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Brain concentrations of cocaine and benzoylecgonine in fatal cases.

Since cocaine in blood rapidly hydrolyzes to benzoylecgonine, cocaine concentrations determined in postmortem blood may not reflect the presence or concentration of cocaine in the body at the time of death. The interpretative value of the determination of cocaine and benzoylecgonine in brain tissue was investigated. Cocaine and benzoylecgonine were quantitated by coextraction and formation of the propyl derivative of benzoylecgonine followed by selected ion monitoring gas chromatography/mass spectrometry (GC/MS) using electron ion impact ionization. Cocaine and benzoylecgonine were found to be evenly distributed throughout the brain. Cocaine and benzoylecgonine concentrations were stable in frozen brain tissue (-4 degrees C) on reanalysis after 1 to 3 months of storage, and in refrigerated tissue (10 degrees C) after 30 days of storage. Blood, brain, and liver concentrations of cocaine and benzoylecgonine in 37 cocaine overdose cases and 46 cases in which cocaine was incidental to the cause of death were reviewed. The ratios of cocaine/benzoylecgonine in the toxic cases (brain mean 14.7 and blood mean 0.64) were clearly different from those found in the incidental cases (brain mean 0.87 and blood mean 0.27). The brain/blood ratios of cocaine and benzoylecgonine concentrations generally were characteristic of the time elapsed since cocaine dosing. In cocaine overdose cases, the mean ratio was 9.6 for cocaine and 0.36 for benzoylecgonine. These are within the range found in animal studies for brain/blood ratios of cocaine and benzoylecgonine 0.5 to 2 h after cocaine administration. In incidental cases, the brain/blood ratios were mean 2.5 for cocaine and 1.4 for benzoylecgonine.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗

Hematocrit levels and race: an argument against the adoption of separate standards in screening for anemia.

The average hematocrit levels of black children have been widely reported to be about two to three percent lower than those of white children. Until recently, the relative contributions of economic, nutritional, and genetic factors to these differences have been unspecified. Based on new evidence and reanalysis of past data, however, some investigators now argue that genetic differences exist which transcend economic status. Separate screening standards are thus recommended for black children-standards which would define fewer as anemic. The present paper discusses methodological inadequacies in the evidence supporting the separate standards argument, focusing on the skewed economic distributions by race which suggest economic disparities within the racial subgroups compared. Findings are presented from a study of children in Washington, DC, to illustrate the role of particular risk factors known to be differentially distributed by income (eg, multiparity, birthweight, source of medical care). These factors are associated with varying hematocrit levels, even among blacks, and they also appear to account for a large part of the black-white hematocrit differentials. Study findings cast doubt on conclusions about the genetic basis of hematocrit differences and suggest that, without better evidence, it would be inappropriate to adopt lower standards for blacks in screening for anemia.

Adult↗

Energetic cost of terrestrial locomotion: biped and quadruped runners compared.

Reanalysis of empirical data relating the energetic ost of running (Erun = cm3 02 g-1 km-1) to body mass (g) indicate the slopes of these regression analyses are indistinguishable when bipeds and quadrupeds are compared. The results agree with previous theoretical conclusions that the cost of transport in all runners scales on body mass (g) raised to the -1/3 power. The comparison also suggests that there is no difference between the energetic cost of maintaining a running posture for bipeds and quadrupeds and this postural cost is much less than original estimates.

Animals↗

Some published data on auditory localization reanalyzed within the framework of a model proposed by Searle, Braida, Davis, and Colburn.

The model for auditory localization proposed by Searle et al (J. Acoust. Soc. Am., 1976, 60, 1164-1175) was predicated on several assumptions and on data from restricted sound source loci. For example, only those studies were included using frontal-median plane sources and Ss with restrained head movements. The authors noted, however, that the model's generality needed to be tested by use of paradigms that gathered data from positions all around the S, and with data in which variables other than those accounted for by the model were utilized. Two studies (Gatehouse and Cox, J. Audit. Res., 1972, 12, 179-183, Gatehouse, J. Audit. Res., 1976, 16, 265-273) had required Ss to identify the position of a loudspeaker in both azimuth and elevation stimultaneously from a matrix of as many as 60 loci, but data had been reported only in per cent correct. The present paper offers a reanalysis of these data using average error in the spherical coordinates system of the model. Average-error analysis proved to be a relatively powerful tool, confirming the model to that extent. For example, a significant superiority of binaural over monaural performance in vertical plane localization was extracted from the data. Again, it could be shown that broadband noise, as compared with pure tones, provides useful binaural information in both the horizontal and vertical planes. Use of the model in studies of complex localization tasks may answer some unresolved issues and inconsistencies found in the general localization literature.

