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Biomedical subjects

G Guidi

Publications and source records attributed to G Guidi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Application of autoregressive methods to multigate spectral analysis.

Multigate analysis is known to be capable of detecting accurate blood velocity profiles from human vessels. Experimental systems so far presented in the literature use time-domain frequency estimations and, more recently, the fast Fourier transform (FFT) for real-time analysis of Doppler signals from multiple range cells. This experimental study is aimed at evaluating the application of an autoregressive (AR) method (Burg algorithm) to multigate Doppler analysis. Both in vitro and in vivo results were collected with a commercial Duplex scanner coupled with a prototype multigate unit developed in our laboratory. The same multigate signals are, thus, processed according to both the FFT and the Burg algorithms. The related spectral and maximum frequency profiles are reported and statistically compared. AR, implemented with the Burg algorithm, is demonstrated to be a way to perform multigate spectral analysis with reduced spectral variance, suitable for maximum velocity profile extraction through a simple threshold.

Artifacts↗
PubMed2000

Intrinsic spectral broadening (ISB) in ultrasound Doppler as a combination of transit time and local geometrical broadening.

Doppler signals collected with a focused transducer are known to be affected by the so-called intrinsic spectral broadening (ISB). This article aims to point out how ISB is, in general, related to both the limited lateral extent of a focused beam (leading to a finite transit time), and the presence of several local insonation angles around the beam axis, due to focusing and diffraction effects (local geometrical broadening). The influence of these two elementary spectral contributions on the whole ISB is shown by considering the Doppler signal as simultaneously modulated in amplitude and frequency, and applying well-known relationships employed in the communication field. Such an analysis reveals that transit time and local geometrical broadening are two different phenomena, whose simultaneous knowledge is necessary for correctly evaluating the overall ISB. Finally, thanks to a novel technique for separately measuring transit time and local geometrical broadening effects on transducers with markedly different focusing properties, more than 1000 experimental acquisitions show how a proper combination of such measured contributions gives an accurate ISB estimation, confirming the theoretical expectations.

Artifacts↗
PubMed2000

Lipoprotein(a): from ancestral benefit to modern pathogen?

We review current concepts regarding the genetic, structural and metabolic features of lipoprotein(a), a major inherited cardiovascular pathogen. Although lipoprotein(a) is almost completely confined to a subset of primates, the hedgehog produces a lipoprotein(a)-like complex, which appears to have evolved independently from that of humans. The physiological role of lipoprotein(a) in humans is still unclear, and individuals with low or null concentrations of plasma lipoprotein(a) manifest no deficiency syndrome or disease. The integration of recent discoveries about the structure and metabolism of this unique lipoprotein particle has allowed the formulation of some hypotheses concerning the evolutionary advantages of synthesizing lipoprotein(a)-like particles.

Animals↗
PubMed2000

Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol.

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.

Alendronate↗
PubMed2000

Laboratory screening for erythropoietin abuse in sport: an emerging challenge.

The growing diffusion of banned practice to improve the athletic performances is forcing clinical laboratories to identify and standardize reliable assays to detect potential unfairness. Among the doping practices, the use of recombinant human erythropoietin is becoming fairly popular, due to simplicity and safeties of administration and troublesome detection. The heterogeneous response rate, the presence of a little but significant amount of naturally occurring hormone, the short half-life exhibited by recombinant human erythropoietin and the lack of standardization of commercial assays appear the main problems to overcome. Aim of the present article is to provide a critical review of some of the more widespread laboratory techniques currently available for the screening for erythropoietin abuse in sport.

Doping in Sports↗
PubMed1999

Biochemical risk factors and patient's outcome: the case of lipoprotein(a).

Lipoprotein(a) (Lp(a)) is a genetic variant of low density lipoproteins and consists of the covalent association of the unique and enigmatic apolipoprotein(a) to apoliprotein B100. Despite the high degree of homology with low density lipoproteins, Lp(a) displays distinctive physico-chemical properties, function and metabolism. The present article reviews the main biological and clinical evidences about the association between raised concentration of Lp(a) and atherothrombotic diseases and provides tentative guidelines to improve the clinical usefulness of Lp(a) measurements.

Arteriosclerosis↗
PubMed1999

Detection of vascular haemodynamics through a high-speed velocity profiler.

