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M Castagneto

Publications and source records attributed to M Castagneto.

At least 37 records · Page 2Linked to original sources

Rapid conversion to sirolimus for chronic progressive deterioration of the renal function in kidney allograft recipients.

The aim of this study was to evaluate the safety of conversion to sirolimus (SRL) immunosuppression among 19 renal transplant recipients (KTX) with progressive chronic renal allograft dysfunction (CRAD). Conversion to SRL was performed with concomitant sharp withdrawal of the calcineurin inhibitor (CI). SRL was added at a starting dose of 3 mg, then adjusted to obtain SRL target trough blood levels of 8 to 10 ng/mL. CI were stopped the evening before starting SRL. All patients enrolled in the study have now completed 6 months of follow-up: all are alive without acute rejection or major infection following rapid conversion to SRL. No significant change in the 6 months postconversion hematologic and hepatic profile was observed compared with the preconversion values, while significant dyslipidemia was induced. After conversion to SRL, significant amelioration of the renal function was found in 36% of patients, stabilization in 21%, and continuous deterioration in 43%. Patients whose renal function improved were found to have been converted at a significantly lower creatinine: (pre 2.6 +/- 0.9 vs post 1.9 +/- 0.2; P =.038) with respect to those patients who had continuous renal deterioration. In KTX with CRAD, sharp withdrawal of CI with concomitant conversion to SRL is safe, avoiding major infections, acute rejections, and significant side effects. Short-term amelioration of the renal function is best obtained when early conversion is performed. Long-term follow-up will be necessary to confirm these preliminary data.

Creatinine↗

Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery.

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.

Adult↗

Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-alpha reduction and GLUT4 expression enhancement.

AIMS/HYPOTHESIS: The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-alpha and GLUT4 expression and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely obese women (BMI>40 kg/m(2)), before and 6 months after low-dietary intake or bariatric malabsorptive surgery (bilio-pancreatic diversion, BPD), by the euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic triglycerides was chemically measured in needle muscle biopsies. Using reverse transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of TNF-alpha and GLUT4 was also investigated. RESULTS: The weight loss after surgery was 25.98+/-5.81 kg (P<0.001), while that obtained with the diet was 5.07+/-5.99 kg (P=NS). Marked decrease in TNF-alpha mRNA levels (76.67+/-12.59 to 14.01+/-5.21 AU, P<0.001) were observed in comparison with pre-treatment, whereas GLUT4 was significantly increased (62.25+/-11.77-124.25+/-21.01 AU, P<0.001) only in BPD patients. Increased glucose uptake (M) was accompanied by a significant decrease of TNF-alpha mRNA (76.67+/-12.59-14.01+/-5.21 AU, P<0.01) and an increase of GLUT4. The amounts of TNF-alpha mRNAs in skeletal muscle correlated inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels. In a step-down regression analysis (r(2)=0.95) TNFalpha mRNA (P=0.0014), muscular TG levels (P=0.018), and GLUT4 mRNA (P=0.028) resulted to be the most powerful independent variables for predicting M values. CONCLUSION/INTERPRETATION: These findings suggest that insulin resistance in morbidly obese patients is positively associated to the intramyocytic triglycerides content and to TNF-alpha gene expression and inversely correlated to GLUT4 expression.

Adult↗

Gender affects reperfusion injury in rat liver.

Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdehyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldehyde and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation.

Animals↗

Anterior rectocele due to obstructed defecation relieved by botulinum toxin.

Background. Surgical repair of rectocele does not always alleviate symptoms related to difficulty in defecation, and some patients have impaired fecal continence after surgical treatment. To avoid complications of surgical repair, we investigated the efficacy of botulinum toxin in treating patients with symptomatic rectocele. Methods. Fourteen female patients with anterior rectocele were included in the study. The patients were studied by using anorectal manometry and defecography, and then treated with a total of 30 units of type A botulinum toxin, injected into 3 sites, 2 on either side of the puborectalis muscle and the third anteriorly in the external anal sphincter, under ultrasonographic guidance. Results. After 2 months, symptomatic improvement was noted in 9 patients (P =.0003). At the same time, rectocele depth (mean +/- SD) was reduced from 4.3 +/- 0.6 cm to 1.8 +/- 0.5 cm (P =.0000001) and rectocele area from 9.2 +/- 1.3 cm(2) to 2.8 +/- 1.6 cm(2) (P =.0000001). Anorectal manometry demonstrated decreased tone during straining from 70 +/- 28 mm Hg at baseline to 41 +/- 19 mm Hg at 1 month (P =.003) and to 41 +/- 22 mm Hg at 2 months (P =.005). No permanent complications were observed in any patient for a mean follow-up period of 18 +/- 4 months. At 1 year evaluation, incomplete or digitally assisted rectal voiding was not reported by any patient, and a rectocele was not found at physical examination. Four recurrent, asymptomatic rectoceles were noted at defecography. Conclusions. Botulinum toxin injections should be considered as a simple therapeutic approach in patients with anterior rectocele. The treatment is safe and less expensive than surgical repair. A more precise method of toxin injections under transrectal ultrasonography accounts for the high success rate. Repeated injections may be necessary to maintain the clinical improvement.

