Biomedical subjects

Antonio Secchi

Publications and source records attributed to Antonio Secchi.

At least 19 recordsLinked to original sources

PubMed2006

International trial of the Edmonton protocol for islet transplantation.

BACKGROUND: Islet transplantation offers the potential to improve glycemic control in a subgroup of patients with type 1 diabetes mellitus who are disabled by refractory hypoglycemia. We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol). METHODS: We enrolled 36 subjects with type 1 diabetes mellitus, who underwent islet transplantation at nine international sites. Islets were prepared from pancreases of deceased donors and were transplanted within 2 hours after purification, without culture. The primary end point was defined as insulin independence with adequate glycemic control 1 year after the final transplantation. RESULTS: Of the 36 subjects, 16 (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had complete graft loss 1 year after the final transplantation. A total of 21 subjects (58%) attained insulin independence with good glycemic control at any point throughout the trial. Of these subjects, 16 (76%) required insulin again at 2 years; 5 of the 16 subjects who reached the primary end point (31%) remained insulin-independent at 2 years. CONCLUSIONS: Islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus and unstable control, but insulin independence is usually not sustainable. Persistent islet function even without insulin independence provides both protection from severe hypoglycemia and improved levels of glycated hemoglobin. (ClinicalTrials.gov number, NCT00014911 [ClinicalTrials.gov].).

Adult↗

PubMed2006

Early increase of retinal arterial and venous blood flow velocities at color Doppler imaging in brittle type 1 diabetes after islet transplant alone.

Little information is currently available about the role of islet transplantation alone (ITA) on the retinal microcirculation. Our purpose was to investigate with color-Doppler-imaging the effect of ITA after one year on the blood flow velocities of central retinal artery and vein. Central retinal arteries and veins of both eyes of 10 ITA patients were evaluated with color-Doppler-imaging before and one year after transplant. Peak systolic velocity (psv), end diastolic velocity (edv) for arteries and maximum velocity (maxv), minimum velocity (minv) for veins were recorded and compared with a control group of type 1 diabetic patients. At one year, a statistically significant increase of blood flow velocities of central retinal arteries (psv: 6.09+/-0.46 vs. 10.12+/-1.20 cm/s, P=0.01) and veins (maxv: 3.12+/-0.28 vs. 6.12+/-1.00 cm/s, P=0.01) was found only in the ITA patients. An early, significant increase of arterial and venous retinal blood flow velocities was found after ITA.

Blood Flow Velocity↗

PubMed2006

Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease.

PURPOSE: To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. DESIGN: Retrospective comparative interventional case series. METHODS SETTINGS: Nine international uveitis specialty clinics. STUDY POPULATION: Forty-eight patients presenting over a three-year period to a study center with acute Vogt-Koyanagi-Harada disease. INTERVENTION: Initial treatment with corticosteroid either orally (Oral only group) or intravenously followed by an oral taper (IV+Oral group). MAIN OUTCOME MEASURES: Change in visual acuity with treatment; development of ocular complications, including visually significant cataract, choroidal neovascularization, subretinal fibrosis, fundus pigment migration, nummular hypopigmented lesions, and diffuse fundus depigmentation; use of immunosuppressive therapy. RESULTS: The Oral only group comprised 15 patients (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months. There was no difference in duration of follow-up between groups (P = .234). There was no difference in the change in visual acuity between groups, adjusting for initial visual acuity (P = .402). There were no differences in the rates of development of visually significant cataract, fundus pigmentary changes, or in the rate of use of subsequent immunosuppressive therapy between treatment groups. No patients developed choroidal neovascularization or subretinal fibrosis over the study period. CONCLUSIONS: Route of administration of corticosteroid had no detectable effect on change in visual acuity nor on the development of visually significant complications over the study period. Prospective trials are necessary to address speed of resolution and definitively answer outcome questions.

Acute Disease↗

PubMed2006

Ocular toxicology: the Draize eye test.

