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Biomedical subjects

M S Elisaf

Publications and source records attributed to M S Elisaf.

At least 55 records · Page 3Linked to original sources

Hypersensitivity syndrome caused by amitriptyline administration.

Adverse cutaneous manifestations are among the most common side effects associated with psychotropic drugs. Skin reactions due to amitriptyline (a tricyclic antidepressant agent) include rashes and hypersensitivity reactions (for example, urticaria and photosensitivity) as well as hyperpigmentation. Hypersensitivity syndrome is a specific severe idiosyncratic reaction causing skin, liver, joint, and haematological abnormalities, which usually resolve after the discontinuation of the implicated drug. A case of a 24 year old woman who experienced hypersensitivity syndrome three weeks after the initiation of amitriptyline is reported.

Adult↗

Treatment of dyslipidaemias in patients with established vascular disease: a revival of the fibrates.

The key 'statin trials' focussed on the beneficial effect of lowering the circulating concentrations of low-density lipoprotein cholesterol (LDL). However, epidemiological surveys, mainly based on healthy populations, indicate that other lipid-related variables, such as high-density cholesterol (HDL), triglycerides (TG), dense LDL subfraction distribution, and possibly lipoprotein (a) (Lp(a)), are also predictors of vascular events. Furthermore, TG and HDL levels influenced outcome within some of the statin trials. Plasma fibrinogen levels have also been shown to be powerful predictors of vascular risk in healthy subjects and patients with established ischaemic heart disease. The fibrates exert beneficial effects on all these variables that predict vascular events. The results from recent trials, the Bezafibrate Infarction Prevention (BIP) study and the Veterans Administration HDL Intervention Trial (VA-HIT) have revived our interest in fibrates. These trials involved bezafibrate and gemfibrozil that have a relatively poor LDL-lowering capacity. Therefore, the benefits reported in BIP and VA-HIT must be attributed to actions on variables other than a reduction in LDL quantity. Ciprofibrate and fenofibrate have significantly greater LDL-lowering capacity than bezafibrate or gemfibrozil. This advantage may render them more effective, especially since they retain the additional beneficial actions associated with this class of lipid-lowering drugs.

Bezafibrate↗

Hyperosmolar nonketotic syndrome with hypernatremia: how can we monitor treatment?

We report the case of a 62 year-old symptomatic patient with severe hyperglycemic hyperosmolality associated with hypernatremia. During treatment, the progressive decrease in serum tonicity, which resulted in the amelioration of the neurological symptoms, followed the decrease in serum glucose and mainly the corrected serum sodium levels rather than the decrease in the uncorrected serum sodium levels. The case illustrates the usefulness of glucose - corrected serum sodium levels to monitor treatment in such conditions in order to avoid neurological consequences caused by the decrease in serum osmolality.

Blood Glucose↗

Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia: case histories.

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipid-lowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipid-lowering drug (fenofibrate) with an additional hypouricaemic effect.

Antihypertensive Agents↗

Severe hypophosphatemia in a patient with acute pancreatitis.

CONTEXT: We describe a patient with alcohol-induced pancreatitis who developed severe life-threatening hypophosphatemia of multifactorial origin during hospitalization. CASE REPORT: Decreased phosphate levels along with urine phosphate wasting were already noticed on the patient's admission due to underlying chronic alcoholism. However, a further deterioration of hypophosphatemia appeared on the second day of hospitalization presumably resulting from an increased transfer of phosphate from extracellular to intracellular fluid. CONCLUSIONS: Phosphate deficiency is often overlooked in patients with acute pancreatitis. Our case emphasizes that serum phosphate levels should be checked along with serum calcium levels in patients with acute pancreatitis, especially in alcoholic patients.

Acute Disease↗

Acid-base and electrolyte abnormalities in patients with acute leukemia.

