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Biomedical subjects

M Salizzoni

Publications and source records attributed to M Salizzoni.

At least 19 recordsLinked to original sources

Antiangiogenic and immunomodulatory effects of rapamycin on islet endothelium: relevance for islet transplantation.

Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angiogenesis-related factors VEGF, alphaVbeta3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation.

Angiogenesis Inhibitors↗

Impact of donor age and year of transplantation on graft and patient survival following liver transplantation for hepatitis C virus.

BACKGROUND: Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation (LT). Graft and patient survival are adversely affected by recurrent infection of the graft. Recent publications have described an inferior outcome for recently transplanted HCV patients and have highlighted the impact of advancing donor age on severity of recurrent HCV. The donor age at which a measurable impact on graft and patient outcome can be observed has not clearly been defined. In addition, the impact of donor age on graft and patient survival for non-HCV patients needs to be examined. METHODS: We have examined a large European liver transplant database to define the impact of transplantation date and donor age on graft and patient survival for HCV patients (n = 4,736) and the impact for a comparison group of transplanted alcoholic liver disease patients (ALD, n = 5,406). RESULTS: For the entire cohorts, graft and patient survival of HCV patients was inferior to ALD patients. Since 1987, there has been a steady and ongoing improvement in the outcome of transplanted ALD patients, an improvement not observed for HCV patients. Every year since 1989, there has been an increase in liver donor age. Graft and patient survival for both ALD and HCV cohorts was adversely affected by advancing donor age. Comparison of graft and patient survival for HCV and ALD cohorts was made according to donor age (donor age subgrouped <20, 20-30, 30-40, 40-50, 50-60 and >60 years of age). For donors younger than 40 years of age, HCV and ALD recipient graft and patient survival are not significantly different. For donors older than 40, HCV recipient graft survival is inferior to ALD graft survival, an inferiority that increases for each advancing decade of donor age. For donors older than 50 years, HCV recipient patient survival is inferior to ALD patient survival, an inferiority that increases when the donor age is greater than 60 years. CONCLUSION: The results of liver transplantation for European HCV patients is inferior to a comparison group of ALD patients, and have not improved during the past 15 years. Liver donor age has increased significantly during that period. Advancing donor age has an adverse influence on graft and patient survival for ALD and HCV patients, but a significantly greater impact is observed for HCV patients when the donor is older than 40 years.

Adolescent↗

Neurological complications of liver cirrhosis and orthotopic liver transplant.

Neurological complications are common in cirrhotic patients with end-stage liver failure. They comprise a wide array of etiologies, which may originate before, during, or after liver transplantation. The objective of this study was to describe the nature of the main neurological complications in patients with end-stage liver failure. Several toxins including ammonia, manganese, benzodiazepine-like substances, gamma-aminobutyric acid-like substances, and impaired dopaminergic neurotransmission are at the top of the list of candidates for hepatic encephalopathy, subclinical encephalopathy, and extrapyramidal signs before liver transplantation. Central pontine myelinolysis, cerebrovascular autoregulation impairment, and paradoxical cerebral embolism are probably responsible for the neurological complications during liver transplantation. Neurological complications represented by alterations of mental status, seizures, and focal motor deficits have been described after liver transplantation. These complications have been attributed to several pathogenetic factors, such as a poorly functioning graft, an intracranial hemorrhage, a cerebral infarction, an infection, or the toxicity of immunosuppressants.

Brain↗

Oesophageal and gastric bile exposure after gastroduodenal surgery with Henley's interposition or a Roux-en-Y loop.

BACKGROUND: The degree which the various reconstruction techniques prevent bile reflux after gastroduodenal surgery has been poorly studied. METHODS: Bile exposure in the intestinal tract just proximal to the jejunal loop was measured with the Bilitec 2000 device for 24 h after gastroduodenal surgery in three groups of patients. Group 1 comprised 24 patients with a 60-cm Henley's loop after total gastrectomy. Group 2 included 31 patients with a 60-cm Roux-en-Y loop after total (22 patients) or subtotal (nine) gastrectomy. Group 3 contained 21 patients with a 60-cm Roux-en-Y loop anastomosed to the proximal duodenum as part of a duodenal switch operation for pathological transpyloric duodenogastric reflux. Bile exposure, measured as the percentage time with bile absorbance greater than 0.25, was classified as nil, within the range of a control population of healthy subjects, or pathological (above the 95th percentile for the control population). Reflux symptoms were scored and all patients had upper gastrointestinal endoscopy. RESULTS: Bile was detected in the intestine proximal to the loop in none of 24 patients in group 1, eight of 31 in group 2 and 12 of 21 in group 3 (P < 0.001). The mean reflux symptom score increased with the degree of bile exposure, and the proportion of patients with oesophagitis or gastritis correlated well with the extent of bile exposure (P < 0.001). CONCLUSION: A long Henley's loop was more effective in preventing bile reflux than a long Roux-en-Y loop. Bilitec data correlated well with the severity of reflux symptoms and the presence of mucosal lesions.