PURPOSE OF REVIEW: Superficial ocular tissues are frequently exposed to damage produced by chemical compounds applied on or around the ocular surface for cosmetic, therapeutic or accidental reasons. An experimental test measuring objectively and in a reproducible way any potential damaging effect would certainly help in prospectively minimizing unwanted effects. The Draize eye test, although commonly employed to date, does not seem to be quite satisfactory in this respect. RECENT FINDINGS: The limits of the Draize eye test and the results of some modified versions of the test are analysed. In particular, the good predictivity of the so-called low-volume Draize eye test and the recent findings of studies on the in-vitro and ex-vivo alternatives to the Draize eye test are presented. SUMMARY: The Draize eye test, despite criticisms, has been used in the clinical setting for a long time and still remains the reference protocol. To date, only a combination of alternative methods, none of which is devoid of serious criticisms, seems to be able to exhaustively recognize potential irritants and avoiding for that purpose, in some cases, the use of living animals.

Animals↗

PubMed2006

Islet cell transplantation.

Islet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The islets, that are only 1% of the total pancreas tissue, are isolated by two steps method starting with collagenase digestion that operates a rapid dissociation of the stromal component of the gland, while preserving islet anatomical integrity. After digestion, islets are then separated from exocrine tissue by centrifugation in density gradients. Transplantation consists of a simple injection of few milliliter-purified tissue in the portal vein through a percutaneous trans-hepatic approach performed in local anesthesia. Several studies have now demonstrated that islet transplant can replace pancreatic endocrine function without major side effects and with liver viability preservation in selected patients affected by long-term type 1 diabetes. It can restore endogenous insulin secretion, achieve insulin independence in more than 80% of patients, and recover the metabolism of glucose, protein and lipids. Improved control of glycated HbA1c, reduced risk of recurrent hypoglycemia and of diabetic complications are also seen as important benefits of islet cell transplantation, irrespective of the status of insulin independence. Many protocols are now on going for reduction of immunosuppression therapy in recipients, induction of tolerance, and prolongation of graft function.

Animals↗

PubMed2005

Cross-sectional assessment of the effect of kidney and kidney-pancreas transplantation on resting left ventricular energy metabolism in type 1 diabetic-uremic patients: a phosphorous-31 magnetic resonance spectroscopy study.

OBJECTIVES: To test whether left ventricular (LV) dysfunction affecting type 1 diabetic-uremic patients was associated with abnormal heart high-energy phosphates (HEPs) and to ascertain whether these alterations were also present in recipients of kidney or kidney-pancreas transplantation. BACKGROUND: Heart failure is the major determinant of mortality in patients with diabetic uremia. Both uremia and diabetes induce alterations of cardiac HEPs metabolism. METHODS: Magnetic resonance imaging and phosphorous magnetic resonance spectroscopy of the LV were performed in the resting state by means of a 1.5-T clinical scanner. Eleven diabetic-uremic patients, 5 nondiabetic patients with uremia, 11 diabetic recipients of kidney transplantation, and 16 diabetic recipients of combined kidney-pancreas transplantation were studied in a cross-sectional fashion. Eleven nondiabetic recipients of kidney-only transplant and 13 healthy subjects served as control groups. RESULTS: Uremic patients had higher LV mass, diastolic dysfunction, and lower phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio in comparison with recipients of kidney-pancreas or nondiabetic recipients of kidney transplant. In diabetic recipients of kidney transplant the PCr/ATP ratio was higher than in uremic patients but was lower than in the controls. Recipients of combined kidney-pancreas transplant had a higher ratio than uremic patients but no difference was found in comparison with controls. CONCLUSIONS: Altered resting myocardial HEPs metabolism may contribute to LV dysfunction in diabetic-uremic patients. In diabetic recipients of kidney transplantation, a certain degree of LV metabolic and functional impairment was found. In combined kidney-pancreas recipients the resting LV metabolism and function were not different than in controls.

