Hybridization techniques provide improved sensitivity for HCMV detection and allow quantitation of the virus in clinical samples

Hybridization techniques (slot-blot and in-situ hybridization assays) and immunostaining using murine monoclonal antibodies directed against different proteins of the human cytomegalovirus (HCMV) were compared for their sensitivity and specificity for detection of HCMV. A model system with HCMV infected human embryonic lung fibroblasts and lung biopsy specimens obtained from patients with culture positive HCMV interstitial pneumonia were used for evaluation of these techniques. The hybridization techniques were found to provide an improved sensitivity compared to immunostaining. Additionally a good correlation was found between the virus dose determined by TCID50 and the amount of viral DNA detected by slot-blot hybridization and by the number of autoradiographic silver grains per 100 cells per 2 weeks exposure time detected in the infected fibroblasts by in-situ hybridization. Thus, at least in the model system quantification of the virus was achieved by hybridization assays.     

Rapid Techniques in Diagnostic Electron Microscopy

This paper summarizes the rapid preparation procedures for electron microscopy published thus far and assesses their strengths and weaknesses. We also discuss whether there is a real need for rapid preparation techniques in diagnostic electron microscopic work.     

Measuring contraceptive values: An alternative approach

Previous assessments of individuals' values for various contraceptive consequences have employed one of four methodologies: free elicitation, direct ratings, multiple regression, or factor analysis. All four methodologies are flawed because they produce group rather than individual values, rely on rating scales, and fail to incorporate information regarding consequence trade-offs. Axiomatic conjoint measurement is proposed as an alternative methodology and used to determine individuals' values for a selected set of contraceptive consequences at two stages of the family-planning career.Preparation of this paper was supported in part by Grants HD-10802 and HD-14403 from the National Institute of Child Health and Human Development. Appreciation is due the Statistical Computing Facility of the University of California at Berkeley. Requests for reprints should be sent to the Publications Librarian, Center for Research on Judgment and Policy, Muenzinger Psychology Building, University of Colorado, Boulder, Colorado 80309-0344.     

Turnaround time, Part 2. Stats too high, yet labs cope

Up to 65% of respondents' workload is ordered Stat, and lab staff view clinicians and nurses as resistant to changing that strategy. MLO's national survey examines Stat necessity and utility.     

Focal hepatic glycogenosis

Foci of altered hepatocytes (FAH) including clear cell foci excessively storing glycogen (focal hepatic glycogenosis) are well known as preneoplastic lesions in animal models of hepatocarcinogenesis induced by chemical, physical or viral agents. The occurrence of similar lesions has been studied in a series of 67 explanted and 2 resected human livers using histological and histochemical approaches. A high incidence of FAH was found in the liver of patients suffering from hepatocellular carcinoma(HCC, 14/14) and liver cirrhosis (21/42). FAH were also detected in one patient each with inborn hepatic glycogenosis type 1a, and cholangiocellular carcinoma. Two patients with focal nodular hyperplasia had FAH-like enzymatic changes within these lesions. No FAH were found in 5 donor livers. FAH excessively storing glycogen including clear and mixed cell foci predominated in most cases with these lesions. The focal hepatic glycogenosis was associated with a significantly increased cell proliferation compared to the extrafocal parenchyma, and with alterations in the activity of various enzymes. In the 175 FAH studied by enzyme histochemistry, two enzymes involved in glycogen breakdown, namely glycogen phosphorylase and glucose-6-phosphatase, showed the most consistent changes, being reduced in 98% and 95%, respectively. In addition, the activities of adenosine triphosphatase and gamma-glutamyltransferase were reduced in 46% and 53% of FAH, respectively. Inconsistent changes were observed in FAH concerning a number of other enzymes. The 14 HCCs investigated histochemically often contained clear cell populations rich in glycogen in well differentiated portions, but were poor in glycogen in moderately and poorly differentiated tumors or tumor components. There were some similarities in the enzyme histochemical pattern of HCC and FAH but also important differences were evident. In contrast to FAH, all HCCs (except one carcinoma of the fibrolamellar type) showed an increase in the activity of the mitochondrial glycerol-3-phosphate dehydrogenase, and 50% of the cases had increased glucose-6-phosphate dehydrogenase activity. The activities of glucose-6-phosphatase and gamma-glutamyltransferase usually showed a reactivation, or even an increase compared to the extrafocal parenchyma, in moderately and poorly differentiated HCCs. Our results indicate that the focal hepatic glycogenosis is a putative preneoplastic lesion in human beings similar to laboratory animals. The focal hepatic glycogenosis appears to be a frequent initial step in neoplastic transformation of hepatocytes, a process associated with a fundamental shift in energy metabolism.     

