Influence of a targeted educational intervention on evidence-based practice in two Malaysian maternity units: the SEA ORCHID project in Malaysia.

We conducted a before and after study to determine whether an educational intervention to build capacity in the understanding and implementation of evidence could result in improved outcomes for mothers and babies in obstetric and neonatal units of two Malaysian hospitals. Twelve practices and thirteen associated outcomes were selected based on clear evidence from the Cochrane Library. There were significant improvements in most practices with little change in outcomes. In the short term a targeted intervention to build capacity in the understanding and implementation of evidence results in an improved process of care without adverse outcomes.

Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan.

In order to assess the association between antibodies to hepatitis C virus (anti-HCV) and hepatocellular carcinoma (HCC), as well as the interaction of anti-HCV with other HCC risk factors in Taiwan, a total of 127 pairs of newly diagnosed HCC patients and healthy community controls were studied. Case-control pairs were individually matched for age (+/- 3 years), sex, residence, and ethnicity. Serum samples from study subjects were examined for anti-HCV by enzyme immunoassays as well as hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) by radioimmunoassays using commercial kits. The habits of cigarette smoking, alcohol drinking, and peanut consumption were obtained through standardized interviews according to a structured questionnaire. Both the anti-HCV as well as the carrier status of HBsAg and HBeAg were significantly associated with HCC showing a multivariate-adjusted odds ratio of 24.8 for carriers of HBsAg alone, 33.5 for carriers of both HBsAg and HBeAg, and 23.7 for those who were positive for anti-HCV. The population-attributable risk percentage was estimated as 3% for anti-HCV alone, 69% for HBsAg carrier status alone, and 6% for both anti-HCV and HBsAg in Taiwan. There were also synergistic effects on HCC development for anti-HCV with HBsAg carrier status, cigarette smoking, and habitual alcohol drinking.

Nongenomic steroidal modulation of high-affinity serotonin transport.

The ability of steroids to modulate high-affinity 5-HT transport was investigated using cell-based models which stably manifest all known properties of this transport system. beta-Estradiol (E2) exhibited noncompetitive, and possibly allosteric, inhibition of both radiolabeled serotonin ([3H]5-HT) transport by, and radiolabeled cocaine congener ([3H]CFT) binding to, this system. Such inhibitory effects were observed within short time courses and unlikely to result from genomic effects normally ascribed to estrogen action. Rather, such nongenomic effects on 5-HT uptake were more akin to modulatory effects of select steroid metabolites on other plasma membrane systems such as neurotransmitter receptors and ionic channels. Beyond E2, preliminary examination of other steroid metabolites and synthetic steroid receptor agonists/antagonists revealed that inhibition of 5-HT transport is additionally attributable only to estriol (E3, an E2 metabolite) and tamoxifen (a nonsteroidal, E2 receptor antagonist). These findings indicate that the present form of transport modulation is only rendered by select compounds and not a general property of steroidal and related agents. Assessments of covalent conjugates of E2 suggested that E2 interacts with the transporter protein at allosteric site(s) inaccessible from the extracellular domain. These findings collectively suggest that steroid-mediated regulation of 5-HT transport may be a physiologically relevant mechanism, and that antidepressant as well as psychostimulant effects in vivo may contain a steroidal component.

Choline pharmacokinetics during intermittent intravenous choline infusion in human subjects.

A study of choline pharmacokinetics was undertaken in four patients receiving long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously infused over a 12-hour period in each subject. The choline concentration was determined in plasma at baseline, 1/4, 1, 3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24-hour urine collections. Analysis of variance showed the data fit a two-compartment model in which elimination from the central compartment was saturable significantly better than a one-compartment model in all four subjects (p < 10(-8) in all cases), and significantly better than a nonsaturating model in three of the four subjects (p = 1.0 x 10(-9), 7.5 x 10(-6), 9.4 x 10(-11), respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first-order rate constants for transfer between central and peripheral compartments, the dissociation constant for the saturable elimination process, the apparent volume of distribution in the central compartment, the steady-state volume of distribution, and the quantities of choline in the central compartment and in the readily exchangeable pool.

Concomitant and hormonally regulated expression of trp genes in bovine aortic endothelial cells.

