Determination of human beta(2)-adrenoceptor haplotypes by denaturation selective amplification and subtractive genotyping.

OBJECTIVE: beta(2)-Adrenoceptor haplotype may be better associated with asthma severity and drug response than a polymorphic variant at any single site. Because present methods of haplotype determination are time consuming and impractical for large population studies, we sought to develop a simple and efficient method of determining haplotype of 3 common polymorphisms at codons -19 (Arg/Cys), 16 (Arg/Gly) and 27 (Glu/Gln). DESIGN: Preliminary studies showed that the C/G base pair of the Arg(-19) allele increases the local melting temperature over the T/A base pair of the Cys(-19) allele by 3.6 degrees C and establishes a new local maximum denaturation temperature. By choosing a suitable denaturation temperature and appropriate primers and coupling them with restriction fragment length polymorphism (RFLP) analysis, we hypothesized that the genotype of one separately amplified allele followed by subtraction from the combined genotype of two alleles would yield the beta(2) haplotype in > 99% of the population. RESULTS: Haplotype determined by our method was in complete agreement with haplotype determined by cloning and sequencing in 29 samples. The frequencies of haplotype pairs in 78 healthy adults, according to our method, were in agreement with published values that were inferred, and were: RGE/CRQ, 26.9%; CRQ/CRQ, 25.6%; RGE/CGQ, 16.7%; CRQ/CGQ, 10.3%; RGE/RGE, 11.5%; CGQ/CGQ, 7.7%. The haplotype pair in one individual was RRE/CRQ (1.3%). CONCLUSION: Our method of determining beta(2)-adrenoceptor haplotype is simple, accurate and cost effective for haplotyping large populations.

Technology assessment and the drug use process.

UNLABELLED: This activity is designed for pharmacists, physicians, physician assistants, nurses, and other healthcare team members, payers for health services, and healthcare executives. OBJECTIVES: Upon completion of this activity, the participant should be able to: 1. Describe the rationale behind, the development of, and the advantages arising from the formulary process, and discuss the health professionals involved in the creation of formularies. 2. Describe the impact of new drug development and technology on the drug use process. 3. Discuss the functions of the pharmacy and therapeutics committee. 4. Describe the impact of consumers on the drug use process.

Bupropion mimics a transient ischemic attack.

OBJECTIVE: To report the development of symptoms suggesting transient ischemic attacks during bupropion treatment for smoking cessation. CASE SUMMARY: A 67-year-old white man experienced paresthesia, dizziness, tinnitus, confusion, and gait impairment shortly after starting bupropion as an aid to smoking cessation. Bupropion was discontinued on hospital admission, and testing for vertebral basilar artery disease was negative. His symptoms resolved, and he remained asymptomatic until restarting bupropion two days after hospital discharge. DISCUSSION: Although separate case reports have reported sensory disturbances, tinnitus, and balance impairement associated with bupropion use, the combination of symptoms occurring in this patient has not been previously published. CONCLUSIONS: The temporal relationship between bupropion exposure and symptomatology suggests that bupropion caused symptoms mimicking transient ischemic attacks in this patient.

Prevention and treatment of drug-resistant tuberculosis.

Therapy recommended for preventing and treating drug-resistant tuberculosis is discussed. Drug-resistant strains of Mycobacterium tuberculosis can be transmitted by an infected individual, or resistance can be acquired during therapy for drug-susceptible disease. At least until susceptibility test data are available, the recommended initial treatment for tuberculosis consists of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Resistance has led to variations on this regimen that sometimes include more toxic alternative drugs, including ethionamide, aminosalicylic acid, cycloserine, and capreomycin, as well as ciprofloxacin and ofloxacin. Drug regimens used for retreatment usually include the alternative drugs. Success in treating drug-resistant tuberculosis varies. Therapy to prevent resistant tuberculosis is recommended for any individual with a positive skin-test result and any of the following: infection with the human immunodeficiency virus (HIV), close contact with a newly diagnosed patient, recent conversion to a positive skin-test result, or a predisposing medical condition. Although isoniazid is the only drug with FDA-approved labeling for use as prophylaxis in patients with latent tuberculosis, the Centers for Disease Control and Prevention suggests several two-drug combinations. Fluoroquinolones are recommended for both treatment and prevention. Patient compliance and HIV infection are special issues in managing resistant tuberculosis. Drug-resistant tuberculosis is a growing problem that must be addressed through appropriate prophylactic and treatment measures.