Publications

BACKGROUND

Physical inactivity, poor diet, excessive alcohol consumption, and smoking are modifiable risk factors associated with development of chronic diseases. Although the prevalence of diseases associated with these detrimental lifestyle behaviors is high among women in the United States, they may not receive adequate counseling from physicians.

METHODS

To predict physicians' lifestyle counseling practices, we assessed personal, professional, and health behavior characteristics from responses to a self-administered survey of breast cancer risk reduction practices. Subjects were California physicians identified through AMA Masterfile, in family practice, internal medicine, or obstetrics/gynecology, who were asked to report the percentages of women patients they counseled on physical activity, diet, alcohol, and smoking.

RESULTS

Of 1647 eligible physicians, 822 (50.0%) responded. Fifty-six percent reported counseling at least 75% of patients about physical activity, 54.6% about diet, and 44.8% about alcohol. More than three quarters (78.7%) counseled at least 75% of patients about smoking. In logistic regression analyses, woman gender, family practice, and internal medicine specialties emerged as significant predictors of counseling for all lifestyle behaviors. Older age was associated with dietary and alcohol counseling. Race/ethnicity was associated only with smoking counseling, and country of medical school was associated with counseling for physical activity and smoking. Sources of new medical knowledge emerged as predictors for all types of counseling, whereas physicians' own level of physical activity only predicted counseling about physical activity.

CONCLUSIONS

Physicians' personal, professional, practice, and health behavior characteristics were associated with reported lifestyle counseling of women patients. Results reveal important directions for future physician-based interventions to improve counseling.

Despite their huge health toll, substance abuse disorders remain underappreciated and underfunded. Reasons include stigma, tolerance of personal choices, acceptance of youthful experimentation, pessimism about treatment efficacy, fragmented and weak leadership, powerful tobacco and alcohol industries, underinvestment in research, and difficult patients. Positive signs include declining prevalence rates, successful counter-marketing campaigns, changing public attitudes, new scientific discoveries that could yield new treatments, and effective new organizations. Further progress will require better treatment, more research, better education of health professionals, more nongovernmental support, and stronger leadership. Policy changes regarding each of the three substance groups are indicated, as are reforms in the criminal justice and educational systems.

A new medical diagnostic code for secondhand smoke exposure became available in 1994, but as of 2004 it remained an invalid entry on a common medical form. Soon after the code appeared, Philip Morris hired a Washington consultant to influence the governmental process for creating and using medical codes. Tobacco industry documents reveal that Philip Morris budgeted more than $2 million for this "ICD-9 Project." Tactics to prevent adoption of the new code included third-party lobbying, Paperwork Reduction Act challenges, and backing an alternative coding arrangement. Philip Morris's reaction reveals the importance of policy decisions related to data collection and paperwork.

BACKGROUND

Cardiac resynchronization therapy (CRT) improves symptoms and the survival rate in patients with advanced heart failure by improving synchrony. However, CRT is not always successful, is costly, and is applied without individualization. There is no specific measure of synchrony. The goal of this study was to analyze new quantitative parameters of synchrony and compare them with established measures.

METHODS AND RESULTS

Equilibrium radionuclide angiography, phase angle (Ø), and amplitude quantitate regional contraction timing and magnitude and are the basis for new synchrony (S) and entropy (E) parameters. S is the vector sum of all amplitudes based on the angular distribution of Ø divided by the scalar sum of the length of all vectors. Complete S equals 1, and its absence equals 0. E measures the disorder in the region of interest, is 1 with random contraction and 0 with full synchrony, and differentiates among differing contraction patterns. Left ventricular S and E were measured in 22 normal equilibrium radionuclide angiography studies, where regions of interest were drawn from the left ventricle, left atrium, and background to analyze model ventricles with normal wall motion (N), ventricles with aneurysm (An), ventricles with severe diffuse dysfunction (Diff), and ventricles with severe regional dysfunction (Reg). The new S and E parameters were highly reproducible and well differentiated among N, An, Diff, and Reg, which were not separated by SD Ø (SD of ventricular phase), which has gained popularity as a measure of synchrony.

