Cardiac allograft rejection correlates with increased expressions of Toll-like receptors 2 and 4 and allograft inflammatory factor 1.

BACKGROUND: Evidence suggests that injury-induced activation of the recipient's innate immune response determines the outcome of allograft transplantation. The mechanism responsible for the induction of such innate immune response is not clear yet. We hypothesized that in cardiac transplantation settings, the initial myocardial ischemia and postischemia graft reperfusion may release allograft inflammatory factor (AIF) 1, causing Toll-like receptor (TLR)-mediated activation of macrophages and dendritic cells, leading to the production of cytokines and the activation of adaptive alloimmunity. Therefore, our goal was to validate the presence of these biomarkers in the peripheral blood and biopsy specimens of patients presenting allograft rejection. METHODS: We studied 90 peripheral blood and 30 endomyocardial biopsy specimens from patients who had undergone cardiac transplantation. Specimens were tested by quantitative reverse-transcription polymerase chain reaction to determine TLR-2 and -4 and AIF-1 expression levels, correlating with clinical rejection grades. The group differences for mRNA transcript levels between the rejection grades were determined by 1-way analysis of variance. The level of significance was set at P < .05 for comparison between the groups. RESULTS: The mean ± SEM level of TLR-2 mRNA expression was increased 1.7-fold in monocytes (P < .05) and 4.2-fold in biopsy samples from groups with grade 3A compared with grade 1A or grade 0 rejection (P < .0001). AIF-1 expression was increased 2.4-fold in monocytes (P < .05) and 4.2-fold in biopsy samples comparing grade 3A versus 1A rejections. The TLR-4 mRNA expression was also increased in the group with 3A rejections; however, the difference was only significant in biopsy specimens (P < .0001). CONCLUSIONS: Our data demonstrated that expression profiles of AIF-1 and TLR-2 correlated with biopsy-proven allograft rejection in both peripheral blood and local tissue, suggesting their potential as diagnostic biomarkers for early detection of allograft rejection.

[Environmental exposure to inorganic lead and neurobehavioural tests among adolescents living in the Sulcis-Iglesiente, Sardinia]. / Esposizione ambientale a piombo e test neuro- comportamentali in adolescenti del Sulcis-Iglesiente.

In several recent studies blood lead levels below 100 microg/L have been associated with reduced neurocognitive capacities and neurobehavioural performances in children, with no clear evidence of the lowest "safe" level not associated to adverse effects on the CNS. We analyzed blood lead concentration and the results of 5 neurocognitive tests, two derived from the Swedish Performance Evaluating System (SPES) and three from the Wechsler Intelligence Scale for Children-Revised (WISC-R), in 139 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and in 72 age-matched students living in S. Antioco, a town about 15 Km far from the same smelter. The blood lead concentrations were lower than 100 microg/l in almost subjects, but, in average, significantly higher particularly among males, in the Portoscuso group compared to controls. The regression coefficients derived from the multivariate stepwise analysis, adjusted for the student's age and gender and for the educational and socio-economic level of parents, showed that reduced performances in neurocognitive test were significantly associated to increasing blood lead concentrations. According to previous our surveys in the same area and to the recent scientific literature on this topic, the present study suggests the need to further low the blood lead levels, considered by the U.S. CDC in 1991 as potentially "safe" for the children's CNS, to a threshold possibly < 50 microg/L.

[Respiratory risk among students in an industrialized area of Sardinia: role of smoking and air pollution]. / Rischio respiratorio in studenti di un'area industrializzata della Sardegna: fumo di tabacco e inquinamento ambientale.

Among 273 students (age 11-16 years) living in two small towns located respectively 2 (Portoscuso) and 15 kilometres (S. Antioco) far from the industrial area of Portovesme, the respiratory risk associated to cigarette smoking and environmental pollution was evaluated by the ISAAC questionnaire and standardized spirometry. The prevalence of parent's smoking was high in both groups (66.3% and 59.4%). Smoking during pregnancy was reported by 15% of mothers, without significant differences between the two schools. The prevalence of smokers among students was similar comparing the two groups (7% vs 6%). The prevalence of asthma in the whole population was significantly associated to skin positivity to common allergens, to the familiarity for asthma and to the environmental tobacco smoking, particularly if maternal. Spirometric values were significantly lower among students living in Portoscuso than among those of the S. Antioco school, with an evident interaction between the residential factor and the tobacco smoking, active and/or passive, in reducing the forced end- expiratory flows. Our results support the significant role of tobacco smoking, active and passive, particularly if derived from maternal smoking during pregnancy, in increasing the prevalence of respiratory disorders and lowering lung function in children. Living in Portoscuso, because of higher environmental exposure to airborne pollutants of industrial origin, has been shown as a relevant factor further lowering the lung function among the studied sample.

