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Biomedical subjects

F Chiarotti

Publications and source records attributed to F Chiarotti.

At least 19 recordsLinked to original sources

The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenopathy: results of multivariate analysis.

BACKGROUND: The role of high resolution pulsed and color Doppler ultrasound in the differential diagnosis of benign and malignant lymphadenopathy is still unclear. METHODS: High resolution pulsed and color Doppler ultrasound was used prospectively to investigate superficial lymph node enlargement in 71 patients undergoing surgical biopsy at the onset of lymphadenopathy. The aim of this study was to define, in multivariate analysis, the ultrasonographic parameters useful in the differential diagnosis of benign and malignant lymphadenopathy. RESULTS: Volume, vascularization score, pulsatility index, and resistive index were significantly higher in the 53 malignant lymph nodes studied than in the 18 benign lymph nodes studied. The long-to-short axis ratio was significantly lower in neoplastic lymph nodes than in reactive lymph nodes. Stepwise logistic regression selected only the long-to-short axis ratio and the vascularization score as parameters that independently and significantly contributed to the differentiation of neoplastic from reactive lymph nodes. The diagnostic efficiency of the combined criteria evaluated by the area under the receiver operating characteristic curve was 0.8339. CONCLUSIONS: High resolution pulsed and color Doppler ultrasound may provide information that is useful in making correct differential diagnoses of malignant or benign lymphadenopathy.

Adolescent

Serum phospholipids are the main environmental determinants of activated factor VII in the most common FVII genotype. European Union Concerted Action "Clotart".

BACKGROUND AND OBJECTIVE: Numerous studies have emphasized the role of triglyceride-rich lipoproteins and of Factor VII (FVII) polymorphisms in determining levels of FVII activity. DESIGN AND METHODS: This study was undertaken to evaluate the role of other lipid fractions and the interaction between lipids and FVII in subjects with recognised genotypes. Volunteer subjects (n=459) from 5 European countries were studied. Blood samples were drawn irrespective of the time of day or fasting status. Levels of FVII activity (FVIIc), activated FVII (FVIIa) and FVII antigen (FVIIAg) were evaluated with reference to a number of lipid parameters (HDL-, LDL- and total cholesterol, triglycerides, phospholipids, lipoprotein(a), and apoliproptein A1). The two most common FVII polymorphisms were analyzed in combination (353R/Q and 5'F7; alleles M1/M2 and A1/A2, respectively). RESULTS: Homozygotes for the A1 and M1 alleles (M11/A11) had significantly higher FVII levels. At multiple regression analysis the strongest predictor of FVIIa and FVIIc was the concentration of phospholipids. This interaction was confined to the A11M11 genotype subjects. INTERPRETATION AND CONCLUSIONS: These data indicate that lipids contribute mainly to FVIIa levels through their phospholipid content, and that the degree of this contribution is strictly dependent on FVII genotypes.

Adult

Determination of antibodies to extractable nuclear antigens by commercial kits: a multicenter study.

Several enzyme immunoassays for serum antibodies to extractable nuclear antigen have recently become available. The aim of this study was to evaluate the results obtained with: (1) the same kit under different conditions; (2) different enzyme immunoassays; (3) Western blot and enzyme immunoassays. Twenty-five sera from patients with autoimmune disorders were tested in five different laboratories by one Western blot and four enzyme immunoassay commercial kits. The different methods produced comparable qualitative results. However, semiquantitative evaluation, based on a cut-off value (index), yielded different results due both to laboratory conditions and to the kits employed. Standardization of commercial products and methods should be improved so that the results of different laboratories can be compared and large-scale and follow-up studies conducted. Western blot analysis could also be useful to analyze complex reactivities, although greater experience is necessary to interpret these results correctly.

Antibodies, Antinuclear

Subclinical visual impairment in phenylketonuria. A neurophysiological study (VEP-P) with clinical, biochemical, and neuroradiological (MRI) correlations.

