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Biomedical subjects

R Mariotti

Publications and source records attributed to R Mariotti.

At least 19 recordsLinked to original sources

Ninety-five percent insulin independence rate 3 years after pancreas transplantation alone with portal-enteric drainage.

AIMS: Portal-enteric drainage (PED) might be particularly suitable for pancreas transplantation alone (PTA), since it has been associated with an immunologic advantage and achieves excellent metabolic results. We describe our experience with a consecutive series of 40 PTAs with PED. METHODS: Between April 2001 and March 2004, 40 consecutive PTAs were performed with PED. Recipients were selected according to the American Diabetic Association recommendations. Donors were selected according to standard criteria irrespective of HLA match, although matching for A and B loci was considered at the time of graft allocation. Immunosuppression consisted of induction treatment with basiliximab (n = 34) or thymoglobulin (n = 6), and maintenance therapy with steroids, mycophenolate mofetil, and tacrolimus. RESULTS: After a mean cold ischemia time of 690 minutes (range, 517-965 min) all pancreases functioned immediately. Three grafts were lost due to hyperacute or accelerated rejection. No graft was lost to vascular thrombosis, although 5 (12.5%) nonocclusive thromboses were identified and the grafts were rescued with intravenous heparin infusion. A repeat laparotomy was required in 7 recipients (17.5%) No patient required multiple repeat laparotomies, and none died. After a mean follow-up of 16.4 months (range, 1-36 mo), 2 recipients were diagnosed with rejection episodes, which were reversed with steroid boluses. Actuarial 3-year patient, and graft survival rates were 100% and 94.9%, respectively. The following parameters showed significant improvement compared with pretransplantation evaluation: hemoglobin A1C concentration, total and high-density lipoprotein cholesterol levels, arterial blood pressure, cardiac performance, retinopathy, proteinuria, and neuropathy. CONCLUSIONS: Pancreas transplantation alone with PED provides high rates of long-term insulin-independence.

Adult↗

Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study.

Type I diabetes mellitus (IDDM) is associated with an increased cardiovascular risk, and eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) are consequently accurate for preoperative cardiovascular assessment. According to our algorithm, coronary angiography in SPKT candidates is indicated for patients not only experiencing previous cardiac events or symptoms, but also those with long-standing diabetes (more than 25 years) and/or age over 45 years. Furthermore, a basal transthoracic echocardiographic exam (TTE) is performed to assess cardiac volumes, left ventricular mass, systolic function, and kinesis. The aims of this study were to evaluate perioperative cardiac morbidity and mortality in 18 SPKT-eligible patients, divided into two groups on the basis of the presence/absence of angiographically evident coronary artery disease (CAD), as well as to assess the impact of left ventricular hypertrophy (LVH) on cardiac complications. Cardiac intraoperative morbidity and mortality and postoperative mortality and major morbidity were absent; minor cardiac morbidity consisted only of silent ischemic ECG alterations, without significant differences between groups, although the incidence seemed to be higher in the CAD-positive population. LVH detected preoperatively by TTE exam also failed to correlate with the incidence of such complications. Selection of SPKT candidates by coronary angiography may have positive effects on perioperative cardiac morbidity and mortality. A larger sample size is needed to give the study statistical power. Medium- and long-term follow-up studies are warranted to evaluate the effects of preoperative selection on survival rates.

Adult↗

Echocardiographic evaluation in type 1 diabetic patients on waiting list for isolated pancreas or kidney-pancreas transplantation.

Type 1 diabetic patients may display abnormalities of left ventricular geometry and systolic and diastolic function. Patients on the waiting list for solitary pancreas or kidney-pancreas transplantation were evaluated by Doppler echocardiography to assess left ventricular geometry and systolic and diastolic function, and correlate these parameters with clinical characteristics. We evaluated 78 patients including 45 men with an overall mean age of 39.5 +/- 7.2 years and a disease duration of 24 +/- 9.8 years. Among these 78 patients, 13 showed isolated retinopathy, 9 isolated arterial hypertension, 45 concomitant retinopathy and hypertension and overt nephropathy, while 11 were free of complications. The results of our study showed an increased left ventricular mass and abnormal diastolic function among patients with simultaneous target organ complications and with hypertension, as has been reported in many previous studies. In contrast study patients with no complications showed normal left ventricular structure and function. This finding conflicts with data from several reports in the medical literature in which diastolic impairment was present in type 1 diabetic patients at an early stage of disease and with no evident microvascular and macrovascular complications.

