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Most moths use ears solely to detect the echolocation calls of hunting, insectivorous bats and evoke evasive flight manoeuvres. This singularity of purpose predicts that this sensoribehavioural network will regress if the selective force that originally maintained it is removed. We tested this with noctuid moths from the islands of Tahiti and Moorea, sites where bats have never existed and where an earlier study demonstrated that the ears of endemic species resemble those of adventives although partially reduced in sensitivity. To determine if these moths still express the anti-bat defensive behaviour of acoustic startle response (ASR) we compared the nocturnal flight times of six endemic to six adventive species in the presence and absence of artificial bat echolocation sounds. Whereas all of the adventive species reduced their flight times when exposed to ultrasound, only one of the six endemic species did so. These differences were significant when tested using a phylogenetically based pairwise comparison and when comparing effect sizes. We conclude that the absence of bats in this habitat has caused the neural circuitry that normally controls the ASR behaviour in bat-exposed moths to become decoupled from the functionally vestigial ears of endemic Tahitian moths.

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Inflicted head injury to the developing brain frequently results in serious disability. The pathogenesis of the neuraxial and ocular findings in infants believed to have suffered inflicted head injury remains the subject of considerable debate. Recent neuropathology studies of fatal cases of inflicted head injury and of a foetal/perinatal non-traumatic model have led to the proposal that there is a 'unified hypothesis', the essential feature of which is hypoxic brain swelling secondary to cervicomedullary injury. It has been suggested that less than violent forces may be involved and even that some cases may not be due to trauma at all. The purpose of this paper is to provide a critical review of the data upon which these suppositions are based on a background of what is already known. It is submitted that there are serious flaws in the methodology; the conclusions reached cannot logically be drawn from the data; and the 'unified hypothesis' is not supported by the evidence. On the basis of the data presented, it is also difficult to sustain the secondary hypothesis purporting to describe a minority cohort with 'infantile encephalopathy with subdural and retinal bleeding' of non-traumatic causation.

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OBJECTIVE: To measure admission cortisol and adrenocorticotrophic hormone (ACTH) levels in children with meningococcal disease to try and determine the prevalence of adrenal insufficiency. DESIGN: Prospective observational study. SETTING: Pediatric departments of four hospitals in Merseyside, United Kingdom. PATIENTS: Ninety-six children with meningococcal disease; 29 with hypotension, ten of whom died. MEASUREMENTS AND MAIN RESULTS: Admission cortisol, ACTH, and proinflammatory cytokine levels were measured. Serial cortisol levels also were measured during the first 48 hrs. Significantly lower cortisol levels were found in those who died compared with survivors. Significantly higher ACTH levels also were found in those who died. However, no child had a cortisol level <5 microg/dL (<138 nmol/L) implying definite adrenal insufficiency. Three of 29 children with hypotension had plasma cortisol levels implying possible adrenal insufficiency (<18 microg/dL [<497 nmol/L]), but high ACTH levels were only found in one of those three. Cortisol levels decreased significantly after antibiotic treatment, unless steroid therapy was administered. ACTH levels did not correlate with cortisol or proinflammatory cytokine levels. CONCLUSIONS: Children with meningococcal disease have a wide range of initial plasma cortisol levels, with lower levels found in those who die. Many factors may affect cortisol levels, but adrenal insufficiency is probably uncommon.

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We describe the successful use of methadone in the restoration of sedation and provision of analgesia in two morphine-tolerant, paediatric patients who had suffered significant thermal injuries and were undergoing mechanical ventilation. Both patients had exhibited escalating requirements for sedative drugs while undergoing ventilation yet remained inadequately sedated. The introduction of i.v. methadone in place of i.v. morphine in the sedative regimen rapidly and effectively restored a state of sedation. Hyperalgesia and morphine tolerance appear to be associated; it is proposed that methadone acts primarily, under these circumstances, by re-establishing the analgesic state. Such use of methadone in the morphine-tolerant patient also afforded a concomitant sedative-sparing effect.