During detailed visual function testing, pattern-reversal visual evoked potentials (VEP), generated by different spatial frequencies (3 c/d, 1 c/d and 0.6 c/d) and visual contrasts (100% and 10%) were recorded in 21 adolescent and young adult phenylketonuric (PKU) patients (11 females and 10 males; mean age 14.8 years, range 9-22.8) on and off diet. In 14 of the 21 patients, disease had been detected at neonatal screening and in 7 later. Ten age-matched healthy subjects acted as controls. Recordings in more than 40% of eyes in the whole group and 30% of eyes in the screening subgroup showed a prolonged P100 latency. All visual pattern stimuli elicited a significantly longer P100 latency in PKU patients than in controls. VEP latencies to 3 c/d, 1 c/d and 1 c/d with 10% contrast--but not to 0.6 c/d--were longer in patients off diet than in patients on diet. No differences were found between VEP latencies in early- and later-detected subjects. To study the link between biochemical variables and VEP latencies, we envisaged either a linear relationship between recent exposure to phenylalanine (Phe) and VEP abnormalities or a threshold model considering phenylalanine (Phe) concentrations among the factors influencing VEP latencies. The correlation analysis detected an association between plasma Phe concentrations and abnormal VEP latencies, predicting that plasma Phe concentrations > 901 mumol/L would prolong VEP latencies to 1 c/d; concentrations > 879 mumol/L would prolong latencies to 3 c/d; and concentrations > 898 mumol/L would prolong latencies to 1 c/d with 10% contrast.

Adolescent

Elevated novelty seeking and peculiar d-amphetamine sensitization in periadolescent mice compared with adult mice.

Novelty seeking as well as amphetamine sensitization were studied in adult (postnatal day "PND" > 60) and periadolescent (PND 3343) mice treated with saline or amphetamine (2 or 10 mg/kg once per day) for 3 days in a familiar environment. After a 48-hr wash-out period, mice were challenged with either saline or amphetamine (2 mg/kg) in the same environment. When given a choice, animals showed a preference for a novel environment, an effect more marked in periadolescents. Acute amphetamine strongly increased novelty seeking in adults, whereas it had an opposite effect in periadolescents. Adult mice in the chronic amphetamine 2 group showed a conditioned preference for the drug-paired compartment, whereas an aversion characterized adult mice in the amphetamine 10 group. Periadolescents in the latter group exhibited a greater sensitization of the locomotor response, but did not show the compulsive licking typical of adults. This appears to be a useful model to study psychobiological risk factors involved in vulnerability to addiction during human adolescence.

Aging

Behavioural characterization of interleukin-6 overexpressing or deficient mice during agonistic encounters.

Interleukin-6 (IL-6) is a cytokine released by activated immune cells which has been shown to affect brain function. In this experiment aggressive and affiliative behaviour exhibited during agonistic encounters by transgenic male mice either not expressing (IL-6 -/-) or overexpressing (NSE-hIL-6) IL-6 in the central nervous system was investigated. All subjects were isolated for 24 days before the aggressive encounter and were 52 days old at the time of testing. Subjects were placed for 5 consecutive days in a neutral cage for 15 min with an opponent of the Balb/c strain that had been previously isolated for the same amount of time. The first and the last test sessions were videotaped to evaluate the first approach and the establishment of the social role, respectively. A number of behavioural categories were later scored. When compared with wild-type controls, IL-6 -/- mice showed a higher degree of aggressive behaviour as indicated by a higher frequency of Offensive Upright Posture, an effect more pronounced on the fifth encounter. On the contrary, NSE-hIL-6 subjects showed a tendency to be more involved in affiliative-type social interactions, displaying a higher frequency and duration of behaviours such as Anogenital, Nose or Body Sniff. IL-6 -/- mice showed a clear tendency to exhibit less affiliative interactions compared with their controls while dopamine levels were found to be modified in a number of brain regions in these mice. Overall, these data suggest that IL-6 affects both aggressive and affiliative-type interactions, although the behaviour of the NSE-hIL-6 subjects was less affected than that of the IL-6 -/- group. The effects of the genetic background of the animal in screening the outcome of gene manipulations on behaviour are also discussed.

3,4-Dihydroxyphenylacetic Acid

Sensitivity and specificity of some neuropsychological markers of Alzheimer dementia.

