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Biomedical subjects

P Rigotti

Publications and source records attributed to P Rigotti.

At least 37 records · Page 2Linked to original sources

Oxidative stress and nitric oxide system in post-transplant hypertension.

BACKGROUND: CsA-induced endothelial dysfunction and CsA-induced hypertension have been attributed to CsA effects on the endothelial-derived factors controlling vasomotor tone, but the mechanisms responsible are unclear. Endothelial nitric oxide (NO) is known to maintain a state of basal vasodilation and recently a NO mediated counterregulatory mechanism protective from CsA-induced vasoconstriction has been suggested. PATIENTS AND METHODS: Our study evaluates ecNOS gene status and NO metabolites in kidney transplanted patients under chronic CsA treatment with CsA-induced hypertension. Since CsA increases superoxide production, which metabolizes NO, plasma hydroperoxides and peroxynitrite were also evaluated as index of the presence of "oxidative stress". RESULTS: Quantification of monocyte ecNOS mRNA and NO metabolites plasma level from patients and control subjects (C) demonstrated NO system up regulation in patients notwithstanding hypertension. The mean ecNOS to beta-actin ratio was 2.00 +/- 0.87 vs 0.29 +/- 0.08 in C, p < 0.04. NO metabolite plasma level was 30.03 +/- 9.62 mM vs 9.37 +/- 3.86, p < 0.001. Hydroperoxides were also increased in patients: 3.6 +/- 1.6 i.a.u. vs 1.4 +/- 0.8, p < 0.007 (from cholesterol esters) and 10.8 +/- 6.6 vs 1.5 +/- 0.9, p < 0.008 (from triglycerides) as well as peroxynitrite plasma level: 0.36+/- 0.14 mM/L vs undetectable in C. CONCLUSIONS: This study confirms a NO system up-regulation in transplanted patients. However, the counterregolatory system to CsA-induced vasoconstriction, could be cancelled by CsA induced superoxide and free radicals production which, increasing NO metabolism could contribute to CsA induced vasoconstriction and hypertension.

Humans↗

Parathyroid hormone and bone metabolism in kidney-transplanted patients.

BACKGROUND: Decreases in bone mass and increased susceptibility to fractures are well-recognized complications in organ transplants. SUBJECTS AND METHODS: We performed a cross-sectional study on 60 patients (40 males, 20 females, mean age 43.2 +/- 1.06, SE range 22 - 70) who underwent kidney transplantation (KTX) 55.6 +/- 4.5 months before. Blood and 24-hour urine samples were analyzed for the main parameters of mineral metabolism, and also for osteocalcin (BGP), bone alkaline phosphatase (b-ALP, urine N-telopeptid (u-NTx) and urine galactosyl-hydroxylysine (u-Ghyl). DEXA scan of the lumbar spine (LS) and proximal femur (PF) and ultrasound determination of the heel (stiffness) was also performed. RESULTS: T-score values for bone density (BD) were 2.14 +/- 0.11 SD's for LS, -2.56 +/- 0.09 for PF and 2.49 +/- 0.15 for stiffness. There were 29 peripheral fractures in 16 patients. The rate of fractures before KTX were 0.0011 per patient/year and 0.0005 after transplantation (p < 0.02). When expressed as number of SD's with respect to normal controls, BGP (1.48 +/- 0.23), b-ALP (0.95 +/- 0.19), u-NTx excretion correlated negatively with BD at the femoral neck (p < 0.02) and trochanter (p < 0.03). Cumulative steroids intake were negatively correlated with b-ALP positively (p < 0.05). Current CsA was positively correlated with b-ALP (p < 0.001). Both cumulative steroid (p < 0.02) and CSA (p < 0.01) intakes were negatively correlated with BD at Wards triangle. CONCLUSIONS: Our data demonstrate an important bone depletion at each stage KTX. PTH plays a major role in the observed increase in bone turnover, exacerbating the negative effects on the bone on immunosuppressive treatment. Glucocorticosteroid therapy is an important risk factor for osteoporosis in this setting also.

Adult↗

Liver-kidney-transplantation in type 1 primary hyperoxaluria: description and comments on a case.

BACKGROUND: Primary hyperoxaluria leads to oxalosis, a systemic illness with fatal prognosis in uremic youngsters because of systemic complications. CASE REPORT: A 14-year old boy with primary type 1 hyperoxaluria who had a long-lasting history of nephrolithiasis and passed from normal renal function to end-stage renal disease within 7 months. MEASUREMENT of alanine: glyoxylate aminotransferase (AGT) catalytic activity in the liver biopsy disclosed very low activity which was not. responsive to pyridoxin., thus the patient entered onto a priority national waiting list for liver-kidney transplantation and a week later received a combined transplant. In order to increase body clearance of oxalate, the patient underwent medical treatment to increase urine oxalate solubility (sodium and potassium citrate oral therapy, magnesium supplementation and increase of diuresis) and intensive dialysis both before and after transplantation. COMMENT: The medical approach to the treatment of this rare illness is discussed. Since the major risk for the grafted kidney is related to the oxalate burden, i.e. oxalate deposition from the body deposits to the kidney that becomes irreversibly damaged, treatment consists of increasing the body clearance of oxalate both by increasing oxalate solubility in the urine and with intensive dialysis performed both before and after combined transplantation. To the same extent (by limiting body oxalate deposits), a relatively early (native GFR 20-25 ml/minute) transplantation is advisable.

