Functional imaging studies in cannabis users.

Cannabis remains the most widely used illegal drug in the United States. This update examines the available literature on neuroimaging studies of the brains of cannabis users. The majority of studies examining the acute effects of delta-9-tetrahydrocannabinol (THC) administration used PET methods and concluded that administration of THC leads to increased activation in frontal and paralimbic regions and the cerebellum. These increases in activation are broadly consistent with the behavioral effects of the drug. Although there is only equivocal evidence that chronic cannabis use might result in structural brain changes, blood-oxygenation-level-dependent-fMRI studies in chronic users consistently show alterations, or neuroadaptation, in the activation of brain networks responsible for higher cognitive functions. It is not yet certain whether these changes are reversible with abstinence. Given the high prevalence of cannabis use among adolescents, studies are needed to evaluate whether cannabis use might affect the developing brain. Considerable further work, employing longitudinal designs, is also required to determine whether cannabis use causes permanent functional alterations in the brains of adults.     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.     

Development of bariatric surgery-specific risk assessment tool.

BACKGROUND: Administrative databases have increasingly been used to assess bariatric surgery outcomes, resulting in policy recommendations about bariatric practice. However, surgical outcomes must be risk adjusted to compare patients of varying potential risk fairly with those to whom the policies will apply. To date, the risk adjustment tools used for database analysis of bariatric surgical outcomes have been those designed for other purposes, and their sensitivity for bariatric outcomes has not been established. METHODS: Bariatric surgical procedures contained in the National Hospital Discharge Summary for 1993-2003 were assembled into a database. The standard set of Elixhauser co-morbidity variables used by the Agency for Healthcare Research and Quality were entered into the database. Those variables that were significantly associated with adverse outcomes were entered into a stepwise-elimination logistic regression equation, yielding a set of variables related to adverse outcomes from bariatric surgery. These were then prospectively applied to another database (the National Inpatient Survey) to determine their sensitivity for predicting outcomes and were compared with the commonly used Charlson score. RESULTS: The variables significantly correlating with bariatric adverse events included chronic pulmonary disease, hypertension, diabetes with chronic complications, fluid and electrolyte disorders, deficiency anemias, and depression. Age and male gender were also signficantly related to adverse events. The c-index (a correlative index, with .5 showing no, and 1, a perfect, relationship) for bariatric surgery mortality with the Charlson index is .52. For the Elixhauser-based system we developed, it is .72. CONCLUSIONS: We have developed a new risk-adjustment tool for bariatric surgery outcomes studies that use administrative databases. Its performance was clearly better than that of the commonly used Charlson co-morbidity score. Bariatric studies that have used the Charlson index should not be considered adequately risk adjusted.     

Once-daily gentamicin dosing for the preterm and term newborn: proposal for a simple regimen that achieves target levels.

OBJECTIVE: Based on recent safety and efficacy data, combined with the known pharmacokinetic parameters of aminoglycosides in the newborn, once-daily gentamicin should be preferable to the many other dosing regimens currently in use. Although there are growing data to support its use in term newborns, experience with preterm infants is more limited. In our Neonatal Intensive Care Unit, we experienced difficulties regarding complicated dosing regimens, actual dosing errors, and the tendency to check trough and peak levels around the third dose for infants receiving only a 48 hour course. Therefore, we conducted a quality improvement initiative in which we developed and tested a clinical practice guideline for the use of once-daily gentamicin for preterm and term infants that we hoped would yield trough and peak levels in our target range. METHODS: We combined a review of the published English language literature with pharmacokinetic analysis of our own data prior to initiation of this new regimen to design the following dosing regimen: <35 weeks gestation: 3 mg/kg q 24 hours, > or =35 weeks gestation: 4 mg/kg q 24 hours. Our goal serum levels were a trough < or =2 microg/ml and a peak between 6 and 12 microg/ml. We collected and analyzed trough and peak levels from all infants receiving this dosing regimen in the first week of life for at least 72 hours between 3/1/99 and 12/31/00. RESULTS: In total, 214 babies met our inclusion criteria, 75 of whom were <35 weeks gestation. 100% of babies of all gestational ages had a nontoxic trough level. For infants <35 weeks gestation, 79% had a therapeutic peak level, with a mean value of 6.8 microg/ml. For infants of at least 35 weeks gestation, 93% had a therapeutic peak level, with a mean value of 8.4 microg/ml. 92% of nontherapeutic peaks were too low. CONCLUSION: This study of once-daily gentamicin represents the largest sample size of pre-term infants published to date. The proposed regimen is simple and yields a high proportion of desirable levels. We recommend it for use in preterm and term newborns.     

