[Diastolic heart failure]. / Lo scompenso cardiaco diastolico: aspetti clinici, fisiopatologici e terapeutici.

Until recently, the development of heart failure was related exclusively to the acute or chronic impairment in systolic function. Currently, the concept of heart failure not sustained primarily by a significant reduction in contractility has been clearly defined by several epidemiological and pathophysiological observations. This condition, defined as 'diastolic heart failure' or 'heart failure with preserved systolic function' can be related to different cardiac diseases with a higher prevalence in the elderly. Afterload mismatch situations, such as hypertension or aortic stenosis, as well as hypertrophic cardiomyopathy or pericardial diseases, determine this common clinical syndrome more frequently. Currently, the treatment of diastolic heart failure is still empirical, as there are few and inconclusive data coming from evidence-based medicine.

[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.

[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.

AMPA-evoked acetylcholine release from cultured spinal cord motoneurons and its inhibition by GABA and glycine.

The release of [(3)H]acetylcholine evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and its inhibition mediated by GABA(A) and glycine receptors were studied in superfused cultured rat embryo spinal cord motoneurons prelabeled with [(3)H]choline. AMPA elicited tritium release, possibly representing [(3)H]acetylcholine release in a concentration-dependent manner. The release was external Ca(2+)-dependent and was sensitive to Cd(2+) ions, omega-conotoxin GVIA and omega-conotoxin MVIIC, but not to nifedipine, suggesting the involvement of N-, P/Q-, but not L-type Ca(2+) channels. The AMPA effect was insensitive to tetrodotoxin. The glutamate receptors involved are AMPA type since the AMPA-evoked [(3)H]acetylcholine release was blocked by LY303070 and was potentiated by the antidesensitizing agent cyclothiazide. Muscimol inhibited completely the AMPA effect on [(3)H]acetylcholine release; muscimol was potentiated by diazepam and antagonized by SR95531, indicating the involvement of benzodiazepine-sensitive GABA(A) receptors. Glycine, acting at strychnine-sensitive receptors, also inhibited the effect of AMPA, but only in part. The inhibitory effects of muscimol and glycine are additive. We conclude that glutamate can act at AMPA receptors sited on spinal motoneurons to evoke release of acetylcholine. GABA and glycine, possibly released as cotransmitters from spinal interneurons, inhibit glutamate-evoked acetylcholine release by activating GABA(A) and glycine receptors on motoneurons.

Amino-terminal modification and tyrosine phosphorylation of [corrected] carboxy-terminal fragments of the amyloid precursor protein in Alzheimer's disease and Down's syndrome brain.

The carboxy-terminal fragments (CTFs) of the amyloid precursor protein (APP) are considered beta-amyloid (Abeta) precursors as well as molecular species possibly amyloidogenic and neurotoxic by [corrected] in vitro or in animal models. The CTF's role in the pathogenesis of Alzheimer's disease (AD) is however relatively unexplored in human brain. In this study, we analyzed brain extracted CTFs in subjects with AD, non-AD control, and Down's syndrome (DS) cases. Our data indicate that: (i) In fetal DS subjects CTFs levels are increased in comparison to age-matched control, suggesting that the enhanced CTFs formation is important for the early occurrence of plaques deposition in DS. No significant difference in CTFs level [corrected] between AD and age-matched control cases. (ii) CTFs modified at their N-terminus are the direct precursors of similarly N-terminally modified Abeta peptides, which constitute the most abundant species in AD and DS plaques. This observation suggests that N-truncated Abeta peptides are formed directly at beta-secretase level and not through a progressive proteolysis of full-length Abeta1-40/42. (iii) Among the differently cleaved CTFs, only the 22- and 12.5-kDa CTF polypeptides are tyrosine phosphorylated in both AD and control brain while the full-length APP and the CTFs migrating below the 12.5-kDa marker are not phosphorylated, suggesting that APP and CTFs may be involved in different pathways depending on their length and sequences. This study provides evidence that CTFs constitute in human brain a molecular species directly involved in AD pathogenesis and in the development of the AD-like pathology in DS subjects.

'High dose' aprotinin and heparin-coated circuits: clinical efficacy and inflammatory response.

