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Background: Concomitantly used cytochrome P450 (CYP) 3A4 inhibitors and inducers have been shown to alter the plasma concentrations of the HMG-CoA reductase inhibitors ('statins') lovastatin and simvastatin. Myopathy is a serious adverse effect of statins. Concurrent use of statins with fibrates in particular seems to increase the risk of this adverse effect.Objective: To evaluate the incidence and clinical consequences of the use of lovastatin or simvastatin with concomitant CYP3A4 inhibitors and inducers, and with fibrates.Methods: An observational database study of hospitalized patients treated in Turku University Hospital, Turku, Finland, covering the period 1 July 1996 to 30 June 2003, and of nationwide community data from the Finnish Prescription Register over the period 1 April to 30 June 2001 was conducted. In the hospital setting, the study population comprised 71 025 patients (93 467 treatment periods) over 7 years, with a total of 5320 treatment periods of lovastatin or simvastatin. The community-based, nationwide survey included all reimbursed prescriptions of lovastatin and simvastatin (n = 91 656) in Finland during a 3-month period. The frequency of drug-drug interactions involving lovastatin or simvastatin was studied. The efficacy and safety of the various statin/concomitant drug combinations was estimated by evaluating patients' laboratory data.Results: Concomitant use of lovastatin or simvastatin with interacting medication was detected in 13.3% (704) and 6.9% (6338) of patients in hospital and community settings, respectively. Co-administration of lovastatin or simvastatin with CYP3A4 inhibitors or inducers did not have a clinically significant effect on serum lipid values. Plasma creatine kinase (CK) activity was significantly higher in patients receiving a statin and a fibrate compared with a statin only (433 U/L vs 209 U/L, p = 0.053). Co-administration of a statin and a CYP3A4 inhibitor did not increase CK activity.Conclusion: Although the pharmacokinetic interactions between lovastatin or simvastatin and CYP3A4 inhibitors and inducers are substantial, their clinical relevance seems to be limited, at least with lower statin doses. However, combining statins with fibrates, especially gemfibrozil, clearly increases the potential for muscular toxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Ambulatory blood pressure (ABP) has been shown to be a better predictor of cardiovascular events than clinical blood pressure (BP) in middle-aged and older populations. This study studied the association of various components of ABP (daytime, night-time, 24-hour ABP) in the presence of coronary heart disease (CHD) in an older Finnish population. METHODS: This cross-sectional, observational, population-based study was carried out in The Lieto Health Centre, Finland, in 1998-99. The study population consisted of 502 subjects (237 men, 265 women) aged 64-87 years. ABP measurements for 24 hours, daytime (awake) and night-time (asleep), were made. Resting electrocardiograms (ECG) were recorded. A person was considered to have CHD if at least one of the following criteria was met: (I) history of coronary by-pass surgery or coronary angioplasty, (II) diagnosis of CHD in previous medical records, (III) ischemia-related changes on ECG. RESULTS: CHD increased by 30% with a 10 mmHg increase in night-time systolic blood pressure (SBP) (OR 1.30, 95% Cl 1.15-1.47). When ambulatory 24-hour and daytime SBP values were each entered separately into the multivariate model, 24-hour SBP, but not daytime SBP, was associated with CHD. CONCLUSIONS: The most important information gained from 24-h BP monitoring in subjects with CHD is night-time BP. Night-time BP may provide new information about the CHD risk which is not identified in common clinical diagnoses of hypertension. ABP measurements should be made to confirm sufficient control of night-time BP, especially SBP, in older people with CHD. [ABSTRACT FROM AUTHOR]