Recent findings have suggested that the vertebrate trp family of channel proteins is the structural basis for Ca2+ influx through the capacitative calcium entry (CCE) pathway. We have discerned, in bovine aortic endothelial cells, the concomitant expression of four such vertebrate genes: trp-1 (two splice variants), trp-3, trp-4 and trp-5. Exogenous hormones rendered dynamic effects on the transcript levels of these genes. Most notably, beta-estradiol significantly down-regulated trp-4 while trans-retinoic acid dramatically up-regulated trp-5; yet these hormones rendered little change in CCE. These findings suggest that the extent of a given trp channel's participation in CCE is not reflected in alterations of its transcript level.

Cloning and expression of the mouse serotonin transporter.

A mouse brain cDNA encoding the high-affinity serotonin transporter (SERT) has been identified and characterized. The mouse transporter sequence (mSERT) encodes a protein of 630 amino acids which contains twelve potential transmembrane domains (TMDs), N-linked glycosylation and kinase-mediated phosphorylation sites, and high levels of homology with rat and human SERTs. Heterologous expression of mSERT in COS-I cells resulted in a [3H]serotonin transport activity characterized by kinetic saturability (Km = 403 +/- 42 nM. Vmax = 1.02 +/- 0.10 pmol/mg/min), Na1 and Cl- dependences (5HT:Na+:Cl- coupling ratio of 1:1:1), and sensitivity to known inhibitors of serotonin transport (including antidepressant and psychostimulant agents). Northern analysis using mSERT cDNA as probe revealed a single 3.4 kb mRNA species expressed in mouse lung, midbrain and brainstem regions, and absent from heart and liver. In situ hybridization studies further established the specific localization of mSERT gene expression to the raphe nuclei of the mouse midbrain. The identified mSERT cDNA sequence provides a new tool for the evaluation of serotonin transport pharmacology in heterologous expression systems and provides an opportunity for the evaluation of mSERT gene expression in a well-characterized model of mammalian development.

The role of serotonin in the actions of psychostimulants: molecular and pharmacological analyses.

Cocaine is a highly abused psychostimulant which is a local anesthetic and inhibitor of the reuptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE). This manuscript details a brief summary and the primary conclusions of several presentations geared to present recent pharmacological analyses of the interaction of cocaine with 5-HT systems. These data illustrate the complexity of actions for cocaine in the brain and emphasize that, to fully understand the mechanisms which underlie its potent behavioural effects, the impact of this drug on 5-HT function as well as the interactions between 5-HT and the function of DA mesolimbic pathways must be considered.

Structure-activity relationships of serotonin transport: relevance to nontricyclic antidepressant interactions.

A transfectant cell model was used to examine the structure-activity relationships of serotonin (5-hydroxytryptamine, 5-HT) transport. The findings suggest that 5-HT interacts largely with nonpolar and sterically-confining environments on the transport system, and that a particular spatial coordination of the amino and phenyl groups (separated by an alkyl backbone) is important for transport interaction. Molecular modelling analyses revealed that this motif is also present in the structures of several nontricyclic antidepressants and specific inhibitors of 5-HT transport, as well as adrenergic agents which also possess 5-HT transport-inhibitory activities. While this amino-phenyl coordination motif seems to be a necessary structural requisite for transport interaction, and therefore likely to be part of the transport pharmacophore, additional phenyl rings present in some of the nontricyclic antidepressants may help to account for their relatively higher affinities in 5-HT transport interaction.

A pharmacokinetic analysis of 3,4-methylenedioxymethamphetamine effects on monoamine concentrations in brain dialysates.

Interpretation of the in vivo actions of 3,4-methylenedioxymethamphetamine (MDMA) is complicated by the formation of the active metabolite, 3,4-methylenedioxyamphetamine (MDA). This study evaluates the role of MDA in the dopamine releasing actions of (+)-MDMA. In the study, rats were given subcutaneous doses of (+)-MDMA and concentrations of monoamines and their metabolites in striatal dialysate were measured at 15 min intervals. In parallel experiments, plasma concentrations of (+)- and (-)-MDMA and MDA were determined by GC/MS procedures. The time course of MDMA levels was comparable for the two isomers as were their bioavailabilities. In contrast, the plasma levels of MDA were about three times higher after (+)-MDMA. (+)-MDMA caused a rapid increase in striatal dialysate levels of dopamine and decreased extracellular levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). There was a significant correlation between dopamine concentration in striatal dialysate and plasma MDMA concentration, but not with plasma MDA. These results indicate that MDMA itself has stereoselective actions on dopamine neurons. However, the higher plasma MDA levels after (+)-MDMA may account for part of the enantiomeric differences in the behavioral and neurotoxicological effects of MDMA.