CONCLUSION

Unique scintigraphic parameters for the evaluation of ventricular synchrony were derived, and their added value was determine compared with established measures. Indications for pacemaker therapy now include the treatment of severe congestive heart failure (CHF). Atrial triggered biventricular pacemakers reduce CHF symptoms and prolong life in patients with cardiomyopathy, severe CHF, left ventricular (LV) ejection fraction (EF) lower than 35%, and QRS greater than 120 milliseconds. Such pacing, or cardiac resynchronization therapy (CRT), seeks to reduce the heterogeneity and increase the synchrony of ventricular activation, conduction, and contraction. CRT has improved hemodynamics, increased exercise tolerance, reduced symptoms and the need for hospitalization, reversed ventricular remodeling, and reduced the all-cause mortality rate in CHF. However, CRT is costly, fails to improve symptoms or activity level in more than 30% of patients, and is applied blindly without individualization or consideration of lead placement sight. A variety of echocardiographic methods have sought to measure synchrony and its serial changes with CRT. A recent study presented evidence of the poor reproducibility of several widely applied echocardiographic measurements by which to determine ventricular synchrony. Magnetic resonance imaging has excellent resolution of regional wall motion and has been applied to assess ventricular synchrony and its response to pacing therapy. However, these methods are complex and are not well established or widely available, and magnetic resonance imaging has not been widely applied after pacing. An accurate and reproducible method is needed by which to objectively measure regional ventricular synchrony. Phase image analysis, a functional method based on the first Fourier harmonic fit of the gated blood pool time versus radioactivity curve, generates the parameters of amplitude (A), which parallels the extent of regional ventricular contraction or stroke volume, and phase angle (Ø), which represents the timing of regional contraction. It was applied early with demonstrated reproducibility to show the linkage between electrical and mechanical dyssynchrony and to characterize the contraction pattern in heart failure and its alteration with CRT. The SD of ventricular Ø, applied as a marker of synchrony, has been shown to demonstrate the beneficial effects of biventricular pacing, and its strong prognostic value has been shown in patients with congestive cardiomyopathy and CHF, superior to LVEF. The SD Ø may not be optimal for synchrony evaluation. We sought improved, more sensitive parameters to better differentiate synchrony among the spectrum of possible patterns of dyssynergy. We derived, initially evaluated, and here present new synchrony (S) and entropy (E) parameters, based on the phase method, to quantitate regional and global ventricular synchrony and applied them in simulation and clinical protocols.

BACKGROUND

Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD).

METHODS

Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239 racially diverse hemodialysis (HD) patients and 252 controls. These individuals were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1 receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic regression for their independent associations with ESRD, and the effect of allele dose of IL-1RN on risk for ESRD was examined. The interaction between race and genotype was also investigated.

RESULTS

A logistic regression model demonstrated that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005). The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated with ESRD, but this is accounted for by race (P= 0.04).

CONCLUSION

Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. This finding is one of the strongest associations between genotype and ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect the risk of development of ESRD.

The vasculature forms an intrinsic functional component of the lung and its development must be tightly regulated and coordinated with lung epithelial morphogenesis. Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in a complementary pattern in the lungs during embryonic development. VEGF is expressed by epithelium and the receptors in the surrounding mesenchyme. To determine the function of VEGF in lung formation, we inhibited its activity using a soluble receptor in lung renal capsule grafts. Inhibition of VEGF results in inhibition of vascular development and significant alteration in epithelial development. Epithelial proliferation is inhibited, sacculation is impaired, and the epithelium undergoes apoptosis. Interestingly, when VEGF is attenuated, epithelial differentiation still proceeds, as shown by acquisition of both proximal and distal markers. These data show that VEGF co-ordinates epithelial and vascular development. It is required for the development of the lung vasculature and the vasculature is necessary for epithelial proliferation and morphogenesis, but not for cell differentiation.

BACKGROUND

Neutrophilic airway inflammation, as defined by cell counts in respiratory tract lining fluid (RTLF), is a key end point in many studies of respiratory toxicity in both healthy and asthmatic subjects. BAL and sputum induction (SI) are the most common methods of sampling RTLF in such studies. However, the comparability of these methods (BAL and SI) after experimental treatment has not been investigated in a head-to-head controlled trial.

METHODS

To determine whether BAL and SI are comparable and can be used in place of each other in the assessment of neutrophilic airway inflammation after ozone (O(3)) exposure, we exposed 13 asthmatic subjects to either 0.2 ppm of O(3) or filtered air (FA) followed by either BAL or SI. Subjects then underwent the alternate (O(3) or FA) exposure followed by the same method of RTLF sampling. Next, subjects repeated the same exposure protocol with the alternate method of RTLF sampling. Differences in inflammatory indexes including the percentage of polymorphonuclear neutrophils (%PMNs) between the exposures were then correlated by regression analysis.

RESULTS

The %PMNs in sputum was poorly correlated with that in BAL fluid (R = 0.12). The correlation between the %PMNs in sputum and in the bronchial fraction of BAL (BFx) fluid, however, was somewhat higher (R = 0.50). Furthermore, the uncertainty of the estimate of %PMN values in BFx fluid and BAL fluid based on those of sputum values, using regression models, was almost as great as the magnitude of the O(3) effect itself (ie, 9.7% and 5.5% estimate errors for O(3) effects of 17.0% and 7.5%, respectively).

CONCLUSION

We concluded that SI and BAL indexes are not directly interchangeable in the assessment of O(3)-induced airway inflammation in asthmatic subjects.

OBJECTIVE

We sought to study respiratory symptoms among automobile assembly workers.

METHODS

In a cross-sectional study, we compared rates of respiratory symptoms and of physician-diagnosed asthma and COPD in painters and welders to those in assembly workers.

RESULTS

Respiratory symptom reporting was significantly increased among welders (odds ratio [OR] = 1.79-2.61) compared with painters or assembly workers, after age, race, and smoking adjustment in multiple logistic regression analyses. Welders also reported significantly more improvement in symptoms on weekends or vacation. However, no significant elevations in adjusted ORs were observed for physician-diagnosed asthma or chronic obstructive pulmonary disease for welders. In contrast, significantly more painters had physician-diagnosed chronic obstructive pulmonary disease (OR = 3.73, 95% confidence interval = 1.27, 11.0).

CONCLUSIONS

Welders and painters in this plant appeared to have increased risk of respiratory health effects compared with assembly workers.