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We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

Objective: To evaluate the effects of hyperbaric oxygen (HBO) therapy on the coagulation cascade using an experimental model of multiple organ failure syndrome (MOFS). Design: MOFS was induced by zymosan (500 mg/kg i. p.) in rats. HBO therapy (2 ATA) was administered in a cylindrical steel chamber 4 and 11 h after zymosan administration. In a separate set of experiments animals were monitored for 72 h, and systemic toxicity was scored. Intervention: Eighteen hours after zymosan administration, rats were killed and blood samples were used for analysis of hemocoagulative parameters, hemodynamics, and arterial blood gas. Main results: Zymosan administration caused MOFS by affecting the coagulation cascade, as shown by a significant increase in plasma levels of fibrinogen, tissue plasminogen activator, inhibitor of tissue plasminogen activator of type 1, and plasma levels of fibrin degradation products vs. control rats. Zymosan-induced MOFS was also characterized by a significant increase in von Willebrand antigen plasma levels vs. controls. Moreover, zymosan administration induced a significant fall in mean arterial blood pressure and alteration in blood gas values. HBO therapy significantly reduced the derangements of coagulation cascade, the fall in mean blood pressure and alteration in blood gas induced by zymosan administration. Conclusions: The hypercoagulability induced by zymosan could be responsible for organ failure and death. Our data demonstrate that HBO therapy significantly prevents the alteration in the coagulation cascade and arterial blood gas in an experimental model of MOFS.

In patients with end-stage renal disease on maintenance hemodialysis, coagulation abnormalities such as hypercoagulability and thrombosis are common. Thrombotic complications in uremic patients are frequent and include those occurring at the vascular access and in the coronary, cerebral, and retinal arteries. Data do not entirely clarify the mechanisms involved and further investigations are necessary. Here we show a summary of coagulation and fibrinolytic disorders in uremia and the novelties foreseen in molecular biology.

OBJECTIVES: To evaluate the possible relationship between angiotensin-converting enzyme (ACE) insertion-deletion (ID) genotype and insulin resistance in a population of healthy older Italian subjects. DESIGN: Prospective recruitment of a convenience sample. SETTING: Outpatient clinic. PARTICIPANTS: One hundred twenty-five subjects age 62 to 105 in good health and not taking any drug known to interfere with glucose metabolism. MEASUREMENTS: Anthropometric measurements; fasting plasma glucose (FPG), and fasting plasma insulin (FPI) concentrations; oral glucose tolerance test; homeostatic method assessment (HOMA) to estimate degree of insulin resistance; and ACE genotype by polymerase chain reaction. RESULTS: In the sample population, the relative frequencies of the ACE genotypes deletion-deletion (DD) (0.424), ID (0.400), and insertion-insertion (II) (0.176) were not significantly different from values predicted by Hardy-Weinberg equilibrium. The genotype distribution was similar in men and women. Subjects carrying the II genotype had a higher FPG (P

Study objectives To investigate whether the FIIA20210 mutation is associated with isolated pulmonaryembolism (PE). Design Case-control study. Setting Five thrombosis centers in southern Italy. Patients Six hundred forty-seven consecutive referredpatients with objectively documented venous thrombosis and 1,329control subjects. Measurements and results Medicalhistories were collected. The G-to-A transition at nucleotide 1691within the factor V gene (FV Leiden) and the G-to-A transition atnucleotide position 20210 within the prothrombin gene locus (FIIA20210), levels of anticoagulant factors, and levelsof antiphospholipid antibodies were determined by standard techniques.Patients with deep venous thrombosis (DVT) of the lower extremities(n = 346) or with additional PEs (n = 175) showed similarprevalences of FV Leiden mutation (24.3% and 16.6%, respectively) andFII A20210 mutation (14.2% and 12.6%, respectively), andsimilar deficiencies of natural anticoagulants (4.9% and 2.3%,respectively). In both groups, the frequencies of FV Leiden and/or FIIA20210 mutation were higher than those observed among 1,329apparently healthy control subjects (4.8% and 4.4%, respectively;p Conclusions FIIA20210 mutation is associated with DVT in the lowerextremities alone or when complicated by PE, but it is not associatedwith isolated PE.