OBJECTIVE: This paper aims at demonstrating that ultrasound Doppler multigate spectral analysis performed with advanced equipment may provide detailed and significant haemodynamic information. METHODS: A novel multigate system was recently introduced and shown capable of performing real-time spectral analysis of Doppler data from 64 resolution cells located at different depths from the transducer. The system extends the typical capabilities of conventional Pulsed Wave (PW) equipment by displaying the full spectral content of Doppler signals over an ultrasound scan line rather than in a single resolution cell. In cases where it is appropriate to display the available information in a simpler form, parameters such as the maximum frequency can be extracted from each spectrum, by using conventional or advanced image processing methods. RESULTS: In-vitro experiments show that the multigate system can perform velocity measurements with good accuracy and precision. Examples of in vivo profiles detected from carotid, femoral and radial arteries are presented. In particular, the first results obtained from the aorta are shown. CONCLUSIONS: Blood flow behavior can be accurately investigated using a real-time multigate system which extends Doppler spectral analysis to a whole scan line.

Aorta↗
PubMed1999

Lipoprotein(a) concentration is not associated with venous thromboembolism in a case control study.

BACKGROUND AND OBJECTIVE: Lipoprotein(a) is an LDL-like particle displaying strong athero-thrombotic properties. Although Lp(a) plays a pivotal role in the genesis and progression of thrombosis in the arterial district, its role in promoting thrombosis in the venous district is still unclear. DESIGN AND METHODS: To give further insight into the thrombotic potential of Lp(a), 100 potentially eligible consecutive outpatients who had suffered from previous episodes of venous thrombosis (deep vein thrombosis with or without pulmonary embolism) were enrolled into the study. Thirty-six of these patients who did not fulfil the entry criteria were then excluded from the study. The concentration of Lp(a) was thus measured in 64 patients, and compared to that of 64 control subjects, matched for sex (p=0.46), age (p=0.25) and pharmacological treatment; no subject belonging to the control group had a familial or personal history of venous thromboembolism. Exclusion criteria for both groups included: diabetes mellitus, liver or kidney diseases and malignancy, as established by both laboratory analysis and physical examination. To rule out false elevations of Lp(a) due to the presence of a concurrent acute phase response, C reactive protein (CRP) was measured in both groups using a commercial immunonephelometric assay. RESULTS: No statistically significant differences were observed in the median Lp(a) concentration between patients and controls (median: 69 vs 83 mg/L, respectively; p=0.34). Neither were any significant differences found between patients who had suffered from deep venous thrombosis with (n=18) or without (n=46) pulmonary embolism (median: 73 vs 69 mg/L, respectively; p=0. 83). The concentration of CRP did not differ significantly between cases and controls (median: 1.8 vs 2.3 g/L, respectively; p=0.37). INTERPRETATION AND CONCLUSIONS: Although there are several plausible biological mechanisms to explain the strong thrombogenicity of Lp(a) in vitro, we failed to demonstrate a convincing association between Lp(a) and thrombosis in the venous district. Besides the proven prothrombotic role of Lp(a) in some selected clinical settings, it is thus conceivable that the contribution of Lp(a) to genesis and progression of the venous thrombosis might be marginal or efficiently counterbalanced in vivo. The clinical usefulness of including the measurement of Lp(a) among the screening tests for thrombophilic patients, therefore, remains questionable.

Aged↗
PubMed1999

[Doping and sports].

Doping is widely known as the use of banned substances and practices by athletes in an attempt to improve sporting performances. The term doping likely derives from "dope", an ancient expression referred to a primitive alcoholic drink that was used as a stimulant in South African ceremonial dances; gradually, the term was extended and finally adopted his current significance. There are at least two essential reasons to support the fight against doping: the potential harmful effects on athletes and the depth corruption of the fair competition. An exhaustive list of banned substances and methods has been drawn by the International Olympic Committee and further accepted by other International Sport Authorities and Federations. This list, regularly updated, is basically divided into doping substances (stimulants, narcotic analgesics, anabolic agents, diuretics, peptide and glycoprotein hormones and analogues), doping methods (blood doping, pharmacological, chemical and physical manipulation) and drugs subjected to certain restrictions (alcohol, marijuana, local anesthetics, corticosteroids and beta-blockers). Although there might be some medical conditions, which could legitimate the need of these substances or methods, there is no place for their use in sport. Thus, an athlete's consume of any of these substances or methods will result in disqualification. Aim of the present review is to provide a synthetic description of both the desirable effects and the potentially harmful consequences of the use of some of the major doping substances and methods.

Adult↗
PubMed1998

Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a) levels after bisphosphonates-induced acute phase response.

Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle displaying strong atherothrombotic properties. Although the concentration of Lp(a) in plasma is under strong genetic regulation, there are emerging evidences that several other factors, such as hormonal disorders, acute phase, liver and renal failure may affect its metabolism. The aim of the present study was to investigate whether bisphosphonates, an effectual drug in the treatment of malignant hypercalcemia and Paget's disease of bone, known to induce a concomitant acute phase, may have a significant influence on Lp(a) concentrations. Nine subjects (four men and five women), with plasma Lp(a) concentrations in the range between 6.4 and 17.7 mg/dl, were subjected to a single intravenous infusion of bisphosphonates (7.5 mg of aminohydroxybutylidene and 5.0 mg of aminohydroxylidene), previously dissolved in 250 ml of saline. Lp(a), apo A-I, apo B, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured at the baseline and after days one, two, four and seven. CRP, ESR and Lp(a) started to increase after two days from the treatment, reaching statistical significance after day two, four and seven, respectively. Apo B and apo A-I decreased significantly after days one and two, respectively. Although patterns and relative amounts of the increase of CRP were substantially different among the subjects studied, the increase of Lp(a) was more homogeneous; the peak of Lp(a) concentrations was reached only seven days after treatment in the group as a whole, in agreement with previous observations. In univariate regression analysis, significant correlations were found only between apo A-I and ESR, and apo A-I and Lp(a). The present study suggest that Lp(a) behaves as an acute phase protein. Besides, we observed a slight but significant decrease of apo A-I and apo B after administration of bisphosphonates.

Acute-Phase Proteins↗
PubMed1998

Effect of pyridoxal 5'-phosphate on human neutrophil respiratory burst and adhesion on serum coated microplates.

The effect of pyridoxal 5'-phosphate (PP) on human polymorphonuclear leukocytes respiratory burst and on cellular adhesion on serum coated microplates was investigated. No dose-response effect was observed after 10 min pre-treatment at 37 degrees C of human neutrophils with increasing doses of PP, ranging from 0.05 mM/L to 0.5 mM/L. The production of superoxide anion (O2-), after challenging cells with 0.5 pM/L formyl-methyonyl-leucyl-phenylalanine, 50 ng/mL phorbol myristate acetate or 50 pg/mL concanavalin A was comparable to that observed by pre-treating cells with phosphate buffered saline only (control, no PP), therefore indicating that PP did not affect neutrophil respiratory burst in our assay conditions. Evaluation of the effect on cellular adhesion onto fetal bovine serum pre-coated microplates produced the same results. As previous results showed that PP in the range of 0.01 mM/L to 0.6 mM/L proved to be an efficient inhibitor of neutrophil aggregation, the evidence reported here might contribute to establish PP as a good in vitro leukocyte anti-aggregant which does not affect other functional parameters.

Adult↗
PubMed1998

Expression of genes involved in nucleotide excision repair and sensitivity to cisplatin and melphalan in human cancer cell lines.

DNA repair has been proposed to be an important determinant of cancer cell sensitivity to alkylating agents and cisplatin (DDP). Nucleotide excision repair (NER), which represents one of the most important cellular DNA repair processes able to remove a broad spectrum of DNA lesions, is involved in the recognition and repair of the crosslinks caused by DDP and melphalan (L-PAM). In this study, the mRNA levels of the different genes involved in NER (ERCC1, XPA, XPB, XPC, XPD, XPF) were examined in a panel of eight different human cancer cell lines, together with the overall DNA repair capacity using a host cell reactivation assay of a damaged plasmid. A statistically significant correlation was observed between the relative expression of XPA/XPC (P < 0.05) and ERCC1/XPC (P < 0.05) mRNAs. No correlation was found between the DDP and L-PAM IC50S and the relative mRNA expression of the tested NER genes. When the overall cellular DNA repair capacity was studied, carcinomas seemed to have a higher repair activity than leukaemias; but this repair DNA activity correlated neither with the mRNA expression of the different NER genes nor with DDP and L-PAM IC50S. These data seem to suggest that even if the NER pathway is an important determinant for the cytotoxicity of alkylating agents, as demonstrated by the extremely high sensitivity to alkylating agents in cells lacking this repair system, other factors have to play a role in regulating the cellular sensitivity/resistance to these antitumour drugs.

Antineoplastic Agents↗
PubMed1998

Positive immunostaining with MLuC1 of bone marrow aspirate predicts poor outcome in patients with small-cell lung cancer.

BACKGROUND: Immunocytochemistry has been proven able to identify tumor cells in bone marrow aspirate (BMA) of patients with SCLC. However, few data exist about the clinical significance of the procedure. PATIENTS AND METHODS: 108 BMA taken from 60 patients were incubated with the MoAb MLuC1 (cluster 6) and stained by the APAAP (alkaline phosphatase-antialkaline phosphatase) method. The serum levels of LDH, TPA, NSE and CEA were also studied in relation to bone marrow involvement by means of discriminant analysis. RESULTS: Immunocytochemistry of the aspirate with MLuC1 detected positive cells in 23 patients (38%) (38 of 108 samples) vs. 13% of the conventional biopsies studied without MLuC1 (P < 0.001). With respect to bone marrow positivity, three groups of patients were identified: those with no positive cells in the aspirate and negative biopsy (group A); those with less than 10 positive cells in the aspirate and negative biopsy (group B); and those with more than 10 positive cells or clumps in the aspirate or positive biopsy (group C). Group C patients had poorer median survivals than those in the other two groups (5.5 vs. 11 months, respectively, P = 0.01). Discriminant analysis showed that the four serum markers were poor discriminators of the degree of bone marrow involvement, with only 55% of grouped cases being correctly classified. CONCLUSIONS: These results show that detection of bone marrow involvement i) can be improved by the use of MLuC1 ii) is not predictable by conventional tumor markers, and iii) is related to poor outcome.

