Effective use of statins to prevent coronary heart disease.

Primary and secondary prevention trials have shown that use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) to lower an elevated low-density lipoprotein cholesterol level can substantially reduce coronary events and death from coronary heart disease. In 1987 and 1993, the National Cholesterol Education Program promulgated guidelines for cholesterol screening and treatment. Thus far, however, primary care physicians have inadequately adopted these guidelines in clinical practice. A 1991 study found that cholesterol screening was performed in only 23 percent of patients. Consequently, many patients with elevated low-density lipoprotein levels and a high risk of primary or recurrent ischemic events remain unidentified and untreated. A study published in 1998 found that fewer than 15 percent of patients with known coronary heart disease have low-density lipoprotein levels at the recommended level of below 100 mg per dL (2.60 mmol per L). By identifying patients with elevated low-density lipoprotein levels and instituting appropriate lipid-lowering therapy, family physicians could help prevent cardiovascular events and death in many of their patients.

Pharmacokinetic interaction between ketoconazole and amprenavir after single doses in healthy men.

STUDY OBJECTIVE: To determine the effects of coadministration of amprenavir and ketoconazole on the pharmacokinetics of both drugs, and to assess the utility of the erythromycin breath test (ERMBT) to predict and explain these effects. DESIGN: Open-label, randomized, balanced, single-dose, three-period crossover study. SETTING: University research center. SUBJECTS: Twelve healthy men. INTERVENTION: Subjects received amprenavir 1200 mg, ketoconazole 400 mg, and amprenavir 1200 mg plus ketoconazole 400 mg. Each treatment was separated by 14 days. MEASUREMENTS AND MAIN RESULTS: Serial plasma samples for amprenavir and ketoconazole concentrations were measured by high-performance liquid chromatography. Coadministration of the drugs increased amprenavir area under the curve extrapolated to infinity (AUCinfinity) by 31% and reduced its maximum concentration (Cmax) by 16%. Amprenavir increased the AUCinfinity of ketoconazole by 44% and increased the drug's half-life and Cmax by 23% and 19%, respectively. Both agents resulted in substantial inhibition of ERMBT. CONCLUSION: Coadministration of ketoconazole and amprenavir results in a statistically significant increase in AUC for both agents, but the changes are not likely to be clinically important.

Pharmacotherapy of dyslipidemia in postmenopausal women: weighing the evidence.

In the United States, coronary heart disease (CHD) is the leading cause of death in women. The incidence of CHD rises dramatically in women following menopause, which can be partially attributed to a more atherogenic lipoprotein profile. For years, observational and epidemiological data have suggested that estrogen and progesterone therapy reduced CHD end points. However, the first prospective trial that evaluated hormone replacement therapy (HRT) for secondary CHD prevention demonstrated no positive cardiovascular benefit of HRT compared with placebo. In interventional studies, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors significantly reduced CHD outcomes in postmenopausal women, and these agents have emerged as the drugs of choice for primary and secondary CHD prevention. The selective estrogen receptor modulators (SERMs) may have a role in CHD prevention, but long-term clinical trials evaluating end points are needed. An evidence-based approach is necessary when deciding the appropriate pharmacotherapy of dyslipidemia in postmenopausal women.

Vitamin E and coronary artery disease.

Various studies have evaluated the antioxidant effects of vitamin E in the prevention or treatment of coronary artery disease (CAD). In vitro data suggest that vitamin E protects against oxidation of low-density lipoprotein and decreases the deposition of atherogenic oxidized low-density lipoprotein in arterial walls. Various observational and epidemiological studies also suggest a relationship between vitamin E serum concentrations or intake and CAD. One prospective, randomized trial suggested that low-dosage vitamin E supplementation (50 IU/d) decreases the risk of angina in patients without previously diagnosed CAD. Another study, using high-dosage vitamin E supplementation (400 or 800 IU/d), demonstrated a decrease in the combined end point of nonfatal myocardial infarction and cardiovascular death in patients with established CAD. Discordant data, however, have been published that imply no cardiovascular benefit of low-dosage vitamin E supplementation (50 IU/d) and detrimental effects if vitamin E is combined with beta carotene. At this point, clinicians should emphasize a low-fat diet with high intake of fruits and vegetable sources containing vitamin E. Supplemental vitamin E may be considered in patients at high risk for CAD or with documented CAD, but the potential beneficial effects should be weighed against possible long-term adverse effects. If vitamin E supplementation is initiated, the literature suggests dosages of 100 to 400 IU/d, with the higher dosage considered in patients with documented CAD. Additional investigation is warranted to further define the role of vitamin E supplementation in CAD and to critically evaluate the optimal dosage, duration of use, and method of consumption (dietary vs supplemental).