Heparin-coated cardiopulmonary bypass circuits reduce the inflammatory response to cardiopulmonary bypass circuit, improve biocompatibility and may protect the postoperative hemostasic mechanisms in routine coronary bypass operations. 'High-dose' aprotinin reduces bloodloss, transfusion needs, and re-explorations as a result of bleeding, and may have an additional role in reducing the inflammatory response of the body to cardiopulmonary bypass circuit. It has not been established, however, if the addition of a heparin-coated circuit to the intraoperative administration of 'high dose' aprotinin further reduces the whole-body inflammatory response to cardiopulmonary bypass circuit and improves the postoperative clinical course of the patients who are undergoing coronary surgery. Thirty patients undergoing primary elective coronary artery bypass grafting were studied. All the patients received, intraoperatively, the serine-protease inhibitor aprotinin according to the 'Hammersmith' protocol and full heparin dose. Patients were randomly allocated to be treated either with a circuit completely coated with surface-bound heparin (n = 15) or with an uncoated, but otherwise identical, circuit (n = 15). Differences in the clinical course of the two groups of patients, as well as differences in the behavior of hematological and inflammatory (interleukin-6 (IL-6) and C-reactive protein) factors before, during and after bypass, were analyzed. There were no significant differences between the two groups in terms of bleeding and transfusional requirements, the time spent on a ventilator, or in duration of stay in the intensive care unit (ICU). In all patients, a significant increase in the total white blood cell count, neutrophils, serum IL-6 and C-reactive protein occurred in relation to cardiopulmonary bypass. This was not influenced by heparin precoating of the circuit. In addition, there was an increase in the monocyte count during follow-up, and there was a trend towards higher monocyte counts in the patients who were treated with heparin-coated circuits. These results suggest that the addition of a heparin-coated circuit to the intraoperative 'high-dose' aprotinin therapy probably had little influence on the clinical course and on the time-course of the inflammatory parameters of the adult patients undergoing primary coronary surgery with a full heparinization protocol.

Serum apolipoprotein(a) concentrations and Apo(a) phenotypes in patients with liver cirrhosis.

OBJECTIVE: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. METHODS: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. RESULTS: Apo(a) serum levels were significantly lower (p < 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations (p = 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. CONCLUSION: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apolipoprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.

Mortality of lead smelter workers with the glucose-6-phosphate dehydrogenase-deficient phenotype.

The mortality experience of 1345 male workers in a lead and zinc smelting plant was followed from 1973 to 1991. Information on the erythrocyte glucose-6-phosphate dehydrogenase (G6PD) phenotype was available for 1,222 (90.9%) cohort members, which provided the opportunity to compare the mortality experience of G6PD-deficient subjects to wild-type-G6PD coworkers with similar exposure to lead. A significant decrease in mortality was observed among the total cohort as well as among the subcohort of production and maintenance workers. Most deaths (27 of 31) and all cancer deaths occurred among production and maintenance workers. Lung cancer mortality was lower than expected. Two deaths from stomach cancer were observed versus 0.6 expected. Mortality from all causes and cancer mortality were lower among production and maintenance workers with the G6PD-deficient phenotype compared to coworkers with the wild-type phenotype. Although the low statistical power of this study prevents conclusive inference, lead smelter workers with the G6PD-deficient phenotype did not suffer adverse health outcomes in terms of mortality from all causes and cancer mortality compared to coworkers with the wild-type G6PD.

Effects of short-term occupational exposure to lead on erythrocyte glucose-6-phosphate dehydrogenase activity and serum cholesterol.

The effect of short-term occupational exposure to lead on erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity and serum cholesterol was studied in 40 male workers of a lead and zinc foundry. All parameters were measured just before employment and after 172 +/- 21.3 days of work. Genetic deficiency of erythrocyte G6PD was observed in 5/40 subjects. Among G6PD normal subjects, increases in enzyme activity followed any change (increase or decrease) in blood lead. At the pre-employment test, serum cholesterol parameters did not show any correlation with GOD activity or blood lead, and they were not affected by exposure. Cholesterol values observed among all the GOD-deficient subjects were within the range of the rest of the study population.

[Infections due to central catheterizations in a cardiac intensive care unit: an evaluation of 6 months of continuous surveillance. The nursing personnel of a cardiac intensive care unit]. / Infezioni da cateterismi centrali in UTIC: valutazione di sei mesi di sorveglianza continua. Personale infermieristico UTIC.

