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Biomedical subjects

M Ferrari

Publications and source records attributed to M Ferrari.

At least 271 records · Page 15Linked to original sources
PubMed1995

HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional contribution to disease risk by the TAP2 locus.

The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, pc < 0.05). Analysis of 73 informative meiotic events in IDDM and control families demonstrated a recombination fraction between HLA DQB1 and TAP2 loci of 0.041 (Log of the odds score = 16.5; p < 10(-8)) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

HLA-DQ screening for risk assessment of insulin dependent diabetes in northern Italy.

Genetic markers may be used to improve the prediction of insulin-dependent diabetes mellitus (type 1) in individuals with islet autoantibodies. In order to develop a risk assessment strategy for the Lombardy region of northern Italy based on genetic and immunological markers, we analyzed HLA DQA1 and DQB1 alleles in 60 type 1 probands and their first-degree relatives and 65 unrelated control subjects from the same area using polymerase chain reaction (PCR) and oligonucleotide probes. The major risk haplotypes were DQA1 *0501-DQB1*0201 (39.1% of diabetic vs. 8.9% of non-diabetic haplotypes) and DQA1 *0301-DQB1*0302(20% of diabetic vs 7.1% of non-diabetic haplotypes). Stratified analysis showed DQA1*0102-DQB1*0502 also to be associated with type 1 susceptibility when found together with DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302. One type 1 patient had the type 1-protective DQA1*0102-DQB1*0602 haplotype. Overall, 88% of patients and 20% of unrelated control subjects had either DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 in the absence of DQA1*0102-DQB1*0602. These data suggest that typing for markers identifying these three haplotypes in the Lombardy population will achieve a sensitivity of almost 90% and exclude 80% of children from subsequent islet autoantibody testing.

Adolescent↗
PubMed1995

The use of a non-specific defence mechanism inducer in calves exposed to bovine herpesvirus-1 infection: preliminary trials.

The efficacy of an immunomodulator, the Baypamun (Bayer AG), was tested in calves which were subsequently exposed to bovine herpesvirus-1 (BHV-1) infection. Two groups of calves, of 8 animals each, were used for two trials. In one trial, 4 calves were treated with the immunomodulator and the remaining 4 were left as untreated controls. Two hours after the first injection of Baypamun, all calves, i.e. the treated and the untreated ones, were challenged with BHV-1. Comparing them to the untreated controls, the calves which were given the immunomodulator developed milder signs of the disease and shed a significantly lower concentration of virus. In the second experiment, 4 calves were given Baypamun and 4 calves were not, as above, but they were not inoculated with BHV-1; however, they were housed together with the calves of the former group (experimentally infected with BHV-1). The 8 calves all became infected but those that had been treated with Baypamun did not show any clinical signs of the disease, whereas the untreated calves underwent a clinical response which was considered to be typical of BHV-1 respiratory infection, as usually seen under natural conditions. In this case the shedding of virus by the calves treated with the immunomodulator also underwent a significant reduction.

Adjuvants, Immunologic↗
PubMed1995

Simultaneous detection of fourteen Italian cystic fibrosis mutations in seven exons by reverse dot-blot analysis.

The increasing number of cystic fibrosis (CF) mutations is a great obstacle to the use of DNA procedures in the detection of gene defects. We describe a fast, cheap and non-radioactive procedure, Reverse dot-blot analysis (RDB), for the simultaneous detection of CF mutations in the Italian population. We used this approach to study seven exons of the CF gene for 14 CF gene defects and were able to characterize 222 of 272 CF chromosomes (80%). The cost of the procedure was $25 per sample analysed.

Alleles↗
PubMed1995

Improved results with mitral valve repair using new surgical techniques.

From January 1987 to July 1994, 299 consecutive patients ranging from 4 to 80 years of age underwent mitral repair for pure valve insufficiency due to degenerative disease (59%), rheumatic disease (23%), endocarditis (12%) or ischemic heart disease (6%). During the initial period, a variety of reparative methods were used following the principles originally described by Carpentier. More recently, in our institution other surgical techniques have been introduced: specifically, prolapse of the anterior leaflet was corrected either by replacing the chordae with polytetrafluoroethylene (PTFE) sutures or simply by anchoring the prolapsing free edge to the facing edge of the posterior leaflet ("edge-to-edge" technique). Chordal transposition has also been used occasionally to correct the prolapse of the anterior leaflet. The hospital mortality rate was 1.3%. According to actuarial methods, the overall survival rate was 94% at 7 years, and freedom from reoperation was 86%. Significant incremental risk factors for reoperation were: no use of prosthetic ring, correction of the prolapse of the anterior leaflet by triangular resection or chordal shortening and ischemic etiology of the mitral insufficiency (freedom from reoperation at 7 years was 61%, 56% and 51%, respectively). In the late postoperative period (mean follow-up 3.6 years), 95% of the patients were in NYHA class I or II; four patients had thromboembolic episodes, two hemorrhagic complications and two endocarditis. No patient in whom the prolapse of the anterior leaflet was corrected by the recently introduced technique has required reoperation. The anterior mitral leaflet prolapse was therefore neutralized as an incremental risk factor for reoperation and this has contributed to the improved overall results of mitral valve repair.

