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Biomedical subjects

M Mancini

Publications and source records attributed to M Mancini.

At least 217 records · Page 12Linked to original sources

Earthquake and coronary heart disease risk factors: a longitudinal study.

The longitudinal association between a number of coronary heart disease risk factors and the experience of a natural disaster (earthquake) was analyzed in a group of workers participating in a longitudinal epidemiologic investigation. The 5-year follow-up examination was interrupted by a major earthquake, and examinations were resumed 2 weeks after the quake. Participants screened after the quake had, on average, higher heart rates, serum cholesterol, and triglycerides than participants examined before the quake; these differences were independent from the coronary heart disease risk factor values measured 5 years previously during the baseline examination. The data collected during the 12-year examination indicated that the observed short-term increase in serum lipids and heart rate was not present long-term (7 years after the quake). These longitudinal data indicate that exposure to a natural disaster can be associated with short-term increases in heart rate, serum cholesterol, and triglycerides but that there is no apparent long-term effect on these coronary heart disease risk factors.

Adult↗

Methylation and sequence analysis around EagI sites: identification of 28 new CpG islands in XQ24-XQ28.

Thirty-two probes for CpG islands of the distal long arm of the human X chromosome have been identified. From a genomic library of DNA of the hamster-human cell hybrid X3000.1 digested with the rare cutter restriction enzyme EagI, 53 different human clones have been isolated and characterized by methylation and sequence analysis. The characteristic pattern of DNA methylation of CpG islands at the 5' end of genes of the X chromosome has been used to distinguish between EagI sites in CpG islands versus isolated EagI sites. The sequence analysis has confirmed and completed the characterization showing that sequences at the 5' end of known genes were among the clones defined CpG islands and that the non-CpG islands clones were mostly repetitive sequences with a non-methylated or variably methylated EagI site. Thus, since clones corresponding to repetitive sequences can be easily identified by sequencing, such libraries are a very good source of CpG islands. The methylation analysis of 28 different new probes allows to state that demethylation of CpG islands of the active X and methylation of those on the inactive X chromosome are the general rule. Moreover, the finding, in all instances, of methylation differences between male and female DNA is in very strong support of the notion that most genes of the distal long arm of the X chromosome are subject to X inactivation.

Amino Acid Sequence↗

Drugs affecting plasma fibrinogen levels.

Current knowledge indicates that high plasma levels of fibrinogen help predict stroke and myocardial infarction. It is known that plasma fibrinogen is synthesized in the liver, that interleukin-6 (IL-6) affects this synthesis, and that, when exposed to appropriate stimuli, monocytes generate a variety of monokines, including IL-6. It is also known that prolonged administration of N-3 fatty acids, ticlopidine, fibrates, pentoxifylline, or alcohol lower plasma fibrinogen levels. The mechanism(s) involved in this effect are poorly understood. However, in view of the role of IL-6 and monocytes in the regulation of plasma fibrinogen levels, it is conceivable that the lowering effect of these drugs involves effects on some steps of the regulatory machinery. In addition to fibrinogen, IL-6 regulates the synthesis of other acute-phase proteins. This raises the question of whether high plasma fibrinogen levels do reflect the response of an acute-phase reactant to the severity of the atherosclerotic vascular damage taking place. Current evidence is inconclusive with respect to this possibility. On the other hand, the epidemiological data available indicate that measurements of plasma fibrinogen should be included in the cardiovascular risk-factor profile. In view of this, we believe that information emerging from population-based studies in which plasma fibrinogen is measured is important to identify appropriate directions to be followed to address unsolved issues in the area.

Fibrinogen↗

Fibrinogen and mechanisms of thrombosis. A difficult link.

