Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

Background  

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process.     

The RANTES promoter polymorphism: a genetic risk factor for near-fatal asthma in Chinese children

BACKGROUND: RANTES promoter polymorphisms were found associated with asthma/atopy in some studies but not others, possibly reflecting the genetic heterogeneity among different ethnicities and different asthma severity. OBJECTIVE: The purpose of this investigation was to test the genetic association between the RANTES -28C/G and -403G/A polymorphisms and asthma/atopy in a cohort of Chinese children, with particular emphasis on those patients who had experienced life-threatening asthma attacks. METHODS: Forty-eight children with near-fatal asthma, 134 children with mild-to-moderate asthma, 69 children with allergic disorders but no asthma, and 107 nonasthmatic nonatopic control children were genotyped through use of a PCR-based assay. RESULTS: No significant difference was demonstrated for frequency of the RANTES -28C/G polymorphism when the mild-to-moderate asthma, atopic/nonasthmatic, and normal control groups were compared. The RANTES -28G allele was present in a significantly higher proportion of the children with near-fatal asthma compared with the nonasthmatic nonatopic controls (odds ratio, 2.93 [1.41-6.06]; P =.006) and the children with mild-to-moderate asthma (odds ratio, 3.52 [1.73-7.16]; P =.001). The frequency of -28G allele carriage correlated with asthma severity. The RANTES -28G allele was also associated with an increased blood eosinophil count and a higher degree of bronchial hyperresponsiveness. The RANTES -403G/A polymorphism did not influence asthma/atopy susceptibility, blood eosinophil count, or bronchial hyperresponsiveness. Interestingly, a higher frequency of -403A allele carriage was observed in the moderate asthma subgroup compared with the mild asthma analog. CONCLUSIONS: We conclude that the RANTES -28C/G polymorphism exacerbates asthma severity, representing a genetic risk factor for life-threatening asthma attacks in Chinese children. In addition, the linkage disequilibrium between these 2 polymorphisms is a potential confounder that must be considered in the design and interpretation of RANTES gene association studies.     

Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.

BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.     

Clinical features and risk factors for mortality in Aeromonas bacteremic adults with hematologic malignancies.

BACKGROUND AND PURPOSE: Aeromonas spp. often cause infections in immunocompromised patients. To specifically understand the clinical features of Aeromonas bacteremic adults with hematologic malignancies, we investigated the demographic, clinical and microbiologic characteristics of Aeromonas bacteremia in this patient population. METHODS: Retrospective study performed in a tertiary medical center in southern Taiwan, in which adults with hematologic malignancies suffered from Aeromonas bacteremia admitted between 1995 and 2003 were included for study. RESULTS: There were 45 episodes of Aeromonas bacteremia in 41 adults with hematologic malignancies. Episodes of Aeromonas bacteremia which occurred at least 2 months apart were counted as separate cases in the analysis. A total of 30 men and 15 women (mean age: 53.2 years), with 4 patients experiencing 2 episodes, was included. The 3 leading underlying hematologic malignancies were acute myelogenous leukemia (37.8%), myelodysplastic syndrome (26.7%) and non-Hodgkin's lymphoma (17.8%). No cluster of Aeromonas bacteremia was found during the study period. Twenty nine (64.4%) of the 31 patients with nosocomial Aeromonas bacteremia had received recent antineoplastic chemotherapy. The 3 leading clinical manifestations were fever (88.9%), septic shock (40%), and altered consciousness (26.7%). Eleven (24.4%) episodes of bacteremia were polymicrobial. Sixteen (35.6%) patients died within 14 days of onset of bacteremia. The mean duration from sampling blood for culture to death was 3.81 days. Altered consciousness (odds ratio, 8.999; 95% confidence interval, 1.787-45.33; p=0.008) was the only independent prognostic factor for mortality. High resistance rates (11.1% to piperacillin and 35.6% to imipenem) among Aeromonas isolates were also noted. CONCLUSION: In febrile patients with hematologic malignancies and suspected Aeromonas infections, particular attention to the development of alteration of consciousness is needed as it is an independent risk factor for mortality.     

Persistent monocytosis after intravenous immunoglobulin therapy correlated with the development of coronary artery lesions in patients with Kawasaki disease.

BACKGROUND AND PURPOSE: This study was conducted to investigate whether changes in the complete blood count (CBC)/differential count (DC) and C-reactive protein (CRP) were correlated to Kawasaki disease (KD) with coronary artery lesions (CALs). METHODS: A retrospective analysis was performed of all children with KD at Chang Gung Memorial Hospital at Kaohsiung from 2001 to 2006. KD patients were divided into those with and without CALs for testing of correlations with changes in CBC/DC and CRP levels. RESULTS: A total of 147 patients were enrolled for this analysis. Serial CBC/DC and CRP measurements and echocardiographic data for determination of CAL formation were obtained before and after intravenous immunoglobulin (IVIG) treatment. There were 44 (29%) KD patients having CAL formation (>3 mm in diameter of internal lumen). There was no significant difference in terms of age distribution and major diagnostic criteria between KD patients with and without CALs. Male KD patients, however, had a significantly higher rate of CAL formation (p=0.009). In multivariate logistical regression analysis, persistent monocytosis after IVIG treatment was the only factor significantly correlated to CAL formation (p=0.003). CONCLUSIONS: Of the febrile routine measurements of CBC/DC and CRP in KD, persistent monocytosis after IVIG treatment was correlated to CAL formation. Further studies to clarify the mechanism of monocytosis may help prevent the CALs of KD.     

Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous infusion

Based on the tail-flick response to noxious thermal stimuli, we determined in the present study that effective antinociception could be achieved in adult male Sprague-Dawley rats 15 min after intravenous infusion of propofol at 60 mg/kg/h. Simultaneous power spectral analysis of the electroencephalographic (EEG) and systemic arterial pressure signals further revealed a concomitant depression of the activity of all EEG frequency bands (δ, θ, , β), alongside hypotension, negative inotropic and chronotropic actions, and attenuated baroreceptor reflex and vasomotor activity. These effects were congruent with a plasma concentration of propofol in the arterial blood of 1.70 ± 0.13 μg/ml, as determined by high-performance liquid chromatography.     

Detecting pre-ovulatory luteinizing hormone surges in urine

The study objectives were to determine (i) if pre-ovulatory luteinizing hormone (LH) surges, undetected in urine by two immunoradiometric assays (IRMA), were detectable by an ultrasensitive immunofluorometric assay (IFMA) and (ii) the influence of creatinine adjustment on the detection and timing of the urinary LH surges. Daily urine specimens were contributed by healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for an epidemiological study conducted in 1983-1985. Specimens were selected as having been previously assayed by two IRMA without consistently detecting LH surges. These urine specimens were remeasured using an IFMA and adjusted for creatinine concentration. IFMA measurements revealed unambiguous LH surges in all cycles. Adjusting IRMA urinary LH values for creatinine concentrations revealed previously undetected LH surges in four of eight cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH surges by 1-5 days. These results demonstrate an IFMA that detects pre- ovulatory LH surges in unpreserved, frozen urine from cycles where such surges were previously undetectable. Further, creatinine adjustment can markedly affect detection and timing of the onset and peak of the urinary LH surge. While our analysis suggests that this adjustment improves the validity of the LH measure, this requires further investigation.