Influence of Viral Infections on Body Weight, Survival, and Tumor Prevalence of B6C3F1 (C57BL/6N ? C3H/HeN) Mice in Carcinogenicity Studies

Sendai virus (SV), mouse hepatitis virus (MHV), and pneumoniavirus of mice (PVM) are common viral infections of mice. Influenceof these viral infections on the prevalence of liver tumors,lung tumors, and lymphoma is of concern in chemical carcinogenicitystudies. Body weight, survival, and tumor prevalence of B6C3F1mice with and without viral infections in 33 male and 34 femaleuntreated control groups and 32 male and 32 female low- andhigh-dose groups of 2-year chemical carcinogenicity studieswere evaluated. In male mice, the SV infection was associatedwith significantly (p < 0.05) higher survival of control,low-dose, and high-dose groups, and higher prevalence of livertumors and lymphoma. The increases in tumor prevalence are possiblydue to an increase in the survival of male mice that had SVinfection. However, when interlaboratory variability and time-relatedeffects were taken into account, the number of significant effectswas consistent with the expected false-positive rate inherentto the statistical procedures. The MHV and PVM infections didnot cause consistent changes in body weight, survival, and tumorprevalences in the control and chemical treatment groups ofmale mice. Viral infections did not cause consistent increasesor decreases in body weight, survival, or tumor prevalence inthe control and chemical treatment groups of female B6C3F1 mice.     

Preclinical Toxicology Studies with Acyclovir: Genetic Toxicity Tests

Preclinical Toxicology Studies with Acyclovir: Genetic ToxicityTests. Clive, D., Turner, N.T., Hozier, J., Batson, A.G. andTucker, W.E., Jr. (1983). Fundam. Appl. Toxicol 3: 587–602.Acyclovir (ACV), an antiviral drug active in the treatment oforal and genital Herpes infections, has been evaluated for mutagenicand carcinogenic potential in a battery of in vitro and in vivoshort-termassays. Negative results were obtained in the following in vitrotests: Ames Salmonella, plate incorporation and preincubationmodification assays; E. coli polA⁺/polA^– DNA repair; yeast(S. cerevisiae D4) gene conversion; Chinese hamster ovary cells(HGPRT, APRT loci and ouabain-resistance marker); L5178 Y mouselymphoma cells (HGPRT locus and ouabain-resistance marker);and C3H/10Tmouse fibroblast neo-plastic transformation assay.All except the last assay were performed in the presence andabsence of an exogenous metabolic activation system. ACV waspositive at high concentrations x exposure times in the absenceof exogenous metabolic activation in the following in vitrosystems and at the indicated concentrations: BALB/c-3T3 neoplastictransformation (50 /µg/mL, 72 h exposure); human lymphocytecytogenetics (250–500 µg/mL, 48 h exposure); andL5178Y mouse lymphoma cells (TK locus, 400–2400 µg/mL,4 h exposure; predominantly small colony mutants of chromosomalorigin produced). No effects were seen in vivo (mouse dominantlethal assay; rat and Chinese hamster bone marrow cytogenetics)at up to maximum tolerated doses (MTD). An unusual clastogeniceffect was seen in Chinese hamsters at 5 times the MTD. Overall,positive effects were seen only at either high concentrations(250 µg/mL in vitro or plasma levels) or prolonged exposure(72 hr in the BALB/ c-3T3 neoplastic transformation assay).These studies support the view that ACV is a chromosomal mutagen,i.e., one which causes multi-locus damage but not single geneeffects. The significance of these results for the genetic riskof ACV to man is discussed.     