Adenosine Triphosphate↗

PubMed2005

Metabolic results 3 years after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation has become accepted therapy for patients with type 1 diabetes and end-stage renal disease. This 3-year study compared the metabolic effects of tacrolimus- and cyclosporin microemulsion (ME)-based immunosuppressive therapy in this clinical setting. METHODS: The study population comprised the 205 patients enrolled in the Euro-SPK 001 study. Glucose metabolism parameters [fasting blood glucose, fasting C-peptide and glycated haemoglobin (HbA1c)], blood lipids (total cholesterol and triglycerides) and pancreatic enzymes (lipase and amylase) were monitored at regular intervals during the study. Blood pressure was also carefully monitored and compared with target levels for diabetic patients. RESULTS: Fasting C-peptide and HbA1c levels were within the normal ranges in the two treatment groups throughout the 3 years. Fasting blood glucose was higher during the first 2 months post-transplant in the tacrolimus group than in the cyclosporin-ME group, but no differences were seen thereafter. From month 2 post-transplant, mean levels of total cholesterol were significantly lower among patients receiving tacrolimus than among those in the cyclosporin-ME group. In addition, patients receiving cyclosporin-ME showed serological features of mild pancreatitis, with elevated blood amylase and lipase levels during the first 6 months post-transplant. The two regimens were comparable with respect to hypertension. CONCLUSIONS: Except for lipid profiles, no major differences in metabolic effects or blood pressure control were observed over the 3 years in SPK transplant patients receiving immunosuppression based on tacrolimus or cyclosporin-ME. In view of the potential risk of hypertension, antihypertensive strategies should be implemented for all patients.

Amylases↗

PubMed2005

Gastrointestinal bleeding from enterically drained transplanted pancreas.

Gastrointestinal bleeding has been described as related complication of pancreas transplantation. Of 166 simultaneous pancreas kidney transplantations, 61 were enteric-drained pancreas transplants (eight done with and 53 without Roux-en-Y loop). The patients were divided into two groups according to Roux (group I, n = 8) or no Roux (group II, n = 53) technique. Seven patients experienced anastomotic hemorrhage between the jejunum and duodenal stump (11%), five cases in group I and two in group II (P < 0.001). No relationships between gastrointestinal bleeding duodenal stump and recipient jejunum blood flow, mean pancreatic cold ischemia time, platelet count, and prothrombin time were observed. Donor age over 40 years and abnormal activated partial thromboplastin time constituted risk factors for hemorrhage from the duodenojejunal anastomosis. There were no significant differences in pancreas graft and patient survival rates between the two groups. Anastomotic hemorrhage did not influence patient and graft survival.

Adult↗

PubMed2005

Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients.

End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3) nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P-Selectin were similar between groups. (iii) Platelet intracellular calcium: Resting intracellular calcium was statistically higher in ESRD compared to the C group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv) Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups showed higher levels of hypercoagulability markers compared to the C group. A reduction in antithrombin activity was evident in ESRD compared to the Ktx group (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel basal membrane compared to the Ktx and C groups with more endothelial sufference. (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a higher homeostasis model assessment provided equations for estimating insulin resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/-0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up, suggesting an improvement of almost haemostatic abnormalities. Kidney transplant is associated with a better atherothrombotic profile in ESRD, platelet intracellular calcium and cytokines seem to be most influenced by the transplant, while most morphological abnormalities are retained.

Adult↗

PubMed2005

Natural history of kidney graft survival, hypertrophy, and vascular function in end-stage renal disease type 1 diabetic kidney-transplanted patients: beneficial impact of pancreas and successful islet cotransplantation.