Epidemiological observations indicate that high plasma fibrinogen levels are strongly correlated to the frequency of two major thrombotic complications of atherosclerosis: stroke and myocardial infarction. Thrombosis is increasingly recognized as a central mechanism in stroke and myocardial infarction, and fibrinogen is involved in events thought to play a major role in thrombosis. Therefore, elucidation of the relationship between fibrinogen and thrombosis may strengthen the predictive value of this protein and define new interventions against stroke and myocardial infarction. In addition, advances in the understanding of the atherogenic potential of several risk factors of coronary heart disease took advantage of information emerging from the measurement of the factor in population-based studies. Thus, it is conceivable that measuring plasma fibrinogen to predict stroke and myocardial infarction is a major direction to be followed to gain insight into the thrombogenic potential on this protein and inspire new strategies against thrombotic complications of atherosclerosis.

Blood Viscosity↗

Progetto ATENA, a study on the etiology of major chronic diseases in women: design, rationale and objectives.

In spite of their important impact on populations, a number of diseases--all types of cancer and coronary heart disease in women--are "rare" events for statistical analysis and often analyzed in designs affected by selection and information biases, such as case-control studies. Large cohort studies based on the storage of biological specimens appear to be the most suitable solution for identifying risks for those diseases. Progetto ATENA, a study on the etiology of major chronic diseases in women is based on this design. Ten thousand women, aged 30-69 years, living in the area of the city of Naples, free of cancer and cardiovascular disease, are being recruited over a four-year period. Ten per cent of the cohort is being randomly selected from the electoral roles, the rest will be volunteers. Information on dietary habits, reproductive history, familiarity for chronic disease, active smoking habits and passive smoking exposure, physical activity, and socio-demographic data are being collected. Clinical data such as blood pressure, anthropometry, and electrocardiogram are also taken. All the participants provide biological samples of blood (fasting drawing) and urine (timed morning spot). The biological samples are processed in order to explore the main areas under study (nutritional markers, metabolism, endocrinology, genetics, environmental exposure markers, thrombogenesis). The samples are stored in liquid nitrogen (-196 degrees C) as soon as the blood and urine processing have been finished. An appropriate follow-up information system on the health status of the participants is being set up to estimate incidence and mortality rates.

Adult↗

Ph-negative and bcr-negative atypical chronic myelogenous leukemia: biological features and clinical outcome.

We report the clinical, hematologic, cytogenetic, and molecular characteristics of 13 patients with Philadelphia-negative (Ph-), bcr-negative atypical chronic myelogenous leukemia (CML). In the majority of cases, the phenotypic features at presentation resembled those of typical CML. However, these patients presented with a higher median age, lower median hemoglobin levels, and lower leukocyte and platelet counts than patients with Ph-positive CML. Cytogenetic analysis showed an abnormal karyotype in only one case. Southern blot investigation, using probes exploring the entire M-bcr region, demonstrated the absence of genomic bcr-abl rearrangements. The assessment of clonality in five patients (study of X-methylation patterns in females heterozygous at the DXS255 locus) indicated the proliferation of a monoclonal cell population. Disease evolution was mostly characterized by bone marrow failure, extramedullary infiltrates, and poor response to chemotherapy, without evidence of overt acute transformation. Our observations suggest that some hematologic and clinical features and the modalities of disease progression are presently the most helpful factors in distinguishing these bcr/abl-negative patients from those with typical bcr+CML. The differences existing also with chronic myelomonocytic leukemia (CMMoL), allow the consideration of ph-/bcr- CML as a separate entity, the nature of which remains to be elucidated.

Cytogenetics↗

Evaluation of lipid metabolism during antihypertensive treatment with nicardipine sr.

The antihypertensive and metabolic effects of oral nicardipine SR 40 mg b.i.d. have been studied in 18 (15 m, 3 f; age 52.7 y) hypertensives with mild hypercholesterolaemia, treated for 3 months after a 2 week period on placebo. An iv Fat Tolerance Test (FTT) was also performed in 8 patients following placebo, treatment with acute nicardipine 20 mg and chronic administration of nicardipine SR. There was a significant fall in BP from 160/97 on placebo to 147/87 after 3 months on nicardipine SR with no change in heart rate. Blood lipids did not change significantly. The disappearance rate of the lipid emulsion in the ivFTT showed no significant change (K2 was 1.93%/min after placebo, 1.84 after nicardipine 20 mg and 1.71 after chronic treatment). The results suggest that nicardipine is an effective antihypertensive drug and that it is devoid of untoward effects on lipid metabolism.

