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Biomedical subjects

E Ros

Publications and source records attributed to E Ros.

At least 19 recordsLinked to original sources
PubMed1999

Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: additive effects of combination treatment on lipid regulation.

The most appropriate therapy for combined hyperlipidemia remains to be determined. We compared the lipid-regulating effects of gemfibrozil and lovastatin in 30 patients with familial combined hyperlipidemia (FCHL) in a randomized, double-blind, placebo-controlled crossover study including 8-week courses of one drug followed by a washout period and a crossover phase to the alternate drug. After completion of the trial, open-label combination therapy was given for up to 12 months. Lovastatin was more efficacious than gemfibrozil in the reduction of total cholesterol (23% v. 9%, P<.001) and low-density lipoprotein (LDL) cholesterol (28% v. 2%, P<.001), whereas gemfibrozil surpassed lovastatin in the reduction of triglycerides (48% v. 0%, P<.001) and very-low-density lipoprotein (VLDL) cholesterol (50% v. 19%, P = .005) and the increase of high-density lipoprotein (HDL) cholesterol (18% v. 4%, P = .005). Lovastatin caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug-induced changes in lipoprotein composition indicated that gemfibrozil reduced both the number and size of VLDL particles and lovastatin decreased the number of LDL particles. Combined treatment was safe and had additive effects on lipids, causing significant (P<.001) reductions in total cholesterol (32%), triglycerides (51%), LDL cholesterol (34%), and apo B (26%) and an increase in HDL cholesterol (19%). Target LDL cholesterol levels were achieved only in 11% of patients given gemfibrozil alone and triglycerides decreased to target levels in 22% after lovastatin alone, whereas combined therapy normalized both lipid fractions in 96% of patients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels but favorably influences the putative atherogenic alterations of lipoprotein composition that are related to hypertriglyceridemia. Conversely, lovastatin markedly decreases LDL cholesterol but has little effect on triglyceride-rich lipoproteins. Combination treatment safely corrects all of the lipid abnormalities in most patients.

Adult↗
PubMed1998

Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia.

The magnitude of serum lipid changes in response to hypolipidemic drugs varies considerably between individuals. These differences may be due to interactions between genetic and environmental factors that effect drug bioavailability or the capacity of the lipid-regulating enzyme and receptor targets to be affected. The apolipoprotein E (apoE) gene locus has been examined in this regard, but reports are conflicting on the effect of its variability on the response to hypolipidemic drugs. We investigated the effect of apoE polymorphism on the serum lipid response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein changes were assessed after 12 weeks of therapy in 106 patients with primary hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in 63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2, E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

Adult↗
PubMed1998

Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia.

AIM: To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. METHODS: VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation related analytes after Cu-induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied. RESULTS: Both drugs reduced the plasma concentration of apo-B lipoproteins (-23% gemfibrozil, -26% lovastatin), but whereas lovastatin affected mainly LDL-cholesterol (-30%), gemfibrozil reduced triglycerides (-49%) and VLDL-cholesterol (-48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL-triglycerides (-32%), and b) increased the proportion (molar%) of 18:3 n-6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%). CONCLUSIONS: Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty acids in VLDL. In the context of a fixed dietary intake, such modifications suggest that the drug influences liver enzyme activities involved in fatty acid chain synthesis (elongases and desaturases).

Double-Blind Method↗
PubMed1997

Prospective evaluation of a minimally invasive approach for treatment of bile-duct calculi in the high-risk patient.

BACKGROUND: The best approach to bile duct stones in high-risk patients is controversial. We showed in a randomized trial that open surgery had a morbi-mortality similar to that of endoscopic sphincterotomy alone (ES) and less late biliary complications. The aim of this study was to evaluate a minimally invasive approach to duct stones in high-risk patients compared with open surgery or ES alone. METHODS: Sixty high-risk patients (mean age 80 years) suspected of duct stones were treated by ES + laparoscopic cholecystectomy (LC). High-risk factors were: age > 70 years, Goldman cardiac index > 13, chronic pulmonary disease, liver cirrhosis, neurologic deficit, and severe obesity. RESULTS: ERCP success was 87%. Duct stones were found in 75%. LC succeeded in 92%. Post-LC stay was 4 days. Overall morbidity was 19% and mortality was 3%. Recurrent symptoms (mean follow-up: 9 months) was 3.6%. When compared with open surgery or ES alone, ES + LC had a similar morbi-mortality, but shorter postop stay (p < 0.001). Late symptoms appeared in 20% after ES alone vs 4% after open surgery or ES plus LC (p < 0.04). CONCLUSIONS: Combined ES + LC is an effective alternative to open surgery or ES alone for treatment of duct stones in high-risk patients.

