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Biomedical subjects

S Morelli

Publications and source records attributed to S Morelli.

At least 55 records · Page 3Linked to original sources
PubMed1998

99mTc SESTAMIBI scintigraphic evaluation of skeletal muscle disease in patients with systemic sclerosis: diagnostic reliability and comparison with cardiac function and perfusion.

The diagnosis of skeletal muscle involvement in patients with systemic sclerosis (SSc) is usually based on clinical, laboratory, electromyographic, and bioptic evidence of muscle disorder, whereas SSc cardiac disease is well established by nuclear medicine techniques (radionuclide ventriculography and myocardial scintigraphy). Previous reports have retrospectively hypothesized a possible relationship between cardiac and muscle involvement in scleroderma patients. In order to improve overall diagnostic accuracy in the qualitative/quantitative assessment of skeletal muscle involvement in these patients and to compare these results with those obtained at the cardiac level, diethylenetriaminepentaacetic acid (DTPA)-99mTc radionuclide ventriculography and 99mTc SESTAMIBI myocardial and muscular scintigraphic examinations were performed in 10 SSc patients and in five healthy subjects. Muscular radioactivity, as assessed at thigh and calf levels by means of a segmental score, was significantly decreased in SSc patients in comparison with healthy subjects (global score value 15.6+/-2.2 vs 22.7+/-1.6, p<0.001), as well as right ventricular ejection fraction (RVEF, 34.3%+/-5.3 vs 53.6%+/-4.2, p<0.001) and myocardial segmental perfusion (global score value, 19.6+/-2 vs 25.9+/-1.1, p<0.01). The results show a high frequency of skeletal muscle involvement in patients with SSc. Moreover, scleroderma patients with muscle disorders, as evidenced by scintigraphy, show a comparable occurrence of cardiac involvement, even in the absence of clinical signs of cardiac dysfunction.

Cardiomyopathies↗
PubMed1998

QT interval and QT dispersion in systemic sclerosis (scleroderma).

OBJECTIVES: To measure QT interval and QT dispersion, and to evaluate possible relationships between these measurements, heart rate variability parameters, and early myocardial involvement in patients with systemic sclerosis (SSc). DESIGN: Prospective study. SETTING: Tertiary care centre, University 'La Sapienza', Rome, Italy. SUBJECTS: Thirty-eight patients with SSc (35 females and three males, mean age 47 +/- 11 years), 19 patients with the diffuse form of disease and 19 with the limited form, and 17 healthy controls (11 females and six males, mean age 43 +/- 10 years) were studied. INTERVENTIONS: Both patients and control subjects underwent resting 12-lead electrocardiogram and 24-hour Holter monitoring. Moreover, resting myocardial scintigraphy with 99 m Tc-sestamibi was performed in all SSc patients. MAIN OUTCOME MEASURES: Bazett's formula was used to obtain rate corrected value of QT interval (QTc). QT and QTc dispersion were defined as the difference between maximum and minimum QT or QTc interval, respectively. Twenty-four-hour heart rate variability was analysed both in the frequency and in the time domain. RESULTS: Twenty-three SSc patients (60.5%) had myocardial resting perfusion defects (group A) and 15 (39.5%) did not (group B). Maximum QTc interval, QT and QTc dispersion were significantly increased in SSc patients compared to the control subjects. No significant differences between group A and group B were observed for all QT measurements. Furthermore, maximum QTc interval, QT dispersion and QTc dispersion were significantly increased in group A patients compared to the control group. Total power, low-frequency, and high-frequency values were significantly lower in all SSc patients, whether in group A or group B, than in control subjects. On the other hand, low-frequency/high-frequency ratio was similar in all groups. Heart rate variability in time domain analysis showed no statistically significant differences between groups. CONCLUSIONS: Patients with SSc have increased QTc interval, QT dispersion, and QTc dispersion. The role of autonomic nervous system and myocardial involvement on ventricular repolarization in patients with SSc needs further investigation.

Adult↗
PubMed1998

[Post-infantile giant cell hepatitis. Clinical and histological response to immunosuppressive therapy].