Tetralogy of Fallot with congenital aortic valvar stenosis: the tetralogy-truncus interrelationship.

Two rare patients are reported with tetralogy of Fallot and congenital aortic valvar stenosis. The anatomic and developmental interrelationship between tetralogy of Fallot and truncus arteriosus is summarized. A study of 100 randomly selected postmortem cases of tetralogy revealed aortic valve pathology in 8%, myxomatous aortic valve leaflets without stenosis in 4%, bicuspid aortic valves without stenosis in 3%, and congenital aortic valvar stenosis in 1%. The frequency of systemic semilunar valve pathology in truncus was much higher (66%): moderate to marked myxomatous change in 44%, mild myxomatous change in 22%, truncal valvar stenosis in 11%, and truncal valvar regurgitation in 15%. Being aware of the tetralogy-truncus interrelationship and knowing that myxomatous aortic valves are prone to premature calcific aortic stenosis and/or regurgitation, physicians should follow the aortic valves of surgically repaired patients with tetralogy of Fallot and truncus arteriosus long term with great care. Timely aortic valvuloplasty or replacement may well prove life-saving in such patients.

[Neurobehavioural testing in lead smelter workers]. / Test neurocomportamentali in lavoratori esposti a piombo inorganico.

Several recent meta-analyses, although some inconsistencies between studies, provide evidence for subtle deficits in neurobehavioural tests being associated with average blood levels (PbB) between 350 and 600 microg/l and for significant correlations between impairments in some test results and increasing indices present andlor cumulative exposure to inorganic lead. In this study we assessed the relationship between blood lead level (PbB) and results of some neurobehavioural tests derived from the SPES battery and from the WAIS-R among a sample of 94 lead smelter workers (median PbB: 302 microg/l; range: 60-690 microg/l). The stepwise multiple regression analysis shows that, even after adjusting for age, education level, score in the vocabulary test and for alcohol and cigarette consumption, the rise of PbB above 300 microg/l was significantly associated with the rise in the number of errors and in the response time of the Symbol Digit test. No significant relationship between PbB and results of the other tests was observed after adjusting for the main confounding factors. Despite the small size of this study and the few number of neurobehavioural tests applied, our results are suggestive for suble potential neurotoxic effects of inorganic lead even at the present exposure levels found in the studied sample of smelter workers and support the ACGIH BEI and the SCOEL recommendation for a biological limit of 300 microg/l of PbB.

[Intellectual quotient and environmental exposure to low doses of lead]. / Quoziente intellettivo ed esposizione ambientale a basse dosi di piombo.

The effects of low-level lead exposure on children's intelligence quotient (IQ) were investigated in 64 Sardinian adolescents (13-16 years old). To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low-level lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PbB) generally below 10 microg/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian children living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microg/dl increase of lead blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the blood lead concentration for children to a threshold significantly below 10 microg/dl, value till now considered "safe" for the children's CNS.

[Study on mortality by specific cause among workers at a lead and zinc foundry in Sardinia]. / Studio di mortalità per cause specifiche in lavoratori di una fonderia di piombo e zinco della Sardegna.

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

Mortality for pancreatic cancer among aluminium smelter workers in Sardinia, Italy.