Actuarial Analysis↗
PubMed1995

The value of dipyridamole echocardiography in risk stratification before vascular surgery. A multicenter study. The EPIC (Echo Persantine International Study) Group--Subproject: Risk Stratification Before Major Vascular Surgery.

PURPOSE: Patients undergoing major vascular surgery are at relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for peri-operative risk stratification. PATIENTS AND METHODS: One hundred and twenty-one patients undergoing vascular surgery (age 65 +/- 7 years) were studied by dipyridamole echocardiography testing in six different centres. Of the total 136 patients, 15 were subsequently excluded because surgery was either cancelled (n = 8) or postponed pending cardiac revascularization (n = 7) because of the presence of a 'high-risk' stress echo response (identified 'a priori' as a positive dipyridamole echocardiography testing with a dipyridamole-time < 5 min and/or a peak wall motion score index > 2, upon scoring each segment from 1 = normal to 4 = dyskinetic in an 11-segment model). RESULTS: No major complications occurred during dipyridamole echocardiography testing. Technically adequate images were obtained in all patients; however, in one patient only the low dipyridamole dose (56 mg.kg-1 over 4 min) was given to limit side effects. Of the 121 patients undergoing surgery 28 (23%) had a positive test. Peri-operative events occurred in nine patients (8%): two deaths, two myocardial infarctions, five cases of unstable angina. Sensitivity and specificity of dipyridamole echocardiography testing for predicting cardiac events were 78% and 81%, respectively, with a positive predictive value of 25% and a negative predictive value of 98%. Dipyridamole echocardiography testing effectively singled out patients with, from those without, events, but neither clinical parameters, such as Detsky score, nor baseline echo parameters, such as resting wall motion score index or ejection fraction were able to distinguish between such patients. CONCLUSION: In conclusion, dipyridamole echocardiography testing is safe and well tolerated in patients undergoing major vascular surgery, and provides an effective pre-operative screening test for risk stratification of these patients mainly due to the extremely high negative predictive value. Stress echocardiography is a better discriminator than clinical and rest echocardiographic variables.

Aged↗
PubMed1995

Verapamil and norverapamil plasma levels in infants and children during chronic oral treatment.

Verapamil and norverapamil trough plasma levels were measured in 22 children, aged from 15 days to 17 years, under chronic oral treatment with the drug (mean daily dose +/- SD: 4.9 +/- 1.4 mg/kg) for supraventricular tachyarrhythmias (n = 20) or hypertrophic cardiomyopathy (n = 2). Overall, 67 determinations were available (1 to 11 per patient) and the mean concentration values (+/- SD) were 43.3 +/- 36.4 ng/ml for verapamil and 41.7 +/- 28.9 ng/ml for norverapamil. Verapamil and norverapamil trough concentrations were correlated with the daily dose (p < 0.05) but a wide intersubject variability was present at any given dose and the regression line did not pass through the origin of axes (x-axis intercept: 1.2 mg/kg for verapamil, 0.9 mg/kg for norverapamil). To study the influence of age on drug kinetics, verapamil plasma concentrations corrected by daily dose/kg ([V]/D) and norverapamil to verapamil concentration ratios (N/V) (taken as an index of metabolic clearance) were divided according to age quartiles. The median [V]/D was higher in the first and in the fourth age quartile than in the other two age groups. On the contrary, median N/V ratio increased with age, suggesting that drug metabolism was improving during the first year of life. Four children developed typical adverse reactions to the drug (bradycardia, AV block, hypotension). In one case verapamil plasma levels were definitely high (294 ng/ml). In the other three cases, concomitant factors (such as very young age and heart disease) seem to have contributed to drug toxicity.

Administration, Oral↗
PubMed1995

A recombination event in the closely linked plasminogen and apolipoprotein(a) gene loci.

