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L Santoro

Publications and source records attributed to L Santoro.

At least 91 records · Page 5Linked to original sources
PubMed1997

CTG repeat number in the nonaffected allele of myotonic dystrophy patients is not critical for disease expression.

To investigate whether unusual allele segregation might explain the dominant negative effect of the expanded allele for myotonic dystrophy on myotonin protein kinase mRNA metabolism, which is suggested to cause the disease, we determined the number of CTG repeats at the DM locus in the nonaffected alleles of 64 DM (dystrophia myotonia) patients. The relative distribution was then compared with the distributions obtained from alleles of the normal parents and normal siblings of DM patients. Comparison was also made with the allele distribution of normal subjects from the same geographic area. It appears that the CTG repeat number of the nonaffected allele in DM patients is not critical for the expression of the disease.

Alleles↗
PubMed1996

A quantitative polymerase chain reaction (PCR) assay completely discriminates between Duchenne and Becker muscular dystrophy deletion carriers and normal females.

Duchenne/Becker muscular dystrophy (DMD/BMD) is a severe X-linked myopathy. In 65% of the patients, the mutations responsible for the disease are macrodeletions in the dystrophin-encoding gene that can be identified with multiplex polymerase chain reaction (PCR) technology. We developed a method for quantitative PCR analysis of deletion carriers involving the use of phosphorimager-based scanning of radioactive-labelled PCR products. We calculated the ratios between the areas of two peaks, one corresponding to the deleted segments to be analysed and the other taken as a reference. In carriers, these ratios (R value) were always about half those obtained in normal females. The final diagnostic result, the diagnostic index (DI), is the ratio of the R values between the propositus and a normal subject. We also assessed the variability of each step of the procedure and the overall variability of the DI value, thus obtaining cut-off values that completely discriminated BMD/DMD deletion carriers from normal females. We were also able to classify, as either 'carrier' or 'normal', several females whose status was not identified with linkage analysis.

DNA Primers↗
PubMed1996

Giardiasis as a cause of hypokalemic myopathy in congenital immunodeficiency.

Hypokalemic myopathy may occur in several infections. We report a case of severe and transient myopathy secondary to hypokalemia induced by chronic intestinal infection with Giardia lamblia in a patient with common variable hypogammaglobulinemia. Hypokalemic myopathy is documented by serum enzymes, electromyography (reduction in the number of voluntarily activated motor unit action potentials and an increase in polyphasic motor unit action potentials, and pathological changes (hematoxylin-eosin, ATPase staining). The case reported involves hypokalemic myopathy induced by giardiasis in a patient with primary immunodeficiency; the histopathological changes observed in a skin/muscle biopsy from this patient are described for the first time.

Agammaglobulinemia↗
PubMed1996

Evaluation of the motor cortex by magnetic stimulation in patients with Alzheimer disease.

Motor evoked potentials (MEPs) from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles elicited by transcranial magnetic stimulation of the motor cortex were studied in 15 patients with Alzheimer disease (AD). An abnormally higher MEP threshold in APB, frequently associated with absence of the MEP in relaxed TA muscles, was found in 40% of patients, almost all of them in the more severe stage of the disease. The MEP amplitude and averaged MEP/MAP ratio were reduced respectively by 20% and 26% in the APB muscle, and by 46.7% and 53.3% in the TA muscle. The less frequent prolongation of the central conduction time (CCT) (20%) might reflect preservation of the impulse propagation along the surviving pyramidal fibers. In 63.6% of the patients the central silent period (cSP) duration in the APB muscle was shortened; the mean value was significantly different between patients and controls. The results of this study suggest that loss and/or dysfunction of motor cortex neurones, including pyramidal cells and inhibitory interneurones may occur in AD patients before clinical signs become apparent.

Aged↗
PubMed1996

Autosomal dominant cerebellar ataxia type I: multimodal electrophysiological study and comparison between SCA1 and SCA2 patients.

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2.

Adolescent↗
PubMed1996

Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes.

We studied 83 patients from 36 Italian families with autosomal dominant cerebellar ataxia type I. Mean onset age +/- SD was 34.2 +/- 12.8 years with a mean anticipation of 12.8 +/- 15.1 in 52 parent-offspring pairs. Onset age anticipation occurred predominantly through paternal transmission. Mean age at death was at 56.5 +/- 15.5 years. The most common associated features were supranuclear ophthalmoplegia, corticospinal signs, peripheral neuropathy and cognitive impairment. Cerebellar atrophy was constant at MRI and usually associated with shrinkage of the pons and degeneration of the pontine transverse fibres. Direct mutation analysis in 29 families showed two families with SCA1 and none with Machado-Joseph/SCA3 mutation. We performed linkage analysis in the ten largest families. Two of them showed linkage to SCA2 locus and none to SCA4 and SCA5 loci. SCA2 patients showed higher occurrence of peripheral neuropathy and slow saccades, rarer corticospinal signs and a milder course of the disease in comparison with SCA1 patients.

