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Biomedical subjects

E Hagen

Publications and source records attributed to E Hagen.

At least 37 records · Page 2Linked to original sources

Changes in plasma apolipoprotein B-containing lipoparticle levels following therapy with fluvastatin and cholestyramine. European Fluvastatin Study Group.

Epidemiologic studies have demonstrated that apolipoprotein (apo) B-containing lipoparticles (LpE:B, LpC-III:B) are associated with the risk of coronary artery disease whereas apo A-1-containing lipoparticles (LpA-I) are protective against coronary artery disease. The effect on lipoparticle levels of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, in combination with cholestyramine, was assessed in a double-blind randomized study. A total of 144 patients with primary hypercholesterolemia were recruited, who had successfully completed an original study comparing the effects of fluvastatin and cholestyramine on plasma lipoparticle levels. All subjects fulfilled the following inclusion criteria: plasma low density lipoprotein cholesterol (LDL-C) levels > 160 mg/dL, with premature coronary artery disease and 2 associated risk factors; or LDL-C > 190 mg/dL, no coronary artery disease, and triglycerides < 300 mg/dL, after a lipid-lowering diet. Patients were randomized to 1 of 3 combination therapy groups: fluvastatin 20 mg/day plus cholestyramine 4 g/day; fluvastatin 20 mg/day plus cholestyramine 8 g/day; and fluvastatin 20 mg/day plus cholestyramine 16 g/day. The study length was 6 weeks and patients were examined at 3-week intervals. Fluvastatin plus cholestyramine produced a significant (p < 0.001), dose-dependent reduction in levels of cholesterol (range, -29 to -34%), LDL-C (range, -30 to -44%), apo B (range, -23 to -34%), and apo E (range, -33 to -43%). LpE:B levels were also reduced (range, -19 to -26%), but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗

Comparison of the effect of fluvastatin, an hydroxymethyl glutaryl coenzyme A reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by apolipoprotein composition.

In a double-blind, parallel-group, randomized study, the effects of fluvastatin (FLUV) 20 and 40 mg/d on lipoprotein particle levels were compared with those of cholestyramine (CME) 16 g/d. Lipoparticles were defined by apolipoprotein composition as either those containing both apolipoprotein (apo) B and apo E or CIII (lipoprotein [Lp] E-B or Lp CIII-B) or those containing apo AI alone (Lp AI) or in association with apo AII (Lp AI-AII). After an 8-week dietary stabilization period, 100 hypercholesterolemic patients were treated with FLUV 20 mg/d for 6 weeks and 40 mg/d for an additional 6 weeks and were compared with 48 hypercholesterolemic subjects treated with CME 16 g/d. Treatment with FLUV (40 mg/d) or CME (16 g/d) for 12 weeks was associated with a significant reduction in plasma cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in high-density lipoprotein (HDL) cholesterol. However, plasma triglyceride levels decreased following FLUV treatment, whereas they increased with CME. These changes were associated with a significant reduction in the levels of apo B (FLUV, -24%, P < .001; CME, -26%, P < .001), apo E (FLUV, -36%, P < .001; CME, -32%, P < .001), and apo CIII (FLUV, -21%, P < .001; CME, -6%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Synthesis and characterization of iodixanol.

Iodixanol (Visipaque) is a new nonionic roentgen contrast medium intended for general use. Visipaque is a pharmaceutical formulation of iodixanol which is isotonic and iso-osmotic with blood. Two synthetic routes from 5-nitro-isophthalic acid to iodixanol are described. The chemical structure is confirmed spectroscopical data ((1)H-NMR, (13)C-NMR, FAB-MS, UV, IR and Raman). Chromotographic characteristics are related to the isomerism of iodixanol.

Chromatography, High Pressure Liquid↗

Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine.

