Reply to: Lipoprotein (a) and chronic obstructive pulmonary disease.
Explore the source record for details and available documents.
Artifacts↗
Biomedical subjects
C Cordova
Publications and source records attributed to C Cordova.
Rebuttal to circulating IL-6 levels in chronic obstructive pulmonary disease.
Explore the source record for details and available documents.
Coronary Disease↗
Soluble P-selectin as a marker of platelet hyperactivity in patients with chronic obstructive pulmonary disease.
A comparative analysis between soluble (s) P-selectin and von Willebrand Factor (vWF) was performed in 40 patients with chronic obstructive pulmonary disease (COPD) and 20 healthy subjects, with the aim of investigating whether the occurrence of elevated levels of sP-selectin may reflect activation of platelets, endothelial cells, or both. Plasma sP-selectin levels were significantly higher in patients compared to controls (P < 0.01). Similarly vWF levels were elevated in patients compared to healthy subjects, although the difference did not reach statistical significance. Lipoprotein (a) [Lp(a)] levels were lower in COPD patients than controls (P < 0.0001). The analysis of the correlation among all the variables demonstrated that plasma sP-selectin did not correlate with vWE. Conversely, plasma sP-selectin levels significantly correlated with either oxygen (rho = -0.41, P < 0.05) or carbon dioxide (rho = 0.47, P < 0.05) tension. An inverse correlation between serum Lp(a) and plasma sP-selectin levels (rho = -0.35, P < 0.05) was also observed. Moreover, increasing levels of sP-selectin in COPD patients significantly correlated with the impairment of blood gas tensions. In conclusion, the results obtained indicate the prominent platelet origin of circulating sP-selectin, suggesting that sP-selectin might be considered a marker of in vivo platelet activation in patients with COPD.
Adult↗
Lipoprotein(a) serum levels in patients affected by chronic obstructive pulmonary disease.
A recent study has suggested that symptoms of chronic bronchitis predict the risk of coronary disease independently of the known major cardiovascular risk factors. High serum levels of lipoprotein(a) (Lp(a)) have also been considered as an independent risk factor for coronary heart disease. Therefore, the aim of the present study was to investigate the behaviour of Lp(a) in patients affected by chronic obstructive pulmonary disease (COPD). Serum levels of total-cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, apolipoprotein (Apo) B-100, and Lp(a) were measured in 90 COPD patients and in 90 normal subjects matched for age, sex and smoking habit. COPD patients showed lower serum levels of Apo B-100 (P<0.0001) and Lp(a) (P<0.003) compared to controls. Conversely, TC, HDL-C, LDL-C and triglycerides were similar between patients and controls. No significant differences were found in Apo B-100 and Lp(a) levels of patients either undergoing different therapeutic regimens, or with different smoking habits. A significant correlation between Apo B-100 and Lp(a) (rho=0.433, P<0. 0001) was also observed. In conclusion, COPD patients do not show an atherogenetic lipid pattern and their increased risk of coronary disease could be attributable to different factors, such as the ongoing hypercoagulability state often associated with COPD.
Adult↗
Soluble P-selectin and proinflammatory cytokines in patients with polygenic type IIa hypercholesterolemia.
Plasma soluble P-selectin (sP-selectin), beta-thromboglobulin (beta-TG), von Willebrand Factor (vWF), prothrombin factor 1+2 (F1+2), IL-6 and IL-1beta levels were analyzed in 35 consecutive patients with polygenic type IIa hypercholesterolemia (HC) and 35 age- and sex-matched healthy subjects. sP-selectin (p < 0.005), beta-TG (p < 0.05) and IL-1beta (p < 0.02) levels were higher in HC patients than healthy subjects whereas no significant difference was observed for vWF. sP-selectin directly correlated with beta-TG (p < 0.05) and IL-1beta levels (p < 0.005), but not with the other variables analyzed. A direct correlation was observed between F1+2 and IL-6 (p < 0.05), total cholesterol (p < 0.05) or LDL cholesterol (p < 0.05). We conclude that HC is associated with an increase of plasma sP-selectin levels, and that sP-selectin may be considered as a marker of in vivo platelet activation in type IIa polygenic HC. The correlations observed among the variables analyzed in the study suggest that proinflammatory cytokines might play a role in the prothrombotic state often associated with HC.
