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PubMed1995

Coronary artery bypass grafting in familial hypercholesterolemia.

Familial hypercholesterolemia is an autosomal dominant disorder caused by a mutation of the gene for the low-density lipoprotein receptor and is characterized by rapidly progressing coronary atherosclerosis. We assessed the long-term results of coronary artery bypass grafting performed during the past 13 years in 62 patients with heterozygous familial hypercholesterolemia, whose mean plasma total and low-density lipoprotein cholesterol level was 327 mg/dl, respectively. The patients had severe coronary atherosclerosis, with coronary stenosis index of 19.7, and the prevalence of extracoronary atherosclerotic lesions was 27%. Sixty-one patients underwent successful coronary artery bypass operation, with an average of 2.5 grafts, and the coronary stenosis index decreased to 7.1. After operation, all patients consumed a cholesterol-lowering diet and received drug therapy with pravastatin, probucol, or cholestyramine. Seven patients who were resistant to drug therapy were treated with plasma low-density lipoprotein apheresis. The cholesterol-lowering therapy reduced plasma total cholesterol level by 37%, low-density lipoprotein cholesterol level by 42%, and low-density lipoprotein/high-density lipoprotein cholesterol ratio by 37% (p < 0.001). During the follow-up period (mean, 52 months; range, 10 to 157 months), there was no cardiac death, but three patients died of malignant disease. The actuarial survival rate was 95% at 5 years and 89% at 12 years after operation. The actuarial freedom from recurrent angina was 90% at 5 years and 53% at 11 years after operation. Four patients underwent reoperation, an average of 8 years postoperatively, because of vein graft atherosclerosis. In spite of severe coronary atherosclerosis, these patients with familial hypercholesterolemia showed good long-term outcome after coronary artery bypass operation. The present findings suggest that aggressive use of arterial grafts, intensive cholesterol-lowering drug therapy, and low-density lipoprotein apheresis may be useful in patients with familial hypercholesterolemia.

Actuarial Analysis↗

PubMed1993

Chronic diarrhea in diabetes mellitus: mechanisms and an approach to diagnosis and treatment.

In this study, our aim was to develop a practical strategy to facilitate the management of patients with diabetes mellitus and chronic diarrhea in a tertiary referral practice. We reviewed the pertinent English-language literature of the past 30 years that described the pathophysiologic mechanisms and treatment of patients with diabetic diarrhea and retrospectively reviewed the medical records of all patients with diabetic diarrhea examined at the Mayo Clinic during 1990. Three typical case studies are described to illustrate the diverse mechanisms that lead to chronic diarrhea in patients with diabetes. No report in the literature has systematically evaluated all the putative mechanisms of chronic diarrhea in any group of patients with diabetes. In our tertiary referral practice, diabetic diarrhea was frequently due to celiac sprue, bacterial overgrowth in the small bowel, or fecal incontinence in conjunction with anorectal dysfunction; however, in almost 50% of the patients, these causes were excluded, and abnormal intestinal motility or secretion was postulated to be one of the likely causes of the diarrhea. These data suggest a practical algorithm based on three sequential assessments: first, tests of blood and stool specimens and flexible sigmoidoscopy to detect evidence of malabsorption or disease in the distal colon; second, small bowel aspirate and biopsy if the results of initial blood or stool tests are abnormal or anorectal function tests if those test results are normal; and, finally, measurement of gastrointestinal transit or therapeutic trials with opioids, clonidine hydrochloride, and, rarely, cholestyramine resin or octreotide acetate (or both methods). The mechanisms whereby abnormal neural function due to diabetes results in altered digestive, secretory, absorptive, or motor function necessitate further elucidation. The management of chronic diarrhea in patients in a tertiary referral practice, however, can be based on a practical algorithm to determine the cause and to adopt specific treatment to correct it.

Animals↗

PubMed1990

Primary sclerosing cholangitis.

