[Significance of 3-methoxytyramine urine measurement in the diagnosis of pheochromocytomas and paragangliomas: about 28 patients]. / Intérêt du dosage urinaire de la 3-méthoxytyramine dans le diagnostic des phéochromocytomes et paragangliomes: à propos de 28 cas.

Measurement of catecholamines derivatives is used to diagnose tumors such as pheochromocytomas and paragangliomas. Despite the low incidence of these diseases, their diagnosis is essential because of potentially lethal episodes of malignant hypertension related to an inappropriate secretion of catecholamines by these tumors. The catecholamines derivatives include 3-methoxytyramine, normetanephrine and metanephrine, assayed in urine or plasma. The significance of the measurement of urinary 3-methoxytyramine was addressed by analysing the records of 28 patients aged 25 to 84 years with isolated elevation of this derivative, with non-pathological urinary rates of metanephrine and normetanephrine, that might help suspect a catecholamine inappropriate secretion. In these situations, no pheochromocytoma or paraganglioma was diagnosed. This study, after discussing possible biases in the clinical care and diagnosis approach of these patients, raises the question of the relevance of this assay in the diagnostic management of these diseases.

The reproducibility of Stewart parameters for acid-base diagnosis using two central laboratory analyzers.

BACKGROUND: Acid-base derangements can be interpreted using the Stewart-Fencl approach, which includes calculation of the apparent strong ion difference (SID(app)), the effective SID (SID(eff)), and the strong ion gap (SIG). These calculations require the measurement of several variables. We hypothesized that the SID and SIG calculated by different analyzers would not be reproducible because of variability in the measured values. METHODS: In this prospective observational study conducted in a biochemistry laboratory, we analyzed 179 routine blood samples from consecutive patients over a 3-mo period using two automated blood chemistry analyzers, the LX20 (Beckman) and the Modular (Roche). Measured and calculated parameters from the two analyzers were compared. RESULTS: Although the correlation between measured values was satisfactory, there were large differences in the limits of agreement for calculated values (SID(app): 9.6 mEq/L, SID(eff): 6.4 mEq/L, and SIG: 11.7 mEq/L) and a weak correlation (SID(app): r(2) = 0.54 and SIG: r(2) = 0.12) between the analyzers. CONCLUSIONS: The results of the Stewart-Fencl approach for interpretation of acid-base status can vary according to the analyzer used. These differences may have important clinical and research implications..

Differential associations between lipid-lowering drugs, statins and fibrates, and venous thromboembolism: role of drug induced homocysteinemia?

BACKGROUND: Previous studies reported that statin use was associated with a decreased risk of venous thromboembolism (VTE), whereas no association was found between fibrate use and VTE. This report aims to test the hypothesis that part of these contrasting associations is related to total homocysteine level (tHcy). MATERIALS AND METHODS: This report from a case-control study included 677 cases hospitalised with confirmed VTE and no major acquired risk factor of VTE and their 677 controls. Statin and fibrate exposure was defined as a current use of drugs at admission. Fasting serum tHcy was measured in all patients. RESULTS: The estimated odds ratio for VTE related to statin use was 0.53 (CI 95% 0.37-0.78), whereas it was 1.88 (CI 95% 1.29-2.74) for fibrate use. No difference was found for tHcy levels between patients who were current users of statin compared to non users (17.7 micromol/L+/-7.3 in users vs 18.4 micromol/L+/-8.4 in non users, p=0.50). In contrast, fibrate users had a significant higher mean level of tHcy than non users (23.2 micromol/L+/-8.7 in users vs 18.4 micromol/L+/-8.4 in non users, p<0.0001). Nevertheless, adjustment on tHcy level did not alter significance and strength of the association between fibrates and VTE (1.66, CI 95% 1.07-2.59). CONCLUSIONS: Statin use was associated with a significant decreased risk of VTE, whereas fibrate use was associated with a significant increased risk of VTE. This last association was independent of tHcy levels.

Interrelation of hyperhomocysteinemia and inherited risk factors for venous thromboembolism. Results from the E.D.I.TH. study: a hospital-based case-control study.

BACKGROUND: Moderate hyperhomocysteinemia and factor V Leiden mutation are among the most prevalent risk factors for venous thromboembolism (VTE). The hypothesis of an interaction between those risks has been raised and conflicting results were reported. METHODS: We designed a hospital-based case-control study to test the interaction between Factor V Leiden and fasting serum total homocysteine (tHcy). We have also analysed the G20210A prothrombin gene variant. This study enrolled 904 hospitalised patients who had an objectively proven deep vein thrombosis and/or pulmonary embolism as well as 904 hospitalised control patients matched for gender, age and major acquired risk factor for VTE. RESULTS: Our data did not detect any multiplicative interaction between hyperhomocysteinemia (>15 mumol/L) and factor V Leiden mutation or G20210A prothrombin gene variant. Odds ratios (95% CI) were 4.0 (1.5-11) and 6.0 (1.3-27) for the combined effect of hyperhomocysteinemia with either factor V Leiden mutation or G20210A prothrombin gene variant, respectively. CONCLUSIONS: Current data provide further knowledge in relationship between hyperhomocysteinemia and inherited risk factors, such as factor V Leiden mutation and G20210A prothrombin gene variant. As those risk factors are not so rare among Caucasians, a better estimate of the risk related to double exposure might help to optimise venous thromboembolism prevention.

Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients.

BACKGROUND: Epidemiological studies have established that a low serum concentration of carotenoids was associated with risk of Age-Related Macular Degeneration (ARMD). The aim of this study was to determine carotenoid levels in serum and in different lipoprotein fractions in patients diagnosed for ARMD and in matched control group. METHOD: Thirty-four ARMD patients and 21 control subjects from Brest area (France) have been included to this study. Lipoproteins have been separated from serum by gradient density ultracentrifugation. We measured concentration of carotenoids and tocopherols in serum and in different lipoprotein fractions by HPLC. RESULTS: No difference was observed between ARMD patients and control subjects in total serum carotenoids. Individual carotenoid levels showed that only lycopene was decreased significantly in serum, LDL and HDL fractions in patients (P<0.05). Concentrations in serum and lipoparticle fractions of lutein and zeaxanthin, the major pigments present in macula were not modified between both groups. CONCLUSIONS: Lycopene, as liposoluble antioxidant nutrient, is the only carotenoid altered in ARMD patients. It cannot be excluded that this effect is related to different dietary habits, but we hypothesise that lower lycopene status could result also from specific antioxidant protection of lutein and zeaxanthin by lycopene.

Testicular adrenal rest tumours in salt wasting congenital adrenal hyperplasia (in vivo and in vitro studies).

We describe the case of a 20-year-old patient with salt-wasting congenital adrenal hyperplasia (CAH) related to 21-hydroxylase deficiency. Bilateral craggy testicular tumours were found, requiring histological evaluation. Prior to the surgical procedure, the patient was treated with dexamethasone (he presented cortisol deficiency) and was stimulated with ACTH. High levels of 11beta-OH steroids measured in the gonadal vein, compared with peripheral blood samples suggested the presence of adrenal rests. Incubation of the tumours (which could not be differentiated histologically, from Leydig tissue), with radioactive steroid precursors was carried out. The results revealed the testicular tumours were of adrenal tissue origin, associated with 21-hydroxylase deficiency. The patient's non-compliance to glucocorticoid treatment was the main cause of his hypogonadotropic hypogonadism.

Effects of oral and transdermal 17 beta-estradiol combined with progesterone on homocysteine metabolism in postmenopausal women: a randomised placebo-controlled trial.

Mild hyperhomocysteinemia is a risk factor for both ischaemic heart disease and venous thromboembolism. The effects of transdermal estrogen replacement therapy (ERT) on homocysteine metabolism in postmenopausal women have scarcely been investigated. This clinical trial aimed to estimate the effects of combined hormone replacement therapy on the fasting total homocysteine levels according to the estrogen route of administration. We enrolled 196 postmenopausal women, who were randomly allocated to receive on a continuous basis either 1mg of 17 beta-estradiol orally (n = 63) or 50 microg transdermally (n = 68) per day, both combined with a daily intake of 100 mg progesterone, or placebo (n = 65) over a period of 6 months. Neither oral nor transdermal ERT significantly affected total plasma homocysteine levels or red-blood cell folate levels. However, oral ERT significantly decreased plasma vitamin B12 levels compared to placebo (mean relative variation difference over 6 months between oral ERT and placebo: -11.7% (95%CI, -21 to -2%) whereas transdermal ERT did not display any significant effects. Our data show that transdermal ERT as well as low dose of oral ERT does not significantly affect the homocysteine metabolism. This finding does not support a role for transdermal estrogen in the prevention of ischaemic heart disease in postmenopausal women.

Is age-related macular degeneration associated with serum lipoprotein and lipoparticle levels?

OBJECTIVE: The etiology of age-related macular degeneration (ARMD) is poorly understood. Risk factors for cardiovascular disease have been thought to be associated with ARMD. Our purpose was to measure the concentration of atherogenic apolipoproteins (apo) and lipoparticles in serum from ARMD patients. METHODS: We analyzed lipids, lipoparticles and apolipoproteins concentrations in 84 unrelated patients with ARMD and compared the results with those of age- and sex-matched control subjects (n=62). Serum lipid concentrations were determined enzymatically; apolipoproteins levels by kinetic nephelometry and lipoparticles by electroimmunodiffusion. RESULTS: No difference in total cholesterol, triglycerides, phospholipids, high- and low-density lipoprotein-cholesterol (lHDL-C and LDL-C) concentrations were observed between ARMD patients and controls. Apo E and LpE non-B concentrations were found to be higher in serum from patients than in serum from controls. In contrast, Apo C-III and LpC-III non-B concentrations were lower in serum from patients than in serum from controls. CONCLUSIONS: The main differences observed between ARMD patients and controls are in Apo E, Apo C-III, LpC-III non-B and LpE non-B concentrations. These lipoparticles belong to the HDL family, which is considered to consist of anti-atherogenic lipoproteins. These results raise the possibility that cardiovascular risk factors are not associated with ARMD. Furthermore, we can hypothesize that ARMD development is linked to perturbations of HDL metabolism.