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Biomedical subjects

F Bernardi

Publications and source records attributed to F Bernardi.

At least 37 records · Page 2Linked to original sources
PubMed2003

Venous thromboembolism, oral contraceptives and high prothrombin levels.

The G20210A prothrombin mutation, associated with elevated prothrombin levels, is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). No data are available on VTE risk of OC use in women with high prothrombin levels, either associated or not with the mutation. The aim of this study was to evaluate the risk of VTE in OC users with high prothrombin levels, either including or excluding carriers of the prothrombin mutation. Prothrombin levels were measured by a chromogenic assay in 152 women who suffered from VTE in reproductive age and in 296 healthy women. Subjects carrying thrombophilic alterations other than the G20210A prothrombin mutation were excluded. Prothrombin levels were stratified into quartiles. The OR of subjects in the upper quartile were 3.10 [95% confidence interval (CI) 1.73-5.55] and 2.07 (95% CI 1.11-3.85) in all women and in those not carrying the prothrombin mutation, respectively. Among the 152 patients, 88 had experienced VTE during OC; in the control group we considered as OC users the women who had used OC for at least 6 months in the 2 years before presentation but had stopped the treatment at least 3 months before the time of blood sampling (n = 127). For the interaction between OC and prothrombin levels only the two extreme strata of prothrombin were considered. Women with the lowest prothrombin levels and who did not use OC were used as reference category. The VTE risk of using OC in subjects with prothrombin levels in the upper quartile was increased 5.4-fold (95% CI 2.38-12.3) and 3.5-fold (95% CI 1.48-8.22) in all women and in those not carrying the prothrombin mutation, respectively. We conclude that elevated prothrombin levels, even in women without the G20210A prothrombin mutation, are associated with an increased risk for venous thromboembolism and that oral contraceptive use potentiates such association.

Adolescent↗
PubMed2003

Thrombosis in inherited factor VII deficiency.

Thrombosis in congenital factor (F) VII deficiency was investigated through extensive phenotypic and molecular-genetic studies. Patients with a history of thrombosis among 514 entries in the FVII Deficiency Study Group database were evaluated. Thrombotic events were arterial in one case, disseminated intravascular coagulation in another and venous in seven. Gene mutations were characterized in eight patients: three were homozygous, three compound heterozygous and two heterozygous. FXa and IIa generation assays were consistent with the genetic lesions. One patient was heterozygous for the FV Leiden and one for the FIIG20210A mutation. In seven patients, surgical interventions and/or replacement therapies had a close temporal relationship with thrombosis, while in the remaining, events were apparently spontaneous. Thromboses were not associated with any specific age, phenotype, mutation zygosity or thrombophilic abnormalities. In particular, severe FVII deficiency did not seem to offer protection from strong thrombosis risk factors such as surgery and replacement therapy.

Adolescent↗
PubMed2003

CNS: sex steroids and SERMs.

The central nervous system (CNS) is one of the main target tissues for sex steroid hormones, which act both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through nongenomic mechanisms, influencing electrical excitability, synaptic function, and morphological features. The identification of the brain as a de novo source of neurosteroids modulating cerebral function, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women could also be related to a modification in the levels of neurosteroids, particularly allopregnanolone and DHEA, GABA-A agonist, and antagonist, respectively. The selective estrogen receptor modulators (SERMs) are compounds that activate the estrogen receptors with different estrogenic and antiestrogenic tissue-specific effects. In addition to the effects of the classic steroid hormones on the CNS, the study of selective estrogen receptor modulators impact on the neuroendocrine system has recently provided encouraging results, indicating that raloxifene analog LY 117018 and the new generation SERM EM-652 have an estrogen-like action on beta-endorphin and on allopregnanolone in ovariectomized rats, while they exert an anti-estrogenic effect in fertile rats and in ovariectomized rats treated with estrogens. In addition, raloxifene administration in postmenopausal women plays an estrogen-like effect on circulating beta-EP and allopregnanolone levels, and it restores the response of beta-EP and allopregnanolone to neuroendocrine tests. In conclusion, the positive effects of HRT on mood and cognition in postmenopausal women occur via the modulation of neuroendocrine pathways and probably also of neurosteroidogenesis. The effects of raloxifene on mood and cognition encourage the efforts in the research of an ideal estrogen replacement therapy, showing all the positive effects of estrogens and fewer side effects.

Aged↗
PubMed2003

Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women.