Objective: Determination of the activity of Crohn's disease at a defined time-point is a challenging task since only endoscopy guidelines are given and secondary clinical findings, subjective symptoms and non-specific laboratory tests have therefore to be relied on. The purpose of the current study was to investigate the ability of blood tests to differentiate patient groups with different clinical disease activity and different clinical outcomes during follow-up in Crohn's disease.Material and Methods: During a visit to hospital, 73 outpatients with Crohn's disease were examined, a clinical score was calculated and blood samples were collected for 22 laboratory tests. The patients were also grouped according to clinical outcome during a 6-year follow-up.Results: Serum group IIA phospholipase A2 and alpha-1-antitrypsin values were outside the reference interval more frequently (62% and 42%, respectively) than the other tests in active Crohn's disease. Only weak correlations were found between the clinical score and the test values, and the best correlation was found with serum lysozyme (r = 0.40). In a logistic regression model, the best prediction of disease activity at entry to the study was reached with a model including serum orosomucoid and serum lysozyme and the best prediction of clinical outcome during follow-up was reached using a model including serum albumin.Conclusions: Serum group IIA phospholipase A2 appeared to be the most sensitive marker of inflammation in Crohn's disease among the 22 blood tests compared. No reliable predictions of disease activity at the time of blood sampling or clinical outcome later during follow-up could be made from the blood tests studied. [ABSTRACT FROM AUTHOR]

Objectives: To study the effect of vitamin D supplementation and the impact of summer season on serum 25-hydroxyvitamin D (S-25(OH)D) in Finnish 9-15-y-old girls. Design: Three-year follow-up study with vitamin D[sub 2] supplementation using D[sub 2] 10 µg daily from October to January for the first and from October to February for the second winter as well as 20 µg daily from October to March for the third winter. Setting: Paavo Nurmi Centre, University of Turku, Turku, Finland. Subjects: A total of 171 female volunteers aged 9-15 y. Methods: Vitamin D and calcium intakes were estimated by a semi-quantitative food frequency questionnaire (FFQ). S-25(OH)D was measured by radioimmunoassay. Results: The median daily dietary intakes of vitamin D and calcium were 3.8 µg (interquartile range (IQR) 2.7-5.0) and 1451 mg (IQR 1196-1812), respectively, over 3 y. The prevalence of severe hypovitaminosis D (S-25(OH)D < 20 nmol/I) was 14% and of moderate hypovitaminosis D (20 nmol/I ≤ S-25(OH)D ≤ 37.5 nmol/I) 75% at baseline in winter. None of the participants had severe hypovitaminosis D in summer. The effect of 10 µg of D[sub 2] daily was insufficient to raise S-25(OH)D from baseline. The daily supplementation of 20 µg of D[sub 2] increased S-25(OH)D significantly in wintertime compared with the nonsupplement users (to 45.5 vs 31.8 nmol/l; P < 0.001 ). None Of the subjects with vitamin D[sub 2] supplementation approximately 20 µg daily had severe hypovitaminosis D; however, 38% of those participants had moderate hypovitaminosis D at 36 months. Sun exposure in summer raised mean S-25(OH)D to 62.0 nmol/L Both the daily supplementation of approximately 20 µg of D[sub 2] and summer sunlight exposure had more effect on those who had severe hypovitaminosis than those who had a normal vitamin D status (increase of 24.2 vs 0.9 nmol/I (P < 0.001 ), and 38.8 vs 18.2 nmol/I (P < 0.001 ), respectively). Conclusion: Vitamin D... [ABSTRACT FROM AUTHOR]

Group II phospholipase A[sub 2] is involved in the pathogenesis of various inflammatory diseases and in the host defence against bacteria. The enzyme is expressed in the epithelial cells of colonic mucosa in ulcerative colitis. In this study, we measured the concentration of group II phospholipase A[sub 2] in serum and colonic mucosa of patients with ulcerative colitis of different severity and of control patients without any inflammatory disease. The activity of ulcerative colitis was assessed by endoscopy. The concentration of group II phospholipase A[sub 2] was measured with an immunoassay. The concentrations of group II phospholipase A[sub 2] in serum and colonic mucosa were significantly higher in patients with active and inactive ulcerative colitis than in controls. However, the group II phospholipase A[sub 2] levels did not separate patients with different disease