Adult↗

Weight reduction lowers blood pressure independently of salt restriction.

The existence of a link between obesity and hypertension is nowadays universally accepted; however, there are still some doubts about the fact that weight reduction induces a significant long-term decrease in blood pressure. This clinical trial aimed at evaluating the effects of marked weight loss (at least 30% of excess body weight) induced by a low-energy (600 Kcal), normal sodium diet in severely obese patients, on blood pressure at rest and during sympathetic stimulation. Eight of the 20 patients initially recruited for the study were able to reach the therapeutical goal and brought their body weight from 107 +/- 6 to 91 +/- 4 kg. Their blood pressure (BP) at rest was at the same time reduced from 137/81 +/- 5/4 to 122/74 +/- 4/4 mmHg. Also, blood pressure measured during three different stimuli (cold pressor test, handgrip and mental arithmetic test) was lowered by this nonpharmacological means. These effects are related solely to weight reduction, since no change in salt intake occurred, as demonstrated by measurements of the 24-h sodium excretion test (191 +/- 13 vs 185 +/- 10 mEq/24 h). In conclusion, these results support the hypothesis that a drastic weight loss, independently of salt restriction, significantly reduces BP at rest and during stimulation of the adrenergic nervous system.

Adult↗

Sodium-lithium countertransport and body fat distribution.

The relationship between erythrocyte sodium-lithium countertransport (Na-Li CT) and body fat distribution is analyzed in a sample (n = 101) of normotensive and untreated hypertensive men participating in an epidemiological study of coronary heart disease risk factors. Na-Li CT is significantly and positively associated with both subscapular skinfold and waist to hip ratio, but not with triceps skinfold. The univariate correlation between Na-Li CT and blood pressure is diminished when adjusted for body mass index and waist to hip ratio. These findings support the existence of an association between Na-Li CT and central body fat distribution and suggest that the metabolic abnormalities associated with centrally distributed body fat could explain, at least in part, the association between Na-Li CT and blood pressure. The maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes has been reported to be directly associated with blood pressure and hypertension in numerous reports from both clinical and epidemiological studies. In most of these studies, indices of weight and/or adiposity (body mass index, in particular) have been shown to be among the most important correlates of Na-Li CT. Adiposity is an important determinant of blood pressure, and there is evidence suggesting that the patterning of the fat cells in the body is linked to a number of metabolic disturbances that could lead to hypertension and an increase in other CHD risk factors. The present report analyses the relationship between Na-Li CT and body fat distribution in a sample of normotensive and untreated hypertensive men participating in an epidemiological study.

Adipose Tissue↗

Unbalanced 6p translocation as primary karyotypic anomaly in secondary acute nonlymphocytic leukemia.

A case of acute nonlymphocytic leukemia after radiochemotherapy for Hodgkin's disease, with a rearrangement of 6p23 region, is described. This chromosome change, which has been previously reported in secondary leukemias or myelodysplastic syndromes, was an isolated karyotypic anomaly in our case, which strongly supports the nonrandom involvement of chromosome 6p in induced leukemias.

Adult↗

Resting blood pressure and cardiovascular response to sympathetic stimulation in adolescents.

