Biomedical subjects
Publications and source records attributed to Christine Lee.
RIDASCREEN norovirus enzyme immunoassay (EIA) detected 80.3% of norovirus-infected feces samples compared to 60.6% by IDEIA NLV GI/GII from 228 patients with no false positives by either assay. RT-PCR and electron microscopy percent sensitivity and specificity were 98.5, 100 and 36.4 and 96.9, respectively.
MOTIVATION: Simulation and modeling is becoming a standard approach to understand complex biochemical processes. Therefore, there is a big need for software tools that allow access to diverse simulation and modeling methods as well as support for the usage of these methods. RESULTS: Here, we present COPASI, a platform-independent and user-friendly biochemical simulator that offers several unique features. We discuss numerical issues with these features; in particular, the criteria to switch between stochastic and deterministic simulation methods, hybrid deterministic-stochastic methods, and the importance of random number generator numerical resolution in stochastic simulation. AVAILABILITY: The complete software is available in binary (executable) for MS Windows, OS X, Linux (Intel) and Sun Solaris (SPARC), as well as the full source code under an open source license from http://www.copasi.org.
BACKGROUND: To date, no randomized trial to address the use of adjunctive rifampin in addition to metronidazole for the treatment of Clostridium difficile-associated diarrhea has been reported. Rifampin has excellent in vitro activity against C. difficile and penetrates into cellular materials where the organisms may persist. METHODS: This was a prospective, randomized, single-blinded study of 39 patients that compared therapy with metronidazole alone versus therapy with metronidazole and rifampin for 10 days to treat laboratory-confirmed primary episode C. difficile-associated diarrhea. Twenty patients were randomly assigned to the metronidazole group, and 19 were randomly assigned to the metronidazole and rifampin group. Data were analyzed by intention-to-treat analysis using the 2-tailed Kaplan-Meier method and the log-rank test. RESULTS: Adjunctive rifampin treatment for 10 days, compared with treatment with metronidazole alone for 10 days, was associated with a similar median time to symptom improvement (9.0 days vs. 6.5 days; P=.74), a similar median time to first relapse (26 days vs. 16 days; P=.23), a similar proportion of patients with relapse by study day 40 (42% vs. 38%; P=1.0), and a similar proportion of patients experiencing nonfatal adverse events (37% vs. 40%; P=.55). There were a significantly higher number of deaths in the metronidazole and rifampin group, compared with the metronidazole group (6 of 19 patients vs. 1 of 20 patients; P=.04), but there were fewer laboratory-confirmed relapses by study day 40 (2 vs. 4; P=.66). CONCLUSIONS: We conclude that there is no role for routine rifampin as an adjunct to treatment with metronidazole for hospitalized patients with C. difficile-associated diarrhea. The cure rates for both treatment groups remain unacceptably low, and better treatments are urgently needed.
OBJECTIVES: To describe the results of laparoscopic management of adnexal masses in women with a history of nongynecologic malignancy. METHODS: We conducted a retrospective review of 262 patients with history of prior nongynecologic malignancy who underwent laparoscopy for management of an adnexal mass between 1/1992 and 6/2004. RESULTS: Median patient age at laparoscopy was 55 years (range, 20-91 years), and median BMI was 25 kg/m2 (range, 14-41 kg/m2). Of the 262 patients, 145 (55.3%) had prior abdominal/pelvic surgery. Prior cancer history included breast (202, 77.1%), lymphoma/leukemia (16, 6.1%), colorectal (8, 3.0%), lung (7, 2.7%), multiple myeloma (5, 1.9%), head/neck (5, 1.9%), genitourinary (5, 1.9%), upper gastrointestinal (4, 1.5%), and other (10, 3.8%). Median ovarian mass diameter measured on radiologic imaging was 3.8 cm (range, 0.2-13.5 cm); median CA-125 was 17.0 U/mL (range, 1-7000 U/mL). In all, 49 (18.7%) patients had malignancy identified at laparoscopy, with 30/49 (61.2%) diagnosed with metastatic malignancy to the ovary and 19/49 (38.8%) having a new primary ovarian malignancy. Median tumor diameter and CA-125 were significantly higher in women found to have a malignancy (4.7 vs. 3.7 cm, and 35 vs. 14 U/mL, respectively). Overall, conversion to laparotomy occurred in 34 (12.9%) cases. Twenty-one of 49 (42.9%) patients with malignancy were converted to laparotomy compared with 13/213 (6.1%) when benign disease was noted (P < 0.001). CONCLUSIONS: Approximately 1 in 5 patients with a history of nongynecologic malignancy who were selected for laparoscopic management of an adnexal mass was found to have malignancy, with 60% being metastatic from other primaries. The majority of cases were managed laparoscopically even if malignancy was identified.
