Trends in incidence and clinical presentation of temporal arteritis in Olmsted County, Minnesota, 1950-1985

Ninety-four Olmsted County, Minnesota residents with temporal arteritis (TA) initially diagnosed between 1950 and 1985 (incidence cohort) were identified. The age- and sex-adjusted incidence of TA per 100,000 population age 50 years or older was 17.0 (95% confidence interval [CI] 13.6-20.5), with a marked increase in incidence with age and a threefold greater incidence in women (23.4, 95% CI 18.2-28.7) than in men (7.4, 95% CI 3.7-11.0). The previously described secular increase in TA incidence in Olmsted County women continued from 1970 through 1985, while TA incidence in men declined in this latter time period. Although the frequency of classic clinical manifestations of TA declined over time, the percentage of patients undergoing biopsy who have positive specimens remained relatively constant (women 41%, men 26%). The incidence rate of temporal artery biopsy also increased for women during this period, but declined for men, suggesting that the differing trends in TA incidence by sex may be partially attributable to a detection bias. Future research in TA etiology and epidemiology should focus on possible causal factors linked to the differential TA incidence by sex.     

Assessment of bronchodilator response to a beta-adrenergic delivered from an ultrasonic nebulizer

We assessed the bronchodilator response to a recently available ultrasonic nebulizer (USN) in a population of 17 stable asthmatic patients. These patients were also evaluated for bronchodilator response to two other aerosol delivery systems routinely used in standard clinical practice, the metered-dose inhaler (MDI) and the jet nebulizer (JN). Albuterol was administered from each of the delivery systems in the following manner: MDI, two actuations (180 micrograms); JN, 0.5 ml of 0.5 percent solution (2.5 mg) in 1.0 ml saline solution diluent; and USN, 0.5 ml of 0.5 percent solution (2.5 mg) in 2.5 ml saline solution diluent. Patients demonstrated significant bronchodilator responses to all three delivery systems (p less than 0.0001). The USN produced a greater percentage of increase in FEV1 15 minutes after treatment with albuterol (35.8 +/- 2.3 percent) than either the MDI (18.2 +/- 3.4 percent) or JN (20.8 +/- 3.1 percent) (p less than 0.005). The mean percentage of increase in FE1 observed over a 4-h period after treatment was also greater for the USN (26.5 +/- 2.5 percent) than either the MDI (18.8 +/- 1.8 percent) or JN (15.0 +/- 1.6 percent) (p less than 0.001). We conclude that the USN yields effective bronchodilation in a population of stable asthmatics.     

Azithromycin protects against hyperoxic lung injury in neonatal rats.

Bronchopulmonary dysplasia (BPD) is a pulmonary disorder that causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis, and mucosal necrosis, which leads to emphysematous coalescence of alveoli. We tested the hypothesis that azithromycin, a macrolide antibiotic, would decrease the severity of lung injury in an animal model of BPD. Sixty-three rat pups were randomly divided equally into control, hyperoxia, and hyperoxia plus azithromycin groups. The hyperoxia groups were exposed to > 95% oxygen from days of life 4 to 14. On day 14, the animals were processed for lung histology and tissue analysis. Lung morphology was assessed by mean linear intercept, a measure of alveolar size, with larger values corresponding to lungs that are more emphysematous. The degree of lung inflammation was assessed by quantifying interleukin-6 (IL-6) from lung homogenate. Fifty pups survived to day 14 (control = 21, hyperoxia = 11, hyperoxia + azithromycin = 18). Mortality was increased in the hyperoxia group versus the control group (p < .0001). Treatment with azithromycin improved survival in animals subjected to hyperoxia (p < .05). Azithromycin significantly decreased lung damage as determined by the mean linear intercept in the hyperoxia groups (p < .001). Finally, azithromycin-treated pups had lower levels of IL-6 in lung homogenate from the hyperoxia groups (p < .05). Azithromycin treatment resulted in improved survival, less emphysematous change, and decreased IL-6 levels in an animal model of BPD.     

Patients' recollections of therapeutic paralysis in the intensive care unit.

BACKGROUND: Neuromuscular blocking agents used for therapeutic purposes, such as facilitating mechanical ventilation and relieving life-threatening agitation, paralyze patients but leave them fully conscious. Aggressive sedation or analgesia is necessary to reduce awareness, relieve fear, produce comfort, decrease anxiety, induce unconsciousness, and minimize possible complications such as posttraumatic stress syndrome. Little information is available on the extent to which patients experience awareness during therapeutic paralysis. OBJECTIVES: To determine and describe the remembered experiences of critical care patients who were given neuromuscular blocking agents and sedatives and/or analgesics to facilitate mechanical ventilation, improve hemodynamic stability, and improve oxygenation. METHODS: A phenomenological approach with in-depth interviews with 11 patients was used. Data were analyzed by using the constant comparative approach. RESULTS: A total of 4 themes and 3 subthemes were identified. The first theme was back and forth between reality and the unreal, between life and death; the subtheme was having weird dreams. The second theme was loss of control; the 2 subthemes were (1) fighting or being tied down and (2) being scared. The third theme was almost dying, and the fourth theme was feeling cared for. CONCLUSIONS: Patients can remember having both negative and positive experiences during neuromuscular blockade. Steps to improve the experiences of patients receiving neuromuscular blockers include improving assessment parameters, developing and using sedation/analgesia guidelines, and investing in quality improvement programs to provide assessment of awareness during therapeutic paralysis and follow-up and referral as necessary. Ways to decrease the use of neuromuscular blockers would also be useful.     

