A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease.

BACKGROUND: The relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown. AIM: To validate associations reported in previous studies and to identify novel environmental exposures among PSC patients. METHODS: We performed a multicenter, case-control analysis utilising self-administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259). RESULTS: Smoking was associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4-0.7) but not among those PSC patients without IBD (OR, 0.9; 95% CI 0.7-1.2). Compared to controls, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT; OR, 0.5; 95% CI 0.4-0.7) and were more likely to have recurrent urinary tract infections (OR, 1.6; 95% CI 1.2-2.3). PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3-0.6) and grilled/barbecued meat (OR, 0.8; 95% CI 0.7-0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well done (OR, 1.3; 95% CI 1.2-1.5). CONCLUSIONS: IBD (rather than PSC) is associated with smoking. Women with PSC are more likely to have recurrent urinary tract infections and less likely to receive HRT. Dietary intake and methods of food preparation differ in PSC patients when compared to controls.

Altered first-pass effects in a liver transplant recipient explained intraindividual variation in calcineurin inhibitor concentrations: a case report.

BACKGROUND: The significant interindividual and intraindividual variability in the blood concentrations of the most commonly used calcineurin inhibitors such as tacrolimus and cyclosporine makes the exact dosing of these agents in transplant recipients very challenging. As both of these drugs have narrow therapeutic index and are metabolized by hepatic and intestinal cytochrome P450 3A, we tested the hypothesis that these variations are secondary to varying first-pass effects in the gut and the liver over a period of time. CASE REPORT: A liver transplant recipient, who had previously presented with tacrolimus toxicity on his usual dosing regimen and intolerant to standard doses of cyclosporine, was selected to undergo the study. Oral and intravenous midazolam was used as the probe to measure hepatic and intestinal CYP3A4 activities at two different time points (phases one and two). Small intestinal biopsies were also obtained for measuring CYP3A4 activity for in vitro studies. On serially determining the patient's hepatic and intestinal CYP3A activities, we concluded that the variability in the dosing requirements is due to altered first-pass effects in the intestine. DISCUSSION: Transplant recipients receive multiple medications that may inhibit or induce these metabolizing enzymes, which eventually determine the concentrations of these narrow therapeutic agents. If no obvious etiology of intolerance to calcineurin inhibitors in a transplant recipient is identified, one should consider altered first-pass effects in the gut and the liver contributing to intraindividual variations in the blood concentrations.

Clinical utility of blood cultures in adult patients with community-acquired pneumonia without defined underlying risks.

STUDY OBJECTIVE: We retrospectively examined the clinical utility of obtaining routine blood cultures before the administration of antibiotics in certain nonimmunosuppressed patients with community-acquired pneumonia (CAP) admitted to the hospital during 1991. DESIGN: Retrospective review. SETTING: Grady Memorial Hospital (a county hospital primarily serving inner-city Atlanta). PATIENTS OR PARTICIPANTS: Hospital discharge diagnosis listings identified 1,250 adults ( > or = 18 years old) with pneumonia. From this group of patients, we selected patients admitted to the hospital with (1) respiratory symptoms and a lobar infiltrate on chest radiograph that were present at the time of hospital admission, (2) two or more sets of blood cultures obtained within 48 h of hospital admission, and (3) absence of defined risk factors: HIV-related illness, malignancy, recent chemotherapy, steroid therapy, sickle cell disease, nursing home residence, or hospital stays within the past 14 days. MEASUREMENTS AND RESULTS: Five hundred seventeen patients (mean age, 52 years;: age range, 18 to 103 years) qualified. Of these 517 patients, 25 patients (4.8%) had growth in blood cultures considered contaminants while 34 (6.6%) had blood cultures positive for the following pathogens: 29 Streptococcus pneumoniae, 3 Haemophilus influenzae, and 1 Streptococcus pyogenes, 1 Escherichia coli. Antibiotic therapy was changed for 7 of the 34 patients with positive blood cultures (1.4% of study patients). Antibiotic regimens were altered in 48 additional patients based on sputum culture, poor clinical response, and allergic reactions. CONCLUSIONS: Few blood cultures were positive for likely infecting organisms in adult patients with CAP without defined underlying risk factors. Furthermore, a total of $34,122 was spent on blood cultures at $66 per patient. In this carefully defined group of patients, blood cultures may have limited clinical utility and questionable cost-effectiveness.