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1.
Methods Inf Med ; 52(3): 239-49, 2013.
Article in English | MEDLINE | ID: mdl-23591822

ABSTRACT

OBJECTIVE: Development of a clinical sensor network system that automatically collects vital sign and its supplemental data, and evaluation the effect of automatic vital sensor value assignment to patients based on locations of sensors. METHODS: The sensor network estimates the data-source, a target patient, from the position of a vital sign sensor obtained from a newly developed proximity sensing system. The proximity sensing system estimates the positions of the devices using a Bluetooth inquiry process. Using Bluetooth access points and the positioning system newly developed in this project, the sensor network collects vital sign and its 4W (who, where, what, and when) supplemental data from any Bluetooth ready vital sign sensors such as Continua-ready devices. The prototype was evaluated in a pseudo clinical setting at Kyoto University Hospital using a cyclic paired comparison and statistical analysis. RESULTS: The result of the cyclic paired analysis shows the subjects evaluated the proposed system is more effective and safer than POCS as well as paper-based operation. It halves the times for vital signs input and eliminates input errors. On the other hand, the prototype failed in its position estimation for 12.6% of all attempts, and the nurses overlooked half of the errors. A detailed investigation clears that an advanced interface to show the system's "confidence", i.e. the probability of estimation error, must be effective to reduce the oversights. CONCLUSIONS: This paper proposed a clinical sensor network system that relieves nurses from vital signs input tasks. The result clearly shows that the proposed system increases the efficiency and safety of the nursing process both subjectively and objectively. It is a step toward new generation of point of nursing care systems where sensors take over the tasks of data input from the nurses.


Subject(s)
Automation/instrumentation , Monitoring, Physiologic/instrumentation , Vital Signs , Efficiency, Organizational , Humans , Japan , Nursing Staff, Hospital , Point-of-Care Systems , Wireless Technology
3.
J Chromatogr B Biomed Sci Appl ; 746(1): 91-4, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-11048744

ABSTRACT

By using electrospray ionization liquid chromatography-mass spectrometry, we demonstrated that glutathionyl hemoglobin (Hb)beta-chain levels are markedly increased in the erythrocytes of diabetic patients as compared with healthy subjects. The administration of vitamin E to the diabetic patients for 8 weeks significantly decreased the levels of glutathionyl Hbbeta, whereas it did not affect the levels of HbA1c, glycated Hbbeta or glycated Hbalpha. Glutathionyl Hb levels can be used as a new clinical marker of oxidative stress.


Subject(s)
Diabetes Mellitus, Type 2/blood , Glutathione/analysis , Hemoglobins/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Vitamin E/administration & dosage , Humans
4.
Int J Clin Pharmacol Ther ; 38(2): 80-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10706195

ABSTRACT

The mainstays of the harmonized final document about ethnic factors in the acceptability of foreign clinical data include a complete clinical data package and a bridging study (for efficacy and/or for safety). A clinical data package that meets all of the regional regulatory requirements is defined as a complete clinical data package for submission and potential approval, irrespective of its geographic origin. The acceptability of the foreign clinical data component of the complete data package depends upon whether it can be extrapolated or employed as a bridge to the population of the new region. Ethnic factors can be defined as the intrinsic characteristics of recipients of a medicine, and extrinsic characteristics associated with the environment and culture in which the subjects reside. Based on retrospective studies, inter-ethnic differences in ADME seem to be not greater than intra-ethnic variations for most medicines, and extrinsic factors appear to be more important than intrinsic factors for the assessment of efficacy and safety of the drug across ethnicity. Medical practice may represent one of the biggest differences and may perhaps prove to be very difficult to provide a harmonization for these extrinsic factors. The bridging study concept has primarily been brought up to overcome the difficulties inherent to extrinsic factors caused by different ethnicity. In Japan, the clinical trials advice division of the organization for pharmaceutical safety and research (OPSR) has been dealing with consultations about bridging studies since February 1998. The contents of consultations can be classified into 5 types. The most common type involves the desire by industries to bridge or extrapolate the results of foreign, phase III, clinical studies by conducting the dose-response studies domestically in the form of bridging studies. Until we have more information and have collected experiences in the variations caused by the regional differences as a result of extrinsic as well as intrinsic ethnic factors, we hope and believe that this document will serve to help provide great advancements in the acceptance of foreign clinical data.