Aged↗
PubMed1997

Chest pain at rest in patients with coronary artery disease. Myocardial ischemia, esophageal dysfunction, or panic disorder?

Severe nonexertional (resting) chest pain may be due to myocardial ischemia, esophageal dysfunction, psychiatric disorder, or any combination thereof and frequently poses a difficult diagnostic challenge. Our aim was to investigate causes of chest pain in patients with coronary artery disease. Forty-five patients with angiographically proven obstructive coronary lesions and recurrent chest pain at rest were studied; 18 had refractory pain despite cardiac therapy (problem group), and 27 had documented myocardial ischemia (control group). Esophageal manometry, edrophonium provocation, 24-hr pH studies, and psychiatric interview were performed in all patients. The clinical evolution and the outcome of specific treatment during follow-up was used to establish the etiology of chest pain. Esophageal dysfunction was identified in all problem patients and in 52% of controls, and the esophagus was incriminated as the source of pain in 8 (44%) and 5 (18.5%), respectively. After a mean follow-up of 49 months (range 24-76 months), the cause of chest pain in the problem group was identified as panic disorder in 9 patients (50%), gastroesophageal reflux in 6 (33%), esophageal dysmotility in 2 (11%), and gallstone disease in 1 (6%). Of the control patients, 18 (67%) had ischemic pain alone, while 9 had concurrent causes: panic disorder in 5 (19%) and esophageal dysfunction in 4 (15%). Esophageal dysfunction and psychiatric disturbances are common in patients with coronary artery disease presenting with resting chest pain, and may contribute to patients' symptoms.

Case-Control Studies↗
PubMed1997

Effects of red wine on 24-hour esophageal pH and pressures in healthy volunteers.

The purpose of this study was to assess the effects of red wine taken with meals on esophageal motility, esophageal exposure to acid, and gastric pH. Following a randomized design, 14 healthy male volunteers (mean age 25 years, range 18-35 years were given 360 ml of red wine or tap water during lunch or dinner. All subjects underwent ambulatory 24-hr esophageal motility and esophagogastric pH monitoring studies. Three different periods were analyzed: during meals (30 min), postprandial (3 hr), and 8-hr supine. Two volunteers complained of heartburn after wine ingestion. An increase in the number of high amplitude waves (> 125 mm Hg, 95th percentile of our motility unit controls) was observed during meals accompanied by wine: water 1.2 (0-10.2), wine 1.6 (0-32.6), P = 0.02 [median (range)]. No other esophageal motility changes occurred. Percent reflux time increased during the postprandial period after wine ingestion in comparison with water: 1.7 (0-14.9) vs 0.1 (0-0.8), P < 0.05. Gastric pH was unaffected by the type of drink. Ingestion of moderate amounts of red wine with meals increases postprandial esophageal exposure to gastric acid in healthy persons.

Adult↗
PubMed1996

Randomised trial of endoscopic sphincterotomy with gallbladder left in situ versus open surgery for common bileduct calculi in high-risk patients.

BACKGROUND: Morbidity and mortality after surgical treatment of bileduct stones increase with age and associated diseases. A proposed alternative therapy is endoscopic sphincterotomy (ES) with the gallbladder left in situ, and we elected to compare this option with standard open surgery in high-risk patients. METHODS: 98 patients (mean age 80 years) with symptoms likely to be due to bileduct stones or a recent episode of biliary pancreatitis were randomised to be treated either by open cholecystectomy with operative cholangiography and (if necessary) bileduct exploration (n=48) or by endoscopic sphincterotomy alone (n=50). FINDINGS: The procedure was accomplished successfully in 94% of the surgery group and 88% of the ES group, and there were no significant differences in immediate morbidity (23% vs 16%) or mortality (4% vs 6%). During mean follow-up of 17 months biliary symptoms recurred in three surgical patients, none of whom underwent repeat surgery, and in 10 ES patients, seven of whom had biliary surgery. By multivariate regression analysis endoscopic sphincterotomy was an independent predictor of recurrent biliary symptoms (odds ratio 6.9; 95% Cl 1.46 to 32.54). INTERPRETATION: In elderly or high-risk patients, surgery is preferable to endoscopic sphincterotomy with the gallbladder left in situ as a definitive treatment for bileduct stones or non-severe biliary pancreatitis.