Primary sclerosing cholangitis is a rare disease of unknown etiology. Sclerosis of the bile ducts may actually be the final result of multiple factors such as autoimmune, bacterial, congenital, drug, or viral injury. The most commonly associated diseases are ulcerative colitis and chronic pancreatitis. Except in the earliest stages of the disease, liver histologic findings are not specific. Most patients present with jaundice, pain, and pruritus, although an increasing number of asymptomatic patients with inflammatory bowel disease and abnormal liver function are being identified. Cholangiography is key to the diagnosis and is usually pathognomonic except in the unusual case where primary sclerosing cholangitis is confused with cholangiocarcinoma. Many forms of medical therapy have been tried, including antibiotics, azathioprine, cholestyramine, colchicine, cyclosporine, D-penicillamine, steroids, and ursodeoxycholic acid. To date, none of these medications has been proved to alter the course of this disease. Recent reports of ursodeoxycholic acid trials have been encouraging, but long-term results of ongoing randomized trials have yet to be published. In recent years, balloon dilatation of biliary strictures has been accomplished via endoscopic and percutaneous transhepatic approaches. However, in patients with primary sclerosing cholangitis, these nonoperative manipulations must be done repeatedly, may entail multiple general anesthetics, and are difficult to perform. We believe that a direct surgical approach to the biliary tree with long-term transhepatic stenting is indicated in selected patients with severe hilar or extrahepatic stricturing, persistent jaundice or recurrent cholangitis, and no evidence of cirrhosis. Hepatic transplantation should be reserved for patients with primary sclerosing cholangitis who have well-established cirrhosis and have not responded to other therapeutic measures.

Cholangitis, Sclerosing↗

PubMed1980

Treatment of pruritus of cholestasis by plasma perfusion through USP-charcoal-coated glass beads.

The accumulation of bile acids has been implicated in the pathogenesis of pruritus of cholestasis. To study the effect of bile-acid depletion on pruritus, 8 patients with chronic cholestasis and intractable pruritus which had not responded to cholestyramine and/or phenobarbitone underwent plasma perfusion through USP-charcoal-coated glass beads. DSuring twenty-two perfusions, between 957 and 6100 ml of plasma were perfused through charcoal columns, resulting in the removal of 126-795 mumol of bile acids. The mean extraction of the perfused bile acids was 81%. After the perfusions, all patients had prompt relief of their pruritus, lasting from 24 h to 5 months. Although the clinical effect may be due to the removal of unidentified pruritogens other than bile acids, charcoal plasma perfusion may improve the quality of life of incapacitated patients with servere intractable pruritus of cholestasis.

Adult↗

PubMed1983

Treatment of hyperlipidaemia retards progression of symptomatic femoral atherosclerosis. A randomised controlled trial.

The effect of plasma lipid reduction on the progression of femoral atherosclerosis was studied in hyperlipidaemic patients with stable intermittent claudication. 24 patients were randomly assigned to treatment and usual-care groups, the former receiving dietary advice and cholestyramine, nicotinic acid, or clofibrate depending on their lipoprotein phenotype. Biplanar arteriography was performed when the study began and after a mean period of 19 months. Angiograms were assessed visually, with blinding, and by computerised image analysis. Therapy reduced mean plasma total cholesterol by 25%, mean low density lipoprotein (LDL) cholesterol by 28%, and mean plasma triglycerides by 45%. Significantly fewer arterial segments showed detectable progression of atherosclerosis in the treatment group. The mean increase in plaque area (mm2/segment/year) in the treatment group was only one third of that in the usual-care group. The mean increase in edge irregularity index (a measure of the severity of disease) in the treatment group was only 40% of that in the usual care group. Twice as many arterial segments showed improvement in the treatment group. In both groups changes in edge irregularity index were directly related to plasma LDL cholesterol concentration. This study, the first randomised controlled trial of its type, provides evidence that effective treatment of hyperlipidaemia favourably influences the natural history of symptomatic peripheral atherosclerosis.

Angiography↗

PubMed1987

Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis?