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed. Fluvastatin (40 mg) reduced LDL cholesterol by 28.0%, triglycerides by 10.5% and increased HDL cholesterol by 3.7%. Cholestyramine (16 g) reduced LDL cholesterol by 35.0%, but raised triglycerides and HDL cholesterol by 12.3% (p < 0.01) and 3.7% respectively. The combination of fluvastatin 20 mg and cholestyramine (4 g, 8 g and 16 g) induced the following reductions in LDL cholesterol: 30.4%, 35.6% and 46.6% respectively. There was no significant change in triglycerides in either group although HDL cholesterol was raised by 4.9%, 8.3% and 7.2% respectively. One patient treated with fluvastatin and two treated with cholestyramine were withdrawn from the study due to elevation of liver transaminases. The most frequent subjective adverse effects in both treatment groups were mild, transient gastrointestinal complaints. Thus, fluvastatin was effective as a lipid-lowering agent; the effect was further enhanced when fluvastatin was combined with cholestyramine.

Anticholesteremic Agents↗

Efficacy of a protocol to distinguish risk of serious bacterial infection in the outpatient evaluation of febrile young infants.

A study of 534 febrile infants ages 4 to 8 weeks evaluated for sepsis assessed the efficacy of the Milwaukee Protocol (MP) for selecting patients at low risk for serious bacterial infection (SBI) who might benefit from outpatient management. Two groups were compared: 1) Infants with uncompromised presentation (UP) who met all MP criteria received ceftriaxone 50 mg/kg and were discharged, then reevaluated within 24 hours. 2) Infants with compromised presentation (CP) who did not meet MP criteria were hospitalized for antibiotic therapy pending culture results. Of 391 CP patients, 23 (5.9%) had SBI; of 143 UP patients, 1 (0.7%) had SBI (P < .02). The MP criteria had a sensitivity of 96% and a 99% negative predictive value for distinguishing SBI outcome. The only UP patient with SBI was afebrile and had a negative repeat blood culture after 24 hours, and recovered with no complications. Managing UP infants as outpatients avoided 48 to 72 hours of hospitalization, decreasing health-care costs by an estimated total of $465,170.

Bacterial Infections↗

A comparison of the accuracy of the TDx-FLM assay, lecithin-sphingomyelin ratio, and phosphatidylglycerol in the prediction of neonatal respiratory distress syndrome.

OBJECTIVE: To ascertain whether the TDx-FLM assay is a better predictor of neonatal respiratory distress syndrome (RDS) than the lecithin-sphingomyelin ratio (L/S) and phosphatidylglycerol (PG). METHODS: Amniotic fluid samples of 140 women requiring assessment of fetal lung maturity and delivering within 72 hours of amniocentesis were analyzed by the three methods. The accuracy in predicting RDS was assessed by conventional statistical techniques. RESULTS: The TDx-FLM test had a better sensitivity (89.6 versus 48.2%; relative risk [RR] 3.9, 95% confidence interval [CI] 1.35-11.23, P = .001) and negative predictive value (96.4 versus 86.8%; RR 0.36, 95% CI 0.12-1.04, P = .02) than the L/S. However, the L/S had a better specificity (89.1 versus 73.8%; RR 0.64, 95% CI 0.49-0.82, P = .005) than the TDx-FLM assay. The PG test had a predictive ability similar to that of the TDx-FLM assay. However, there was no significant difference in the overall accuracy of the three tests, and the areas under the receiver-operating characteristic curves for the L/S and TDx-FLM (0.80 and 0.87) were similar. CONCLUSIONS: The TDx-FLM assay performs similarly to the L/S and PG tests in the prediction of RDS and is quantitative, rapid, and reproducible.

Albumins↗

Ultrastructure of rabbit retinal nerve fibre layer--neuro-glial relationships, myelination, and nerve fibre spectrum.