Aged↗
PubMed1996

[Thoracic pain of esophageal origin. Assessment of 125 consecutive patients with resting angina and angiographically normal coronary arteries].

BACKGROUND: The esophagus may be the origin of chest pain clinically indistinguishable from that of myocardial ischemia. Gastroesophageal reflux (GER) and esophageal motility disorders (EMDs) are the main causes of esophageal chest pain, and esophageal motility tests are important for an appropriate diagnosis. We studied 125 unselected patients with angiographically normal coronary arteries presenting with atypical (resting) angina which was shown not to be of cardiac origin. METHODS: Stationary esophageal manometry and 24-hour pH studies were performed in all patients, and 116 of them were submitted to edrophonium provocation test (Tensilon, 10 mg as IV bolus). RESULTS: Spastic EMDs were identified as an isolated abnormality in 23 patients (18%), whereas GER was documented in 70 patients (56%). Esophageal dysmotility at baseline manometry (n = 40), a positive edrophonium test (n = 19), abnormal acid reflux indices by 24-hour pH recording (n = 62), and association of chest pain with acid reflux during pH testing (n = 24) variably overlapped in many patients. The esophagus was directly blamed as the source of atypical angina in 33 patients (26%) who had induction of their usual chest pain by cholinergic stimulation and/or association of spontaneous pain events with acid reflux. CONCLUSIONS: Esophageal dysfunction in common in patients with atypical angina considered not to be of cardiac origin and contributes to patients' symptoms. Because they may detect treatable causes of chest pain such as GER or contribute to management by assessing the diagnosis of EMD, esophageal motility tests are indicated in many patients with noncardiac chest pain.

Adult↗
PubMed1996

Apolipoprotein E polymorphism and gallstones.

BACKGROUND & AIMS: Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism and the risk of both atherosclerosis and Alzheimer's disease. As opposed to common apo E3, apo E2 decreases and apo E4 increases hepatic lipoprotein uptake; hence, apo E4 could promote gallstone formation by increasing hepatic and biliary cholesterol concentrations. This study was designed to evaluate whether apo E polymorphism is related to gallstone risk. METHODS: apo E phenotype was determined in subjects older than 40 years of age (160 with and 125 without gallstones) and in 61 patients with cholesterol gallstones who underwent cholecystectomy. Bile composition, nucleation time, and gallstone features were analyzed in surgical patients. RESULTS: The E4/3 phenotype was enriched in both patients with gallstones and those who underwent cholecystectomy, with significantly (P < 0.006) higher epsilon 4 allele frequencies than in gallstone-free subjects (odds ratio, 2.67 [95% confidence limits, 1.23-5.93] and 3.62 [95% confidence limits, 1.49-8.91], respectively); women, but not men, accounted for these differences. The prevalence of the epsilon 4 allele increased with age in patients with gallstones, whereas the opposite occurred in gallstone-free subjects. Biliary lipid and gallstone cholesterol content tended to increase in the sequence E4 > E3 > E2 in patients who underwent cholecystectomy. CONCLUSIONS: Carrying the apo E4 isoform is a genetic risk factor for cholelithiasis in humans, thus adding another adverse effect of apo E polymorphism on health.

Adult↗
PubMed1996

High amplitude contractions in the middle third of the oesophagus: a manometric marker of chronic alcoholism?