Analysis of Variance↗

Limitations of qualitative serum beta-HCG assays in the diagnosis of ectopic pregnancy.

Seventy-four patients had ectopic pregnancies proven by surgery. Three of them had a serum beta-HCG test for pregnancy that was reported as negative (less than 25-35 mIU/ml). We sought a threshold for positive in the serum beta-HCG test that would maximize its usefulness in diagnosing ectopic pregnancy. Sera from 52 of the patients were available for reanalysis. Quantitative values of beta-HCG were determined. Lowering the threshold for positive from 25-35 to 10 mIU/ml might increase the test's sensitivity without sacrificing specificity but would still not ensure detection of all ectopic pregnancies. Of 445 cases of ectopic pregnancy described in the literature, 6 had serum beta-HCG values reported as negative. In the published reports and in our own cases, clinical histories and histologies indicated that a nonviable ectopic pregnancy can be expected to have an associated serum concentration of beta-HCG that may be below the sensitivity of detection even with current, commercially available quantitative tests.

Adult↗

The uterotrophic effect of delta 9 THC in ovariectomized rats and mice.

We have reanalyzed the statistics on uterine weights used by Virgo in his article, The Estrogenicity of Delta-9-Tetrahydrocannabinol (THC): THC Neither Blocks nor Induces Ovum Implantation, nor does it Effect Uterine Growth, which appeared in Res. Comm. Chem. Path. and Pharmacol. 25:65-77 (1979). The reanalysis shows that administration of 3 and 6 mg/kg delta 9 THC to ovariectomized mice results in highly significant (P < .002; P < .0001 respectively) increases in uterine weights. These data are in accord with the uterotrophic effect of delta 9 THC observed in ovariectomized rats.

Animals↗

Human lymphocyte subpopulations identified by using three-color immunofluorescence and flow cytometry analysis: correlation of Leu-2, Leu-3, Leu-7, Leu-8, and Leu-11 cell surface antigen expression.

Three-color immunofluorescence has been used to determine the co-expression of cell surface antigens on human peripheral blood lymphocytes. Monoclonal antibodies or avidin were coupled to either FITC (green), phycoerythrin (orange), or Texas Red (red) fluorochromes. These three fluorochromes could be independently measured by using a dual laser FACS IV system equipped with an argon ion laser (488 nm) and a dye laser (600 nm). Human peripheral blood lymphocytes were stained with the following combinations of reagents: (1) FITC anti-Leu-11a + PE anti-Leu-2a + TR avidin/biotin anti-Leu-7; (2) FITC anti-Leu-11a + PE anti-Leu-3a + TR avidin/biotin anti-Leu-7; (3) FITC anti-Leu-8 + PE anti-Leu-2a + TR avidin/biotin anti-Leu-7; and (4) FITC anti-Leu-11a + PE anti-Leu-2 + TR avidin/biotin anti-Leu-8. The light scatter, green fluorescence, orange fluorescence, and red fluorescence signals for each sample were stored by a Consort 40 PDP/11 computer in list mode files. Sequential reanalysis of the data directly demonstrated the existence of several unrecognized subpopulations of lymphocytes. Previously, we reported that the anti-Leu-7 and anti-Leu-11 antibodies can be used to identify discrete subsets of human NK cells with distinct functional capacities. In this report, we show that these subsets can be further subdivided on the basis of Leu-8 and Leu-2 expression. Thus, these studies illustrate how multicolor and multiparameter flow cytometry can further our understanding of cellular heterogeneity within this group of lymphocytes.

Adult↗

Freud's Irma dream and the origins of psychoanalysis.