Adult↗
Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress.
Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2alpha-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2alpha-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2alpha-III were significantly higher in patients with COPD (median, 84 pmol/ mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol/mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = -0.38, p = 0. 019). Aspirin treatment failed to decrease urinary levels of iPF2alpha-III (102 +/- 8 versus 99.2 +/- 7.3 pmol/ mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 +/- 74 versus 95 +/- 10 pmol/mmol creatinine) (p < 0.0001). Elevated levels of iPF2alpha-III (median, 125 pmol/mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol/mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2alpha-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.
Age Factors↗
Enhanced lipid peroxidation in hepatic cirrhosis.
BACKGROUND: Lipid peroxidation is thought to play a role in the evolution of liver damage, based on evidence in experimental models. However, evidence that lipid peroxidation occurs in patients with liver disease remains to be provided. We addressed the hypothesis by measuring levels of 8-epi Prostaglandin F2 alpha a bioactive prostaglandin isomer produced by free radical catalyzed peroxidation of arachidonic acid, in patients with liver cirrhosis. METHODS: In 42 patients with hepatic cirrhosis 8-epi Prostaglandin F2 alpha, factor VII activity, endotoxemia, carotenoids and alpha-tocopherol were measured. In 10 patients 8-epi Prostaglandin F2 alpha was also measured before and 30 days after 300 mg b.i.d. vitamin E administration. RESULTS: Cirrhotic patients had significant higher 8-epi Prostaglandin F2 alpha, excretion than controls [median (range): 199.2 (60.0-812) vs 85.9 (55.6-160.0) pg/mg creatinine, p < 0.0001]. Patients with urinary 8-epi Prostaglandin F2 alpha above the range in controls were more likely to have moderate or severe than mild liver failure (p < 0.004). They also had lower factor VII activity (62 +/- 19 vs 74 +/- 15%, P < 0.02) than patients with normal levels of the isoprostane. Urinary excretion of 8-epi Prostaglandin F2 alpha correlated directly with endotoxemia (Rho = 0.56, p < 0.0002) and inversely with factor VII (Rho = -0.39, p < 0.02). Cirrhotic patients given vitamin E showed a significant decrease of urinary 8-epi Prostaglandin F 2 alpha [median (range): 342.5 (170 - 812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04]. CONCLUSION: This study demonstrated that lipid peroxidation is increased in vivo in patients with cirrhosis and suggests that oxidant stress might contribute to the deterioration of liver disease.
Adult↗
Increased thromboxane metabolites excretion in liver cirrhosis.
An augmented systemic production of thromboxane (TX) A2, as assessed by urinary excretion of the thromboxane metabolites, has been described in severe liver cirrhosis. However, the significance of this finding remains unclear since in liver cirrhosis a number of phenomena i.e. altered hepatic TXA2 metabolism, increased intrasplenic platelet destruction, may affect TXA2 entry into systemic circulation as well as its metabolism. In order to further clarify this, we measured both major enzymatic metabolites of TXB2 in the urine of 44 patients affected by liver cirrhosis, subdivided in three classes on the basis of Child-Pugh criteria. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were assayed with previously validated RIA techniques. The urinary excretion rate of 11-dehydro-TXB2 was significantly (p = 0.0001) increased in the cirrhotic patients (673.5 pg/mg cr, median) in comparison with the controls (275 pg/mg cr, median) but no significant difference could be demonstrated among the excretion rates of the three patient subgroups. The excretion rate of 2,3 dinor-TXB2 was also significantly (p = 0.0001) increased in the patients (824 pg/mg cr, median) in comparison with controls (175 pg/mg cr, median), with a significant (p < 0.05) increase from class A (381 pg/mg cr) to class C (1337 pg/mg cr). The sum of the two enzymatic metabolites was significantly (p = 0.0001 ) increased in the cirrhotic patients in comparison to controls, with a progressive increase from class A (1003 pg/mg cr, median) to class C (2240 pg/mg cr, median). The urinary excretion of 2,3 dinor-TXB2 was significantly (p = 0.008) related to plasma prothrombin fragment 1+2 (F1+2). This study provides further evidence of increased thromboxane biosynthesis in liver cirrhosis. Moreover, we demonstrate intraliver shift of thromboxane metabolic disposition, due to progressive liver decompensation, because only the fraction undergoing beta-oxidation to 2,3-dinor-TXB2 was progressively increased with the degree of liver failure. We, also, find a significant correlation between urinary excretion of 2,3-dinor-TXB2 and plasma F1+2, suggesting that clotting activation could partly account for in vivo platelet activation.