Theophylline for chronic symptomatic bradycardia in the elderly.

The treatment of choice for chronic, symptomatic bradycardia is the placement of a cardiac pacemaker. Individuals who refuse or cannot tolerate pacemaker insertion usually require pharmacologic therapy. Hydralazine, prazosin, anticholinergics, and sympathomimetic agents have been administered for this indication, but adverse effects and limited data hinder routine, long-term use. Theophylline has emerged as a reasonable alternative strategy. For the medical management of bradycardia in the elderly, the literature supports theophylline dosages between 400 and 600 mg/d (approximately 8 mg/kg/d) administered in divided doses. This dosage range should result in a steady-state serum concentration between 5 and 15 mg/L. While some investigators recommend potentially higher initial doses (up to 12 mg/kg/d), lower dosages are more appropriate in the elderly due to decreased theophylline clearance. Initial dosage titration may be indicated and prolonged therapy is expected on the basis of the common etiologies of bradycardia in this patient group. Patient specifics such as altered theophylline metabolism (e.g., smoking), drug interactions (e.g., ciprofloxacin), and concomitant disease states (e.g., hepatic disease, heart failure) should always be considered in theophylline dosage recommendations. Clinicians should adjust the theophylline dose on the basis of patient response, including heart rate and clinical symptomatology, as well as measurement of occasional theophylline concentrations, if deemed appropriate. Theophylline should be avoided in the bradycardia-tachycardia manifestations of sick sinus syndrome or when ventricular ectopy is frequent. Additional investigation will further define the role of theophylline in elderly patients with chronic, symptomatic bradycardia.

Caucasian versus African-American differences in orosomucoid: potential implications for therapy.

We conducted a prospective, nonrandomized study in healthy volunteers to determine if racial differences exist in orosomucoid (ORM) and its variants, and to examine quinidine and lidocaine binding to the protein. Total ORM serum concentrations were measured by Laurell-Rocket immunoelectrophoresis. Allele types were determined by isoelectric focusing and immunoblotting. Total and unbound quinidine and lidocaine concentrations were measured with standard fluorescence polarization immunoassays after ultrafiltration. The frequency of the common ORM alleles was similar between 38 Caucasians and 67 African-Americans. Mean total ORM concentration was significantly lower in Caucasians (57.3 +/- 25.4 vs 73.2 +/- 33.9 mg/dl, p=0.01). However, more Caucasians took oral contraceptives, which may have decreased ORM concentrations. Quinidine unbound fraction (UF) was related to ORM phenotype. The highest UF was found with ORM 1-S (p=0.009). There were no significant relationships between ORM phenotype and lidocaine UF. Overall, African-Americans had higher ORM concentrations than Caucasians. Quinidine binding showed significant relationships to specific ORM variants.

Warfarin resistance in a patient with short bowel syndrome.

Drug therapy in short bowel syndrome can be complicated by inadequate or incomplete absorption of drugs in the small intestine. Many case reports claim that warfarin absorption is not affected by the syndrome. We treated a patient with oral warfarin for recurring deep vein thrombosis; up to 20 mg/day was administered with no increase in the international normalized ratio. Drug-drug interactions that may prevent absorption, increase metabolism, or antagonize the effects of warfarin were ruled out. Intravenous lipid administration, which is anecdotally reported to precipitate warfarin resistance, may have contributed to the condition, but dosing was less frequent than in published reports. The most probable explanation of warfarin resistance is the reduced surface area for drug absorption secondary to surgical removal of the patient's duodenum and gastrojejunostomy.

Adjunctive intracoronary thrombolysis in complicated coronary angioplasty.

