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Biomedical subjects

M Merli

Publications and source records attributed to M Merli.

At least 55 records · Page 3Linked to original sources
PubMed1997

Altered G1 phase regulation in osteosarcoma.

Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin D1 and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80% of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin D1 revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p < 0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin D1 were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin D1 had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.

Bone Neoplasms↗
PubMed1997

Impaired nonoxidative glucose metabolism in patients with liver cirrhosis: effects of two insulin doses.

Glucose intolerance is encountered in the majority of cirrhotic patients. This alteration has been attributed to a defective insulin-mediated glucose uptake in peripheral tissue, where nonoxidative glucose disposal seems to be chiefly impaired. To further investigate insulin action under euglycemic conditions, we studied how physiological (100 microU/mL) and pharmacological (1,000 microU/mL) plasma insulin concentrations affect whole-body insulin-mediated glucose uptake, as well as oxidative and nonoxidative glucose disposal, in cirrhotic patients and controls. To this aim, a sequential two-step insulin euglycemic clamp combined with indirect calorimetry was performed in eight cirrhotic patients and six control subjects. During the first step of the clamp, total glucose uptake was reduced by 40% in cirrhotic patients versus controls (4.42 +/- 1.39 v 7.63 +/- 1.60 mg/kg/min, P = .002). By increasing insulin to pharmacological levels, glucose disposal increased in both groups. However, the maximum rate of glucose metabolism achieved in cirrhotic patients was lower than in controls at all times (10.29 +/- 2.04 v 12.82 +/- 0.51 mg/kg/min, P = .012). Glucose oxidation was lower in cirrhotics in the basal state, but similar in both groups during insulin/glucose infusion. On the other hand, the reduced nonoxidative glucose disposal observed in cirrhotic patients was not normalized even by increasing insulin to pharmacological levels. In conclusion, in liver cirrhosis a reduced insulin sensitivity is associated with a reduced insulin responsiveness that is mainly caused by defective nonoxidative glucose disposal.

Adult↗
PubMed1997

Combined heart and kidney transplantation: an effective therapeutic option--report of six cases.

Six cases of combined heart and kidney transplantation with organs from the same donor are reported. All six patients suffered from primary end-stage kidney disease, two chronic glomerulonephritis, two glomerulosclerosis, one chronic pyelonephritis and one with unknown etiology. Four patients were undergoing hemodialysis. Three patients had the diagnosis of ischemic heart disease, one dilated cardiomyopathy secondary to congenital heart disease, two idiopathic dilated cardiomyopathy. Five were males and one female. Ages ranged from 38 to 54 years. On-site or short-distance young donors with normal renal function and good cardiac function necessitating low inotropic support were selected. ABO compatibility was used exclusively. Orthotopic heart transplantation was performed first. During cardiopulmonary bypass, hemofiltration was used in four cases. Kidney transplantation was performed immediately after the closure of the chest. Diuresis was immediate in all cases. No cardiac rejection was documented at EMB. Renal function normalized within few days with no signs of kidney rejection. All six patients are alive and well with normal cardiac and renal function at a mean follow-up of 43 months. Patients and donors selection associated with a proper surgical strategy and prompt immunosuppressive therapy administration make the combined heart and kidney transplantation an effective therapeutic option.

ABO Blood-Group System↗
PubMed1997

Whole body and regional body composition analysis by dual-energy X-ray absorptiometry in cirrhotic patients.

OBJECTIVES: To compare whole body and regional (arms, legs and trunk) fat mass, fat-free mineral-free mass bone mineral content and bone mineral density, measured by DXA, in cirrhotic patients and age, sex and BMI matched healthy volunteers. DESIGN: Cross-sectional study. SETTING: Two medical research institutions. SUBJECTS: Twenty-two non ascitic cirrhotic patients and 16 age, sex and BMI matched healthy volunteers. INTERVENTIONS: The Lunar DPX whole-body X-ray densitometer with Lunar software version 3.6z (Lunar Radiation Corp., Madison WI, USA) was used. Regional analysis was performed on the arms, legs, trunk and head. RESULTS: Compared to controls, cirrhotic patients showed a significant reduction in percentage body fat. When differentiated by gender, however, the reduction in percentage body fat was evident in female cirrhotics only, particularly in the trunk. In male cirrhotic patients fat-free mineral-free mass was reduced in absolute terms in the whole body and the limbs. For both genders and in each body segment bone mineral content and density were reduced in cirrhotics compared to controls. In cirrhotic patients bone mineral density was significantly correlated to both fat-free, mineral-free mass (r = 0.85; P < 0.001) and to the Physical Activity Index (r = 0.52; P < 0.01). CONCLUSIONS: Two different patterns of soft tissue loss may be found in cirrhotic patients: in women lean tissue is maintained while fat stores are reduced, as in early starvation; in men lean tissue is reduced, as seen under conditions of stress. Moreover, factors influencing lean body mass, such as nutritional depletion and physical inactivity, may contribute to the reduction of bone density frequently observed in cirrhotic patients.