To investigate the relationship between exposure to polycyclic aromatic hydrocarbons (PAHs) and mortality for specifc cancer sites, 1152 men, employed for at least 1 year at a prebake aluminium smelter, were followed-up from 1972 until 31 December 2001. Exposure to PAHs was estimated from a detailed reconstruction of the working history experienced in the plant by each cohort member and from several environmental and personal shift-sampling measurements available, by task and working department, since 1979. Furthermore, information on smoking habits, previous jobs before engagement in the smelter and main clinical findings observed during the follow-up were collected from the personal medical files. This study showed no increased mortality for lung cancer or bladder cancer associated to exposure to PAHs. Mortality for pancreatic cancer, based on 6 observed deaths, was significantly higher than expected in the whole cohort (SMR 2.4; 95%CI 1.1-5.2) and particularly among workers employed in the anodes factory of the plant (SMR 5.0, 95%CI 2.1-12.1), where a relatively consistent exposure to PAHs has been estimated. The nested case-control study planned for pancreatic cancer cases, confirmed that, also after controlling for cigarette smoking, PAH exposure experienced in the anodes factory was associated with a significant increased risk of pancreatic cancer. A pre-existent diabetes mellitus and a potential occupational exposure to pesticides experienced in previous agricultural jobs were found as concurrent significant covariates increasing the risk. In conclusion, the relatively high exposure to PAHs, experienced in the anodes factory and particularly in the green-mill department of this prebake aluminium reduction plant, cannot be ruled out as one of the main factors in the multifactorial aetiology of the pancreatic cancers observed in this study.

[Silica, silicosis, and lung cancer: analysis if the literature and mortality studies of minor workers in Sardinia]. / Silice, silicosi e cancro del polmone: analisi della letteratura e studi di mortalità in minatori della Sardegna.

Starting from a short review of the recent epidemiological studies available in the international literature concerning the association between silica, silicosis and lung cancer, the results of two mortality studies performed in Sardinia are reported. The first study concerns a 20-year follow-up of 1741 miners employed in 1973 in two metalliferous Sardinian mines. In the second study the cause specific mortality of 724 patients with silicosis, firstly diagnosed by standard chest x-ray between 1964 and 1970 in our Institute, has been analysed by a cohort study extended to December 31, 1997. The findings indicate that the slight increased lung cancer mortality observed in these cohorts, more than to the severity of radiological silicosis or to the entity of the cumulative exposure to crystalline silica dust in itself, was significantly associated to other risk factors as cigarette smoking, airflow obstruction and radon-daughters exposure in underground mines.

[Cognitive and performance capacity among adolescents living near a lead and zinc smelter]. / Capacità cognitive e di performance in adolescenti residenti in prossimità di una fonderia di piombo e zinco.

To estimate potential early adverse effects on the Central Nervous System (CNS) due to very low exposure to inorganic lead, the Intelligence Quotient (IQ) of adolescents with present blood lead concentrations (PhB) generally below 10 micrograms/dl was measured. We analyzed blood lead concentration and individual IQ of 32 Sardinian adolescents living in Portoscuso, a town 2 Km far from a lead smelter, and of other 32 controls living in S. Antioco, a town about 15 Km far from the same smelter. The Wechsler Intelligence Scale for Children Revised (WISC-R) was administered. The relation between IQ and blood lead concentration was estimated by linear multivariate models adjusting for several potential confounders, such as the educational and socio-economic level of the parents. The blood lead concentration was in average significantly higher in the Portoscuso group compared to controls. The linear model applied to the total population studied (n 64) showed that the blood lead concentration was inversely and significantly associated with IQ, with an extrapolated decline of 1.29 points in total IQ for each microgram/dl increase of blood concentration. According to the recent scientific literature on this topic, results of our pilot study suggest the need to further lower the definition of an elevated blood lead concentration for children to a threshold significantly below 10 micrograms/dl, value till now considered "safe" for the children's CNS.

[Mortality from lung cancer among workers of a Sardinian lead smelter [Follow-up: 1972-2001]]. / Mortalità per cancro polmonare in lavoratori di una fonderia di piombo della Sardegna [Follow-up: 1972-2001].

The mortality of 918 Sardinian lead-smelter workers followed between 1972 and 2001 is reported. The assessment of individual exposure to inorganic lead was based on several environmental and blood lead measurements available, for each department and task, between 1985 and 2001. The mortality for all cancers was within the expected numbers (SMR 1.01, n 108). Even if not statistically significant, the mortality for gastric cancer (SMR 1.22, n 4), for lung cancer (SMR 1.21, n 18) and for lymphomas and leukaemias (SMR 1.82, n 6) was higher than that expected from the regional rates during the follow-up. Only for the lung cancer mortality a statistically significant upward trend with increasing categories of lead exposure was observed (SMR 1.96, 95% CI 1.02-3.68 for the highest exposure group). Our study, even if of small size, suggests an association between occupational exposure to inorganic lead and lung cancer risk.

