Pharmacologic management of constipation in the critically ill patient

STUDY OBJECTIVE: To compare the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU). DESIGN: Retrospective medical record review. SETTING: MICU of an academic medical center. PATIENTS: Ninety-five patients admitted to the MICU from July 1-October 31, 2004. MEASUREMENTS AND MAIN RESULTS: Fifty patients satisfied the inclusion criteria. Patient-specific data such as age, weight, sex, length of MICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake, opioid intake, laxative intake, and bowel movements were recorded during the first 96 hours of admission. Logistic regression analysis was used to compare patients who did and did not have a bowel movement. Of the 50 patients, 25 did not have a bowel movement during the first 96 hours of MICU admission. Patients given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative (lactulose, milk of magnesia) were more likely to have a bowel movement (odds ratio [OR] 26.6, 95% confidence interval [CI] 3.2-221, p=0.002). Opioid intake, expressed as logarithmic morphine equivalents, was negatively associated with occurrence of a bowel movement (OR 0.76, 95% CI 0.59-0.97, p=0.027). Disease severity, as determined by APACHE II score, was also negatively associated with a bowel movement (OR 0.84, 95% CI 0.7-0.99, p=0.04). CONCLUSION: Critically ill patients have a high frequency of constipation, and opioid therapy is a significant risk factor. Routine administration of stimulant or osmotic laxatives should be considered for this patient population.     

Retrospective evaluation of inhaled prostaglandins in patients with acute respiratory distress syndrome

STUDY OBJECTIVES: To determine whether use of inhaled alprostadil (PGE 1 ) or epoprostenol (PGI 2 ) significantly improved oxygenation in patients with acute respiratory distress syndrome (ARDS), and to determine whether differences between the two drugs exist with regard to oxygenation, duration of mechanical ventilation and hospitalization, adverse effects, and survival. DESIGN: Retrospective chart review. SETTING: A 360-bed tertiary care teaching facility with medical and surgical intensive care units. PATIENTS: Twenty-seven patients admitted to the hospital who received either PGI 2 or PGE 1 for a primary or secondary diagnosis of ARDS. MEASUREMENTS AND MAIN RESULTS: Seventeen patients received inhaled PGE 1 and 10 received inhaled PGI 2 . There were no significant changes in the ratio of arterial partial pressure of oxygen (PaO 2 ):fraction of inspired oxygen (FiO 2 ) and in the PaO 2 , from baseline to any time point that was analyzed during treatment, for patients receiving either PGE 1 (p=0.2120 and 0.3399, respectively) or PGI 2 (p=0.1655 and 0.0784, respectively). CONCLUSION: No statistically significant improvement in oxygenation was observed in patients receiving either PGE 1 or PGI 2 . In addition, no significant differences were found between the two prostaglandins for the variables studied. Until positive results from large, prospective studies are available, we recommend that these inhaled prostaglandins not be used to treat ARDS.     

The Dental Caries Pandemic and Disparities Problem

Understanding caries etiology and distribution is central to understanding potential opportunities for and likely impact of new biotechnologies and biomaterials to reduce the caries burden worldwide. This review asserts the appropriateness of characterizing caries as a "pandemic" and considers static and temporal trend reports of worldwide caries distribution. Oral health disparities within and between countries are related to sugar consumption, fluoride usage, dental care, and social determinants of health. Findings of international and U.S. studies are considered in promoting World Health Organization's and others' recommendations for science-based preventive and disease management interventions at the individual, clinical, public health, and public policy levels.     

Estimation of creatinine clearance in end-stage liver disease

BACKGROUND: Estimation of renal function in patients with end-stage liver disease (ESLD) is complicated by several factors. OBJECTIVE: To develop a practical and relatively inexpensive method for estimating creatinine production and clearance in patients with ESLD. METHODS: Serum creatinine concentrations and urinary excretion of creatinine were measured in 27 patients with moderate-to-severe liver disease with the goal of developing equations to predict creatinine clearance from serum creatinine. Subjects were studied during an initial evaluation for a liver transplant program. Two 24 hour urine specimens were collected along with 3 serum samples over a 2 day evaluation period. Serum and urine creatinine concentrations were determined using both a modified Jaffé (autoanalyzer) method and an HPLC method. The data were analyzed using nonlinear mixed-effects modeling. RESULTS: Considering both statistical criteria and physiological conventions through allometric scaling theory, creatinine clearance (mL/min) in males can be estimated as (80/serum creatinine) x (actual body weight/70)0.75. For females, the same equation is valid, but the result is multiplied by 0.661. A simplified equation without the exponent is presented, along with equations that are appropriate when an HPLC assay is used for greater specificity. CONCLUSIONS: These equations offer potential for improved estimation of creatinine clearance in patients with liver impairment; however, they need further validation using an independent group of subjects.     

Gli1 induces G2/M arrest and apoptosis in hippocampal but not tumor-derived neural stem cells

Sonic hedgehog (Shh) is necessary for sustaining the proliferation of neural stem cells (NSCs), yet little is known about its mechanisms. Whereas Gli1, Gli2, and Gli3, the primary mediators of Shh signaling, were all expressed in hippocampal neural progenitors, Shh treatment of NSCs induced only Gli1 expression. Acute depletion of Gli1 in postnatal NSCs by short-hairpin RNA decreased proliferation, whereas germline deletion of Gli1 did not affect NSC proliferation, suggesting a difference in mechanisms of Gli1 compensation that may be developmentally dependent. To determine whether Gli1 was sufficient to enhance NSC proliferation, we overexpressed this mitogen and were surprised to find that Gli1 resulted in decreased proliferation, accumulation of NSCs in the G2/M phase of cell cycle, and apoptosis. In contrast, Gli1-expressing lineage-restricted neural precursors demonstrated a 4.5-fold proliferation enhancement. Expression analyses of Gli1-expressing NSCs identified significant induction of Gadd45a and decreased cyclin A2 and Stag1 mRNA, genes involved in the G2-M transition and apoptosis. Furthermore, Gadd45a overexpression was sufficient to partially recapitulate the Gli1-induced G2/M accumulation and cell death of NSCs. In contrast to normal stem cells, tumor-derived stem cells had markedly higher basal Gli1 expression and did not undergo apoptosis with further elevation of Gli1. Our data suggest that Gli1-induced apoptosis may serve as a protective mechanism against premature mitosis and may give insight into mechanisms by which nonmalignant stem cells restrain hyperproliferation in the context of potentially transforming mitogenic signals. Tumor-derived stem cells apparently lack these mechanisms, which may contribute to their unrestrained proliferation and malignant potential.