Absorptiometry, Photon↗
PubMed1997

Ongoing prothrombotic state in the portal circulation of cirrhotic patients.

Portal thrombosis may complicate the clinical course of cirrhosis, but the pathophysiologic mechanism is unclear. Aim of the study was to evaluate the behavior of clotting system and endotoxemia in portal vein and in peripheral circulation of 11 cirrhotic patients undergoing transjugular port-systemic shunt (TIPS). Portal blood showed higher values of F1 + 2 [Median (range): 2.5 (1.1-5.3) vs. 1.1 (0.6-2.1) nM, p < 0.01], D-dimer [765 (184-1713) vs. 192 (64-813) ng/ml, p < 0.01] and endotoxemia [31 (16-47.2) vs. 13.7 (7.5-23.5) pg/ml, p < 0.01] than peripheral circulation. In the portal vein, all but one sample had F1 + 2 > 1.2 nM (upper limit of control values), all but one had D-dimer > 216 mg/dl (mean + 2 SD of controls) and 100% had values of endotoxemia > 9.6 pg/ml (upper limit of control values). Fibrinogen was lower in the portal circulation compared to peripheral circulation but the difference was not significant [85 (58-195) vs. 134 (75-244) mg/dl, p > 0.05]. Endotoxemia was directly correlated with F1 + 2 (Rho = 0.92 p < 0.006) and D-dimer (Rho = 0.93, p < 0.005). This study shows that an ongoing prothrombotic state is present in the portal circulation of cirrhotic patients and may play a pivotal role in the thrombotic episodes occurring in this clinical setting.

Adult↗
PubMed1997

[Heart transplantation 1985-1995: 10 years experience at the "Angelo De Gasperis" center. Improvement of results by progress in operative criteria].

BACKGROUND: At 10-years from beginning of transplant experience in our Center we analyzed the overall results in an attempt to identify risk factors for early (3 months) and late (over 3 months) mortality after heart transplantation (HTx). METHODS: The data of 313 patients transplanted from November 1985 to June 1995 were studied and analyzed with a multivariate logistic regression and Cox's proportional hazard model. Seventy pre, intra and postoperative variables were considered: demographics, clinical status, hemodynamic parameters, donor characteristics, donor-recipient mismatch, complications, immunosuppressive protocols. In this paper we compared results in patients operated on from 1985 to 1990 (Group I) and from 1991 to 1995 (Group II) in order to assess improvements due to changes in HTx indication and in perioperative treatments. RESULTS: Overall mortality in the entire group was 19.8% (62/313): 30-days, 3 months and late mortality rates were 8.0%, 10.2%, 10.7% respectively. In Group II mortality rates were 7.1%, 8.6% and 2.8% respectively despite significant increase in Status I patients (21.5% in Group I vs 40.1% in Group II, p = 0.0008). Main causes of early death were: graft failure (46.9%), infection (28.1%), acute- rejection (12.5%). Main causes of late death were: cardiac allograft vasculopathy (40.0%) and neoplasm (23.3%). The mean follow-up of the 281 survivors more than 3 months is 45.6 +/- 30.0 months (range 3 to 120 months). Actuarial survival is 86.9 +/- 1.9%, 78.4 +/- 2.7% and 70.7 +/- 3.9% at 1, 5 and 10 years respectively. The difference in the 5-years actuarial survival between Group I and Group II patients is statistically significant (70.7 +/- 4.2% vs 84.5 +/- 4.5%, p = 0.005). TPG (OR 1.19), RAP (OR 1.13) and MD-HD inotropic support of donor (OR 3.81) were identified as independent risk factors for early mortality. Number of moderate rejection at biopsy (OR 1.56) and early postTx infection (OR 3.37) were identified as independent risk factors for late mortality. CONCLUSIONS: The overall results of our ten-year experience are very satisfying in relation to early and late mortality, with a significant favourable trend between patients transplanted in the early era (1985-1990) and those transplanted in the recent era (1991-1995). The study confirm that morbidity and mortality have the highest incidence during the early post-transplantation phase. Pulmonary hypertension and elevated preoperative right filling pressure appear to indicate a significantly increased risk of early death and only marginally influence late survival that is principally related to the severe postoperative complications. Differently from other observations, among the donor-related and recipient-donor matching variables, this analysis evidenced as significant only the need for MD-HD catecolamines during donor-management.