Adolescent↗

Mycophenolate mofetil (MMF) versus azathioprine (AZA) in pancreas transplantation: a single-center experience.

AIM: Advances in immunosuppression and careful monitoring for rejection are largely responsible for improved results in pancreas transplantation. We conducted a retrospective study to establish the effectiveness of immunosuppressive therapy with mycophenolate mofetil (MMF) instead of azatioprine (AZA) in pancreas transplantation and to assess adverse effects in the two different immunosuppressive regimes. SUBJECTS AND METHODS: Since 1991, 27 pancreas transplantations were performed in 25 patients at our Institute. For induction therapy, immunosuppressant protocol consisted of quadruple immunosuppressive therapy with cyclosporine, steroids, antilymphocyte globulin and AZA in 13 patients or MMF in 12 patients respectively. RESULTS: Acute rejection occurred in 76% of patients in the AZA group compared with 53% in the MMF group. Steroid-resistant rejection was observed in 7% in the MMF group compared to 38% of patients on AZA (p < 0.01). Two kidney grafts were lost due to acute rejection in the AZA group, one pancreas was lost due to acute rejection and one to chronic rejection in the MMF group. There were no significant differences in CMV infection. Severe fungal infections were noted in 2 patients treated with MMF. Malignancy occurred in 1 patient (pancreas graft lymphoma) in MMF. CONCLUSIONS: In conclusion, patients treated with MMF required less frequent and less intensive treatment for acute rejection. However, its short- and long-term side effects should be further investigated.

Adult↗

Laparoscopic treatment of lymphocele after kidney transplantation.

BACKGROUND: Laparoscopic treatment of pelvic lymphocele secondary to kidney transplant has gained popularity in the last few years, although lesions of the urinary tract (ureter, renal pelvis, and bladder) have been reported frequently. To evaluate the result of this treatment and the associated risk of urinary tract lesions, we reviewed our experience and reports in the medical literature on open and laparoscopic surgery. METHODS: From 1991 to 1999, we laparoscopically treated 12 patients (7 men and 5 women; median age, 43 years; range, 17-59 years) with symptomatic pelvic lymphocele causing a deterioration of renal function because of compression on the ureter in 10 of the 12 patients and lymphocele compression of the iliac vein in the other 2 patients. In nine patients, the lymphocele wall was opened and sutured to the peritoneum to keep the window open. In two patients, an omentoplasty was performed, and in the remaining patient, both techniques were used. All patients were followed up clinically with ultrasound and biochemistry for a median period of 33 months (range, 1-96 months). Using Medline, we reviewed the medical literature from 1980 to 1998 and collected 252 cases in which operations had been performed to drain an internal lymphocele secondary to kidney transplantation. RESULTS: Laparoscopic treatment was successful in 11 of the 12 patients. One patient was converted to open surgery because of a lesion in the transplanted ureter. One patient needed repeat laparoscopy 24 hours after the operation because of bleeding from the peritoneal window. The median duration of the operation was 120 min (range, 70-200 min), and the median postoperative hospital stay was 5 days (range, 2-12 days). None of the patients needed to discontinue oral cyclosporine assumption. The serum creatinine level dropped significantly after surgery (p < 0. 05). No symptomatic recurrences were observed. Of the 252 patients found in the medical literature, in 129 the procedure was performed with open surgery and in 123 laparoscopically (our 12 patients included). The prevalence of iatrogenic lesions to the urinary tract increased threefold with the use of laparoscopic surgery (from 1.6% in open surgery to 7% in laparoscopy). The recurrence rate of symptomatic lymphocele, however, decreased from 15% to 4%. CONCLUSIONS: Laparoscopic drainage of posttransplantation lymphocele is a relatively simple method for treating this complication, although it bears the burden of an increased incidence of urinary tract lesions, as confirmed by a review of the literature. The major advantage of the laparoscopic approach is the absence of postoperative ileus with the opportunity to continue the enteral immunosuppressive regimen and a lower recurrence rate. These data suggest that laparoscopic lymphocele treatment might be considered the therapy of choice, provided the iatrogenic lesions of the urinary tract diminish as more experience with this technique is gained.

Adolescent↗

The protective effects of L-arginine after liver ischaemia/reperfusion injury in a pig model.