The effects of hormone replacement therapy (HRT) on the central nervous system in postmenopausal women might be mediated by changes in neurosteroid synthesis and/or release. The aim of this study was to evaluate the impact of HRT on the levels of allopregnanolone, a sedative anxiolytic GABA(A) agonist steroid, and dehydroepiandrosterone (DHEA), a GABA(A) antagonist steroid. We evaluated allopregnanolone and DHEA circulating levels after 1, 3, 6, 9 and 12 months of HRT with ten different estrogen or estrogen-progestin molecules, regimens and routes of administration in 186 postmenopausal women. Cortisol, luteinizing hormone, follicle stimulating hormone, estradiol and progesterone levels were also evaluated. Allopregnanolone levels significantly increased during follow-up with all HRT preparations. The addition of progestin molecules (except for 19-nor derivatives) to transdermal estradiol administration alone determined a higher increase in allopregnanolone levels. Transdermal HRT showed a significantly higher percentage change in allopregnanolone levels compared with oral HRT. DHEA levels showed a progressive decline starting from the 3-month follow-up, without significant differences between the transdermal and oral groups, as well as among the ten groups, independently of the presence and type of progestin molecule used. In conclusion, HRT strongly modifies circulating neurosteroid levels in postmenopausal women.

Administration, Cutaneous↗
PubMed2002

Genealogical analyses of rabies virus strains from Brazil based on N gene alleles.

Thirty rabies virus isolates from cows and vampire bats from different regions of São Paulo State, Southeastern Brazil and three rabies vaccines were studied genetically. The analysis was based on direct sequencing of PCR-amplified products of 600 nucleotides coding for the amino terminus of nucleoprotein gene. The sequences were checked to verify their genealogical and evolutionary relationships and possible implication for health programmes. Statistical data indicated that there were no significant genetic differences between samples isolated from distinct hosts, from different geographical regions and between samples collected in the last two decades. According to the HKA test, the variability observed in the sequences is probably due to genetic drift. Since changes in genetic material may produce modifications in the protein responsible for immunogenicity of virus, which may eventually cause vaccine failure in herds, we suggest that continuous efforts in monitoring genetic diversity in rabies virus field strains, in relation to vaccine strains, must be conducted.

Animals↗
PubMed2002

Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use.

AIMS: The interaction between the R506Q mutation of factor V and the G20210A mutation of prothrombin with oral contraceptives on venous thromboembolism was evaluated. METHODS AND RESULTS: Three hundred and one women of reproductive age who had venous thromboembolism (140 while using oral contraceptives) and 650 healthy women (173 on oral contraceptives at presentation) were examined. Of the patients, 19.3% were carriers of R506Q (two homozygotes) and 9.6% were heterozygous carriers of G20210A; eight patients (2.7%) were heterozygous for both mutations. Among controls, 2.9% were carriers of R506Q, 3.1% of G20210A, while one case was a heterozygous carrier of both mutations. The relative risk (odds ratio) associated with carriership of R506Q or G20210A mutations was 10.3 and 4.7, respectively; it was 45.6 in carriers of both mutations. The odds ratio of using oral contraceptives in the absence of both mutations was 2.4. The odds ratios according to oral contraceptives use and the presence of R506Q or G20210A or both mutations were 41.0, 58.6 and 86.5, respectively. While the odds ratio for R506Q remains elevated (8.9) in non-oral contraceptive users, the odds ratio for G20210A was 2.0 and did not reach statistical significance. CONCLUSIONS: Our data showed a strong interaction between oral contraceptive use and the presence of either R506Q or G20210A mutations. In non-oral contraceptive users the risk of venous thromboembolism was significantly increased in carriers of R506Q but not in those with the G20210A mutation.

Adolescent↗
PubMed2002

A heminested polymerase chain reaction for the detection of Brazilian rabies isolates from vampire bats and herbivores.

A heminested-PCR (hn-PCR) using primers to the nucleoprotein-coding gene in a nested set was evaluated in the detection of Brazilian strains of rabies virus (RV). A representative number of RV nucleoprotein sequences belonging to genotype 1 were aligned. Based on such alignment, primers were directed to highly conserved regions. All 42 clinical samples positive by both fluorescent antibody and mouse inoculation tests were also positive by the hn-PCR. Brain tissue that had been left to decompose, obtained from an experimentally inoculated mouse was tested by hn-PCR and yielded positive results. In conclusion, primers designed here were capable of amplifying Brazilian RV isolates obtained from a rural epidemiological cycle.

Animals↗
PubMed2002

Enamel matrix proteins and guided tissue regeneration with titanium-reinforced expanded polytetrafluoroethylene membranes in the treatment of infrabony defects: a comparative controlled clinical trial.

