness was the only meat quality parameter slightly affected by corticosteroid administration.

Administration of dexamethasone per os in finishing bulls. II. Effects on blood parameters used as indicators of animal welfare.

A set of hormonal, haematological and biochemical parameters was used to evaluate the physiological response and welfare status of 14 finishing Marchigiana bulls treated for 49 days with a low daily dosage (0.75 mg/head per day) of dexamethasone per os. Compared to the Control group, dexamethasone decreased cortisol concentrations (42.3 v. 5.7 nmol/l; s.e.d. = 4.17; P < 0.001), and led to the reversal of the leukocyte formula in the animals treated (P < 0.05). Total serum proteins (70.2 v. 73.9 g/l; s.e.d. = 1.55; P < 0.05), in particular ß1 globulins (7.5 v. 9.1 g/l; s.e.d. = 0.24; P < 0.01) and fibrinogen (199 v. 258 mg/dl; s.e.d. = 32.70; P < 0.05), increased as a consequence of treatment. Prolonged dexamethasone administration led the bulls to an apparently chronic stress condition. Moreover, the study indicated various blood parameters that might be used by health officials as effective tools in identifying beef cattle suspected of being illegally treated with dexamethasone.

Reconstruction of conjunctiva with amniotic membrane after excision of large conjunctival melanoma: a long-term study.

PURPOSE: To evaluate, on a long- term basis, the role of amniotic membrane in the reconstruction of large conjunctival defects after excision of large conjunctival melanoma. METHODS: Four consecutive patients with diffuse conjunctival melanoma involving both bulbar and palpebral conjunctiva were studied. Conjunctival melanoma was completely excised (with wide clinically disease-free margins) and amniotic membrane immediately sutured to the surrounding conjunctiva and sclera to cover the conjunctival defect. Minimum follow-up was 48 months. RESULTS: Successful conjunctival surface reconstruction and physiologic fornical depth were achieved in all patients within 6 weeks. No recurrence of primary melanoma was observed during long-term follow-up. CONCLUSIONS: Amniotic membrane transplantation is an effective alternative in ocular surface repairing surgery after removal of large conjunctival tumors.

Field experiences in the control of avian influenza outbreaks in densely populated poultry areas.

From 1997 to 2003, Italy has been affected by two epidemics of highly pathogenic avian influenza (HPAI) and by several outbreaks of low pathogenic avian influenza (LPAI). In 1999-2000 a severe HPAI epidemic affected the country, causing 413 outbreaks: a total of about 16 million birds died or were stamped out. From August 2000 to March 2001, a H7N1 LPAI strain infected 78 poultry farms. The last affected flock was stamped out on the 26th of March 2001. In October 2002, another LPAI virus of the H7N3 subtype emerged and infected a total of 388 poultry holdings. Eradication measures were based on stamping out or controlled marketing of slaughtered birds on infected farms and on the prohibition of restocking. Restriction measures on the movement of live poultry, vehicles and staff were also imposed. To supplement these disease control measures, two emergency vaccination programmes, based on the "DIVA" (Differentiating Infected from Vaccinated Animals) strategy were implemented. The two vaccination campaigns (2000-2002 and 2002-2003) both resulted in the eradication of infection. However, the first campaign appeared to be more successful that the second and possible explanations are discussed.

Effect of lercanidipine compared with ramipril on albumin excretion rate in hypertensive Type 2 diabetic patients with microalbuminuria: DIAL study (diabete, ipertensione, albuminuria, lercanidipina).