Adolescent↗
PubMed1996

Monoclonal IgG as antigens: reduction is an early intracellular event of their processing by antigen-presenting cells.

Murine mAb injected into patients behave as exogenous antigens and trigger a specific immune response characterized mainly by CD4+ T lymphocytes. They are recognized by T cells under a processed form and in a MHC class II-restricted fashion. IgG degradation which occurs in antigen-presenting cells (APC) has been studied in vitro. We have shown that partial reduction of this antigen is an early event which is significant for the generation of class II-restricted fragments presentable to antigen-specific T cells. Two different murine mAb were used as antigens and human monocytic U937 or antigen non-specific Epstein-Barr virus-transformed B cells as APC. Upon cellular internalization IgG are rapidly cleaved leading to 24-25 kDa fragments. One of the major and early events corresponds to partial reduction of IgG--the light chain is released from the intact molecule, heavy chains remaining bound together. Partial in vitro reduction of IgG followed by presentation by fixed B cells to specific T cells showed that only kappa light chain-specific T cell clones are stimulated, in contrast to heavy chain-specific T cell clones. The response to the kappa chains of specific T cells points to a significant role played by the early IgG partial reduction in the generation of kappa light chain class II binding fragments.

Antibodies, Monoclonal↗
PubMed1996

The prognostic value of predischarge quantitative two-dimensional echocardiographic measurements and the effects of early lisinopril treatment on left ventricular structure and function after acute myocardial infarction in the GISSI-3 Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.

BACKGROUND: Left ventricular dilatation and a low ejection fraction after acute myocardial infarction are independent indicators of a poor prognosis. ACE inhibitors have been shown to decrease left ventricular dilatation after myocardial infarction. In the GISSI-3 trial, patients were randomly assigned, within 24 h of onset of myocardial infarction symptoms, to 6 weeks of treatment with lisinopril, nitroglycerin, both or neither, in an open, 2 x 2 factorial design. The study showed that early treatment in relatively unselected patients with lisinopril decreases mortality at 6 weeks and severe left ventricular dysfunction. We assessed (1) the prognostic value of pre-discharge 2-D echocardiographic variables, and (2) the effects of lisinopril on the progression of left ventricular dilatation. METHODS AND RESULTS: 2-D echocardiograms were available pre-discharge in 8619 GISSI-3 trial patients discharged alive. In 6405 of these patients, a 2-D echocardiographic study was also available at 6 weeks, and at 6 months. Pre-discharge end-diastolic and end-systolic volumes, and ejection fraction predicted 6-month mortality and non-fatal clinical congestive heart failure (P < 0.01). The increase in left ventricular volumes over time was significantly reduced by 6 weeks' lisinopril treatment in patients with wall motion asynergy pre-discharge of > or = 27%. Patients with wall motion asynergy < 27% showed no dilatation and lisinopril did not affect volumes at 6 months. Patients randomized to lisinopril also had smaller volumes after withdrawal of treatment at 6 weeks. Lisinopril did not affect left ventricular ejection fraction. CONCLUSIONS: 2-D echocardiography independently contributes to pre-discharge risk stratification in terms of 6-month mortality and clinical heart failure after myocardial infarction, and early, short-term treatment with lisinopril in unselected myocardial infarction patients attenuates left ventricular dilatation; an effect evident in patients with larger infarcts. These results probably only partly explain the effect of lisinopril on total mortality concentrated in the first week after infarction.

Aged↗
PubMed1996

Prognostic value of a history of hypertension in 11,483 patients with acute myocardial infarction treated with thrombolysis. GISSI-2 Investigators. Gruppo Italiano per lo Studio della, Sopravvivena nell'Infarto Miocardico.