Acrylamide: Dermal Exposure Produces Genetic Damage in Male Mouse Germ Cells

Acrylamide is used extensively in sewage and wastewater treatmentplants, in the paper and pulp industry, in treatment of potablewater, and in research laboratories for chromatography, electrophoresis,and electron microscopy. Dermal contact is a major route ofhuman exposure. It has been shown that acrylamide is highlyeffective in breaking chromosomes of germ cells of male miceand rats when administered intraperitoneally or orally, resultingboth in the early death of conceptuses and in the transmissionof reciprocal translocations to live-born progeny. It is nowreported that acrylamide is absorbed through the skin of malemice, reaches the germ cells, and induces chromosomal damage.The magnitude of genetic damage appears to be proportional tothe dose administered topically.     

A Tridimensional View of Intradermal Nevi as Revealed by Scanning Electron Microscopy

When scanning electron microscopy (SEM) was applied to the study of intradermal nevi, interesting tridimensional features were recognized. The free surface of the lesions showed ruffled keratinized cells. "Normal" hairs as well as "corkscrew" hairs emerged from the follicular openings. Nevus cells were either round or elongated and surrounded by connective tissue fibers.     

The effects of routine oxytocic administration in the management of the third stage of labour: an overview of the evidence from controlled trials

Summary. Recent claims that routine active management of the third stage of labour increases rather than decreases maternal and neonatal morbidity have prompted us to conduct a systematic review of the relevant controlled trials. In this paper we have analysed data derived from a total of nine published reports of controlled trials in which an oxytocic drug was compared with either a placebo or no routine prophylactic. Oxytocic drugs used routinely appear to reduce the risk of postpartum haemorrhage by about 40% (typical odds ratio 0·57, 95% confidence interval 0·44–0·73) implying that for every 22 women given such an oxytocic, one postpartum haemorrhage could be prevented. The available data are insufficient to assess the possible effects of this policy on the incidence of retained placenta, hypertension and other possible adverse effects.     

Classical versus low-segment transverse incision for preterm caesarean section: maternal complications and outcome of subsequent pregnancies

Summary. In a retrospective, controlled, follow-up study of 326 women who had a primary preterm caesarean section, the risks of postoperative maternal morbidity and uterine rupture or dehiscence in subsequent pregnancies were investigated in relation to the mode of incision (classical compared with low-segment transverse incision). The classical incision was associated with a higher frequency of postpartum fever in the immediate postoperative period (16% compared with 6%, P<0·01). Of the 326 patients reviewed 286 (88%) were contacted for information about subsequent pregnancies. Information was obtained for 70 pregnancies subsequent to a classical caesarean section, and 71 pregnancies subsequent to a low-segment transverse caesarean section, which had continued for more than 20 weeks gestation. Of the pregnancies after the classical operation 13% had abnormal scars compared with none of those after the low-segment transverse operation ( P =0·0014). The frequency of scar dehiscence was 6% after a classical scar compared with none after a low-segment transverse scar (P=0·0581).     

Vecuronium titration for muscle relaxation in myotonic dystrophy

A 14-year-old boy with pronounced myotonic dystrophy and cardiac malformation had a normal ED₉₅ (53 μg·kg^?1) of vecuronium, whereas the recovery index (25-75% twitch recovery) was three times as long as in the absence of neuromuscular disease. We conclude that in young patients with dystrophic muscle disease individual titration of the muscle relaxant with the aid of a nerve stimulator does not preclude a considerable delay in the recovery of neuromuscular transmission.     

Working memory and preparation elicit different patterns of slow wave event-related brain potentials

Some event-related brain potential (ERP) studies of working memory have used delayed match-to-sample designs in which a stimulus (S1) is held in memory for comparison with a subsequent stimulus (S2). During the S1-S2 interval, ERP slow negativities varied with both the type and amount of material held in working memory. One interpretation is that these slow waves index working memory operations. An alternative explanation is that they only reflect general preparatory processing for the response to S2. To decide between these explanations, we used two visual processing tasks that required similar preparation for S2. In one task, visual memory rehearsal operations were required. During the S1-S2 interval, there were clear differences between the amplitudes, topographies, and the effect of information load on the slow waves in the two tasks, thus ruling out preparation only as an explanation.