BACKGROUND: Oesophageal motor abnormalities have been reported in alcoholism. AIM: To investigate the effects of chronic alcoholism and its withdrawal on oesophageal disease. PATIENTS: 23 chronic alcoholic patients (20 men and three women; mean age 43, range 23 to 54). METHODS: Endoscopy, manometry, and 24 hour pH monitoring 7-10 days and six months after ethanol withdrawal. Tests for autonomic and peripheral neuropathy were also performed. Motility and pH tracings were compared with those of age and sex matched control groups: healthy volunteers, nutcracker oesophagus, and gastro-oesophageal reflux disease. RESULTS: 14 (61%) alcoholic patients had reflux symptoms, and endoscopy with biopsy showed oesophageal inflammation in 10 patients. One patient had an asymptomatic squamous cell carcinoma. Oesophageal motility studies in the alcoholic patients showed that peristaltic amplitude in the middle third was > 150 mm Hg (95th percentile (P95) of healthy controls) in 13 (57%), the ratio lower/ middle amplitude was < 0.9 in 15 (65%) (> 0.9 in all control groups), and the lower oesophageal sphincter was hypertensive (> 23.4 mm Hg, P95 of healthy controls) in 13 (57%). All three abnormalities were present in five (22%). Abnormal reflux (per cent reflux time > 2.9, P95 of healthy controls) was shown in 12 (52%) alcoholic patients, and was unrelated to peristaltic dysfunction. Subclinical neuropathy in 10 patients did not effect oesophageal abnormalities. Oesophageal motility abnormalities persisted at six months in six patients with ongoing alcoholism, whereas they reverted towards normal in 13 who remained abstinent; reflux, however, was unaffected. CONCLUSIONS: Oesophageal peristaltic dysfunction and reflux are frequent in alcoholism. High amplitude contractions in the middle third of the oesophagus seem to be a marker of excessive alcohol consumption, and tend to improve with abstinence.

Adult↗
PubMed1995

[Carotid atherosclerosis evaluated by two-dimensional ultrasonography in patients with primary hypercholesterolemia].

BACKGROUND: Two-dimension ultrasonography permits to noninvasively quantify extracoronary atherosclerosis. The objective of this study was to assess preclinical atherosclerosis of the extracranial carotid arteries in patients with primary hypercholesterolemia. METHODS: Lipid and nonlipid cardiovascular risk factors were evaluated in 206 patients with dyslipidemia (127 men and 79 women, mean age 49 years, range 18-75), and a multifactorial cardiovascular risk profile was constructed for each patient. Ultrasound measurements of the intima-media thickness in the common carotid artery of each side were taken, and the number and height of any atheroma plaques present were quantified. RESULTS: Asymptomatic plaques were found in 120 patients (58%), and were more frequent in men than in women (65 vs 47%, p = 0.009), and in patients with than in those without prior coronary heart disease (80 vs 50%, p < 0.001). Both intimal thickening, indicative of early atherosclerosis, and the extent of arterial wall involvement with plaques, which represents an advanced stage of the disease, increased significantly with age and with increasing multifactorial cardiovascular risk, reflecting a positive relation between signs of atherosclerosis and the burden of risk factors. Intima-media thickness also increased with increasing plaque score, indicating the generalization of atherosclerosis. CONCLUSIONS: The high prevalence of preclinical carotid atherosclerosis confirms the atherogenic risk of primary dyslipidemias. The relation between carotid lesions and both coronary heart disease and multifactorial risk supports the validity of arterial ultrasound studies for cardiovascular risk prediction.

Adolescent↗
PubMed1995

Homozygosity for a splice junction mutation in exon 8 of the gene encoding lysosomal acid lipase in a Spanish kindred with cholesterol ester storage disease (CESD).

Deficiency of lysosomal acid lipase is expressed in two distinct recognizable phenotypes. Wolman disease represents the severe early onset form, whereas cholesterol ester storage disease is the more benign late onset type. Previous studies have indicated that compound heterozygosity consisting of a G-->A mutation at the 3'-splice junction of exon 8 (E8SJM-allele) together with a null allele of the gene encoding lysosomal acid lipase leads to cholesterol ester storage disease. We have now observed homozygosity for the G-->A splice junction mutation in a non-related Spanish kindred with the same disease. As expected, the residual activity of lysosomal acid lipase is higher in this case, suggesting that the E8SJM-allele is associated with low residual acid lipase activity. However, the phenotype of the homozygous propositus is more severe compared with the previously described case, indicating that no direct relationship exists between the genotype or residual LAL activity and the precise cholesterol or triglyceride levels in a given patient. Nevertheless, our findings provide convincing evidence that homozygosity for the E8SJM-allele causes cholesterol ester storage disease to at least the same extent as compound heterozygosity consisting of this allele and a null allele.

