Prolonged intravenous remifentanil infusion for labor analgesia

IMPLICATIONS: A 34-h remifentanil infusion was administered for labor analgesia in a patient with thrombocytopenia and renal insufficiency. Compared with other opioids, remifentanil may produce fewer cumulative effects during prolonged infusion because of its unique metabolism.     

Effects of insulin deficiency or excess on hepatic gluconeogenic flux during glycogenolytic inhibition in the conscious dog

The direct acute effects of insulin on the regulation of hepatic gluconeogenic flux to glucose-6-phosphate (G6P) in vivo may be masked by the hormone's effects on net hepatic glycogenolytic flux and the resulting changes in glycolysis. To investigate this possibility, we used a glycogen phosphorylase inhibitor (BAY R3401) to inhibit glycogen breakdown in the overnight-fasted dog, and the effects of complete insulin deficiency or a fourfold rise in the plasma insulin level were assessed during a 5-h experimental period. Hormone levels were controlled using somatostatin with portal insulin and glucagon infusion. After the control period, plasma insulin infusion 1) was discontinued, creating insulin deficiency; 2) increased fourfold; or 3) was continued at the basal rate. During insulin deficiency, glucose production and the plasma level and net hepatic uptake of nonesterified free fatty acids increased, whereas during hyperinsulinemia they decreased. Net hepatic lactate uptake increased sixfold during insulin deficiency and 2.5-fold during hyperinsulinemia. Net hepatic gluconeogenic flux increased more than fourfold during insulin deficiency but was not reduced by hyperinsulinemia. We conclude that in the absence of appreciable glycogen breakdown, an acute gluconeogenic effect of hypoinsulinemia becomes manifest, whereas inhibition of the process by a physiologic rise in insulin was not evident.     

Evaluating the quality of teaching in medical education: are we using the evidence for both formative and summative purposes?

Heightened focus on the quality of teaching in medical schools has led to increased use of student surveys as a means of evaluating teaching. In some institutions, however, the summative purpose is emphasized over the developmental or self-improvement objective. The aim of this study was to examine the utility of a student evaluation of teaching questionnaire for use in administrative decision making (summative purpose) and in identification of faculty whose instruction needs improvement (formative purpose). Results of this analysis are discussed in addition to related issues regarding faculty development and the importance of adopting multiple methods of evaluating and documenting teaching and other educational activity.     

Tuberculosis screening among foreign-born persons applying for permanent US residence

OBJECTIVES: This study sought to determine adherence of physicians to tuberculosis (TB) screening guidelines among foreign-born persons living in the United States who were applying for permanent residency. METHODS: Medical forms of applicants from 5 geographic areas were reviewed, along with information from a national physician database on attending physicians. Applicant and corresponding physician characteristics were compared among those who were and were not correctly screened. RESULTS: Of 5739 applicants eligible for screening via tuberculin skin test, 75% were appropriately screened. Except in San Diego, where 11% of the applicants received no screening, most of the inappropriate screening resulted from the use of chest x-rays as the initial screening tool. CONCLUSIONS: Focused physician education and periodic monitoring of adherence to screening guidelines are warranted.     

Brief butyltin exposure induces irreversible inhibition of the cytotoxic function on human natural killer cells, in vitro

Despite mounting evidence on butyltin (BT) contamination and related immunotoxic effects on wildlife, very little is known about BT-associated immunotoxic effects on humans, particularly the effects on human natural killer (NK) lymphocyte function. Our earlier studies demonstrated that in vitro exposure to environmentally relevant concentrations of BTs negatively affect human NK cells and that there are measurable levels of BTs in human blood. In this study we examined whether the inhibition of NK cell cytotoxic function induced by a brief exposure (1 h) to BTs is reversible when the cells are allowed to recover in BT-free media for up to 6 days. Standard methods were used in chemical preparation, blood sampling, NK cell isolation, and 51-Chromium release assay. The results revealed that exposure to 300 nM TBT for 1 h caused an approximately 65- decrease in NK cytotoxic function, whether the lymphocytes were given as long as a 6-day recovery period or no recovery period. There was no recovery (nor any further loss) of NK cytotoxic function following removal of the compound. Exposure to 5 microM DBT for 1 h showed a 41% decrease in cytotoxic function with 0-h recovery and an 83% decrease after a 24-h recovery period. Thus, not only is there no significant recovery of NK cytotoxic function when the lymphocytes are allowed to incubate in BT-free medium for up to 6 days but there is additional loss of cytotoxic function. The results indicated that short-term exposure to BTs causes persistent negative effects on NK cell ability to kill cancer cells.     