Giant cell transformation of hepatocytes combined with variable degrees of hepatocyte necrosis and liver fibrosis is distinctly uncommon in adults. In this age group it has most often been associated with autoimmunity, drug reaction and viral infection. Prognosis is considered quite severe ranging from mild fibrosis to established cirrhosis. We report a case of giant cell hepatitis that occurred in a 30 yrs old man, who had been taking ticlopidine for 3 years. The causative role of the drug is uncertain because aminotransferase did not fall after withdrawal. The patient fulfilled most of the criteria for a diagnosis of autoimmune hepatitis and was treated accordingly with prednisolone and azathioprine. Immunosuppressive therapy led to a clinical, biochemical and histological response.

Adult↗
PubMed1998

Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms.

Flutamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic cancer. Hepatotoxic reactions due to flutamide have been reported with an incidence ranging from 1% to 5%. These reactions are usually reversible upon withdrawal of the drug but can occasionally be life-threatening. The mechanism of flutamide-associated hepatotoxicity is not well established. We report a case of a 69-year-old man with prostatic carcinoma in whom flutamide induced an acute hepatitis which resolved completely soon after drug withdrawal. In this patient, we have studied the possible involvement of an immunological mechanism in causing flutamide hepatitis by investigating the presence of circulating antibodies directed against reactive metabolites of flutamide bound to liver proteins with enzyme-linked immunosorbent assay technique. Although, in the present case, we have failed to detect IgG reacting with rat liver microsomes incubated in vitro with flutamide, this does not completely rule out the possibility of an immunological involvement in flutamide hepatotoxicity. The possibility of severe flutamide-related injury, independently of the underlying pathogenic mechanism, strongly suggests the need for careful monitoring of liver enzymes in patients taking this drug.

Acute Disease↗
PubMed1997

The antisense bcl-2-IgH transcript is an optimal target for synthetic oligonucleotides.

In most human follicular B cell lymphomas the bcl-2 gene is up-regulated as a result of the t(14;18) chromosomal translocation generating a hybrid bcl-2-IgH mRNA. Recently, we have identified in t(14;18)-positive cells a bcl-2-IgH mRNA in the antisense orientation, putatively responsible for the overexpression of bcl-2. Herein we show that this chimeric antisense transcript is an optimal target for synthetic oligodeoxynucleotides (ODNs). A variety of sense-oriented oligonucleotides have been designed that target the antisense transcript in regions endowed with a sequence specificity presumably restricted to an individual cell line (the bcl-2-IgH fusion regions) or extended to all t(14;18) cells (the ectopic bcl-2 segment upstream from the major breakpoint region and the IgH segment). All sense-oriented ODNs complementary to the antisense transcript induced an early strong inhibition of cell growth and a late fulminant cell death. As expected, the activity of ODNs targeting the fusion region was restricted to each individual cell line, whereas the activity of all ODNs targeting the common bcl-2 and IgH segments was extended to all t(14;18) cell lines tested. These sense ODNs were not effective in untranslocated cell lines. Antisense-oriented ODNs, complementary to the bcl-2-IgH mRNA, and control ODNs (scrambled, inverted, or mismatched) were biologically ineffective. The selectivity and efficacy of all sense ODNs tested provide support for the development of therapeutic ODNs targeting the bcl-2-IgH antisense transcript expressed in human follicular lymphomas.

Apoptosis↗
PubMed1997

Plasma endothelin-1 levels during transient acute myocardial ischaemia in men: effects of coronary revascularization.