Subject(s)
Clinical Trials as Topic/methods , Drug Therapy/methods , International Cooperation , Asian People , Clinical Trials as Topic/standards , Drug Therapy/standards , Drug-Related Side Effects and Adverse Reactions , Ethnicity , Humans , Japan
5.
Clin Chem ; 46(1): 82-8, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10620575

ABSTRACT

BACKGROUND: Erythrocytes contain a large amount of glutathione (GSH), which protects cells from oxidative injury. The purpose of this study was to examine whether hemoglobin (Hb) is modified with glutathione by oxidation of the thiol groups in diabetes mellitus and hyperlipidemia, and to determine the oxygen affinity of glutathionyl Hb. METHODS: Hb samples obtained from patients with type 2 diabetes, patients with hyperlipidemia, and healthy subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS). Glutathionyl Hb was synthesized in vitro by incubating Hb with GSH. The oxygen affinity of glutathionyl Hb was determined by measuring its oxygen dissociation curve. RESULTS: We first demonstrated that the concentration of glutathionyl Hbbeta chains is markedly increased in the diabetic patients and hyperlipidemic patients compared with healthy subjects. The in vitro synthesis of glutathionyl Hb by incubation of Hb with GSH was enhanced by adding H(2)O(2), a reactive oxygen species, into the incubation solution. The glutathionyl Hb prepared in vitro by incubating Hb with GSH showed a marked increase in oxygen affinity and a marked decrease in the Hill coefficient compared with Hb incubated without GSH. CONCLUSIONS: Glutathionyl Hb may be useful as a clinical marker of oxidative stress. The increased concentrations of glutathionyl Hb with high oxygen affinity and low cooperativity in diabetes and hyperlipidemia may lead to reduced tissue oxygen delivery.


Subject(s)
Diabetes Mellitus/blood , Glutathione/metabolism , Hemoglobins/metabolism , Hyperlipidemias/blood , Chromatography, Liquid , Female , Glutathione/chemistry , Hemoglobins/chemistry , Humans , Male , Mass Spectrometry , Oxygen/chemistry
6.
Jpn Circ J ; 64(12): 943-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11194288

ABSTRACT

Among the original selection criteria for the Fontan operation, the recommended age at the time of surgery has been 4 years or older, but recent clinical data have indicated the feasibility of this procedure in younger patients. Because age may influence the properties of the systemic vascular bed, changes in systemic vascular resistance (Rs) and systemic vascular compliance (Cs) associated with physical development were quantified in 86 pediatric patients without known abnormalities of the systemic circulation, and the effects of age (body size) on Fontan circulation were then analyzed using an analytical model of the cardiovascular system. As the body surface area (BSA) of the patient decreased, Cs also decreased significantly (r=0.81, p<0.001). Based upon this relationship between BSA and Cs, the analytical model showed that the impedance (ventricular afterload) of the Fontan circulation significantly increased as Cs decreased with the decrease in BSA. Moreover, the increase in impedance in response to changes in heart rate or Rs was inversely proportional to the BSA. However, these findings were significant only when the BSA was below 0.3 m2. Small BSA, or a lower age, has minimal effects on the Fontan circulation until it comes close to the infant value, and thus the Fontan procedure may be feasible much earlier than formerly recommended when the hemodynamics are otherwise acceptable.


Subject(s)
Body Constitution/physiology , Fontan Procedure , Models, Cardiovascular , Age Factors , Blood Circulation , Child, Preschool , Elasticity , Humans , Infant , Linear Models , Regional Blood Flow , Vascular Resistance
7.
J Chromatogr B Biomed Sci Appl ; 731(1): 121-4, 1999 Aug 06.
Article in English | MEDLINE | ID: mdl-10491997

ABSTRACT

We first detected glutathionyl hemoglobin (Hb) beta-chain in hemodialysis patients and healthy subjects using electrospray ionization liquid chromatography-mass spectrometry. The ratio of glutathionyl Hb beta-chain to total beta-chain was markedly increased in the hemodialysis patients as compared with healthy subjects. Glutathionyl Hb will be used as a new clinical marker of oxidative stress.