The effects of ursodeoxycholic acid (UDCA, 13-15 mg/kg body weight daily) were prospectively evaluated in fifteen patients with primary biliary cirrhosis (PBC). The mean concentration of UDCA in serum expressed as the percentage of total bile acids rose from 0% at baseline to 58% (SEM 9%) after 2 years' treatment, whereas total serum bile acid levels did not change significantly. The proportion of patients with pruritus necessitating the use of cholestyramine was significantly lower at 2 years than at baseline. Standard liver function tests improved in all the patients. At 2 years the average activities of gamma-glutamyltranspeptidase, alkaline phosphatases, and alanine aminotransferase and bilirubin levels were reduced (respectively 78%, 65%, 68%, and 36% of pretreatment values). In three patients who agreed to interrupt the ingestion of UDCA for 3 months after 2 years' treatment there was clear deterioration in liver function tests, which again improved after reinstitution of UDCA. These results suggest that long-term UDCA might be a safe and effective treatment for PBC, but a randomised, controlled, double-blind trial is urgently needed.

Adult↗

PubMed1999

A population-based treat-to-target pharmacoeconomic analysis of HMG-CoA reductase inhibitors in hypercholesterolemia.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have become the drugs of choice for the treatment of patients with hypercholesterolemia. However, one of the major concerns with these drugs is cost. In an attempt to develop a cost-effective treatment strategy for patients referred to our lipid clinic, we conducted a meta-analysis to estimate the lipid-lowering efficacy of the various HMG-CoA reductase inhibitors alone or in combination with niacin or cholestyramine. Based on cholesterol-lowering efficacy estimates derived from a literature-based meta-analysis, we performed a population-based treat-to-target analysis. Fifty-six trials with 101 monotherapy cohorts and 20 trials with 31 combination-therapy cohorts (573 patients) were included in the meta-analysis. Based on reduction in low-density lipoprotein cholesterol (LDL-C), the most effective monotherapy was atorvastatin and the least effective monotherapy was fluvastatin. Combination therapy was more effective in reducing LDL-C than monotherapy with the respective HMG-CoA reductase inhibitor. However, on the basis of dollars spent per percentage of LDL-C reduction, combination therapy was frequently less cost-effective than monotherapy. In addition, combination therapy was associated with a higher rate of noncompliance and a greater risk of drug-drug interactions. As a result, we based our treat-to-target analysis on the use of monotherapy as first-line treatment, with combination therapy reserved for patients failing to achieve the target LDL-C levels of the US National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP-II) with monotherapy. In the population-based treat-to-target analysis, atorvastatin was the most cost-effective drug for high-risk patients (those with coronary heart disease [CHD]), whereas fluvastatin was the most cost-effective agent for low-risk patients (<2 risk factors for CHD) and moderate-risk patients (> or =2 risk factors for CHD). If 1 drug is chosen to treat all patients (i.e., in cases of formulary restriction), atorvastatin would be the most cost-effective agent. In adapting the findings on cholesterol-lowering efficacy from this analysis to our lipid clinic, we concluded that the most cost-effective treatment approach is to individualize the selection of an HMG-CoA reductase inhibitor based on both coronary risk and the LDL-C reduction required to achieve NCEP ATP-II goals. Based on our results, 2 agents--atorvastatin and fluvastatin--should be available on the formulary.

Cholesterol↗

PubMed2001

Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease.

