Determinants of all causes of death in samples of Italian middle-aged men followed up for 25 years.

A total of 1712 men aged 40 to 59 years in two rural cohorts of northern and central Italy have been followed up for 25 years after an entry examination in 1960. Forty one individual characteristics have been considered as possible predictors of death in the next 25 years. After exclusion of 55 men with life threatening diseases (cardiovascular and cancer) and of 161 men because of missing measurements, 1495 men have been analysed for relation between entry factors and subsequent death (n = 670). Twelve factors eventually emerged as powerful predictors of future death: in hierarchical order, age, blood pressure, forced expiratory volume, cigarette smoking, xanthelasma, mother life-status, arm circumference, father life-status, shoulder-pelvis ratio, vital capacity, arcus senilis, and serum cholesterol. Discrimination as provided by logistic modelling placed 19.6% of all cases in the upper decile of the estimated risk, 36.8% in the upper quintile, 2.5% in the lowest decile, and 7.1% in the lowest quintile. Out of those located in the lowest decile of risk, 11.4% died within 25 years while the corresponding percentage in the upper decile was 87.3%. Use of the Cox model yielded slightly better coefficients than logistic function.     

The predictive value of specific immunoglobulin E levels for the first diagnosis of cow''s milk allergy. A critical analysis of pediatric literature

Investigators have tried to identify a level of seric specific immunoglobulin E (IgE) that had a sufficient predictive value to diagnose a food allergy without having will resort to the food challenge. To search in literature, all the studies that have estimated the possibility to identify a level of seric specific cow milk IgE with a positive predictive value (PPV) of 95% for the first diagnosis of cow's milk allergy (CMA) in pediatric age. We have identified six studies, nearly all studies suffer from relevant methodological bias. Proposed cut-off are all different. The studied pediatric populations were highly selected. Also neglecting the methodological bias of the studies and the great difference of value between the proposed cut-off, it always remains to consider that the pre-test probability of having a CMA between the children enrolled in the six studies included in this review is particularly high. The likelihood ratio helps to transfer the results of a study on a diagnostic test just to our population, and it is more realistic rather than to entrust itself to the PPV or the negative predictive value, that are much influenced from the prevalence of the disease in the studied population.     

Primary pulmonary hypertension: an Italian multicenter study. A retrospective epidemiological survey in the period 1975-1985

An epidemiological retrospective survey on primary pulmonary hypertension was undertaken in Italy in 1985-6. The aim of the study was to obtain clinical and laboratory data on patients observed in the major cardiological Institutions, both Universities and Hospital Clinical Centers, in the period 1975-85. Forms were sent to 67 centers and twenty-three of them communicated their data on 124 cases of primary pulmonary hypertension. The diagnosis was considered certain or probable in 91 patients by the referring center. The mean age of patients was 38.5 years, with an overall female-to-male ratio of 2:1. Data were subjected to statistical analysis which confirmed the poor prognosis of the disease particularly for patients with high pulmonary resistances, low cardiac output and in class 3-4 of the NYHA. Half of the 124 cases were treated with calcium antagonists after 1980, but the results of therapy in modifying the clinical course of the disease could not be assessed by the study. Like all retrospective studies even the Italian Multicenter Study is biased but it can be considered as an useful preliminary investigation which can form the basis for a prospective registry of primary pulmonary hypertension cases.     

Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study

Sixteen cohorts of men aged 40–59 years at entry were examined with the measurement of some risk factors and then followed-up for mortality and causes of death for 25 years. These cohorts were located in the USA (1 cohort), Finland (2), the Netherlands (1), Italy (3), the former Yugoslavia (5), Greece (2), and Japan (2), and included a total of 12,763 subjects.Large differences in age-adjusted coronary heart disease (CHD) death rates were found, with extremes of 45 per 1000 in 25 years in Tanushimaru, Japan, to 288 per 1000 in 25 years in East Finland. In general, higher rates were found in the US and Northern European cohorts as compared to the Southern European and Japanese cohorts. However, during the last 10 years of follow-up large increases of CHD death rates were found in some Yugoslavian areas. Out of 5 measured entry characteristics treated as age-adjusted levels (serum cholesterol, systolic blood pressure, cigarette smoking, body mass index and physical activity at work), only serum cholesterol was significant in explaining cohort differences in CHD death rates.Over 50% of the variance in CHD death rates in 25 years was accounted for by the difference in mean serum cholesterol. This association tended to decline with increasing length of follow-up, but this was due to the great changes in mean serum cholesterol in the two Jugoslavian cohorts of Velika Krsna and Zrenjanin. When these two cohorts were excluded the association increased with time.Changes in mean serum cholesterol between year 0 and 10 helped in explaining differences in CHD death rates from year 10 onward.It can be concluded that this study suggests that mean serum cholesterol is the major risk factor in explaining cross-cultural differences in CHD.     

Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine

Chronic alcoholism is a major public health problem and causes multiorgan diseases and toxicity. Although the majority of ethanol ingested is metabolized by the liver, it has intoxicating effects in the brain. Evidence is accumulating that intermediates of oxygen reduction may be associated with the development of alcoholic disease. Several studies have shown the capacity of carnitine and its derivatives to influence ethanol metabolism. We have previously demonstrated that preadministration of L-carnitine to rats receiving ethanol significantly reduced fatty acid ethyl esters in different organs and that the carnitine/acylcarnitine system is crucial for maintaining a functional acetyl-CoA/CoA ratio under conditions in which cellular homeostasis is exposed to the deleterious effects of accumulating organic acids. Ethanol, administered to rats for 20 months, induced significant changes in the status of glutathione, primarily in the brain regions of hippocampus and cerebellum, followed by cortex and striatum, where a decrease in reduced glutathione (GSH) and the GSH/oxidized glutathione ratio was found. The same brain regions showed a significant increase in free radical-induced luminescence and hydroxynonenal (HNE), which were associated with decreased GSH reductase activity. Long-term supplementation with acetyl carnitine significantly reduced GSH depletion, particularly in the brain regions of hippocampus, an effect associated with decreased luminescence and HNE formation. In addition, acetyl carnitine treatment increased GSH reductase and arginase activities. Our results indicate that decreased GSH reductase activities associated with thiol depletion are important factors sustaining a pathogenic role in alcohol-related pathologies. Administration of acetyl carnitine greatly reduces these metabolic abnormalities. This evidence supports the pharmacological potential of acetyl carnitine in the management of alcoholic disturbances.     

Hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and abnormal recirculation of OKT4 lymphocytes in a girl with chronic lymphadenopathy

We describe here one 8-year-old girl with an unusual form of immunodeficiency, characterized by hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and chronic lymphadenopathy. Patient's B cells failed to produce IgG or IgA in vitro following stimulation with either pokeweed mitogen or Epstein-Barr virus, suggesting an intrinsic B-cell defect. Abnormal T-cell function was demonstrated by impaired in vivo delayed type hypersensitivity, reduction of mitogen-induced proliferation and interleukin 2 production, reduction of interferon-gamma production, and marked decrease of circulating OKT4+ cells. The latter cells were found in normal proportion in the patient's lymph node tissue. This finding suggests that the decrease of OKT4+ cells in peripheral blood was due to the abnormal recirculation of these cells. The identity of this syndrome with the infantile form of the acquired immunodeficiency syndrome was apparently ruled out by the failure to demonstrate HTLV-III-related sequences in patient's lymphocytes or virus-specific serum antibodies.