A standardized neuropsychological test battery was administered to 167 patients with different forms of mild-to-moderate dementia: probable Alzheimer dementia (AD: n = 49), multi-infarct dementia (n = 43), idiopathic Parkinson disease with dementia (n = 35), depressive pseudodementia (n = 26), and progressive supranuclear palsy (n = 14). Results obtained were used (a) to analyze the profiles of cognitive impairment shown by the different dementia groups; (b) to assess the incidence of some neuropsychological patterns that we hypothesized to be more characteristic of AD, in the various groups; and hence (c) to evaluate the reliability of these patterns as diagnostic markers of AD. Four of the patterns investigated were derived from a verbal learning task (Rey's Auditory Verbal Learning test): (1) absence of the primacy effect; (2) tendency to produce intrusion errors during free recall of a word list; (3) absolute decay of memory trace; and (4) tendency to produce false alarms during delayed recognition of the same word list. Two additional patterns were derived from visual-spatial tasks (copying drawings and Raven's Coloured Progressive Matrices): (5) occurrence of the closing-in phenomenon in copying drawings; and (6) tendency to choose globalistic or odd responses in Raven's matrices. Though all the six patterns were somewhat useful for identifying AD patients, no pattern met the criteria of being both highly sensitive and highly specific, which should characterize an ideal marker. In fact, intrusions and false alarms were observed in many AD patients, but also in patients affected by other forms of dementia. The absence of the primacy effect, the closing-in phenomenon, and the absolute decay of memory trace were more specific, but could be observed in only one-third of AD patients. We also computed the number of positive patterns shown by each patient and assumed the presence of two or more patterns as a global index suggestive of a dementia of the Alzheimer type. With this cumulative method, a higher level of sensitivity and specificity was achieved in the identification of AD patients.

Aged

Collateral flow prevents unintentional myocardial ischemia during antegrade cardioplegia in patients undergoing coronary artery bypass grafting.

OBJECTIVE: We evaluated, in the prevention of perioperative unintentional myocardial ischemia, the role of coronary collateral flow in patients with left anterior descending coronary artery stenosis or occlusion who underwent elective coronary artery bypass grafting. METHODS: Coronary lesions and collaterals were assessed by coronary angiography in 21 patients. Anteroseptal myocardial viability was evaluated by dobutamine echocardiography. Antegrade perfusion of cardioplegic solution was assessed by myocardial contrast echocardiography. Time-intensity curves were generated from the anteroseptal region. Twelve parameters were measured and averaged in the following four groups of patients: those with stenosis of the left anterior descending artery and poor collaterals; those with stenosis of the left anterior descending artery and good collaterals; those with occlusion of the left anterior descending artery and good collaterals; and those with occlusion of the left anterior descending artery and poor collaterals. RESULTS: Time-intensity curves were significantly different in patients with stenosis versus occlusion of the left anterior descending artery (p < 0.005); multiple comparisons with Bonferroni's correction showed that this difference was mainly a result of the impact of collateral circulation (p < 0.01). However, the role of collaterals was nonsignificant within the groups with stenosis and occlusion of the left anterior descending artery. Patients with occlusion of the left anterior descending artery and good collaterals had perfusion parameters similar to those of patients with stenosis of the left anterior descending artery (p = not significant), except for the ascending slope and time to peak values (p < 0.05 and p < 0.01, respectively), which reflected a higher flow resistance in the collateral circulation. Regional systolic function after coronary artery bypass grafting was depressed in patients with poor collaterals and poor perfusion of cardioplegic solution, as compared with findings in other subgroups. CONCLUSIONS: Incomplete myocardial protection may impair the early recovery of function after coronary artery bypass grafting.

Cell Survival

Contribution of factor VII genotype to activated FVII levels. Differences in genotype frequencies between northern and southern European populations.

The relationship between coagulation factor VII (FVII) levels in plasma and FVII genotypes, determined by three polymorphisms (5'F7, IVS7, and 353R/Q), were studied in 500 control subjects enrolled in European multicenter study. The selection of particular FVII genotypes and the analysis of variance clearly indicated the independent contribution of a single 5'F7 insertion (A2) or 353Q (M2) allele to lowering plasma levels of activated FVII (FVIIa) (by a mean 25%). The M2 allele alone was found to make a major contribution to the genetically determined component of the FVIIa levels. Genotypes associated with low FVII levels were significantly rarer in the northern part of Europe (Oslo) than in the southern part (Rome, Murcia). The contribution made by the FVII genotype to the total variance of FVIIa levels was higher (30%) than that made to either FVII activity (25%) or FVII antigen (12%). Subjects with different FVII genotypes showed up to fivefold differences in mean FVIIa values, thus allowing attribution of a substantial part of the considerable interindividual variation to genetic variation, which may be of assistance in the interpretation of FVIIa levels on an individual basis. When FVII levels were adjusted by age and by triglyceride levels, the contribution of FVII genotypes to the FVII phenotypic variance was virtually unchanged. Taken together, these data indicate that in healthy control subjects the FVII genotype is a major predictor of plasma FVIIa levels and would support further study on the role of FVII genetic components in the development of cardiovascular disease.

Adult

Behavioural disturbances in adult CD-1 mice and absence of effects on their offspring upon SO2 exposure.