[Urinary and blood markers of internal mercury dose in workers from a chlorakali plant and in subjects not occupationally exposed: relation to dental amalgam and fish consumption]. / Indicatori urinari ed ematici di dose interna di mercurio in lavoratori di un impianto clorosoda e in soggetti non professionalmente esposti: relazione con gli amalgami dentali ed il consumo di pesce di mare.

OBJECTIVES: The aim of this paper was both to evaluate the internal dose of Hg in occupationally exposed workers (35 Chloralkali workers) compared to that of non occupationally exposed controls (40 workers of the same plant of Portotorres and 22 residents on the island of Carloforte, usual consumers of local fish, mostly tuna fish with relatively high Hg levels) and to assess the relevance of environmental and individual exposure factors linked to lifestyle, sea fish consumption and amalgam fillings. METHODS: All subjects filled out a questionnaire concerning the working history and lifestyle. The amalgam fillings area was measured by medical inspection using a standardised schedule attached to the questionnaire. Mercury in urine (HgU) was measured in all cases, while in a subgroup of our study total blood mercury (HgB) and its organic and inorganic component were also assessed. Furthermore, for 8 of the Carloforte group mercury in hair was also available. RESULTS: Values of urinary mercury excretion of the Chloralkali workers were significantly higher (median value of 15.4, range 4.8-35.0 micrograms/g creatinine, 94.3% of the cases having values > 5 micrograms/g creatinine) than those observed both among the reference group (median value of 1.9, range 0.4-5.6 micrograms/g creatinine, 12.5% of the cases having values a little greater than 5 micrograms/g creatinine) and among the residents in Carloforte (median value of 6.5, range 1.8-21.5 micrograms/g creatinine, 59.1% of the cases having values > 5 mcg/g creatinine). The HgU values observed in this group were in turn significantly higher than those of the non occupationally exposed workers living near Sassari (p = 0.03). Only in this last group were the HgU concentrations statistically significantly related to the extension of the amalgam fillings area (Pearson r = 0.53, p < 0.01). In the Carloforte group HgU was significantly related to the number of fish meal consumed per week (Pearson r = 0.48, p < 0.02). HgB (median value of 5.9, range 3.4-21.6 micrograms/l) as well as its inorganic component (median value of 2.4, range 1.8-4.6 micrograms/l) were significantly higher in the Chloralkali group compared to the other two groups. In all cases of the Carloforte group the ratio between the organic component and the total HgB was higher than 85%, while this ratio was significantly lower in the other two groups. The relationship between HgU and HgB was statistically significant, considering both total blood mercury and the inorganic and the organic components separately. A statistically significant relationship between the sea fish consumption per week and both total HgB (Pearson r = 0.82) and the organic component in this matrix (Pearson r = 0.84, p < 0.001) was observed among 16 non-occupationally exposed subjects. However, the significant relationship between organic blood mercury and sea fish consumption was almost entirely supported by the data observed in the Carloforte group. Total hair mercury levels analysed in 8 subjects of the Carloforte group were high (median value of 9.6, range 1.4-34.5 micrograms/g) and significantly related to sea fish consumption, and to both the individual Hg urinary excretion (Pearson r = 0.83) and to the organic component of blood mercury (Pearson r = 0.87). CONCLUSIONS: According to several experimental human and animal trials and to some recent studies on methylmercury toxicokinetic models, our results suggest that the organic compounds absorbed by usual sea fish consumption may be partially demethylated, increasing the inorganic Hg concentration in the kidney and consequently its urinary excretion, as was observed in the Carloforte group.

[Neuroendocrine and neurobehavioral effects associated with exposure to low doses of mercury from habitual consumption of marine fish]. / Effetti neuroendocrini e neurocomportamentali associati con esposizione a basse dosi di mercurio derivanti da consumo abituale di pesce di mare.