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OBJECTIVES: Although maternal active smoking has been established to be associated with fetal growth retardation, evidence of an effect of environmental tobacco smoke exposure on birthweight is still limited and inconclusive. This study addressed the relationship between prenatal environmental tobacco smoke exposure and birthweight and fetal growth retardation in Shanghai, China. METHODS: Data on 1785 full-term live-born normal infants of nonsmoking mothers were used from the Shanghai Birth Defects and Perinatal Death Monitoring conducted between October 1986 and September 1987. Environmental tobacco smoke exposure was defined as exposure to paternal smoking. RESULTS: Infants with environmental tobacco smoking exposure were, on average, 30 g lower in birthweight than nonexposed infants, after adjustment for gestational age, parity, maternal age, and occupation. CONCLUSION: Consistent with previous research, this study suggests that environmental tobacco smoking exposure may have a modestly adverse effect on birthweight.

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Animal data suggest that prenatal exposure to certain tobacco smoke components such as nicotine may affect the development of the male gonadal axis, which may in turn affect future adult fertility. There are no previous epidemiologic studies on the potential effects of early (prenatal and childhood) exposure to maternal smoking on the reproductive system in adult male offspring. To investigate this question, we used data from a follow-up study of reproductive function and fertility among young adult sons of mothers who had participated in a randomized clinical trial of diethylstilbestrol use during pregnancy. We observed no significant effects of early exposure to maternal smoking on conventional semen characteristics, hormone levels (follicle stimulating hormone [FSH], luteinizing hormone [LH] and testosterone), urogenital abnormalities and diseases, or perceived infertility problems. Current active smoking by the men was, however, associated with a significant decrease in the percentage of sperm with normal morphology.

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The substrate load of the pump-priming fluid, especially glucose and lactate, has a major influence on the metabolic response of children during cardiac operations and may be detrimental neurologically. It is possible to cleanse the priming fluid of these excess substrates by ultrafiltration followed by the addition of a balanced electrolyte solution. We have used this technique in the bypass management of nine children over 1 year of age and weighing less than 18 kg who were studied from induction of anesthesia to 6 hours postoperatively. Frequent blood samples were taken for measurement of electrolytes, intermediary metabolites, and stress-related hormones. Throughout the study period electrolyte concentrations were maintained within the physiologic range and changes in blood glucose and lactate were minimized compared with those of matched historical controls from previous studies. During the period of cardiopulmonary bypass mean serum glucose concentrations varied between 4.4 and 7.7 mmol/L and peaked at 10.7 mmol/L just before skin closure. The mean serum lactate concentration did not exceed 2.3 mmol/L during the period studied. Thus ultrafiltration of the priming fluid and replacement with a balanced electrolyte solution results in the delivery to the patient of a reasonably physiologic substrate load, which is reflected in improved control of mean plasma intermediary metabolite concentrations. The method may form the basis of further clinical studies to determine specific aspects of the metabolic stress response in children.

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Clinical experience of 50 patients with the CHARGE association is reviewed and problems with management of children born with multiple system involvement is highlighted. It was found that the outlook for survival was poor if more than one of the following three features was present: cyanotic cardiac lesions, bilateral posterior choanal atresia, or tracheo-oesophageal fistula. Mortality was largely due not to the structural heart defects or choanal abnormalities, but reflected underlying pharyngeal and laryngeal incoordination, which resulted in aspiration of secretions. Outcome is likely to be improved if collaboration between specialist surgical teams allows necessary procedures to be performed using the minimum number of anaesthetics. Examination of both the short and long term management of these children has stressed the importance of a multidisciplinary approach to their care.

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In an unusual set of triplets, two monozygous girls presented with CHARGE association. Dissimilar surgical management of identical cardiovascular lesions has resulted in a disparate effect on their clinical state. Their case poses interesting questions concerning how CHARGE association may develop.

