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Biomedical subjects

A Crippa

Publications and source records attributed to A Crippa.

At least 19 recordsLinked to original sources

Possible interchromosomal effect in embryos generated by gametes from translocation carriers.

BACKGROUND: The incidence of abnormal pregnancies in carriers of balanced translocations depends strictly on the chromosomes involved in the translocations. The aim of this study was to verify whether conventional aneuploidy screening could be advantageously combined with preimplantation genetic diagnosis (PGD) for translocations. METHODS: Twenty-eight carriers of Robertsonian and reciprocal translocations underwent 43 PGD cycles; specific probes were used to screen the translocation in 172 embryos generated by 35 cycles; most of these embryos were also screened for chromosomes 13, 16, 18, 21, 22 (n = 166), XY (n = 107), 1 (n = 17) and 15 (n = 88). For the remaining eight cycles (carriers of reciprocal translocations) only the chromosomes involved in common aneuploidy screening were investigated on the 40 embryos generated in vitro. RESULTS: In Robertsonian translocations, the proportion of embryos with abnormalities due to the translocation was 21%, common aneuploidies contributed 31% of total abnormalities, whereas the remaining 36% of embryos had abnormalities due to both types of chromosome. For reciprocal translocations, the chromosomes involved in the translocation were responsible for 65% of total abnormalities; only 6% of the embryos were abnormal for common aneuploidies and 16% carried abnormalities due to both the chromosomes involved in the translocation and those not related to the translocation. CONCLUSIONS: An interchromosomal effect seems to play a role in the case of Robertsonian translocations, where the relevant contribution of aneuploidy exposes the couple to an additional risk of abnormal pregnancy.

Aneuploidy↗

Do static or dynamic AFOs improve balance?

OBJECTIVE: To verify if partial or total limitation of degrees of freedom at ankle joints could help patients with balance disorders in standing and walking. DESIGN: A cross-over design was chosen. Patients with multiple sclerosis (MS) were tested in three experimental conditions: barefooted, wearing ankle foot orthoses (AFOs), and wearing AFOs that allowed plantar flexion. SETTING: Neurorehabilitation unit in a rehabilitation centre. SUBJECTS: Fourteen patients suffering from MS with mild strength problems and balance disorders that required them to use walking aids outside. MAIN OUTCOME MEASURES: Tests inferring static and dynamic skills were carried out in the three experimental conditions described above. RESULTS: Improvements were obtained in static balance tests especially wearing dynamic AFOs; the number of patients who were able to pass tasks on balance in upright position such as 'standing with feet together, head extended' increased from three to nine. Dynamic balance was impaired especially with static AFOs; the time spent walking 10 metres with these orthoses increased by 172% with respect to barefoot; less difference (113%) has been reported wearing dynamic AFOs. CONCLUSION: Static and dynamic AFOs improved static balance, while dynamic balance was impaired especially by static AFOs; less negative influence on dynamic balance has been found while wearing dynamic AFOs.

Adolescent↗

Induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor RPR-115135: role of gene mutations.

To investigate the relationship between oncogene activation and induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor, RPR-115135, two isogenic cell lines, human colon cancer line HCT-116, which harbors a K-ras mutation, and spontaneously immortalized human breast epithelial cell line MCF-10A, were utilized. HCT-116 cells were transfected with an empty control pCMV vector (clone CMV-2) or with a dominant negative mutated p53 transgene (clone Mu-p53-2) to disrupt p53 function. In both clones RPR-115135 induced a significant increase in the frequency of micronucleation at concentrations that did not affect cell membrane integrity. RPR-115135 produced a significant increase in the ratio of CREST+ to CREST- micronuclei. MCF-10A cells were stably transfected with either c-Ha-ras or c-erbB-2 or both H-ras + c-erbB-2. No induction of micronuclei was observed. No induction of micronuclei was reported in human lymphocytes and in primary spinal cells obtained from 7-day chick embryos. In conclusion, RPR-115135 acts as an aneugenic agent in a complex manner, dependent upon the complement of mutations in cell regulatory genes in tumour cells and this activity may be independent of ras genotype.

Alkyl and Aryl Transferases↗

RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

Alkyl and Aryl Transferases↗

[Rheologic modifications induced by heparin therapy. Capillary blood viscosity, erythrocyte deformability, aggregation index].