Adult↗

Priming by muscle inflammation alters the response and vulnerability to axotomy-induced damage of the rat facial motor nucleus.

To ascertain whether signaling due to peripheral inflammation affects motoneuron vulnerability, we examined in adult rats the reaction to axonal injury of facial motoneurons primed by muscle inflammation. In this double-hit paradigm, preconditioning was achieved by injections into the facial muscles of the T cell mitogen phytohemagglutinin, which was found in a previous study ( 11 ) to elicit a retrograde response in motoneurons. Facial nerve transection was used as test lesion. Intramuscular injections of saline prior to axotomy were used as control for lectin pretreatment. In rats pretreated with phytohemagglutinin injection, upregulation of the expression of the antiapoptotic bcl-2 gene, examined with in situ hybridization, was significantly higher in facial motoneurons at 2 days postaxotomy compared with saline-injected control cases. After repeated phytohemagglutinin injections followed by nerve transection, induction in facial motoneurons of nitric oxide synthase, revealed by histochemistry and immunohistochemistry, as well as activation of the surrounding microglia, was enhanced at 14 days postaxotomy with respect to the saline-treated control cases. At the same time point, no significant intergroup difference was detected in the intensity of astrocytic activation. At 1 month postaxotomy, stereological cell counts revealed that motoneuron loss was significantly greater in the cases pretreated with phytohemagglutinin than in the saline-treated cases. The data point out that the response of the facial motor nucleus to axonal damage is altered by previous exposure to peripheral inflammation and that such preconditioning stimulus enhances motoneuron vulnerability to nerve injury.

Animals↗

Altered reaction of facial motoneurons to axonal damage in the presymptomatic phase of a murine model of familial amyotrophic lateral sclerosis.

In transgenic mice carrying the G93A human mutation of Cu/Zn superoxide dismutase (SOD1), which provide a model of familial amyotrophic lateral sclerosis, we investigated, before the onset of symptoms, two parameters of the response of facial motoneurons to nerve transection, i.e. nitric oxide synthase induction and motoneuron loss. Axotomy elicited after 2 and 3 weeks high nitric oxide synthase expression in facial motoneurons of wild-type mice, whereas the induction was very weak or absent in transgenic mice. At 1 month post-axotomy, loss of facial motoneurons was significantly higher in mutant mice than in wild-type littermates. Thus, SOD1 mutation interferes with the oxidative cascade elicited by axonal injury in cranial motoneurons. The results also indicate that the adverse gain of function of the mutant SOD1 enhances the vulnerability of motoneurons to peripheral stressful conditions.

Amyotrophic Lateral Sclerosis↗

Retrograde response of the rat facial motor nucleus to muscle inflammation elicited by phytohaemagglutinin.

To investigate whether motoneurons react to signals deriving from target inflammation, we studied the facial motor nucleus after injections of phytohaemagglutinin in the snout of adult rats. This plant lectin is a tool widely used to induce proliferation and activation of T lymphocytes, and we observed marked lymphocyte infiltration in the injected facial muscles. Retrograde labelling of motoneurons was not detected after peripheral injections of fluorochrome-conjugated phytohaemagglutinin. Nitric oxide synthase, revealed by NADPH-diaphorase histochemistry, OX-42-immunoreactive microglia, and expression of the cell death repressor gene bcl-2, investigated with nonradioactive in situ hybridization and immunohistochemistry, were evaluated in the facial nucleus. Daily phytohaemagglutinin injections for 4 days, mimicking repeated muscle exposure to inflammatory stimuli, resulted after 2-day survival in NADPH-diaphorase induction in motoneurons and marked activation of the surrounding microglia. Quantitative image analysis of NADPH-diaphorase staining, and OX-42 immunoreactivity and microglial cell counts indicated highly significant increases with respect to saline-injected control cases. The occurrence of a neuroprotective retrograde response was evaluated monitoring bcl-2 expression. Following single phytohaemagglutinin administration, bcl-2 mRNA was significantly upregulated at 6 h in facial motoneurons and returned to basal levels at 24 h. Bcl-2 immunoreactivity was markedly upregulated at 24 h and was still significantly higher than in controls at 7 days, when concomitant NADPH-diaphorase induction in motoneurons and microglia activation was also observed. No degenerative features were observed in motoneurons after phytohaemagglutinin injections at the examined time-points. The data point out that local muscle inflammation retrogradely elicits gene activation in motoneurons and their microenvironment.

Animals↗

Acute-phase reactants in acute myocardial infarction: impact on 5-year prognosis.