In vitro cytotoxicity of a remineralizing resin-based calcium phosphate cement.

Recently, a resin-based calcium phosphate cement (RCPC) has been reported as a remineralizing pulp-capping or lining cement. RCPC consists mainly of tetracalcium and dicalcium phosphates, ethoxylated bisphenol A dimethacrylate and pyromellitic glycerol dimethacrylate monomers and photo- and chemical initiators. OBJECTIVES: Here, the cytotoxic effects of RCPC were evaluated. The hypothesis was that RCPC induced only minor cytotoxic response in immortalized murine odontoblast and pulp cells, comparable to that produced by similar dimethacrylates due to unpolymerized dimethacrylate monomer present after curing. METHODS: Cytotoxicity was determined following the changes in cell succinate dehydrogenase activity after 24 h exposure to the cement components and after a 24 h recovery period. A fourfold range of concentrations was tested of the monomers, the eluate of cured RCPC leached in Dulbecco's modified Eagle's medium, and crushed cured cement in dimethyl sulfoxide. RESULTS: The monomers themselves had cytotoxicities similar to those reported for other dimethacrylates, although they are significantly less toxic than Bis-GMA. Differential cell sensitivity was demonstrated, with the pulp cells having greater sensitivity to the unpolymerized monomer than the odontoblast-like cells. The leached components have cytotoxicity similar to that of the free monomers. The crushed material demonstrated no apparent cytotoxicity at the dilutions tested. SIGNIFICANCE: These data demonstrate that RCPC has an in vitro cytotoxicity that is comparable to other materials containing dimethacrylate monomers and suggest that the material may be suitable for use in dental restorations. The data also indicate that the pulp cells appear more sensitive to dimethacrylates than the odontoblasts.     

Assessment of alcohol and other drug use behaviors in health professions students.

Alcohol and other drug (AOD) use behaviors of health professions students (HPS) were assessed by surveying both university-based HPS and other nursing programs in a Midwestern state in 1999. Response was 2,646 (56.4%) of surveyed students. Family history of alcohol-related and drug-related problems were reported by 39.8% and 13.9%, respectively, with 42.6% of respondents reporting one or both. Among nursing respondents, 48.1%, 19.2% and 51.1%, respectively, reported family problems with alcohol, drugs, or one or both. Past-year alcohol use was comparable to undergraduate college students (UCS) nationally (83%); heavy drinking, tobacco and recreational drug use by HPS were lower. Past year drug use was highest among medical students. Marijuana was the predominant illicit drug; medical students and males most often reported use. Health professions educational systems should proactively address student AOD prevention, education and assistance needs.     

Nonspecific immunity in pregnancy: monocyte surface Fcγ receptor expression and function

The state of pregnancy is an immunological enigma during which the body must prevent rejection of the antigenically foreign fetus while at the same time maintain sufficient maternal host defense mechanisms to combat infection. Although most studies on the immunology of pregnancy focus on immune suppression, several studies have shown an increase in nonspecific host defense, which is postulated to be a compensatory mechanism for decreased specific immunity during pregnancy. Studies in this laboratory have shown that monocyte surface FcγRI (CD64) and FcγRII (CD32) expression progressively increase throughout pregnancy, while surface MHC class II expression remains unchanged. Functional studies revealed that the number of phagocytic monocytes which could be isolated from pregnant women was increased. These cells exhibited an increased capacity to ingest IgG-opsonized human erythrocytes. This study shows for the first time that monocyte surface FcγR expression and FcγR-mediated functions are increased during pregnancy. These results support the hypothesis that nonspecific immunity as represented by FcγR expression and function is increased during pregnancy.