OBJECTIVE: To assess the prognostic value of a history of hypertension in patients with acute myocardial infarction (AMI) treated with thrombolysis. DESIGN: Retrospective adjusted analysis of outcome data of patients with AMI randomly allocated to treatment in a controlled study of alteplase versus streptokinase and heparin versus no heparin. SETTING: A highly representative sample (about 90%) of Italian Coronary Care Units. PATIENTS: Patients with (n = 3306) and without (n = 7406) a history of treated hypertension. MAIN OUTCOME MEASURES: Morbidity and mortality during hospital stay and the next 6 months. RESULTS: Patients with a history of hypertension had a significantly higher mortality, both in hospital and during the next 6 months. The difference persisted also after a multivariate analysis including all major prognostic factors for in-hospital and 6-month mortality, respectively. Left ventricular failure and recurrent ischaemic events (angina and re-infarction) were also significantly more frequent in hypertensives both during their hospital stay and during follow-up study. CONCLUSIONS: A history of hypertension is a negative independent prognostic factor after acute myocardial infarction treated with thrombolysis.

Aged↗
PubMed1995

Diabetes mellitus in Kearns-Sayre syndrome: a case with a 10-year follow-up.

An 11-year-old girl with Kearns-Sayre Syndrome developed diabetes mellitus with ketoacidosis at onset and immediate insulin-requirement. In a 10-year follow-up, while neuromuscular disease was progressively increasing, diabetes was well controlled by once-a-day insulin therapy. Insulin secretion appears low, but without impairment during the years. This case points out the diabetes' features in Kearns-Sayre syndrome.

Age of Onset↗
PubMed1995

Charcot-Marie-Tooth disease: molecular characterization of patients from central and southern Italy.

The syndrome of peroneal muscular atrophy, or Charcot-Marie-Tooth (CMT), disease represents the most common inherited peripheral neuropathy, with a prevalence of about 1 per 2500. The disease is usually transmitted in an autosomal dominant fashion, although it can display all the mendelian patterns of inheritance. The chromosome 17-linked form (CMT1a) appears to be the most common form of the disease in all the ethnic groups studied so far, Italians included, and is due to a tandem duplication in 17p11.2. In order to study the distribution of CMT types and to establish a genotype-phenotype correlation in patients from Central and Southern Italy, we collected 19 CMT pedigrees diagnosed in the years 1992-1993. Simple tandem repeats (STR) polymorphism analysis with the marker RM11-GT and Southern blotting with the probes pVAW409R3 and pVAW412 were performed, demonstrating a high prevalence (about 60%) of 17p duplication in the families studied. No clinical or electrophysiological differences were noted between CMT1 patients with or without 17p duplication, respectively. Two families affected by CMT2 showed no evidence of rearrangement at the D17S122 locus. These data are consistent with the hypothesis of a different molecular basis for CMT2.

Blotting, Southern↗
PubMed1995

Has spinocerebellar ataxia type 2 a distinct phenotype? Genetic and clinical study of an Italian family.

The gene for spinocerebellar ataxia type 2 (SCA2) is mapped to chromosome 12q23-24.1. Using D12S79 and D12S105, we performed linkage analysis in nine individuals including six affected members of a four-generation family in which we excluded SCA1 by direct mutation analysis. We obtained a lod score = 2.37 at theta = 0.00 for the compound haplotype. The clinical picture appeared homogeneous, showing the absence of corticospinal signs and the presence of peripheral neuropathy. The present study suggests that this SCA2 family is clinically different from most SCA1 families.

Adult↗
PubMed1995

[Atenolol i.v. in the acute phase of AMI: the indications, contraindications and interactions with thrombolytic drugs in the GISSI-2 study. The GISSI-2 Researchers. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico].