The human nail penetration of the antifungal ciclopirox was determined for marketed gel containing 0.77% of ciclopirox, an experimental gel containing 2% of ciclopirox, and a marketed lacquer containing 8% of ciclopirox. After 14 days dosing, unabsorbed drug remaining on the surface, drug within the infection-prone area, and the amount that had penetrated through the nail were determined. Ciclopirox delivery into and through the nail was significantly greater from the marketed gel, than from either the experimental gel or the nail lacquer (p < 0.05). In addition, the surface nail contained more unabsorbed drug from the lacquer. Further, the drug penetrating into and through the nail was also greater from the marketed gel, leading to a higher Calculated Efficacy Coefficient for the marketed gel, than from the marketed lacquer or the experimental gel. The formulation plays an important role in the enhancement of ciclopirox permeation into and through the human nail plate, and the concentration of ciclopirox in the formulation was not a factor in determining penetration.
This study determines the enhancing effects of 2-n-nonyl-1,3-dioxolane on the penetration of econazole, an antifungal drug, into the deeper layers of the human nail where fungal infection resides. Aliquots (10 microL) of Econail lacquer formulation containing 0.45 mg of [(14)C]-econazole with 18% 2-n-nonyl-1,3-dioxolane (test group) or without 2-n-nonyl-1,3-dioxolane (control group) were applied twice daily for 14 days to human nails that had been washed with ethanol before each morning's application. The hydration of the nail sample was well controlled to simulate normal physiological conditions. After 14 days of dosing, the inner ventral section of the nail plate was assayed for absorbed drug content, using a micrometer-controlled drilling and nail powder removal system. The mass balance values of [(14)C]-econazole in this study were 90.8 and 96.4% for the test and control groups, respectively. The weight-normalized econazole content in the ventral/intermediate nail plate center in the test group was 6-fold greater than that in the control (p = 0.008). The total econazole absorbed into the supporting bed cotton ball in the test group was nearly 200-fold greater than that in the control group (p = 0.008) over the 14-day period. The amount of econazole after dosing in the inner part of the human nail (potential diseased area) was 11.1 +/- 2.6 (SD) microg/mg of nail powder with 2-n-nonyl-1,3-dioxolane in the lacquer and 1.78 +/- 0.32 microg/mg without 2-n-nonyl-1,3-dioxolane (p = 0.008). The surface nail contained more econazole (p = 0.004), that is, nonabsorbed drug, where 2-n-nonyl-1,3-dioxolane was not part of the dosing solution. Econazole in the support bed under the nail (the total absorbed dose) was 47.5 +/- 22.0 mg in the lacquer with 2-n-nonyl-1,3-dioxolane and 0.2 +/- 0.1 mg in the lacquer without 2-n-nonyl-1,3-dioxolane (p = 0.008). Moreover the concentration in the deep nail layer in the test group is 14,000 times higher than minimum inhibitory concentration (MIC) believed necessary to inhibit the growth of infecting fungi (Dermatophytes species). In a subsequent study, [(14)C]-dioxolane did not penetrate the nail well. Therefore, the mechanism of enhancement of econazole penetration is at the formulation/nail interface.
Several studies have suggested that patients with Parkinson's disease (PD) have sentence comprehension difficulty in part because of their limited executive resources. However, these assessments confound the executive resources contributing to sentence comprehension with the resources needed for task performance. In the present study, we used a word detection technique that minimizes task demands in order to evaluate attentional and processing speed resources during the comprehension of simple sentences without subordinate clauses and sentences containing subject-relative and object-relative center-embedded subordinate clauses. We found that PD patients have poor sensitivity to phonetic errors embedded in unbound grammatical morphemes, regardless of the clausal structure of the sentence, suggesting difficulty attending to grammatical morphemes. We also found that PD patients are significantly slowed in their sensitivity to phonetic errors in content words embedded in object-relative center-embedded sentences. Slowed sensitivity to content words in object-relative sentences was correlated with timed executive measures of planning. On a traditional measure of comprehension, these PD patients were impaired for sentences containing object-relative center-embedded clauses compared to sentences with subject-relative center-embedded clauses, and comprehension of object-relative sentences was correlated with executive measures. Our findings are consistent with the claim that limited executive resources for strategic attention and processing speed contribute to the sentence comprehension difficulties of PD patients.