The ultrastructure of the rabbit retinal nerve fibre layer was studied both in retinal centre and periphery. The central nerve fibre layer was found to contain large masses of--mostly myelinated--nerve fibres, somata and processes of astrocytes and oligodendrocytes, vitreal processes of Müller cells, and blood vessels. Astrocyte and Müller cell processes could be discriminated both by their direction and by the thickness of their intermediate filaments which was about 7 nm in Müller cells and about 10 nm in astrocytes. Some peculiarities of nuclei and cytoplasmic organelles of rabbit retinal astrocytes and oligodendrocytes are described. Myelin sheaths are demonstrated to be derived from oligodendrocytes; in some cases, two axons were found within a common myelin sheath. In the retinal periphery, only sparse thin bundles of unmyelinated axons were found in between a thick row of big Müller cell endfeet; astrocytes, oligodendrocytes, and blood vessels were missing here. In both retinal regions, node-like membrane specializations of optic axons were found; these were always surrounded by a corona of fine glial processes arising from astrocytes as well as from Müller cells. The features of myelination within the rabbit nerve fibre layer were quantified, and compared with recent literature data. A hypothesis is offered relating the production of myelin to the release of diffusable substance(s) by active axons. This hypotheses allows to account for the striking finding that relatively thick axons remain unmyelinated in the nerve fibre layer of most mammalian retinae like in the rabbit retinal periphery whereas they become myelinated in the central rabbit retina like in central nervous system in general.

Animals↗

Acute hemodynamic and hormonal effects of lisinopril (MK-521) in congestive heart failure.

The acute hemodynamic and hormonal effects of the oral angiotensin-converting enzyme (ACE) inhibitor lisinopril (MK-521) were assessed over a period of 96 hours in 12 patients with heart failure. This compound is the lysine analogue of enalaprilat (MK-422), is biologically active following absorption, and is cleared via the urine without any known metabolic transformation. Single doses of lisinopril, ranging from 1.25 mg to 10 mg, were administered on days 1 and 3, each followed by 48 hours of intensive hemodynamic observation. Across all doses, maximal reductions in mean arterial pressure (17.2%), mean pulmonary capillary wedge pressure (28%), and systemic vascular resistance (25.6%) were observed compared to baseline values. No significant changes in heart rate were recorded. Arterial blood was sampled at frequent intervals for angiotensin II, ACE activity, plasma renin activity, renin substrate, plasma aldosterone, and serum drug levels. Right atrial blood was sampled simultaneously for angiotensin I, thus permitting assessment of the degree of pulmonary conversion to angiotensin II. The results indicate potent inhibition of the renin-angiotensin-aldosterone system along with hemodynamic efficacy over a period exceeding 24 hours. Frequent clinical follow-up on long-term chronic therapy has revealed no adverse experience.

Adult↗

Using conventional infant ventilators at unconventional rates.

The effect of progressive increases in ventilator rate on delivered tidal and minute volumes, and the effect of changing peak inspiratory pressure (Pmax), positive end-expiratory pressure (PEEP), and inspiration to expiration (I:E) ratio at different ventilator rates were examined. Five different continuous-flow, time-cycled, pressure-preset infant ventilators were studied using a pneumotachograph, an airway pressure monitor, and a lung simulator. As rates increased from 10 to 150 breaths per minute, tidal volume stayed constant until 25 to 30 breaths per minute; then progressively decreased. In all, tidal volume began to decrease when proximal airway pressure waves lost inspiratory pressure plateaus. As rates increased, minute volume increased until 75 breaths per minute, then leveled off, then decreased. Substituting helium for O2 increased the ventilator rate at which this minute volume plateau effect occurred. Increasing peak inspiratory pressure consistently increased tidal volume. Increasing positive end-expiratory pressure decreased tidal volume. At rates less than 75 breaths per minute, inspiratory time (inspiration to expiration ratio) had little effect on delivered volume. At rates greater than 75 breaths per minute, inspiratory time became an important determinant of minute volume. For any given combination of lung compliance and airway resistance: there is a maximum ventilator rate beyond which tidal volume progressively decreases and another maximum ventilator rate beyond which minute volume progressively decreases; at slower rates, delivered volumes are determined primarily by changes in proximal airway pressures; at very rapid rates, inspiratory time becomes a key determinant of delivered volume.

Humans↗