Prenatal ethanol exposure decreases GAP-43 phosphorylation and protein kinase C activity in the hippocampus of adult rat offspring

Consumption of moderate quantities of ethanol during pregnancy produces deficits in long-term potentiation in the hippocampal formation of adult offspring. Protein kinase C (PKC)-mediated phosphorylation of the presynaptic protein GAP-43 is critical for the induction of long-term potentiation. We tested the hypothesis that this system is affected in fetal alcohol-exposed (FAE) rats by measuring GAP-43 phosphorylation and PKC activity in the hippocampus of adult offspring of rat dams that had consumed one of three diets throughout gestation: (a) a 5% ethanol liquid diet, which produced a maternal blood ethanol concentration of 83 mg/dl (FAE); (b) an isocalorically equivalent 0% ethanol diet (pair-fed); or (c) lab chow ad libitum. Western blot analysis using specific antibodies to PKC-phosphorylated GAP-43 revealed that FAE rats had an approximately 50% reduction in the proportion of phosphorylated GAP-43. Similarly, we found that PKC-mediated incorporation of 32P into GAP-43 was reduced by 85% in hippocampal slices from FAE rats compared with both control groups. FAE animals also showed a 50% reduction in total hippocampal PKC activity, whereas the levels of six major PKC isozymes did not change in any of the diet groups. These results suggest that GAP-43 phosphorylation deficits in rats prenatally exposed to moderate levels of ethanol are not due to alterations in the expression of either the enzyme or substrate protein, but rather to a defect in kinase activation.     

Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments

OBJECTIVE: To evaluate an experimental heroin maintenance programme. Design: Randomised trial. SETTING: Outpatient clinic in Geneva, Switzerland. SUBJECTS: Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments. INTERVENTION: Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance). Main outcome measures: Self reported drug use, health status (SF-36), and social functioning. RESULTS: 25 experimental patients completed 6 months in the programme, receiving a median of 480 mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up. CONCLUSIONS: A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids.     

Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study

This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 +/- 13 years, mean +/- SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p < 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p < 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental factors. Significant environmental correlations were only found for BMD measurements and ranged between 0.50 and 0.65 (p < 0.001). These data suggest that QUS and BMD measurements are highly heritable traits. While it appears that there is a common set of genes influencing both QUS and BMD measurements, specific genes yet to be identified appear to have greater effects than that of shared genes in each trait.     

The diagnosis and treatment of bladder cancer metastases

Central hemodynamics was studied by thermodilution in 16 patients with acquired mitral defect during surgery under conditions of hypothermia without perfusion. Cooling and surgical correction were carried out under superficial ether anesthesia with morphine and droperidol. A 28% decrease of the minute circulation volume is observed as early as under general anesthesia and at the very beginning of cooling (10.8% more); this decrease is caused by rarer heart contractions and increase of the total peripheral vascular resistance as a result of body response to cool exposure. An almost 10 degrees C drop of body temperature (to 27.2 +/- 0.2 degrees C) involves a just 13% decrease of the cardiac index in comparison with the value at the beginning of cooling. Injection of droperidol before cooling blocks the increase of the total peripheral resistance in a dose-dependent mode (about 0.13 mg/kg of droperidol is needed for sufficiently complete prevention of the increase of total peripheral resistance), and thus maintains the stroke and cardiac indexes at a sufficiently high level. Morphine (in doses of up to 2.3 mg/kg) did not bring about such an effect.     

Specific IgE-dependent sensitization, atopy, and bronchial hyperresponsiveness in apprentices starting exposure to protein-derived agents

Atopy, specific IgE sensitization, and bronchial hyperresponsiveness (BHR) were examined in a cohort of 769 apprentices starting career programs in animal health or veterinary medicine (Group 1), pastry making (Group 2), and dental hygiene (Group 3). The hypothesis were that: (1) a proportion of subjects can be "sensitized" although no significant specific occupational exposure has occurred; and (2) there is a relationship between baseline specific sensitization to work-related antigens and host characteristics. Skin tests were administered using 11 common inhalants and specific allergens, including six laboratory animal extracts, three cereal antigens, alpha-amylase, and latex. Methacholine challenge tests were performed. The prevalence of atopy was 54.4% in Group 1, 58.1% in Group 2, and 52.5% in Group 3. Skin reactivity to work-specific proteins was as follows: laboratory animal proteins, 13.8% in Group 1, 14.0% in Group 2, and 15.6% in Group 3. No subject was sensitized to alpha-amylase, whereas 1.2% in Group 1, 5% in Group 2, and 4.1% in Group 3 were sensitized to flour. Five subjects reacted to latex. BHR (PC20 < or = 8 mg/ml) was present in 17.6%, 21.2%, and 14.8% of subjects in Groups 1, 2, and 3, respectively. Specific sensitization was associated with positive skin reactions to common allergens, work-related symptoms, and BHR. These results suggest that students starting career programs with exposure to high-molecular-weight allergens have a low but substantial frequency of specific sensitization to work-related allergens that is related to atopy and BHR.     