We report the case of a 31-year-old woman who, at the age of 26 suffered from an episode of superficial thrombophlebitis in the left leg, experienced two episodes of transient ischemic attacks at the age of 30 and had an ischemic stroke with left-sided hemiparesis at the age of 31 years. A cerebral CT scan showed an ischemic lesion in the right sylvian area involving the opercular and nucleocapsular regions. Her father had had an ischemic stroke at the age of 54 years and died at the age of 58; her mother had had a myocardial infarction at the age of 48 years and died at 51 years from breast cancer. Laboratory investigation of the patient demontrated high levels of fibrinogen, F II, F VII, F 1 + 2, FPA and ACA-IgG with low levels of HDL cholesterol associated with homozygosity for the 20210 A genotype. There were no other genetic or acquired prothrombotic defects. In conclusion, this case strongly suggests a clinically significant role ot the prothrombin gene mutation in both arterial and venous thrombosis.

Objective To compare the effects of GnRH–agonist/recombinant rFSH versus GnRH-antagonist/recombinant FSH stimulation on follicular fluid levels of soluble intercellular adhesion molecule (sICAM)-1 and vascular cell adhesion molecule-1 (sVCAM-1) during in vitro fertilization (IVF). Design Prospective, randomized study. Setting University hospital. Patient(s) Seventy-three women underwent IVF. Intervention(s) GnRH-agonist/rFSH or GnRH-antagonist/rFSH administration and collection of follicular fluid from 3 small (11–14 mm in diameter) and 3 large (18–21 mm in diameter) follicles on the day of oocyte retrieval. Main Outcome Measure(s) Follicular fluid levels of sICAM-1 and sVCAM-1 and intrafollicular estradiol and progesterone were also measured. Result(s) Women who underwent GnRH-agonist/rFSH showed higher concentrations of sICAM-1 in both small and large follicles were compared with patients who received GnRH-antagonist/rFSH treatment; follicular fluid levels of sVCAM-1 were similar between the 2 stimulation protocols. Content of sICAM-1 in small and large follicles positively correlated with the number of follicles of ≥15 mm and the number of oocytes that were retrieved in both study groups. Concentrations of follicular fluid sVCAM-1 and progesterone were higher in large than in small follicles and were correlated positively to each other in both follicular classes. Conclusion(s) In IVF, GnRH-agonist/rFSH is associated with higher follicular fluid levels of sICAM-1 compared with GnRH-antagonist/rFSH regimen. Intrafollicular sICAM-1 content may predict ovarian response, and sVCAM-1 appears as an indicator of the degree of follicular luteinization.

Background Benign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH. Patients and methods The incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background. Results The number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p < .001; Fisher Exact Test). Moderate to high titers of anticardiolipin antibodies (β2-Glycoprotein type I) were found in 8 out of 17 patients. Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p < .001; Fisher Exact Test). Gene polymorphisms for factor V Leiden mutation, prothrombin mutation 20210 A/G, MTHFR 677 C/T, PAI-1 4G/5G, ACE I/D were detected in 13 patients. Discussion In agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH. Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

This study has evaluated whether systemic changes of plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) parallel the adhesions development and whether they could be used as predictors of adhesion risk. This has been studied in an animal model of post-surgical peritoneal adhesion by monitoring for 10 days the plasma and tissue levels of t-PA and PAI-1. The results showed that both tissular and plasmatic levels of t-PA were decreased in concomitance with the development of peritoneal adhesions. In contrast, PAI-1 was found increased into the tissue and into the plasma samples of the rats taken at 5 and 10 days time points. Inflammatory mediators such as ICAM-1, VCAM-1, and IL-6 within the peritoneal lavage fluid also correlated with the adhesion formation process. In conclusion, post-surgical peritoneal adhesions provide alterations of local inflammatory components and local and systemic fibrinolytic components, possibly with PAI-1 quenching t-PA. This may have potential for the identification of high-risk patients.