Microalbuminuria and hypertension are risk factors for diabetic nephropathy in Type 2 diabetic patients. Recent data suggest that blockade of the renin-angiotensin system slows the progression of diabetic nephropathy; in contrast, the results on the renoprotective effect of calcium channel antagonists are conflicting. We evaluated the effectiveness of lercanidipine, in comparison with ramipril, on the reduction in albumin excretion rate (AER) and blood pressure in mild-to-moderate hypertensive patients with Type 2 diabetes and persistent microalbuminuria. A total of 277 patients were enrolled in a multicentric, randomized, double-blind, active-controlled, parallel-group trial; 180 were randomized to receive 10-20 mg/day of lercanidipine or 5-10 mg/day of ramipril and followed up for 9-12 months. The primary outcome was the change in AER from baseline. After 9-12 months of follow-up, a reduction in AER of -17.4+/-65 microg/min (p<0.05) and -19.7+/-52.5 (p<0.05) in the lercanidipine and ramipril group, respectively, was observed, without differences between the groups. A significant reduction in systolic and diastolic blood pressure was observed in both the lercanidipine and ramipril-based treatment groups (p<0.0001 for both). This study demonstrated that treatment with lercanidipine 10-20 mg/day does not worsen albuminuria in microalbuminuric Type 2 diabetic patients with hypertension. Indeed, both lercanidipine and ramipril treatments resulted in a significant reduction in AER without a statistically significant difference between the two groups.

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Secretory defects induced by immunosuppressive agents on human pancreatic beta-cells.

Despite the considerable interest for islet and pancreas transplantation, remarkably little is known about the direct effects of immunosuppressive drugs on human beta-cell function. We measured different insulin secretory parameters and insulin gene expression of human islets cultured for 5 days in the presence of mycophenolate mofetil (MMF), cyclosporin A (CsA), tacrolimus (FK506) or a mixture of 3 cytokines. Basal insulin release after exposure to cytokines and FK506 was significantly higher than in control islets. Responsiveness to an acute glucose stimulus did not differ significantly between control and treated islets. However, absolute incremental insulin responses (delta-AUCs) of islets exposed to cytokines or FK506 were significantly higher compared to islets exposed to CsA or MMF, mainly because of the higher basal release. Indeed, maximal over basal release (stimulation index, SI) tended to be lower in islets exposed to FK506 than in control islets. Insulin gene expression was significantly reduced only in islets exposed to CsA. FK506 was, among those tested, the immunosuppressive drug that most profoundly altered the normal insulin secretory pattern of human beta-cells, whereas CsA was the only inhibiting insulin gene expression. Although the abnormalities induced by the immunosoppressive drugs utilized in this study were modest, these in vitro data are consistent with the reported in vivo diabetogenicity of CsA and FK506 and point to MMF as the ideal immunosuppressive agent from a pancreatic beta-cell point of view.

Cardiovascular outcomes after kidney-pancreas and kidney-alone transplantation.

BACKGROUND: This study retrospectively assessed, with an intention-to-treat analysis, the effect of kidney-pancreas transplantation (KP) on survival and cardiovascular outcome in type 1 diabetic uremic patients. METHODS: A total of 351 uremic type 1 diabetic patients were enrolled on a waiting list for KP: 130 underwent KP transplantation, 25 underwent kidney transplantation alone (KA), whereas 196 patients remained on dialysis (WL). The three populations had similar cardiovascular conditions. Actuarial survival rates and causes of death were recorded over a period of seven years. Finally, 23 KP and 13 KA patients underwent left radionuclide ventriculography, during a follow-up of four years. RESULTS: In the entire group of 351 patients the seven-year survival rate was 77.4% for KP, 56.0% for KA and 39.6% for WL (KP vs. WL, P = 0.01). Cardiovascular death rate was 7.6% in KP, 20.0% in KA and 16.1% in WL (KP versus WL, P = 0.03; KP vs. KA, P = 0.16). In the subsample studied with radionuclide ventriculography, left ventricular ejection fraction improved in KP, but did not in KA, with significant differences between groups at two and four years. At four years only the KP patients presented normal values of diastolic parameters, including the peak filling rate, time-to-peak filling rate, and peak filling rate/peak ejection rate ratio. Glycated hemoglobin was negatively associated with the ejection fraction, peak filling rate and peak filling rate/peak ejection rate ratio, and positively associated with the time-to-peak filling rate. CONCLUSIONS: Normalization of blood glucose metabolism and improvement of blood pressure control obtained with KP transplant is associated with positive effects on survival, cardiovascular death rate, and left ventricular function.

Autoantibody response to islet transplantation in type 1 diabetes.