BACKGROUND: Acute-phase reactants have recently been shown to have a short-term and possibly long-term prognostic value in acute coronary syndromes. The aim of the present study was to retrospectively verify whether serum levels of inflammation markers can predict the occurrence of early and late cardiac events after myocardial infarction. METHODS: We reevaluated 58 consecutive patients (43 men and 15 women, mean age 66 +/- 12 years) admitted to our Center during 1993 with a first myocardial infarction. Patients with non-cardiac causes of inflammation were excluded, as well as patients with a left ventricular ejection fraction <40%. From the first blood sample obtained at admission, we evaluated C-reactive protein (CRP) and alpha1-acid glycoprotein (alpha1-AGP) serum levels, the erythrocyte sedimentation rate (ESR), fibrinogen levels, and the white blood cell (WBC) count. We also evaluated the highest level of serum cardiac markers. Follow-up data were collected for 55 patients in June 1999. RESULTS: Five in-hospital and 13 delayed cardiac deaths occurred. The mean follow-up of current survivors was 5.9 +/- 0.4 years. Patients in whom cardiac death occurred had significantly higher CRP (7.4 +/- 4.1 vs 3.0 +/- 2.4 mg/dl, p < 0.001) and alpha1-AGP levels (160 +/- 38 vs 113 +/- 24 mg/dl, p < 0.001), ESR (63 +/- 30 vs 37 +/- 25 mm/hour, p < 0.001), and WBC count (13,727 +/- 3,853 vs 10,936 +/- 3,358/mm3, p = 0.004). At multivariate analysis, higher alpha1-AGP (p < 0.001) and CRP serum levels (p = 0.02) were independent predictors of cardiac death. Patients in whom cardiac events occurred during follow-up showed higher CRP (5.7 +/- 3.7 vs 1.6 +/- 1.5 mg/dl, p < 0.001) and alpha1-AGP levels (140 +/- 36 vs 101 +/- 23 mg/dl, p < 0.001) and ESR (50 +/- 30 vs 34 +/- 26 mm/hour, p = 0.06). Higher alpha1-AGP (p < 0.001) and CRP serum levels (p = 0.03) were independent predictors of the occurrence of cardiac events. CONCLUSIONS: The present study shows that CRP and alpha1-AGP have an independent prognostic value in patients presenting with a first, uncomplicated myocardial infarction. Assays of these markers may help to better stratify patients hospitalized for acute coronary syndromes.

Acute-Phase Proteins↗

Cardiopulmonary exercise test in young women affected by anorexia nervosa.

BACKGROUND: The aim of this study was to evaluate exercise performance in patients affected by anorexia nervosa. METHODS: We studied 19 patients (all females, mean age 23.1 +/- 5.2 years) affected by anorexia nervosa (mean weight 37.3 kg, body mass index 14.04 +/- 1.4 kg/m2) and 20 constitutionally thin women, matched for age, height and physical activity, with a body mass index < 19 kg/m2. All these women underwent clinical examination, standard ECG and a cardiopulmonary stress test. RESULTS: Patients affected by anorexia nervosa showed a lower heart rate and systolic blood pressure at peak exercise (148.8 +/- 13.8 vs 171 +/- 9.2 b/min, p < 0.001, and 130 +/- 9.5 vs 152 +/- 11.2 mmHg, p < 0.001), work load (85.5 +/- 15.1 vs 117.2 +/- 20.3 W, p < 0.001), rate-pressure product (19 371 +/- 2391 vs 25,986 +/- 2218 b/min/mmHg, p < 0.001), oxygen uptake (VO2) at rest and maximum VO2 (5.4 +/- 1.7 vs 7.1 +/- 1.1 ml/kg/min, p < 0.001, and 28.08 +/- 6.3 vs 40.2 +/- 7.1 ml/kg/min, p < 0.001), anaerobic threshold (15.7 +/- 1.9 vs 20.4 +/- 2.1 ml/kg/min, p < 0.001), VO2 during exercise (9.5 +/- 1.2 vs 12.8 +/- 1.3 ml/min/W, p < 0.001), maximum minute ventilation (34.5 +/- 9.9 vs 48.4 +/- 10.3 /min, p < 0.001), and oxygen pulse (7.2 +/- 2 vs 10.9 +/- 2.4 ml/b, p < 0.001). CONCLUSIONS: These data show an abnormal working capacity and cardiovascular responses to exercise in patients affected by anorexia nervosa. The low VO2, both at rest and during exercise, allows them to maintain a relatively high level of physical activity, which contributes to increase the energy expenditure needed for weight loss.