BACKGROUND: Previous health economic studies have demonstrated the cost-effectiveness of simvastatin in the treatment of coronary heart disease (CHD) based on clinical results of the Scandinavian Simvastatin Survival Study. A prior analysis evaluated the "cost of getting to goal," but ignored all costs after titration. However, when evaluating the cost-effectiveness of long-term therapies, it is important to consider the maintenance costs as well. OBJECTIVE: The purpose of this study was to evaluate the maintenance costs of treatment with simvastatin versus that of treatment with another more recently available statin, atorvastatin, in a European context. METHODS: We assessed the long-term maintenance cost of simvastatin versus atorvastatin in terms of the cost of reducing low-density lipoprotein cholesterol (LDL-C) levels to the recommended goals based on a previously published clinical trial in patients with CHD. The analysis focused on the patients in the original clinical trial who were randomized to treatment with simvastatin or atorvastatin. Patients began therapy with 10 mg of simvastatin or atorvastatin; the dose of study drug was titrated every 12 weeks up to 40 mg simvastatin or 80 mg atorvastatin, with the addition of up to 8 g/d of cholestyramine until a modified European Atherosclerosis Society LDL-C goal (<2.84 mmol/L) was reached. As there was no significant difference between the 2 groups in resource utilization for adverse events, only drug costs were included. The calculated average annual maintenance cost was based on the distribution of the final daily dosing regimens and the public drug prices for each regimen. Individual country analyses were conducted using each local currency. RESULTS: There was no significant difference between groups in the percentage of patients reaching their LDL-C goal over the study period (80% for simvastatin-treated pa- tients vs 89% for atorvastatin-treated patients, P = 0.135). However, the cost of maintaining a similar percentage of patients at their appropriate LDL-C levels was significantly lower in the simvastatin group compared with the atorvastatin group in 13 of the 17 countries assessed. In the remaining 4 countries, there was a cost advantage for simvastatin, but it did not reach statistical significance. CONCLUSIONS: Across Europe there was a significant reduction in the cost of maintaining patients at their appropriate LDL-C levels with simvastatin versus atorvastatin. The results of this analysis, along with the proven clinical benefits of simvastatin, support the use of this drug as the treatment of choice in the secondary prevention of CHD.

Anticholesteremic Agents↗

PubMed1998

Cloning and sequencing of a novel murine liver carboxylesterase cDNA.

Carboxylesterases (EC 3.1.1.1) comprise a group of serine hydrolases with at least 20 genetically distinct loci in mice. Here, we describe differential display PCR-based cloning of a cDNA, encoding a novel murine carboxylesterase termed ES-x, which was expressed predominantly in liver but also in kidney and lung. The cDNA of ES-x spanned a 2249-bp sequence with an open reading frame encoding 565 amino acids, including an N-terminal hydrophobic signal peptide which directs the synthesis into microsomal lumen and a C-terminal HVEL consensus sequence for retaining the protein in the lumen of the endoplasmic reticulum. The predicted amino acid sequence of ES-x exhibited 75% identity with rat liver pI 6.1 esterase. We further demonstrate that feeding mice with diets containing cholestyramine or sodium cholate increases mRNA-expression of ES-x in liver 2.5- to 3-fold.

Amino Acid Sequence↗

PubMed1998

Microparticle resins as a potential nasal drug delivery system for insulin.

The application of various resins for the nasal delivery of insulin was examined in rabbits. Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase. The blood glucose level decreased from 118.8 +/- 18.5 mg/dl to 65.8 +/- 13.8 mg/dl at 45 min after administration. These results were superior to those obtained with the unfractionated resin. Styrene-divinylbenzene copolymer (a nonionic resin; 20-45 microns fraction) showed similar enhancement of nasal insulin absorption. In contrast, polyacrylester (a nonionic resin; 20-45 microns fraction) and cholestyramine (a cationic resin) did not promote insulin absorption. These results suggest that some resins may be useful for nasal delivery of insulin.

Administration, Intranasal↗

PubMed2003

Prolonged cholestasis and ductopenia associated with tenoxicam.

Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

Adult↗

PubMed1993

Ursodeoxycholic acid for symptomatic primary biliary cirrhosis. Preliminary analysis of a double-blind multicenter trial. Italian Multicenter Group for the Study of UDCA in PBC.