Allelic polymorphism of the DNA-loci met and D7S23, linked to the mucoviscidosis gene in human populations of the Volga-Ural region

Data on allelic polymorphism of MET and D7S23 DNA loci linked to the human cystic fibrosis gene studied in three Bashkir ethnic groups and some Volga-Ural populations (Tartars, Maris, Mordovians, Udmurts, Chuvashs, and Komis) are presented. Udmurts were found to be substantially different from Bashkirs, Tartars, Mordovians, and Chuvashs by the allele frequency distribution observed for MET, while Komis and Bashkirs differed by this parameter from Mordovians and Maris. Comparative analysis of restriction fragment length polymorphism (RFLP) at the D7S23 locus revealed statistically significant differences in genotype frequencies between Bashkirs of the Arkhangel' skii region and populations of Mordva and Udmurtia. In this respect, the Mordovian population appeared to be notably different from the populations of Bashkortostan, Tatarstan, Marii-El, Udmurtiya, Chuvashiya, and Komis. Genetic distances were calculated and corresponding dendrograms were constructed on the basis of data on Met-H, CS.7, and the ApoB locus hypervariable region allelic frequencies. Three ethnogeographic Bashkir groups belonging to one tree branch were found to be closely related to the populations of Tartars, Maris, Udmurts, and Chuvashs and substantially different from Komis and Mordovians. Thus, the position of Volga-Ural populations on the dendrogram corresponds to the degree of relationship between the Finno-Ugric and Turkic populations, confirming the usefulness of DNA polymorphism analysis for the study of the genetic structure of populations.     

Effects of emoxipine and histochrome on lipid peroxidation and activity of serum MB-creatine phosphokinase in patients with ischemic heart disease during aortocoronary shunting]

Comparative study of the cardioprotective effect of antioxidants emoxipin and hystochrom was conducted in patients with chronic ICD during and after operation for aorto-coronary shunting. Both drugs effectively inhibited LPO activation and reduced the reperfusion damage to the myocardium recorded according to the release of MB-PCK into the blood. The new antioxidant hystochrom proved to be more effective. Its prevalent effect is associated with its higher antioxidant activity.     

A comparison of the association of helicopter and ground ambulance transport with the outcome of injury in trauma patients transported from the scene

INTRODUCTION: Comprehensive emergency medical services and helicopter aeromedical transport systems have been developed based on the principle that early definitive care improves outcome. The purpose of this study was to compare outcomes between patients transported by helicopter and those transported by ground. METHODS: Data were obtained from the North Carolina Trauma Registry for the period between 1987 and 1993 on all patients transported by helicopter and ground admitted to one of the eight state designated trauma centers. Study patients included only those who were transported directly from the scene of injury to the trauma center (interhospital transfers were excluded). Mortality (outcome) was compared after patient stratification by injury severity and transport time, using Cochran-Mantel-Haenszel statistics and logistic regression-derived probabilities of survival. RESULTS: One thousand three hundred forty-six patients (7.3% of the total) were transported from scene to trauma center by helicopter and 17,144 were transported by ground. In patients transported by helicopter, the mean Trauma Score was lower (12 +/- 3.6) versus 14.3 +/- 3.6 (p < 0.001) and the mean Injury Severity Score was higher (17 +/- 11.1) versus 10.8 +/- 8.4 (p < 0.001). A trend toward increased survival was observed among patients transported by helicopter with a higher Injury Severity Score. Statistical significance was achieved only for patients with a Trauma Score between 5 and 12 and Injury Severity Score between 21 and 30. CONCLUSION: The large majority of trauma patients transported by both helicopter and ground ambulance have low injury severity measures. Outcomes were not uniformly better among patients transported by helicopter. Only a very small subset of patients transported by helicopter appear to have any chance of improved survival based on their helicopter transport. This study suggests that further effort should be expended to try to better identify patients who may benefit from this expensive and risky mode of transport.     

Hemodynamic structure of antiorthostatic reactions: relationship of mechanical activity of the heart and arterial pressure

This paper is an update on the issue of dental student debt and provides additional data and an exploration of continued trends which were outlined by Douglass and Fein in the 1995 IOM study of The Future of Dental Education. Dental school tuitions have continued to increase at rates at or above the consumer price index. These tuition bills are increasingly being met by debt financing on the part of the students. These trends are described and then related to recent data on the future plans of dental school seniors. The second part of the paper will provide new updated date on dentists' incomes and analyze the trend in dental fees versus the consumer price index. The final section provides a summary of pay back mechanisms currently being offered to students.