Subject(s)
Biomarkers/analysis , Chromatography, Gas/methods , Glutathione/analysis , Hemoglobins/analysis , Mass Spectrometry/methods , Renal Dialysis , Adult , Humans , Oxidative Stress
8.
Reprod Fertil Dev ; 11(3): 147-51, 1999.
Article in English | MEDLINE | ID: mdl-10864170

ABSTRACT

The concentration and affinity of luteinizing hormone (LH) receptors in bovine luteal tissues during the oestrous cycle and pregnancy were investigated by Scatchard analysis of the binding of 125I-labeled human chorionic gonadotropin. Corpora lutea (CL) were classified into five stages of the oestrous cycle and three stages of pregnancy. The concentration of LH receptors sharply increased from the early I stage of the oestrous cycle (Days 2-3; 3.09 fmol mg(-1) protein) to the early II stage (Days 5-6; 9.44 fmol mg(-1) protein) and then remained constant until the late luteal stage (Days 15-17; 8.14-9.56 fmol mg(-1) protein). The LH receptors could not be analysed in the regressed luteal tissue due to the small amounts of binding. There was no significant difference in the concentrations of LH receptors (5.63-9.64 fmol mg(-1) protein) among the three stages of pregnancy. Moreover, the concentrations of the receptors in the CL of pregnancy were comparable to those in the mid-cycle CL. The binding affinity did not change significantly during the oestrous cycle and pregnancy. Based on these results, it is assumed that the luteal function during the entire period of pregnancy might be regulated, at least in part, by LH, which is mediated via its specific receptors, and that the luteal function during pregnancy seems not to be regulated by changes in the binding capacity and affinity of LH receptors. To understand the physiological roles of LH in regulating luteal function in pregnant cows, further studies are required.


Subject(s)
Corpus Luteum/chemistry , Estrus/metabolism , Receptors, LH/analysis , Animals , Cattle , Chorionic Gonadotropin/metabolism , Corpus Luteum/physiology , Female , Iodine Radioisotopes , Pregnancy , Receptors, LH/metabolism
9.
J Nutr Sci Vitaminol (Tokyo) ; 44(2): 329-36, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9675713

ABSTRACT

When an anion-exchange resin column (Plasorba BR-350) was used for the treatment of unconjugated hyperbilirubinemia, we found an unexpected decrease in plasma retinol (vitamin A) concentrations in a patient with type I Crigler-Najjar syndrome. The purpose of our study was to investigate the mechanism of this decrease in plasma retinol. When the patient's serum bilirubin exceeded the bilirubin binding capacity of 14.7 mumol bilirubin/g serum albumin (i.e., 720 mumol/L of bilirubin), abrupt deterioration of the patient's neurologic status (suppression in his gait and speech) occurred, so the need to apply plasmapheresis to reduce the unconjugated bilirubin was indicated. Blood was drawn from the radial artery at a flow rate of 160 mL/min and pumped into a membrane plasma separator at a rate of 40 mL/min. The plasma was passed through the bilirubin adsorbent column and returned to the venous blood line of the plasma separator. Plasma samples were taken at the inlet and outlet of the bilirubin adsorbent column before and after treatment. The concentration of unconjugated bilirubin in plasma was effectively reduced by the perfusion, but plasma retinol was coincidentally decreased by the perfusion to vitamin A deficiency levels. The patient's plasma retinol was 2,127 nmol/L at the beginning of therapy and decreased to 1,492 nmol/L after repeated adsorption treatments. As the amounts of decrease in retinol (912 +/- 123 nmol/L) after the perfusion were almost equal to those in retinol-binding protein (1,010 +/- 192 nmol/L), retinol may have been removed as a form of holo retinol-binding protein. Decreases in retinol and retinol-binding protein levels were also observed in low-density lipoprotein (LDL) apheresis with a dextran sulfate column (i.e., a cation-exchange resin column). In the patient with Crigler-Najjar syndrome, retinol taken dietarily was removed by plasmapheresis. However, the patient manifested no clinical symptoms associated with vitamin A deficiency, since his liver storage of retinol could supply the loss caused by plasmapheresis treatment. We should measure plasma retinol concentrations to evaluate the loss of retinol during plasmapheresis treatment coupled with an anion-exchange resin column.


