Edited by Phil B. Fontanarosa, MD, and Catherine D. DeAngelis, MD, MPH
In the CALM-PD trial, the onset of dopaminergic motor complications
after 2 years of follow-up was delayed in patients with early Parkinson disease
who received initial treatment with pramipexole compared with those who received
levodopa therapy. In this neuroimaging substudy of the CALM-PD trial, the
Parkinson Study Group used single-photon emission computed tomography with β-CIT
imaging ligand, a biomarker of dopamine transporter density, to compare rates
of dopamine neuron degeneration in the 2 study groups. Loss of striatal β-CIT
uptake was significantly less in the pramipexole group compared with the levodopa
group at 22, 34, and 46 months after baseline.
Two studies reported in this issue of THE JOURNAL evaluated the usefulness
of up-regulated genes that were identified as potential biomarkers for prostate
and ovarian cancer using complementary DNA microarray techniques. Rubin and
colleaguesArticle found an association between α-methylacyl coenzyme A racemase
protein expression and prostate cancer in prostatectomy specimens and in prostate
needle-biopsy specimens. Kim and colleaguesArticle found an association between levels
of osteopontin expressed in ovarian cancer cells and tissue specimens and
levels measured in plasma and ovarian cancer.
Genetic polymorphisms for drug receptors, drug-metabolizing enzymes,
and drug-effector pathways may modify the response of patients to pharmacotherapy.
Psaty and colleaguesArticle found that in patients with hypertension who carried
the Trp460 variant allele of the α-adducin
gene, which has been associated with high rates of renal sodium reabsorption
and salt-sensitive hypertension, diuretic therapy was associated with a lower
risk of the combined outcome of myocardial infarction or stroke than other
antihypertensive therapies. Higashi and colleaguesArticle found an association between
2 genetic variants of the hepatic microsomal enzyme CYP2CP, the principal
enzyme involved in warfarin metabolism, and increased risk of excess anticoagulation
and bleeding events in patients receiving warfarin.
Nontypeable Haemophilus influenzae strains
colonize the nasopharyngeal tract as part of the normal flora but may also
cause acute infections in the respiratory tract and other sites. Vitovski
and colleagues found that nontypeable H influenzae
strains isolated from symptomatic patients had significantly higher IgA1 protease
levels compared with strains from throat swabs of asymptomatic carriers.
Three investigations in this issue of THE JOURNAL used experimental
models to identify factors that may be important in the pathogenesis of disease.
Bodary and colleaguesArticle found that leptin contributed to arterial thrombosis
following vascular injury in mice, an effect that appeared to be mediated
through the platelet leptin receptor. Ehrlich and colleaguesArticle demonstrated
the presence of viable bacteria growing as a mucosal biofilm in a chinchilla
model of otitis media, and suggest that biofilm formation may be an important
factor in the pathogenesis of chronic otitis media with effusion. Coopersmith
and colleaguesArticle found that inhibition of gut epithelial apoptosis by overexpression
of the antiapoptotic protein Bcl-2 in the intestinal epithelium of transgenic
mice was associated with improved survival in a murine model of Pseudomonas aeruginosa pneumonia–induced sepsis.
Building on knowledge gleaned from laboratory studies, many researchers
are developing and testing a host of new anti-HIV agents.
Frist highlights notable achievements of federally funded research in
the United States and discusses the need for collaboration among government
agencies, the scientific and medical communities, and the public to improve
translation of research advances into better clinical care and patient outcomes.
Pollard describes the reductionistic approach in biomedical research,
which links molecular mechanisms, often studied in model organisms, to human
physiology and disease states, and discusses how new knowledge of molecular
mechanisms of disease will alter clinical practice.
For your patients: Information about basic science research.
This Week in JAMA. JAMA. 2002;287(13):1613. doi:10.1001/jama.287.13.1613