C. Wayne Weart

The Triglyceride Connection in Atherosclerosis

OBJECTIVE: To examine the proposed mechanism of triglyceride-induced atherogenesis, to address the controversy surrounding serum triglycerides as a coronary heart disease (CHD) risk factor, and to recommend an appropriate therapeutic approach to hypertriglyceridemia. DATA SOURCES: Studies, review articles, and editorials published since 1976. A MEDLINE search of English-language literature was conducted using the terms triglyceride and hypertriglyceridemia. STUDY SELECTION: Studies, review articles, and editorials were selected for detailed review if they addressed the pathogenesis of triglyceride-induced atherosclerosis, the controversy associated with elevated serum triglyceride as a CHD risk factor, and hypertriglyceridemia treatment options. DATA EXTRACTION: Data were reviewed that described the atherogenicity of chylomicron and very low-density lipoprotein (VLDL) remnants, the inverse relationship that exists between high-density lipoprotein (HDL) and serum triglyceride, the hypertriglyceridemia treatment controversy, and the treatment options of diet, exercise, weight control, alcohol restriction, and medication. DATA SYNTHESIS: Hypertriglyceridemia is a well-known risk factor for pancreatitis. However, its role in atherogenesis is less well defined. Several proposed connections appear to exist between hypertriglyceridemia and atherosclerosis, including the inverse correlation between triglycerides and HDL, the presumed atherogenicity of triglyceride-rich lipoprotein remnant particles, the potential resultant increase in the serum concentration and atherogenicity of low-density lipoprotein (LDL), and the proposed interaction between serum triglyceride and the fibrinolytic/coagulation system. Clinical trials addressing this issue offer mixed results that are subject to interpretation. Diet, exercise, weight control, alcohol restriction, and certain lipid-lowering medications are effective at reducing serum triglyceride. CONCLUSIONS: Hypertriglyceridemia is a theoretical risk factor for CHD because of the increased production of atherogenic chylomicron and VLDL remnants, the inverse relationship present between serum triglyceride and HDL, the possible resultant increase in LDL attributable to remnant-reduced hepatic LDL-receptors as well as the formation of more dense and, therefore, more atherogenic LDL, and to the interaction between serum triglyceride and the fibrinolytic/coagulation system. However, most clinical trials that have found hypertriglyceridemia to be a risk factor for CHD do not include other CHD risk factors in their analyses. Therapeutic intervention to lower serum triglyceride with diet, exercise, and/or drugs is definitely recommended in the treatment and/or prevention of pancreatitis; however, the role of triglyceride-lowering to reduce CHD risk remains controversial.

Effects of magnesium oxide on the lipid profile of healthy volunteers

Elevated serum cholesterol is a risk factor in the development of coronary artery disease. Magnesium has been reported to decrease total serum cholesterol, low density lipoprotein, and very low density lipoprotein, and increase high density lipoprotein. A randomized, double-blind, placebo-controlled, crossover study was completed to determine if supplemented magnesium, in the form of magnesium oxide, would produce changes in the lipid profile. Fifty normal volunteers received placebo or magnesium oxide, 400 mg capsules, twice a day for 60 days, then switched to the alternate treatment. Weight, height, blood pressure, serum potassium, serum magnesium, and a lipid profile were determined initially and after each treatment. Analysis of variance (ANOVA), comparing the mean of each component of the lipid profile at baseline and after each treatment, showed no significant difference. In conclusion, supplemental magnesium oxide did not produce statistically significant changes in the lipid profile in this group of healthy volunteers.

Issues Surrounding Tight Glycemic Control in People with Type 2 Diabetes Mellitus