Adult male and female CD-1 mice were exposed to different SO2 concentrations (0,5,12, or 30 ppm) for 24 days, from 9 days before the formation of breeding pairs to pregnancy day 12-14. This exposure was near-continuous, covering about 80% of the total time indicated. The offspring of exposed dams were cross-fostered shortly after birth to dams not previously exposed. Videorecordings of the adult subjects' activities during the first hour after the start of exposure showed marked, acute transient behavioural effects such as increase of rearing and social interactions, which were more pronounced in males than in females. Subsequent activity tests on exposure days 3, 6, and 9 showed subacute effects including a dose-dependent decrease of grooming and an increase of digging as well as changes in chamber crossing and wall-rearing which were not dose-dependent; most of these effects were more pronounced in females than in males. Food and water consumption and body weight declined in a dose-dependent fashion only after the formation of breeding pairs, when consummatory responses were enhanced in the controls. Reproductive performance as well as postnatal somatic and neurobehavioural development of the offspring (the latter assessed by an observational test battery including eight reflexes and responses) were not affected by SO2. Passive avoidance acquisition and retention at the young adult stage (60 days) and response changes produced by repeated apparatus exposure in non-reinforced animals (habituation) were similarly unaffected. Overall, the data indicate that SO2 produces transient, acute behavioural disturbances and more subtle subacute response changes in adult mice which may be due, at least partly, to a functional interference with olfactory modulation of mouse behaviour. The absence of effects on reproductive performance and neurobehavioural development of the offspring suggests that the risk to the developing organism from gestational SO2 exposure is low.

Animals

Nerve growth factor affects passive avoidance learning and retention in developing mice.

The present studies investigate the effects of early nerve growth factor (NGF) administration on the ontogenetic profile of learning and retention capacities in mice. The learning paradigm used required the animals to withhold an escape response from a vibrating platform to avoid a punishment (step-down passive avoidance). In Experiment 1, acquisition of step-down passive avoidance was essentially the same in 11- and 15-day-old mice whereas only the latter showed significant retention after 24 h. In younger animals, data pointed to a facilitating effect of familiarization with the test environment. In Experiment 2 ICV NGF treatment on postnatal day 9 increased step-down latencies in both reinforced and nonreinforced pups on day 11. Moreover, NGF mice exposed in nonreinforcement condition on day 11 failed to acquire the avoidance response 24 h later, suggesting that the treatment anticipated the appearance of latent inhibition. Results of Experiment 3, investigating the effects of different durations of preexposure to the test apparatus on passive avoidance acquisition 24 h later, supported the specificity of NGF effects on the emergence of latent inhibition. These findings suggest that neural populations responsive to NGF trophic effect are involved in the maturation of early learning and retention capacities in rodents.

Animals

Primary repair of coarctation of the thoracic aorta by patch graft aortoplasty. A three-decade experience and follow-up in 60 patients.

OBJECTIVES: The present report is a critical review on primary repair of aortic coarctation by patch aortoplasty on the basis of over 30 years surgical experience. METHODS: Since 1962, 60 patients (mean age 9.4 +/- 4.8 years, range 2-25 years), affected by aortic coarctation, underwent patch aortoplasty repair. During the operation protective guidelines were adopted: additional external Dacron was placed around the repaired site in cases of friable host tissue, the aortic ridge was not excised to leave the posterior aortic wall intact, and the patent ductus arteriosus or ligamentum arteriosum was transected and sutured. Prophylactic measures of neurologic sequelae were: dual pressure monitoring, sequential aortic clamping, surgical shunt or left heart bypass associated with moderate hypothermia when the distal aortic pressure was less than 50 mmHg. RESULTS: No early deaths occurred. The overall survival rate was 92.77 +/- 4.04% at 31 years from surgery. Three late deaths occurred. Pressure gradients across the patch ranged between 9 and 20 mmHg. Late aneurysm occurred in one patient (1.3%), 2 years after bacterial endocarditis had developed on a biscuspid aortic valve. CONCLUSIONS: Patch aortoplasty is an effective and safe surgical procedure for primary repair of isthmic aortic coarctation when other surgical techniques cannot be performed.

Adolescent

Patent foramen ovale and transcranial Doppler. Comparison of different procedures.