BACKGROUND: In the pre-thrombolytic era, several studies showed the effectiveness of beta-blocker administration in the treatment of patients (pts) with acute Myocardial Infarction (MI). Results from the ISIS-1 and GISSI trials suggested that the combined administration of beta-blocker and of thrombolytic drugs in the acute phase of infarction could lead to a better prognosis. The possibility of synergic effects from the associated administration of these drugs was confirmed by small clinical trials. In GISSI-2 study a large number of patients treated with thrombolytic drugs were given i.v. atenolol (10 mg) as recommended therapy, not following a randomized study design. AIM: We reviewed the data of the GISSI-2 study population in order to evaluate: 1) the number of pts treated with i.v. atenolol; 2) the anamnestic and clinical characteristics of treated und untreated pts; 3) the causes of exclusion from the beta-blocker therapy; 4) the causes of scheduled dose withdrawal and the incidence of side effects related to atenolol administration; 5) the interaction between atenolol and streptokinase (SK) and rtPA; 6) the incidence of relevant clinical events and the causes of death during the in-hospital period. RESULTS: Among 12377 evaluated pts, 5616 (45.4%) were given atenolol i.v., 2772 received SK (49.5%) and 2844 (50.5%) rtPA. Mean age was 59.5 +/- 11.3 yrs in atenolol treated pts vs 63.4 +/- 10.9 yrs in untreated pts (p < 0.001); 34.1% of pts aged > 70 yrs vs 48.6% of younger pts (p < 0.00001) and 42.1% of females vs 46.2% of males (p < 0.003) received atenolol. Pts with previous MI received less frequently atenolol than those without MI (17.5% vs 13.5%, p < 0.00001). 88.5% of the treated pts was in Killip class I at entry (untreated 69.5%, p < 0.00001); anterior and lateral site, non-Q type and > or = 5 electrocardiographic leads with ST segment elevation were more frequently found in atenolol treated pts, inferior and unknown site in untreated pts. Among 6761 untreated pts, 32% did not receive atenolol for the occurrence of bradycardia, 15.2% for hypotension, 14.1% for heart failure, 7.2% for bronchospasm or history of asthma, 6.2% for bradycardia and hypotension, 0.3% for death; in 25% of the untreated pts, none of the above-mentioned causes was detectable. 1064 pts (18.9%) did not complete the scheduled dose of atenolol for the occurrence of bradycardia or atrioventricular block > or = II degree (7.3%), hypotension (7%), bradycardia and hypotension (1.8%), heart failure (0.7%), death (0.03%), other causes (1.9%). Transient hypotension was found more frequently in pts treated with SK than in those receiving rtPA (9.3% vs 4.8%, p < 0.0001), but the rate of persistent hypotension was not different in both groups (4.6%). During the hospital phase a higher incidence of advanced atrioventricular block (12.3% vs 4.3%), need of temporary or permanent pacing (5.6% vs 1.9%), sustained ventricular tachycardia (4.5% vs 2.8%), heart failure (12% vs 7.1%), ventricular fibrillation (8% vs 4.9%) and death (11.9% vs 5.1%) were shown in pts that were not given i.v. atenolol. Heart failure was the main cause of death in both groups (untreated 2.3% vs 2.2%); ventricular fibrillation (0.2% vs 0.48%), cardiac rupture (0.5% vs 1.4%), and electromechanical dissociation (0.9% vs 1.9%) were less frequent in treated pts. CONCLUSIONS: The absence of randomized design of atenolol administration limits the value of the differences found in the clinical outcome of the two groups of pts. In spite of that, the low incidence of death and side effects in treated pts, and the high percentage of pts who completed the scheduled dose of atenolol, confirm that the iv. administration of beta-blockers in the acute phase of the myocardial infarction is safe, well tolerated and suitable in almost an half of the patients submitted to thrombolytic therapy with SK or rtPA.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Covalent binding of C3b to monoclonal antibodies selectively up-regulates heavy chain epitope recognition by T cells.

Protein C3 of the complement system is known for its role in the nonspecific immune response. Covalent binding of C3b to antigen upon complement activation also plays a significant role in specific T cell immune response. C3b-antigen complexes can bind to complement receptors on the antigen-presenting cell, and the C3b antigen link (most often an ester link) remains fairly stable inside the cells. In this study, IgG1,kappa and IgG2a,kappa murine monoclonal antibodies (mAb) were used as antigens; covalent complexes between mAb and C3b were produced and purified in vitro from purified proteins; human B cell lines and T cell clones were raised from tumor patients who received mAb injections for cancer therapy or diagnosis. Recognition of epitopes of these mAb by T cell clones when the mAb were processed alone or bound to C3b was compared. IgG or IgG-C3b complexes presented by B cell lines were able to stimulate proliferation of kappa light chain-specific T cell clones at similar concentrations. In contrast, IgG-C3b complex recognition by heavy chain-specific T cell clones required 100-fold less IgG-C3b than uncomplexed IgG. As C3b was shown to be covalently bound only to the IgG heavy chains in the complexes, C3b chaperoning is restricted to only the IgG heavy chain and selectively influences intracellular steps of IgG heavy chain processing. This differential modulation of C3b suggests an early dissociation of IgG heavy and light chains in antigen-presenting cells.

Animals↗
PubMed1994

Evoked potentials in inherited ataxias: a multimodal electrophysiological study.

A multimodal electrophysiological study, including median nerve somatosensory evoked potentials (SSEPs), motor cortical stimulation (CS) and brainstem evoked potentials (BAEPs), was performed on 34 patients with hereditary ataxias (HAs): 15 with Friedreich's disease (FD), 10 with early onset cerebellar ataxia (EOCA), and 9 with autosomal dominant cerebellar ataxia (ADCA). A higher incidence of abnormal central motor conduction was observed in FD than in EOCA patients, but was never observed in ADCA. A relationship between central motor conduction abnormalities and disease duration and clinical impairment was found only in FD patients. All FD patients showed severe impairment of the SSEPs that was not related to disease duration. In EOCA patients, less frequent and more variable SSEP abnormalities were observed. The lowest incidence of central SSEP abnormalities was observed in ADCA. The BAEP findings in all 3 groups of patients (but particularly those with EOCA) suggest prevalent brainstem damage.