BACKGROUND: The most important problem with which doctors have to deal every day in their practice, is occlusive vascular disease, at the basis of which there is commonly a process of thrombosis. For this reason, it is very important to define early the subjects at thrombosis risk and an appropriate therapeutic strategy. METHODS: We considered 13 inpatients at thrombosis risk, c/o sezione di Clinica Medica I, dipartimento di Medicina Interna e Terapia Medica, Università di Pavia, IRCCS Policlinico S. Matteo, and 12 healthy volunteers, between March and June 1998, evaluating age, sex, weight, diseases and ongoing therapy, hemocytological, hemocoagulational and hemorheological tests before and after heparinic therapy. RESULTS: General blood viscosity, measured by the rotational and double-filtration method, presented no significant changes; on the contrary, capillary blood viscosity and erythrocyte deformability, measured by our new double-filtration method, showed respectively an increase and a decrease. CONCLUSIONS: Calcium heparin is the most frequently used antithrombotic drug in thrombotic diseases and their prevention, but its action on the hemorheological profile is not clear. This study showed that it increases erythrocyte aggregation rate and decreases erythrocyte deformability, having a negative effect on the microcirculation.

Anticoagulants↗

[Hemorheology in different types of obesity].

BACKGROUND: Obesity is a symptom of impaired fat metabolism, organs and system of which are: the liver where fat synthesis and oxidation occur and the adipose tissue with a storage function. Obesity in NIDDM, insulism and suprarenalism is due to an increased synthesis in triglycerides and their deposit in fat cells. Aetiologic factors of primitive obesity act on the fat tissue promoting lipogenesis (hypertrophic or hyperplastic action) and/or reducing fat release. METHODS: Thirty-two women suffering from obesity but without cardiovascular pathologies were investigated. Obesity degree and type were defined by the anthropometric method. The following tests were carried out: glycemia, insulinemia, C-peptide in OGTT, tryglicerides, cholesterolemia and cortisolemia. Plasma viscosity (V) and whole blood V were determined with rotational microviscosimeter; erythrocyte V and plasma-erythrocyte V were performed with double filtering method and values expressed in cP. Deformability was calculated as a ratio between viscosities determined with both filtering methods. RESULTS: On the basis of the type of obesity three groups were characterized: gynoid, intermediate and android. Rheological parameters are increased in all women: increase of plasmatic V, increase especially of erythrocytic viscosity with a considerable decrease in deformability. There are interesting differences among the three groups. CONCLUSIONS: The relationship between obesity and cardiovascular disease is well known and the early rheological impairment could be the factor linking both pathologies. Some factors involved in obesity, such as hyperglycemia and hyperinsulinemia, are also suspected of impairing hemorheology promoting changes in the microcirculation.

Adult↗

Attachment of Vibrio alginolyticus to chitin mediated by chitin-binding proteins.

Vibrio alginolyticus is the only culturable vibrio associated with the chitinaceous carapace of the copepod Tigriopus fulvus (Fisher 1860) living in Ligurian coastal rock pools (Tyrrhenian Sea). The characteristics of the interaction between chitin particles and V. alginolyticus were studied by analysing strains isolated both from the copepod surface and from rock-pool water. The highest degree of attachment to chitin was observed at 20 degrees C, in the presence of 3% NaCl. Bacterial treatment with N-acetylglucosamine and pronase E caused a reduction in attachment of 52-62% and 77-94%, respectively. Chitin pretreatment with either wheat germ agglutinin or membrane proteins (MPs) from V. alginolyticus caused a reduction in attachment, of 50-57% and 53-70%, respectively. No inhibition was observed when bacteria were pretreated with D-glucose, D-fucose or D-fructose, or when chitin was pretreated with concanavalin A and Escherichia coli DH5 alpha MPs. V. alginolyticus MPs able to bind chitin were isolated and analysed by SDS-PAGE. Four chitin-binding proteins were visualized in all tested strains (53, 35, 20 and 14 kDa); in vivo these peptides may efficiently mediate V. alginolyticus attachment to chitin-containing substrates.

Acetylglucosamine↗

[Cardiac troponin I in unstable angina].

