Medical University of South Carolina

About: Medical University of South Carolina is a education organization based out in Charleston, South Carolina, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23436 authors who have published 45440 publications receiving 1769397 citations. The organization is also known as: MUSC & Medical College of the State of South Carolina.

Effect of St John's Wort on Drug Metabolism by Induction of Cytochrome P450 3A4 Enzyme

Abstract: ContextSt John's wort is a popular herbal product used to treat depression but it has been implicated in drug interactions.ObjectiveTo assess the potential of St John's wort administration to alter the activity of the cytochrome P450 (CYP) enzymes extensively involved in drug metabolism.Design, Setting, and ParticipantsOpen-label crossover study with fixed treatment order conducted March 2002 to February 2003 in a US general clinical research center involving 12 healthy volunteers (6 men and 6 women) aged 22 to 38 years before and after 14 days of administration of St John's wort.InterventionParticipants were given probe drugs (30 mg of dextromethorphan and 2 mg of alprazolam) to establish baseline CYP 3A4 and CYP 2D6 activity. After a minimum 7-day washout period, participants began taking one 300-mg tablet 3 times per day. After 14 days of St John's wort administration, participants were given the probe drugs along with 1 St John's wort tablet to establish postadministration CYP activity; the St John's wort dosing regimen was continued for 48 hours.Main Outcome MeasuresChanges in plasma pharmacokinetics of alprazolam as a probe for CYP 3A4 activity and the ratio of dextromethorphan to its metabolite, dextrorphan, in urine as a probe for CYP 2D6 activity.ResultsA 2-fold decrease in the area under the curve for alprazolam plasma concentration vs time (P<.001) and a 2-fold increase in alprazolam clearance (P<.001) were observed following St John's wort administration. Alprazolam elimination half-life was shortened from a mean (SD) of 12.4 (3.9) hours to 6.0 (2.4) hours (P<.001). The mean (SD) urinary ratio of dextromethorphan to its metabolite was 0.006 (0.010) at baseline and 0.014 (0.025) after St John's wort administration (P = .26).ConclusionsA 14-day course of St John's wort administration significantly induced the activity of CYP 3A4 as measured by changes in alprazolam pharmacokinetics. This suggests that long-term administration of St John's wort may result in diminished clinical effectiveness or increased dosage requirements for all CYP 3A4 substrates, which represent at least 50% of all marketed medications.

Low birth weights contribute to the high rates of early-onset chronic renal failure in the Southeastern United States

Abstract: Background The southeastern United States is a region in which rates of cardiovascular and renal diseases are excessive. Within the Southeast, South Carolina has unusually high rates of end-stage renal disease (ESRD) in young people, with more than 70% of cases attributed to hypertension and diabetes. Objective To determine whether the increased vulnerability to early-onset ESRD might originate through impaired renal development in utero as measured by low birth weight. Methods Patients who were diagnosed with renal failure and undergoing dialysis from 1991 through 1996 were identified from the ESRD registry maintained by the Southeastern Kidney Council, Raleigh, NC. Birth weights reported on birth certificates were selected for the ESRD cases and non-ESRD controls who were born in South Carolina in 1950 and later. Birth weights were compared for 1230 cases and 2460 controls who were matched for age, sex, and race. Results Low birth weight was associated with ESRD among men and women as well as blacks and whites. Among people whose birth weight was less than 2.5 kg, the odds ratio for ESRD was 1.4 (95% confidence interval, 1.1-1.8) compared with people who weighed 3 to 3.5 kg. This association was present for renal failure resulting from diabetes, hypertension, and other causes. Conclusions Low birth weights, which reflect adverse effects on development in utero, contribute to the early onset of ESRD in South Carolina. Since low birth weight increases the risk of ESRD from multiple causes, the data suggest that an adverse environment in utero impairs kidney development and makes it more vulnerable to damage from a range of pathological processes.

Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials

Abstract: Who would have guessed that a scale introduced by Dr John Rankin in 1957 would become the primary outcome scale for almost all acute stroke trials?1 The Rankin Scale was modified to its current form by Charles Warlow and others as part of the UK-TIA (United Kingdom Transient Ischaemic Attack) trial in the 1980s,2 and its reproducibility was first examined by van Swieten et al, in 1988 (Table 1).3 View this table: Table 1. The Modified Rankin Scale (mRS) There is no perfect stroke outcome scale. Regardless, the 7-level, modified Rankin Scale (mRS) has several major strengths: it covers the entire range of functional outcomes from no symptoms to death, its categories are intuitive and easily grasped by both clinicians and patients, its concurrent validity is demonstrated by strong correlation with measures of stroke pathology (eg, infarct volumes) and agreement with other stroke scales,4 and its use has demarcated effective and ineffective acute stroke therapies in trials with appropriately powered sample sizes. With a limited number of levels, the mRS may be less responsive to change than some other stroke scales; however, a single-point change on the mRS is clinically relevant.4 A limitation of the mRS has been the subjective determination between categories and the reproducibility of the score by examiners and patients.4 A systematic review and meta-analysis of studies describing interobserver variability of the mRS reports pooled reliability across 10 published studies (n=587 patients) of a κ=0.46 and a weighted κ of 0.90.5 Multimedia training and certification of examiners in the use of the mRS (http://rankinscale.org/), structured interviews and questionnaires,6–10 and centralized review of videotape assessments11 have sought to address these issues, but reproducibility remains a concern. But the challenge for a trialist designing a new acute stroke trial is not whether …