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Biomedical subjects

G Lippi

Publications and source records attributed to G Lippi.

At least 55 records · Page 3Linked to original sources

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↗

Volatile alkanes and increased concentrations of isoprene in exhaled air during hemodialysis.

In this study we examined breath volatile hydrocarbon concentrations in exhaled air of hemodialysis patients. We assessed both C(2)-C(5) alkanes - among them ethane and pentane the production of which in man is essentially due to the action free radicals exert on polyunsaturated fatty acids - and isoprene, an unsaturated hydrocarbon the biosynthesis and biological effects of which are the subject of controversy and mounting interest. Twenty patients were studied. Evaluation was performed intrapatient in the breath of patients with chronic renal failure, before and after dialysis (20 patients) and, in the same cases, during hemodialytic treatment (10 patients). Breath concentrations of these volatile hydrocarbons, determined before dialysis, were not different from those of normal subjects. Dialysis did not modify the levels of the C(2)-C(5) saturated hydrocarbons ethane, propane, butane and pentane. Instead, there was a marked increase in isoprene in all patients (basal values rose by a mean of 270%). Since isoprene was not present in the fluids or filters used for dialysis and there were only traces in the ambient air, the isoprene must have been produced endogenously during hemodialysis. As no situation has previously been reported to increase endogenous production of isoprene in humans, patients in hemodialysis offer a unique opportunity to investigate in depth the medical, biological and toxicological aspects of isoprene.

Adult↗

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↗

[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↗

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↗

Hereditary motor and sensory neuropathy with deafness, mental retardation, and absence of sensory large myelinated fibers: confirmation of a new entity.

We describe two brothers, 11 and 13 years old, respectively, with an early-onset hereditary motor and sensory neuropathy, deafness, and mental retardation. Electrophysiological studies showed marked reduction of motor and sensory conduction velocity and absence of sensory action potentials. Sural nerve biopsy, performed in both patients, showed absence of large myelinated fibers with normal density of small myelinated fibers without axonal degeneration. Signs of demyelination were found only in the younger patient. We suggest that motorsensory neuropathy associated with deafness and mental retardation with absence of large myelinated fibers on sural nerve biopsy represents a distinct clinicopathological entity, which is transmitted in families probably as an autosomal recessive trait.

Adolescent↗

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↗

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↗

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↗

Evaluation of the analytical performances of a new fully automated commercial immunonephelometric assay for lipoprotein(a).

Several commercial methods have been proposed for lipoprotein(a) (Lp(a)) measurements over the past decades. However, only a few of them appear completely suitable in terms of analytical performance, costs and practicability. We evaluated the analytical performance of a new commercial fully automated immunonephelometric assay for Lp(a) measurements on the IMMAGE Immunochemistry System. Mean within- and between-run coefficients of variation were 2.7% (range 1.2-4.7%) and 3.8% (range 1.8-7.9%), respectively. The linearity of the assay was confirmed up to 102 mg/dl and the deviation from the expected values did not exceed 4% (mean deviation: 1.9%). Moreover, the relative non-linearity was acceptable, ranging from 1.4% to 1.6% and hence constantly lower than the 2.5% upper limit. Since there is no reference method for Lp(a) measurements, 100 routine random serum samples measured by the IMMAGE Immunochemistry System immunonephelometric assay were further compared with two other commercial immunonephelometric assays (Array LPA immunonephelometric assay and BNA Latex-Enhanced Lp(a) nephelometric assay). Non-parametric regression and relative Spearman's correlation coefficients were satisfactory, (y=1.009x - 1.38; r=0.998 IMMAGE Immunochemistry System vs. Array LPA and y=0.922x - 0.40; r=0.989 IMMAGE Immunochemistry System vs. Behring Nephelometer Analyzer (BNA) Latex Lp(a) assay). On the basis of the results of the present evaluation we conclude that the analytical performance and the main technical features of the IMMAGE Immunochemistry System immunonephelometric assay make it a suitable method for Lp(a) measurement in clinical laboratories.

