Mortality studies of machining fluid exposure in the automobile industry III: A case-control study of larynx cancer

A case-control study of larynx cancer was conducted within a cohort of automobile workers exposed to metal working fluids, commonly referred to as machining fluids (MF). Results are based on 108 cases of larynx cancer and 5:1 matched controls. Risks associated with specific types of MF, as well as specific components of the fluids were evaluated. Based on a retrospective exposure assessment, lifetime exposures to straight and soluble fluids, grinding particulate, biocides, selected metals, sulfur, and chlorine were examined. Exposure to asbestos and acid mists at two of the three study sites was also characterized. Results suggest that straight mineral oils are associated with almost a two-fold excess in larynx cancer risk. There was also evidence of an association with elemental sulfur, commonly added to straight MF to improve the integrity of the materials under extreme pressure and heat. It is not clear whether sulfur is causally related to an excess relative risk of larynx cancer or whether the observed association is the result of unmeasured confounding by another contaminant or process feature. For example, the high stress operations that require MF enriched with sulfur are also more likely to produce polycyclic aromatic hydrocarbons (PAHs) during the process. Thus, the observed association with sulfur may be due to an association with PAH. The finding of excess risk of laryngeal cancer associated with MF is consistent with several previous reports in the literature. This is the first study, however, to distinguish straight mineral oils from other types of MF. Based on these findings, a general reduction in concentrations of straight mineral oil particulate in occupational environments would be prudent.     

Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect

Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain (Hildebrand et al., 1979). Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons.     

Mortality studies of machining-fluid exposure in the automobile industry. II. Risks associated with specific fluid types.

Excesses of digestive and respiratory cancers have been reported previously in association with exposure to machining fluids, agents in widespread use as coolants and lubricants in machining operations. Previous studies have had limited power to distinguish the effects of the different types of machining fluids in use. In a cohort of over 30,000 workers employed at two automotive plants in Michigan, mortality patterns were studied in relation to exposure to each of the three major fluid types--straight oils, soluble oils, and synthetic fluids. Standardized mortality ratios were estimated for subgroups of the cohort ever exposed to each of the three fluid types, and Poisson regression analyses were used to assess trends in risk with duration of exposure. The data suggest modest positive associations between exposure to straight oils and rectal, laryngeal, and prostatic cancer and a negative association between soluble and synthetic fluid exposure and lung cancer.     

Spatial and temporal pattern of purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia

Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively in a rat mutant (shaker) with differential hereditary cerebellar ataxia and Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do not degenerate. In strong shaker mutants, Purkinje cell degeneration is temporally protracted and spatially restricted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d, and -d have degenerated. Numerous Purkinje cells in the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in parasagittally oriented stripes or transversely oriented bands. Purkinje cells continue to degenerate in localized areas of the posterior lobe such that, by 18 months of age, surviving Purkinje cells are limited primarily to lobules VIc, VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells in these lobules degenerate.     

Exogenous cholecystokinin (CCK) reduces neonatal rat brain opioid receptor density and CCK levels

Newborn rats were given saline or cholecystokinin8 (CCK8) (5 micrograms/kg, twice daily) i.p. for 3 weeks. On day 21, effects on brain development were assessed. CCK-like immunoreactivity was measured in 7 brain regions; a small (12-18%) but significant decrease in endogenous levels of this peptide was detected in cerebral cortex, medulla and pons of the CCK-treated rats. Morphometric measurements revealed a slight reduction in thickness of most cerebral cortical sections within the CCK-treated group. The area of a midsagittal section of the cerebellum was unchanged except for the Purkinje/granule cell layer, which was smaller in CCK-treated animals. Levels of mu-, delta- and kappa-opioid receptors were estimated by homologous displacement binding assays using selective radioligands. The CCK treatment resulted in a significant decrease in levels of mu- (11%) and delta- (13%)-sites in the cerebral cortex. Neither binding affinities nor kappa-receptor densities were altered. Other animals received the same treatment regimens for 21 days and were maintained for an additional 29 days without treatment; these rats had reductions only in cortical mu-sites (15%). Chronic intraventricular administration of CCK (0.1 microgram/h) to adult rats did not elicit a similar down-regulation of cortical mu or delta receptors, suggesting that the effects observed in neonates reflected developmental processes.     

Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4⁺ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H₂-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H₁- and H₃-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H₂-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma.     

An HRP and autoradiographic study of cerebellar corticonuclear-nucleocortical reciprocity in the monkey

Summary Combined injections of ³H-leucine and HRP were made into the monkey cerebellar cortex in order to identify any reciprocal connections between the corticonuclear and the nucleocortical pathways. These combined intraaxonal labeling experiments have demonstrated a considerable overlap of orthogradely labeled Purkinje cell axons and terminals with retrogradely labeled HRP-positive neurons in the ventrolateral region of the dentate nucleus following combined injections into the lateral hemisphere, and in the dorsal area of the dentate following combined injections into medial cortical areas of the anterior lobe. There were also areas within the deep cerebellar nuclei where orthogradely labeled corticonuclear terminals did not overlap with retrogradely labeled nucleocortical neurons.     

The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Resolution of late-developing periprosthetic breast infections without prosthesis removal

Based on prior experience with implant exposure, an aggressive regimen to eradicate periprosthetic infections has proven successful in delayed gram-positive and gram-negative bacterial infections and in atypical microbacterial infections. The objective of the salvage procedure is to retain a prosthesis, to maintain breast contour, and to avoid psychological and physical consequences of prosthesis removal. The salvage procedure involves topical antisepsis, contracture release if needed, systemic and topical antibiotics with intermittent or continuous irrigation, and reinforcement of incision lines in selected cases using local tissue flaps.     

International air medical transport. Part I: Methods and logistics

International air medical transport requires reliable equipment, skilled personnel and precise planning. A report is presented of an experience with 29 international transports. Details concerning equipment, personnel and logistics are presented. Results and problem areas are discussed. This early experience demonstrates the capability for the repatriation of critically ill patients, and the evacuation of patients who require access to a level of care which may be unavailable outside the United States.