Antibodies, Monoclonal↗
PubMed1998

Usefulness of lipids, lipoprotein(a) and fibrinogen measurements in identifying subjects at risk of occlusive complications following vascular and endovascular surgery.

The study was designed to establish the usefulness of measuring lipoprotein(a) [Lp(a)], total cholesterol, triglycerides, low-density lipoprotein [LDL]-cholesterol, high-density lipoprotein [HDL]-cholesterol, total-to-HDL-cholesterol ratio and fibrinogen in identifying subjects at risk of occlusive complications following vascular and endovascular surgery, including primary successful ileofemoral percutaneous transluminal angioplasty, infrainguinal and aortic bypass graft and carotid endarterectomy. A total of 68 volunteers subjected to vascular and endovascular surgery were recruited to the study. Six months after successful interventions, no occlusive complications verified by angiography were observed in 45 patients (66%; No-restenosis group), whereas significant restenosis or reocclusion occurred in 23 patients (34%; Restenosis group). Significant lower concentrations of Lp(a) (p=0.032), total cholesterol (p<0.0001), LDL-cholesterol (p=0.001) and total-to-HDL-cholesterol ratio (p<0.0001) and higher concentrations of HDL-cholesterol (p=0.048) were observed in the No-restenosis group compared to the Restenosis group. The concentrations of triglycerides (p=0.080) and fibrinogen (p=0.510) did not differ significantly between groups. In multivariate discriminant analysis, the best predictors of restenosis or reocclusion were in decreasing order: LDL-cholesterol, Lp(a), total-to-HDL-cholesterol ratio, HDL-cholesterol and total cholesterol. A statistical difference of particular interest was observed in the overall distribution of Lp(a) concentrations between groups (p<0.0001), occlusive complications being unlikely to occur in patients with Lp(a) concentrations below 50 mg L(-1). The potential interference from a concurrent acute phase response, the most common source of elevation of Lp(a) in humans, was less likely in view of the absence of differences in erythrocyte sedimentation rate between the No-restenosis and Restenosis groups (p=0.463). In conclusion, the results of the present investigation point to a definite role of the combined measurements LDL-cholesterol, Lp(a), total-to-HDL-cholesterol ratio, HDL-cholesterol and total cholesterol in the identification of subjects at risk of occlusive events following vascular and endovascular surgical procedures.

Angioplasty, Balloon↗
PubMed1998

Pulmonary manifestations of Gaucher disease: an increased risk for L444P homozygotes?

Pulmonary disease is a complication of Gaucher disease (GD), a lysosomal disorder due to the deficiency of glucocerebrosidase. Lung involvement was investigated through chest radiography, high-resolution computed tomography of the chest, pulmonary function tests (PFT), and oxygen saturation (SaO2) at 21% FI(O2) in 13 Italian GD patients, six homoallelic for the L444P mutation (Group A), seven with various genotypes (Group B). Echocardiography and transcutaneous oxygen tension measurement at room air and after breathing 100% oxygen were performed to exclude pulmonary hypertension and/or intrapulmonary shunts. A score index (SI) including lung involvement evaluated the severity of GD. In three Group A patients with respiratory symptoms and in an asymptomatic male interstitial involvement was demonstrated; one child died of aspiration pneumonia. Group B patients had no signs of lung damage; PFT were normal in all cases but one. SaO2 was normal in both groups. Pulmonary vascular disease was ruled out in three cases with respiratory symptoms. In Groups A and B the median SI were 22 and 13, respectively (p < 0.01). L444P homozygotes appear at major risk for developing pulmonary disease, even at earlier ages. A comprehensive evaluation of lung involvement is recommended primarily in these subjects.

Adolescent↗
PubMed1998

Standardization and clinical management of lipoprotein(a) measurements.

The present article proposes personal suggestions to improve determinations and clinical interpretation of results of lipoprotein(a) assays. Methods and procedures for sampling and quantification of the various isoforms of lipoprotein(a) in serum, plasma and urine are reviewed with the aim of improving the reliability and reproducibility of results and reinforcing the clinical utility of lipoprotein(a) measurements.

Arteriosclerosis↗