This paper investigates Freud's Irma dream as a response, in part, to the publication of Studies on Hysteria (Breuer & Freud, 1893-1895). As such, Freud's dream and associations reveal a great deal regarding the origins of psychoanalysis. The preamble to the dream reflects Freud's concern with the ground rules and boundaries of the psychotherapeutic technique that he was in the process of developing. This paper cites evidence for Freud's concerns regarding the consequences of alterations in these basic tenets. The Irma dream and Freud's associations also convey a deep and apparently unconscious concern within Freud in respect to the concept of transference, which he may have realized on some level had been used to defensively deny disturbing inputs by the therapist into the treatment situation and patient. The dream may be understood also as reflecting a deep sense of concern regarding unrecognized harmful effects of psychoanalytic psychotherapy and Freud's concern that the treatment process might be more destructive than helpful. The curative aspects of psychotherapy are viewed in terms of action-discharge rather than insight. In all, this reanalysis of the Irma dream focuses on Freud's unconscious conflicts, fantasies, and anxieties at a time when he, along with Breuer, presented a burgeoning psychoanalytic treatment modality to the professional world.

Austria↗

Weight, smoking, and mortality.

A controversy has existed concerning the relationship between body habitus and mortality. Original studies found that overweight persons were at risk for increased mortality, but later studies suggested that the very lean were also at high risk. The existence of a U-shaped relationship between mortality and body mass index was confirmed in a reanalysis of a 25-year follow-up of 1,503 men and 1,464 women, initially aged 40 to 65 years. Cigarette smoking did not explain the higher mortality among persons in the lowest body mass index category.

Adult↗

Segregation analysis incorporating linkage markers. I. Single-locus models with an application to type I diabetes.

A method is described for segregation analysis that incorporates linkage markers. The model allows for segregation (penetrance), linkage (recombination fraction), and association (linkage disequilibrium) parameters. A single-locus-multiple-allele model underlying the trait phenotype is assumed. When families have been ascertained in a systematic fashion, a joint (markers, phenotypes) likelihood with ascertainment is advocated. When ascertainment correction is not feasible, a conditional (markers given phenotypes) approach is recommended, which is also valid in the presence of reduced fertility and assortative mating. This approach, oriented toward determining mode of inheritance, differs from conventional linkage analysis, which is oriented toward detection of linkage. Therefore, it is more appropriately considered an extension of the affected sib-pair method to arbitrary pedigrees, including association information and allowing for multiple alleles. Incorporation of coupling parameters allows for discrimination between pleiotropy and linkage disequilibrium. The method is demonstrated through a reanalysis of four recently published family studies on type 1 diabetes and HLA. Recessive inheritance is rejected in all four data sets. For three of them, dominant inheritance is not rejected, while in the fourth, all two-allele models are rejected in favor of three alleles. Although association with the DR3 and DR4 alleles is quite strong, pleiotropy with regard to these alleles is unlikely. The results also suggest an additional familial factor(s) (e.g., locus).

Adult↗

Clinical usefulness of estriol assay for predicting "light-for-dates" infants.

A method was developed for determining clinical usefulness of a test for predicting "light-for-dates" infants before birth. The method was applied in a prospective study of assay of maternal estriol at 35-36 weeks of gestation as a means of identifying such infants. With the tenth centile for estriol values as the cutoff, low estriol values identified less than a third of all light-for-dates infants, and less than a third of pregnancies with low estriol values were associated with births of light-for-dates infants. Our reanalysis of data from three other published studies, using the same method of assessment, gave similar results. When laboratory tests are expected to provide clinically relevant information, we urge that data should be appropriately collected, analyzed, and reported, so clinical usefulness can be evaluated.

Estriol↗

Differential expression of Ia glycoprotein complexes in F1 hybrid mice detected with alloreactive cloned T cell lines.

T cell lines alloreactive to Aeb:E alpha Ia antigen complexes have been prepared and used to determine the relative amount of Aeb:E alpha expressed by stimulator cells in homozygous recombinant and F1 mice expressing these complexes. We find that homozygous cells stimulate most strongly and therefore probably express the highest density of Aeb:E alpha. Among heterozygotes, H-2bxd F1 mice preferentially express Aeb:E alpha d complexes, H-2bxa F1 mice express relatively fewer Aeb:E alpha k complexes, and H-2bxu F1 mice express preferentially Aeu:E alpha u complexes. This differential association of Aeb chains with E alpha chains thus influences the biologic activity of these Ia antigens in this and other functional assays. The functional data are supported by biochemical analysis of Aeb:E alpha complex expression. These findings suggest that a reanalysis of HLA-DR associations with human diseases should be undertaken in which both HLA-DR alleles are included, with the prediction that certain combinations would show greater susceptibility, whereas others would show less susceptibility than predicted from the susceptibility associated with presence of a single allele at HLA-DR.

