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Biomedical subjects

M Elisaf

Publications and source records attributed to M Elisaf.

At least 73 records · Page 4Linked to original sources

Increased platelet reactivity to the aggregatory effect of platelet activating factor, in vitro, in patients with heterozygous familial hypercholesterolaemia.

Patients with familial hypercholesterolaemia (FH) present with high plasma total- and low density lipoprotein (LDL)-cholesterol levels and develop premature and often severe atherosclerosis. Elevations of total- and LDL cholesterol levels are not only related to an increased risk of atherosclerosis, but may also exert prothrombotic effects via platelet activation leading to acute coronary events. In the present work, the platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to the plasma PAF-acetylhydrolase (PAF-AH) activity and to their lipidemic profile was studied in 20 heterozygous FH patients. The PAF EC(50) aggregation values in the patient group were significantly decreased ( P < 0.03) compared with the control group (19.5 5.2 nM and 30.4 7.2 nM, respectively). Moreover, the maximal percentage of aggregation to 100 nM PAF was significantly increased in the patient group compared with controls (26.5 8.2% vs 15.2 3.1%, respectively, P < 0.03). Both platelet aggregation parameters were correlated to the plasma total- and LDL-cholesterol levels, as well as to the apolipoprotein B (apo B) levels. The maximal percentage of aggregation to 10 microM ADP was also significantly increased in the patient group compared with controls (51.5 10.3% vs 32.4 9.0%, respectively, P < 0.02) but was not correlated to any plasma lipid parameter. The total plasma PAF-AH activity in the heterozygous FH patients was significantly higher compared with controls (109.8 15.9 nmol/ml per min vs 68.4 18.0 nmol/ml per min, respectively, P < 0.0001), whereas the HDL-associated PAF-AH activity did not differ significantly between the two groups. Our results suggest that the increased aggregatory response of platelets to PAF despite the significantly higher plasma PAF-AH activity, could be an important factor contributing to the higher atherogenicity and incidence of acute coronary events observed in patients with heterozygous FH.

Journal Article↗

The incidence of thyroid function abnormalities in patients attending an outpatient lipid clinic.

Thyroid disorders are known to influence lipoprotein metabolism. In the current study we examined the incidence of thyroid function abnormalities in patients attending our outpatient lipid clinic. During the last 2 years, 248 patients were admitted to our lipid clinic for the diagnosis and management of dyslipidemia. In all cases, a detailed medical history was obtained and a thorough physical examination was performed with emphasis on the presence of symptoms/signs indicative of underlying thyroid diseases. In addition to lipid parameters, thyrotropin (TSH) and free thyroxine (FT4) levels were measured in a fasting blood sample. Seven female asymptomatic patients (2.8%) had frank biochemical hypothyroidism, and 11 patients (9 female, 2 male) (4.4%) had subclinical hypothyroidism with TSH levels between 5.8-19 mU/L. After restoration of a euthyroid state with levothyroxine therapy, no significant changes in serum lipid parameters were observed in the whole group of patients with subclinical hypothyroidism. However, in 4 patients with TSH levels >12 mU/L relatively small doses of levothyroxine (75 microg/day) were followed by a significant improvement of serum lipid profile. Interestingly, 3 patients exhibited clinical or subclinical hyperthyroidism that influenced serum lipid parameters as well as the effectiveness of hypolipidemic treatment. It is concluded that thyroid function abnormalities are relatively common in dyslipidemic patients attending a lipid clinic and could significantly affect the patients' lipid profile as well as the patients' management.

Dose-Response Relationship, Drug↗

Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia.