Genetic studies as well as in situ hybridisation data have strongly demonstrated that the genes coding for apoprotein(a) and plasminogen are linked and localised to chromosome 6 at band 6q26-27. We describe in this report the presence of a recombination event in a region of approximately 50 kb of DNA separating the two genes. The recombination was found in an Italian family, in which a mutation affecting both plasminogen plasma level and activity of plasminogen activity has been detected. Polymerase chain reaction and sequencing analysis showed the presence of a mutation different from those previously reported in two Japanese families.

Adult↗
PubMed1995

A study of two mutant strains of pseudorabies virus (PRV) unable to express thymidine kinase (TK) function.

Two mutant strains of pseudorabies virus (PRV) were selected from the virulent 86/27V virus treated with chemical drugs. The viruses, named 6A1 and 6C2, respectively, appeared to be unable to express thymidine kinase function, as demonstrated by the autoradiography test. They showed a reduced virulence for some susceptible animal species (chickens, mice, rabbits, calves, lambs and piglets) and virus was isolated sporadically. The mutant viruses appeared to be able to protect animals against infection with the virulent strain of PRV. At gross, as well as at histological examination, no lesions in apparatus, system and tissues were detected in pigs inoculated with 6A1 and 6C2 viruses. By contrast, rabbits treated with 6C2 mutant strain presented lymphomononucleated cuffs, microgliosis, and neuronophagia in some areas of the brain. This focal spreading, together with the absence of neuronal necrosis and intranuclear inclusions, suggest an infection induced by a modified strain of PRV.

Animals↗
PubMed1995

Cat brain cytochrome-c oxidase redox changes induced by hypoxia after blood-fluorocarbon exchange transfusion.

We used rapid-scanning near-infrared (NIR) spectroscopy (730-960 nm) to study the effects of graded or acute hypoxia on cerebral cytochrome-c oxidase (cyt aa3) redox state in blood-perfluoro-carbon-exchanged cats with somatosensory evoked potential (SEP) monitoring. In graded hypoxia [10 min each at fractional inspiratory O2 concentration (FIO2) 0.9, 0.8, 0.7, 0.6, and 0.5], cyt aa3 reduction occurred at FIO2 0.6 when cerebral O2 delivery was < 3.5 ml.100 g-1.min-1. In acute hypoxia (FIO2 0.6 for 10 min), significant cyt aa3 reduction occurred from 5 to 10 min (cerebral O2 delivery 3.1 +/- 0.3 ml.100 g-1.min-1) and recovered with reoxygenation (FIO2 1.0). Cyt aa3 redox changes preceded or coincided with SEP alterations in both hypoxia protocols. These results demonstrate that cerebral cyt aa3 reduction occurs with severe reduction of cerebral O2 delivery, but no significant change in cerebral cyt aa3 redox state occurs with small reductions of cerebral O2 delivery. We conclude that substantial changes in cerebral cyt aa3 do not occur at physiological levels of O2 delivery and that current NIR clinical instruments would detect oxygen-dependent cerebral cyt aa3 redox changes only when O2 delivery is extremely compromised.

Animals↗
PubMed1995

Effect of three different doses of a slow-release theophylline formulation on bronchial response to inhaled methacholine in asthmatic patients.

This study investigated whether or not a sustained release formulation of theophylline (SRT) at different dosages had any effect on bronchial hyperresponsiveness as measured by the methacholine challenge. On four separate occasions, 16 patients with mild asthma took either placebo or 300, 400, 500 mg of SRT twice a day. SRT had a slight bronchodilating effect that was not dose-related, but produced a dose-related decrease in the bronchial response to inhaled methacholine (r = 0.39, p = 0.007). This effect was present after all three treatment periods with the active drug when mean +/- SE theophylline serum concentrations of 10.3 +/- 0.7, 12.6 +/- 0.9 and 17.1 +/- 1.1 mg/l respectively were reached. A highly significant relationship between theophylline serum concentration and the degree of protection against methacholine bronchospasm was also found (r = 0.45, p = 0.001). It is concluded that oral theophylline does reduce bronchial hyperresponsiveness in a dose dependent fashion, this effect being present at all the serum concentrations within the normal range.

Adult↗
PubMed1995

Tussive effect of capsaicin in patients with gastroesophageal reflux without cough.