Adult↗
PubMed1995

Effect of apolipoprotein E polymorphism on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids in patients with hypercholesterolemia and combined hyperlipidemia.

We investigated the effect of variation at the apolipoprotein (apo) E gene locus on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids (MUFA). Lipoprotein changes were assessed in 122 outpatients with type IIa (n = 70) and type IIb (n = 52) hyperlipidemia [80 men and 42 women with apo E phenotypes 3/2 (n = 27), 3/3 (n = 48), and 4/3 (n = 47)] who were switched from their basal diet containing 40% fat (22% MUFA) to an isoenergetic diet containing 31% fat (MUFA content similar to that of the basal diet) for 12 wk. Significant (P < 0.005) reductions of total, LDL, and VLDL cholesterol; triglycerides; and apo B occurred in subjects regardless of WHO phenotype. Triglycerides and VLDL cholesterol decreased more in type IIb than in type IIa subjects: 25% vs 12% and 21% vs 15%, respectively (P = 0.01). HDL cholesterol tended to decrease only in women. The heterogeneity of lipoprotein responses to dietary intervention was unrelated to apo E phenotypes. In these hyperlipidemic subjects, however, diet-induced favorable changes in serum lipoproteins were selectively influenced by WHO phenotype.

Adult↗
PubMed1994

Value of Nissen fundoplication in patients with gastro-oesophageal reflux judged by long-term symptom control.

A total of 160 patients treated by Nissen fundoplication for uncomplicated gastro-oesophageal reflux disease were studied over a 20-year period. Recurrent reflux and side-effects were assessed yearly after surgery. No objective tests for reflux were performed during follow-up if patients were asymptomatic. Perioperative mortality and technique-related morbidity rates were both 2 per cent. At the latest evaluation, 79 per cent of patients were completely relieved of reflux symptoms, 85 per cent had symptoms of Visick grade 1 or 2 and 89 per cent would be willing to undergo surgery again under the same conditions. Actuarial analysis showed that the success rate of fundoplication was 92 per cent at 20 years. Fourteen patients (9 per cent) developed side-effects after fundoplication and had continuing disability. Nissen fundoplication achieves permanent control of reflux symptoms in most patients with few complications and has a high degree of patient satisfaction.

Female↗
PubMed1994

Symptomatic versus silent gallstones. Radiographic features and eligibility for nonsurgical treatment.

It is unknown whether demography, gallbladder function, or the radiographic appearance of gallstones predispose them to cause symptoms. We investigated these features in a consecutive series of 260 patients with newly diagnosed, uncomplicated gallstone disease, of whom 146 had experienced biliary pain and 114 were asymptomatic. All patients underwent double-dose oral cholecystography and cholecystosonography, and the combined data of these examinations were used to assess gallbladder function and stone number, size, and radiopacity. The gallstones were multiple in 68%, radiolucent in 73%, and in visualized gallbladders in 79% of the 260 patients. The comparison of different variables in patients with and without biliary pain showed that the female gender (P = 0.030; odds ratio 1.86), a family history of gallbladder disease (P = 0.022; odds ratio 1.89), a nonvisualized gallbladder (P < 0.001; odds ratio 3.14), multiple stones (P = 0.036; odds ratio 1.89), and those which were small (P = 0.009; odds ratio 2.08) or of dissimilar size (P = 0.041; odds ratio 1.91) were associated with biliary pain. Women with silent stones had been pregnant more often (P < 0.001, difference between means 1) than those with biliary pain. Gallbladder function and the radiologic characteristics of stones were unrelated to age and gender. Estimates of eligibility for nonsurgical therapies among the 146 symptomatic patients were 44% for bile acid therapy, 16% for lithotripsy, and 56% for methyl tert-butyl ether. In conclusion, some inherent features of gallstones are associated with biliary pain. Whether they have predictive value of future symptom development in subjects with silent stones can be determined by prospective follow up.

Adult↗