It has been reported that micronized fenofibrate and losartan can significantly decrease serum uric acid levels by augmenting uric acid excretion. We undertook this study to evaluate the effects of the combination treatment with micronized fenofibrate and losartan in nondiabetic hypertensive dyslipidemic patients with hyperuricemia (serum uric acid, >7 mg/ dl). A total of 25 patients (15 men, 10 women) aged 21-66 years was studied. In all patients, serum lipid parameters, including Lp(a), fibrinogen, and uric acid levels, as well as fractional excretion of uric acid (FEUA) were obtained before treatment, 8 weeks after micronized fenofibrate treatment (200 mg daily), and 8 weeks after combination therapy with micronized fenofibrate (200 mg daily) and losartan (50 mg daily). Fenofibrate alone significantly decreased total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, Apo B, Lp(a), fibrinogen, and uric acid levels (from 7.6+/-0.55 to 5.6 +/-0.5 mg/dl; p < 0.0001) and increased high-density lipoprotein (HDL) cholesterol, Apo A1, and FEUA (from 6.5+/-1.8% to 12.2+/-4%; p < 0.0001). The addition of losartan beyond the decrease in blood pressure values did not significantly alter serum metabolic parameters. However, a small additional decrease in serum uric acid levels (from 5.6+/-0.5 to 4.9+/-1 mg/dl; p < 0.05) was found because of a further increase in FEUA (from 12.2+/-4% to 14+/-5.5%; p < 0.05). It is concluded that the combination of micronized fenofibrate and losartan is useful for the management of patients with multiple metabolic abnormalities, including hyperuricemia.

Adult↗

Assessment of the performances of three oscillometric blood pressure monitors for neonates using a simulator.

BACKGROUND: The majority of monitors for non-invasive measurement of blood pressure in neonates and infants use the oscillometric method. OBJECTIVE: To use a simulator to investigate the overall system accuracy for three oscillometric blood pressure monitors. The tested devices are DINAMAP 8100 (Critikon), SpaceLabs M90426 (SpaceLabs Medical)and the module HP M 1008B (Hewlett-Packard). METHODS: The blood pressure values obtained by the three devices were compared with those of the invasive reference. A blood pressure simulator was used for testing the performance of the three blood pressure monitors. RESULTS: The Dinamap and SpaceLabs readings are generally in good agreement with the invasive reference. In contrast, the HP M 1008B readings for the diastolic and mean arterial pressures are inaccurate (the mean errors are 21 and 15mmHg, respectively). CONCLUSION: These results contradict our previously published data obtained when a different simulator (Cufflink)was used. These findings are important, because blood pressure values that are too low can result in a different therapeutic approach being applied, for newborn babies have only a small range of mean arterial pressure for the autoregulation of the cerebral blood flow.

Blood Pressure↗

Severe muscle weakness due to hypokalemia as a manifestation of small-cell carcinoma.

We describe the case of a 56-year-old man with severe muscle weakness due to heavy hypokalemia (serum potassium 1.44 mmol/l) associated with inappropriate kaliuria and alkalemia. Subsequent investigation revealed the presence of ectopic ACTH hypersecretion due to a small-cell lung carcinoma. A significant clinical/laboratory improvement was achieved following chemotherapy-induced regression of the primary tumor. The profound hypokalemia was probably the result of cortisol hypersecretion, which in concert with the ACTH-induced decreased 11beta-hydroxysteroid dehydrogenase activity can exhibit an increased mineralocorticoid activity. In addition, other ACTH-dependent mineralocorticoids may play a contributory role in the development of severe hypokalemia.

ACTH Syndrome, Ectopic↗

Antibodies to hepatitis E virus among several populations in Greece: increased prevalence in an hemodialysis unit.