BACKGROUND: Several studies have documented the clinical efficacy of guided tissue regeneration (GTR) with non-resorbable expanded polytetrafluoroethylene (ePTFE) membranes and enamel matrix proteins (EMP) in the treatment of infrabony defects. The objective of this controlled clinical study was to compare the clinical outcomes of 3 surgical modalities in the treatment of deep interproximal infrabony defects. METHODS: Ninety (90) defects in 90 healthy subjects affected by chronic periodontitis were assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with the application of EMP and the simplified papilla preservation (SPP) technique; the second group was treated with titanium-reinforced ePFTE membranes and the SPP technique; and the third group was treated with the SPP technique used as access flap control procedure. No differences were observed in terms of baseline oral hygiene and defect characteristics among the 3 groups, indicating that the blocking approach was effective. A stringent infection control program was adopted for 1 year. RESULTS: The 1-year results indicated that: 1) all treatment modalities resulted in clinically significant improvements in clinical attachment levels (CAL) and reduction in probing depth (PD); 2) a statistically significant treatment effect was demonstrated comparing the EMP test, the membrane control, and the flap control groups in terms of CAL gains; 3) both the EMP test and the membrane control groups showed significant CAL gains compared to the flap control group; 4) a statistically significantly greater amount of CAL gain was demonstrated in GTR-treated compared to EMP-treated patients; 5) deeper residual probing depths but smaller increases in gingival recession were demonstrated following EMP therapy; and 6) smoking habits reduced the clinical outcomes of both regenerative procedures. CONCLUSIONS: The use of a regenerative procedure is indicated in the treatment of deep vertical bony defects since both the regenerative techniques (GTR and EMD) in the present study resulted in clinically and statistically significant improvements in clinical parameters compared to the access flap procedure. The use of EMP can be helpful in esthetically-sensitive sites and in reducing patient morbidity.

Adult↗
PubMed2002

Reduced activation of the Gla19Ala FX variant via the extrinsic coagulation pathway results in symptomatic CRMred FX deficiency.

We characterized a symptomatic CRMred factor X (FX) deficiency produced by the Glu19Ala mutation in the gamma-carboxyglutamic-rich domain. FX activity levels in plasma were markedly reduced in prothrombin time assays (< 1-5%), whereas in activated partial thromboplastin assays (16%) and in RVV assays (17%) the reduction in activity mirrored that in antigen levels (17%). Activation of recombinant 19Ala-FX by factor IXa/factor VIIIa or RVV, and the activity in thrombin generation assays, were comparable to those of wild-type FX. Differently, complete activation of recombinant 19Ala-FX required a factor VIIa/TF concentration 30-fold higher than that of wild-type FX. The recombinant FVIIa significantly reduced PT values in 19Ala-FX reconstituted plasma, thus suggesting an alternative approach for treatment of FX deficiencies characterized by defective FX activation. The study of this FX deficiency provides an "in vivo" and "in vitro" model for the investigation of Gla domain interactions.

Blood Coagulation↗
PubMed2002

Estrogen effects on neuroendocrine function: the new challenge of pulsed therapy.

A growing body of evidence shows a beneficial effect of hormone replacement therapy (HRT) on climacteric symptoms, well-being, and prevention of long-term consequences of estrogen deprivation. Nevertheless, only a relatively small number of women are users, and the mean duration of treatment is only about 18-24 months. This evident reluctance to prescribe and use HRT, so-called poor compliance, is without doubt not only due to a misunderstanding of the beneficial effects of HRT but also (and mainly) due to a discordance between expectations and treatment available. In order to improve compliance and to meet the expectations of physicians and patients, there is a need for a new treatment. This new treatment has to be effective, better tolerated, reassuring for physicians and women, convenient, easy to prescribe, easy to use and also feminine. 17beta-Estradiol remains the only natural estrogen available. It is almost identical to that secreted by the ovaries, is effective on all the consequences of estrogen deprivation, and is obviously the one to choose. Research on the intimate intracellular mode of action of estrogen is progressing on a daily basis. Today, we know that there are different estrogen receptor isoforms, that the distribution of these receptors is not uniform among the tissues, and that there are different mechanisms of action: genomic and non-genomic, with rapid (seconds or minutes) or delayed (hours or days) effects. Natural hormonal stimulation of target tissues is not a continuous event over the day. Up to now, all available forms of estrogen stimulate target cells in a continuous fashion over the day and might lead to unsatisfactory reactions. Aerodiol, the first-ever pulsed estrogen therapy with its specific mode of action, a brief stimulation of estrogen receptors made possible by its unique pharmacokinetic profile and its innovative route of administration, represents a new approach in the field of HRT. Aerodiol is not only a new route of administration but really a new way to treat hormone deficiency. Data collected during phase-3 studies provide evidence that Aerodiol is at least as effective as continuous therapy such as with oral and transdermal estrogens, is better tolerated gynecologically, and may be safer. If we consider that improvement in compliance is the key issue of HRT, we have to consider women as decision-makers in this process and we have to provide them with something that meets their expectations. With two out of three women (66%) choosing Aerodiol to continue their treatment for 1 year and 85% of women continuing their treatment after 1 year, Aerodiol goes at least some way to meeting these.