Hepatic ischaemia/reperfusion is characterized by circulatory and metabolic derangement, liver dysfunction, and tissue damage. To evaluate the role of L-arginine, a substrate of nitric oxide, in ischaemia/reperfusion injury, total liver ischaemia was induced for 120 min in 22 Landrace x Large White female pigs, which were randomly assigned to a treatment group (10 animals) or a control group (12 animals). An L-arginine bolus (540 mg/kg i.v.) was administered to the treatment group 1 h before clamping the hepatic hilum, at clamping, at reperfusion, and at 1 and 2 h after reperfusion. The control animals received normal saline and an i.v. infusion. Liver function tests and analysis of serum, erythrocyte, and tissue malondialdehyde contents were performed at commencement of laparotomy, before reperfusion, and at 30 min and 7 days after reperfusion. Liver biopsies were taken at laparotomy, at 30 min, and at 7 days after reperfusion for histological and ultrastructural examination. Assessment of apoptosis included in situ end-labelling analysis and DNA gel electrophoresis. Survival at 7 days was better in the treated animals than in the controls (9/10 vs. 7/12). Tissue malondialdehyde content, aspartate aminotransferase, and lactate dehydrogenase levels were lower in the treatment group, in which morphological changes were significantly less evident than in the controls 30 min after reperfusion. At 7 days, differences between the groups with respect to cell integrity were apparent only on ultrastructural analysis. Glycogen content, 7 days after reperfusion, was higher in the treatment group than in the controls: 70.25 per cent vs. 21.66 per cent positive hepatocytes (score 3 vs. score 1). Multiparametric analysis showed fewer apoptotic cells in the treatment group at all times. Our data show that the administration of L-arginine reduces damage to liver tissue after ischaemia/reperfusion injury in a pig model. This may be explained not only by the known vasodilator, anti-aggregation, and superoxide inactivation effects of increased nitric oxide release, but possibly also by some other action of L-arginine, such as its influence on cellular metabolism.

Animals↗

Oesophageal and cardia function in patients with paraoesophageal hiatus hernia.

BACKGROUND: The decision to add an antireflux procedure when a paraoesophageal hernia is repaired is still controversial. The aim of this study was to investigate oesophageal and cardia function in these patients to verify whether fundoplication was needed. METHODS: Eighteen patients with paraoesophageal hernia were evaluated by oesophageal manometry, 24-h pH monitoring, endoscopy and barium swallow. All patients underwent surgery including antireflux fundoplication. Fourteen patients with sliding hernia plus reflux disease and 16 healthy volunteers formed the control groups. RESULTS: Patients with paraoesophageal hernia had a shorter lower oesophageal sphincter and a greater acid exposure than healthy controls (P < 0.05). Fifteen of 18 patients had either abnormal acid exposure and/or a defective lower oesophageal sphincter at manometry. Postfundoplication symptoms were observed in only one of 16 patients at 6 months' follow-up. CONCLUSION: Since 15 of 18 patients had abnormal acid exposure or were considered prone to developing gastro-oesophageal reflux disease because of a defective lower oesophageal sphincter, this study strongly supports the need to add an antireflux operation to hernia repair.

Adult↗

Protective effect of superoxide dismutase and polyethylene glycol-linked superoxide dismutase against renal warm ischemia/reperfusion injury.

The protective effect of oxygen free radical scavenger superoxide dismutase (SOD) against the warm ischemic damage that occurs in kidneys harvested from non-heart-beating donors is controversial because of its short half-life. In this model, we compared the protective effect of SOD and two longer lasting polyethylene glycol (PEG)-linked forms of SOD in a model of renal ischemia induced by 60 min of arterial clamping in rats. Rats treated with PEG1-SOD and PEG2-SOD had a better renal function than controls, with significantly lower serum creatinine levels throughout the follow-up period and a significantly higher creatinine clearance on postoperative days 1, 2, and 4. In native SOD treated-rats, serum creatinine was lower than in controls, though not significantly so, and creatinine clearance was significantly higher on postoperative day 4. Our results indicate that the protective effect of SOD against renal warm ischemia can be enhanced by prolonging its half-life by binding the enzyme to PEG.

Animals↗

Two cases of Kaposi's sarcoma in renal and liver transplant recipients treated with interferon.

We report two cases of Kaposi's sarcoma in recipients of solid organ transplants, presenting (Case 1) 12 months after liver transplantation and (Case 2) 7 months after kidney transplantation. Both patients share the following features: natives from the Mediterranean area (Southern Italy), multiple immunosuppressive regimen, infection with hepatitis B and cytomegalovirus. During the 3 yr of follow-up after the diagnosis, their immunosuppressive regimen was reduced and they were treated with alpha interferon with remission of the clinical findings. The management of Kaposi's sarcoma in organ transplant recipients remains a controversial issue because of the risks of organ rejection associated with the reduction of immunosuppression and with the use of interferon.

Adult↗