Human chorionic gonadotropin levels after blastocyst transfer are highly predictive of pregnancy outcome.

OBJECTIVE: To determine the predictive value(s) of beta-hCG serum levels for pregnancy outcome following blastocyst transfer. DESIGN: Retrospective review. SETTING: University-based assisted reproductive technology (ART) program. PATIENTS: All ART patients enrolled from January 1998 to December 1999. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Beta-hCG serum levels and pregnancy outcomes. RESULT(S): Of the 836 ART cycles initiated, 608 embryo transfers met study criteria and were assigned to one of two groups: 248 day 5 blastocyst transfers or 360 day 3 embryo transfers. In the day 5 blastocyst group, 147 pregnancies occurred (59.2%), and day 3 transfers resulted in 165 pregnancies (45.8%). For day 3 and day 5 transfers, mean values of beta-hCG on day 16 post-retrieval of spontaneous abortions were lower than ongoing pregnancies (P< .05). A beta-hCG value on day 16 of >300 mIU/mL predicted an ongoing pregnancy for day 5 transfer group in 97% of pregnancies compared with 92% for day 3 embryo transfers. A multiple gestation was observed in 70% of pregnancies with a beta-hCG level >400 mIU/mL in the day 5 group compared with 63% for the day 3 group. The incidence of higher-order multiple gestations was significantly lower in the day 5 blastocyst group (P< .05). CONCLUSION(S): Beta-hCG serum levels on day 16 post-retrieval were highly predictive of pregnancy outcome after a blastocyst transfer.

Human leukocyte antigen (HLA) frequency among patients with nasopharyngeal carcinoma in Taiwan.

In order to assess the association between human leukocyte antigens (HLA) and nasopharyngeal carcinoma (NPC), a total of 10 familial and 10 sporadic NPC patients and 171 unrelated healthy controls were studied. HLA typing was performed using commercial trays which defined 30 specificities of HLA-A, B and C loci and 10 specificities of HLA-D locus according to the method of Tiwari and Terasaki. HLA-A2, B16 and DR1 were found to be higher among patients with NPC than unrelated healthy controls with an odds ratio (OR) and a 95% confidence interval of 5.91 (2.1-16.6), 6.00 (2.0-18.0) and 6.89 (1.3-37.5), respectively. Further analysis showed that A2(+) B16(+) haplotype was significantly associated with a much higher risk of NPC (OR = 15.5) as compared with A2(-) B16(-) haplotype. No difference in frequency distributions of HLA-A, B, C and D antigens was observed between familial and sporadic NPC patients.

Hepatitis B virus e antigen and primary hepatocellular carcinoma.

Serum samples from 243 cases of primary hepatocellular carcinoma (PHC) and 302 non-PHC hospital controls were tested for hepatitis B virus (HBV) surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to HBV core antigen (anti-HBc), HBV e antigen (HBeAg) and antibody to HBeAg (anti-HBe) with radioimmunoassays using commercial kits. A total of 236 (97%) PHC cases and 302 (100%) hospital controls were positive for one or more HBV markers. While 188 (77%) PHC cases and 57 (19%) controls were positive for HBsAg, 44 (18%) PHC cases and 5 (2%) controls were positive for both BHsAg and HBeAg. Statistically significant associations with PHC were observed for HBsAg and HBeAg with an odds ratio (OR) of 10.0 and 3.2, respectively, when age, sex and other markers were adjusted. The stratification analysis of interactive effects of HBV infection markers on the development of PHC showed that HBeAg carrier status may increase PHC risk associated with HBsAg status.

Epidemiologic characteristics and multiple risk factors of stomach cancer in Taiwan.