Adult↗
Simvastatin reduces monocyte-tissue-factor expression type IIa hypercholesterolaemia.
Explore the source record for details and available documents.
Anticholesteremic Agents↗
Lipoprotein (a) serum levels in patients with hepatocarcinoma.
Lipoprotein (a) [Lp(a)] is synthesised by liver cells, and patients with liver cirrhosis (LC) show low serum levels of Lp(a) associated with the degree of liver failure. On the contrary, increased serum levels of Lp(a) have been reported in patients with cancer. In this report, the behaviour of Lp(a) serum levels in patients with hepatocarcinoma (HC), a complication of LC, has been evaluated with the aim to study whether HC cells were able to cause an increase of serum concentrations of this lipoprotein when impaired liver protein synthesis is present. We selected eighteen patients affected by LC + HC, eighteen patients matched for sex, age and degree of liver failure with LC only, and eighteen patients with other cancer types. A significant increase of serum levels of Lp(a) was observed in patients affected by LC + HC or other cancer types compared with healthy subjects. Forty-four percent of LC + HC patients showed Lp(a) values more than 70.4 Units/dl, i.e., the upper limit of values observed in patients with LC only. Lp(a) serum concentrations were significantly associated with serum albumin both in LC and in LC + HC but not in other cancer-type patients. Thus, comparing patients with similar serum albumin concentrations, Lp(a) serum levels were significantly higher in patients with LC + HC than in patients with only LC and quite similar to those observed in patients with other cancer types. In conclusion, HC cells, in vivo, seem able to produce a greater amount of Lp(a) despite the reduced liver protein synthesis typical of LC.
Aged↗
Proinflammatory cytokines and hemostatic system in patients with chronic obstructive pulmonary disease.
The prothrombotic state frequently observed in patients with chronic obstructive pulmonary disease (COPD) may be related to a systemic inflammatory response. In the present study plasma interleukin-6 (IL-6), IL-2 and IL-1beta levels have been investigated in 33 patients with COPD. In vitro platelet activity, plasma C-reactive protein (CRP) and fibrinogen levels were also determined in all patients. The results obtained demonstrated that plasma IL-6 levels were significantly higher in the patient group compared with a control population age and sex-matched ( P < 0.02), while plasma IL-2 and IL-1beta levels were not significantly modified. An overall condition of platelet hyperactivity in COPD patients was also observed. A comparative analysis of platelet activity and blood gas levels demonstrated a correlation between platelet hyperactivity and a severe impairment of oxygen ( P < 0.001) and carbon dioxide tensions ( P < 0.01). Finally, a statistical analysis of the population under study showed the presence of a significant correlation between elevated plasma IL-6 ( P < 0.001) and IL-1beta levels ( P < 0.007), and an increased sensitivity of platelets to arachidonic acid, suggesting a possible correlation between the inflammatory response and the prothrombotic state observed in patients with COPD.
Journal Article↗
Enhanced thromboxane biosynthesis in patients with chronic obstructive pulmonary disease. The Chronic Obstructive Bronchitis and Haemostasis Study Group.