Animals↗

A rapid and sensitive method for the determination of non-volatile n-nitroso compounds in foods and human urine: recent data concerning volatile N-nitrosamines in dried foods and malt-based beverages.

Methods are described for the rapid screening of various foods for the presence of nitrosamino acids (mainly NPRO and NSAR) and of hydroxylated nitrosamines (mainly BHBN, NHPYR and NDELA). Rapid screening methods (HPLC-TEA and GC-TEA) are also described for the determination of the above mentioned nitrosamines in human urine. Recent monitoring data indicate that, in Canada, the NDMA levels in both malt and beer have decreased significantly during the last two years. Contrary to published reports, no volatile nitrosamines could be detected in vegetable oils or pasteurized milk. A new method, based on oxidation of nitrosamines and nitramines and reanalysis by GC-TEA, is described for the confirmation of low microgram/kg levels of volatile nitrosamines in foods.

Beer↗

Search heuristics of chess players of different calibers.

Information-processing models of chess-playing ability have distinguished between players of different calibers solely in terms of perceptual encoding and recognition of chess configurations. A reanalysis of deGroot's verbal protocols of 1965 indicates that players of different calibers direct their attention toward different areas of the board. Grandmasters and masters consider squares that are affected by many pieces, while lesser players direct their attention toward squares on which the pieces are located. In a recall experiment, chess positions were presented that had been randomly generated so as to differ only in the degree to which the pieces converge on the same squares. Masters showed superior recall for briefly presented positions only when the material affects a highly centralized area of the board.

Attention↗

Circadian murine ouabain chronotolerance revisited.

Data published earlier on a possible circadian variation in murine susceptibility to intravenously-administered ouabain and analyzed by conventional biometric methods, were reanalyzed by cosinor procedures. A statistically significant circadian rhythm could thus be demonstrated, contradicting the earlier conclusion that there was no circadian rhythm in susceptibility to ouabain when injected intravenously. Results from this reanalysis agreed with those from previous investigations in which ouabain was injected intraperitoneally or subcutaneously. Thus, a circadian rhythm characterizes murine susceptibility to ouabain given via 3 different routes.

Animals↗

Breast cancer in DES-exposed mothers: absence of association.

Reports in the popular press have suggested that exposure to diethylstilbestrol (DES) is followed by an abnormally high incidence of breast cancer. The reports were based on a reanalysis of data not considered ominous originally; and both data and analyses are summarized here. In addition, new data are presented on mothers of young women enrolled in the National DESAD Project at its Mayo Clinic Center. Among 408 women given DES, there were 8 confirmed instances of breast cancer, in comparison with an expected number of 8.1, based on breast cancer incidence rates among parous women in the local population. A previous case-control study of the possible association of antihypertensive therapy and breast cancer in the local population revealed DES exposure in 10% of the breast cancer group and 12% of the controls. These apparently negative results clearly indicate a need of further studies of the alleged effect of DES.

Adult↗

Circadian and circannual aspects of the complement cascade - new and old results, differing in specificity.

Single cosinor analyses of several elements in the complement cascade suggest the occurrence of circadian rhythms in this immunochemical system. Some earlier results, obtained with less specific methods and reported as properdin, on reanalysis also reveal circadian and circannual rhythms in the aspects of immunology represented. The topic of the complement cascade as a whole is briefly reviewed in the content of modern knowledge.

Adult↗

Principles of selection and use of antibacterial agents.

Treatment of infection involves a complex interaction among the infecting organism (susceptibility to the therapeutic agent), host factors (immune function, site of infection, renal and hepatic metabolism), and pharmacokinetics (rate of absorption, distribution and excretion). Successful therapy requires careful consideration of these factors, and unsuccessful treatment should invoke a careful reanalysis of them.

Anti-Bacterial Agents↗