activity. The concentration of group II phospholipase A[sub 2] in colonic mucosa corresponded with the mucosal inflammatory activity (higher in active colonic areas) intra-individually, but not between different patients with ulcerative colitis. Serum group II phospholipase A[sub 2] values were above the normal reference range more often than the values of 11 standard laboratory blood tests widely used for the follow-up of inflammatory activity in ulcerative colitis. These results indicate that the concentration of group II phospholipase A[sub 2] is increased in serum and colonic mucosa of patients with ulcerative colitis. The clinical value of the measurement of group II phospholipase A[sub 2] in the follow-up of ulcerative colitis remains to be clarified. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to evaluate the effect of estrogen replacement therapy on sleep complaints by postmenopausal women and to assess the predictive factors involved.Study Design: Sixty-three postmenopausal women entered a 7-month prospective, randomized, double-blind, crossover study consisting of two 3-month treatments with estrogen and placebo with a 1-month washout period between. Eight Visual Analogic Scale statements about different sleep complaints, the Basic Nordic Sleep Questionnaire, scoring of climacteric symptoms, The Beck Depression Inventory, and serum estradiol and follicle-stimulating hormone level controls were the main outcome measures.Results: Estrogen replacement therapy improved sleep quality, facilitated falling asleep, and decreased nocturnal restlessness and awakenings (p < 0.001). The subjects were less tired in the mornings and in the daytime (p < 0.001) when taking estrogen replacement therapy. Estrogen-induced sleep improvement was associated with alleviation of vasomotor symptoms (r range 0.27 to 0.55), alleviation of somatic symptoms (palpitations and muscular pain, r range 0.26 to 0.36), and alleviation of mood symptoms (r range 0.28 to 0.37) on estrogen replacement therapy. The severity of initial insomnia predicted only one estrogen-induced sleep improvement effect: the more the subjects experienced insomnia, the better the estrogen replacement therapy facilitated falling asleep (r = 0.26, p = 0.040). Estrogen-induced sleep improvement was also reported by the 15 climacterically asymptomatic subjects. In these subjects initial insomnia scores strongly predicted estrogen-induced sleep improvement (r range 0.50 to 0.75).Conclusions: Estrogen replacement therapy significantly diminished sleep complaints among postmenopausal women. Alleviation of climacteric symptoms was the most important predictive factor for the beneficial effect of estrogen replacement therapy on sleep complaints. The use of estrogen replacement therapy in women without self-reported climacteric symptoms could also be considered because women do not always recognize their climacteric symptoms or they ignore them. [ABSTRACT FROM AUTHOR]

Female hyperandrogenism is often associated with hyperinsulinaemia and insulin resistance. We evaluated the hormone responses in an oral glucose tolerance test to investigate the interactions of gonadotrophins, insulin, C-peptide and androgens in women with polycystic ovarian disease (PCOD). In 28 patients with ultrasonographically diagnosed PCOD, hyperinsulinaemia and insulin resistance were mainly associated with obesity. Both basal and cumulative sum of insulin to C-peptide ratios were high in obese subjects, suggesting decreasing hepatic removal of insulin caused by obesity. Nevertheless, in some lean PCOD women, despite normal fasting insulin concentrations, insulin hypersecretion existed. The mean concentration of testosterone decreased significantly during the oral glucose tolerance test both in PCOD and control women, and of androstenedione in the PCOD patients only. However, an increase in androgen responses was found in a subgroup of PCOD patients, who had both elevated luteinizing hormone (LH) concentrations and hyperinsulinaemic response to oral glucose. In the remaining PCOD patients an inverse correlation between LH and insulin was found. The patients with hyperinsulinaemia together with LH hypersecretion may represent a subgroup of PCOD with deranged regulation of androgen secretion. [ABSTRACT FROM AUTHOR]