Both descriptive and analytical studies were carried out to examine epidemiologic characteristics and multiple risk factors of stomach cancer in Taiwan. The age-adjusted mortality rate of stomach cancer has been decreasing since the early 1970s for both males and females. The male-to-female ratio of the disease has remained around 2:1 in the past three decades. Comparison of the incidence of stomach cancer among Chinese in different countries showed a much lower incidence among Chinese in the USA than those in southeastern Asia. A hospital-based matched case-control study carried out in Taipei metropolitan areas showed a positive association of stomach cancer with blood type A, chronic gastric diseases, cigarette smoking, alcohol drinking, green tea drinking as well as consumption of salted meat, cured meat, smoked food, fried food and fermented beans. There was also a significant negative association between the disease and the consumption of milk.

Epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan.

The specific aim of this study was to examine epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan. The age-adjusted mortality from lung cancer has been increasing since the early 1950s with a constant male-to-female ratio of around 2.0. International comparison of cumulative mortality from lung cancer showed a much lower male-to-female ratio in Chinese than in other populations. Significantly high mortality from lung cancer was observed in highly urbanized cities and the endemic area of chronic arsenicism in Taiwan. Significant associations of active and passive cigarette smoking with epidermoid carcinoma, small cell carcinoma and adenocarcinoma of the lung were observed in a hospital-based case-control study carried out in Taipei metropolitan areas. Alcohol drinking, coffee drinking and various types of indoor air pollution were not related to lung cancer after the cigarette smoking habit was adjusted through a multiple logistic regression analysis.

Incomplete reversibility of an experimentally induced hypocholinergic state: biochemical and physiological, but not behavioral, recovery.

In previous reports, we described the experimental development of a hypocholinergic state in rats following the total replacement of dietary choline by an artificial isostere, N-aminodeanol (NADe). NADe shares most of the physicochemical and biochemical characteristics of choline (Ch) but is utilized less efficiently in pathways leading to the formation of both acetylcholine and phospholipids. This experimental model mimics many of the features of human degenrative dementias. We now discuss the behavioral and physiological effects of restoring a normal diet after the hypocholinergic state has become well established. The procedure by which that state was induced has been described in detail in earlier publications. After replacing Ch in the diets of weanling rats for 270 days, NADe replaced 70-85% of the phospholipid-bound Ch in plasma, brain, and peripheral tissue. When dietary NADe was removed and Ch was restored in the diet, NADe disappeared and plasma and erythrocyte (RBC) choline levels returned to normal within 30-60 days. Quinuclidinyl benzilate (QNB) binding showed that muscarinic receptors continued to be depressed in animals remaining on the NADe diet, but returned to control levels in the reversal group. There were no differences in cholinesterase activity among the three treatments. Choline acetyltransferase activity returned to control levels, while continuing to be lower in the NADe animals. Liver lipids were elevated in the latter and not significantly different in the control and reversal groups. Among physiological functions, body weight increased more rapidly in the reversal group than in animals continuing on the NADe diet. Brain weights of the reversal animals were significantly greater than those of animals not reversed, but less than controls. Core body temperatures did not differ from controls at any time during the reversal period. Behaviorally, nociceptive thresholds indicative of sensory-reflexive and sensory-perceptual responses remained significantly below normal, that is, a hyperalgesic state. Reversal animals also remained hyperactive and displayed memory significantly poorer than those on the normal diet, that is, no improvement over animals continuing on NADe. In general, the results suggest that behavioral losses induced by NADe reflect persisting changes in the CNS, despite essentially complete recovery of biochemical parameters. The changes may be morphological or be associated with adaptive changes in other neurochemical events in the CNS.

Measurement of lumbar lordosis. Evaluation of intraobserver, interobserver, and technique variability.

