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Biomedical subjects

P Fontana

Publications and source records attributed to P Fontana.

At least 19 recordsLinked to original sources
PubMed2006

[Haemostasis. Aspirin and clopidogrel platelet resistances].

Articles on antiplatelet "resistance" or "nonresponder" subjects now appear in the medical literature or in the media on a regular basis. The clinical consequences of such biological resistances are yet uncertain. In this review, we describe the concepts of specific and non specific resistances according to the tests used and summarize the main studies up to now. If antiplatelet drug resistances are shown to be predictive of cardiovascular events in large prospective studies, tailoring antiplatelet drugs could be beneficial and, therefore, warranted. New compounds with a more potent effect are emerging and might be useful in clinically relevant resistances.

Aspirin↗
PubMed2006

Indications on suitable scaffold as carrier of stem cells in the alveoloplasty of cleft palate.

Autologous iliac crest bone is used to close the residual alveolar bone defect in cleft palate patients during late mixed dentition. Surgery involves physical and anaesthesiologic risks, long-time hospitalization, high costs and not always good results (15% failure rate). Alternatives to iliac crest bone grafting are going to be evaluated: synthetic, xenograft and allograft matrices combined with platelet-rich plasma or recombined bone morphogenic proteins for osteoinductivity are commercially available. These alternatives have not yet been determined to be equivalent to the previous treatment. A new field of research is represented by stem cells, which have been also used to regenerate ischaemic cardiac tissue after heart attack, to treat hypophosphatasia and osteoporosis. Our aim was to use osteoblasts from stem cells to close the residual palate cleft in association with a suitable carrier. Stem cells are expanded in the Aastrom bioreactor, differentiated into osteoblasts and positioned in the bone defect by means of a Spongostan scaffold. This scaffold has the best characteristics as commercial availability, low cost, good manageability, absence of allergic reactions or other side effects on patient, biocompatibility, imbibition, radiotransparency, reabsorbability and osteoinductivity. Previous studies encourage Spongostan scaffold application.

Alveoloplasty↗
PubMed2006

Biological effects of aspirin and clopidogrel in a randomized cross-over study in 96 healthy volunteers.

BACKGROUND: Some data suggest that biological 'resistance' to aspirin or clopidogrel may influence clinical outcome. OBJECTIVE: The aim of this study was to evaluate the relationship between aspirin and clopidogrel responsiveness in healthy subjects. METHODS: Ninety-six healthy subjects were randomly assigned to receive a 1-week course of aspirin 100 mg day(-1) followed by a 1-week course of clopidogrel (300 mg on day 1, then 75 mg day(-1)), or the reverse sequence, separated by a 2-week wash-out period. The drug effects were assessed by means of serum TxB2 assay, platelet aggregation tests, and the PFA -100 and Ultegra RPFA -Verify Now methods. RESULTS: Only one subject had true aspirin resistance, defined as a serum TxB2 level > 80 pg microL(-1) at the end of aspirin administration and confirmed by platelet incubation with aspirin. PFA-100 values were normal in 29% of the subjects after aspirin intake, despite a drastic reduction in TxB2 production; these subjects were considered to have aspirin pseudo-resistance. Clopidogrel responsiveness was not related to aspirin pseudo-resistance. Selected polymorphisms of platelet receptor genes were not associated with either aspirin or clopidogrel responsiveness. CONCLUSIONS: In healthy subjects, true aspirin resistance is rare and aspirin pseudo-resistance is not related to clopidogrel responsiveness.

Adolescent↗
PubMed2005

Comparative analysis of expressed sequence tags from different organs of Vitis vinifera L.