OBJECTIVES: To evaluate neuroendocrine and neurobehavioral effects possibly associated with increased dietary intake of organic mercury (Hg), a group of 22 subjects living on the island of Carloforte (south-west Sardinia) was examined, who were regular consumers of tuna fish with relatively high Hg content. This group, never exposed occupationally to either Hg or to other neurotoxic substances, was compared with 22 age-matched controls employed at a chemical plant in Portotorres (northern Sardinia). METHODS: Hg in urine (HgU) and serum prolactin (PRL) were measured in all cases, whereas measurements of total (HgB) and organic blood mercury were available only for 10 subjects from Carloforte and 6 controls. Data about working history and lifestyle (education, smoking habit, alcohol and sea fish consumption) were collected by an interviewer using a standardised questionnaire. Neurotoxic symptoms were evaluated by a self-administered questionnaire, whereas a test battery, including some computerised tests of the Swedish Performance Evaluation System (SPES) to assess vigilance and psychomotor performance, some tests on motor coordination (Luria-Nebraska and Branches Alternate Movement Task) and one memory test for numbers (Digit Span) was administered to assess neurobehavioral changes associated with exposure to dietary intake of organic mercury. In all cases, characteristics of hand tremor were evaluated by the CATSYS System 7.0. RESULTS: HgU values were significantly higher in the Carloforte group (median 6.5, range 1.8-21.5 micrograms/g creatinine) compared with controls (median 1.5, range 0.5-5.3 micrograms/g creatinine). Serum PRL was significantly higher among subjects from Carloforte and correlated with both urine and blood Hg levels. The scores of each item of the questionnaire investigating neurological symptoms were not statistically different in the two groups. In some tests of the SPES battery (Color Word Vigilance, Digit Symbol and Finger Tapping) the performance of the Carloforte group was significantly worse than that of controls, whereas in the other neurobehavioral tests poorer performances by the Carloforte group were not statistically significant. None of the tremor parameters was significantly different comparing the two groups. Multivariate analysis--controlling for education level and other covariates--carried out for the Symbol-Digit Reaction Time and for the Branches Alternate Movement Task (BAMT) showed that organic Hg concentration in blood was the most significant factor negatively affecting individual performance in these tests. Serum PRL was correlated with some neurobehavioral tests (Digit Symbol, Finger Tapping and BAMT). CONCLUSIONS: Some of the neurobehavioral tests were sensitive enough to discriminate groups with different Hg body burden, even in the low-dose range. However, the pattern of results suggests adverse neurobehavioral effects, especially on psycho-motor coordination, with a significant dose-effect relationship, mostly associated with long-term exposure to low levels of organic mercury due to the usual consumption of large fish with relatively high levels of Hg in the flash.

Mortality from lung cancer among silicotic patients in Sardinia: an update study with 10 more years of follow up.

OBJECTIVES: To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997. METHODS: Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society's criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates. RESULTS: The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox's proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates. CONCLUSIONS: The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors-such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines-rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself.

Induction of oxidative stress by homocyst(e)ine impairs endothelial function.

Previous studies have demonstrated a relationship between hyperhomocysteinemia and endothelial dysfunction, reduced bioavailability of nitric oxide, elastinolysis and, vascular muscle cell proliferation. In vivo decreased nitric oxide production is associated with increased matrix metalloproteinase (MMP) activity and formation of nitrotyrosine. To test the hypothesis that homocysteine neutralizes vascular endothelial nitric oxide, activates metalloproteinase, causes elastinolysis and vascular hypertrophy, we isolated aortas from normotensive Wistar rats and cultured them in medium containing homocysteine, and calf serum for 14 days. Homocysteine-mediated impairment of endothelial-dependent vasodilatation was reversed by co-incubation of homocysteine with nicotinamide (an inhibitor of peroxinitrite and nitrotyrosine), suggesting a role of homocysteine in redox-mediating endothelial dysfunction and nitrotyrosine formation. The Western blot analysis, using anti-nitrotyrosine antibody, on aortic tissue homogeneates demonstrated decreased nitrotyrosine in hyperhomocysteinemic vessels treated with nicotinamide. Zymographic analysis revealed increased elastinolytic gelatinase A and B (MMP-2, -9) in homocysteine treated vessels and the treatment with nicotinamide decreases the homocysteine-induced MMP activation. Morphometric analyses revealed significant medial hypertrophic thickening (1.4 +/- 0.2-fold of control, P = 0.03) and elastin disruption in homocysteine-treated vessels as compared to control. To determine whether homocysteine causes endothelial cell injury, cross-sections of aortas were analyzed for caspase activity by incubating with Ac-YVAD-AMC (substrate for apoptotic enzyme, caspase). The endothelium of homocysteine treated vessels, and endothelial cells treated with homocysteine, showed marked labeling for caspase. The length-tension relationship of homocysteine treated aortas was shifted to the left as compared to untreated aortas, indicating reduced vascular elastic compliance in homocysteine-treated vessels. Co-incubation of homocysteine and inhibitors of MMP, tissue inhibitor of metalloproteinase-4 (TIMP-4), and caspase, YVAD-CHO, improved vascular function. The results suggest that alteration in vascular elastin/collagen ratio and activation of MMP-2 are associated with decreased NO production in hyperhomocysteinemia.