OBJECTIVE: Diabetes, hypertension, infections, and nephrotoxicity of certain immunosuppressive drugs (i.e., calcineurin inhibitors) can reduce functional survival of the kidney graft. Our aim was to evaluate survival, hypertrophy, and vascular function of the kidney graft in end-stage renal disease (ESRD) type 1 diabetic patients after transplant. RESEARCH DESIGN AND METHODS: The study population consisted of 234 ESRD type 1 diabetic patients who underwent kidney-pancreas (KP; 166 patients), successful kidney-islet (KI-s; 24 patients), and kidney (KD; 44 patients) transplant. Kidney size, graft survival, vascular function, and microalbuminuria were evaluated prospectively yearly for 6 years. Sixty-eight protocol kidney biopsies were performed routinely between 1993 and 1998 cross-sectionally (3.2 +/- 0.3 years from kidney transplant). RESULTS: The KP and KI-s groups had better cumulative kidney graft survival at 6 years than did the KD group (KP: 73%; KI-s: 86%; KD: 42%, P < 0.01). The KP group but not the KI-s/KD groups showed a persistent kidney graft hypertrophy up to 6 years of follow-up. A significant increase in creatinine levels from baseline to year 6 was evident in the KD group (1.58 +/- 0.08 to 2.78 +/- 0.44 mg/dl, P < 0.05) but not in the KP/KI-s groups. The KP/KI-s groups only showed a reduction of renal resistance index from baseline to year 6 (KP at baseline: 0.74 +/- 0.01 to 0.68 +/- 0.01%, P < 0.01; KI-s at baseline: 0.72 +/- 0.02 to 0.69 +/- 0.02%, P < 0.05). At year 6, an increase from baseline in urinary albumin excretion was observed only in the KD group (31.4 +/- 9.0 to 82.9 +/- 33.6 mg/l, P < 0.05). Preliminary data suggested that graft nitric oxide (NO) expression was higher in the KP/KI-s groups than in the KD group (data not shown). CONCLUSIONS: In ESRD type 1 diabetic patients, KP and KI-s compared with KD resulted in enhanced kidney graft survival, hypertrophy, and vascular function.

Adult↗

PubMed2005

Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients.

OBJECTIVE: Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS: We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group). RESULTS: GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 +/- 3.5% at baseline to 74.9 +/- 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 +/- 0.25 to 4.20 +/- 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 +/- 4.9 to 44.6 +/- 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 +/- 8.3 to 57.2 +/- 4.6 ms, P < 0.05) with higher erythrocytes Na(+)-K(+)-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness. CONCLUSIONS: Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft.

Atrial Natriuretic Factor↗

PubMed2005

Minimal focal steatosis of liver after islet transplantation in humans: a long-term study.

Several reports have been published on islet transplantation in humans, but few data are available on the effect of islet infusion on the hepatic structure. Our aim was to evaluate in a longitudinal study the impact on the liver of intrahepatic islet transplantation. Clinical outcome and liver imaging were evaluated in 31 cases of islet-kidney transplantation (follow-up 38 +/- 4 months, range 12-96 months). Patients were divided into three groups: full function (FF, 9 cases: established insulin independence); partial function (PF, 16 cases: transient insulin independence, prolonged C-peptide secretion): no function (NF, 6 cases: exhaustion of C-peptide secretion within the first year). Upper abdomen sonogram was regularly performed during the whole follow-up period. Percutaneous liver biopsy was performed in case of echographic abnormalities. Multiple small areas of focal hyperechogenicity were observed in nine cases after 6-12 months. These findings were observed only in FF (two) and in PF (seven) patients. Fasting C-peptide levels at the time of echography were higher in negative than in positive patients (2.42 +/- 0.16 vs. 1.51 +/- 0.10 ng/ml, p = 0,0001). Liver biopsies showed focal macrovesicular steatosis, surrounded by normal liver parenchyma. Normal liver function was maintained. In conclusion, our results indicate that islet transplantation can lead to structural changes of the liver parenchyma (focal steatosis). It is more often observed in patients with partial function. Sonogram can be considered a specific method to reveal liver changes after islet transplantation.

Adult↗

PubMed2004

Technique, complications, and therapeutic efficacy of percutaneous transplantation of human pancreatic islet cells in type 1 diabetes: the role of US.