Expressed sequence tags (ESTs) are providing a valuable approach to sampling organism-expressed genomes, especially when studying large genomes such as those of many plants. We report on the comparison of 8,647 ESTs generated from six different grape (Vitis vinifera L.) organs: berry, root, leaf, bud, shoot and inflorescence. Clustering and assembly of these ESTs resulted in 4,203 unique sequences and revealed that at this level of EST sampling, each organ shares a low percentage of transcripts with the others. To define organ relationships based on EST counts, we calculated a distance matrix of pairwise correlation coefficients between the libraries which indicated bud, inflorescence and shoot as a group distinct from the other organs considered in this study. A putative function was identified for about 85% of the unique sequences. By assigning them to specific functional classes, we were able to highlight strong differences between organs in the metabolism, protein biosynthesis and photosynthesis categories. This grape EST collection has also proven to be a valuable source for the development of 'functional' simple sequence repeats (SSRs) markers: a total of 405 SSRs have been identified. EST sequences and annotation results have been organised in the IASMA-grape database, freely available at the address http://genomics.iasma.it.

DNA, Complementary↗
PubMed2005

[Pharmacogenetics and antiplatelet drugs].

PURPOSE: The observation of inherited drug response variability gave rise to the field of pharmacogenetics. Pharmacogenetic research on drug targets, particularly platelet enzymes and receptors, is more recent and is becoming an emerging field. CURRENT KNOWLEDGE AND KEY POINTS: In the Framingham study, the heritability of platelet aggregation response ranges from 44 to 62%, depending on the agonists used. The gene coding for GPIIIa, a sub-unit of the fibrinogen receptor GPIIbIIIa, is one of the most extensively studied gene in relation with aggregation tests and antiplatelet drugs. The GPIIIa PLA1/PLA2 polymorphism has been associated with clopidogrel and orbofiban platelet response. However, data are more controversial concerning the association with aspirin response. Recently, Cox-1 and GPIa (part of the GPIaIIa collagen receptor) genetic variations have also been pointed out as possible candidates to explain part of the variability of the response to antiplatelet agents. Finally, the H1/H2 polymorphism of the platelet ADP receptor P2Y12 gene has been associated with ADP-induced platelet aggregation response and peripheral arterial disease. This polymorphism may modulate the effect of P2Y12 antagonists like clopidogrel and its clinical implication is currently under study. FUTURE PROSPECTS AND PROJECTS: Gene-expression profiling and proteomics may allow the identification of new candidate genes whose variations may be associated with the heritability of platelet aggregation response. In the next future, phenotypic or genotypic studies could be available to tailor the prescription of antiplatelet drugs.

Gene Expression Profiling↗
PubMed2005

Vascular Thoracic Outlet Syndrome staging and treatment.

Thoracic Outlet Syndrome (TOS) is a well known lesion. Sophisticated imaging techniques can clearly highlight any anatomical damage and a wide range of therapeutic choices are available. It would seem obvious that any given patient should obtain the same treatment irrespective of the medical institution he contacts, but this is not the case. Instead each specialist may recommend different treatments: physiatrist, neurologist, surgeons (thoracic, vascular, neuro, orthopedic). Everyone preserves his specific language and there is no univocal treatment plan consensus for this complex syndrome. Evidently, the correct staging of TOS is still an unresolved question. In order to solve this problem, we collected all clinical and instrumental aspects of the syndrome into a clear, precise classification. Similar to TNM staging of malignant diseases, we used a grouping model based on the three mainly involved anatomical structures: N (= Nerves; brachial plexus and sympathetic fibers), A (= Artery; subclavian-axillary), V (= Vein; subclavian-axillary). We named it the NAV staging of TOS. A retrospective examination of our case records confirmed a valid and useful correlation between the proposed NAV staging and the therapeutic procedures that were actually applied. It is now essential to perform a multi-centre study to extend the validity of our staging.

Decompression, Surgical↗
PubMed2005

Not all statins interfere with clopidogrel during antiplatelet therapy.