Disturbances of acid-base balance and electrolyte abnormalities are commonly seen in patients with acute leukemia. Our study aimed at illuminating the probable pathogenetic mechanisms responsible for these disturbances in patients with acute leukemia admitted to our hospital. We studied 66 patients (24 men and 44 women) aged between 17 and 87 years old on their admission and prior to any therapeutic intervention. Patients with diabetes mellitus, acute or chronic renal failure, hepatic failure, patients receiving drugs that influence acid-base status and electrolyte parameters during the last month, such as corticosteroids, cisplatin, diuretics, antacids, aminoglycosides, amphotericin, penicillin, and K(+), PO(4)(3-), or Mg(2+) supplements were excluded. Forty-one patients had at least one acid-base or electrolyte disturbance. There were no significant differences in the incidence of acid-base balance and electrolyte abnormalities between patients with acute myeloid leukemia (AML) and patients with acute lymphoblastic leukemia (ALL). The most frequent electrolyte abnormality was hypokalemia, observed in 41 patients (63%), namely in 34 patients with AML, and 7 with ALL; the main underlying pathophysiologic mechanism was inappropriate kaliuresis. Furthermore, hypokalemic patients more frequently experienced concurrent electrolyte disturbances (i.e., hyponatremia, hypocalcemia, hypophosphatemia, and hypomagnesemia), as well as various acid-base abnormalities compared to normokalemic patients. Hypokalemia in patients with acute leukemia may serve as an indicator of multiple concurrent, interrelated electrolyte disturbances, especially in patients with AML.

Acid-Base Imbalance↗

Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with renal failure.

Patients with renal failure have an increased incidence of atherosclerotic disease. Numerous studies have shown that these patients show increased serum lipoprotein(a) [Lp(a)] concentrations compared with the control population. However, variable alleles at the apolipoprotein(a) [apo(a)] gene locus determine to a large extent the Lp(a) concentration in the general population. We therefore undertook the present study to evaluate apo(a) phenotypes and Lp(a) serum concentrations in a large number of patients with renal disease. Seventy-nine patients treated by hemodialysis (HD), 47 patients treated by continuous ambulatory peritoneal dialysis (CAPD), 68 patients with mild/moderate chronic renal failure (CRF) and serum creatinine levels of 1.8 to 8 mg/dL, and 73 healthy controls were studied. All patients showed significantly elevated median serum Lp(a) concentrations in comparison with controls: HD patients, 15.7 mg/dL (P < 0.01); CAPD patients, 20 mg/dL (P < 0. 005); CRF patients, 15.1 mg/dL (P < 0.01) versus controls, 7 mg/dL. The greater Lp(a) values in all groups were not explained by differences in isoform frequencies, whereas their increase was apo(a)-type specific. Thus, patients in all groups with high-molecular-weight (HMW) apo(a) isoforms showed a significant elevation of Lp(a) levels, whereas serum Lp(a) concentrations in patients with low-molecular-weight (LMW) isoforms were not significantly different from controls, except for CAPD patients, who presented increased serum Lp(a) concentrations. We conclude that in patients with renal failure, even of mild/moderate degree, as well as in patients with end-stage renal disease undergoing HD or CAPD, elevated Lp(a) concentrations are mainly observed in those with HMW apo(a) phenotypes.

Adult↗

Effectiveness and metabolic effects of perindopril and diuretics combination in primary hypertension.

The effectiveness as well as the metabolic effects of the combination of diuretics [hydrochlorothiazide (HCT) vs indapamide (IND)] and perindopril (P) in 14 patients (7 male, 7 female) aged 37-62 years with mild idiopathic hypertension were studied. Following a 4-week wash-out period and a 4-week period of monotherapy with P (4 mg/daily), IND (2.5 mg/daily) or HCT (25 mg/daily) was added for 4 weeks. Selection of the diuretic agent was random. Following a 4-week wash-out period from the diuretic, in which only P was given, the alternative diuretic was administered for another period of 4 weeks. P decreased blood pressure levels significantly. However, the drug was more efficacious in patients with higher plasma renin activity (PRA). Combination treatment induced an additional decrease in the blood pressure levels, mainly in patients with lower PRA. The combination of P + HCT was more effective than the combination P + IND. The addition of either HCT or IND evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge. However, insulin levels did not change significantly during the study. Small but not statistically significant changes in serum electrolytes and lipid parameters were observed during the various phases of the study, while a statistically significant increase in the serum uric acid was noticed when the combination P + HCT was given. We conclude: (1) P in small doses is an effective and safe antihypertensive agent, (2) PRA has a predictive value in determining the effectiveness of P treatment, (3) the combination of P with small doses of HCT or IND is more efficacious than P alone, (4) the combination treatment has adverse effects in the carbohydrate tolerance, while there are not significant changes in serum electrolyte and lipid parameters.

Adult↗

The effect of moxonidine on plasma lipid profile and on LDL subclass distribution.