The aim of this study was to clarify the influence of gastroesophageal reflux (GER) on cough threshold in patients with digestive symptoms but free from respiratory involvement. Of 57 consecutive subjects referred for 24-h esophageal pH monitoring because of digestive reflux symptoms, 29 patients free from respiratory disorders were studied. They underwent esophageal pH monitoring and manometry, upper gastrointestinal endoscopy, pulmonary function tests, and methacholine and capsaicin challenges. The methacholine test was performed by inhalation of increasing doses of methacholine up to 4,000 micrograms; the results were expressed as the dose causing a 20% decrease in FEV1 from baseline (PD20). The capsaicin threshold was evaluated by inhalation of increasing doses of capsaicin from 0.3 up to 9.84 nmol, expressing the results as the dose of capsaicin eliciting five coughs (PD5). Fifteen patients were considered refluxers on the basis of a total esophageal acid exposure time above 4.7%. Esophagitis grade 0 was found in 15 patients, grade 1 in seven patients, grade 2 in seven patients. PD5 was significantly lower in refluxers (median 0.51 micrograms, range 0.22 to 19.8) than in nonrefluxers (19.8 micrograms, range 0.31 to 19.8) (p < 0.001); there was no difference in baseline ventilatory parameters and in airway responsiveness to methacholine between the two groups. All patients with a pathologic acid exposure time but one had a low cough threshold, irrespective of the presence or absence of esophagitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsaicin↗
PubMed1995

Intraoperative blood salvage: a new artificial organ?

Optimal blood supply is critical to modern medical practice. Among the different possibilities of improving the quality and safety of blood, it is generally felt that autologous donation has played an important role and has contributed to changing transfusional practices, mainly since the appearance of HIV and HCV on the blood transfusion scene. At the San Martino Hospital Immunohematology Service, the autotransfusion era began in 1985. Autologous predeposit donation was the first to be introduced, followed by intentional perioperative hemodilution, intraoperative blood salvage with DFC apparatuses and lastly post-operative blood salvage. From about 200 autologous donations in 1985 we reached 5,372 in 1993 and more than 6,000 autologous donations are expected for 1994. Only 189 intraoperative blood salvages, were carried out in 1986, 593 in 1989, 1,207 in 1993 and more than 1,500 blood salvage sessions are anticipated for 1994. In the meantime, the total number of homologous RBC units employed in the Hospital dropped from 45,000 in 1985 to 18,000 in 1994, with the Onco-hematological Divisions using approximately 10,000 units of packed RBC.

Blood Platelets↗
PubMed1995

[An echocardiographic study of left ventricular diastolic function in patients with diabetes mellitus type 2].

AIM OF THE STUDY: To evaluate left ventricular diastolic function by Doppler echocardiography in patients with type 2 (non-insulin-dependent) diabetes mellitus, without coronary artery disease. BACKGROUND: Previous studies suggest that the velocity curve obtained by Doppler echocardiography of the mitral inflow may reflect the filling pattern of the left ventricle. METHODS AND RESULTS: To evaluate the presence of diastolic impairment of the left ventricle in diabetic patients without evidence of coronary artery disease, 30 patients with non-insulin-dependent diabetes mellitus and 20 normal control subjects underwent M-mode, two-dimensional (2-D) and Doppler echocardiography. In the group of diabetic patients (Diabetics), the peak E wave velocity was 0.70 +/- 0.11 m/sec, while in the control group (Controls) it was 1.1 +/- 0.23 m/sec (mean values, +SD, p < 0.001). The peak A wave velocity was 0.89 +/- 0.17 in Diabetics, versus 0.60 +/- 0.34 in Controls. Consequently, E/A ratio was 0.81 +/- 0.18 in Diabetics, versus 1.73 +/- 0.29 in Controls (p < 0.001). Isovolumic relaxation time was 0.08 +/- 0.021 sec in Diabetics, while in Controls it was 0.04 +/- 0.02 sec (p < 0.001). Left atrium diameter was 41 +/- 11 mm in Diabetics, and 37 +/- 4 mm in Controls (p = NS). Left ventricular volumes, ejection fraction, interventricular septal and posterior wall thickness were similar in both groups. No correlation was found between diabetes duration and diastolic function indexes. In Diabetics no correlation was found between age and E/A ratio (correlation coefficient +/- 0.11) while in Controls E/A ratio was lower in the older subjects (r = +/- 0.75). This ratio was 1.89 +/- 0.20 in Controls aged < 65 years, and 1.6 +/- 0.33 in Controls aged > or = 65 years. (p = 0.06). These data suggest that 1) E/A ratio and isovolumic relaxation time are significantly altered in non-insulin-dependent diabetic patients without coronary artery disease; 2) Doppler echocardiography is a useful technique to detect left ventricular diastolic impairment; 3) diastolic impairment seems not to correlate with disease duration; 4) systolic function is normal in our group of type 2 diabetic patients.

Adult↗