Thrombotic complications of pulmonary circulation occur in patients with chronic obstructive pulmonary disease (COPD). In the present study, we sought to evaluate in vivo platelet activation through the measurement of 11/dehydro-thromboxane (Tx) B2 TxA2 major metabolite in the urine, in 29 patients with COPD, compared with 29 sex- and age-matched healthy subjects. The urinary excretion of 11-dehydro-TxB2 was significantly higher in patients with COPD than in control subjects: median (range), 753 (277-4,409) and 275 (129-612) pg/mg creatinine, respectively; p < 0.0001). Moreover, 11-dehydro-TxB2 excretion was inversely related with arterial oxygen tension (rho = -0.46; p = 0.0145). In five of the 29 patients a short-term therapeutic course with oxygen supplementation induced a significant decrease of urinary 11-dehydro-TxB2 excretion: median range, 941 (452-2,640) to 445 (166-1,560) pg/mg creatinine. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin was associated with more than 90% inhibition of thromboxane metabolite excretion, demonstrating its being of platelet origin. Plasma levels of prothrombin fragment F1 + 2 were higher in patients than in control subjects (2.6 +/- 1.5 versus 0.9 +/- 0.4 nM, p = 0.0001). No relation between 11-dehydro-TxB2 excretion and plasma F1 + 2 levels was found. We conclude that platelet TxA2 biosynthesis is enhanced in patients with COPD and may be influenced by arterial oxygen tension changes.
Aged↗
Potential usefulness of antiplatelet agents in patients with chronic obstructive pulmonary disease.
Explore the source record for details and available documents.
Aged↗
Signal-averaged electrocardiography and echocardiography in the evaluation of myocardial involvement in progressive systemic sclerosis.
To assess the myocardial involvement in progressive systemic sclerosis we evaluated the presence of late potentials by signal-averaged electrocardiography (signal-averaged ECG) and the left ventricular function by M-mode, two dimensional and Doppler echocardiography. Fifteen outpatients, 7 with diffuse progressive systemic sclerosis and 8 with CREST syndrome variant, without clinical or electrocardiographic evidence of cardiac disease were studied and compared with 18 normal subjects. Late potentials occurred in 5 out of 15 progressive systemic sclerosis patients (33%) with a significant difference versus controls (P < 0.05) and were present only in the patients with diffuse progressive systemic sclerosis (P < or = 0.001 vs. controls). All progressive systemic sclerosis patients showed a normal left ventricular systolic function. Abnormal left ventricular filling was found in 9 progressive systemic sclerosis patients (5 with diffuse progressive systemic sclerosis and 4 with CREST). A more severe impairment of the mean values of diastolic function indexes was found in diffuse progressive systemic sclerosis than in CREST. In all diffuse progressive systemic sclerosis patients at least one method showed altered results, whereas half the CREST patients showed no pathological findings with both techniques. These results confirm a lower myocardial involvement in the CREST syndrome than in diffuse progressive systemic sclerosis and consequently this is probably related to a better prognosis.
Adult↗
Bleeding time does not predict gastrointestinal bleeding in patients with cirrhosis. The CALC Group. Coagulation Abnormalities in Liver Cirrhosis.
BACKGROUND/AIMS: Bleeding time, a laboratory test which explores primary hemostasis, may be prolonged in cirrhosis, but whether abnormal bleeding time identifies patients with cirrhosis who are at risk of bleeding has never been investigated. The aim of this study was to analyze the relationship between bleeding time and the risk of gastrointestinal bleeding. METHODS: Eighty consecutive patients with liver cirrhosis (47 males, 33 females; age, 60 +/- 9 years; range 31 to 83 years) and esophageal varices were enrolled in the study. RESULTS: In the whole series of patients bleeding time was 11 +/- 6 min; it increased as the degree of liver deficiency increased, from low to severe (p = 0.007). During 14 +/- 9 (median (range): 12 (1-34) months of follow-up, 28 (35%) patients experienced gastrointestinal bleeding. They had a longer bleeding time, higher incidence of previous bleeding, more severe liver failure and larger variceal size than patients who did not bleed. However, multivariate analysis (Cox's model) showed that only previous bleeding, liver failure and variceal size were independently associated with bleeding. Similar data were obtained in patients with moderate-severe liver insufficiency (B and C degree according to Child-Pugh's classification). In patients who had never bled (n = 54), the severity of liver failure and variceal size were independent predictors of bleeding. CONCLUSIONS: This study shows that bleeding time is not a predictor of gastrointestinal bleeding in patients with cirrhosis.