Moxonidine is a new antihypertensive agent whose mechanism of action appears to involve specific stimulation of imidazoline receptors resulting in an inhibition of the activity of the central and peripheral sympathetic nervous system. The drug seems to behave neutrally with respect to plasma lipid parameters. However, there are no data on the effects of moxonidine on the low-density lipoprotein (LDL) subclass pattern or on the LDL oxidation susceptibility, both of which are known to play a prominent role in the pathogenesis of atherosclerosis. Thus, we undertook the present study to examine the influence of moxonidine on the LDL subspecies profile and their susceptibility to copper-induced oxidative modification in 20 hypertensive patients (11 men, 9 women) aged 38-61 years. Moxonidine administered at a dose of 0.4 mg daily for 8 weeks produced a significant decrease in both systolic and diastolic blood pressure (from 147 +/- 10 to 131 +/- 11 mm Hg, P < 0.001, and from 98 +/- 4.5 to 86 +/- 5 mm Hg, P < 0.001, respectively). No significant change in plasma lipid profile was observed after moxonidine administration. Additionally, no change in the susceptibility of LDL subclasses to copper-induced oxidative modification was noticed. Finally, drug therapy was not followed by any change in either LDL phenotype or in mass and composition of the three LDL subfractions. We conclude, that unlike other antihypertensive drugs, such as beta-blockers which may predispose to expression of a relatively atherogenic lipoprotein subclass pattern, moxonidine does not affect either plasma lipid parameters or lipoprotein composition.

Adult↗

Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures.

UNLABELLED: Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures. BACKGROUND: Platelet-activating factor (PAF) is a potent inflammatory mediator associated with several physiopathological conditions, including renal diseases. PAF is degraded to the inactive metabolite lyso-PAF by PAF-acetylhydrolase (PAF-AH), which is considered as a potent anti-inflammatory and anti-atherogenic enzyme associated with lipoproteins. In this study, we evaluated the plasma- and lipoprotein(a) [Lp(a)]-associated PAF-AH activity in relationship to plasma lipid parameters and Lp(a) isoform size in patients with mild/moderate chronic renal failure (CRF), as well as in hemodialysis (HD) and chronic ambulatory peritoneal dialysis (CAPD) patients. METHODS: We studied 74 patients undergoing maintenance HD, 44 patients undergoing CAPD, 56 patients with mild/moderate CRF, and 98 healthy subjects whose lipid profile, as well as plasma and high-density lipoprotein (HDL)-associated PAF-AH activity, was determined. Moreover, the effect of Lp(a) plasma levels on the distribution of PAF-AH among plasma lipoproteins, as well as the specific activity and kinetic properties of PAF-AH on two different Lp(a) isoforms, was measured in each studied group. RESULTS: The plasma PAF-AH activity in all studied groups was significantly higher than in controls, and the increase was more profound in CAPD patients. The HDL-associated PAF-AH activity, expressed per milliliter of plasma, was similar among all studied groups; however, when it was expressed as either per milligrams of HDL cholesterol or per milligrams of plasma apolipoprotein (apo) AI, the PAF-AH activity was significantly higher in all patient groups compared with controls. All patient groups had significantly elevated plasma Lp(a) levels, which altered the distribution of PAF-AH among the plasma lipoproteins compared with that observed in subjects with very low plasma Lp(a) levels (<8 mg/dl). Additionally, in each studied group, the specific activity as well as the apparent Km and Vmax values of the 19K4 apo(a) isoform were significantly higher (P < 0.01) compared with the values of the 23K4 isoform. However, the specific activity, as well as the Km and Vmax values on either the 19K4 apo(a) isoform or the 23K4 isoform, was significantly higher in CAPD patients compared with the other three groups. CONCLUSIONS: Plasma PAF-AH activity is increased in uremic patients. This elevation is more profound in CAPD patients, who also exhibit a more atherogenic lipid profile and more pronounced alterations in the specific activity and the kinetic constants of Lp(a)-associated PAF-AH.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Platelet function and lipid-lowering interventions.

Platelets play an important role in the process of atherothrombosis, and antiplatelet therapy is of proven efficacy in the prevention of vascular events in high-risk patients. In this review, we briefly consider the studies reporting that circulating atherogenic lipoproteins enhance platelet activity. We also evaluate the evidence showing that lipid-lowering interventions (including the use of statins) are associated with the normalisation of platelet activity. This beneficial effect should enhance the anti-atherogenic and anti-thrombotic potential of lipid-lowering interventions.

Journal Article↗