Actuarial Analysis↗
PubMed1997

Iron overload in patients with chronic viral hepatitis: how common is it?

OBJECTIVES: To establish the prevalence of increased hepatic iron content in patients with hepatitis C virus-related chronic hepatitis and to assess the accuracy of serum iron and ferritin in detecting tissue iron overload. METHODS: Serum iron, serum ferritin, and hepatic iron content were determined in 81 consecutive patients undergoing liver biopsy for chronic ALT elevation and hepatitis C virus infection. Moreover, in a subgroup of 28 patients, outcome of a 6-month course of interferon (IFN) treatment (6 million U of recombinant IFN, three times weekly) was determined after a mean follow-up of 24 +/- 6 months and the outcome was compared with the pretreatment values of hepatic iron content. RESULTS: Elevated serum iron or ferritin levels were detected in approximately 40% of patients, but elevated hepatic iron content was observed in only eight patients (10%). One of these patients had a hepatic iron index > 1.9, indicating hemochromatosis. Liver iron content and serum iron levels were not correlated. No differences in hepatic iron content were observed among patients with a sustained response to IFN (seven patients), short-term responders (seven patients), or nonresponders (14 patients). CONCLUSIONS: Ten percent of patients with chronic hepatitis C have elevated hepatic iron content. These patients cannot be identified using serum markers of iron status. The relationship between liver iron and response to IFN treatment requires further prospective investigations.

Adult↗
PubMed1997

[Flexibility of the surgical model of intestinal transplantation in swine].

AIM: To verify the feasibility to introduce variations in the technique of intestinal transplantation, we developed three different intestinal transplant models in pigs. EXPERIMENTAL DESIGN: Feasibility and comparative study. ENVIRONMENT: Pre-clinical organ transplant surgery. MATERIALS AND METHODS: Sixty outbread piglets (mean weight 27.1 +/- 4.4 kg) received a total orthotopic intestinal allograft from equivalent donors perfused through the aorta with UW solution at 4 degrees C. Intraluminal flushing of the graft was always avoided. The animals were divided in 3 groups according to the transplantation procedure adopted. Group 1 (n = 9): excision of small and large bowel and replacement with small bowel only; group 2 (n = 39): excision of small bowel and its replacement; group 3 (n = 12): excision of small and large bowel and their "en-bloc" replacement. The superior mesenteric artery and vein were anastomosed end-to-end in all groups. RESULTS: The lowest perioperative mortality occurred in group 2 (28%), followed by group 3 (58%) and group 1 (78%). However, in group 1 the incidence of perioperative deaths was influenced by our learning curve in surgical and anesthesiologic management. No significant differences were noted in terms of cold and warm ischaemia time of the grafts, length of operative time, histopathologic analysis of preservation injury. The addition of the colon in the transplanted graft resulted in a more critical hemodynamic profile at reperfusion. CONCLUSION: Three different experimental models of intestinal transplantation are feasible in pigs. The choice can be made based on the type of study needed.

Analysis of Variance↗
PubMed1996

Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi).

