Use of specific inhalation challenge in the evaluation of workers at risk for occupational asthma: a survey of pulmonary, allergy, and occupational medicine residency training programs in the United States and Canada

STUDY OBJECTIVES: To document the current practice of occupational asthma (OA) diagnosis and use of specific inhalation challenge (SIC). DESIGN, SETTING, AND PARTICIPANTS: A survey evaluating the current practice of SIC was mailed to 259 residency training programs in adult pulmonary diseases, allergy and immunology, and occupational medicine accredited in the United States and Canada during the year 2000. RESULTS: Forty-six percent (123 of 259 programs) participated. Ninety-two programs reported that patients with OA were seen during the previous year, 15 programs reported that SIC had been performed, and 10 programs reported that patients had been referred to other sites for SIC. A total of 259 patients underwent SIC. No unexpected adverse reactions were reported. Forty-one programs reported that they had been willing to undertake SIC but were unable to do so. The most common barriers cited were lack of availability of SIC within the evaluating institution, inability to locate a site for referral, concerns about reimbursement, and lack of an appropriate diagnostic reagent for use in SIC. Seventy-four programs indicated that SIC was useful, and 34 programs included training in the use of SIC was part of the residency curriculum. CONCLUSION: Although SIC is considered the "gold standard" for objective documentation of OA, the test is performed in only a few institutions in the United States and Canada. Many institutions indicate that SIC is not available, even when desired for patient management. Only a minority of participating residency training programs include SIC as a formal part of the training curriculum.     

Comparison of paclitaxel-eluting stent and sirolimus-eluting stent expansion at incremental delivery pressures

OBJECTIVES: We sought to compare the adequacy of paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) expansion based on intravascular ultrasound (IVUS) imaging criteria at conventional delivery pressures. METHODS: Forty-six patients underwent SES implantation and 42 patients underwent PES implantation for de novo native coronary lesions<33 mm in length with reference lumen diameters of 2.5-3.5 mm. Stents were serially expanded with gradual balloon inflations at 14 and 20 atm. IVUS imaging was performed prior to intervention and after each balloon inflation. Stent expansion (minimal stent cross-sectional area/reference lumen cross-sectional area) was measured. Inadequate stent expansion was defined using the MUSIC criteria (all struts apposed, no tissue protrusion, and final lumen cross-sectional area>80% of the reference or >90% if minimal lumen cross-sectional area was <9 mm2). RESULTS: The baseline characteristics of the two groups were similar except for shorter lesion length, larger mean lumen cross-sectional area, larger lumen diameter, and lower plaque burden in the PES group. Stent expansion was inadequate in 80% of patients with SES versus 63% of patients with PES at 14 atm, although this was not statistically significant. After 20 atm, 48% of patients with SES remained underexpanded as compared with 35% of patients with PES. CONCLUSION: Drug-eluting stents showed significant underexpansion by MUSIC criteria at conventionally used inflation pressures. Higher balloon inflations are required especially during deployment of a SES. IVUS guidance is recommended to ensure optimal results and outcomes with both stents.     

Tuberculosis mortality by industry in the United States, 1990-1999.

OBJECTIVE: To identify occupations and industries with elevated respiratory tuberculosis (TB) mortality in the United States for the period 1990-1999, we used National Center for Health Statistics multiple-cause-of-death data, restricted to certain states for which information on decedents' usual industry and occupational information was available and limited to US residents aged > or =15 years. DESIGN: A total of 7686 deaths between 1990 and 1999 were attributed to respiratory TB. Proportionate mortality ratios (PMRs), adjusted for age, sex, and race, were calculated from US census occupation and industry classifications. RESULTS: Industries and occupations involving potential contact with infected cases (e.g., health care workers), those with silica exposure and silicosis (e.g., mining and construction), and those associated with low socioeconomic status had significantly elevated TB mortality. CONCLUSIONS: Overall, the pattern of findings echoes that described in various prior reports, which indicates that the potential for exposure and disease development still persists among certain worker groups. The findings should be useful in guiding occupationally targeted TB prevention programs.     

Specificity of Doppler echocardiography for the assessment of changes in valvular regurgitation: comparison of side-by-side versus serial interpretation

OBJECTIVES: We sought to determine the specificity of two different methods for assessing change in aortic (AR), mitral (MR) and tricuspid (TR) valvular regurgitation. BACKGROUND: Echocardiographic imaging with Doppler is the standard noninvasive diagnostic tool for assessing valvular structure and function. Change can be assessed using either independent evaluations (serial) or using a side-by-side comparison. METHODS: Subjects were from the placebo arm of a randomized, double-blind, clinical trial. Three echocardiograms over 10 months were performed. An initial and three-month echocardiogram were read as independent groups, blinded to all parameters except sequence. The initial and 10-month echocardiograms were read side-by-side, blinded to all parameters including sequence. RESULTS: Two hundred nineteen predominantly healthy, obese, white, middle-aged women had initial and three-month echocardiograms (acquisition interval 105 +/- 28 days) evaluated by the serial method (mean 167 +/- 61 days between interpretations). The same subjects had the initial and 10-month studies (acquisition interval 303 +/- 27 days) compared side-by-side. The specificity of the serial versus side-by-side method for determining change in MR grade was 55.8% versus 93.2% (p < 0.001); TR: 63.8% versus 97.6% (p < 0.001) and AR: 93.7% versus 97.6 (p = 0.08). Notably, most of the change occurred in a range (none versus physiologic/mild) that has limited clinical significance. Furthermore, the percentage of echocardiograms interpreted as nonevaluable was lower with the side-by-side method for MR (5.0% vs. 16.0%, p = 0.06), TR (4.6% vs. 15.5%, p < 0.001) and AR (4.1% vs. 12.3%, p = 0.002). CONCLUSIONS: The side-by-side method of assessing change in valvular regurgitation appears to be the more reliable method with a higher specificity and minimal data loss.     

Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia

OBJECTIVES: We tested the hypothesis that intramyocardial injection of autologous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1). BACKGROUND: The natural processes leading to collateral development are extremely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may, therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells that secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis. METHODS: Bone marrow was cultured four weeks in vitro. Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation. Four weeks after left circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/injection at 12 sites). Echocardiography to assess myocardial thickening and microspheres to assess perfusion were performed at rest and during stress. RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner. The conditioned medium enhanced, in a dose-related manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 100) improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs. 77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs. 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23). CONCLUSIONS: Bone marrow cells secrete angiogenic factors that induce endothelial cell proliferation and, when injected transendocardially, augment collateral perfusion and myocardial function in ischemic myocardium.     

Genes in one megabase of the HLA class I region.

To define the gene content of the HLA class I region, cDNA selection was applied to three overlapping yeast artificial chromosomes (YACs) that spanned 1 megabase (Mb) of this region of the human major histocompatibility complex. These YACs extended from the region centromeric to HLA-E to the region telomeric to HLA-F. In addition to the recognized class I genes and pseudogenes and the anonymous non-class-I genes described recently by us and others, 20 additional anonymous cDNA clones were identified from this 1-Mb region. We also identified a long repetitive DNA element in the region between HLA-B and HLA-E. Homologues of this element were located at several sites in the human genome outside of the HLA complex. The portion of the HLA class I region represented by these YACs shows an average gene density as high as the class II and class III regions. Thus, the high gene density portion of the HLA complex is extended to more than 3 Mb.     

Changes in integrin expression are associated with altered homing properties of Lin(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) hematopoietic stem cells following mobilization by cyclophosphamide/granulocyte colony-stimulating factor

OBJECTIVE: Although migration of hematopoietic stem cells (HSC) is essential for normal hematopoiesis and successful hematopoietic cell transplantation, little is known about the mechanisms that underlie this movement. We have sought to characterize the factors that regulate HSC migration by analyzing changes in expression of particular adhesion receptors associated with cyclophosphamide/granulocyte colony-stimulating factor (Cy/G-CSF)-induced HSC mobilization. METHODS: Expression by Lineage(-/lo)Thy1.1(lo)Sca-1(+)c-kit(+) HSC of members of the beta1 integrin family of adhesion molecules was assessed in untreated or Cy/G-CSF-treated mice by multiparameter flow cytometry. In parallel, the in vivo homing properties of normal and mobilized HSC were compared following intravenous transfer of fluorescently marked HSC. RESULTS: Normal adult HSC express high levels of several beta1 integrin family members. Following Cy/G treatment, bone marrow HSC selectively downregulate alpha 2 integrin expression and upregulate alpha 5 expression. HSC found in the blood following Cy/G-CSF treatment express significantly lower levels of multiple integrins than their bone marrow and/or splenic counterparts. Changes in integrin expression by blood-borne HSC correlate with a 50% decrease in their ability to home to the bone marrow in short-term assays, and with previously observed defects in competitive engraftment by these HSC. Similar reductions in bone marrow (BM) homing are observed for BM HSC treated with alpha 4 integrin function blocking mAb prior to injection. Modulation of integrin expression induced by mobilization was not associated with cell-cycle progression. CONCLUSION: Changes in integrin expression and function are associated with HSC mobilization and likely significantly affect the engraftment potential of hematopoietic stem cells.     

Effect of routine intensive care interactions on metabolic rate

The alterations in metabolic (oxygen consumption [VO2] and carbon dioxide production [VCO2]) and hemodynamic (heart rate and blood pressure) parameters caused by various common intensive care activities were examined in a group of 23 mechanically-ventilated critically-ill patients. The observed variations in metabolic rate can be classified into four categories as follows: (a) the lowest energy expenditure, which was associated with sleeping in the majority (83 percent) of instances; (b) resting, which was defined as a state where the patient was lying motionless with eyes open and responding to surrounding events, where VO2 and VCO2 averaged 9.1 +/- 7.5(SD) percent and 7.5 +/- 7.3 percent, respectively, above the lowest values; (c) a variety of routine daily care activities (eg, bathing, performing a physical examination) that although not particularly painful, caused arousal from the resting state. During these situations, VO2 and VCO2 averaged about 20 percent above lowest values; and (d) chest physical therapy, which was associated with metabolic increases of 35 percent above lowest values as well as increases in both heart rate and blood pressure. This study demonstrates that routine daily ICU activities can significantly alter metabolic rate, and thus, it is important to couple such measurements with astute observations of the patients' activity state. In addition, we have defined an activity state--resting--that can be used in the calculation of energy expenditure as well as for intrapatient and interpatient comparisons.