Patients with Parkinson's disease (PD) have sentence comprehension difficulty, but it is unclear whether this is due to a deficit in grammatical processing or to an executive resource limitation. To assess grammatical processing in PD while minimizing task-related demands, PD patients and healthy control subjects performed a word detection procedure that assesses sensitivity to grammatical agreements in sentences in an "on-line" fashion. With this technique, we found that control subjects and PD patients are equally sensitive to grammatical agreement violations in sentences. A traditional, resource-demanding measure of sentence comprehension was also administered to the same PD patients. In comparison to healthy controls, PD patients were significantly impaired in their relative comprehension of sentences containing object-gap subordinate clauses compared to subject-gap subordinate clauses. Performance on several executive resource measures was also impaired in PD, and this correlated with their comprehension performance. Sensitivity to grammatical agreements with the word detection procedure, in the context of sentence comprehension difficulty on a traditional measure, suggests that PD patients' executive resource limitations contribute to their sentence comprehension difficulty.
This study tests the hypothesis that sentence comprehension difficulty in Parkinson's disease (PD) is related in part to altered information processing speed that plays a crucial role in grammatical processing. The authors measured information processing speed in 32 PD patients without dementia using a lexical list-priming paradigm in which the interstimulus interval (ISI) between the prime and the target varied. Sentence comprehension accuracy was also assessed in 22 of these patients. Sentence comprehension accuracy for object-relative center-embedded sentences was impaired in a subgroup of PD patients. This subgroup of PD patients primed at an abnormally long ISI. Similarly, only PD patients who primed at a long ISI had greater difficulty understanding sentences with an object-relative clause than a subject-relative clause. Findings suggest that slowed information processing speed contributes to sentence comprehension difficulty in PD.
Studies in previously treated patients (PTPs) have been conducted for the three recombinant factor VIII (rFVIII) concentrates currently licensed. Kogenate, has shown a recovery of 2.7% per IU/kg and a half-life of 15.8 hours. A prospective 5-year study in 58 patients showed that 82% of bleeds resolved with one treatment; the average dose was 25 IU/kg. For Recombinate, the recovery was 2.4% per IU/kg and the half-life was 14.7 hours. In 69 patients, the average dose used to treat a bleed was 27.5 IU/kg, and 91% of responses were categorized as good or excellent. B-domain depleted rFVIII, Refacto, has shown a recovery of 2.7% per IU/kg and a half-life of 14 hours. In 113 PTPs, the average dose used was 29.5 IU/kg, and 71% of bleeds responded to one treatment. All three recombinant products have been shown to be safe and effective in very similar dosing regimens. In view of the good recoveries, it is probable that smaller doses, such as 20 IU/kg, could be recommended to treat a bleed effectively with one dose, given that dosing regimens were previously established using intermediate products. Clearly, this would have considerable financial advantages.
BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.
BACKGROUND: Factors predictive of death at South Australian major trauma services were investigated among 8,654 patients who had experienced severe trauma from 1997 to 2000. METHOD: Univariate and multivariate analyses of age, sex, injury severity, presence of comorbid conditions, and calendar year of presentation were performed. RESULTS: Multiple logistic regression indicated that factors predictive of death were older age; higher injury severity as indicated by the New Injury Severity Score and the Revised Trauma Score; and accompanying chronic liver disease, ischemic heart disease, and chronic renal failure. A decrease in risk of death by calendar year was statistically significant (p = 0.001). Using 1997 as the reference, the relative odds of death were 0.86 (95% confidence limits) (0.53, 1.39) for 1998, 0.60 (0.36, 0.99) for 1999, and 0.45 (0.27, 0.76) for 2000. CONCLUSION: Results show a decrease in risk of death of patients attending South Australian major trauma services, from injuries of equivalent severity, during the first 4 years of operation of the State Trauma System.
We sought to quantify the fractal scaling properties of human respiratory dynamics and determine whether they are altered with healthy aging and gender. Continuous respiratory datasets (obtained by inductive plethysmography) were collected from 40 healthy adults (10 young men, 10 young women, 10 elderly men, and 10 elderly women) during 120 min of spontaneous breathing. The interbreath interval (IBI) time series were extracted by a new algorithm and fractal scaling exponents that quantify power-law correlations were computed using detrended fluctuation analysis. Under supine, resting, and spontaneous breathing conditions, both healthy young and elderly subjects had scaling exponents for the IBI time series that indicate long-range (fractal) correlations across multiple time scales. Furthermore, the scaling exponents (mean +/- SD) for the IBI time series were significantly (p < 0.03) lower (indicating decreased correlations) in the healthy elderly male (0.60 +/- 0.08) compared to the young male (0.68 +/- 0.07), young female (0.70 +/- 0.07), and elderly female (0.67 +/- 0.06) subjects. These results provide evidence for fractal organization in physiologic human breathing cycle dynamics, and for their degradation in elderly men. These findings may have implications for modeling integrated respiratory control mechanisms, quantifying their changes in aging or disease, and assessing the outcome of interventions aimed toward restoring normal physiologic respiratory dynamics.