BACKGROUND: Unstable angina implies high risk of myocardial infarction and sudden death. Increased levels of cytoplasmatic enzymes and proteins (creatine phosphokinase, MB creatine phosphokinase troponin T, etc.) were described in unstable angina, providing information about incoming major coronary events. Cardiac troponin I (cTn-I) is a structural protein inhibiting the actinomyosine ATPase; it is only found in myocardial cells. Serum titration of cTn-I has been recently introduced into clinical practice as a sensitive and specific marker of myocardial cellular necrosis. OBJECTIVES: The aim of our prospective study was to assess the presence of cTn-I in blood samples of patients with unstable angina and no signs of myocardial necrosis. Furthermore we intended to test the possible use of cTn-I in unstable angina as a prognostic marker of major coronary events on short and middle term. METHODS: We studied 33 consecutive patients admitted to our CCU for unstable angina. According to unstable angina Braunwald's classification, 6 patients were included in the first class, 4 patients in the second class and 23 patients in the third class. We excluded patients with acute or recent myocardial infarction. Blood samples of all patients were obtained at the time of CCU admission and every eight hours in the first and second day. Serum cTn-I titration was performed with the sandwich immunoenzymometric method, recently introduced by Diagnostic Pasteur. Two months follow-up was carried out in order to survey major coronary events and revascularization procedures, either angioplasty or coronary artery bypass surgery. RESULTS: No patients with unstable angina exhibited cTn-I in their blood samples; accordingly, cTn-I was not found in the first blood sample of a patient who underwent myocardial infarction during hospitalization. During the follow-up 2 patients died of myocardial infarction, 9 patients had surgical revascularization and 5 patients angioplasty. CONCLUSIONS: CTn-I is a sensitive and specific marker of myocardial necrosis. It is not found in patients with unstable angina; therefore it has no role as a prognostic marker of major coronary events.

Adult↗

[Cardiac troponin I and T in unstable angina: incidence, correlation, kinetics of release and prognostic value].

BACKGROUND: The aim of this study was to ascertain the incidence of altered serum cardiac Troponin-T (cTnT) and cardiac Troponin I (cTnI) in patients with unstable angina, the concordance between findings for the two proteins, their release kinetics and their utility in predicting coronary events. METHODS: We studied 32 consecutive patients (pts) admitted to the Coronary Unit with a diagnosis of unstable angina; following Braunwald classification criteria, 5 pts were in class I, 4 class II, 23 class III. A blood sample was taken on admission to hospital and subsequently every 8 hours for two days, a total of 7 samples being obtained per pt. Cardiac-TnT values ranging from 0-0.17 mugr/L (Boehringer Mannheim) were considered normal, as were cTnI values ranging from 0 to 0.7 mugr/L (Stratus-Dade). RESULTS: Among 218 samples, altered cTnT values (0.18-0.68 mugr/L) were found in 19 (3 pts), and 13 of these samples were positive for cTnI (0.8-5.5 mugr/L), while the remaining 6 showed borderline values for cTnI (0.5-0.7 mugr/L). No cTnT negative samples were found to be positive for cTnI. The release kinetics of cTnT and cTnI were comparable in all three cases, with a "plateau" pattern, unlike the kinetics in the course of acute myocardial infarction (AMI). The mean follow-up was 13 months on average (range 1-19). In two pts with altered cTnT and cTnI values, symptoms were controlled with medical therapy, while the remaining patient failed to respond to medical therapy and therefore underwent PTCA. Fifteen months later, they are alive and have not had myocardial infarction. Of the 29 pts with normal cTnT and cTnI values, three developed AMI, which in two cases was fatal. Seven pts were submitted PTCA, seven to aorto-coronary bypass surgery, two were subsequently rehospitalized for a recurrent angina symptoms. In 13 pts complete control of symptoms was achieved with medical therapy. CONCLUSIONS: Our findings demonstrate that the incidence of altered cTnT and cTnI values in pts with unstable angina is low; there is close agreement between findings for the two proteins; in cases of angina, the cTnT and cTnI release kinetics are different from those in AMI. The finding of altered cTnT and cTnI values in the serum of our pts with unstable angina does not appear to be of prognostic value for future coronary events.

Adult↗

[Hemorheologic assessment in hypoxic and hypoxic-hypercapnic states].

