Evagelos N. Liberopoulos

Dyslipidaemia, Hypercoagulability and the Metabolic Syndrome

The metabolic syndrome is a clustering of risk factors including central obesity, insulin resistance, dyslipidaemia and hypertension. This syndrome is associated with increased risk of cardiovascular disease and is a common early abnormality in the development of type 2 diabetes. The pathogenesis of the syndrome has multiple origins. Obesity and sedentary lifestyle coupled with genetic factors interact to produce the syndrome. Here, we consider two components of the metabolic syndrome, dyslipidaemia and hypercoagulability.

A review of the lipid-related effects of fluvastatin

ABSTRACT Background: Statin therapy has been shown to significantly decrease vascular events and overall mortality in primary and secondary prevention trials. This review considers the pharmacology, non-lipid-lowering effects and clinical trial evidence of fluvastatin based on a survey of PubMed entries. Findings: Recent clinical data show that treatment with fluvastatin is associated with a variety of benefits in different high-risk populations along with a good safety profile. Fluvastatin exerts non-lipid lowering-associated pleiotropic effects in both clinical and experimental studies. Furthermore, an extended-release formulation of fluvastatin with a favourable pharmacokinetic profile is available. Conclusion: Treatment with fluvastatin offers a convenient, safe and evidence-based approach to managing dyslipidaemias and preventing vascular events.

Aminoglycoside-Induced Reversible Tubular Dysfunction

Nonoliguric renal insufficiency is a well-known nephrotoxic consequence of aminoglycosides, although reversible tubular damage in the absence of any change in the renal function has been occasionally found. Reported herein are 2 representative cases of a reversible tubular damage due to prolonged aminoglycoside administration: a patient with a Fanconi-like syndrome of proximal tubular dysfunction and a patient with a syndrome of hypokalemic metabolic alkalosis associated with hypomagnesemia.

Combined Treatment With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: A Review of the Current Evidence

Several studies have shown that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are useful in the treatment of hypertension, cardiovascular disease, chronic heart failure, and some types of nephropathy. In this context, dual renin-angiotensin system blockade with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may be more effective than treatment with each agent alone. Many clinical trials have demonstrated the beneficial effect of this combined treatment on proteinuria, hypertension, heart failure, and cardiovascular events. Moreover, these studies demonstrated that dual renin-angiotensin system blockade is generally safe and well tolerated. Long-term studies are under way to confirm these effects and also investigate the effectiveness of dual reninangiotensin system blockade on cerebrovascular disease and prevention of type 2 diabetes mellitus. These studies are expected to define the optimal use of combination treatment in everyday clinical practice. This review considers the most important clinical trials that evaluated the effect of dual renin-angiotensin system blockade on blood pressure, heart failure, and renal function.

Alcohol intake, serum uric acid concentrations, and risk of gout

In their Article, Hyun Choi and colleagues (Apr 17, p 1277) clearly show that alcohol intake is strongly associated with heightened risk of gout in men. Although serum uric acid concentrations were not measured, the authors proposed alcohol-induced hyperuricaemia due to raised urate production and diminished renal excretion as a main mechanism for this reported association. This mechanism, however, might not be the case in heavy alcohol drinkers. In fact, reduced concentrations of serum uric acid have been reported in patients with alcoholic liver cirrhosis, due to loss of hepatic xanthine oxidase activity, resulting in decreased urate production. Furthermore, De Marchi and co-workers have shown that serum urate concentrations were slightly, although not significantly, reduced in alcoholic patients without liver disease compared with the control population (297·5 mol/L [SD 71·4] vs 321·3 mol/L [107·1]). Serum uric acid concentrations as low as 95·2 mol/L, with profound renal urate, potassium, phosphate, and magnesium wasting, have been described in such patients. On alcohol withdrawal, serum urate concentrations significantly increased to 321·3 mol/L [71·4] (p<0·05), and 178·5 mol/L, respectively, in the previously mentioned studies. Ethanol misuse might result in reversible generalised proximal renal tubular dysfunction leading to uricosuria and various acid-base and electrolyte disorders. This hypothesis is supported by studies reporting that ethanol interferes Correspondence

The effects of the addition of micronised fenofibrate on uric acid metabolism in patients receiving indapamide.