BACKGROUND: Clopidogrel and statins are frequently coadministered in patients with ischemic heart diseases. Recent reports suggested that clopidogrel's effectiveness in inhibiting adenosine diphosphate (ADP)-induced platelets aggregation is attenuated by co-administration of certain statins. The objective of the present study was to define which statin might interfere with the antiaggregation property of clopidogrel. METHODS: We designed a pharmacokinetic study and tested ex vivo platelet function on 21 healthy volunteers who received clopidogrel and all currently commercially available statins: rosuvastatin [10 mg o.d.], simvastatin [20 mg o.d.], fluvastatin [80 mg o.d.], pravastatin [40 mg o.d.], and atorvastatin [20 mg o.d.]. Each statin was administered for 7 days followed by 1 week of wash-out period with clopidogrel treatment alone. Detection of the statins in the plasma was performed on all blood samples, using HPLC analytical method. RESULTS: All individuals, except one, were responders to clopidogrel with inhibition of ex vivo ADP induced platelet aggregation. All statins, except pravastatin, were detectable in the plasma at the end of each treatment period in all patients, and no statin was detectable after any of the wash-out periods. Clopidogrel was significantly less efficient to prevent platelet aggregation when coadministrated with simvastatin or fluvastatin. No difference was observed in clopidogrel efficacy when coadministered with rosuvastatin, pravastatin or atorvastatin. CONCLUSIONS: This is the first study investigating clopidogrel-statin interactions on ex vivo platelet function with all commercially available statins and which were administered to the same individuals. It demonstrates in healthy volunteers that at the doses used in this study, simvastatin and fluvastatin, but not atorvastatin, pravastatin or rosuvastatin interfere with the anti-aggregation effect of clopidogrel.

Adult↗
PubMed2004

The factor II G20210A gene polymorphism, but not factor V Arg506Gln, is associated with peripheral arterial disease: results of a case-control study.

BACKGROUND: The FIIG20210A polymorphism has been associated with arterial wall thickness and atherothrombotic diseases in selected subgroups. The FVArg506Gln polymorphism does not seem to be associated with arterial diseases. Few data are available on these polymorphisms and the risk of peripheral arterial disease (PAD). OBJECTIVES: To study the association between the FIIG20210A and FVArg506Gln polymorphisms and PAD and its clinical severity. To examine the potential interactions with traditional vascular risk factors. PATIENTS AND METHODS: We studied 184 consecutive male patients under 70 years of age with symptomatic PAD and 330 age-matched male controls free of symptomatic PAD and with no cardiovascular history. We evaluated the FIIG20210A and FVArg506Gln polymorphisms in all subjects. RESULTS: Mean age was 57.1 +/- 7.2 years (cases) and 56.7 +/- 7.6 years (controls). The FII20210A allele was more frequent in PAD patients with odds ratios (OR) of 3.77 (1.39-10.2) in univariate analysis and 4.30 (1.3-14.7) after adjustment for diabetes, smoking, hypertension and hypercholesterolemia. In smokers or past smokers the magnitude of the association was markedly increased but there was no evidence of an interaction between tobacco exposure and FIIG20210A. In case subjects, the FII20210A allele was also associated with critical ischemia [OR = 4.1 (1.1-15.7), P = 0.039 in multivariate analysis]. FVArg506Gln was not associated with PAD [OR = 0.65 (0.27-1.54) and 0.77 (0.28-2.1) in univariate and multivariate analyses, respectively]. CONCLUSIONS: The FIIG20210A gene polymorphism may be a risk factor for PAD and its severity. In contrast, the FVArg506Gln polymorphism is not associated with PAD.

Aged↗
PubMed2004

[Set up of in vitro methods able to detect the safety of astringent liquids].