STUDY DESIGN: Sixty radiographs were measured on two separate occasions by three physicians using four different techniques to evaluate the reliability and reproducibility of the measurement of lumbar lordosis. OBJECTIVE: To evaluate clinical methods of measuring lumbar lordosis, determining intraobserver and interobserver reliability. SUMMARY OF BACKGROUND DATA: Several different methods are used to measure lumbar lordosis. The reliability and reproducibility of these has not been well studied. METHODS: Sixty lateral full spine radiographs were obtained, labeled, and the lumbar lordosis measured independently by three practitioners who routinely perform these measurements. Four measurement techniques were used. These included measurements from the inferior endplate of T12 to the superior endplate of S1; the superior endplate of L1 to the superior endplate of S1; the inferior endplate of T12 to the inferior endplate of L5; and the superior endplate of L1 to the inferior endplate of L5. The measurements then were repeated after relabeling. RESULTS: Intraobserver reliability coefficients ranged from 0.83 to 0.92, indicating excellent reproducibility. Ninety-two percent of repeat measures were within 10 degrees. High overall and pairwise agreement among the three observers also was present; the interobserver reliability coefficients ranged from 0.81 to 0.92. CONCLUSIONS: The measurement of lumbar lordosis is reproducible and reliable if the technique is specified and one accepts 10 degrees as acceptable variation. Factors that affect the reproducibility of measurement include end vertebra selection (especially with transitional segments) and vertebral endplate architecture.

Measurement of thoracic and lumbar fracture kyphosis: evaluation of intraobserver, interobserver, and technique variability.

STUDY DESIGN: Statistical analysis of various measurement techniques for thoracolumbar burst fracture kyphosis on lateral radiograph. OBJECTIVE: To determine the most reliable measurement technique. SUMMARY OF BACKGROUND DATA: The treatment of thoracic and lumbar burst fractures involves many factors, including the degree of resultant kyphosis. Although various methods have been described, no study has directly compared these methods for reliability and reproducibility. METHODS: Fifty lateral radiographs of thoracic and lumbar burst fractures were randomly selected and measured on two separate occasions by three spine surgeons using five different measurement techniques. Radiograph quality, fracture type, and the center beam location were determined. Statistical analysis included analysis of variance for repeated measures and analysis of variance using a generalized linear model. RESULTS: Intraclass correlation coefficients were most consistent for Method 1 (rho = 0.83-0.94) followed by Method 4 (rho = 0.65-0.89) and Method 5 (rho = 0.73-0. 85). Intraobserver agreement (% of repeated measures within 5 degrees of the original measurement) ranged between 72% and 98% for all techniques for all three observers, with Method 1 showing the best agreement (84%-98%). Paired comparisons between observers varied considerably with interobserver reliability correlation coefficients ranging from 0.52 to 0.93. Method 1 showed the highest interobserver reliability coefficient (0.81, range 0.71-0.93) followed by Method 5 (0.71, range 0.68-0.75). Method 1 also had the highest percentage of agreement within categories (90% within 5 degrees ). CONCLUSIONS: Method 1 (measuring from the superior endplate of the vertebral body one level above the injured vertebral body to the inferior endplate of the vertebral body one level below) showed the best intraobserver and interobserver reliability overall.

Reading activities of registered nurses.

This national study was designed to gather baseline data about the reading activities of registered nurses. Questionnaires were administered by nurse continuing educators to subjects (N = 1406) at 44 sites in 25 states and the District of Columbia. In a week, the mean amount of time devoted to professional literature was four hours, 48 minutes (SD = 3.88) plus eight hours, 12 minutes (SD = 5.15) to general material. This translated to reading one hour and 51 minutes per day, slightly more than the average adult. Educational level, position, and memberships were the best predictors of how much time was spent reading job-related material that might lead to self-development and enhancement of nursing practice.

Self-care burden, stress appraisal, and mood among persons receiving radiotherapy.

This study was undertaken to describe the self-care burden (SCB) of persons receiving radiation as outpatients, to identify factors contributing to SCB, and to test a model of the effects of SCB, symptom distress, and appraisal of illness on mood. The subjects were 72 adults with cancer who had been in treatment an average of 4 weeks. Fatigue was reported to be the most distressing symptom. Among health deviation self-care tasks, coming for treatment was the most demanding, and self-treatment, such as administering medications, was the most difficult. Universal self-care activities most disrupted by treatment were social and recreational activities. Path analysis revealed that dependency was the primary predictor of health deviation SCB, while symptom distress was the best predictor of universal SCB. Universal SCB and family hardiness were the best predictors of appraisal scores. Symptom distress and somatic mood were highly correlated, suggesting collinearity between these factors. Four variables--appraisal, symptom distress, family hardiness, and health deviation SCB--explained 55% of the variance in affective mood scores. Theoretical and clinical implications are discussed.