Adult↗
[Arrhythmias in the aged: prevalence and correlation with symptoms].
Objective of our study was to evaluate the prevalence of arrhythmias as well as their correlation with the reported anamnestic symptomatology in the elderly population. With 24 hour ambulatory electrocardiography (Holter ECG) 913 patients, (440 males and 473 females, range 60-89 years, mean age 71) were consecutively studied and subdivided according to the following criteria: (1) age (3 classes: 60-69 [I], 70-79 [II], > or = 80 [III]; (2) presence/absence of "guide" symptoms (syncope/faintness, chest pain, palpitation), and (3) Holter electrocardiography results. We have demonstrated a high prevalence of arrhythmias: 72% (657), which was significantly higher in age classes II (80.5%) and III (79.1%) in comparison to class I (60.6%). A notably higher prevalence of tachyarrhythmias is documented compared to bradyarrhythmias (5:1). With a higher age the prevalence of supraventricular tachyarrhythmias increases significantly, while bradyarrhythmias do not have the same trend. We have a similar prevalence of arrhythmias between symptomatic (77.4%) and asymptomatic patients (63.6%) and no significant correlation between anamnestic symptoms and presence of arrhythmias are observed. Considering the high prevalence of arrhythmias during Holter ECG we think that the clinical importance and prognosis should be evaluated with caution.
Age Factors↗
Association between high values of D-dimer and tissue-plasminogen activator activity and first gastrointestinal bleeding in cirrhotic patients. CALC Group.
Cirrhotic patients with decompensated state and high serum levels of fibrin(ogen) degradation products are at high risk of bleeding. The aim of this study was to further analyse the relationship between hyperfibrinolysis and bleeding in cirrhosis by measuring plasma values of D-dimer and tissue plasminogen activator (t-PA) activity. One-hundred-twelve cirrhotic patients with oesophageal varices and without previous upper-gastrointestinal bleeding entered the study and were followed-up for 3 years. Patients were considered to have hyperfibrinolysis if they concomitantly had high values of D-dimer and t-PA activity. During the follow-up 34 (30%) patients bled. They had more severe liver failure (p = 0.0001) and variceal size (p = 0.0031) and higher prevalence of ascites (p = 0.0003), varices with red signs and hyperfibrinolysis (p = 0.0001) than patients who did not bleed. Multivariate analysis disclosed hyperfibrinolysis as the only marker predictive of bleeding (Hazard Ratio = 42.5, p < 0.001). Our findings suggest that screening for hyperfibrinolysis may be useful to identify cirrhotic patients at risk of bleeding.
Adult↗
[The usefulness of plasmapheresis in a case of nephrotic syndrome in Berger's disease].
Berger's disease, or IgA mesangial nephropathy, is a frequent form of focal and/or segmental proliferative glomerulonephritis that occasionally may present as nephrotic syndrome. The authors reports a clinical case of a young woman come to their observation with a severe clinical picture characterized by asthenia, anasarca, serious no selective proteinuria, microscopic hematuria, blood hypotension from mesangial proliferative glomerulonephritis IgA. Because of the null response to traditional therapy the patient was submitted to plasmapheresis "cascade model", or double filtration, a certainly experimental treatment for this disease, and a remission of the nephrotic syndrome was obtained as confirmed by follow-up at three, six months and one year. Since at present times the therapy is supportive only and no therapeutic maneuvers have been found to be consistently effective in the Berger's disease, plasma exchange plus immunodepressive therapy seems to be useful particularly in the rare patients with rapidly progressive glomerulonephritis. Further and more extensive studies and a fair follow-up are necessary to prove our results.
Adult↗