OBJECTIVE: To review the prospective evidence surrounding the issue of tight glycemic control in people with type 2 diabetes mellitus and resultant long-term complications. DATA SOURCE: Conference proceedings and a MEDLINE search (1966–February 1998) identified pertinent English-language publications on type 2 diabetes in humans. Key search terms included insulin resistance, diabetes mellitus, non-insulin-dependent, macrovascular complications, microvascular complications, and intensive glycemic control. STUDY SELECTION: Selection of prospective epidemiologic and clinical studies were limited to those focusing on the management of type 2 diabetes. All articles with pertinent information relevant to the scope of this article were reviewed. DATA SYNTHESIS: The pathophysiology of type 1 and type 2 diabetes differ; however, both share chronic complications that significantly affect morbidity and mortality. People with type 1 diabetes have an absolute deficiency of insulin, whereas people with type 2 diabetes have varying degrees of insulin resistance and an inadequate compensatory insulin secretory response. The Diabetes Control and Complications Trial (DCCT) has clearly indicated that intense control of blood glucose in type 1 diabetes prevents and slows the progression of microvascular (i.e., retinopathy, nephropathy) and neuropathic complications. The Kumamoto study showed similar results in nonobese patients with type 2 diabetes. Intense insulin therapy in both populations has proven advantageous, thus supporting a common pathophysiologic process for the microvascular and neuropathic complications. Trends were seen toward fewer macrovascular (atherosclerotic disease) complications in the intensive insulin arm of the DCCT. Conversely, trends were seen toward an increase in macrovascular complications in the VA Cooperative study in people with type 2 diabetes using intensive insulin therapy. This may suggest a discordance in the pathophysiology of macrovascular disease between type 1 and type 2 diabetes. Additionally, it remains uncertain whether tight glycemic control prevents the onset or slows the progression of macrovascular disease. Two studies (the University Group Diabetes Program and the Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes) to date have examined pharmacotherapy options for patients with type 2 diabetes and resultant macrovascular complications. It has yet to be determined whether any therapeutic intervention will decrease the morbidity and mortality of macrovascular disease in this population. CONCLUSIONS: In type 2 diabetes, limited prospective evidence does support tight glycemic control to help prevent or slow the progression of microvascular and neuropathic complications. It is uncertain whether tight glycemic control decreases macrovascular complications and which pharmacotherapeutic agent(s) is/are the best options. However, therapy that improves glucose control in combination with aggressive risk factor management should be initiated and enforced in patients with type 2 diabetes in an effort to reduce long-term complications.

Prevention and Regression of Atherosclerosis: Effects of Hmg-CoA Reductase Inhibitors

OBJECTIVE: TO review the current literature on the effects of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors in secondary prevention and regression of atherosclerosis. DATA SOURCES A MEDLINE and journal search of recent studies evaluating the effects of lipid lowering with HMG-CoA reductase inhibitors on serum cholesterol as well as progression and regression of atherosclerotic coronary or carotid disease in patients with established atherosclerotic disease was conducted. Articles addressing the pathophysiology of atherosclerotic disease were identified by using the same sources. STUDY SELECTION: All available studies evaluating the use of HMG-CoA reductase inhibitors in the progression and regression of coronary and carotid atherosclerosis were reviewed. DATA SYNTHESIS: Lowering of total serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increasing high-density lipoprotein cholesterol can be achieved with HMG-CoA reductase inhibitors. Aggressive lipid lowering has been demonstrated to alter progression of established atherosclerotic disease and, in some patients, actually induce regression of the atheroma. An unexpected finding of several trials was the early and significant reduction in clinical cardiac events. Other mechanisms by which clinical event reduction may be explained include plaque stabilization and restoration of endothelium vasodilation. CONCLUSIONS: Aggressive lipid-lowering therapy using HMG-CoA reductase inhibitors appears to alter the natural progression and promote regression of atherosclerosis in selected patients with established coronary or carotid atherosclerosis. However, it is unlikely that regression of atherosclerosis alone is responsible for the marked reduction in clinical cardiac events seen in these trials.

Limulus lysate assay in detection of gonorrhea in women from a low-incidence population

An evaluation of the limulus amebocyte lysate assay for detection of gonococcal endotoxin in cervical secretions was undertaken in 48 women from an ambulatory population with a low incidence of gonococcal infection. When cervical secretions were diluted 1 : 2,000, positive limulus amebocyte lysate assay results were obtained in four women (100%) with culture-proved gonococcal infection, and negative results were obtained in 25 of 44 women (57%) with culture-negative specimens. The limulus amebocyte lysate assay was not sufficiently specific in a low-incidence, largely asymptomatic population to be recommended as a rapid diagnostic procedure (60 minutes) in such a group. Standardization of sampling technique, size, and reagent preparation and elimination of vaginal contamination of cervical secretions may produce a limulus amebocyte lysate test with more consistent performance characteristics in varied populations. Since the predictive value of a test varies with the prevalence of the disease in the populations tested, a test proposed for use in a population with a low likelihood of disease must be tested in such a population.

