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Seventeen adult subjects participated in a multicentre trial to compare the performance between an NRT‐based MAP and their behavioural MAP. The NRT‐based MAP was made using a correction factor to predict T/C levels, calculated from the difference between the ECAP threshold (‘T‐NRT’) and the measured T/C levels at electrode 10, as described by Brown et al. (2000). A secondary aim was to compare T/C levels in behavioural MAPs at different stimulation rates with the predicted T/C levels in NRT‐based MAPs. Performance with both MAPs was evaluated using CNC words and sentences. Variations in the T/C levels between all MAPs were found, although results of the speech discrimination tests demonstrated no statistically significant difference between behavioural and NRT‐based MAPs. Copyright © 2003 Whurr Publishers Ltd.

Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis, whereas few data are available on the total cysteine (tCy) levels in thrombophilic patients. We studied 82 patients with a previous myocardial infarction (MI; group 1), 68 patients with a previous deep venous thrombosis (group 2), and 100 control subjects (group 3). We assayed total homocysteine (tHcy) and tCy levels by high-performance liquid chromatography with fluorimetric detection. The odds ratios (ORs) for high levels of tCy and tHcy in venous thrombosis and MI were markedly increased in group 1 (fasting tCy: OR, 3.6; 95% confidence interval [CI], 1.6-11.2; postmethionine tCy: OR, 0.97; CI, 0.3-4.0; fasting tHcy: OR, 8.3; CI, 3.9-18.6; postmethionine tHcy: OR, 12.5; CI, 6.8-27.2) and in group 2 (fasting tCy: OR, 2.9; CI, 1.1-7.8; postmethionine tCy: OR, 0.86; CI 0.2-2.6; fasting tHcy: OR, 8.0; CI 3.6-18.0; postmethionine tHcy: OR, 11.0; CI, 6.0-22.1). Our data suggest that plasma tCy levels are a risk factor for venous thrombosis and MI independently of tHcy levels and that it may be appropriate to study both variables simultaneously to thoroughly study the methionine metabolism.

AbstractLong‐term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis‐related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age‐ and sex‐matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor‐1 (PAI‐1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P< 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI‐1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2‐45.5) vs 7.9 IU/ml (4‐18.0); P< 0.0001] with an odd ratio (OR) of 11.8 (4.9‐28.5) in univariate analysis and of 5.8 (2.1‐15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1‐992) vs 100.5 mg/l (10‐412); P< 0.005] with an OR of 5.9 (1.9‐18.4) in univariate analysis and of 3.5 (0.9‐13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 μmol/l (4.0‐68) vs 8.1 μmol/l (2.0‐24.0); P< 0.00001] with an OR of 40.4 (14.7‐111) in univariate analysis and of 33.1 (11.1‐115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95 %). Finally, we found a significant correlation between tHcy and PAI‐1 plasma levels (r= 0.76; P< 0.000001). Our results show a high prevalence of hemostasis‐related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long‐term survival and to tailor therapy.

Abstract Long-term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis-related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age- and sex-matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P &lt; 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI-1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2–45.5) vs 7.9 IU/ml (4–18.0); P &lt; 0.0001] with an odd ratio (OR) of 11.8 (4.9–28.5) in univariate analysis and of 5.8 (2.1–15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1–992) vs 100.5 mg/l (10–412); P &lt; 0.005] with an OR of 5.9 (1.9–18.4) in univariate analysis and of 3.5 (0.9–13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 μmol/l (4.0–68) vs 8.1 μmol/l (2.0–24.0); P &lt; 0.00001] with an OR of 40.4 (14.7–111) in univariate analysis and of 33.1 (11.1–115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95 %). Finally, we found a significant correlation between tHcy and PAI-1 plasma levels (r = 0.76; P &lt; 0.000 001). Our results show a high prevalence of hemostasis-related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long-term survival and to tailor therapy.

Abstract: Mild hyperhomocysteinemia is associated to mutations either in cystathionine ß-synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In 1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common CBS mutation (T833C) detected in homocystinuric patients. Recently, this double mutation has been detected in Italian and North-American controls. Compared to a group of patients affected by coronary artery disease, North-American controls showed not statistically significant difference. Moreover, Italian controls displayed a microheterogeneity in the mutant allele frequency distribution depending on their geographical origin (North or South of Italy). Aim of our study was to evaluate the prevalence of the double in cis mutation in different populations. We studied 377 healthy subjects belonging to various human groups. Genomic DNA, extracted from peripheral blood samples, was amplified using specific primers; PCR fragments were digested with Bsr I restriction enzyme to detect the double mutation. Our data show a significant heterogeneity among the populations studied, therefore this mutation turned out to be a reliable anthropogenetic marker. The distribution of the double mutation will contribute, with other DNA polymorphisms, to evaluate the genetic admixture of mixed populations such as Afro-Americans

In order to furtherly clarify the mechanisms regulating the fatty acid composition of platelet phospholipids the relationships between the fatty acid composition of major phospholipid fractions from plasma and platelets were investigated in 30 healthy male subjects. Strict correlations between all but two plasma and platelet fatty acids were observed for phosphatidylcholine (PC) (r = 0.51-0.95, at least P < 0.01), whereas only poor correlations were found for the other fractions. These results suggest that the direct transfer of PC molecules from plasma to platelet membrane is a pivotal mechanism for renovation of platelet PC fatty acids, while other mechanisms appear to play a major role for renovation of other phospholipid fractions of the platelet membrane.

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), a1-antitrypsin (AAT), al-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.

Monocyte stimulation may be induced by various agents. Monocytes generate procoagulant activity (PCA) in response to stimulation; they widely interact with the hemostatic system and participate in thrombin formation. Extensive placental thrombotic infarction has been implicated in fetal death in poly abortive patients with lupus anticoagulant (LA).We investigated 38 polyabortive women: 17 LA negative (LA-) and 18 LA positive (LA+). We compared the results with 25 clinically normal women.After four hours of incubation, the mean value of monocyte PCA in the LA+ women was significantly higher than in either the LA- or the control group (p < 0.0001). The monocyte PCA was out of the range of the controls in 9 of the 18 LA+ women.No correlation was observed between the levels of LA and monocyte PCA (r = 0.02; p = 0.94).No differences were found in monocyte PCA increase when induced by LA-, LA+ or control plasma; in all cases the increase was about five-six fold.Our results indicate that an increased monocyte PCA is present in some LA+ polyabortive women, thus suggesting that monocyte activation might be involved in the formation of thrombotic placental infarction and the consequent fetal loss in some patients. It might also suggest that these patients, in particular, could benefit from corticosteroid treatment, which is known to inhibit the formation of monocyte PCA.