Outbreak of serogroup C meningococcal disease associated with campus bar patronage

Between February 1991 and April 1992, eight undergraduates at a US residential university and one at a nearby 2-year college contracted serogroup C meningococcal disease. A case-control investigation with 20 controls per case, oropharyngeal carriage surveys, and multilocus enzyme electrophoresis (MEE) of serogroup C isolates were used to identify factors contributing to the outbreak. All eight sterile-site isolates from cases were closely related by MEE and were similar (though not identical) to the strain associated with the 1991-1992 epidemic of meningococcal disease in eastern Canada. Disease was associated with cigarette smoking (p = 0.012), recent patronage of campus-area bars (p = 0.034), estimated amount of time spent in campus-area bars (p = 0.0003), and, especially, recent patronage of one specific bar, bar A (p = 0.0006; odds ratio = 23.1, 95% confidence interval 3.0-571.5). In carriage surveys, 1,528 throat cultures taken from (primarily student) noncases yielded only five (0.3%) strains that were identical by MEE to those from cases. Two of these were found among 22 cultures obtained from bar A employees in spring 1992. Some cases in this outbreak may have followed transmission of the epidemic strain in bar A. Campus bar environments may facilitate the spread of meningococcal disease among teenagers and young adults.     

Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat

In normal subjects, if an acoustic startle stimulus is immediately preceded by a small brief change in background noise intensity, the magnitude of the subsequent startle response is decreased. This prepulse inhibition (PPI) of an acoustic startle response has been shown to be associated with sensorimotor gating. PPI is disrupted in schizophrenic patients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 mumol/kg IP) (equivalent to 0.03, 0.1, and 0.3 mg/kg base) and the nicotinic cholinergic receptor (nAChR) channel blocker, mecamylamine (5.0 and 50 mumol/kg IP) (equivalent to 1.0 and 10.0 mg/kg) on PPI of the acoustic startle response in the rat. Nicotine increased the PPI at the lowest prepulse signal levels but not at the stronger levels. Mecamylamine was without effect at 5.0 mumol/kg, but the 50 mumol/kg dose decreased the inhibition at both weak and strong prepulse (PP) levels. Mecamylamine (5.0 mumol/kg) pretreatment did not block the (-)-nicotine-induced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mumol/kg IP) (equivalent to 0.071, 0.23, 0.71, and 2.3 mg/kg) was without effect. These results are consistent with a mecamylamine-insensitive effect of nicotine to improve gating in normal rats. The nAChR subtype involved in producing nicotine's increase of PPI needs further investigation.     

Temporal bone volumetric image deblurring in spiral computed tomography scanning

RATIONALE AND OBJECTIVES: We developed a method for volumetric image deblurring in spiral (helical) computed tomography (CT) scanning with a three-dimensional (3D) Gaussian point spread function (PSF) to improve the quality of temporal bone spiral CT images for assessing the position of cochlear implants electrodes. METHODS: A patient was scanned after cochlear implantation, and the temporal bone was reconstructed into a volume with 128 voxels per dimension, 0.1 mm per voxel side, and x 10 gray-scale expansion. The 3D PSF in spiral CT imaging was assumed to be Gaussian separable transversely and longitudinally. Standard deviations of the PSF were derived and subjectively adjusted. The image was then deconvolved using Wiener filtering and maximum-likelihood deconvolution methods. Image quality was assessed both visually and quantitatively using cross-sectional area at half of the maximum (CAHM) of the implanted array as the figure of merit. RESULTS: Substantial image deblurring was achieved via deconvolution. Subjectively, anatomic structures were more clearly shown. Deconvolution reduced the CAHM by approximately one third, on average. Three-dimensional deconvolution had better image quality than two-dimensional deconvolution. The maximum-likelihood method produced superior image quality but took longer to process relative to Wiener filtering. CONCLUSION: Volumetric image deblurring is practical with a Gaussian PSF. The maximum-likelihood method is preferred if time permits. Deconvolution facilitates the study of fine details of the temporal bone and cochlear implant.     

Bone marrow and renal injury associated with haloalkene cysteine conjugates in calves