Adolescent↗
PubMed1994

A simple electrocardiographic predictor of the outcome of patients with acute myocardial infarction treated with a thrombolytic agent. A Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2)-Derived Analysis.

OBJECTIVES: This analysis aimed to evaluate in a large patient cohort the relation between ST segment alterations after fibrinolytic therapy for acute myocardial infarction and 1) the combined end point of in-hospital mortality plus clinical congestive heart failure or extensive left ventricular damage, and 2) mortality 30 and 180 days after randomization. BACKGROUND: Angina relief, enzyme release acceleration and ST segment normalization are related to coronary artery reperfusion and prognosis. Electrocardiographic (ECG) evaluation before and after fibrinolytic drug administration has been used to predict short- and long-term clinical outcome in acute myocardial infarction. METHODS: Patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial underwent a standard ECG on admission and after 4 h of alteplase or streptokinase therapy; 7,426 recordings were suitable for ST segment analysis. A decrease > or = 50% in the sum of ST segment elevation in all ECG leads was adopted as the cutoff for predicting coronary artery patency. Recanalization was deemed to have occurred in 4,951 patients (group A) versus 2,475 patients without reperfusion (group B). RESULTS: Group A patients experienced a lower incidence of the combined end point than did group B patients (16.2% vs. 22.9%, respectively), as well as of all its components (death, clinical heart failure, ejection fraction < 35%, injured myocardial segment > 45%, QRS score > 10). Thirty- and 180-day mortality rates were lower in group A than group B (3.5% and 5.7% vs. 7.4% and 9.9%, respectively); relative risk (Cox) was 0.46 (95% confidence interval [CI] 0.37 to 0.57) for 30-day and 0.58 (95% CI 0.48 to 0.70) for 180-day mortality. Patients in group A had significantly less ventricular fibrillation and sustained ventricular tachycardia but more ischemic episodes (early recurrent angina plus myocardial infarction recurrence). CONCLUSIONS: A simple, inexpensive instrumental evaluation, unaffected by different epidemiologic and clinical characteristics of the population analyzed, can allow early assessment of the effectiveness of fibrinolytic treatment with respect to the main clinical outcomes.

Aged↗
PubMed1994

Frequency of predischarge ventricular arrhythmias in postmyocardial infarction patients depends on residual left ventricular pump performance and is independent of the occurrence of acute reperfusion. The GISSI-2 Investigators.

OBJECTIVES: To test whether acute reperfusion of the infarct-related vessel after an acute myocardial infarction is associated with a subsequent reduction in spontaneous ventricular arrhythmias that is independent of ventricular ejection fraction, 1,944 patients from the GISSI-2 study population were studied. The patients were selected on the basis of a first myocardial infarction and the availability of two-dimensional echocardiographic ejection fraction and data on the number of premature ventricular contractions per hour on Holter monitoring. BACKGROUND: It has been suggested that postthrombolytic reperfusion of the culprit vessel may be associated with an increased electrical stability of the infarcted heart, irrespective of its residual pump performance. METHODS: The predischarge relation between ejection fraction and number of premature ventricular contractions per hour was plotted according to the occurrence (1,309 patients) or not (635 patients) of acute reperfusion, identified noninvasively according to the modifications of the ST segment in serial electrocardiograms obtained in the first 24 h after infarction. RESULTS: The frequency of premature ventricular contractions increased in a linear fashion with decreasing ejection fraction in both cohorts (p < 0.005 and p < 0.0001); however, there was no significant difference between the slopes and the intercepts of the two regression lines, so that the relation between ejection fraction and number of premature ventricular contractions per hour could be adequately described by a single equation: y (number of premature ventricular contractions) = 33.0-0.42x (ejection fraction) (r = -0.107, p < 0.0001). The results were the same even when differences between group characteristics were accounted for in a multiple regression model. CONCLUSIONS: It is concluded that 1) the number of premature ventricular contractions per hour after an acute myocardial infarction is dependent in a linear, inverse fashion on the residual ventricular ejection fraction, and 2) this relation is independent of the occurrence of reperfusion in the acute phase of infarction.

Aged↗