The prevalence of significant hypertension in childhood may be higher than expected. We have measured sitting blood pressure in 168 11-yr-old children attending a pre-high school in the Neapolitan area on four occasions over a 3-month period. We have also measured blood pressure and heart rate during a mental arithmetic test and during isometric exercise. Prevalence of significant hypertension (diastolic blood pressure 82-90 mmHg) was 13% at the first visit and decreased to 6.5% at the last visit; prevalence of severe hypertension (diastolic blood pressure greater than or equal to 90 mmHg) decreased from 5.4% to 1.2% from the 1st to the 4th visit. No sex-related difference was observed. A more frequently positive family history of hypertension (50% vs 30% in the fifth and first quintile of blood pressure, respectively) and higher body weight (body mass index = 21.4 vs 19.3 kg/m2) were found in children in the 5th quintile of blood pressure distribution. Blood pressure increased during mental arithmetic by 10/13% of the resting values in the first quintile and by 6/11% in the last one during mental test; during handgrip the increase was of 20/37% and 24/46%, respectively: differences between quintiles did not reach statistical significance. These data show that about 8% of a Neapolitan sample of school population have high blood pressure levels, while no difference in vascular reactivity to sympathetic stimulation was detected in children with higher blood pressure.

Age Factors↗

Recognition of shared melanoma antigens by human tumor-infiltrating lymphocytes.

We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor-infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2- melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines.

Antigens, Neoplasm↗

Human immunodeficiency virus type 1 major neutralizing determinant exposed on hepatitis B surface antigen particles is highly immunogenic in primates.

Hepatitis B surface antigen (HBsAg) produced by recombinant DNA technology is now widely and safely used worldwide for hepatitis B vaccination. We used the HBsAg particle as a carrier molecule for presentation of selected human immunodeficiency virus type 1 (HIV-1) determinants to the immune system. Immunization of rhesus monkeys with an HBsAg chimera carrying the HIV-1 envelope major neutralizing determinant allowed us to generate proliferative T-cell responses and, in some cases, neutralizing antibodies and antibody-dependent cellular cytotoxicity. Since there is an overlap between populations at risk for hepatitis B virus and HIV, HBsAg recombinant particles may be relevant carriers for HIV-1 epitopes and could offer a new approach to the development of an AIDS vaccine.

Amino Acid Sequence↗

Long-term magnesium supplementation in essential hypertension.

The main objective of this clinical trial was to evaluate the effects of magnesium pidolate (15 mmol/day) on blood pressure at rest and during sympathetic stimulation induced by cold, isometric and tilt test; peripheral blood flow has been evaluated by strain-gauge plethysmography. Fourteen mild to moderate hypertensives (8 males, 6 females, age range 40-60 years) were randomly given magnesium or placebo in a double-blind parallel clinical trial for 6 months. In the actively treated group magnesium urinary excretion increased from 5.3 +/- 2 to 7.7 +/- 2 mmol/24 h, and serum magnesium changed from 0.9 +/- 0.1 to 1.0 +/- 0.2 mmol/l. On magnesium, BP changed at rest from 156/97 +/- 12/4 to 149/90 +/- 8/3 mm Hg, during cold pressor test from 169/105 +/- 9/6 to 174/105 +/- 15/4, during isometric exercise from 170/107 +/- 13/9 to 170/105 +/- 20/6, and during tilt test from 149/96 +/- 11/6 to 153/96 +/- 17/7 mm Hg. Similar changes were observed in the placebo group. Peripheral resistances were 14.7 +/- 4 and 9.8 +/- 2 PRU before and after magnesium, respectively. These data indicate that long-term magnesium pidolate supplementation does not affect blood pressure at rest and during sympathetic stimulation, despite a slight, nonsignificant reduction in forearm peripheral resistance.

Adult↗

Prevalence of peripheral arterial disease and related risk factors in elderly institutionalized subjects.

Blood pressure was measured at the posterior tibial artery by Doppler ultrasonography in 124 elderly subjects (37 men and 87 women) living in two retirement homes in Naples (Italy). Ankle-to-arm systolic pressure ratios below 0.97 and 0.90 was considered as a probable and definite pathological sign of peripheral arterial disease, respectively. Half of the subjects (48% of men and 51% of women) gave a value below 0.97, while a third (35% of men and 33% of women) had a value below 0.90. By multiple regression analysis, mean blood pressure, plasma cholesterol levels and cigarette smoking were all negatively correlated with ankle systolic pressure values with a progressively lower significance. Most of the patients with pathological Doppler examination were asymptomatic at a questionnaire for intermittent claudication.