Adolescent↗

Sequential liver-kidney transplantation.

The indications for sequential liver and kidney transplantation have not been well defined. Two categories of patients may benefit from this procedure: patients with primary renal disease associated with hepatic disorders (glomerulonephritis, tubulointerstitial nephritis, metabolic diseases, and structural diseases) and patients who develop renal failure after liver transplantation. Chronic renal failure is a frequent long-term complication after liver transplantation. End-stage renal disease develops in 2% to 10% of cases by 10 years after transplantation. Kidney transplantation appears to be a better option than dialysis for the treatment of end-stage renal disease after liver transplantation. In contrast, survival rates, after kidney transplantation are significantly lower among liver transplant patients than primary-only kidney transplant recipients. Considering the donor shortage, kidney transplantation should be cautiously considered in liver transplantation patients. New immunosuppressive drugs and protocols are needed to reduce chronic renal failure after liver transplantation.

Humans↗

[Some remarks on the management of liver donor].

We evaluated 481 liver donors in order to assess the incidence of positive cultures on samples obtained before harvesting, at harvesting and on preservation fluid; to determine factors related to positive cultures in the donor; to analyse the bacterial and fungal transmission from donor to recipient; to verify the influence of donor culture positivity on graft and patient survival. Cultures were positive in 232 of 481 (48%) donors. Bacteremia was present in 101 of 481 (20%) donors. Intensive care length of stay was significantly longer in culture-positive donors. A Gram-negative bacteria transmission from the infected donor to the graft recipient was proven in 1 case. No differences in 1-year survival and retransplantation rates were found between patients receiving livers from culture-positive or negative donors. In conclusion, even if rare, donor to host infection transmission is proven. Extended criteria for organ procurement may explain the high number of culture-positive donors we report. Careful microbiological surveillance and treatment can reduce the clinical negative impact on recipient outcome.

Humans↗

Use of arterial conduit as an alternative technique in arterial revascularization during orthotopic liver transplantation.

BACKGROUND: The risk of hepatic artery thrombosis after orthotopic liver transplantation is higher in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, unsafe native hepatic arteries. AIMS: To assess the use of arterial conduits as alternative technique for graft revascularization. PATIENTS: At the Liver Transplant Center of the "S. Giovanni Battista" Hospital in Torino, a review has been made of 600 consecutive orthotopic liver transplantations in 545 adult patients from 1990 to 1999. METHODS: In 95 orthotopic liver transplantations (15.8%) in 88 patients, the graft was supplied by infrarenal conduit, while in 505 orthotopic liver transplantations (84.2%) in 457 patients, a direct anastomosis was used. RESULTS AND CONCLUSIONS: The overall incidence of hepatic artery thrombosis in our series was 3.5% (21/600): 5.3% (5/91) for conduits and 3.2% (16/505) for standard technique (p=ns, chi2 test). The actuarial 5-year graft survival was 67.7% for conduits and 68.6% for the standard technique; p (log rank): ns. The iliac prosthesis torsion was the only complication related to the use of infrarenal iliac conduit. The arterial conduit, performed with donor iliac artery, is an effective and safe revascularization technique in patients at high risk of arterial thrombosis.

Adolescent↗

Bile exposure of the denervated stomach as an esophageal substitute.

BACKGROUND: Both the supine position and the existence of a gastric drainage procedure are suspected to promote reflux of duodenal juice into the denervated intrathoracic stomach. Erythromycin has been shown to weaken pyloric resistance to gastric outflow and to enhance antral motility, gastric emptying, and gallbladder contractility. METHODS: The presence of bile in the gastric transplant of 79 patients was monitored over a 24-hour period with use of the Bilitec 2000 optoelectronic device 3 to 195 months after subtotal esophagectomy. Ten patients were reinvestigated after a 3-year period. Five groups were studied: group I: n = 12, no gastric drainage, never given erythromycin, group 2: n = 40, gastric drainage, never given erythromycin, group 3: n = 7, no gastric drainage, given erythromycin, group 4: n = 13, gastric drainage, given erythromycin, and group 5: n = 7, no longer given erythromycin (with or without gastric drainage). The percentage of time gastric bile absorbance was more than 0.25 was calculated for the total, supine, and upright periods of recording in reference to data from 25 healthy volunteers. RESULTS: The Bilitec test was pathologic in 9 of the 12 patients of group 1 whereas it was normal in three. Gastric exposure to bile was longer in group I patients than in controls for the total (p = 0.012) and supine (0.036) periods, but the difference did not reach statistical significance for the upright period (p = 0.080). Bile exposure in group 4 did not significantly differ from controls (total: p = 0.701; supine: p = 0.124; upright: p = 0.712). Bile exposure for the total period did not significantly differ whether patients were taking erythromycin or the drug had been discontinued at the time of the study (p = 0.234); and it tended to decrease with time in patients investigated twice (p = 0.046). CONCLUSIONS: Gastric exposure to bile after truncal vagotomy and transposition of the stomach up to the neck is pathologic in three quarters of patients. It is more marked in the supine than in the upright position and tends to decrease with time. The addition of a gastric drainage procedure in combination with erythromycin therapy tends to normalize gastric exposure to bile. The effects of erythromycin may persist after discontinuation of the drug.