Summary Objective: Hyperuricaemia is associated with indapamide administration. In contrast, micronised fenofibrate can significantly decrease serum uric acid levels. However, there are no data on the effect of combination therapy of indapamide with micronised fenofibrate on uric acid metabolism. Methods: We studied 20 non-diabetic hypertensive patients with mixed dyslipidaemia in whom serum metabolic parameters, including uric acid levels in serum and urine, were measured before and after eight weeks of indapamide administration (2.5 mg once daily). This study was continued for a further eight weeks, when the indapamide was combined with micronised fenofibrate (200 mg once daily). Results: Indapamide significantly decreased mean systolic and diastolic blood pressure (BP) from 153±9/97±8mmHgto 138 ± 8/93 ± 4mmHg (p < 0.05 for both comparisons). A significant increase in serumuric acid levels occurred after indapamide administration [from a mean value of5.6± 1.3mg/dl (0.33 ± 0.07 mmol/l) to 6.4 ± 1.1 mg/dl (0.38 ± 0.06mmol/l), p< 0.01]. This effect was associated with a decrease in the fractional excretion of uric acid (from a mean value of 9.5 ± 5% to 7 ± 5.5%, p < 0.05). The addition of micronised fenofibrate significantly decreased plasma fibrinogen levels as well as total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB) and triglycerides, and increased high-density lipoprotein cholesterol and ApoA1 levels. Fenofibrate administration was followed by a significant decrease in serum uric acid levels to 4.7± 1.2 mg/dl (0.28 ± 0.07 mmol/l), p < 0.01, owing to a substantial increase in fractionalurate excretion to 11 ± 3%, p < 0.01. Conclusion: The addition of micronised fenofibrate can correct the hyperuricaemic effect of indapamide administration.

Effect of Apolipoprotein E Polymorphism on Serum Uric Acid Levels in Healthy Subjects

Background We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels. Methods Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants. Results The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3 ± 101.1 μmol/L [5.4 ± 1.7 mg/dL]) compared with the apo E-3 allele (261.8 ± 89.2 μmol/L [4.4 ± 1.5 mg/dL]; p = .012) and the apo E-4 allele (243.9 ± 65.4 μmol/L [4.1 ± 1.1 mg/dL]; p = .010), whereas the apo E-2 allele was associated with a nonsignificant decrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9 ± 2.2% vs 8.7 ± 4.2% vs 8.9 ± 5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA. Conclusions Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.

Successful Treatment of Human Immunodeficiency Virus-Related Castleman’s Disease: A Case Report and Literature Review

Multicentric Castleman’s disease is increasingly recognized as an aggressive illness with a rapidly fatal outcome in human immunodeficiency virus (HIV)-infected patients. In the absence of optimal therapy, various therapeutic interventions have been tested with disappointing results; only five reports with a successful outcome have been described. Presented herein is a 66-year-old HIV-infected man with multicentric Castleman’s disease. Early administration of cyclophosphamide, doxorubicin, vincristine and prednisone resulted in prolonged clinical recovery. The relevant literature is also reviewed.

Possible Cefotaxime-Induced Stevens–Johnson Syndrome

OBJECTIVE: To report a case of possible cefotaxime-induced Stevens–Johnson syndrome (SJS). CASE SUMMARY: A 72-year-old woman with an upper urinary tract infection developed erosions and blisters on the skin and the mucous membranes, as well as fever and prostration, soon after the administration of cefotaxime. This presentation is consistent with the features of SJS. Resolution of the clinical manifestations was observed after discontinuation of the drug; all other drugs, infections, or immunologic disorders that could have caused this syndrome were carefully excluded. An objective causality assessment revealed that SJS was possibly associated with the use of cefotaxime. DISCUSSION: Although cephalosporins have been associated with an increased risk for SJS and cefotaxime has been suspected of being associated with SJS in a previous case–control study, this is the first full report for cefotaxime-related SJS in the literature. An immunologically mediated reaction may be the underlying mechanism. CONCLUSIONS: Although cefotaxime administration seems to be the underlying cause of the SJS observed in our patient, establishment of a definite causal relationship requires additional cases and supportive data.

SIADH and Hyponatremia with Theophylline

OBJECTIVE: To report a case of possible theophylline-induced hyponatremia due to the syndrome of inappropriate antidiuretic hormone (SIADH). CASE SUMMARY: An 88-year-old man developed severe symptomatic hyponatremia (serum sodium 112 mEq/L) associated with inappropriate natriuresis (urinary sodium 58 mEq/L) temporally related to the initiation of theophylline. The patient fulfilled the criteria for the diagnosis of SIADH after all other causes of hyponatremia were excluded. Furthermore, no other drugs or conditions that could have evoked SIADH were found. DISCUSSION: Theophylline has rarely been associated with hyponatremia. A thiazide-like action of the drug on the stimulation of SIADH could be the underlying mechanism for SIADH. CONCLUSIONS: Theophylline should be considered as a possible cause of hyponatremia.