In uremia, plasma levels of anti-protein C and anti-protein S antibodies are associated with thrombosis. Background Vascular access thrombosis is an important cause of morbidity in patients with end-stage renal failure on maintenance hemodialysis (MHD). However, little is known about its risk factors. The present study was undertaken to evaluate the role of coagulation factors, fibrinolytic factors, and anti-phospholipid antibodies (aPL). In particular, we have evaluated the role of anti-protein C and anti-protein S antibodies in patients on MHD with and without thrombosis because no data are available in the literature. Methods The study group comprised 30 patients with thrombotic complications (TC), 40 patients matched for age, sex, and dialytic age with no thrombotic complications (NTC) and 400 controls. We have measured: anti-protein C antibodies, anti-protein S antibodies, anticardiolipin antibodies (ACA), anti-β2-glycoprotein antibodies (β2-GPI), and anti-prothrombin antibodies (aPT), along with prothrombin time, fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, APC-resistance test, D-dimer, tissue-type plasminogen's activator, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, factors of the intrinsic and extrinsic pathway, C-reactive protein, and homocysteine. Results There were no significant differences between groups for prothrombin time, fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, activated protein C (APC) resistance, D-dimer, tPA, C-reactive protein, Factors II, X, and VII. The anti-β2-GP1 and aPT were elevated in both TC and NTC patients, compared to the control group. Significant differences between TC and NTC groups were found for anti-protein C and anti-protein S antibodies, ACA-IgM, PAI-1, Factor VIII, prothrombin fragments 1+2, and homocysteine. Conclusion The most novel finding was a significant elevation of anti-protein C antibodies and anti-protein S antibodies in the TC group (i.e., in patients on MHD with thrombosis of vascular access). It indicates that other pathogenetic mechanisms in addition to endothelial damage may cause hypercoagulability in uremia.

To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P

Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non–systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition, there was a reduction of factor XII during the treatment. It is possible to assume in the TC group and, to a lesser extent, also in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen, which causes hypofibrinolysis. In addition, an excess of factor VIII is activated by endothelial dysfunction with subsequent activation of the coagulation cascade as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of interfering with the system of protein C, a potent anticoagulant factor that inactivates cofactors Va and VIIIa. They also induce the expression of procoagulant factors on the surface of the endothelial cells. In conclusion, the hypercoagulable state caused by alterations of coagulation and fibrinolytic factors is a cause of vascular access dysfunction and thrombosis of other vessels.

Previous studies demonstrated a relationship between the degree of insulin resistance and plasma plasminogen activator inhibitor type-1 (PAI-1) levels. We aim at investigating the relationship between the degree of insulin resistance and plasma PAI-1 levels in aged subjects (n=83) and in healthy centenarians (n=42). In all subjects the degree of insulin resistance was assessed by HOMA method. Our data demonstrated that healthy centenarians have higher plasma PAI-1 levels (73.1+/-13.9 vs 23.7+/-14.7 ng/ml, P0.001) and lower degree of insulin resistance (1.4+/-0.5 vs 3.3+/-1.3, P0.001) than aged subjects. In aged subjects plasma PAI-1 levels correlated with the degree of insulin resistance (r=0.61, P0.001), fasting plasma triglycerides (r=0.74, P0.001) and age (r=0.33, P0.001). All such associations were lost in centenarians. Plasma PAI-1 Ag levels were also similar in aged subjects and centenarians even after categorization for PAI gene polymorphism. In multivariate analysis, a model made by age, sex, body mass index, fasting plasma triglycerides, HOMA and PAI-1 gene explained 65 and 50% of plasma PAI-1 level variations in aged subjects and centenarians, respectively. Nevertheless, HOMA (P0.001) was significantly and independently associated with plasma PAI-1 levels only in aged subjects. In conclusion, our data demonstrates that in healthy centenarians, plasma PAI-1 were not associated with the degree of insulin resistance as in aged subjects. Frequency of PAI-1 genotype does not provide an explanation for such differences between aged subjects and centenarians.

Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by a hemorrhagic diathesis of variable severity. Although more than 100 families with this disorder have been described, genetic defects have been characterized in few cases. An investigation of a young propositus, offspring of a consanguineous marriage, with undetectable levels of functional and quantitative fibrinogen, was conducted. Sequence analysis of the fibrinogen genes showed a homozygous G-to-A mutation at the fifth nucleotide (nt 2395) of the third intervening sequence (IVS) of the γ-chain gene. Her first-degree relatives, who had approximately half the normal fibrinogen values and showed concordance between functional and immunologic levels, were heterozygtes. The G-to-A change predicts the disappearance of a donor splice site. After transfection with a construct, containing either the wild-type or the mutated sequence, cells with the mutant construct showed an aberrant messenger RNA (mRNA), consistent with skipping of exon 3, but not the expected mRNA. Sequencing of the abnormal mRNA showed the complete absence of exon 3. Skipping of exon 3 predicts the deletion of amino acid sequence from residue 16 to residue 75 and shifting of reading frame at amino acid 76 with a premature stop codon within exon 4 at position 77. Thus, the truncated γ-chain gene product would not interact with other chains to form the mature fibrinogen molecule. The current findings show that mutations within highly conserved IVS regions of fibrinogen genes could affect the efficiency of normal splicing, giving rise to congenital afibrinogenemia.

The objective of this study was to evaluate the relationship of whole blood viscosity and its major determinants (plasma fibrinogen level, hematocrit, hemoglobin and blood cell count) to advancing age. A total of 249 subjects (mean age 49.9+/-21.5; range 19-102 years) were included in the study. They were divided into three groups, (A)30 years of age, n, 58; (B) 30-60 years, n, 107; (C)60 years, n, 84. Whole blood viscosity at two different rates of shear (450 and 45 s(-1)) was evaluated using a cone-plate digital viscosimeter. The hematological parameters (hematocrit, hemoglobin and blood cell count) were evaluated using an automatic Coulter Counter. Plasma fibrinogen concentration was measured by a clotting method. When both sexes are considered together, whole blood viscosity shows no significant difference among age groups. Plasma fibrinogen concentration significantly increases with age (P0.001); hemoglobin, red blood cell count and platelet count, on contrary, are significantly lower in aged group. In the male sex, blood viscosity at higher shear rate (450 s(-1)) negatively correlates with advancing age (P0.005). The age-related decrease of hematocrit value in the male sex accounts for this occurrence.

Extensores digitorum longi of rats, infarcted and denervated by different surgical procedures, were used to analyze by biochemical and cytochemical methods the acetylcholinesterase (AChE) changes during muscle degeneration, regeneration, and early or delayed reinnervation. Biochemical tests showed that the regenerating muscle produces globular AChE forms (36% of controls) and small amounts of A12 (16S) asymmetric form (5% of controls); at the end of the regeneration, innervation and electromechanical function are required for the complete recovery of globular forms, and are absolutely critical to prevent A12 (16S) disappearance. Cytochemical observations showed that, unlike nicotinic receptor, AChE deposited at the neuromuscular junction before ischemic necrosis is protected from breakdown, as is the basal lamina of muscle fibers. Taken together, these observations contribute to the understanding of the factors that play a critical role in muscle repair and are, therefore, of clinical relevance.

Context: Increased levels of homocysteine are associated with risk of cardiovascular disease. Homocysteine may cause this risk by impairing endothelial cell function. Objective: To evaluate the effect of acute hyperhomocysteinemia with and without antioxidant vitamin pretreatment on cardiovascular risk factors and endothelial functions. Design and Setting: Observer-blinded, randomized crossover study conducted at a university hospital in Italy. Subjects: Twenty healthy hospital staff volunteers (10 men, 10 women) aged 25 to 45 years. Interventions: Subjects were given each of 3 loads in random order at 1-week intervals: oral methionine, 100 mg/kg in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine- free fruit juice (placebo). Ten of the 20 subjects also ingested a placebo load with vitamins. Main Outcome Measures: Lipid, coagulation, glucose, and circulating adhesion molecule parameters, blood pressure, and endothelial functions as assessed by hemodynamic and rheologic responses to L-arginine, evaluated at baseline and 4 hours following ingestion of the loads. Results: The oral methionine load increased mean (SD) plasma homocysteine level from 10.5 (3.8) μmol/L at baseline to 27.1 (6.7) μmol/L at 4 hours (P