PURPOSE: To retrospectively evaluate the role of ultrasonography (US) with regard to the technique, complications, and therapeutic efficacy of percutaneous intrahepatic transplantation of human pancreatic islet cells with combined US and fluoroscopic guidance. MATERIALS AND METHODS: The institutional review board approved the study, and informed consent was obtained from all patients. After kidney transplantation, 34 uremic diabetic patients (20 men, 14 women; mean age, 40.9 years; age range, 29-61 years) underwent percutaneous intrahepatic transplantation of islet cells. Portal vein patency and liver echotexture were preliminarily assessed with color Doppler US. US also was used to identify early complications and presence (group A patients) or absence (group B patients) of hepatic parenchymal changes. Differences between the two groups in C peptide serum level and range were analyzed (Mann-Whitney test). Therapeutic efficacy of transplantation was assessed with regard to insulin independence period (rate and duration), exogenous insulin requirement, glycated hemoglobin, and C peptide level. A C peptide level of more than 0.5 ng/mL was considered to indicate well-functioning islet cells. RESULTS: Fifty-eight procedures were technically successful, with a single puncture used in 51 of 58 patients. Complications occurred in three of 58 patients (hemoperitoneum, hemothorax, and thrombosis in one patient each) and were conservatively treated and resolved. Duration of insulin independence in 12 patients was more than 3 months (mean, 21 months). Well-functioning islet cells at 6 years were found in 19 of 34 patients. Hyperechoic parenchymal changes were evident at US in 12 of 34. No statistically significant difference in C peptide level was found between groups (P > .05), but a wider range of values was recorded in group B. CONCLUSION: Complication rate of transplantation with US and fluoroscopic guidance was low. Well-functioning islet cells were found in about 50% of patients at 6 years of follow-up. Hepatic implantation of islet cells was evident on US images in more than one-third of patients.

Adult↗

PubMed2004

Selective intra-graft apoptosis and down-regulation of lymphocyte bcl-2, iNOs and CD95L expression in kidney-pancreas transplanted patients after anti-Thymoglobulin induction.

Intra-graft infiltrating cells apoptosis was evaluated in 20 consecutive kidney-pancreas transplanted (KP) patients without kidney rejection. Two fine-needle aspirated biopsy (FNAB) and two peripheral blood lymphocytes (PBL) samples were obtained 14 days after transplantation. Immunosuppression was based on anti-Thymoglobulins (ATG) induction for 7 days and cyclosporine/mofetil mycophenolate as maintenance therapy. Ten matched healthy subjects were chosen as controls for PBL. Lymphocyte phenotypes and activation markers, apoptotic rate and lymphocyte expression of pro/anti-apoptotic molecules were analysed by flow cytometry analysis (FACS). Lymphocyte phenotypes and activation markers: higher levels of CD8 and CD4DR were evident in the graft (p < 0.05) than in PBL, CD3CD25 in PBL were higher in transplanted patients than in controls. Apoptotic rate and lymphocyte expression of pro- and anti-apoptotic molecules: a higher expression of annexin V, together with reduced lymphocytes CD95L, iNOs and Bcl-2 expression (PBL = 97.7+/-1.1% vs FNAB = 81.9+/-15.1%; p < 0.05) were evident in the graft than in PBL. In KP patients intra-graft apoptosis and reduced anti-apoptotic molecules were evident after ATG induction.

Adult↗

PubMed2004

Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) transplantation has become an accepted therapy for type 1 diabetic patients with end-stage renal disease. This open-label, multicenter study compared the efficacy and safety of tacrolimus with the microemulsion (ME) formulation of cyclosporine in a clinical setting. The 1-year results are reported here. METHODS: The study was conducted in 10 European centers and one center in Israel. One hundred three patients were randomly assigned to tacrolimus and 102 to cyclosporine-ME. All patients received concomitant rabbit anti-T-cell globulin induction therapy, mycophenolate mofetil (MMF), and short-term cortico-steroids. The initial daily oral doses were 0.2 mg/kg for tacrolimus, 7 mg/kg for cyclosporine-ME, and 2 to 3 g for MMF. RESULTS: The 1-year incidence of biopsy-proven kidney or pancreas acute rejection was lower with tacrolimus (27.2%) than with cyclosporine-ME (38.2%; P = 0.09). Pancreas graft survival at 1 year was 91.3% with tacrolimus and 74.5% with cyclosporine-ME (P <0.0005). Renal graft survival was similar in the two study groups. There were no significant treatment-related differences in pancreatic or renal graft function. In total, 34 patients switched treatment from cyclosporine-ME to tacrolimus, but only 6 patients receiving tacrolimus required alternative therapy. Mean doses of MMF at 1 year were also lower in the tacrolimus group (1.36 vs. 1.67 g/day; P = 0.007). CONCLUSION: These findings support the use of tacrolimus therapy for uremic patients with type 1 diabetes who are undergoing SPK transplantation.