BACKGROUND: Hepatitis E virus (HEV) has been found to be the causative agent of enterically transmitted non-A, non-B hepatitis in tropical and subtropical countries. Several investigators, however, have indicated that HEV could be endemic in Europe, albeit at a low prevalence. STUDY DESIGN AND METHODS: The purpose of this study was to estimate the prevalence of anti-HEV in various populations in northwestern Greece (Epirus region). Healthy blood donors (2636), refugees from southern Albania (350), children (165), injecting drug users (IDUs) (65), multiply transfused patients (62), patients with chronic viral hepatitis (75), and chronic hemodialysis patients (149) were investigated for anti-HEV by enzyme immunoassay and confirmatory Western blot assay. In addition, 380 consecutive healthy blood donors and 62 hemodialysis patients from a neighboring area (Agrinion, Greece) were investigated. RESULTS: A very low presence of anti-HEV antibody was found among healthy blood donors from Epirus (0.23%) and Agrinion (0.53%). Anti-HEV was not detected in children, IDUs, or multiply transfused patients. In contrast, a low but significant prevalence of anti-HEV was found among refugees (4.85%), patients with chronic viral hepatitis (5.3%), and hemodialysis patients from Epirus (1.34%), as compared with healthy blood donors from Epirus: p < 0.0001, p < 0.00001, and p < 0.10, respectively. A high prevalence (9.7%) of anti-HEV was revealed in patients at the hemodialysis unit of the General Hospital of Agrinion (p < 0.00005, compared to healthy blood donors from Agrinion). No significant association was found between anti-HEV positivity and the age or sex of donors, the duration of hemodialysis, positivity for hepatitis B or C virus infection markers, history of hepatitis, increased alanine aminotransferase, renal transplantation, a history of transfusion, or the number of units transfused. CONCLUSION: This study demonstrated a high prevalence of anti-HEV in a separate hemodialysis unit, without an association with the known routes of transmission of blood-borne viruses. This observation suggests that a still-undefined intra-unit factor or other factors are associated with HEV transmission.

Adolescent↗

Absence of HCV viraemia in anti-HCV-negative haemodialysis patients.

BACKGROUND: Immunologic alterations have been reported in chronic haemodialysis (HD) patients. Some HD patients may have, therefore, an inability to produce detectable amounts of serum antibodies to hepatitis C virus (anti-HCV). Previous studies have shown the presence of HCV viraemia in anti-HCV-negative HD patients (ranging from 1 to 15%). However, the universal epidemiologic impact of these cases remains uncertain since there are conflicting results. In this context, we conducted a study in an attempt to investigate the presence of HCV viraemia among anti-HCV-negative HD patients in a well-defined geographic area of the northwestern part of Greece. METHODS: During a 6 month period, 81 anti-HCV-negative HD patients were tested twice for the presence of HCV RNA, using the reverse transcriptase polymerase chain reaction (RT-PCR) combined with a DNA enzyme immunoassay (DEIA). At the same time, periodic testing for anti-HCV by two commercially available third generation assays was done. In addition, 15 anti-HCV-positive HD patients and 20 non-HD patients with well established chronic HCV infection used as internal controls were tested for the presence of HCV RNA and anti-HCV. RESULTS: None of the anti-HCV-negative HD patients were shown to be viraemic by the combined RT-PCR and DEIA method. During the same time period, all remained anti-HCV negative by the third generation assays. By contrast, all the patients with known HCV-infection were positive by the two enzyme immunoassays, whereas 13 anti-HCV-positive HD patients (86.7%) and 18 non-HD patients (90%) were viraemic by RT-PCR. CONCLUSIONS: This study demonstrated that routine HCV RNA testing in anti-HCV-negative HD patients appears not to be necessary particularly when third generation assays are used for the detection of anti-HCV.

Adolescent↗

Effect of L-carnitine supplementation on lipid parameters in hemodialysis patients.

It has been reported that cumulative carnitine losses through dialysis membranes may worsen hyperlipidemia during long-term hemodialysis. However, carnitine supplementation has not shown a consistent beneficial response. We undertook the present study to determine if there is any hypolipidemic effect of L-carnitine on Greek dialysis patients in concert with the dialysate buffer composition (acetate or bicarbonate). A total of 28 patients (16 male, 12 female), mean age 43 years (range 21-61), with end-stage renal disease on maintenance hemodialysis for a mean period of 25 months (range 7-84) were studied. The dialysis schedule was 4 h, 3 times/week using cuprophane hollow-fiber dialyzers and acetate (n = 14) or bicarbonate (n = 14) dialysate. In all patients L-carnitine (5 mg/kg body weight) was infused intravenously 3 times/week at the end of each hemodialysis session. Blood samples for carnitine and lipid determinations were obtained before treatment, and 3 and 6 months following treatment. Even though L-carnitine did not modify most of the serum lipid levels, a significant decrease in serum triglycerides was evident in the whole group of patients (from 225 +/- 76 to 201 +/- 75 mg/dl, p = 0.03). Furthermore, L-carnitine could decrease serum triglycerides only in hypertriglyceridemic patients (from 260 +/- 64 to 226 +/- 82 mg/dl, p < 0.05). L-Carnitine resulted in a reduction of serum triglycerides in both patients on bicarbonate and on acetate dialysis, while there were no significant differences in the changes of lipid parameters after L-carnitine between the two groups of hemodialysis patients. We conclude that relatively low doses of L-carnitine supplementation could contribute to the management of some hypertriglyceridemic hemodialysis patients.