The endothelium-derived peptide endothelin-1 (ET-1) was evaluated in 14 male patients [mean age 52.74 years (SEM 1.10)] affected by coronary artery disease during a bicycle electrocardiographic stress test and dipyridamole echocardiogram. Both tests were performed before and after coronary revascularization. Fourteen healthy male subjects served as controls [mean age 53.21 years (SEM 1.63)]. Baseline plasma endothelin-1 levels were higher (P < 0.0001) in ischaemic patients [1.81 pg mL-1 (0.15, n = 14)] than in control subjects [0.61 pg mL-1 (0.03, n = 14)], but did not increase with exercise in both groups. Similar results were obtained with dipyridamole infusion. Endothelin-1 levels significantly decreased after coronary revascularization [before: mean 1.81 pg mL-1 (SEM 0.15, n = 14); after: mean 1.16 pg mL-1 (SEM 0.11), P < 0.002], without changes in the peptide response to both tests. In conclusion, elevated plasma endothelin-1 concentrations were found in patients with stable angina compared with non-ischaemic subjects. No changes were observed during exercise or dipyridamole infusion in both groups. Coronary revascularization was followed by a significant decrease in plasma endothelin-1 levels.

Adult↗
PubMed1997

Relationship between cutaneous and pulmonary involvement in systemic sclerosis.

OBJECTIVE: Pulmonary disease may shorten survival in patients affected by systemic sclerosis (SSc). However, pulmonary involvement may commonly be silent, whereas skin fibrosis is usually the clinical feature drawing most attention. We investigated the relationship between cutaneous and pulmonary involvement during SSc. METHODS: We studied 52 patients (mean age 50.2 +/- 13.7 years) affected by SSc (mean duration of disease 13.8 +/- 9.5 years). Twenty-eight had the diffuse form of the disease (dSSc) and 24 the limited form (lSSc). All patients underwent pulmonary function studies, high resolution computed tomography (HRCT) of the lungs, and complete echocardiographic examination. Pulmonary artery systolic pressure was measured by Doppler echocardiography. Pulmonary interstitial fibrosis and skin fibrosis were evaluated using a point system. RESULTS: Mean percentages of predicted values of forced vital capacity and total lung capacity were significantly reduced in patients with dSSc compared to lSSc (80.0 +/- 18.9 vs 98.4 +/- 16.8%, p < 0.001; and 81.3 +/- 13.9 vs 92.1 +/- 14.2%, p < 0.01, respectively). The overall HRCT score was 6.1 +/- 4.9, with no significant differences between disease subgroups. However, a HRCT score of 10 or more was present in 10 patients with dSSc vs 2 patients with lSSc (p = 0.02). Pulmonary hypertension was present in 27 patients, 15 with lSSC and 12 with dSSc (p = NS). No significant correlation was observed between skin score and lung volumes, carbon monoxide diffusing capacity, HRCT score, or pulmonary artery systolic pressure for all patients and subgroups. CONCLUSION: Extent and severity of cutaneous and pulmonary involvement in SSc are not directly correlated. Nevertheless, different patterns of pulmonary involvement between SSc subgroups were observed. Restrictive lung disease was more frequent in patients with dSSc, while a trend to higher prevalence of pulmonary hypertension was observed in patients with lSSc.

Adult↗
PubMed1997

Noninvasive assessment of myocardial involvement in patients with systemic sclerosis: role of signal averaged electrocardiography.

OBJECTIVE: To assess the role of late ventricular potentials (LVP) in detecting early myocardial involvement in patients with systemic sclerosis (SSc). METHODS: Seventy-seven patients with SSc (68 women, 9 men, mean age 50 +/- 13 yrs) and 33 control subjects (18 women, 15 men, mean age 46 +/- 10 yrs) underwent resting electrocardiogram (ECG), 24 h Holter monitoring, complete echocardiographic and Doppler echocardiographic examination, and signal averaged ECG at high pass setting of 40 Hz, with the low pass fixed at 250 Hz. Patients with SSc underwent resting myocardial scintigraphy and radionuclide angioventriculography. RESULTS: The prevalence of LVP at 40 Hz was 20.5%. Compared to control subjects, patients with SSc showed higher prevalence of septal infarction pattern (p = 0.05), complex ventricular arrhythmias (p = 0.03), pulmonary arterial hypertension (p < 0.001), and LVP (p = 0.02). Forty-four patients with SSc (57.1%) had resting perfusion defects by myocardial scintigraphy. Fourteen of 15 patients with LVP showed perfusion defects compared to 29 of 58 without LVP (p = 0.002). Linear regression analysis showed that myocardial perfusion defect score was significantly correlated to either the filtered QRS duration, or the duration of low amplitude signals < 40 microV of the terminal QRS, or the root mean square voltage of the last 40 ms of the QRS complex. After a mean followup period of 20 months, 8 patients died. In 2 patients who died suddenly, LVP were present. CONCLUSION: Signal averaged ECG is a sensitive and inexpensive technique in the clinical assessment and followup of patients with SSc.

