Are the effects of tamoxifen on the serum lipid profile modified by apolipoprotein E phenotypes?

BACKGROUND: Tamoxifen has favorable effects on the serum lipid profile. It has been suggested that the apolipoprotein (Apo) E phenotype can influence serum lipid parameters; the ApoE allele 4 (ApoE4) is associated with higher total and low-density lipoprotein (LDL) cholesterol levels. The ApoE phenotype also affects lipid responses to diets or treatment with statins. However, the effect of tamoxifen on the lipid profile in different ApoE phenotypes is unknown. PATIENTS AND METHODS: In the present study, we evaluated the effects of tamoxifen on the serum lipid profile in 11 ApoE4-positive postmenopausal women with breast cancer (phenotypes 3/4 and 4/4) compared with 33 ApoE4-negative women (phenotypes 3/2 and 3/3). Serum lipid parameters [high-density (HDL), LDL and total cholesterol, triglycerides, ApoAI, ApoB and lipoprotein (a)] were measured after an overnight fast before treatment and after 3 and 12 months. ApoE isoforms were determined by isoelectric focusing of delipidated very-low-density lipoproteins (VLDL). RESULTS: During the follow-up period, serum levels of total and LDL cholesterol and ApoB decreased significantly in both groups, but no significant differences were found. Concentrations of serum HDL cholesterol were not significantly different between both groups. However, serum ApoAI levels increased significantly in ApoE4-negative subjects (p = 0.00005), but no significant changes in ApoE4-positive women were observed. Serum triglyceride levels increased by 23.2% (p < 0.05) in ApoE4-positive patients, but they did not change significantly in ApoE4-negative patients. The LDL/HDL cholesterol ratio decreased similarly in the two groups, but the ApoAI/ApoB ratio, which may be a better predictor of cardiovascular events, significantly changed in the ApoE4-negative subjects. Finally, the median level of Lp(a) decreased by 43.4% in the ApoE4-negative patients, whereas it did not change significantly in the ApoE4-positive group. CONCLUSION: In postmenopausal Greek women with breast cancer, the levels of Lp(a) and triglycerides and the ApoAI/ApoB ratio respond more favorably to tamoxifen treatment in ApoE4-negative than in ApoE4-positive patients.     

Effect of rosuvastatin monotherapy or in combination with fenofibrate or ω-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome

Background: Raised triglycerides (TG), decreased high‐density lipoprotein cholesterol (HDL‐C) levels and a predominance of small dense low density lipoproteins (sdLDL) are characteristics of the metabolic syndrome (MetS). Objective: To compare the effect of high‐dose rosuvastatin monotherapy with moderate dosing combined with fenofibrate or ω‐3 fatty acids on the lipoprotein subfraction profile in patients with mixed dyslipidaemia and MetS. Methods: We previously randomised patients with low‐density lipoprotein cholesterol (LDL‐C) > 160 and TG > 200 mg/dl to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or ω‐3 fatty acids 2 g/day (Rω group, n = 30). In the present study, only patients with MetS were included (24, 23 and 24 in the R, RF and Rω groups respectively). At baseline and after 12 weeks of treatment, the lipoprotein subfraction profile was determined by polyacrylamide 3% gel electrophoresis. Results: The mean LDL size was significantly increased in all groups. This change was more prominent with RF than with other treatments in parallel with its greater hypotriglyceridemic capacity (p < 0.05 compared with R and Rω). A decrease in insulin resistance by RF was also noted. Only RF significantly raised HDL‐C levels (by 7.7%, p < 0.05) by increasing the cholesterol of small HDL particles. The cholesterol of larger HDL subclasses was significantly increased by R and Rω. Conclusions: All regimens increased mean LDL size; RF was the most effective. A differential effect of treatments was noted on the HDL subfraction profile.     

One versus two embryo transfer after IVF and ICSI: a randomized study

BACKGROUND: The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups. RESULTS: The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS: Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.     

Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia

Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Preferably this treatment should involve low optimally tolerable doses of hypolipidemic drugs. Thus, we undertook a study to determine the safety and efficacy of combination therapy with fibrates and small doses of atorvastatin. Twenty-two patients with mixed hyperlipidemia were started on a fibrate regimen (micronised fenofibrate 200mg/day or ciprofibrate 100 mg/day). Because after 12 weeks of therapy the fibrate failed to normalise the serum lipid profile, small doses of atorvastatin (5 mg/day) were added for a further 12 weeks. The administration of the fibrates resulted in a significant decrease in total and LDL-cholesterol levels, as well as in triglycerides, and an increase in HDL-cholesterol levels. The addition of atorvastatin (5 mg/day) resulted in a further decrease in total and LDL-cholesterol levels. Consequently, the hypolipidemic therapy target was achieved in most of the patents. Combination therapy was well tolerated and no significant increases in serum liver and muscle enzymes were noticed. We conclude that the careful administration of small doses of atorvastatin in patients with mixed dyslipidemia receiving fibrates is associated with a significant amelioration of lipid abnormalities.     

Ischemic heart disease,factor predisposing to Barrett's adenocarcinoma: A case control study

AIM:To define the significance of ischemic heart disease(IHD)(stable angina to infarction) co-existance in Barrett esophagus(BE) patients and patients with esophageal adenocarcinoma(AdE).METHODS: All BE/AdE patients in Blackpool-Wyre-Fylde area and Trikala prefecture identified from medical records. Patient clinical details were obtained from hospital and General Practitioner records. Additional information was gathered from validated questionnaire.RESULTS: Forty(33%) AdE and 83(19%) BE patients had IHD(P = 0.002). Eighteen(15%) AdE and 34(8%) BE patients had suffered a myocardial infarction(P = 0.03). Three(3%) AdE and 7(2%) BE patients had severe heart failure(P = 0.82). Thirty-nine(47%) BE with IHD and 8(20%) AdE patients with IHD consumed aspirin daily(P = 0.004). Seventh-seven(93%) BE patients with IHD and 36(90%) AdE patients with IHD were on statins(P = 0.86). Logistic regression analysis: AdE was more frequent in the elderly,with long termreflux,long BE and concurrent IHD(odds ratio: 2.086,P = 0.001) not consuming statins. Eighteen(22%) BE patients with IHD [16(84%) with myocardial infarction] vs 33(10%) without IHD died from non-neoplastic causes within 24 mo from BE diagnosis(P = 0.005). CONCLUSION: IHD is more prevalent in AdE than BE patients. Increased prevalence of AdE is related with the presence of myocardial infarction but not severe heart failure,possibly because patients with BE and se-vere IHD have low life expectancy.     

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.     

Study of growth hormone secretion and action in growth-retarded children with juvenile chronic arthritis (JCA).

The stimulated and spontaneous growth hormone (GH) secretion and the response to GH action were assessed in growth-retarded children with juvenile chronic arthritis (JCA), in order to determine the underlying mechanisms of growth retardation in such children. Six children (4 boys and 2 girls aged 10.7-13.8 years) with active JCA of systemic onset were included in the study which involved: (1) anthropometric measurements; (2) assessment of GH responses to insulin-induced hypoglycaemia and clonidine stimulation; (3) assessment of the nocturnal pulsatile GH secretion by measuring GH in blood samples obtained every 20 min from 20.00 to 08.00 h; and (4) the IGF-I generation test. As a control, the latter test was also performed in eight aged-matched children with physiological delay in puberty. Biosynthetic hGH (0.1 IU/kg BW) was administered s. c. for 4 days and blood samples were taken at baseline and the morning after the last GH injection for measurement of IGF-I and IGFBP-3.All six children with JCA were prepubertal and their growth velocity was <3 cm/year. The GH responses to both stimulation tests were normal (peak GH >20 mU/l). Analysis of the pulsatile GH secretion during the night revealed three-to-four GH pulses of normal amplitude (>20 mU/l). IGF-I (26.7+/-4.6 nmol/l, mean+/-SD) and IGFBP-3 (2.1+/-0.2 mg/l) levels were lower in the patients compared with the controls (43.0+/-3.7 nmol/l and 2.8+/-0.2 mg/l, respectively, P<0.01). Following stimulation with exogenous hGH, there was a significant increase in IGF-I and IGFBP-3 levels in the control group (85 and 73%, respectively), but only a small increase in the patients (31 and 14%).It appears that stimulated and spontaneous GH secretion is normal in children with active systemic JCA, but the response to endogenous and exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children.