Adult↗

Multiple electrolyte abnormalities after pamidronate administration.

Pamidronate constitutes a major advance in the treatment of tumor-associated hypercalcemia. However, transient electrolyte abnormalities have been reported after pamidronate administration. We describe here a patient with multiple myeloma and severe hypercalcemia who developed transient but significant electrolyte disturbances (mainly hypophosphatemia and hypomagnesemia) after a single dose of 90 mg of pamidronate, focusing on the underlying pathophysiological mechanisms.

Antineoplastic Agents↗

Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients?

The dysfunction of the immune system has been implicated in the cause of essential hypertension (EH). On the other hand, interleukin- 1beta (IL-1beta) has strongly been involved in the pathogenesis of atheromatosis, whereas our preliminary experiments in serum samples from hypertensive patients before any drug therapy have shown the presence of high concentrations of IL-1beta and the absence of interleukin-2 (IL-2). The aim of this study was first to confirm our preliminary findings and second to investigate the possible interrelation(s) among the parameters studied, particularly between the immunologic markers and the blood pressure or the lipid parameters, because so far there are no data regarding the possible participation of IL-1beta in the cascade phenomena presented during the process of EH such as atherogenesis. Serum samples from 28 consecutive unselected patients with EH before any drug administration or after discontinuation of the antihypertensive therapy for at least 4 weeks, 31 normotensive patients with familial hypercholesterolemia (FH, disease control group), and 35 healthy individuals In a control group matched for age and sex were investigated for the presence of IL-1beta (commercial enzyme immunoassay), soluble IL-2 receptors (slL-2Rs, sandwich enzyme-linked immunosorbent assay set up in our laboratory), and some of the acute phase proteins by nephelometry. In addition, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A1 and B, and lipoprotein (a) were determined by standard methods. The data were analyzed by unpaired t test, Mann Whitney-U, chi-squared analysis after Yate's correction, analysis of variance, or Kruskal-Wallis where applicable. Correlation coefficient was calculated by simple regression analysis (r) or nonparametric Spearman correlation coefficient (rs). We found that (1) none of the patients had increased concentrations of sIL-2Rs, and (2) the IL-1beta levels significantly differed in the three groups (p = 0.0001). In more detail, the concentrations of IL-1beta were significantly higher in patients with EH compared with those in patients with FH (p < 0.0005) and the healthy control group (p = 0.0001). By contrast, the IL-1beta concentrations did not differ between patients with FH and the healthy control group. (3) Sixteen (57.1%) patients with EH and only 6 (19.4%) patients with FH (p < 0.01) had increased levels of IL-1beta, and (4) the IL-1beta was not correlated with the acute phase reactants or the lipid parameters in the groups studied. However, the group of patients with EH and increased IL-1beta levels had significantly higher mean concentrations of triglycerides (p < 0.05) and significantly lower mean concentrations of high-density lipoprotein cholesterol (p < 0.05) than those who had IL-1beta levels lower than the cutoff point. (5) The IL-1beta concentrations were positively though slightly correlated with the mean blood pressure only in the group of patients with EH (r = 0.38, p < 0.05). This study demonstrated the presence of high concentrations of IL-1beta and the absence of indicators of cellular immune activation in the systemic circulation of patients with EH, suggesting that this cytokine may be involved in the pathogenesis of EH. In addition, this study showed that the high levels of IL-1beta were associated with lipid indicators of atheromatosis only in the group of patients with EH. More studies are required in an attempt to address whether IL-1beta could have a pathogenetic importance in EH. Taking into account these findings, however, it can be suggested that the presence of high IL-1beta levels may be an additional and perhaps independent risk factor for atheromatosis in patients with EH.

Acute-Phase Proteins↗