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To evaluate whether long term exposure to 2-ethoxyethanol (2EE) may affect semen quality, a cross sectional study was conducted among men exposed to 2EE used as a binder slurry in a metal castings process. Full shift breathing zone exposures to 2EE ranged from non-detectable to 24 ppm (geometric mean 6.6 ppm). Because of the potential for substantial absorption of 2EE through skin exposure, urine measurements of the metabolite of 2EE, 2-ethoxyacetic acid (2EAA) were conducted, showing levels of 2EAA ranging from non-detectable to 163 mg 2EAA/g creatinine. Only 37 exposed men (50% participation) and 39 non-exposed comparison (26% participation) from elsewhere in the plant provided a sperm sample. A questionnaire to determine personal habits, and medical and work histories, and a physical examination of the urogenital tract were also administered. The average sperm count per ejaculate among the workers exposed to 2EE was significantly lower than that of the unexposed group (113 v 154 million sperm per ejaculate respectively; p = 0.05) after consideration of abstinence, sample age, subjects' age, tobacco, alcohol and caffeine use, urogenital disorders, fever, and other illnesses. The mean sperm concentrations of the exposed and unexposed groups did not significantly differ from each other (44 and 53 million/ml respectively). No effect of exposure to 2EE on semen volume, sperm viability, motility, velocity, and normal morphology or testicular volume was detected, although some differences in the proportion of abnormal sperm shapes were observed. These data suggest that there may be an effect of 2EE on sperm count among these workers, although the possibility that other factors may be affecting the semen quality in both exposed and unexposed men in this population or that the results reflect bias introduced by the low participation rates cannot be excluded.

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The major metabolic response to open-heart surgery using cardiopulmonary bypass has been shown in adults to be modified by the components of the pump priming fluid. This effect is likely to be more significant in children. Data on 29 children less than 15 kg body weight are presented. Patients were randomised to receive a prime containing one of three crystalloid priming fluids: 100% Hartmann's (H), 50% Hartmann's + 50% 5%-Dextrose (HD), or 100% Plasmalyte 148 (P). The remainder of the prime was CPD stored blood and the prime was buffered with sodium bicarbonate. Severe hyperglycaemia 22.4 +/- 1.3 mmol/l occurred during bypass in the HD group but moderate hyperglycaemia occurred in the other prime groups. Hyperlactataemia occurred in all prime groups during bypass and was highest in the H prime group at 3.9 +/- 0.4 mmol/l. These changes in intermediary metabolites were only partly explained by the crystalloid components of the priming fluid. A subsiduary study revealed the important contribution of CPD stored blood to those intermediary metabolite concentrations. Therefore, the well recognised changes in intermediary metabolites as components of the metabolic response to surgery, namely hyperglycaemia and hyperlactataemia were augmented by the composition of the priming fluids. In addition, CPD stored blood and the sodium bicarbonate buffer increased the sodium concentration of the prime to hypernatraemic levels in both the H and P groups which caused an increase in sodium concentration during bypass. Therefore important changes during bypass occur as a direct result of the individual components of the priming fluid. These changes may result in osmolal flux, hyperglycaemia and hyperlactataemia, all of which have been reported to be potentially harmful.

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Two occupational field studies were conducted to determine the effects of ethylene dibromide (EDB) exposure on male reproductive potential. The first study was a longitudinal study of 10 EDB-exposed forestry employees and 6 unexposed men conducted in Colorado in the summer of 1983. The exposure time was approximately 6 weeks. The second study was a cross-sectional study of 46 EDB-exposed papaya workers and 43 unexposed men conducted in Hawaii in December 1983 in which the average term of employment was about 5 years. In the longitudinal study, sperm velocity decreased in all 10 exposed men and in only two unexposed men. Semen volume was also decreased in 9 of the 10 exposed men (there was no change in the other man); only two unexposed men had a decrease in their semen volume. The longer term EDB exposure resulted in decreases in sperm motility and viability, suggesting that the short term exposure may slow sperm velocity, but longer exposures cause immotility and cell death. An apparent decrease in semen volume that was observed in the longitudinal study was not statistically significant in the cross sectional study of workers having chronic exposure. However, a significantly higher semen pH was observed in the exposed men compared to the unexposed men in the cross-sectional study. The results from both studies suggest that the accessory sex glands may be affected by EDB exposure.