BACKGROUND: Infections in intensive care unit are nowadays well documented. As no recent papers about catheter related infections in cardiological intensive care units were found, we decided to approach them during a period of six months with a surveillance study including a clinical, nursing and microbiological protocol. METHODS: The microbiological protocol the semiquantitative Maki cultural evaluation of the tips, the interior of the hubs and the skin around the catheter insertion point. In addition, all the samples were additionally cultured in liquid media. A total of 432 biological samples were analysed, from 125 patients entered into our cardiological intensive care unit: 144 from catheter tips, 144 from the hubs and 144 from the skin around the catheter insertion. RESULTS: Three hundred and eighty-four biological samples (88.9%) were completely negative. Thirteen tips resulted positive (27.1% of the 48 total positive biological samples): 92.3% (12/13) of the positive catheters were infected from internal origin, hub and skin resulting culture negative. Of the 144 catheter tips 12 were colonized (C.F.U. < 15) while only 2 resulted infected (C.F.U. > or = 15). Only one patient was infected with an exogenous infection presenting tip, hub and skin positivity. The overall positivity was of 214 microorganisms mainly represented (93.5%) by gram positives; 87% of them were coagulase-negative staphylococci (C.N.S.). In addition, the tip detection of a Candida guillermondii strain in a pacemaker patient is a relevant finding. CONCLUSIONS: The very low number of cutaneous contaminations (1.3%) and patient's infections (0.69%) showed the good sensibilisation of the medical and nursing teams in the infection control and surveillance.

Occupational exposure to lead and blood cholesterol in glucose-6-phosphate dehydrogenase deficient and normal subjects.

The effect of chronic lead poisoning on blood cholesterol levels of 148 patients, admitted to the Institute of Occupational Medicine of the University of Cagliari (Italy), was studied in connection with the genetic pattern of Glucose-6-Phosphate Dehydrogenase (G6PD) activity. The erythrocyte G6PD activity of twenty-six patients was genetically deficient. Multiple regressions were elaborated including the following in the model as independent variables: age, Quetelet index and blood lead or urinary lead in the 24 hours following 15 mg/Kg of i.v. calcium ethylen-diamine-tetracetate (EDTA) (PbUEDTA), expressed as a ratio with body weight (PbUEDTA/Kg). Dependent variables were alternatively, total cholesterol, cholesterol esters, LDL and HDL cholesterol. The analysis showed that G6PD deficient subjects have generally lower intercepts, but only for HDL the difference approached the statistical significance. Lead poisoning affected blood cholesterol of G6PD deficient subjects differently from normal ones: while total cholesterol and LDL tended to decrease in both, positive slopes were observed for cholesterol esters in G6PD deficient and for HDL in G6PD normal subjects.

Impact-fracture energy of human premolar teeth.

The fracture strength of contralateral pairs of premolar teeth was determined by an in vitro method wherein impact loads of equal energy were applied to the medial aspects of the buccal cusps. Absorbed energy values quantified the fracture resistance of unprepared teeth and teeth restored with MOD amalgams, MOD amalgam overlays, MOD gold overlays, and full gold crowns. It was established that unprepared lower premolar teeth had a greater resistance to fracture than upper premolar teeth, and lower first premolar teeth were more resistant to fracture than the other premolar teeth; the fracture resistance of premolar teeth restored with MOD amalgams was significantly reduced compared with unprepared control teeth; MOD amalgam overlays in premolar teeth produced fracture resistances not significantly different from those for the unprepared controls; and restoration of premolar teeth with MOD gold overlays and full gold crowns enhanced fracture resistance to a level much greater than that of the unprepared control teeth.

The vestibular cortical projection during spinal decompensation.

The removal of spinal afferents in rabbits submitted to unilateral lesion of the labyrinth and fully compensated greatly modified the field potentials as well as the single unit responses recorded from the cortical vestibular area during stimulation of the intact eighth nerve. In particular, an increase of contralateral and a decrease of ipsilateral potentials were observed. These asymmetrical responses indicate that the influence of the spinal cord in compensating the effects of unilateral lesion of the labyrinth is directed to balance not only the electrical activity of the brain-stem structures, but also that of the cerebral cortex. It appears, therefore, that spinal signals intervene not only in the compensation of vestibulospinal and vestibulo-oculomotor functions but also of cortical functions, such as that related to vestibular sensation.