Adult↗

Glucose disposal in morbidly obese patients in the early post-operative period.

BACKGROUND: In surgical patients, operative stress causes protein catabolism, muscle mass loss, and impaired glucose tolerance. We investigated fuel metabolism and glucose and protein turnover in 15 obese subjects who underwent biliopancreatic diversion (BPD) by using stable labelled isotopes. METHODS: 6 males and 9 females (age 45.11 +/- 8.9 years, BMI of 48.85 +/- 4.43 kg/m2) who underwent BPD were studied, and the APACHE II score was calculated. Patients were studied 3 times (before BPD, 1st and 3rd postoperative day). Glycemia was stable--maintained by continuously infusing Rapid insulin. Each day of the study, the patients received a primed, constant infusion of [15N2] urea, and, 180 min after, a [6.6-2H] glucose infusion started and continued for 3 hours. Indirect calorimetry was performed during the study, under TPN (30 kcal/kg). RESULTS: The APACHE score was lower on the 3rd postoperative day than on the 1st postoperative day (7.4 +/- 2.7 vs 6.3 +/- 2.6, p < 0.05). The npRQ was different throughout the post-operative period (0.82 +/- 0.03 vs 0.9 +/- 0.06, p < 0.05), while urinary nitrogen excretion, energy expenditure and glycemia did not change. The insulin amount infused was lower during the 3rd post-operative day (44.25 +/- 12.3 vs 64.12 +/- 11 UI on the 1st one, p < 0.05). Insulinemia was lower during the 3rd than during the 1st postoperative day (66.4 +/- 9.49 vs 117.44 +/- 8.49 microU/ml, p < 0.05). Non-essential fatty acid levels were higher on the 3rd post-operative day than on the 1st one (0.98 +/- 0.6 vs 0.45 +/- 0.34 mmol/L, p < 0.01). No differences were observed in glucose and urea turn-over. CONCLUSION: The metabolic pattern of morbidly obese patients operated by BPD was similar to that of other critically ill patients previously studied in the literature. Furthermore, the increased glucose oxidation rate observed on the 3rd post-operative day was coupled with an improved clinical condition.

APACHE↗

Taurine and pulmonary hemodynamics in sepsis.

This study has been performed to characterize the relationship between changes in plasma taurine (TAU) and hemodynamic patterns in sepsis. Analysis of 249 plasma aminoacidograms (AA-grams) and associated measurements in a group of critically ill, mechanically ventilated septic patients, showed that decreases in TAU were significantly correlated with increases in pulmonary artery pressure and pulmonary vascular resistance, and with worsening of pulmonary dysfunction. All cases requiring positive end-expiratory pressure greater than 10cmH2O had TAU lower than 50 microM/L. Low TAU was paralleled by decreases in other sulfur-containing AA, phosphoethanolamine, beta-alanine, glutamate and aspartate, within a pattern of greater metabolic dysregulation. These data provide evidence of a link between severity of pulmonary dysfunction and reduced TAU availability in clinical sepsis. The implications relate also to the need for specific investigations of the clinical effect of exogenous TAU on proinflammatory mediator-induced pulmonary dysfunction.

Adolescent↗

HHV8 in renal transplant recipients.

Human herpevirus 8 (HHV8) DNA sequences have been found in lesions from patients with Kaposi's sarcoma (KS) in several forms including immunosuppressed transplant patients. We wanted to study the transmission of HHV8 in kidney transplant recipients and to assess the risk of development of KS related to the viral infection in this group of patients. We tested sera of 120 renal transplant recipients with serological assay for antibodies to HHV8 antigens before transplantation and then we tested sera of 66 patients of the same group after transplantation. Antibodies were detectable in 27.5% of the patients before transplantation. In the seropositive population 15.1% developed KS and in the negative group 1.1%. Analysing 66 posttransplant sera we noticed that 24% of the seronegative patients became positive after transplantation. Our data suggest that being positive for HHV8 before transplantation could be an important risk factor for the development of KS.

Antibodies, Viral↗