Interleukins 2 and 12 produce recovery of cytotoxic function in tributyltin-exposed human natural killer cells

Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2 and 12 are both potent stimulators of NK cell cytotoxic function. Tributyltin (TBT) is used in a variety of consumer products and industrial applications. TBT is found in dairy products, meat, and fish. We and others have shown that there are measurable levels of TBT in human blood. Butyltins appear to increase the risk of cancer and viral infections in exposed individuals. We have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a l-h exposure to TBT and that this inhibition persists even after removal of the compound. In the current study we examine the effects of the NK-stimulatory ILs, IL2 and IL12, on the ability of NK cells to recover from the persistent inhibitory effects of a 1-h TBT treatment. Highly purified NK cells (> 95% CD16(+)) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 300 nM TBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in TBT-free media containing no interleukin, 1000 U/mL IL2, 20 ng/mL IL l2, or a combination of IL2 plus IL12. Tumor killing function was then tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no interleukin is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period.     

Interleukins 2 and 12 produce significant recovery of cytotoxic function in dibutyltin-exposed human natural killer cells

Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2, 12, 15, and 18 and Interferon gamma (IFNgamma) are potent stimulators of NK cell cytotoxicity. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. Recently, we have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a 1-h exposure to dibutyltin. This inhibition of tumor killing function continues even after removal of the compound. There is no significant recovery of NK cytotoxic function even when the cells are allowed to recover for 6 days. In the current study we examine the effects of NK-stimulatory cytokines on the ability of NK cells to recover from the inhibitory effects of a 1-h DBT treatment. Highly purified NK cells (>95% CD16(+)) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 5 microM DBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in DBT-free medium containing either no cytokine or a maximally stimulatory dose of several NK-stimulatory cytokines. Tumor killing function was tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no cytokine is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period. The other cytokines tested (IL15, IL18, and IFNgamma) were unable to increase the cytotoxicity of DBT-exposed NK cells.     

Do written action plans improve patient outcomes in asthma? An evidence-based analysis

OBJECTIVE: Current guidelines recommend use of written action plans and peak flow monitoring as key components of asthma care. Our study assesses whether written action plans, with or without peak flow monitoring, have an independent effect on outcomes when used as a component of asthma self-management. STUDY DESIGN: This was a systematic review of published studies. Two independent reviewers followed a prospective protocol for study selection and data abstraction. Outcome data were synthesized qualitatively; they were not appropriate for quantitative meta-analysis. Our comprehensive literature search used MEDLINE, EMBASE, the Cochrane Library, and a hand search of recent bibliographies. The search was limited to full-length, peer-reviewed articles with abstracts in English. The studies were randomized controlled trials that compared the outcomes of an asthma self-management intervention with and without the use a written action plan. The primary outcomes of interest are utilization measures, such as hospitalizations and ER visits. Other outcomes of interest include measures of symptom control and lung function. POPULATION: There were 1501 evaluable patients with asthma; 1410 adults and 91 children. OUTCOMES MEASURED: We measured the frequency of waiting and examination room companions, the reasons for accompaniment, the influence on the encounter, and the overall helpfulness of the companion as assessed by patients and companions. We also determined the physicianamprsquos assessment of the companionamprsquos influence, helpfulness, and behavior during the encounter. RESULTS: Nine randomized controlled trials enrolling a total of 1501 patients met selection criteria. The majority of comparisons in these studies do not demonstrate improved outcomes associated with a written action plan. There are notable methodologic limitations: studies reporting negative findings lack sufficient power, and studies reporting positive findings demonstrate systematic bias. CONCLUSIONS: Although written action plans are widely used, there is insufficient evidence to determine whether their use, with or without peak flow monitoring, improves outcomes.