Low urethral pressure and stress urinary incontinence in women: risk factor for failed retropubic surgical procedure

Nineteen women with stress urinary incontinence (SUI) and low urethral pressure were compared with 106 patients with SUI and normal urethral pressure. All underwent either a revised Pereyra procedure or Burch retropubic urethropexy, and all had detailed clinical and urodynamic evaluations before their operation and one year postoperatively. Surgical procedures effectively stabilized the bladder base and enabled adequate abdominal pressure transmission to the urethra in both groups of women. In spite of these urodynamic findings, the failure rate in women with stress urinary incontinence and low urethral pressure was significantly higher compared with women with good urethral pressure (50% vs 23% for the Pereyra procedure and 33% vs 12% for the Burch procedure [p less than 0.05]), indicating an etiology for their incontinence other than poor support to the urethrovesical junction; therefore, the need for another approach to cure stress incontinence.     

AIDS/HIV Education for Preservice Elementary Teachers

Professional preparation programs should provide future elementary teachers opportunities to develop competence in dealing with school-related AIDS issues. Curriculum writers and instructors of preservice elementary teachers could be more effective if they were aware of this groups' beliefs about school-related AIDS issues. A survey was conducted to assess the beliefs and opinions of preservice elementary teachers about school-related AIDS issues. Subjects (n = 157) generally agreed they would eventually have a child with AIDS in their classroom and agreed AIDS education should be included in the elementary grades, yet a substantial number did not believe they understood the basics about AIDS. Less than one-third indicated they knew how to clean up blood or body fluids safely. About one-third indicated they would feel personally threatened to teach a student with AIDS. These results are reflected in recommended AIDS educational content and resources for preservice elementary teachers and future research in this area.     

Hematological Complications of Alcoholism

Numerous clinical observations support the notion that ethanol has multiple pathologic effects on hematopoietic tissue. The effects of alcohol on blood are diverse. The long-term ingestion of large quantities of ethanol has been shown to alter a substantial number of physiologic and biochemical variables. Abnormalities involving leukocytes, platelets, and erythrocytes may occur singly or in various combinations. Due to the frequent concomitant presence of alcohol-related hepatic disease, nutritional deficiencies, infection, and other chronic diseases, it is often difficult to distinguish the specific hematologic toxicities of alcohol ingestion from the hematologic toxicities of associated morbid conditions. Depressed hematopoietic cell formation (Table 2), increased destruction, and alterations in morphology and function of hematopoietic cells have been described.     

Detection of Legionella pneumophila using a real-time PCR hybridization assay

A real-time PCR hybridization assay for Legionella pneumophila is described; the assay uses LightCycler (Idaho Technology) methodology to specifically detect 2.5 CFU/reaction, equivalent to 1,000 CFU/liter of starting water sample. The assay, including DNA extraction and confirmation of product identity, is completed within 90 min of receipt of a sample.     

Mutational analysis of the enzymatic domain of Clostridium difficile toxin B reveals novel inhibitors of the wild-type toxin

Toxin B (TcdB), a major Clostridium difficile virulence factor, glucosylates and inactivates the small GTP-binding proteins Rho, Rac, and Cdc42. In the present study we provide evidence that enzymatically inactive fragments of the TcdB enzymatic domain are effective intracellular inhibitors of native TcdB. Site-directed and deletion mutants of the TcdB enzymatic region (residues 1 to 556), lacking receptor binding and cell entry domains, were analyzed for attenuation of glucosyltransferase and glucosylhydrolase activity. Five of six derivatives from TcdB(1-556) were found to be devoid of enzymatic activity. In order to facilitate cell entry, mutants were genetically fused to lfn, which encodes the protective antigen binding region of anthrax toxin lethal factor and mediates the cell entry of heterologous proteins. In line with reduced enzymatic activity, the mutants also lacked cytotoxicity. Remarkably, pretreatment or cotreatment of cells with four of the mutants provided protection against the cytotoxic effects of native TcdB. Furthermore, a CHO cell line expressing enzymatically active TcdB(1-556) was also protected by the mutant-derived inhibitors, suggesting that inhibition occurred at an intracellular location. Protection also was afforded by the inhibitor to cells treated with Clostridium sordellii lethal toxin (TcsL), which uses the same cosubstrate as TcdB but shares Rac only as a common substrate target. Finally, the inhibitor did not provide protection against Clostridium novyi alpha-toxin (Tcnalpha), which shares similar substrates with TcdB yet uses a different cosubstrate. This is the first report to demonstrate that the potential exists to inhibit toxins at their intracellular site of action by using inactive mutants.