Subject(s)
Anion Exchange Resins , Bilirubin/blood , Crigler-Najjar Syndrome/blood , Crigler-Najjar Syndrome/therapy , Plasmapheresis , Vitamin A/blood , Adolescent , Adsorption , Diterpenes , Humans , Liver/metabolism , Male , Retinol-Binding Proteins/metabolism , Retinol-Binding Proteins, Cellular , Retinol-Binding Proteins, Plasma , Retinyl Esters , Serum Albumin/metabolism , Vitamin A/analogs & derivatives , Vitamin A/metabolism
10.
Eur J Clin Invest ; 24(7): 468-75, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7957504

ABSTRACT

While serum concentrations of triglyceride (TG) and apolipoprotein (apo) E decreased significantly after 75 g glucose load, serum triglyceride concentration increased markedly and apoB concentration decreased significantly after 100 g fat load in 10 healthy men. Chylomicrons and very low density lipoproteins (VLDL) increased after the fat load but decreased after the glucose load. ApoB-100/B-48 ratio in VLDL fraction decreased slightly at 30 min and increased markedly at 60 min after the glucose load. On the other hand, the ratio decreased definitely at 30 min and then increased until 90 min after the fat load. Isoelectric focusing (IEF) and two-dimensional gel electrophoresis revealed that the relative concentration of sialilated apoE in VLDL fraction decreased after the glucose load and increased after the fat load. In hypertriglyceridaemic patients, apoE3S1/E3 ratio in VLDL fraction was significantly higher than that in normal and hypercholesterolaemic patients. The results suggest that some structural changes in apoE, due probably to sialilation, may exert an influence on the hepatic uptake of the lipoproteins.


Subject(s)
Apolipoproteins B/blood , Apolipoproteins E/blood , Fats/administration & dosage , Glucose/administration & dosage , Lipoproteins, VLDL/chemistry , Triglycerides/blood , Administration, Oral , Adult , Female , Humans , Hypercholesterolemia/blood , Hypertriglyceridemia/blood , Lipoproteins, VLDL/blood , Male , Middle Aged , Sialoglycoproteins/blood , Time Factors
12.
Article in English | MEDLINE | ID: mdl-1751669

ABSTRACT

LDL-apheresis is introduced in many cases all over Japan. Among them, evaluation of long-term effect on ischemic heart disease (IHD) has made on 10 cases with homozygous familial hypercholesterolemia (FH) and 49 cases with heterozygous FH. As to homozygous FH, 3 patients had angina pectoris. Mean duration of treatment was 26 months (52 treatments). The changes in total cholesterol (TC) in each treatment was from 426 mg/dl to 151 mg/dl. Improvement in IHD was observed in 5 out of 10 cases. As to heterozygous FH, 17 cases had history of myocardial infarction and 12 had angina pectoris. Mean duration of treatment was 13 months (19 treatments). Mean TC was decreased from 271 mg/dl to 126 mg/dl by each treatment. Regression in Achilles tendon thickenting or skin and palpebral xanthomas was observed. Frequency of anginal attacks decreased in 8 out of 17 cases. Ischemic change in ECG were improved in 3 out of 26 cases. Coronary angiography performed with 2 to 3 years of interval in some cases revealed regression or no progression in coronary stenosis. As a whole, IHD improved in 15 cases and exacerbated in 2 cases. Main side effect was hypotension attack. Bradycardia and anginal attack during treatment were observed in some cases. LDL-apheresis was judged as effective in 25 out of 44 patients with IHD or xanthoma.