The administration of ursodeoxycholic acid, a hydrophilic bile acid not hepatotoxic to humans, has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage. Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease. In January 1988, to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease, we started a multicenter, double-blind, placebo-controlled trial in patients with symptomatic disease, that is, with pruritus or serum bilirubin exceeding 2 mg/dl. Forty-four patients were assigned to ursodeoxycholic acid, 500 mg daily (corresponding to about 8.7 mg/kg body weight in these patients), and 44 to a placebo. As planned at the beginning of the study, a preliminary analysis was performed when all patients had been followed for at least 6 months (33 patients up to 12 months). Pruritus, self-evaluated by the patients, and cholestyramine consumption, as recorded in a diary, decreased significantly (p < 0.01) in both groups. In patients who initially had abnormal levels, serum bilirubin decreased significantly (p < 0.05) in the ursodeoxycholic acid group compared to placebo. After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group: a composite weighted biochemical index taking into account the changes in serum bilirubin, alkaline phosphatase, gamma-GT and AST (p < 0.001); serum prealbumin (p < 0.05); IgG (p < 0.01) and IgM (p < 0.01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗

PubMed1996

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia.

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35-75 years of age with low-density lipoprotein (LDL) cholesterol of 115-190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30-75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.

Adult↗

PubMed1986

Usefulness of gas chromatographic profiles of plasma total lipids in diagnosis of phytosterolemia.

A Cambodian male (aged 5 years and 9 months) presented with subcutaneous and tendon xanthomas in association with hypercholesterolemia. He was erroneously diagnosed as having familial hypercholesterolemia and treated with a low cholesterol diet (+/- cholestyramine) to which he did not respond. A determination of plasma total lipid profile by high-temperature gas chromatography revealed elevated plasma levels of free and esterified plant sterols along with the hypercholesterolemia. Introduction and maintenance of a diet low in cholesterol and plant sterols resulted in significant reduction in the blood concentration of these sterols, which returned to pretreatment level upon discontinuation of the low sterol regimen. The rapid identification and quantitation of the plant sterols by high-temperature gas chromatography provides a sensitive means of distinguishing phytosterolemia, which might be more common than previously suspected, from other forms of dyslipidemia, and for following the course of any treatment.

Adult↗

PubMed1997

Disturbances in dietary fat metabolism and their role in the development of atherosclerosis.

It was suggested that postprandial lipoproteins (PPLp) may play an important role in atherogenesis. To examine this hypothesis, we studied PPLp metabolism in normolipidemic individuals and hyperlipoproteinemic (HLP) patients on various diets, physical activity programs and hypolipidemic drugs as well as in patients with coronary artery disease (CAD). We used the vitamin A-fat loading test, which labels intestinally derived lipoproteins with retinyl palmitate. Type IV HLP patients demonstrated a severe defect in chylomicron clearance. Type III HLP patients showed severely disordered clearance of chylomicron remnants. Compared to the saturated fatty acid enriched diet, the omega 6 polyunsaturated acid enriched diet reduced chylomicrons and their remnant levels by 56% and 38%, respectively. The diet enriched in omega 3 polyunsaturated acid decreased chylomicrons and their remnant levels by 67% and 53%, respectively. Physical conditioning reduced chylomicron levels by 37%. Gemfibrozil decreased chylomicron levels in type IV HLP patients. Cholestyramine increased chylomicron levels by 88%. Bezafibrate reduced chylomicrons and their remnants levels and increased fasting HDL-C in patients with isolated low HDL-C levels. Continuous prolonged intravenous heparin administration inhibited chylomicron clearance. Normolipidemic patients with CAD had significantly higher plasma levels of chylomicron remnants than matched controls with normal coronary arteries. The studies reported here demonstrate that both chylomicrons and their remnants are present in the plasma of normolipidemic people and more so for hyper- or dyslipidemic patients for a prolonged period of time after fat ingestion. The duration and magnitude of this postprandial lipemia can be regulated or altered by such interventions as diet, physical activity, and drugs. Our case control studies strongly support the hypothesis that PPLp may play a crucial part in atherogenesis, and therefore justify measuring their levels in high risk patients. We believe that in selected patient groups the use of one or more of the interventions mentioned here is warranted.

Arteriosclerosis↗

PubMed2001

Understanding pruritus in systemic disease.