Esmolol,an ultrashort-acting,selective β1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties

The effects of esmolol at different rates of infusion (100, 250 and 500 g·kg^–1 BW·min^–1) were compared with -adrenoceptor occupancy (₁ and ₂, estimated by a subtype selective radioreceptor assay) and plasma concentrations of esmolol and its acid metabolite were measured by HPLC. Up to a rate of infusion of esmolol of 500 g·kg^–1 BW·min^–1 there was a maximal ₁-receptor occupancy of 84.7% while ₂-receptor occupancy was below the detection limit; confirming the ₁ selectivity of esmolol. Exercise-induced increases in heart rate and systolic blood pressure were reduced by esmolol in a dose-dependent manner. The estimated EC₅₀ values of rate of infusion for the reduction in heart rate and systolic blood pressure during exercise were 113 and 134 g·kg^–1 BW · min^–1, respectively. Additionally, heart rate and systolic blood pressure were reduced moderately at rest. Because of the short elimination half-life of esmolol caused by the rapid hydrolysis to its acid metabolite, 45 min after end of infusion high plasma concentrations of the metabolite (maximally 80 g·ml^–1) but no esmolol were detectable. Since no in vivo effects have been observed, despite the presence of high plasma concentrations of the metabolite, the metabolite did not participate in the observed effects up to an infusion rate of esmolol of 500 g·kg^–1 BW·min^–1. The plasma concentrations of antagonist detected by radioreceptor assay and plasma concentrations of esmolol detected by HPLC showed a good correlation (r=0.97). Since the cardiovascular effects, determined before and 45 min after termination of infusion of esmolol were similar, it can be concluded that the observed effects on heart rate and systolic blood pressure are exclusively mediated by esmolol.Dedicated to Dr. P.Rajagopal, Kuantan Specialist Hospital, Kuantan, Malaysia     

Sexual orientation and performance on sexually dimorphic motor tasks

Performance of homosexual and heterosexual men and women on two motor tasks which reliably demonstrate sex differences in opposite directions was examined. A Throw-to-Target Task and the Purdue Pegboard were administered to undergraduate students matched for age and program of study. A two-way ANOVA (Sex × Sexual Orientation) of the Throw data showed a significant interaction,F(1, 90) = 16.22,p 0.001, and a trend for an effect of sex,F(1, 90) = 3.72,p < 0.06. Heterosexual men outperformed heterosexual women, whereas gay men threw less accurately and lesbians tended to throw more accurately than their heterosexual counterparts. Differences in sports history or hand strength did not account for these effects. Analysis of the Pegboard scores found no interaction or main effect of sexual orientation, but the effect of sex was significant,F(1,63) = 7.01,p 0.02. Regardless of sexual orientation, women outperformed men and this difference remained significant even when a measure of finger size was partialed out. This study provides new evidence suggesting an association between sexual orientation and motor-performance profiles. As with cognitive tasks, the motor-performance profiles of homosexuals are composites of some male-typical and some female-typical abilities. To the extent that sociological factors have been controlled, the study suggests that both sexual orientation and motor/cognitive predispositions may have early biological contributions.This research was supported by a grant from the Medical Research Council, Ottawa, to D. Kimura.