AIM: Most of dental operators agree about a gengival retraction impregnated cord in order to obtain an accurate and overwide dental impression. Hemostatic agents allow the formation of the primary coagulum that determines/causes the retraction of gum connective. Sometimes these astringent liquids cause local inflammation reaction as reported in literature. Aim of this work was the evaluation of the cytotoxic and inflammatory action of the most common astringent liquid on human gum primary cells by in vitro tests. METHODS: For this purpose primary cultures of normal human oral keratinocytes were established, following used either as monolayer or as reconstituted model. All dental preparations were dissolved in CEC medium, diluted to the designed concentrations and applied to the cultured cells. The cytotoxicity was determined by using MTT test, able to evaluate the succinate dehydrogenase activity and therefore the cell viability. Control cultures were treated with CED alone, whereas sodium dodecyl sulphate (SDS) was used as a positive control. Furthermore, the inflammatory response, determined by measuring TNF-alpha and IFN-gamma release, was evaluated on a reconstituted multilayer human oral epidermis model. RESULTS: All agents tested showed a dose-dependent increase in the cytotoxicity to normal human gingival keratinocytes over the dose range examined. In particular the results obtained suggest the higher toxicity of the Astringedent X compound. CONCLUSION: The results obtained from the present studies not only provide useful estimates of relative toxicities of these preparations to human oral mucose, but also can be useful as a standard for cytotoxic and inflammatory assessment of newly developed dental preparations to be topically applied to the oral mucosa. It is important to note, however, that the interpolation of these findings to in vivo conditions remains to be done.

Astringents↗
PubMed2003

Changes of autonomic cardiac profile after a 3-week integrated body weight reduction program in severely obese patients.

The autonomic control of the heart is abnormal in obese subjects due to a prevalence of sympathetic over parasympathetic limb of the autonomic balance. We evaluated the effects of a short-term (3 weeks) integrated body weight reduction program (consisting of energy restricted diet and high-intensity exercise training) on heart rate variability (HRV) in severely obese, normotensive patients. The HRV was evaluated both in the time and frequency domain over a 18-hour Holter recording period obtained before and at the end of the third week. Three-week body weight reduction program reduced BMI (from 41.4 +/- 4.6 to 39.5 +/- 4.3 kg/m2, -4.6%, p<0.0001) and heart rate (from 77.8 +/- 8.6 to 73.6 +/- 8.7 b/min, p=0.0003). Significant changes in the autonomic profile were observed both in the time and frequency domain (SD of RR interval, SDRR: +16.1%; mean squared successive difference: (MSSD) +16.7%; percentage of RR intervals differing more than 50 msec from the preceding one, pNN50: +31.8%; low frequency oscillation, LF: +17.1%; high frequency oscillation, HF: +/- 18.2%). In conclusion, this study demonstrates that a short-term, integrated body weight reduction program is able to favorably modify the autonomic profile in a population of normotensive, severely obese subjects. The reduction of heart rate and the increase in parasympathetic activity may consistently contribute to a reduction of the risk of cardiovascular morbidity and of sudden cardiac death, still high in this patients' group.

Adult↗
PubMed2003

Short-term changes of fatigability and muscle performance in severe obese patients after an integrated body mass reduction program.

The effects of a short-term (3-week) integrated body weight reduction (BWR) program on fatigue perception and on lower limb anaerobic power output were evaluated in 200 severely obese in-patients (40 males and 160 females, age: 18-83 yr, BMI: 35.0-65.3 kg/m2). Fatigue was assessed by a 7-point Likert-type scale questionnaire (Fatigue Severity Scale, FSS), while average lower limb power output (W) during a maximal effort was determined with a modification of the Margaria test for stair climbing. In both genders, total FSS score was influenced by both age and obesity level, resulting significantly (p < 0.001) lower in younger subjects (< 45 yr) than in older (> 45 yr) and in patients with lower BMI (< 40 kg/m2) than in those with a higher one (> 40 kg/m2). An opposite trend was observed in W. The 3-week BWR integrated program with moderate aerobic exercise and free standing and ground gymnastic routines induced a significant reduction in body weight (p < 0.001), in total FSS score (p < 0.001) and a significant increase in W, both in absolute terms (p < 0.05) and relative to body mass (p < 0.001). Total FSS score and absolute or relative power output were positively correlated both before and after the BWR program (p < 0.001, Wilcoxon rank test). It is concluded that: a) subjective fatigue perception, assessed by a FSS questionnaire, can be considered an indirect indicator of effective lower limb power output in severely obese patients and, b) in spite of a relatively small, although significant, decline of BMI, the full-time participation in a hospital-based, integrated BWR program with moderate exercise activity is associated with significant short-term improvements of both fatigue sensation and power output. Dia