Many pruritic conditions do not originate in the skin, but are the result of systemic abnormality. Among the diseases that can cause pruritus are renal insufficiency, cholestasis, Hodgkin's lymphoma, polycythemia vera, solid tumors, and many others. Other pruritic conditions appear to be iatrogenic; opioid-induced pruritus may be the most important in palliative medicine. Successful treatment of the underlying condition usually relieves itch. But, with time, many diseases progress and treatment of the cause will be impossible. Topical treatments may be of limited value. Strategies involving systemic treatments include use of antidepressants, oral opioid antagonists, or cholestyramine. There is no one cure for all pruritic symptoms. Better understanding of mechanisms of pruritus may help develop better treatments.

Humans↗

PubMed1998

Mortality rates in treated hypertensive men with additional risk factors are high but can be reduced: a randomized intervention study.

The aim was to examine the feasibility and efficacy of a multifactorial risk factor intervention program in hypertensive patients at high cardiovascular risk. Treated hypertensive men, aged 50 to 72 years, with at least one of the following: serum cholesterol concentration > or = 6.5 mmol/L, diabetes mellitus, or smoking were randomized to multifactorial risk factor intervention (n = 253) or usual care (n = 255). The specific intervention was based on group meetings to encourage a lipid lowering diet and smoking cessation. Cholestyramine, nicotinic acid, fibrates, and later statins were used either as single drug therapy or in combination, following agreed guidelines in patients in whom the nonpharmacological intervention was judged to be insufficient. Usual care was given according to clinical practice. The median follow-up time was 6.6 years. Sixty-four patients (25.1%) died in the usual care group, compared with 41 patients (16.2%) in the intervention group (P = .016; 95% confidence interval, relative risk 0.42 to 0.92). The overall risk for fatal and nonfatal cardiovascular events was 29% lower in the intervention group than in the usual care group (P = .041). Relative to usual care, the intervention program lowered mean in-trial serum concentrations of total cholesterol (6.3%, P < .0001), LDL cholesterol (9.1%, P < .0001), and blood glucose (0.2 mmol/L, P < .05). Among smokers, at entry, cotinine-adjusted quit rates were 28% in the intervention group and 11% in the usual care group (P = .012) after 3 years. This study illustrates the very high cardiovascular risk in hypertensive patients 50 to 72 years of age with additional risk factors. The results indicate, however, that the gloomy prognosis may be improved by a dedicated risk factor intervention program.

Aged↗

PubMed1998

Effect of ion exchange resins on the drug release from matrix tablets.

Ion exchange resins were incorporated into hydroxypropylmethylcellulose (HPMC) matrix tablets to modify the release of oppositely charged drugs. The drug release from HPMC tablets containing drug-resin complexes was significantly slower than from HPMC tablets containing drug without resin. A physical mixture of drug and ion exchange resin (cationic drug, propranolol HCl, with the cation exchange resin, Amberlite IRP 69, or the anionic drug, sodium diclofenac, with the anion exchange resin, cholestyramine (Duolite ATP-143)) resulted in almost the same drug release as tablets containing preformed drug-resin complexes. Upon contact with the dissolution medium, a gel layer formed rapidly around the solid tablet core and the complex between the drug and the resin formed in situ within the gelled regions. No effect of pH of the dissolution medium (0.1 N HCl or pH 7.4 phosphate buffer) or resin counterion was observed with the strong cation exchanger, Amberlite IRP 69. The resin was dissociated at both pH-values, allowing drug binding. With the weak cation exchange resin, Amberlite IRP 88, in situ complex formation and retardation was only observed in pH 7.4 buffer but not in 0.1 N HCl because of the non-ionization of the carboxyl groups. The drug release depended also on the amount and particle size of the resin particles and the type of carrier. The use of smaller resin particles eliminated the burst release seen with larger resin particles. Upon comparing different carrier materials, a rapid formation of the gel layer was important for the in situ complex formation. The drug release was in the order of Gelucire 54/02 (glyceryl palmitostearate) > polyethylene oxide 400K > HPMC K15M.

Adrenergic beta-Antagonists↗