Adult↗
PubMed1997

Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic women: comparison between type 1, type 2 and gestational diabetes mellitus.

The chronic hyperglycemia can lead to an increase of the advanced glycosylation end-products (AGE) levels on proteins and macromolecules. Abnormal levels of AGE in several tissues has been associated with the pathogenesis of late diabetic complications. In diabetic pregnant women, high AGE levels might influence the delicate maternal-fetal balance and therefore alter the pregnancy outcome. In this preliminary study, we have measured the AGE in sera of 44 diabetic women in two trimester. Sixteen sera from non diabetic pregnant women have been used as controls. The AGE have been analyzed by means of an ELISA method with an antiserum anti-RNAse-AGE, produced in the Laboratory of Clinical Biochemistry of the Istituto Superiore di Sanità. Diabetic patients type 1 and type 2, in good metabolic control, showed normal AGE levels at both trimester. Patients with gestational diabetes showed significantly high serum AGE levels (p < 0.05). A more extended study will give better insight on the association between AGE levels and a physiopathology of diabetic pregnancy.

Adult↗
PubMed1996

Relationships between electrocardiographic and echocardiographic findings in systemic sclerosis (scleroderma).

We assessed the prevalence of electrocardiographic abnormalities in patients with systemic sclerosis and evaluated their functional significance through a comparison with echocardiographic findings. Seventy-two patients with systemic sclerosis and 64 controls underwent resting electrocardiogram (ECG) and M-mode, two-dimensional, Doppler and color Doppler echocardiography. Electrocardiographic abnormalities were observed in 48.7% of patients. Conduction disturbances (27.7%) infarction pattern (13.8%), non-specific ST-T wave changes (13.8%) and right ventricular hypertrophy (11.1%) were the most frequent abnormalities. QTc interval was significantly longer in patients with systemic sclerosis than in controls. Significant differences between patients and controls were found in the prevalence of long QTc interval (p = 0.0016) infarction pattern (p = 0.0016), right ventricular hypertrophy (p = 0.007) and non-specific ST-T wave abnormalities (p = 0.0016). All patients with infarction pattern and 90% of patients with prolonged QTc interval had some echocardiographic abnormalities. Electrocardiographic signs of right ventricular hypertrophy were 16% sensitive and 93% specific for pulmonary hypertension; the sensitivity and specificity of the combination of right ventricular hypertrophy, right atrial enlargement and right bundle branch block were 35% and 90%, respectively. Standard ECG is useful to assess cardiac involvement in patients with systemic sclerosis. If infarction pattern, right ventricular hypertrophy or long QTc interval are present, a cardiac involvement is very likely.

Adult↗
PubMed1996

Ruptured aortic cusp aneurysm in infective endocarditis.

We describe a patient affected by infective endocarditis with aortic aneurysm, waiting for valve replacement, in which aortic cusp rupture determined sudden heart failure. Diagnosis was performed by serial transthoracic echocardiograms and successful surgical valve replacement was performed in emergency.

Aneurysm, Ruptured↗
PubMed1996

1,25(OH)2-vitamin D3 stimulation of phospholipases C and D in muscle cells involves extracellular calcium and a pertussis-sensitive G protein.

The steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] activates in chick myoblasts the breakdown of phosphoinositides by phospholipase C and the hydrolysis of phosphatidylcholine by phospholipase D. Extracellular Ca2+ requirement and GTP-binding protein mediation of 1,25(OH)2D3-dependent activation of phospholipases C and D were investigated in cells prelabelled with [3H]glycerol or [3H]arachidonic acid. Generation of diacylglycerol by phospholipase C and phosphatidylethanol by phospholipase D were shown to be dependent on extracellular calcium, since both responses were suppressed by EGTA and the Ca(2+)-channel blockers nifedipine and verapamil, and were mimicked by the calcium ionophore A23187. The G-protein activators guanosine 5'-O-(3-thiotriphosphate) and AlF4- strongly enhanced diacylglycerol and phosphatidylethanol release in myoblasts while guanosine 5'-O-(2-thiodiphosphate), which inhibits G-protein-mediated signals, abolished 1,25(OH)2D3-dependent diacylglycerol and phosphatidylethanol release. Bordetella pertussis toxin pretreatment suppressed the hormone action. These results suggest that 1,25(OH)2D3-stimulation of phosphoinositide-specific phospholipase C and phospholipase D in chick myoblasts is mediated by a pertussis-sensitive GTP-binding protein(s) and the influx of extracellular calcium.

Aluminum Compounds↗
PubMed1996

A bcl-2/IgH antisense transcript deregulates bcl-2 gene expression in human follicular lymphoma t(14;18) cell lines.

The 14;18 chromosome translocation, characteristic of most human follicular B-cell lymphomas, juxtaposes the bcl-2 gene with the IgH locus, creating a bcl-2/IgH hybrid gene. By mechanisms that are still under investigation, this event increases the cellular levels of the bcl-2 mRNA and thereby induces an overproduction of the antiapoptotic BCL-2 protein which is likely responsible for neoplastic transformation. In an effort to identify potential upregulators of bcl-2 activity in t(14;18) cells, we found, by strand-specific RT-PCR, a bcl-2 antisense transcript that is present in the t(14;18) DOHH2 and SU-DHL-4 but not in the t(14;18)-negative Raji and Jurkat lymphoid cell lines, and thus appears to be dependent on the bcl-2/IgH fusion. This antisense transcript is a hybrid bc1-2/IgH RNA, that originates in the IgH locus, encompasses the t(14;18) fusion site and spans at least the complete 3' UTR region of the bcl-2 mRNA. To achieve some insight into its biological function, we treated the t(14;18) DOHH2 cell line with oligonucleotides (ODNs) by specifically targeting the bc1-2/IgH antisense strand. These ODNs lowered bcl-2 gene expression, inhibited neoplastic cell growth by inducing apoptosis. We would like to propose the hypothesis that the bc1-2/IgH antisense transcript may contribute, by an unknown mechanism, to upregulation of bcl-2 gene expression in t(14;18) cells. The possibility has been considered that the hybrid antisense transcript mask AU-rich motifs present in the 3' UTR of the bcl-2 mRNA characterized in other genes as mRNA destabilizing elements.

Apoptosis↗
PubMed1996

Analysis of antisense oligonucleotides by capillary electrophoresis, gel-slab electrophoresis, and HPLC: a comparison.

Three techniques are evaluated for assessing the purity of synthetic oligodeoxyribonucleotides: reversed phase high-performance liquid chromatography (RP-HPLC), polyacrylamide gel-slab electrophoresis (PAGE), and capillary zone electrophoresis highly concentrated (18% T) entangled polymer networks (CZE). RP-HPLC does not seem to be able to discriminate and resolve the spectrum of failed sequences expected to accompany an oligonucleotide of a given length. The purity data, as given by the manufacturer, are most often close to 100%. PAGE in 20% T matrices, followed by ethidium bromide staining, gives a good resolution of failure sequences and purity assessments decidedly more realistic. CZE in 18% liquid polyacrylamide is able to resolve to baseline all shorter fragments and to give a precise evaluation of the amount of impurities, based on the intrinsic DNA absorbance at 254 nm. Most of the 18 mer oligonucleotides (and of their phosphorothioate derivatives) analyzed by us, as supplied by three different manufacturers, were found to be contaminated by a spectrum of failed and truncated sequences, ranging in size from 7 mer to 17 mer. The purity data rarely exceeded 80% and most often were of the order of 60%-70%. Conditions for a good routine performance of the CZE technique are described.

Base Sequence↗