Almost 40 years ago, it was reported that cattle-feed which had been extracted with hot trichloroethylene and then fed to calves produced renal injury and a fatal aplastic anaemia. The toxic factor was subsequently identified as S-(1,2-dichlorovinyl)-L-cysteine (DCVC). These original findings have been confirmed, a single intravenous dose of DCVC at 4 mg/kg, or 0.4 mg/kg intravenously per day administered for 10 days to calves produced aplastic anaemia, and renal injury after a single dose of 4 mg/kg. The toxicity to calves of a number of other haloalkene cysteine conjugates has been examined to ascertain whether, like DCVC, they produce bone marrow and renal injury. Intravenous administration of the N-acetyl cysteine conjugate of DCVC produced renal but not bone marrow injury at a molar equivalent dose to DCVC, indicating that the calf can deacetylate the mercapturic acid and further that sufficient chemical had reached the kidney to be a substrate for the enzyme cysteine conjugate beta-lyase. However, intravenous administration of the alpha-methyl analogue of DCVC, which cannot undergo metabolism via the enzyme cysteine conjugate beta-lyase, was without toxicity at doses about five-fold higher than DCVC. These latter findings provide strong evidence that metabolism of DCVC via the enzyme beta-lyase is necessary for bone marrow and renal injury to occur. The cysteine conjugates of perchloroethylene and hexachloro-1,3-butadiene(HCBD) when given intravenously to calves at molar equivalent doses to DCVC, or above, did not produce either bone marrow or renal injury. In contrast, intravenous administration of the cysteine conjugate of tetrafluoroethylene (TFEC) produced severe renal tubular injury in calves without affecting the bone marrow. In vitro studies with these haloalkene cysteine conjugates showed, like DCVC, that they were good substrates for calf renal cysteine conjugate beta-lyase and toxic to renal cells as judged by their ability to reduce organic anion and cation transport by slices of calf renal cortex and inhibit the renal enzyme glutathione reductase. Calves were also dosed either orally or intravenously with HCBD to assess its toxicity. HCBD at higher molar equivalent doses than DCVC produced mid-zonal necrosis in the liver, renal tubular necrosis but no bone marrow injury in calves. The key findings emerging from these studies are (1) that none of the other cysteine conjugates, at molar equivalent doses to DCVC and above, produce bone marrow injury in calves, (2) TFEC produced only renal injury, suggesting that sufficient of the other conjugates had not reached the kidney for metabolism by beta-lyase to produce cytotoxicity and (3) that HCBD itself is more toxic than its cysteine or mercapturic acid conjugate, suggesting that pharmaco-kinetics and disposition are important factors in determining the toxicity of these conjugates to calves. Further studies are needed to understand the basis for the selective toxicity of DCVC to the bone marrow of calves.     

The use of toxicologic data in mechanistic risk assessment: 1,3-butadiene as a case study

The National Research Council (NRC) recently published a report. Science and Judgment in Risk Assessment, that critiqued the current approaches to characterizing human cancer risks from exposure to chemicals. One issue raised in the report relates to the use of default options for quantitation of cancer risks. Default options are general guidelines that can be used for risk assessment when specific information about a chemical is absent. Research on 1,3-butadiene represents an interesting case study in which existing knowledge on this chemical indicates that two default options may no longer be tenable: (1) humans are as sensitive as the most sensitive animal species, and (2) the rate of metabolism is a function of body surface area rather than inherent species differences in metabolic capacity. Butadiene, a major commodity chemical used in the production of synthetic rubber, is listed as one of 189 hazardous air pollutants under the 1990 Clean Air Act Amendments. Butadiene is a carcinogen in rats and mice, with mice being substantially more sensitive than rats. The extent to which butadiene poses a cancer risk to humans exposed to this chemical is uncertain. Butadiene requires metabolic activation to DNA-reactive epoxides to exert its mutagenic and carcinogenic effects. Research is directed toward obtaining a better understanding of the cancer risks of butadiene in humans by evaluating species-dependent differences in the formation of the toxic butadiene epoxide metabolites, epoxybutene and diepoxybutane. The data include in-vitro studies on butadiene metabolism using tissues from humans, rats, and mice as well as experimental data and physiological model predictions for butadiene in blood and butadiene epoxides in blood, lung, and liver after exposure of rats and mice to inhaled butadiene. The findings suggest that humans are more like rats and less like mice regarding the formation of butadiene epoxides. The research approach employed can be a useful strategy for developing mechanistic and toxicokinetic data to supplant default options used in carcinogen risk assessments for butadiene.     

Cognitive shifting as a predictor of progress in social understanding in high-functioning adolescents with autism: a prospective study

The pyrolytic behavior of inulin, a (2-->1)-linked fructofuranan, is described. Parallel investigations of the pyrolysis of glucose and of fructose were conducted to supplement the inulin results and to aid comparison with previous results from glucans. Effects of neutral and basic additives are emphasized. As with glucans, the addition of such additives (especially basic) increases the yields of the one-, two-, and three-carbon products (as well as of hexosaccharinolactones), while generally decreasing the yields of anhydro sugar and furan derivatives. The former products include glycolaldehyde, acetol, dihydroxy-acetone, acetic acid, formic acid, and lactic acid. Mechanistic speculations are made regarding the origins of these compounds, as well as of furan derivatives and saccharinic acid lactones. Parallels with alkaline degradation are considered.     

An information-processing perspective on childhood anxiety

In the past decade, cognitive theories of adult anxiety disorders have become increasingly complex, reflecting enhanced understanding of anxiety-related information-processing. This growth has fostered the development and enhancement of numerous assessment and treatment methods. Unfortunately, similar growth has been slower to occur in theories of childhood anxiety. This paper attempts to foster such growth by adopting an information-processing perspective. Doing so expands the extant cognitive perspective on childhood anxiety in four major ways. First, the division of cognitive processing into a sequence of steps provides a framework for organizing predictions regarding cognitive factors in childhood anxiety. Second, consideration of the cognitive operations active during each stage in the sequence facilitates elaboration of the types of cognitive deficits and distortions characteristic of anxious children. Third, it promotes development and application of performance-based assessment methodologies. Finally, an information-processing perspective highlights several targets for clinical intervention that may promote widespread change in an anxiety-supporting cognitive system.