Biomedical subjects

Lakshmi Durairaj

Publications and source records attributed to Lakshmi Durairaj.

7 recordsLinked to original sources

PubMed2006

Safety assessment of inhaled xylitol in subjects with cystic fibrosis.

BACKGROUND: Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in subjects with cystic fibrosis. METHODS: In this pilot study, 6 subjects with cystic fibrosis and an FEV1>60% predicted underwent a baseline spirometry followed by exposures to aerosolized saline (10 ml) and 5% xylitol (10 ml). Serum osmolarity and electrolytes were measured at baseline and after xylitol exposure. Spirometry, oxygen saturation and respiratory symptom questionnaire using visual analog scale were tested at baseline and after each exposure. Sputum for cytokine analysis was collected after saline and xylitol nebulizations. RESULTS: There was no change in FEV1 after xylitol exposure compared with baseline or normal saline exposure (p=0.19). Laboratory values and respiratory symptoms were not affected by xylitol inhalation. The mean IL-8 level in the sputum was similar with saline and xylitol exposures (3.5+/-0.5 vs. 3.5+/-0.6 ng/ml). CONCLUSIONS: A single dose inhalation of aerosolized iso-osmotic xylitol was well tolerated by subjects with cystic fibrosis. Future studies of long term safety are required.

Adjuvants, Immunologic↗

PubMed2006

Bronchoscopic assessment of airway retention time of aerosolized xylitol.

BACKGROUND: Human airway surface liquid (ASL) has abundant antimicrobial peptides whose potency increases as the salt concentration decreases. Xylitol is a 5-carbon sugar that has the ability to lower ASL salt concentration, potentially enhancing innate immunity. Xylitol was detected for 8 hours in the ASL after application in airway epithelium in vitro. We tested the airway retention time of aerosolized iso-osmotic xylitol in healthy volunteers. METHODS: After a screening spirometry, volunteers received 10 ml of nebulized 5% xylitol. Bronchoscopy was done at 20 minutes (n = 6), 90 minutes (n = 6), and 3 hours (n = 5) after nebulization and ASL was collected using microsampling probes, followed by bronchoalveolar lavage (BAL). Xylitol concentration was measured by nuclear magnetic resonance spectroscopy and corrected for dilution using urea concentration. RESULTS: All subjects tolerated nebulization and bronchoscopy well. Mean ASL volume recovered from the probes was 49 +/- 23 microl. The mean ASL xylitol concentration at 20, 90, and 180 minutes was 1.6 +/- 1.9 microg/microl, 0.6 +/- 0.6 microg/microl, and 0.1 +/- 0.1 microg/microl, respectively. Corresponding BAL concentration corrected for dilution was consistently lower at all time points. The terminal half-life of aerosolized xylitol obtained by the probes was 45 minutes with a mean residence time of 65 minutes in ASL. Corresponding BAL values were 36 and 50 minutes, respectively. CONCLUSION: After a single dose nebulization, xylitol was detected in ASL for 3 hours, which was shorter than our in vitro measurement. The microsampling probe performed superior to BAL when sampling bronchial ASL.

Adult↗

PubMed2005

Hospital volume-outcome relationships among medical admissions to ICUs.

BACKGROUND: Positive relationships between hospital volume and outcomes have been demonstrated for several surgeries and medical conditions. However, little is known about the volume-outcome relationship in patients admitted to medical ICUs. OBJECTIVE: To determine the relationship between hospital volume and risk-adjusted in-hospital mortality for patients admitted to ICUs with respiratory, neurologic, and GI disorders. DESIGN: Retrospective cohort study. SETTING: Twenty-nine hospitals in a single metropolitan area. PATIENTS: Adult ICU admissions from 1991 through 1997. METHODS: Using Cox proportional hazards models, we compared in-hospital mortality between tertiles of hospital volume (high, medium, and low) for respiratory (n = 16,949), neurologic (n = 13,805), and GI (n = 12,881) diseases after adjusting for age, gender, admission severity of illness, admitting diagnosis, and source. Severity of illness was measured using the APACHE (acute physiology and chronic health evaluation) III methodology. RESULTS: Among respiratory and neurologic ICU admissions, hazard ratios were similar (p > or = 0.05) in patients in low-, medium-, and high-volume hospitals. However, among GI diagnoses, risk of mortality was lower in high-volume hospitals, relative to low-volume hospitals (hazard ratio, 0.68; 95% confidence interval [CI], 0.54 to 0.85; p < 0.001), and was somewhat lower in medium-volume hospitals (hazard ratio, 0.83; 95% CI, 0.68 to 1.01; p = 0.06). Among subgroups based on severity of illness, high-volume hospitals had lower mortality, relative to low-volume hospitals, among sicker patients (APACHE III score > 57) in the respiratory cohort (hazard ratio, 0.77; 95% CI, 0.59 to 0.99) and the GI cohort (hazard ratio, 0.67; 95% CI, 0.53 to 0.85). CONCLUSIONS: Associations between ICU volume and risk-adjusted mortality were significant for patients with GI diagnoses and for sicker patients with respiratory diagnoses. However, associations were not significant for patients with neurologic diagnoses. The lack of a consistent volume-outcome relationship may reflect unmeasured patient complexity in higher-volume hospitals, relative standardization of care across ICUs, or lack of efficacy of some accepted ICU processes of care.