Administration, Cutaneous↗
PubMed2001

The heterozygous 20210 G/A genotype prevalence in patients affected by central and branch retinal vein occlusion: a pilot study.

BACKGROUND: Several inherited conditions have been associated with an increased or decreased incidence of retinal vein occlusion (RVO). The A allele in the 20210 G/A prothrombin gene has been found to be associated with systemic venous thrombosis. The aim of this study has been to verify the prevalence of this mutation in patients affected by central RVO (CRVO) or branch RVO (BRVO). METHODS: A retrospective study was carried out on 100 consecutive patients suffering from RVO, more than 50 years old, unaffected by systemic diseases known to be associated with markedly increased RVO occurrence. We determined the frequency of this mutation by performing mutagenised amplification of exon 14 followed by restriction analysis of the amplified DNA fragment. RESULTS: The overall frequency of prothrombin 20210A allele in RVO patients was 6.0%. All heterozygous patients had suffered from CRVO. In this study subgroup, the frequency of the 20210 G/A prothrombin heterozygosis was 12.0%. The difference in the frequency of this the genetic variant between the CRVO and BRVO groups was statistically significant. None of the conventional RVO risk factors were statistically related to the occurrence of the disease in either the CRVO or the BRVO subgroup. CONCLUSION: The prevalence of the prothrombin 20210A mutation observed in CRVO patients is significantly higher than in the normal Italian population. Moreover, the prevalence is significantly greater in CRVO than in BRVO patients. These results raise the possibility that the prothrombin 20210A variant may be considered as a risk factor for CRVO.

Aged↗
PubMed2001

Effect of compliant intermediate airways on total respiratory resistance and elastance in mechanical ventilation.

Total respiratory resistance and elastance were estimated off-line in a sample of 60 patients undergoing mechanical ventilation by means of two regression models in order to analyse and understand a possible physiological mechanism determining differences in inspiration and expiration. The first model considered a single value for resistance and elastance over a whole breathing cycle, whereas the second model considered separate values for inspiratory and expiratory resistance and a single value for elastance. Inspiratory resistance was found to be lower than expiratory resistance, and intermediate values were obtained for resistance estimated over the whole breathing cycle. Student's t-test showed a highly significant difference between these resistance estimates, and principal components analysis demonstrated a significant increase in information when both inspiratory and expiratory resistances were used. Minor differences were found between values of elastance calculated with the two approaches. In an attempt to interpret these experimental results, a lung model incorporating the non-linear viscoelastic properties of the intermediate airways was considered. This model suggested that changes in intermediate airway volume play a significant role in breathing mechanics during artificial ventilation and indicated that inspiratory and expiratory resistance could be useful parameters for locating airway obstruction.

Airway Resistance↗
PubMed2001

Self-preventive oral behavior in an Italian university student population.

BACKGROUND/AIM: The aim of this study was to assess the oral hygiene attitude and the professional preventive examination compliance in Italian university students. METHOD: A sample of 202 students attending the University of Bologna was randomly selected and interviewed about their preventive oral health attitude and compliance. All students reported using toothpaste and most of them (92.1%) brushed their teeth at least 2x a day using artificial, medium stiffness bristles. The toothbrush was generally (81.6%) replaced within 3 months. Few subjects (14.9%) said they used dental floss daily or utilized other devices. A majority of subjects (59.9%) had a dental examination within the year previous to the interview. Cluster analysis was performed. RESULTS: 4 groups were identified with homogeneous oral hygiene behavior and compliance toward professional preventive examination. Only one cluster, representing 33.6% of the sample, showed consistent frequency and modalities of oral hygiene habits. The other clusters seemed to be defective with interproximal cleaning procedures and compliance toward professional preventive care. Since the sample was characterized by a young, urbanized, homogeneous group with a high educational level and frequently from an upper middle class social status, the analysis probably gives a supra-estimation of the positive behavior. CONCLUSION: It is rational to suppose that strategies to promote dental service utilization, patients' compliance and a professional style oriented toward prevention may be useful to improve the oral health condition in the young adult Italian population.

Adult↗