Context.—C1 inhibitor (C1-INH) is an α2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The α-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE).Objective.—To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE.Design.—Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate.Patients.—In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria.Measurements.—Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5μM; collagen, 5 μg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay).Results.—After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate– and collagen-induced platelet aggregation versus preinfusion values (maximum after 1–2 days; P < .001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively.Conclusions.—These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.

Low-to-high frequency ratio (LF/HF) is an indirect index of sympathovagal balance derived by heart rate spectral analysis. We investigated the effect of glucose ingestion on LF/HF in 17 healthy, normotensive young subjects (9 male, 8 female) with a wide body fat content range (body fat = 29 +/- 5.9%; range = 19-42%) and a normal thyroid hormone status. Before and after an oral glucose tolerance test (OGTT), the Holter technique and indirect calorimetry allowed us to determine heart rate and substrate oxidation in all subjects. At baseline, LF/HF correlated with body fat (r = 0.60, P < 0.005), waist-to-hip ratio (r = 0.57, P < 0.01), fasting plasma insulin (r = 0.55, P < 0.04), leptin (r = 0.56, P < 0.01), and norepinephrine (r = 0.58, P < 0.009) concentrations. Age-, body fat-, content-, and fat-free mass-adjusted respiratory quotient (r = 0.59, P < 0.007) and basal metabolic rate (r = 0.61, P < 0.001) were also correlated with basal LF/HF. Along with OGTT plasma glucose, insulin and norepinephrine concentrations and basal LF/HF significantly rose at 60 min and then declined throughout the test. Area under the curve (AUC) for LF/HF correlated with body fat (r = -0.66, P < 0.004), fasting plasma leptin concentration (r = -0.57, P < 0.01), glucose induced thermogenesis (r = 0.62, P < 0.001), glucose uptake (r = 0.59, P < 0.007), and AUC for plasma norepinephrine concentration (r = 0.63, P < 0.001). Water instead of glucose ingestion does not significantly affect LF/HF (n = 8). In conclusion, our study supports the hypothesis that glucose ingestion affects LF/HF and that such change is related to the amount of body fat.

Abstract —At a young age, ischemic stroke is an uncommon event in which prothrombotic factors are likely to play an important role. In 202 referred cases, 105 men and 97 women, median age 39 years (range, 3 to 50), with a history of ischemic stroke and in 1036 age frequency-matched apparently healthy individuals from the same ethnic background, we have investigated whether inherited prothrombotic conditions increase the risk of ischemic stroke. Neither abnormal plasma levels of natural anticoagulants and fibrinogen nor significant increase of the prothrombin A 20210 allele was found in stroke cases compared with controls. Hypertension (odds ratio [OR], 22.61), male sex (OR, 2.30), smoking (OR, 2.78) and alcohol habits (OR, 0.14), a personal history of venous thromboembolism (OR, 4.53), a family history of stroke (OR, 1.93), high circulating levels of fibrinogen ( P =0.0190), and total cholesterol ( P =0.101) were all independently associated with ischemic stroke. Compared with noncarriers, carriers of the factor V (FV) Leiden mutation (OR, 2.56), and to a lesser extent, of the methylenetetrahydrofolate reductase (MTHFR) TT genotype (OR, 1.60), had an independent higher estimated risk of having a history of ischemic stroke. The relationship with the FV Leiden mutation was greater in women (OR, 3.95). Thus, in addition to established determinants, FV Leiden mutation is independently associated with the occurrence of ischemic stroke in this setting. The greater association in women suggests the possibility of an interaction of this genotype with female hormones.