Publications

To determine the incidence of physician-diagnosed Lyme disease in an endemic area of California, an active surveillance program was implemented in Lake, Mendocino, Sonoma, and southern Humboldt counties. More than 200 medical care providers were called monthly for their list of suspected cases of Lyme disease. Pertinent information was abstracted from the medical record of each patient. Of 153 cases of possible early Lyme disease ascertained from July 1991 to December 1992, 37% consisted of physician-diagnosed erythema migrans. Only 58% of erythema migrans rashes were at least 5 cm in diameter. An additional 43 patients had suspicious rashes not classified as erythema migrans. Of 166 patients with possible late-stage Lyme disease, 31% had specific clinical symptoms and 75% had a positive serologic test. With an incident case defined as physician-diagnosed erythema migrans of at least 5 cm in diameter, the annual incidence of Lyme disease in northwestern coastal California according to active surveillance only was 5.5 per 100,000. The rate of Lyme disease in California is substantially lower than that in the Atlantic northeastern United States. Many suspected cases of Lyme disease in this endemic area do not meet surveillance criteria, which are intentionally restrictive. Although some of the illnesses not meeting surveillance criteria may be due to infection with Borrelia burgdorferi, it appears that Lyme disease is being overdiagnosed in this area.

The hemodynamic factors contributing to reduced exercise capacity in adults with congenital heart disease are not fully defined. We hypothesized that they would demonstrate reduced exercise capacity compared with age-matched control subjects because of abnormal exercise hemodynamics and ventricular performance demonstrable by echocardiography. We retrospectively analyzed the results of all studies in all patients with congenital heart disease (from 1988 to 1993) and found that the peak work load and double product achieved were decreased in comparison with normal values (79 +/- 47 W vs 149 +/- 52 W [p < 0.0001] and 19,210 +/- 6805 vs 25,701 +/- 6440 [p = 0.005], respectively). Seven patients achieved work loads < 40 W associated with an exaggerated exercise pulmonary artery pressure response, decreases in right and/or left ventricular function with exercise, or both. Normal or near-normal exercise tolerance was observed in the following patient groups: (1) repaired tetralogy of Fallot, (2) uncomplicated I-transposition of the great arteries, and (3) Ebstein's anomaly with atrial septal defect. We conclude that exercise echocardiography provides new hemodynamic information for evaluating functional limitations in congenital heart disease.

The integrin alpha v beta 6 is expressed primarily in epithelial cells and mediates attachment to the extracellular matrix protein fibronectin. We recently observed that alpha v beta 6 localizes to focal contacts when cells that express the receptor are plated on fibronectin. To determine which regions of the beta 6 cytoplasmic domain are required for recruitment to focal contacts, the wild type human beta 6 cytoplasmic domain are required for recruitment to focal contacts, the wild type human beta 6 subunit and mutants containing selective deletions within the beta 6 cytoplasmic domain were stably expressed in Chinese Hamster Ovary cells. The beta 6 cytoplasmic domain is composed of a 41 amino acid region that is highly conserved among integrin beta subunits, and a unique 11 amino acid carboxy terminal extension. The 11 amino acid extension was not required for localization to focal contacts; in fact, its removal appeared to increase receptor localization. However, removal of any of the 3 conserved regions previously identified as important for the localization of beta 1 integrins to focal contacts (Reszka, et al., 1992, J. Cell Biol. 117:1321-30) eliminated recruitment of beta 6 to focal contacts. These data suggest that, as with the integrin beta 1 subunit, multiple regions within the first 41 amino acids of the beta 6 cytoplasmic domain are necessary for recruitment of alpha v beta 6 to focal contacts. However, the unique 11 amino acid carboxy terminus of beta 6 is not required for this recruitment, and may actually play a negative regulatory role.

As part of a larger investigation of inhalational toxic exposures, we studied occupationally related cases in order to examine possible preventive strategies. We analyzed data from 224 structured interviews. Of the interviewed subjects, 48 (21%) reported closed space exposures and 44 (20%) concomitant skin exposure at the time of inhalation. Chlorine gas and bleach mixtures were the most common single reported exposure type, occurring in 54 (24%) of cases. The most common occupational groups represented were crafts workers, operatives, and laborers (n = 84, 38%), and service workers (n = 64, 29%). Adjusting for occupational group in a multiple logistic regression analysis that also included length of hire and access to personal respiratory protective equipment, report of prior specific chemical safety training was significantly protective against closed space inhalation (odds ratio (OR) = 0.2; 95% confidence interval (CI) 0.1-0.4) and concomitant skin exposure (OR = 0.3, 95% CI = 0.1-0.7). These data suggest that chemical safety training may be an effective preventive strategy for potentially high-risk inhalational exposure scenarios.