A total of 1,053 cirrhotic patients were included in a prospective study to determine whether malnutrition is a risk factor for mortality in cirrhotic patients. Child-Pugh classification as well as clinical and biochemical variables were used to assess the severity of cirrhosis. Nutritional status was evaluated both by anthropometric and clinical measurements. Patients were defined as malnourished when midarm muscle area (MAMA) and/or midarm fat area (MAFA) were below the 5th percentile of an age- and sex-matched population. During follow-up, 419 patients died. The estimated survival rate was 82.7% at 1 year, 65.1% at 3 years, and 50.7% at 5 years. The presence of muscle depletion and/or of a steep reduction in fat deposits was associated with a higher risk of mortality (midarm muscle area, < 5th percentile, relative risk = 1.79; midarm fat area, < 5th percentile, relative risk = 1.35). When patients were stratified according to the Child-Pugh classification, cumulative survival was lower in patients with a reduction in muscle mass in Child-Pugh classes A and B (log rank: P = .027; P = .022, respectively) but not in class C. Conversely, a significant reduction in adipose tissue deposits appeared to have no independent impact on survival in any Child-Pugh class. When examined using a multivariate Cox proportional hazard analysis, age, sex, bilirubin, cholinesterase, ascites, and esophageal varices were selected, whereas the parameters of nutritional status were not. This suggests that malnutrition, while strongly associated with the deterioration of liver function, cannot be considered an independent risk factor for mortality in a general population of cirrhotic patients.

Female↗
PubMed1996

Increased nonoxidative glucose metabolism in idiopathic reactive hypoglycemia.

Idiopathic reactive hypoglycemia (IRH) is responsible for postprandial hypoglycemia. Normal insulin secretion and reduced response of glucagon to acute hypoglycemia, but mostly increased insulin sensitivity, represent the metabolic features of this syndrome- The present study has two aims: first, to investigate the fate of glucose utilization inside the cells to assess whether increased glucose disposal in IRH is due to the oxidative and/or nonoxidative pathway; and second, to evaluate glucagon response to prolonged insulin-induced hypoglycemia. In eight patients with IRH and eight normal (N) subjects, we performed two studies on different days: (1) 120-minute euglycemic-hyperinsulinemic (1.0 mU . kg-1 . min-1 regular human insulin) clamp associated with indirect calorimetry; and (2) 180-minute hypoglycemic (2.22 to 2.49 mmo/L achieved through 0.85 mU . kg-1 . min-1 intravenous [IV] regular human insulin) clamp. The results showed an increased insulin-mediated glucose uptake in IRH (9.10 +/- 0.19 v 6.78 +/- 0.18 mg kg-1 . min-1, P < .005). Glucose oxidation was similar in IRH subjects and controls both in basal conditions (1.39 +/- 0.16 v 1.42 +/- 0.15 mg . kg-1 . min-1 and during the clamp studies (2.57 +/- 0.21 v 2.78 +/- 0.26 mg . kg-1 . min-1. In contrast, nonoxidative glucose disposal was significantly higher in IRH than in N subjects (6.53 +/- 0.30 v 4.00 +/- 0.21 mg . kg-1 . min-1, P < .001). During insulinization, fat oxidation was reduced slightly more in IRH than in control subjects. During the hypoglycemic clamp, a significant (P < .01) increase in plasma glucagon concentrations was observed in normal subjects as compared with baseline, whereas no change occurred in IRH patients. In conclusion, in IRH: (1) increased insulin-mediated glucose disposal is due to the increase of nonoxidative glucose metabolism; and (2) glucagon secretion has been confirmed to be inadequate. The increase of insulin sensitivity associated with a deficiency in glucagon secretion can widely explain the occurrence of hypoglycemia in the late postprandial phase.

Adult↗
PubMed1994

Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.

Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating.

Absorption↗
PubMed1994

[Transjugular intrahepatic porto-systemic shunt (TIPS): indications and results].

