Sources of Variability in the Detection of Cerebral Emboli with Transcranial Doppler During Cardiac Surgery

OBJECTIVE: The application of intensity thresholds for embolus detection with transcranial Doppler (TCD) can exclude from analysis an unrecognized proportion of high-intensity transient signals (HITS))whose intensities are below the threshold. The lack of consistent threshold criteria between clinical trials may explain part of the discrepancy in the reported HITS counts. We investigated the effect of choosing different thresholds on the sensitivity and specificity of detecting HITS during cardiopulmonary bypass (CPB). METHODS: Two observers independently analyzed TCD recordings from 8 patients under CPB. Doppler signals were classified as true HITS, equivocal HITS, artifacts, and Doppler speckles according to preestablished criteria. The relative intensity of Doppler signals was measured by two different methods (TCD software vs manual). Receiver Operating Characteristic curves determined the optimal threshold for each of the two intensity methods. RESULTS: Reviewers achieved agreement in 96% of 2190 Doppler signals (kappa = 0.90). Relative intensities calculated with the TCD-software method were 3 dB (95% CI: 3.0-3.4) higher than the manual method. The optimal threshold was found at 10 dB (sensitivity: 99%; specificity: 90.8%) with the software method and at 7 dB with the manual method (sensitivity: 96%; specificity: 83%). The use of an intensity threshold 2 dB higher than the optimal increased the rejection of true HITS by 8% and 14%, respectively. CONCLUSIONS: Using intensity thresholds higher than the optimal for embolus detection decreases HITS counts. Choosing a threshold depends on the type of method used for measuring the signal intensity. Uniform threshold criteria and comparative studies between different Doppler devices are necessary for making clinical trials more comparable.     

Periodontal status of orthodontic patients and the relationship between dental aesthetic index and community periodontal index of treatment need

This prospective clinic-based study evaluated the pretreatment periodontal status of the orthodontic patients seen at the University College Hospital, Ibadan, Nigeria, and assessed the relationship between dental aesthetic index (DAI) scores and periodontal status according to community periodontal index of treatment needs (CPITN) scores. One hundred forty five patients-70 (48.3%) males and 75 (51.7%) females from 6 to 45 years (mean 15.8 +/- 7.5)-were seen. World Health Organization (WHO) guidelines were followed in the examination and reporting of the periodontal status, and DAI scores were assessed based on WHO guidelines. The chi-square test was used to determine the association between the DAI and the CPITN scores. Most patients were in the 6-15 (55.9%) or 16-25 (35.9%) age groups. Based on the WHO preferred cumulative calculations of treatment need (TN), 35.2% of the patients had TN 0, 64.9% had TN 1, 24.9% had TN 2, and only 0.7% had TN 3. The relationship between DAI scores and periodontal treatment needs was not statistically significant (P >.05). Although many patients were yet to attain the WHO goal of no more than 1 sextant affected by bleeding or calculus at the age of 15, over one third had satisfactory periodontal health.     

Human hepatocellular carcinoma tumor xenografts

Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivostudies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.     

Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Influence of Inhaled Corticosteroids and Dietary Intake on Bone Density and Metabolism in Patients With Moderate to Severe Asthma

Objectives Compare the effect of high doses of inhaled corticosteroids on bone loss in subjects with moderate to severe asthma or mild asthma, and examine the influence of dietary intake on bone metabolism. Design A survey on the effects of corticotherapy and nutrition on bone density was conducted in 74 subjects currently being treated for asthma in the asthma clinic of Hospital Laval (Sainte-Foy, Quebec, Canada). Fifty-eight subjects completed the study (attrition RATE=15%).

Main outcome measures In all subjects expiratory volumes were determined and urinary analysis was conducted for hydroxyproline, calcium, phosphorus, and cortisol levels. Osteocalcin, calcium, phosphorus, cortisol, alkaline phosphatase, and γ-glutamyltransferase levels were measured in blood samples. Bone density of the lumbar spine was determined by means of dual-energy x-ray absorptiometry. Nutrition evaluation was based on a 3-day food diary analyzed using progiciel Nutri 91. The nutritional parameters examined were calcium; phosphorus; magnesium; zinc; vitamins A, C, and D; protein; total fiber; oxalates; energy; caffeine; and alcohol in relation to bone density.

Subjects Thirty-one patients with moderate to severe asthma who had been taking more than 1,000 μg beclomethasone per day or the equivalent for more than 2 years and 27 patients with mild asthma who were taking less than 500 μg beclomethasone per day or the equivalent.

Statistical analyses performed Four factor analysis of variance with hierarchized interactions of four levels, Duncan's test, Pearson correlation coefficients.

Results Blood levels of osteocalcin and protein intake were lower in patients with moderate to severe asthma than in those with mild asthma (P<.05). Significant correlations (P<.02) were observed between bone density and calcium intake (r=.40), phosphorus intake (r=.35), protein intake (r=.30), and serum alkaline phosphatase level (r=−.30). Bone density was not significantly different between the two groups of patients with asthma.

Applications A follow-up of patients with asthma who are taking inhaled corticosteroids is needed to assess bone density, osteocalcin levels, and dietary intakes of calcium. Verify if osteocalcin level decreases over time in patients with moderate to severe asthma, monitor possible modifications in bone density, and verify if the correlation between dietary calcium and bone density is maintained. J Am Diet Assoc. 1997;97:1401–1406.     

Functional and immunohistochemical studies of cultured rat microglia

We studied functional and immunohistochemical characteristics of cultured rat microglia. Unstimulated microglia did not proliferate. Microglia stimulated with LCM (L929 conditioned medium: colony stimulating factor-1) had proliferative activity and increased acid phosphatase activity. LPS (lipopolysaccharide) and IFN gamma (interferon-gamma) but did not affect proliferative activity. Immunohistochemically, RCA-1 lectin and GS-1 lectin, which react to beta-D-galactose and alpha-D-galactose respectively, strongly reacted to the cytoplasm and membrane of unstimulated microglia. After stimulation with LCM, microglia elongated processes and decreased response to these lectins. On the other hand, microglia stimulated with LCM showed increased reactivity to monoclonal antibody of vimentin. Microglia stimulated with LPS had round shape and had response to these lectins and vimentin. Microglia stimulated with IFN gamma had adhesive activity and weakly stained with these lectins but not with vimentin. ED-1 (monoclonal antibody of rat monocytes/macrophages) reacted to unstimulated and stimulated microglia. In flow cytometry, unstimulated microglia expressed OX-18 (MHC class I) and W3/25 (CD4) antigen. After stimulation with IFN gamma, microglia were induced to express these antigens. CD4 antigen is a marker of helper/inducer T cells and thought to be a receptor of HIV. The results that microglia had CD4 antigen which was further induced with IFN gamma are important to investigate infection of the CNS with HIV. OX-6 (Ia) antigen was induced with IFN gamma. This indicates that the microglia plays a central role in the CNS immune reaction. These characteristics of cultured rat microglia provide useful informations to investigate the pathogenesis of the CNS disorders.