Citations

Thromboangiitis obliterans (TAO) is often cited as an extreme phenotype of vasculopathy and tobacco dependence. Although tobacco exposure is essential to progression of arterial ischemia in TAO, expert opinion differs regarding the degree of tobacco dependence in this population. The authors designed a prospective, case-control study to test the hypothesis that subjects with TAO have a greater degree of tobacco dependence than control subjects with coronary atherosclerosis (coronary artery disease [CAD]) do. Subjects with TAO (n=218, confirmed by angiography, biopsy, or noninvasive arterial testing) or CAD (n=343, diagnosed by coronary angiography) were mailed a standardized questionnaire regarding tobacco use, to which 103 and 273 responded, respectively. The degree of tobacco dependence in each group was ascertained by several methods, including the Fagerström Test for Nicotine Dependence Questionnaire. The TAO group was younger at index date (year of first diagnosis for TAO patients, year of percutaneous transluminal coronary angioplasty [PTCA] for CAD patients) (TAO 37.6 ±9.0 vs CAD 43.3 ±4.9 yr, p<0.0001), but the groups did not differ in age at first tobacco exposure (TAO 16.7 ±3.1 vs CAD 17.3 ±4.2 yr, p=0.67), current tobacco use at time of survey (TAO 54% vs CAD 46%, p=0.17), or Fagerström score (TAO 4.7 ±2.3 vs CAD 5.1 ±2.3, p=0.24). Kaplan-Meier curves showed no significant difference in time to stopping tobacco use after first diagnosis (p=0.076). TAO subjects smoked fewer cigarettes per day than CAD subjects (TAO 22.3 ±10.7 vs CAD 27.7 ±15.3 cigarettes/day, p=0.003). Among current smokers (n=170), TAO subjects also smoked fewer cigarettes/day (20.2 ±8.2 vs 24.6 ±12.7, p=0.03), and were more likely to have made a serious attempt to stop (97% vs 90%, p=0.03). In contrast to case reports of extreme tobacco dependence in the TAO population, the degree of tobacco dependence in subjects with TAO is similar to that in subjects with CAD.

Ischemic vascular ulcerations of the upper extremities are an uncommon and frequently painful condition most often associated with scleroderma and small vessel inflammatory diseases. Digital amputation has been advocated as primary therapy because of the poor outcome with medical care. Intermittent pneumatic compression (IPC) pump therapy can improve ulcer healing in lower extremity ischemic ulcerations; however, the value of this treatment in upper extremity ischemic ulcerations is not known. This observational pilot study consisted of a consecutive series of 26 patients with 27 upper extremity ischemic vascular ulcers seen at the Mayo Gonda Vascular Center from 1996 to 2003. Inclusion criteria were documented index of ulcer size and follow-up ulcer size and use of the IPC pump as adjunctive wound treatment. Twenty-six of 27 ulcers (96%) healed with the use of the IPC pump. Mean baseline ulcer size was 1.0 cm 2 (SD=0.3 cm 2 ) and scleroderma was the underlying disease in 65% (17/26) of cases. Laser Doppler blood flow in the affected digit was 7 flux units (normal greater than 100). The mean ulcer duration before IPC treatment was 31 weeks. The average pump use was 5 hours per day. The mean time to wound healing was 25 weeks. Twenty-five of 26 patients reported an improvement in wound pain with pump use. Intensive IPC pump use is feasible and associated with a high rate of healing in upper extremity ischemic ulcers. A prospective, randomized, sham-controlled study of IPC is needed to determine whether IPC treatment improves wound healing compared to standard medical care.

Abstract Previous studies have suggested that the proinflammatory cytokine, TNF-α, contributes to airway hyperresponsivness by altering airway smooth muscle (ASM) Ca2+ responses to agonist stimulation. The present study examined the effects of TNF-α on Ca2+ influx pathways in cultured human ASM cells (HASMCs). Proteins encoded by the transient receptor potential (TRP) gene family function as channels through which receptor-operated and store-operated Ca2+ entry (SOCE) occur. In the present study, the presence of TRPC1, TRPC3, TRPC4, TRPC5, and TRPC6 mRNA and protein expression was confirmed in cultured HASMCs using RT-PCR and Western blot analysis. TNF-α treatment significantly increased TRPC3 mRNA and protein levels in HASMCs as well as SOCE. TNF-α treatment also increased both the peak and plateau intracellular Ca2+ concentration responses in HASMCs elicited by acetylcholine and bradykinin. The effects of TNF-α treatment on SOCE and agonist-induced intracellular Ca2+ concentration responses were attenuated using small interfering RNA transfection, which knocked down TRPC3 expression. Thus, in inflammatory airway diseases, TNF-α treatment may result in increased myocyte activation due to altered Ca2+ influx pathways. These results suggest that TRPC3 may be an important therapeutic target in inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.

The goal of this study was to excite and measure, in a noncontact manner, the vibrational modes of the reed from a reed organ pipe. To perform ultrasound stimulated excitation, the audio-range difference frequency between a pair of ultrasound beams produced a radiation force that induced vibrations. The resulting vibrational deflection shapes were measured with a scanning laser vibrometer. The resonances of any relatively small object can be studied in air using this technique. For a 36mm×6mm brass reed, displacements and velocities in excess of 5μm and 4mm∕s could be imparted at the fundamental frequency of 145Hz. Using the same ultrasound transducer, excitation across the entire range of audio frequencies was obtained. Since the beam was focused on the reed, ultrasound stimulated excitation eliminated background effects observed during mechanical shaker excitation, such as vibrations of clamps and supports. The results obtained using single, dual and confocal ultrasound transducers in AM and two-beam modes, along with results obtained using a mechanical shaker and audio excitation using a speaker are discussed.

ABSTRACT The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 μg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 μg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 μg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2 × 10 6 IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum ( C max )/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment ( P < 0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and C max /MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

The microtubule-binding protein tau has been implicated in the pathogenesis of Alzheimer's disease and related disorders. However, the mechanisms underlying tau-mediated neurotoxicity remain unclear. We created a genetic model of tau-related neurodegenerative disease by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila melanogaster . Transgenic flies showed key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary tangle formation that is seen in human disease and some rodent tauopathy models. This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.