Adolescent↗

Activation and response to axotomy of microglia in the facial motor nuclei of G93A superoxide dismutase transgenic mice.

Mice over-expressing a human mutation of Cu(2+)/Zn(2+) superoxide dismutase (SOD1) provide a model of amyotrophic lateral sclerosis. Using tomato lectin histochemistry, we analyzed microglia in the facial nuclei of SOD1(G93A) transgenic mice in the late stage of disease. In these animals, microglia was markedly activated, and ensheathed facial motoneurons as observed in wild-type mice 1 week after nerve transection. In the axotomized facial nucleus of transgenic mice at the same time point, microglia activation was enhanced and exhibited phagocytic features. The findings show that in the facial nucleus microglial cells react to motoneuron disease caused by the SOD1 mutation and to axotomy-induced damage of facial motoneurons.

Alanine↗

The impact of coronary artery disease on the coronary vasomotor response to nonionic contrast media.

BACKGROUND: Coronary artery disease (CAD) alters the vasomotor response to a variety of pharmacological agents. We tested the hypothesis that CAD also has an impact on the coronary vasomotor response to radiologic contrast media. METHODS AND RESULTS: We performed quantitative coronary angiography in 42 patients without angiographic evidence of CAD and 38 patients with CAD in the left coronary artery. Angiographically smooth coronary segments (n=235) were analyzed for changes on luminal diameters and coronary venous oxygen saturation in response to 3 media: the nonionic dimer iodixanol, the nonionic monomer iopromide, and the ionic agent ioxaglate. In subjects without CAD, we assessed the effects of intracoronary administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine and of the cyclooxygenase inhibitor indomethacin on such changes. Iodixanol induced coronary vasodilation in subjects without CAD (8.8+/-8.6%, P<0.001). Patients with CAD exhibited no significant diameter changes in segments >/=20 mm apart from a stenosis (4.7+/-9.4%, P=NS) and significant constriction in segments <20 mm from a stenosis (-3.8+/-4.6%, P<0. 05). Similar results were obtained with iopromide, but no changes were found with ioxaglate. All contrast media induced transient (<35 seconds) increases in coronary venous oxygen saturation in all subjects. Indomethacin, but not N(G)-monomethyl-L-arginine, blunted the vasodilating effect of iodixanol and iopromide (by 80% and 76%, respectively; P<0.001). CONCLUSIONS: Nonionic contrast media induce a vasodilatory response in normal vessels not by a mechanism involving increased flow or endothelial nitric oxide synthesis, but rather by depending on preserved vascular cyclooxygenase activity. CAD changes normal epicardial vasodilatory response into vasoconstriction.

Aged↗

Symptomatic improvement after transmyocardial laser revascularization: how long does it last?

BACKGROUND: The aim of this study was to determine whether short-term clinical improvement after isolated transmyocardial holmium laser revascularization (TMLR) in patients with coronary artery disease not amenable to traditional treatment is maintained through a longer follow-up. METHODS: Between November 1995 and June 1999 34 patients underwent TMLR (mean age, 67+/-7 years); previous revascularization procedures had been performed in 76%. Preoperatively, mean angina class was 3.6+/-0.5 in 12 patients with unstable angina; mean left ventricular ejection fraction was 47%+/-9%. RESULTS: There was 1 early death due to low cardiac output. Mean duration of TMLR and of the entire operation was 25+/-12 minutes and 125+/-43 minutes, respectively. There were no major postoperative complications; mean hospital stay was 8+/-4 days. There were 8 late deaths caused by stroke (2 patients), cardiac failure (1 patient), and myocardial infarction (5 patients). Follow-up of current survivors ranges from 4 to 48 months (mean, 32+/-12 months). At 1-year follow-up mean angina class was 1.8+/-0.8; but at a later follow-up (mean, 35+/-10 months) it significantly increased to 2.2+/-0.7 (p = 0.005). Three-year actuarial survival was 76%+/-8% and freedom from cardiac events 44%+/-10%. CONCLUSIONS: Our results show that after initial clinical improvement many patients experience return of angina or cardiac events; this questions the long-term symptomatic benefit of TMLR.

Aged↗

Usefulness of carotid intima-media thickness measurement and peripheral B-mode ultrasound scan in the clinical screening of patients with coronary artery disease.

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p<0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p<0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultrasound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

Adult↗