This study was aimed at describing some technical features of the transjugular portosystemic shunt (TIPS). December 1991 to November 1993, fifty-five TIPS were performed in our department. The right internal jugular vein, which is the most direct path to the inferior vena cava, was punctured in 48 cases, the left one in seven cases. The right suprahepatic vein was catheterized in 43 cases, and the median suprahepatic vein in 12 cases. The puncture of the portal vein was performed in 21 cases in the right portal branch, in the left one in 23 cases, and in the portal bifurcation in 11 cases. In all cases in which the puncture site was questionable, an X-ray exam with lateral or oblique projection was performed, to be sure that the needle had entered the intrahepatic portion of the portal vein. A landmark to locate the portal system, such as a catheter in the hepatic artery, a skin landmark or a metallic coil near the porta, were positioned in 30 patients. Particularly, in 20 patients, a 0.018-inch guidewire with platinum tip was placed at the bifurcation; in seven cases a 3F catheter was advanced over the guidewire, to visualize the portal bifurcation directly with contrast medium injection. In our experience, a total number of 83 stents were positioned in 55 patients: 53 Wallstents, 13 Palmaz stents, and 17 Strecker-Nitinol stents. One single stent was placed in 31 patients, two stents in 21 patients, three stents in two patients, and, finally, four stents were positioned in one patient. In our series the technical success rate was 100%. The use of a metallic landmark significantly decreased procedures duration, ranging 40 minutes to 2 hours, and, above all, it allowed for significantly fewer puncture attempts, which varied from a minimum of 1-2 in 80% of cases, to a maximum of 20 especially in these patients with ascitis and with small and hard liver.

Procedural Sedation↗
PubMed1993

Myocardial blood flow distribution in patients with ischemic heart disease or dilated cardiomyopathy undergoing heart transplantation.

BACKGROUND: The present investigation was designed to obtain an absolute measurement of myocardial blood flow and of its transmural distribution in ischemic heart disease and idiopathic dilated cardiomyopathy and to provide a reference standard for cardiac imaging in nuclear cardiology. METHODS AND RESULTS: Regional myocardial blood flow and its transmural distribution were estimated by the reference microsphere method in eight patients with idiopathic dilated cardiomyopathy (n = 4) or ischemic heart disease (n = 4) during heart transplant procedure. Before aortic clamping, 99mTc-labeled human albumin microspheres were injected into the left atrium while arterial blood was sampled from the aorta at a constant rate. No complications were observed during or after the procedure. From the excised heart, myocardial slices for gamma camera imaging and well counting analysis were obtained. Myocardial blood flow was assessed by a well counter, correlated with the extent of fibrosis expressed as collagen per total tissue proteins obtained from 4-hydroxyproline and glycine as determined by high-performance liquid chromatography. Microsphere distribution, as seen by gamma camera images in a different slice, was correlated with the extent of fibrosis assessed by histological analysis of the same myocardial specimen. Mean transmural myocardial blood flow was 0.49 +/- 0.17 and 0.38 +/- 0.15 mL.min-1 x g-1 in idiopathic dilated cardiomyopathy and ischemic heart disease, respectively (P < .01). Endocardial-to-epicardial flow ratio was lower in ischemic heart disease than in idiopathic dilated cardiomyopathy patients (0.99 +/- 0.33 versus 1.16 +/- 0.30, P < .05). Mean myocardial fibrosis was 9 +/- 6% in idiopathic dilated cardiomyopathy and 25 +/- 28% in ischemic heart disease. In both groups, no correlation was found between myocardial blood flow values and the extent of fibrosis. In ischemic heart disease, regional myocardial blood flow was not significantly affected by the severity of coronary stenosis (< or = 70% or > 70%) either in the endocardium (0.44 +/- 0.24 versus 0.36 +/- 0.16 mL.min-1 x g-1, P = NS) or in the epicardium (0.50 +/- 0.33 versus 0.38 +/- 0.33 mL.min-1 x g-1, P = NS). By gamma camera imaging, transmural microsphere distribution appeared more homogeneous in idiopathic dilated cardiomyopathy than in ischemic heart disease (mean coefficient variation, 18% and 27%, respectively; P < .02); the severity of perfusion impairment did not correlate with the extent of fibrosis evaluated by histological criteria. CONCLUSIONS: Heart transplant surgery offers a valuable model to assess absolute myocardial perfusion in human heart failure. Myocardial blood flow is markedly depressed in failing hearts of both ischemic heart disease and idiopathic dilated cardiomyopathy patients; a different transmural myocardial blood flow distribution is observed in ischemic heart disease than in idiopathic dilated cardiomyopathy, with prevalent endocardial perfusion in the latter but not the former condition. In patients with end-stage heart failure, myocardial blood flow appears to be similarly impaired in fibrotic and viable regions. Mechanisms other than myocardial fibrosis and coronary lesions appear to operate in determining myocardial blood flow impairment in heart failure.

Adult↗