[Incremental stress test: comparison between protocols and cardiorespiratory reference values in healthy workers]. / Prove da sforzo a carico crescente: confronto tra protocolli e valori di riferimento cardiorespiratori in lavoratori sani.

The aim of this study was double: to compare two different incremental stress protocols and to obtain reference values for a standardised exercise test in healthy workers. Firstly, eighty healthy male workers, 40 coal miners and 40 hospital workers, aged 19-54, performed in 2 different days 2 cycle ergometer tests up to exhaustion, increasing the work load respectively by 30 watts every 3 minutes (protocol A) and by 30 watts each minute (protocol B). Ventilatory and gas exchange measurements were done by a breath-by-breath apparatus equipped with a turbine and fast gas analysers for O2 and CO2. For each test the ventilatory anaerobic threshold (VAT) was blindly determined as oxygen uptake (V'O2 VAT) using standardised gas exchange and ventilatory indices (V'CO2, V'E, V'E/V'O2) that were found giving comparable results with those derived from the blood lactacte curve. Significant differences were observed between the two protocols only concerning the average work load at exhaustion and at the VAT: the highest being with the protocol B. Conversely, either the maximal oxygen uptake (V'O2 max) and the V'O2 VAT were comparable between protocols, as well as the other cardio-respiratory parameters were at these exercise levels. Oxygen uptake and heart rate increased in average linearly with the work load with very similar slopes in both protocols. Comparable results between protocols were found also as what concerns the slopes of the other physiological variables (V'E, V'CO2) analysed against the V'O2, particularly for exercise levels lower or equal to the individual VAT. Thus, these results suggest a very good comparability between the two protocols, concerning both the levels of maximal and sub-maximal aerobic capacity (V'O2 max, V'O2 VAT) and the cardio-respiratory pattern related to the oxygen uptake. Reference values for the 30 watts/3 minutes cycle ergometer stress test were achieved in other 320 healthy Sardinian workers concerning both the maximal (V'O2 max) and sub-maximal (V'O2 VAT) aerobic capacity and the range of normality for the cardio-respiratory pattern during the test, particularly for completely aerobic work loads, namely work loads not above the V'O2 VAT. These prediction equations can be useful for the evaluation of working capacity of workers employed in manual jobs characterised by moderate-to-high dynamic energy expenditure.

Origin of the left pulmonary artery from the aorta: embryologic considerations.

We observed a case of anomalous origin of the left pulmonary artery from the aorta in which the media of the abnormal vessel and the main pulmonary artery were fused, but without communication. This is the fifth isolated case of repair without the use of cardiopulmonary bypass reported in the literature. This pathology should be included in the aortic arch anomalies as a partial or complete failure of development of the left sixth arch.

Replacement of the mitral valve in an infant with group B streptococcal endocarditis.

Endocarditis due to group B streptococcus is very rare in infants, and may be associated with significant morbidity and mortality. Review of the literature reveals only a single reported case of an infant with this type of streptococcal endocarditis involving the mitral valve. This infant had underlying congenital heart disease, and died shortly after catheterization. We now report group B streptococcal endocarditis occurring in an infant with a structurally normal heart who was treated successfully by replacement of the mitral valve.