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Increasing attention has been paid to the use of semen analysis as an indicator of exposure to potential mutagenic and reproductive hazards. In the infertility clinic setting, semen evaluations include the measurement of sperm concentration, volume, pH, motility, velocity and morphology, the analysis of seminal plasma to evaluate accessory sex gland function and, in some cases, the in vitro evaluation of fertilization capacity and sperm-cervical mucus interaction (Ann Intern Med 1985;103:906-919). To date, however, the study of semen characteristics of occupationally exposed populations has been confined principally to the measurement of sperm concentration and sperm morphology. This has been largely due to the unavailability of portable equipment suitable for the measurement of other semen characteristics and the difficulty of obtaining fresh semen samples in the field setting. National Institute for Occupational Safety and Health researchers have developed mobile laboratory facilities which enable us to evaluate fresh samples, in the field, for semen characteristics in addition to concentration and morphology. This paper describes the application of these methods using the example of our recent cross-sectional study of workers occupationally exposed to ethylene dibromide in the papaya fumigation industry. We discuss our findings in the context of the usefulness of semen analysis as an indicator of occupational hazards to male reproduction.

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To examine whether long term occupational exposure to ethylene dibromide (EDB) affects semen quality a cross sectional study of semen quality was conducted among 46 men employed in the papaya fumigation industry in Hawaii, with an average duration of exposure of five years and a geometric mean breathing zone exposure to airborne EDB of 88 ppb (eight hour time weighted average) and peak exposures of up to 262 ppb. The comparison group consisted of 43 unexposed men from a nearby sugar refinery. Statistically significant decreases in sperm count per ejaculate, the percentage of viable and motile sperm, and increases in the proportion of sperm with specific morphological abnormalities (tapered heads, absent heads, and abnormal tails) were observed among exposed men by comparison with controls after consideration of smoking, caffeine and alcohol consumption, subject's age, abstinence, history of urogenital disorders, and other potentially confounding variables. No effect of exposure to EDB on sperm velocity, the overall proportion of sperm with normal morphology, or YFF bodies was observed. These data strongly suggest that EDB may increase the risk of reproductive impairment in workers at exposure levels near the National Institute for Occupational Safety and Health recommended limit of 45 ppb (as an eight hour time weighted average) and far below the current standard of the Occupational Safety and Health Administration of 20 ppm.

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Plasma electrolyte, intermediary metabolite, and hormone concentrations were measured in samples of 110 units of citrate phosphate dextrose blood being used for clinical transfusions. The most important changes from the physiological range were in sodium, potassium, glucose, and lactate concentrations. Mean sodium concentrations fell from 170 mmol/l at the beginning of storage to 156 mmol/l at the end and mean potassium concentrations rose from 7 mmol/l to 25 mmol/l. Glucose had a mean concentration of 20 mmol/l at the beginning of storage and had only fallen to 15 mmol/l at the end. Mean lactate concentrations increased from 7 mmol/l at the beginning of storage to 25 mmol/l at the end. Many samples had cortisol, insulin, and growth hormone concentrations within the physiological range. Citrate phosphate dextrose blood contains a large substrate load that changes during storage and that should be taken into account when infants are transfused large volumes of blood. The strong correlation coefficients with duration of storage for sodium, potassium, and lactate (-0.71, 0.91, and 0.90, respectively) indicate that concentrations of these substrates can be predicted within a narrow range if the duration of blood storage is known.