Automation↗

Evaluation of the activated partial thromboplastin time (APTT) sensitivity to heparin using five commercial reagents: implications for therapeutic monitoring.

Heparin is an effective drug for prevention and treatment of thromboembolic conditions. Although several biological assays have been proposed for monitoring unfractionated heparin therapy, the measurement of the activated partial thromboplastin time (APTT) is the most widely employed test, and the overall risk of thromboembolic episodes was markedly reduced by maintaining APTT ratios above 1.5. However, the adjustment of the heparin therapy on the basis of APTT presents several questions which are still unresolved. Major discrepancies were found in APTTs performed using different reagents in both ex vivo and in vitro heparinized samples and occasionally with different lots of the same reagents; poor correlation was observed between APTT values and plasma heparin concentrations. In order to gain further insights into this phenomenon, we analysed the sensitivity to heparin of five commercial reagents for APTT measurement in 19 ex vivo heparinized samples. Differences were observed; correlation coefficients ranged from 0.820 to 0.985 and slopes of linear regressions from 0.26 to 1.14. Moreover, unsatisfactory correlations were obtained when APTT ratios were compared with heparin plasma concentrations in the same patients' samples. In the heparin therapeutic range of 0.35 - 0.70 U/ml, reagent-dependent differences were observed in the corresponding APTT values. These results point out a critical role of the assay methodology in monitoring heparin therapy by APTT. We suggest that reference materials and methods should be urgently identified, a universally agreed scale for reporting results should be established and reference ranges for the unfractionated heparin therapy should be reconsidered taking on account the reagent employed.

Case-Control Studies↗

Effects of nandrolone decanoate (Decadurabolin) on serum Lp(a), lipids and lipoproteins in women with postmenopausal osteoporosis.

Although lipoprotein(a) (Lp(a)) concentrations are mainly regulated genetically, it has been reported that variations in sex hormone concentrations may have effects on serum Lp(a). We evaluated the effect of nandrolone decanoate, a testosterone-derived synthetic anabolic steroid, on serum Lp(a), lipids and lipoproteins in 19 postmenopausal women who were given parenteral nandrolone decanoate (Decadurabolin) once a week for 3 weeks. At the 4th week, a significant decrease was observed for total cholesterol (p = 0.003), Lp(a) (p = 0.0003), apolipoprotein A-I (apo A-I) (p < 0.0001), and high density lipoprotein-cholesterol (HDL-C) (p < 0.0001). Moreover, a significant decrease in serum albumin concentration (p = 0.002) was concomitantly observed. We conclude that the administration of nandrolone decanoate significantly affects the lipid profile of postmenopausal women, showing controversial effects in terms of cardiovascular risk.

Anabolic Agents↗

Blood pressure trend and cardiovascular events in nuns in a secluded order: a 30-year follow-up study.

30-year data are presented on blood pressure and cardiovascular morbidity and mortality for 144 nuns living in a secluded order in six nunnerlie in Umbria, central Italy and 138 lay women from the same region. There were no significant differences at baseline regarding age, blood pressure, body mass index, race, ethnic background, menarche, family history of hypertension or 24-hour urinary sodium excretion. None of the women were smokers and none took birth control pills nor did they use estrogen replacement therapy. During the observation period blood pressure remained remarkably stable among the nuns. None showed a rise in diastolic blood pressure to above 90 mm Hg. On the contrary the lay women showed the expected rise in blood pressure with age. This resulted in a gradually greater difference (delta > 30/15 mm Hg) in blood pressure between the two groups, which was statistically significant. There were 31 fatal and 69 non-fatal cardiovascular events during the 30 years of follow-up. These were significantly more common in the lay women, 10 vs. 21 fatal and 21 vs. 48 non-fatal in the nuns and lay women respectively. It appears reasonable to assume that the difference in psychosocial stress is the main underlying factor for the observed findings.

Adult↗