BACKGROUND AND PURPOSE: The capability of transcranial Doppler sonography (TCD) to detect a patent foramen ovale (PFO) has been established. However, which provocative maneuver and what timing of contrast injection are most effective to induce a right-to-left shunt has not yet been determined. METHODS: We selected 38 cerebrovascular patients (21 men, 17 women) with positive contrast study for PFO on transesophageal echocardiography. Patients underwent a TCD with bilateral monitoring of the middle cerebral arteries (MCAs) and injection of a contrast solution. The injection was repeated (1) during normal breathing (basal conditions); (2) before Valsalva maneuver (VM); (3) during VM; (4) immediately after VM; and (5) during cough. The latency time and the total number of microbubbles for each side were recorded. RESULTS: TCD found positive results for PFO in 30 patients. Twenty were positive even during basal conditions. The number of positive cases varied according to the timing of the VM in relation to the contrast injection: 28, 25, and 27 cases were positive when the injection was performed before, during, and after VM, respectively, while 26 were positive during cough. There were significant differences in the number of microbubbles in the MCAs between the procedures (P < .001, ANOVA): the highest number was detected in the injection before VM and the lowest number during basal conditions (P < .001, Wilcoxon's test with Bonferroni's correction). The latency time was significantly shorter when the injection followed VM. CONCLUSIONS: The injection performed before VM appeared to be the most effective TCD procedure in determining the transit of microbubbles through a PFO and subsequently in the MCAs.

Adult

Factor VII gene polymorphisms contribute about one third of the factor VII level variation in plasma.

To assess the role of genetic variation in determining factor VII (FVII) activity and antigen levels we studied a polymorphism located in the 5' region of the gene (5'F7), an intronic mutation (IVS7), and the 353Arg-Gln polymorphism. All the polymorphisms, which showed strong allelic association, analyzed separately or in combination by the one-way analysis of variance, were associated with significantly different FVII levels. The 5'F7 and 353Arg-Gln polymorphic systems, which have very similar allele frequencies, contributed to a similar extent to the total phenotypic variance, whereas the contribution of the IVS7 polymorphism was lower. Genetic variation at the FVII locus, evaluated on combined genotypes, accounted for up to 40% of the phenotype FVII variance. As also shown by the two-way analysis of variance, the use of two out of three markers is advisable, and since the 5'F7 polymorphism can be screened by a simple immunoassay, it should be preferred for population-based studies. No substantial differences between FVII activity and FVII antigen levels were found, thus suggesting that the variation was due to biosynthesis- or stability-mediated mechanisms. The genetic control of FVII levels described in this study plays an important role in determining plasma FVII level variability, which may influence the hemostatic balance.

Adolescent

CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme immunoassay.

Assessment of the CD4 lymphocyte number, currently performed by flow cytometry, is one of the main laboratory tests for establishing progression to acquired immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been commercialized which can be very useful for counting CD4 cells in laboratories where flow cytometers are not available. In the present study, a comparative evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001), and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05, not significant). Some differences could be found at low CD4 lymphocyte levels since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the whole blood sample could cause overestimation of CD4 cell numbers by the enzyme assay.

Acquired Immunodeficiency Syndrome

Limited changes of mouse maternal care after prenatal oxazepam: dissociation from pup-related stimulus perception.

There is evidence that activity at the GABA/benzodiazepine receptor complex in specific brain areas might be enhanced during rodent motherhood. We tested the hypothesis that the manipulation of this neurochemical system by prenatal benzodiazepine exposure affects typical behavioral responses of lactating mouse dams. Outbred CD-1 mouse fetuses were administered either oxazepam (OX, 15 mg/kg) or vehicle twice a day on embryonic days 12-16 and fostered at birth to untreated dams. Female offspring were subsequently mated at the young adult stage. In a first experiment, the behavioural repertoire of the two groups of lactating females was scored (single 10-min session) from postpartum days 3 to 18. When compared with VEH dams, OX females showed a shorter duration of pup-sniffing at 7-10 days and enhanced crouching behaviour when pups had reached the age of 14-18 days. In addition, OX-treated dams used more cotton for nest construction than the controls. The two female groups were differentiated only in the presence of their offspring. In a second experiment aimed at investigating possible OX-induced changes in pup-stimulus perception, the same lactating females were challenged in sequence on postpartum day 8 with three different patterns of pup-related cues consisting of: three 8-day-old live male pups (LP), three same-age dead pups DP, or three dead pups accompanied by pre-recorded ultrasounds (DPU). In the absence of carry-over effects of prenatal dam treatment, LP stimuli elicited a higher frequency of sniffing and digging than the others, whereas the level of licking, and grooming was reduced. In conclusion, the present results indicate that the slight alteration in maternal care resulting from prenatal OX treatment can be dissociated from changes in pup-related stimulus perception.

Animals