Percutaneous transluminal coronary angioplasty is complicated by abrupt closure in 4.4-9.5% of procedures. Although the etiology of closure is difficult to determine, arterial dissection and thrombus formation are often involved. When abrupt closure occurs, repeat balloon dilation of the affected vessel is the mainstay of treatment and results in a mean angiographic success rate of 44% (range 35-51%). Other interventions, such as stent implantation and atherectomy, may also be attempted. I.c. thrombolysis is an alternative rescue strategy for the treatment of abrupt coronary closure during angioplasty. Initial angiographic success with i.c. thrombolysis, in combination with repeat balloon dilation ranges from 52% to 90%. These results are encouraging, but vessel reocclusion occurs in up to 55% of patients, resulting in diminished clinical success. Two trials suggest thrombolysis is ineffective or detrimental in this patient population. Most studies evaluating i.c. thrombolysis are retrospective, noncomparative, lack standardized protocols, and evaluate dissimilar patient populations. Therefore, the contribution of confounding variable such as operator experience, balloon size, duration of balloon inflation, and investigator bias cannot be assessed. I.c. thrombolysis has a limited role in the treatment of abrupt closure. This therapy should be considered only if thrombus formation is definitively the cause of occlusion, and avoided if intimal dissection is present, due to possible detrimental effects. The results of thrombolysis as a sole rescue therapy for abrupt closure are disappointing. Therefore, repeat balloon dilation should always be performed concomitantly with drug administration. In select patients, streptokinase, alteplase, or urokinase may be given for abrupt closure. Urokinase is favored due to increased experience with this agent and decreased cost. Ambrose recommends 250,000-1,000,000 units of urokinase, infused for up to 30 minutes (average wholesale price $419-1676). Additional data indicate a lower dose of urokinase may be sufficient for closure resolution, but this has not been adequately assessed. I.c. rather than intravenous thrombolytic administration may cause fewer systemic effects; however, contraindications to thrombolytic therapy should always be evaluated and weighed against potential benefits. The future role of thrombolysis in the treatment of complicated coronary angioplasty is unclear. Only randomized, controlled trials can evaluate the merits of this treatment approach compared with other rescue strategies.

Altered protein binding of quinidine in patients with atrial fibrillation and flutter.

STUDY OBJECTIVES: To determine if alpha1-acid glycoprotein (AAG) concentrations are altered in patients with atrial fibrillation and flutter (AFF), and to establish if fluctuations in AAG change the free fraction of quinidine. DESIGN: Prospective, controlled, nonrandomized. SETTING: Tertiary care medical center and outpatient clinics. PATIENTS: Thirty patients with AFF and 16 matched controls. INTERVENTIONS: Serial blood samples were collected from patients with AFF at baseline and for 28 days after cardioversion. The control group received no treatment and a single blood sample was obtained. MEASUREMENTS AND MAIN RESULTS: Concentrations of AAG were measured by Laurell-Rocket immunoelectrophoresis. Quinidine concentrations were determined by fluorescence polarization immunoassay using the Abbott TDx system. Baseline AAG concentrations in patients with AFF (122 +/- 55 mg/dl) were significantly increased compared with the control group (62 +/- 28 mg/dl, p<0.0005). Concentrations of AAG remained elevated after conversion to sinus rhythm and did not significantly change over the study period, regardless of method of cardioversion (p>0.2). In patients with AFF, the free fraction of quinidine at the highest AAG concentration was 8.5 +/- 2.3%. This was significantly reduced compared with the value in the control group (12.5 +/- 3.0%, p<0.05) as well as that in patients with AFF at the lowest AAG concentration (11.0 +/- 2.5%, p<0.05). Overall at the highest AAG concentration, patients with AFF had a relative reduction in the quinidine free fraction by 32% compared with controls. Regression analysis showed an indirect relationship between serum AAG concentration and the unbound fraction of quinidine (r=0.56) CONCLUSIONS: Concentrations of AAG are increased in patients with AFF and remain elevated for at least 28 days after cardioversion. Elevated AAG concentrations significantly reduce the free fraction of quinidine.

Octreotide acetate in refractory bone marrow transplant-associated diarrhea.