Intravenous Streptomycin Use in a Patient Infected with High-Level, Gentamicin-Resistant Streptococcus Faecalis

OBJECTIVE: To report a case of intravenous streptomycin sulfate use in a patient infected with high-level, gentamicin-resistant Streptococcus faecalis. CASE SUMMARY: A 37-year-old woman with a history of schizoaffective disorder, diabetes insipidus possibly induced by lithium, chronic renal insufficiency, and anemia presented with a two-day history of decreased responsiveness, decreased verbalization, and tremulousness. Her hospital course was complicated by polymicrobial sepsis (S. faecalis, coagulase-negative staphylococci, Citrobacter diversus, Enterobacter aerogenes, and unidentified gram-negative bacilli #2) requiring vancomycin and gentamicin therapy. Gentamicin was discontinued after two doses because she developed acute-on-chronic renal insufficiency. Subsequent susceptibility data showed the enterococcus to be highly resistant to gentamicin. The patient deteriorated clinically when treated only with vancomycin. She remained septic with a blood pressure of 80/40 mm Hg; streptomycin was added to her regimen. We were concerned that streptomycin concentrations obtained following intramuscular administration would not be adequate because of possible hypoperfusion. Based on limited published literature, streptomycin was administered intravenously via a central intravenous catheter. DISCUSSION: A review of high-level aminoglycoside-resistant S. faecalis and treatment with intravenous streptomycin therapy are discussed. The availability and monitoring of streptomycin therapy are also described. CONCLUSIONS: Streptomycin is an antimicrobial agent that must be used with vancomycin in serious infections to eradicate high-level, gentamicin-resistant S. faecalis. Its unique administration and monitoring concerns require individual patient assessment.

Update on Childhood Immunizations

OBJECTIVE: To provide an overview of childhood immunizations with emphasis in new recommendations, as well as recent vaccine developments and special populations. DATA SOURCES: English language literature identified via a MEDLINE search. Additional references were obtained from cited references. STUDY SELECTION AND DATA EXTRACTION: Original articles, reviews, and official publications were used to obtain the most accurate data on safety and efficacy of available pediatric vaccines, as well as current recommendations for their use. DATA SYNTHESIS: Immunizations have been an area of vigorous research for several years. New vaccines have been developed by improving older products to maximize immunogenicity and minimize adverse effects. Some of these novel vaccines, like the Haemophilus influenzae type b conjugate vaccines (HibCV), have already contributed significantly to the prevention of diseases in childhood. New recommendations have been issued to help speed this process. Adverse effects of routine immunizations are generally mild and transient. CONCLUSIONS: The development of new effective and safe vaccines for children is an important step in the global eradication of contagious diseases. A new generation of combination vaccines has started with the combination of the diphtheria-tetanus-pertussis vaccine and HibCV. Some other combined products are yet to come that would eventually make immunization schedules more costeffective and improve compliance rates. Our colleagues in the community and in the ambulatory care setting must actively participate in the implementation of vaccination programs and provide education to parents regarding all aspects of the immunization process.

Opportunities for Pharmacists to Aid in the Management of Acid-Peptic Disorders

There is increasing evidence that pharmacists practicing in a myriad of clinical settings, including outpatient clinics and community pharmacies, can play a key role in efforts to manage many chronic diseases. This is especially true for conditions that are prevalent, costly, and where patients frequently self-medicate using over-the-counter drugs. The acid-peptic disorders (e.g. peptic ulcer disease, gastroesophageal reflux, and reflux esophagitis) meet these criteria and present pharmacists with an ideal opportunity to improve patient outcomes, acting independently or as part of a more comprehensive disease management initiative. The opportunity exists for pharmacists to enhance the care of patients with acid-peptic disorders by identifying patients who have one of these conditions, assessing their risk for serious diagnoses (e.g. cancer) or complications (e.g. bleeding), educating patients on self management, and optimizing medical regimens through collaboration with physicians. The major barrier for integrating pharmacists into disease management programs is reimbursement; however, some patients may be willing to pay for these services, and innovative payors may begin to provide compensation to pharmacists, Pharmacists should play a key role in new disease management models designed for conditions, such as acid-peptic disorders, that meet the criteria discussed in this article.

Family Medicine Clinical Pharmacy: The South Carolina Experience

Since its inception over 25 years ago, clinical pharmacy has extended into virtually every subspecialty of medicine, including Family Medicine. Family Medicine philosophically supports a team approach to health care that has welcomed the pharmacist as an active member for over 15 years. The association between Family Medicine physicians and pharmacists has evolved into one that embodies the concept of pharmaceutical care. This article provides a historical perspective of the pioneers in Family Medicine clinical pharmacy in South Carolina, reviews the goals and visions of the early pharmacists, and reevaluates this information as it applies to clinical pharmacy today.