Acute Disease↗

PubMed2004

Correlation between non-reversible thallium-201 myocardial perfusion defect and ECG criteria in the diagnosis of apical myocardial infarction.

BACKGROUND: ECG identification of apical myocardial infarction (MI) is controversial and lacks of accuracy. Our aim was to investigate the sensitivity of different proposed ECG criteria in the presence of apical perfusion defects assessed with SPECT analysis. METHODS: One hundred twenty-four (98 M, 26 F) out of 1500 patients with suspected coronary artery disease, showed apical perfusion defect not reversible at rest and after reinjection at tomographic SPECT analysis during thallium-201 scintigraphy. RESULTS: In the group of 29 patients presenting wide isolated apical perfusion defect (wAPD) Q waves in anterior segments with definition of antero-septal MI was prevalent (51.7%), while few patients (41.3%) presented the ECG criteria of apical MI as proposed in the literature. In 19 of the 25 patients with partial isolated apical perfusion defect (pAPD), the absence of Q wave was clearly prevalent. Fifty patients had a wAPD partially extended in surrounding regions, as anterior or septal, inferior or lateral myocardial segments, in these patients, the site of Q wave location was more variable, with prevalent Q wave in anterior leads, but with more incidence of Q waves in leads II III aVF, especially in patients with associated perfusion defect in inferior segments. Substantially, the same finding resulted in the 20 patients showing a pAPD extended in surrounding myocardial segments. CONCLUSION: In conclusion, the low diagnostic sensitivity of the ECG criteria of identification of apical MI is clearly demonstrated by our analysis carried out using SPECT perfusion scintigraphy, with ECG findings of anterior/anterior-septal myocardial necrosis in the patients with wAPD.

Adult↗

PubMed2004

Tissue factor and CCL2/monocyte chemoattractant protein-1 released by human islets affect islet engraftment in type 1 diabetic recipients.

Islet survival in the early posttransplantation period is likely to be influenced by inflammatory events in and around islets. Twenty-seven human islet preparations were transplanted by 24 infusions into 14 patients with brittle type 1 diabetes under the Edmonton protocol. Patients were monitored for their coagulation [cross-linked fibrin degradation products (XDPs)] and liver function test [aspartate and alanine aminotransferase (AST and ALT)] as markers of early posttransplant complications, and these were correlated with in vitro islet number, purification, volume, monocyte-chemoattractant protein-1 (CCL2/MCP-1) and tissue factor (TF) islet release. Consistent with activation of coagulation pathways and hepatic damage, serum XDP values increased early after 11 infusions and transaminase after 13 of 24 infusions. TF and CCL2/MCP-1 were detected in supernatants of 21 and 22 islet preparations, respectively. Serum XDP peak values were correlated with TF/equivalent islets (EI) (r(2)=0.26, P = 0.001) and CCL2/MCP-1/EI (r(2) = 0.42; P < 0.001); serum transaminase areas under the curve in the first week posttransplantation were correlated with CCL2/MCP-1/EI (r(2) = 0.55; P < 0.001 for ALT and r(2) = 0.51; P = 0.001 for AST) and TF/EI (r(2) = 0.31; P = 0.002 for ALT, and r(2) = 0.36; P = 0.002 for AST). These data suggest that reducing the islet proinflammatory state may be a means to reduce the early posttransplant complications and perhaps improve islet engraftment.

Chemokine CCL2↗

PubMed2004

Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation.

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients.

Adult↗