APACHE↗

PubMed2004

Safety assessment of inhaled xylitol in mice and healthy volunteers.

BACKGROUND: Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. METHODS: This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. RESULTS: In naive mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naive and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were below the detection limits after xylitol exposure in normal volunteers. CONCLUSIONS: Inhalation of aerosolized iso-osmotic xylitol was well-tolerated by naive and atopic mice, and by healthy human volunteers.

Administration, Inhalation↗

PubMed2003

Prognostic factors for mortality following interhospital transfers to the medical intensive care unit of a tertiary referral center.

OBJECTIVE: To describe characteristics of patients transferred from outside hospitals to a tertiary medical intensive care unit and to identify patient-level and system-level prognostic factors. DESIGN: Retrospective cohort study. SETTING: Tertiary university hospital. PATIENTS: We studied 3,347 patients who were transferred to the medical intensive care unit from outside hospitals from January 1990 through September 1999. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data collected included patient demographics, insurance type, discharge diagnoses, length of stay, mortality, admitting service, and distance traveled. The Charlson Comorbidity Score was used to adjust for comorbidity and the diagnostic related group risk level for risk of adverse outcome. Multivariate logistic models of early mortality (<72 hrs) and overall hospital mortality rate were developed. The most common major diagnostic categories included neurologic (10%), respiratory (10%), digestive diseases (10%), and drug overdose (10%). Most patients (70%) were transferred from >60 miles away. Mean medical intensive care unit length of stay was 5.3 days vs. 3.9 days for nontransfer patients. Transfer patients accounted for 49% of medical intensive care unit admits and 56% of intensive care unit patient-days. The overall mortality rate for transfer patients to the medical intensive care unit was 25% (95% confidence interval, 23-26), significantly higher than the 21% (95% confidence interval, 19-22) mortality rate among those admitted directly. Independent prognostic factors for early death (<72 hrs) included male gender, summer season, admitting service, diagnostic related group level, Charlson Comorbidity Score, insurance type, and major diagnostic category. Independent prognostic factors for overall hospital mortality rate included length of stay, medical complication, distance traveled, insurance type, and major diagnostic category. CONCLUSIONS: Interhospital transfers to the medical intensive care unit are patients at high risk for mortality and other adverse outcomes. System-level and patient-level characteristics influence both early and overall hospital mortality rates. These variables should be considered when risk stratifying medical intensive care unit patients and in studying outcomes of care.

Adult↗

PubMed2002

Antibiotic resistance: a survey of physician perceptions.

BACKGROUND: Antibiotic resistance is caused partly by excessive antibiotic prescribing, yet little is known about prescribers' views on this problem. METHODS: We surveyed 490 internal medicine physicians at 4 Chicago-area hospitals to assess their attitudes about the importance of antibiotic resistance, knowledge of its prevalence, self-reported experience with antibiotic resistance, beliefs about its causes, and attitudes about interventions designed to address the problem. RESULTS: The response rate was 87% (424 of 490 physicians). Antibiotic resistance was perceived as a very important national problem by 87% of the respondents, but only 55% rated the problem as very important at their own hospitals. Nearly all physicians (97%) believed that widespread and inappropriate antibiotic use were important causes of resistance. Yet, only 60% favored restricting use of broad-spectrum antibiotics, although this percentage varied by hospital and physician group. CONCLUSIONS: Although most physicians view antibiotic resistance as a serious national problem, perceptions about its local importance, its causes, and possible solutions vary more widely. Disparities in physician knowledge, beliefs, and attitudes may compromise efforts to improve antibiotic prescribing and infection control practices.

Anti-Bacterial Agents↗

PubMed2002

Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial.

BACKGROUND: The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed. We have investigated this question in a randomised, double-blind, controlled trial. METHODS: Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g). All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer. The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater. Analysis was by intention to treat. FINDINGS: The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited. On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 [95% CI -0.20 to 0.26], p=0.8). 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% [-10% to 9%], p>0.9). There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group. Most patients (81%) reported benefit from the albuterol inhaler. INTERPRETATION: Azithromycin is no better than low-dose vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder.

Acute Disease↗