Subject(s)
Blood Component Removal , Cholesterol, LDL/isolation & purification , Hyperlipoproteinemia Type II/therapy , Blood Component Removal/adverse effects , Cholesterol/blood , Coronary Disease/blood , Coronary Disease/therapy , Heterozygote , Homozygote , Humans , Hyperlipoproteinemia Type II/genetics , Japan/epidemiology , Lipids/blood , Time Factors , Xanthomatosis/therapy
13.
Blood Purif ; 9(2): 85-91, 1991.
Article in English | MEDLINE | ID: mdl-1760146

ABSTRACT

For assessment of the usefulness of a dextran sulfate cellulose (DSC) column in the conduct of plasmapheresis (DSC lipoprotein adsorption, DSC-LA) for patients with hypertriglyceridemia on hemodialysis, a study was conducted to determine whether the adsorption of lipoproteins on a column varies in response to a variation in the lipoprotein composition. A patient with type V hyperlipoproteinemia on hemodialysis, a patient with type IIa homozygous, and a patient with type IIa heterozygous familial hypercholesterolemia were used in this study. In all patients, apolipoprotein B- and E-containing lipoproteins were removed preferentially by a DSC column. Following DSC-LA, abdominal pain before DSC-LA in a patient with type V hyperlipoproteinemia subsided, and regression of tuberous and tendinous xanthomas was induced in familial hypercholesterolemia. In cases of hyperlipoproteinemia, this column thus appears to exert a therapeutic effect regardless of the type of disease.


Subject(s)
Chromatography, Liquid , Dextran Sulfate , Hyperlipoproteinemia Type II/therapy , Hypertriglyceridemia/therapy , Plasmapheresis/methods , Achilles Tendon , Adsorption , Adult , Female , Humans , Hyperlipoproteinemia Type II/blood , Hypertriglyceridemia/blood , Lipoproteins/pharmacokinetics , Male , Middle Aged , Muscular Diseases/therapy , Xanthomatosis/therapy
15.
Curr Med Res Opin ; 12(2): 100-7, 1990.
Article in English | MEDLINE | ID: mdl-2118022

ABSTRACT

Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, suppresses new synthesis of cholesterol via HMG-CoA in hepatocytes. As a result, low density lipoprotein (LDL) receptor activity in the liver is enhanced, which leads to lowering of plasma cholesterol. Inhibitors are shown to be effective in heterozygous familial hypercholesterolaemia (FH). Although FH heterozygotes are defined genetically as possessing half the normal LDL receptor activity, some heterogeneity of LDL receptor activity is observed in these patients. To see whether the effect of an inhibitor is related to LDL receptor activity in each patient, pravastatin was administered to 7 FH heterozygotes for 3 months at a daily dose of 10 mg; their mean LDL receptor activities measured before the therapy were 45.0 +/- 9.9% of the normal control. After medication, mean serum total cholesterol decreased from 349.0 to 279.7 mg/dl (p less than 0.05), and LDL-cholesterol decreased from 272.6 to 207.7 mg/dl (p less than 0.05). A significant correlation between the initial LDL receptor activity and the effect of pravastatin was not proved. However, the pre-treatment level of LDL-cholesterol was positively correlated (r = 0.795) with the absolute decrement of LDL-cholesterol after 3 months (p less than 0.05). This implies that the more LDL-cholesterol was elevated, the more pravastatin was effective.


Subject(s)
Anticholesteremic Agents , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipoproteinemia Type II/drug therapy , Naphthalenes/therapeutic use , Receptors, LDL/drug effects , Adult , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Heterozygote , Humans , Hyperlipoproteinemia Type II/genetics , Male , Middle Aged , Pravastatin , Receptors, LDL/genetics , Triglycerides/blood
17.
Artif Organs ; 13(3): 190-6, 1989 Jun.
Article in English | MEDLINE | ID: mdl-2764758