METHODS: Twenty-four male and female people have been examined. They were afflicted with respiratory failure; on blood gas analysis they have been divided into two groups: hypoxic and hypoxic-hypercapnic subjects, disregarding the base pathology. We have used both the rotatory and double filtration methods, using a constant 15 cm water filtration pressure. The following rheological values have been defined: plasmo-erythrocytic viscosity, plasmatic viscosity, erythrocytic viscosity and erythrocytic deformability. The values have been expressed in cP. We have also considered haemacytometric parameters. RESULTS: It came out that all the rheological parameters were highly different in both groups, with an increase of, more or less, 30% in plasmo-erythrocytic viscosity; a four times increase of erythrocytic viscosity compared to normal values and a decrease of 60% in erythrocytic deformability. The plasmatic viscosity was also very increased: we must correlate this phenomenon with phlogotic or neoplastic pulmonary pathology of the people we have examined. Regarding haemacytometric parameters, from the hypoxic-hypercapnic group comes out significant higher MCV values and MCHC lower ones, with a higher anisocytosis level. CONCLUSIONS: From these results we think that the altered systemic rheology makes hypoxic condition wider, while, at pulmonary level, help the haemodynamic resistances to increase, with the onset of a hypertensive condition.

Aged↗

[Blood rheology and fibrinogenemia: two independent parameters in the assessment of cerebral vascular damage].

The increase in fibrinogen level is consequent on several hurtful events: inflammatory, traumatic, stress reaction. Traumatic event, during cerebral vasculopathies, often causes an inflammatory reaction, certainly in the acute phase, inducing fibrinogen synthesis. There are also other inflammatory changes as the increase in WBC and PLT counts and in other hematic components, both in increase and in decrease. Patients with cerebral vasculopathies were divided in two groups according to the clinic picture seriousness. Haemorheologic characteristics were measured with a double filtering method I (with 5 and 12 mu filters) and under a filtering pressure of 15 cm H2O, eliminating WBC interference even if using native blood. In this way we have determined whole blood, plasma, and plasma-erythrocyte viscosities. From these measures we have obtained corpuscular viscosity and erythrocyte deformability. Fibrinogen concentration is increased in all patients with acute vasculopathies, but there is not a difference in relation to the clinic pictures seriousness. Also other inflammatory parameters, namely: total protein, gamma-globulins, ESR, are increased in a significant way without difference in relation the clinic seriousness. The WBC count is more increased in the group with Stroke than in the other one with TIA. The corpuscular viscosity is almost doubled with consequent decrease in deformability; plasma-erythrocyte viscosity, measured with both methods, is quite increased. These parameters show the same behaviour in both groups. Only plasma viscosity increased in the group with Stroke. Haemorheology alteration is not statistically correlated to the fibrinogen level. The decrease in deformability can be related to the viscouselastic membrane properties, and the fibrinogen, because of its adhesive properties, can contribute to such a decrease.

Aged↗

Outpatient Treatment of Clinically Node-negative Breast Cancer in Elderly Women.

Successful management of elderly women with breast cancer presents a wide range of issues and challenges. The Istituto Nazionale per lo Studio e la Curo dei Tumori of Milan has performed a series of studies of women over age 70 years with clinically localized breast cancer which confirms the safety and effectiveness of wide local excision without lymph node dissection on an outpatient basis and under local anesthesia when axillary nodes are not palpable. Size and biologic characteristics such as hormone receptor status and proliferative activity have been used to determine the extent of effect of additional treatment with breast irradiation and tamoxifen on disease-free survival and actual survival. Factors affecting compliance to treatment protocols are being assessed.

Journal Article↗

[Relationship between hemorheology and pro- and anti-coagulation factors in inflammatory and degenerative vascular diseases].

After having found out an increase in the Von Willebrand Factor (vWF) and a relation between its persistance and seriousness of some vasculities, we looked for a link between changes in vWF level and hemorheology, their role and interdependence in the evolution of the vascular diseases, in complications and in relapses. We studied patients affected with degenerative and inflammatory vascular diseases and we determined rheologic parameters, in traditional and personal innovative way, pro- and anti-coagulation factors, other inflammatory proteins and hematic parameters. As regards coagulation only the vWF appeared increased in a significant way, without differences between two types of vascular diseases. As regards hemorheology, in both of them we measured an increase in the whole blood viscosity but with a different behaviour of its components. In the degenerative vascular diseases there was an increase both in corpuscular viscosity and in the plasma-erythrocyte one, a no significant increase in the plasma viscosity whereas the erythrocyte deformability was in the normal range. In vasculitis there was the highest increase in the plasma and corpuscular viscosities with a decrease in the deformability without changes in the plasma-erythrocyte viscosity. We give some interpretations on their different behaviour and a right meaning of the involved phenomena in every kind of rheologic parameter.

Aged↗

[Factor VIII/Ag (von Willebrand) and protein C. Erythrocyte deformability and aggregability. The risk parameters of retinal vein occlusion].