Islet allotransplantation into patients with autoimmune type 1 diabetes represents a reexposure to autoantigen. Here, measurement of antibodies to GAD and IA-2 autoantigens before and after islet transplantation in 36 patients (33 receiving islet plus kidney grafts with cyclosporin and steroid-based immunosuppression, and 3 receiving solitary islet transplants with mycophenolate but cyclosporin-free immunosuppression) demonstrated marked rises in GAD antibodies within 7 days posttransplantation in 5 patients (3 receiving islet after kidney transplants, and 2 receiving solitary islet transplants) and within 30 days in the third patient receiving solitary islet transplantation. GAD antibodies were of the IgG1 subclass, against major autoantigenic epitopes, and in cases of islet after kidney transplants, the responses were short-lived and not accompanied by HLA antibodies. Two of these patients had subsequent marked rises of IA-2 antibodies, and an additional patient had a marked rise in IgM-GAD antibodies 3 years after transplantation. Insulin independence was not achieved in patients with autoantibody elevations and was significantly less frequent in these patients. These data are consistent with a reactivation of autoimmunity that may be dependent on immunosuppression therapy and is associated with impaired graft function.

Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine.

There is growing evidence that hypertriglyceridemia exacerbates ischemic injury. We tested the hypothesis that triglycerides impair myocardial recovery from low-flow ischemia in an ex vivo model and that such an effect is related to endothelin-1. Hyperglycemic (glucose concentration = 12 mmol/l) and hyperinsulinemic (insulin concentration = 1.2 micromol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (PO(2) = 670 mmHg, pH 7.4, 37 degrees C) added with increasing triglycerides (0, 1,000, 2,000, and 4,000 mg/dl, n = 6-9 rats/group). Hearts were exposed to 60 min of low-flow ischemia (10% of basal coronary flow), followed by 30 min of reperfusion. We found that increasing triglycerides impaired both the diastolic (P < 0.005) and systolic (P < 0.02) recovery. The release of endothelin-1 during reperfusion increased linearly with triglyceride concentration (P = 0.0009). Elevated triglycerides also increased the release of nitrite and nitrate (NO(x)), the end products of nitric oxide, up to 6 micromol/min. Trimetazidine (1 micromol) further increased NO(x) release, blunted endothelin-1 release, and protected myocardial function during recovery. We conclude that high triglyceride levels impair myocardial recovery after low-flow ischemia in association with endothelin-1 release. The endothelium-mediated effect of triglycerides on both contractile recovery and endothelin-1 release is prevented by 1 microM trimetazidine.

Prediction of the long-term metabolic success of the pancreatic graft function.

BACKGROUND: Strategies to prevent the return to the diabetic state for graft loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether daily glucose, insulin, and c-peptide profiles and studies of insulin sensitivity and secretion after transplantation predict pancreatic graft failure. METHODS: Fifty-three subjects with type 1 diabetes with end-stage renal failure who received a combined pancreas and kidney transplant underwent the following procedures 1 year after transplantation: 1-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n=51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin secretion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitivity (M value, n=14). The recipients were then followed up to 8 years (mean follow-up 4.8+/-0.3 years) to evaluate the return to the diabetic state. RESULTS: Survival analysis showed that plasma glucose in the profiles and insulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL, corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cutoff value of insulin delta peak <32 microU/ml in the IVGTT predicted the return to the diabetic state within 4 years from transplantation with a 75% specificity and a 75% sensitivity. In contrast, the M value in the clamp was devoid of predictive value. CONCLUSIONS: This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabetic state. The risk is related to defects in insulin secretion and not to insulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early determinants of graft failure.

Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients.