Adolescent↗
PubMed2002

Hypothermia reduces neurological damage in asphyxiated newborn infants.

BACKGROUND: Perinatal asphyxia remains one of the most devastating neurologic processes. There is experimental and clinical evidence that cerebral cooling may suppress the biochemical cascades leading to delayed cerebral damage. OBJECTIVE: To determine if hypothermia started soon after delivery reduces cerebral damage in term infants. DESIGN/METHODS: Retrospective chart analysis with historical controls. Ten asphyxiated newborns treated with hypothermia between October 1998 and October 1999 were compared to 11 asphyxiated newborns admitted from September 1997 to September 1998. Characteristics at birth of infants of the two groups (control and hypothermia) were comparable. After obtaining parental consent, whole-body hypothermia was induced before the 6th hour of life by placing a cold blanket (Polar Air, Augustine Medical Inc., model 600) around the body of the patients. Rectal temperature was maintained between 32 and 34 degrees C for 72 h. Outcome was assessed by neurological evaluation at birth and every 3 months up to the 12th month. Brain MRI was performed in the 2nd month. We had no evidence of severe adverse events related to hypothermia. In the hypothermic group there was a significant (p < 0.05) reduction of major neurologic abnormalities at follow-up and abnormal MRI findings. CONCLUSIONS: Hypothermia appears to be safe. Our results on morphological damage evaluated by brain MRI and neurological outcome are encouraging: randomized controlled trials are needed to confirm this experience.

Asphyxia Neonatorum↗
PubMed2001

[Recurrent acute myocardial infarction in a patient with nocturnal paroxysmal hemoglobinuria].

Paroxysmal nocturnal hemoglobinuria is a form of acquired hemolytic anemia with a high incidence of thrombotic complications, generally in the venous district; arterial thrombosis is rare, and exceptional in the coronary tree. We describe the case of a man who had two episodes of myocardial infarction, both during a hemoglobinuric crisis; this patient was free from cardiovascular risk factors and angiography revealed that there was no coronary stenosis. The clinical course was favorable and the patient's response to thrombolytic and dicumarol therapy was satisfactory. To our knowledge, this is the second case of coronary involvement in paroxysmal nocturnal hemoglobinuria described in the literature.

Hemoglobinuria, Paroxysmal↗
PubMed2000

Influence of age and menopausal status on pathologic and biologic features of breast cancer.

The distribution of the main prognostic factors in different age groups was evaluated in 1226 patients operated on for primary breast cancer, in order to identify those influenced by age and/or menopausal status. Patients were divided into the following groups: 1) 40 years of age and under; 2) premenopausal over 40 years of age; 3) postmenopausal under 75 years of age and 4) 75 years of age and over. Our findings showed that the youngest patients had the worst prognostic pattern, which improves as age increases and is the best in patients over 75 years of age. Some of the parameters investigated (tumour size, histologic and nuclear grade, tumour infiltrating lymphocytes, p53 and Ki 67) were found to be influenced by age, some (necrosis and oestrogen receptors) were influenced by menopausal status and/or age, some (vascular invasion, ploidy, S-phase and progesterone receptors) showed significant differences in different age groups but there was no consistent relation with patient age or menopausal status, and others (node status, ErbB2/Neu and Cathepsin D) were not influenced by age or menopause.

Journal Article↗