Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin.

OBJECTIVES: This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (< or = 100 mg/dl [2.59 mmol/liter]). BACKGROUND: For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains > or = 130 mg/dl (3.36 mmol/liter). METHODS: A total of 318 men or women with documented atherosclerosis and LDL cholesterol > or = 130 mg/dl (3.36 mmol/liter) and < or = 250 mg/dl (6.5 mmol/liter), and triglycerides < or = 400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated. RESULTS: At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day. CONCLUSIONS: A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.

Blood ferritin concentrations in newborn infants and the sudden infant death syndrome.

Liver iron concentrations have been shown to be higher in victims of SIDS than in postmortem controls suggesting that high levels of tissue iron may be implicated in SIDS. To determine whether infants who subsequently die from SIDS are born with greater iron stores than those who do not, the iron stores in newborn infants were assessed retrospectively by measuring blood ferritin concentration in spots from Guthrie cards (collected from almost all infants born in the UK in the first week of life). A method for extracting and measuring ferritin from stored blood spots is described. Eighteen cases of SIDS were identified in South Glamorgan along with four controls for each case. Ferritin concentrations did not differ in SIDS victims and controls suggesting that victims of SIDS are not born with abnormal concentrations of stored iron. If iron stores are found to be higher in SIDS victims than in healthy live infants of the same age then it is more likely that the iron will have been acquired after birth.

The clinical value of serum prolactin measurement in the differential diagnosis of complex partial seizures.

The time course of changes in serum prolactin after complex partial seizures has been determined and compared to similar changes after other types of seizure and non-epileptic attacks. Seizures in 33 subjects were recorded on video EEG telemetry. Peak serum prolactin concentrations occurred 15-20 min after tonic-clonic seizures, 10 min after complex partial seizures, and were highest after generalised tonic-clonic seizures. Serum prolactin concentrations remained less than 1000 mU/l after absences and non-epileptic attacks. Application of Bayes' theorem showed that where serum prolactin was greater than 1000 mU/l 5-10 min post event this would identify genuine tonic-clonic or complex partial seizures. The false negative rate of this test was 9% for tonic-clonic seizures and 38% for complex partial seizures. Failure of serum prolactin to rise after an attack is of little value in distinguishing complex partial seizures from non-epileptic attacks.

Testosterone levels during systemic and inhaled corticosteroid therapy.

Testosterone has importance both as a sex hormone and as an anabolic steroid promoting bone formation. Osteoporosis is associated with both hypogonadism and corticosteroid therapy. Testosterone levels are reduced by long term prednisolone treatment. Although high dose inhaled corticosteroid therapy may cause a variety of systemic effects including adrenal suppression, dermal thinning and a reduction in total bone calcium, its effect on testosterone levels is not known. Testosterone, luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin were therefore measured in 35 male patients with respiratory disease attending an outpatient clinic (median age 58, range 21-75 years). They were grouped according to steroid therapy and compared with 19 age matched controls. Mean (SD) testosterone levels were 33% lower in 12 men on long term oral prednisolone [14.5 (6.0) nmol 1-1] than in controls [21.7 (6.3) nmol 1-1], but were not significantly reduced in 10 patients on low dose inhaled beclomethasone [200-800 micrograms day-1: 19.7 (3.7)] nor in 13 men taking high dose inhaled beclomethasone [1500-2,250 micrograms day-1: 17.9 (5.6)]. Levels of luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin were similar in all four groups. These cross sectional data confirm that long term systemic corticosteroid therapy reduces testosterone levels. However, testosterone was reduced by only 18% (NS) by long term inhaled corticosteroids. Other mechanisms to explain the disordered bone metabolism should now be explored.

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin.

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.

Two years' experience with an enhanced chemiluminescent assay for neonatal blood spot TSH.

We have developed a blood spot assay for thyroid stimulating hormone (TSH) based on the Amerlite TSH-30 serum assay for use in the Welsh neonatal hypothyroid screening programme. A total of 67,656 infants were screened in 1994 and 1995, and 28 cases of primary hypothyroidism were detected, giving a prevalence of one in 2416. The method is sensitive and rapid, results being available within 3 h of receipt of samples. The assay enables much faster detection of primary hypothyroidism than was previously possible, and therefore contributes to earlier treatment of affected infants.

Antibody interference in a two-site immunometric assay for thyrotrophin.

Of 1585 consecutive serum samples referred for thyroid function testing, 14 gave erroneously high values from a two-site immunoenzymometric assay for thyrotrophin. The addition of mouse or newborn calf serum to the assay failed to correct the interference. In serum samples from 11 patients who were available for follow up a higher concentration of mouse, but not of horse, sheep or rabbit serum reduced the interference. The interference was associated only with assay systems which employed horseradish peroxidase but not 125I as a label. Addition of mouse serum and anti-IgM to the assay reagents successfully removed the interference.

Chemical and physical context for life in terrestrial hydrothermal systems: chemical reactors for the early development of life and hydrothermal ecosystems.

The diversity of terrestrial hot spring systems, resulting from the large scale coupled transfer of heat and mass in the Earth's crust, maximizes opportunities for evolving ecosystems by the continuous supply of nutrients (P, N, C, S) together with the metals (e.g. K, Mg, Mo, Zn) essential to biogenesis. Cyclic, evaporative micro-environments are common, and potentially catalytic mineral surfaces are also continually created through rock alteration and mineral deposition in and around hot springs. These dynamical systems constitute highly interactive, open, chemical environments capable of establishing complex biochemical microreactors. Volcanic collapse settings on oceanic islands, provide a highly dynamic scenario for the initiation of life and development of diverse ecosystems at the earliest stages of development of the Earth's crust.

Chemiluminescence in the presence of ferritin.

The ability of ferritins with differing iron contents to catalyze the oxidation of luminol by hydrogen peroxide was studied. The least efficient catalysts were iron-rich ferritins, and the most potent were those with iron to protein ratios of less than 0.1.