UNLABELLED: The aim of this study was to evaluate whether long-term administration of arginine acting through a normalization of NO/cyclic-guanosine-3' 5'-cyclic monophosphate (cGMP) pathway was able to ameliorate peripheral and hepatic insulin sensitivity in 12 lean type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind study was performed for 3 months. In the first month, patients were treated with their usual diet. Then they were randomly allocated into to groups. In group 1, patients were treated with diet plus placebo (orally three times per day) for 2 months. In group 2 patients were treated for 1 month with diet plus placebo orally, three times per day) and then for 1 month with diet plus L-arginine (3 g three times per day). At the end of the first and the second month of therapy, patients underwent a euglycemic-hyperinsulinemic clamp combined with [6,6-2H2] glucose infusion. A total of 10 normal subjects underwent the same test as control subjects. RESULTS: In group 1, no changes in basal cGMP levels, systolic blood pressure, forearm blood flow, glucose disposal, and endogenous glucose production were observed throughout. In group 2, L-arginine normalized basal cGMP levels and significantly increased forearm blood flow by 36% and glucose disposal during the clamp by 34% whereas it decreased systolic blood pressure and endogenous glucose production by 14 and 29%, respectively. However, compared with normal subjects, L-arginine treatment was not able to completely overcome the defect in glucose disposal. CONCLUSIONS: L-Arginine treatment significantly improves but does not completely normalizc peripheral and hepatic insulin sensitivity in type 2 diabetic patients.

Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients.

Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 +/- 0.02 U x kg(-1) body wt x day(-1); fasting plasma glucose < 7.7 mmol/l; HbA1c < or = 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U x kg(-1) body wt x day(-1)), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U x kg(-1) body wt x day(-1)), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-2H3]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levels for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 micromol/l) and branched-chain amino acids (337.6 +/- 16.6 micromol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of approximately 60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone.

Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in patients with uremia and type 1 diabetes.

Cardiovascular disease and the development of coronary artery disease play a pivotal role in increasing mortality in patients with type 1 diabetes. The aim of our study was to evaluate the effects of pancreas transplantation on atherosclerotic risk factors, endothelial-dependent dilation (EDD), and progression of intima media thickness (IMT) in patients with uremia and type 1 diabetes after kidney-alone (KA) or kidney-pancreas (KP) transplantation. A cross-sectional study comparing two groups of patients with type 1 diabetes was performed. Sixty patients underwent KP transplantation and 30 patients underwent KA transplantation. Age and cardiovascular risk profile were comparable in patients before transplantation. In all patients, atherosclerotic risks factors (lipid profile, fasting and post-methionine load plasma homocysteine, von Willebrand factor levels, D-dimer fragments, and fibrinogen) were assessed and Doppler echographic evaluation of IMT and endothelial function with flow-mediated and nitrate dilation of the brachial artery was performed. Twenty healthy subjects were chosen as controls (C) for EDD. Compared with patients undergoing KA transplantation, patients undergoing KP transplantation showed lower values for HbA1c (KP = 6.2 +/- 0.1% vs. KA = 8.4 +/- 0.5%; P < 0.01), fasting homocysteine (KP = 14.0 +/- 0.7 mcromol/l vs. KA = 19.0 +/- 2.0 micromol/l; P = 0.02), von Willebrand factor levels (KP = 157.9 +/- 8.6% vs. KA = 212.5 +/- 16.2%; P < 0.01), D-dimer fragments (KP = 0.29 +/- 0.02 microg/ml vs. KA = 0.73 +/- 0.11 microg/ml;P < 0.01), fibrinogen (KP = 363.0 +/- 11.1 mg/dl vs. KA = 397.6 +/- 19.4 mg/dl; NS), triglycerides (KP = 122.7 +/- 8.6 mg/dl vs. KA = 187.0 +/- 30.1 mg/dl; P = 0.01), and urinary albumin excretion rate (KP = 13.5 +/- 1.9 mg/24 h vs. KA = 57.3 +/- 26.3 mg/24 h; P < 0.01). Patients undergoing KP transplantation showed a normal EDD (KP = 6.21 +/- 2.42%, KA = 0.65 +/- 2.74%, C = 8.1 +/- 2.1%; P < 0.01), whereas no differences were observed in nitrate-dependent dilation. Moreover, IMT was lower in patients undergoing KP transplantation than in patients undergoing KA transplantation (KP = 0.74 +/- 0.03 mm vs. KA = 0.86 +/- 0.09 mm; P = 0.04). Our study showed that patients with type 1 diabetes have a lower atherosclerotic risk profile after KP transplantation than after KA transplantation. These differences are tightly correlated with metabolic control, fasting homocysteine levels, lower D-dimer fragments, and lower von Willebrand factor levels. Normal endothelial function and reduction of IMT was observed only in patients undergoing KP transplantation.