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Data from 4,500 workplaces surveyed by the National Institute for Occupational Safety and Health (NIOSH) in the National Occupational Hazard Survey (1972 to 1974) and National Occupational Exposure Survey (1981 to 1983) show an increase in both preplacement and periodic medical screening in US industries during the past decade. The distribution of screening is primarily related to plant size, but also varies considerably by industry type; further, plants with industrial hygiene and safety programs and/or unions are more likely to provide screening examinations than those without, irrespective of plant size. As for workers potentially exposed to selected chemical hazards, the first survey provides no consistent evidence that such workers were more likely to receive exposure-specific tests than other workers. The significance of these findings is discussed in the context of the proposed framework for medical screening practices developed by NIOSH researchers.

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Domperidone is an effective antiemetic for children receiving cytotoxic therapy. There have been reports of cardiac arrest in older patients associated with domperidone. We carried out continuous ECG monitoring of 18 children receiving domperidone intravenously in a dose of 1 mg/kg body weight. No serious dysrhythmias were noted during 379 h of recording. Single premature beats, transient sinus pauses, and nodal block were occasionally associated with vomiting and were no more common than would be expected in a population of normal children.

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Urine specimens from a total of 26 subjects who were either nurses, pharmacists, or pharmacy technicians engaged in the preparation, handling, or administration of cancer chemotherapeutic agents were analyzed for the presence of mutagenic substances. Assays were performed using bacterial strains TA98 and TA100 in the Salmonella/mammalian microsomal mutagenicity assay developed by Ames et al. (Mutat. Res., 31: 347-364, 1975). Findings were compared with results from similar assays of urine specimens for 38 hospital personnel not exposed to cancer chemotherapeutic agents. There was no evidence of an association between occupational exposure to chemotherapy drugs and the presence of mutagenic substances that could be detected by this assay procedure in either specimens of filter-sterilized urine or extracts of urine concentrated with XAD-2 resins. An association was observed, however, between smoking and increased urinary excretion of mutagens. None of the observed associations was changed substantially by statistical adjustment for the occupational category of the subject (nurse or pharmacist), hospital of employment, or values of concurrent solvent controls for the mutagenesis assays. Associations with occupational exposures were not changed by controlling for smoking history. In addition to the large increases for smokers, testing of extracts of urine from nonsmokers with bacterial strain TA98 yielded mutagenicity values that averaged about 50% higher than values for solvent controls. Similar small increases were observed in previous published reports of human urine mutagenicity assays using tester strains TA1538 and TA98. We found little evidence to suggest that the small increases observed for nonsmokers were associated with technical factors such as the presence in the extracts of histidine or other substances promoting bacterial growth or contamination of the specimens during collection or extraction procedures. Since it appears that technical factors can be excluded, we believe that the increases were associated with urinary excretion of low levels of mutagen by a high proportion of subjects tested. The lack of an association of mutagenicity with occupational exposure to chemotherapeutic drugs may have been due to protective measures at the hospitals surveyed and suggests that, with appropriate procedures, these agents can be administered in a manner such that human exposure cannot be detected using this approach.(ABSTRACT TRUNCATED AT 400 WORDS)

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Blood lead levels in some pre-schoolchildren living near a lead works and particularly in some children with fathers employed at the lead works showed evidence of increased exposure. Forty-seven of them took part three years later in a follow-up study of their developmental and behavioural functions. The children were aged between 4 and 5 1/2 years and were closely matched for age, sex, social class, parental education, area, and length of residence. Only three children had moved house since their blood lead levels had been examined at two years of age; these levels ranged between 18 and 64 microgram/100 ml. None of the children had clinical symptoms of plumbism. No statistically significant (P less than or equal to 0.05) differences were found on developmental and behavioural scores when the children were divided into two groups of less than or equal to 35 microgram/100 ml (n = 23) and greater than 35 microgram/100 ml (n = 24). The differences in scores were of the same order as those between boys and girls, which were themselves generally not significant. Behaviour ratings did not differ. The variations in developmental skills were generally found to be more related to age and schooling; neither these factors nor the difference in sex was related to blood lead levels.

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