In 32 patients with retinal vein occlusion we measured coagulative and hematic parameters. The coagulative factors were in the normal range, save C-Protein, that was decreased and the Von Willebrand Factor that appeared increased in a significant way. These changes do not affect the coagulation state, but, in a local vascular district, they can interfere with mechanisms of thromboresistance, over all in the retinal district owing to its peculiar structure and its flow of terminal kind. The hemorheologic alterations consist in a decrease in the erythrocyte deformability and in an increase in the plasma-erythrocyte and plasma viscosities, measured both with a rotational method and with a filtering one. We have not found any correlation between coagulative factors and hemorheologic parameters, nevertheless these last ones determine a lowering down of the local flow, that with the morphological changes in the vascular system, give rise to conditions for an occlusion event.

Aged↗

[Rheologic features of erythrocytes in beta-thalassemia minor].

The study assessed the physical characteristics of erythrocytes, viscosity and deformability, measured by a widely described double-filtration method. At the same plasma-cell viscosity was measured and the importance of the rigidity of RBC was evaluated as one of the many forces which interact among the cells and between the plasma and cells. The results showed a marked increase in corpuscular viscosity with reduced deformability, and a significant diminution of plasma-erythrocytic viscosity, whereas total viscosity remained unaltered. These parameters do not correlate with the quantitative pathological alterations of HbA2, but only with RDW-SD. Alterations of the proteic components with a relative increase in the alpha-chains of the erythrocytic membrane are thought to be responsible for these anomalies, by means af the modifications that the excess of alpha-globin causes to the structure and function of erythrocytic membrane; but the quantity of globin is not the decisive factor, and in fact the introduction of the beta-chains are able to correct erythrocytic deformability (Sorensen). Membrane rigidity is probably independent and unrelated to microcytemia, because these erythrocytes, have an excess of surface in relation to their volume, due to the simultaneous alteration of permeability. The diminished plasma-erythrocytic viscosity should be connected with the prevalence of repulsing forces, due to erythrocytic rigidity in relation to the attracting forces due to the proteic fractions which remain unchanged.

Adult↗

[Plasma-erythrocyte viscosity and evaluation of several pro- and anti-aggregating factors in NIDDM patients in metabolic decompensation state].

In NIDDM diabetic subjects, the microcirculatory damage shows a double aspect: an alteration of the vascular wall, particularly of the arteriolar capillary, and a hemorheological alteration at the level of the capillary district. In the microcirculation, because of the low velocity of the flow and the inverse relationship between capillary size and RBC diameter, the viscosity has an important role with its components: RBC viscosity and deformability. Even the erythrocyte aggregation has a key role as resultant of the attracting and repulsing forces, among which the plasma-RBC viscosity and the deformability play opposite role. Our method allows to evaluate the erythrocyte, the whole blood, the plasma and the plasma-RBC viscosity, and the deformability. Studies from this laboratory in NIDDM subjects show an increase in the blood viscosity, a decrease in the erythrocyte deformability and plasma-RBC viscosity. It is suggested that in microcirculatory district the flow reductions are particularly of hemorheological type and that the sludged blood is an "optical" phenomenon with poor meaning. We consider some hematological parameters, namely the Hgb A1c %, Hgb concentration, RBC count, MCV, etcetera.

Aged↗

[Relations between plasma-erythrocyte viscosity factors and ESR].

The ESR is usually put in relationship: to the real density of the RBCs (erythrocytes) (difference between the RBC specific gravity and the plasma one), and to the resistance that the RBCs meet moving in a medium, which is due to the plasma viscosity and to the total external RBC surface. When the RBCs take shape of aggregates, their external surface is decreased and ESR increases. The most important plasma factor causing changes in ESR is the fibrinogen level followed by the plasma globulins and by the products arising from the tissue damage. The resistance that the RBCs meet moving in the plasma is well expressed by the measurement of the plasma-RBC viscosity considering that is inclusive of both factors that are the plasma viscosity and the external RBC surface. The plasma-RBC viscosity is the resultant of several factors: Fa = Fb - Fe - Fs - Fm, were: Fa is the resultant, Fb the attracting forces due to the proteic macromolecules, Fe the repulsing forces due the negative charges. Fs the repulsing forces due to the shear-stress, Fm the force which opposes itself against the surface tension of the aggregation; it depends on the RBC morphology and on the RBC rigidity. The ESR has been recently used like an index of the RBC aggregation. The Authors study the relationship between several hemorheological parameters and the ESR in infective and inflammatory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Sedimentation↗