Adult↗

Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis.

BACKGROUND/AIMS: Treatment with hepatitis B virus immune globulins (HBIG) or lamivudine has reduced the rate of hepatitis B recurrence after liver transplantation to approximately 50%. METHODS: To further decrease hepatitis B recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated with lamivudine before liver transplantation and with lamivudine together with low-dose HBIG (46 500 IU the first month followed by 5,000 lU/monthly) after surgery. RESULTS: While on lamivudine, serum HBV DNA level decreased significantly in all patients and in 11 (33%) the Child-Pugh score improved. Twenty-six patients were transplanted. Among the 25 who survived for longer than 12 months, only one (4%) experienced a hepatitis B recurrence over an average follow-up of 31 months, a rate significantly lower (P = 0.0002) than the 50% recurrence rate among a historical control group of 12 patients. However, low-level HBV replication was detected sporadically throughout the follow-up in 64% of patients. CONCLUSIONS: Over the medium-term, combined prophylaxis with lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence after liver transplantation. Though low-level HBV infection recurred in two thirds of patients, the pathogenic expression of HBV was prevented.

Adult↗

Effect of macrovescicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation.

The influence of steatosis and of other donor and recipient characteristics in affecting liver performance post-orthotopic liver transplantation (OLT) was evaluated in 311 consecutive liver transplantations made in 278 patients. Donor variables considered were age, sex, blood group, cause of death, intensive care unit (ICU) days, need for vasopressors, hepatic enzymes and bilirubin, total and warm ischemia time, and macro- and microvescicular steatosis. Recipient variables considered were age, sex, blood group, biliary output, and post-OLT peak levels of hepatic enzymes. Patient and graft survival were the main outcome indicators. In the multivariate analysis, macrovescicular steatosis involving 25% or more of the hepatocytes was the only variable independently associated with shorter patient survival (p < 0.05). Five (62.5%) of the eight livers with macrovescicular steatosis involving 25% or more of the hepatocytes incurred in a delayed non-function (DNF) and one (12.5%) in a primary non-function (PRNF). The incidence of DNF and PRNF in the group with macrovescicular steatosis involving less than 25% of the liver cells was 1.6% (p < 0.001) and 2.3%, respectively. Microvescicular steatosis of any degree was not associated with a worse prognosis. Macrovescicular steatosis involving 25% or more of the hepatocytes identifies marginal livers, the use of which significantly increases the risk of graft non-function post-OLT.

Adult↗

Denervated stomach as an esophageal substitute recovers intraluminal acidity with time.

OBJECTIVE: To determine whether the denervated stomach as an esophageal substitute recovers normal intraluminal acidity with time. SUMMARY BACKGROUND DATA: Bilateral truncal vagotomy to the stomach as an esophageal substitute reduces both gastric acid production and antral motility, but a spontaneous motor recovery process takes place over years. METHODS: Intraluminal gastric pH and bile were monitored during a 24-hour period 1 to 195 months after transthoracic elevation of the stomach as esophageal replacement in 91 and 76 patients, respectively. Nine patients underwent a second gastric pH monitoring after a 3-year period. The percentages of time that the gastric pH was less than 2 and bile absorbance exceeded 0.25 were calculated in reference to values from 25 healthy volunteers. Eighty-nine upper gastrointestinal endoscopies were performed in 83 patients. Patients were divided into three groups depending on length of follow-up: group 1, less than 1 year; group 2, 1 to 3 years; group 3, more than 3 years. RESULTS: The prevalence of a normal gastric pH profile was 32.3% in group 1, 81.5% in group 2, and 97.6% in group 3. The percentage of time that the gastric pH was less than 2 increased from group 1 (27.3%) to group 2 (56.1%) and group 3 (70.5%), parallel to an increase in the prevalence of cervical heartburn and esophagitis. The percentage of time that the gastric pH was less than 2 increased from 28.7% to 81.2% in the nine patients investigated twice. Exposure of the gastric mucosa to bile was 12.8% in patients with a high gastric pH profile versus 19.3% in those with normal acidity. In the esophageal remnant in six patients, Barrett's metaplasia developed, intestinal (n = 2) or gastric (n = 4) in type. CONCLUSIONS: Early after vagotomy, intraluminal gastric acidity is reduced in two thirds of patients, but the stomach recovers a normal intraluminal pH profile with time, so that in more than one third of patients, disabling cervical heartburn and esophagitis develop. The potential for the development of Barrett's metaplasia in the esophageal remnant brings into question the use of the stomach as an esophageal substitute in benign and early neoplastic disease.

Adult↗