ABSTRACT

Two diabetic patients with marked intractable hypertriglyceridemia under treatment with hemodialysis for chronic renal failure were treated by either an apolipoprotein B-dependent removal of lipoproteins using dextran sulfate cellulose column plasmapheresis or a size-dependent removal of lipoproteins using hollow-fiber filtration plasmapheresis. In one patient, a column packed with hollow fibers was used as a plasma separator and a dextran sulfate cellulose column as an adsorbent. In another patient, because the hollow-fiber column did not separate plasma from whole blood, a centrifuge-type blood cell separator was used for the plasma separation. The amounts of plasma cholesterol, triglycerides, and phospholipids removed by plasmapheresis were 30%, 33%, and 30%, respectively, when the combination of a hollow-fiber column and a dextran sulfate cellulose column was used. Corresponding values were 31%, 29%, and 27%, respectively, when the combination of the centrifuge-type blood cell separator and the hollow-fiber column was used. The efficiency of lipid removal was almost the same with both techniques. As for plasma separation, the centrifuge-type blood cell separator was more efficient than the hollow-fiber column. Some losses of albumin and platelets were observed when combination plasmapheresis using the centrifuge-type blood cell separator and the hollow-fiber column was performed. In conclusion, we prefer the centrifuge-type blood cell separator to the hollow-fiber column for plasma separation of marked hypertriglyceridemia. The second filter must be chosen for each patient according to the size of the lipoproteins.


Subject(s)
Diabetic Nephropathies/complications , Hypertriglyceridemia/therapy , Lipoproteins/blood , Plasmapheresis , Triglycerides/blood , Adult , Apolipoproteins/blood , Cholesterol/blood , Female , Humans , Kidney Failure, Chronic/therapy , Middle Aged , Phospholipids/blood , Plasmapheresis/methods , Renal Dialysis
19.
Clin Chem ; 34(11): 2224-7, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3141083

ABSTRACT

The correlation between low-density lipoprotein (LDL) receptor activity and concentrations of lipids and apolipoproteins in serum was examined in 12 subjects with heterozygous familial hypercholesterolemia (FH) and in four with non-FH type II hyperlipoproteinemia. Concentrations of high-density lipoprotein cholesterol and of apolipoproteins (apo) A-I, C-II, and C-III were significantly positively correlated with LDL receptor activity, whereas LDL receptor activity was significantly inversely correlated with LDL cholesterol and apo B concentrations, and with apo ratios B/A-I and B/A-II. Neither total serum cholesterol, triglyceride, phospholipid, apo A-I, nor apo E concentrations correlated significantly with LDL receptor activity. Multiple regression analysis, with LDL receptor activity as the dependent variable, revealed concentrations of apo B and apo C-II to be the principal determinant factors. To confirm this, we subsequently calculated the LDL receptor activities before and after administration of CS-514, an inhibitor of hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88), which increases the hepatic LDL receptor activity and decreases the concentration of cholesterol in serum. This drug increased calculated LDL receptor activities significantly, with a significant decrease in serum cholesterol.


Subject(s)
Apolipoproteins B/blood , Apolipoproteins C/blood , Receptors, LDL/blood , Apolipoprotein C-II , Apolipoproteins/blood , Cholesterol/blood , Female , Heptanoic Acids/pharmacology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipoproteinemia Type II/blood , Lipids/blood , Male , Middle Aged , Naphthalenes/pharmacology , Pravastatin
20.
Atherosclerosis ; 72(2-3): 205-11, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3145746

ABSTRACT

The hypolipidemic effect of a new HMG-CoA reductase inhibitor, pravastatin, was examined. The reductions of serum cholesterol and LDL-cholesterol were dose-dependent and significant differences were observed between placebo and 10 or 20 mg groups (P less than 0.01), and 10 and 20 mg (P less than 0.05) groups. The reduction rate of cholesterol after 8 weeks during medication was 16.1% in the 10 mg group, 20.5% in the 20 mg group compared to baseline serum cholesterol levels. LDL-cholesterol decreased by 23.9% in the 10 mg group, and 29.8% compared to baseline LDL-cholesterol in the 20 mg group. The lowering of total cholesterol was entirely attributed to a reduction in LDL-cholesterol.


Subject(s)
Anticholesteremic Agents/therapeutic use , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypercholesterolemia/drug therapy , Naphthalenes/therapeutic use , Adult , Aged , Apolipoproteins/blood , Cholesterol/blood , Cholesterol, LDL/blood , Clinical Trials as Topic , Dose-Response Relationship, Drug , Double-Blind Method , Heptanoic Acids/adverse effects , Humans , Hypercholesterolemia/blood , Middle Aged , Naphthalenes/adverse effects , Pravastatin , Time Factors
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