OBJECTIVE: To evaluate the effectiveness of octreotide acetate in the treatment of refractory bone marrow transplant-associated diarrhea. DESIGN: Case series encompassing 30 months. SETTING: A 12-bed bone marrow transplant unit at a tertiary care medical center. PARTICIPANTS: Twenty-four patients with bone marrow transplant-associated diarrhea who did not improve with supportive or attapulgite therapy. INTERVENTIONS: Patients received subcutaneous octreotide acetate at doses ranging from 50 to 250 micrograms 2 to 3 times daily. Concurrent treatment with antimotility or antisecretory agents did not occur. MAIN OUTCOME MEASURES: The number of bowel movements and stool volumes were recorded daily. Complete response to octreotide therapy was defined as a reduction of both stool output and stool frequency by more than 50% within 72 hours. Partial response was defined as a reduction of either stool output or stool frequency by more than 50% within 72 hours. Treatment failure occurred if neither of the two parameters decreased by 50% within the designated time period. RESULTS: Twenty-eight treatment challenges were initiated in the 24 patients evaluated. Diarrhea completely or partially subsided in 23 of 28 challenges (82.1%) within 72 hours. Stool output decreased from 1143 +/- 595 at baseline to 252 +/- 356 mL/d within 72 hours (p < 0.005). Stool frequency decreased from a baseline of 7.5 +/- 3.4 to 2.7 +/- 2.2 stools per day within 72 hours (p < 0.005). Adverse effects associated with octreotide were pain or burning at the injection site (24.1%), abdominal pain (13.8%), and increased stool output (6.9%). CONCLUSIONS: These data suggest octreotide acetate significantly reduces stool output and frequency in patients with refractory bone marrow transplant-associated diarrhea. Additional research is necessary before this agent can be recommended for routine use in this patient population.

Current concepts in autologous bone marrow transplantation.

BMT is the treatment of disease with high-dose chemotherapy and/or radiation therapy accompanied with bone marrow rescue. An autologous BMT is performed with marrow acquired from the patient. The marrow is obtained from the bone marrow or from peripheral blood progenitor cells (PBPCs), also known as stem cell transplants. Marrow purging of malignant cells and autologous BMT with only PBPC continues to be an area of active research.

Urokinase therapy in mesenteric venous thrombosis: a case study.

Mesenteric venous thrombosis is an emergency usually treated by bowel resection with an end-to-end anastomosis and in some cases anticoagulant therapy. The survival rate is low. The literature records many cases of mesenteric venous thrombosis and various treatment modalities. An 18-year-old man was successfully treated for mesenteric venous thrombosis by the placement of a femoral infusion catheter in the superior mesenteric artery for continuous infusion of urokinase (Abbot Laboratories, N. Chicago, Ill.). This case study and overview of the disease process reviews the nursing implications of this problem.

Rapid estimate of adult literacy in medicine: a shortened screening instrument.

BACKGROUND: This study was conducted to validate a shortened version of the Rapid Estimate of Adult Literacy in Medicine (REALM). This screening instrument is designed to be used in public health and primary care settings to identify patients with low reading levels. It provides reading grade estimates for patients who read below a ninth-grade level. The REALM can be administered in one to two minutes by personnel with minimal training. METHODS: Two hundred and three patients in four university hospital clinics (internal medicine, family practice, ambulatory care, and obstetrics/gynecology) were given the REALM and three other standardized reading tests: the reading recognition section of the Peabody Individual Achievement Test-Revised (PIAT-R), the Wide Range Achievement Test-Revised (WRAT-R), and the Slosson Oral Reading Test-Revised (SORT-R). One hundred inmates at a state prison were also given the REALM twice, one week apart, to determine test-retest reliability. RESULTS: The REALM correlated well with the three other tests. (Correlation coefficients were 0.97 [PIAT-R], 0.96 [SORT-R], and 0.88 [WRAT-R].) All correlations were significant at P < .0001. Test-retest reliability was 0.99 (P < .001). CONCLUSIONS: The REALM provides an estimate of patient reading ability, displays excellent concurrent validity with standardized reading tests, and is a practical instrument for busy primary care settings.

Heparin-induced thrombocytopenia and thrombosis.

Heparin is one of the most frequently prescribed medications in the United States; yet, a significant number of patients receiving heparin develop heparin-induced thrombocytopenia and thrombosis syndrome. This detailed case report demonstrates the significant role nurses play in early detection and prevention of the numerous multisystem complications of this heparin toxicity.

Patient reading ability: an overlooked problem in health care.

Health care workers often assume that patients who have completed a certain grade in school can read at that level. This study examines the relationships between patient reading ability, the last grade completed, and the reading ability necessary to comprehend commonly used written materials. We tested 528 patients during regular visits to seven outpatient clinics serving a predominantly indigent population. In addition, we analyzed the readability of 280 brochures and consent forms used in these clinics. Most patients had reading abilities on a level far below their last grade completed, while almost all materials tested were written on a level far above average patient reading ability. We conclude that patient reading ability should be routinely tested and that written materials should be developed on a level commensurate with patient reading ability.