Age Factors↗

[Surgical day hospital: technical possibilities and organizational model].

The Authors propose an organizational model for a surgical day hospital program, which is being used for a pilot day surgery unit in the I Department of Surgery of the Rome University "La Sapienza". The program requires little capital investment, as it is closely linked, geographically and administratively, to the main surgical unit, and uses the present staff, facilities and support services. The model is based on a computerized LAN (Local Area Network), providing fast recording, scheduling, management and trannsfer of medical data for each patient. The present situation is reported in detail. Data from the authors' outpatient department for 1988, have been recorded and elaborated. The results show a low use of surgical day care, limited to minor surgical procedures, and with not a single operation performed under general anesthesia. The authors hope to see a growth in the use of day surgery and a more selective use of inpatient care.

Adolescent↗

Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure.

A double-blind phase II study of propionyl-L-carnitine (CAS 17298-37-2) versus placebo was carried out on a group of 60 patients with mild to moderate (II and III NYHA class) congestive heart failure. The group was made up of men and women aged between 48 and 73 years in chronic treatment with digitalis and diuretics for at least 3 months and who still displayed symptoms. Thirty of these patients were chosen randomly and for 180 days, 500 mg of propionyl-L-carnitine was orally administered, 3 times a day in addition to their usual treatment. At basal conditions and after 30, 90 and 180 days the maximum exercise time was evaluated using an exercise tolerance test performed on an ergometer bicycle and the left ventricular ejection fraction was tested by means of bidimensional echocardiography. After one month of treatment, the patients treated with propionyl-L-carnitine, compared to the control group, showed significant increases in the values of both tests, increases which became even more evident after 90 and 180 days. At the stated times the increases in the maximum exercise time were 16.4%, 22.9%, and 25.9%, respectively. The ventricular ejection fraction increased by 8.4%, 11.6% and 13.6%, respectively. On the basis of these results, having studied the particular mechanism of action of propionyl-L-carnitine the authors conclude that it represents a drug of undoubted therapeutic interest in patients with congestive heart failure, in whom it could be efficaciously administered along with a standard pharmacological therapy.

Aged↗

Deficits in cholinergic neurotransmission markers induced by ethylcholine mustard aziridinium (AF64A) in the rat hippocampus: sensitivity to treatment with the monoamine oxidase-B inhibitor L-deprenyl.

Assessment was made of the effects of intracerebroventricular (i.c.v.) administration of ethylcholine mustard aziridinium (AF64A) and of the monoamine oxidase (MAO)-B inhibitor L-deprenyl on the acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT), on the ACh catabolic enzyme acetylcholinesterase (AChE) and on the density of ACh muscarinic M-1 and M-2 receptor sites. In addition, the effect of AF64A and of L-deprenyl treatment on the localization of AChE activity in the CA-1 and CA-3 fields of the hippocampus was evaluated by combined enzyme histochemistry and microdensitometry techniques. I.c.v. injection of AF64A induced, 4 weeks after administration of the neurotoxin, a remarkable increase of MAO-B activity, and a significant reduction of ChAT and AChE activities in the hippocampus but not in the neostriatum which was used as a reference tissue. Hippocampal muscarinic M-1 receptors were unaffected by AF64A administration, whereas M-2 sites were reduced after neurotoxin injection. Enzyme histochemistry analysis showed that the loss of AChE induced by AF64A was more pronounced in the CA-3 than in the CA-1 field of the hippocampus. Treatment with L-deprenyl induced, from a dose of 11.17 microM/kg/day, a significant reduction of MAO-B activity in the hippocampus. The expression of ChAT and AChE, as well as the density of M-2 receptors, was increased after L-deprenyl administration in the hippocampus but not in the neostriatum. An increase in AChE reactivity was noticeable in the CA-1 and CA-3 fields of the hippocampus of AF64A-injected rats treated with L-deprenyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