Employing dynamical and chemical processes for contaminant mixtures outdoors to the indoor environment: the implications for total human exposure analysis and prevention

There are many physical and chemical processes that affect the accumulation of outdoor pollutants. In recent years some of the information and concepts previously ascribed to outdoor pollution has been found to be useful in examining indoor dynamic and chemical processes. Further, becau se of the confining nature of the indoor environment, processes such as the "grasshopper effect" can lead to sustained higher levels of semivolatile chemicals indoors and affect multiroute (inhalation, dermal, incidental dietary, and nondietary ingestion) exposures. Such processes can also lead to a complex mixture of both semivolatile and volatile compounds in indoor air and on surfaces or within objects. This article specifically examines the above in combination with another indoor issue, indoor chemistry, and places the results into a context that can be used to evaluate (1) multipollutant cumulative or aggregate exposures and risks indoors, (2) exposure reduction strategies that can create healthy indoor environments. It is not a review of the entire field of the indoor environment or indoor air or the indoor environment, which has been covered in numerous volumes and reports. The complexities of the scientific issues are discussed by also placing them into our traditional approaches outdoor and indoor to pollution management, to indicate the difficulty in establishing the exposures that require mitigation or prevention. Further, some emerging issues are discussed as well as how to specifically address long-term single or multiroute exposures to semivolatile compounds within the "Total Indoor Environment."     

Tuberous sclerosis: A presentation of less‐commonly encountered stigmata

The protean manifestations of the tuberous sclerosis complex have lent this condition to extensive review in textbooks and in the medical literature. This condition generally presents by virtue of its neurological manifestations. Osseous stigmata, when encountered, are generally asymptomatic and do not require specific treatment owing to their benignity. We present the case of a young man with a slowly enlarging facial swelling for whom cosmetic surgery was considered. The swelling, present since childhood, had in time assumed disfiguring proportions. In what was hitherto considered an isolated facial deformity, a skull radiograph followed by CT revealed neurological stigmata of tuberous sclerosis. A large cerebellar hamartoma, proliferative soft tissue in the scalp adjacent to focal hyperostosis of the calvarium and the accompanying hemifacial changes seen in this patient constitute less commonly described features of tuberous sclerosis.     

Heavy caffeine intake in pregnancy and sudden infant death syndrome. New Zealand Cot Death Study Group

AIMS: To examine the association between maternal caffeine consumption during pregnancy and the risk of sudden infant death syndrome (SIDS). METHODS: A nationwide case-control study surveying parents of 393 SIDS victims and parents of 1592 control infants. Caffeine consumption in each of the first and third trimesters was estimated by questionnaire. Heavy caffeine intake was defined as 400 mg/day or more (equivalent to four or more cups of coffee per day). RESULTS: Infants whose mothers had heavy caffeine consumption throughout their pregnancy had a significantly increased risk for SIDS (odds ratio 1.65; 95% confidence interval 1.15 to 2.35) after adjusting for likely confounding factors. CONCLUSION: Caffeine intake has been associated with fetal harm and now SIDS. Reducing heavy caffeine intake during pregnancy could be another way to lessen the risk of SIDS. This needs confirmation by others.     

Clinical and laboratory findings in referrals for mitochondrial DNA analysis

BACKGROUND: Increasingly, mutations of mitochondrial DNA (mtDNA) are being considered when investigating the aetiology of neurological diseases in childhood. However, they are often difficult to predict clinically. METHOD: Mitochondrial DNA analysis was carried out on 190 children from 1992 to 1996. Most patients were screened for large scale rearrangements and point mutations at nucleotide positions 3243, 3271, 8344, and 8993. RESULTS: Mutations were found in only 15 patients (7.9%) and were either large scale rearrangements (seven patients) or point mutations at nucleotide position 3243 (eight patients). Other point mutations were screened for depending on the clinical picture. The age of symptom onset was significantly older in children with an mtDNA mutation (mean 7.0 years) compared with children without a mutation (mean 2.8 years). Neither Leigh's syndrome (28 cases) nor severe infantile lactic acidosis (12 cases) was associated with mtDNA mutation. Only three clinical features were significantly associated with an mtDNA mutation: progressive external ophthalmoplegia, myopathy, and pigmentary retinopathy. Family history was valuable: the point mutation at nucleotide 3243 (but not the large scale rearrangements) was associated with maternal inheritance; and consanguinity was not associated with mtDNA mutations. The only investigation that provided specific evidence of an underlying mtDNA mutation was histochemical staining of muscle biopsy specimens. The large scale mutations associated with Kearns-Sayre syndrome and progressive external ophthalmoplegia were found in DNA from muscle only, not leucocyte DNA; whereas point mutations were found in leucocyte DNA. CONCLUSIONS: Even among children seen at a neurogenetic referral centre, mtDNA mutations were very uncommon. Muscle biopsy was the only investigation to provide evidence of mtDNA abnormality.     

Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene

O6-alkylguanine DNA-alkyltransferase (ATase) provides protection against the toxic, mutagenic and carcinogenic effects of alkylating agents, principally by removing the promutagenic lesion O6-alkylguanine from DNA. Differences in ATase activity in human tissue may thus determine mutational susceptibility. As GC-->AT transitions, which can be induced by O6-alkylguanine in DNA, are commonly observed in the K- ras oncogene of alkylating agent induced animal tumours and in human colorectal tumours, we have examined whether differences in ATase activity may affect the risk of K-ras mutations in humans with colorectal tumours. NTase activity in normal tissue from individuals with a K-ras mutation in colorectal tissue and more specifically a GC-- >AT transition (but not a transversion mutation) was significantly lower than that in individuals without a mutation (P < 0.01). Thus, individuals with low ATase activity in normal tissue (i.e. below the median) were at increased risk of having a transition (OR 10.1; 95% CI 1.9-99.0), but not a transversion mutation (OR 1.7; 95% CI 0.3-12.2). There were no significant differences in tumour ATase activity in individuals with or without a mutation. These results suggest that ATase can protect colorectal tissue against the mutagenic effects of alkylating agents and furthermore, that alkylating agent exposure plays a role in the aetiology of colorectal tumours containing a GC-->AT transition in the K-ras oncogene.      

Antibiotic management of pneumococcal infections in an era of increased resistance

Abstract: Pneumococci are a leading cause of bacterial meningitis and bacteraemia, as well as pneumonia, otitis media and sinusitis in childhood. These organisms recently have shown a dramatic increase in antibiotic resistance. Penicillin-resistant pneumococci are of special concern as they are often resistant to other unrelated antibiotics. This is of particular significance to Aboriginal children who have among the highest rates of pneumococcal infection in the world. Laboratories should now test all invasive pneumococcal isolates for penicillin and third generation cephalosporin resistance. Local treatment guidelines are required for pneumococcal infections, especially for meningitis, taking into account the prevalence of resistant strains within the community. At present, penicillin and amoxycillin remain the drugs of choice for pneumococcal infections, with the exception of meningitis where initial empirical therapy must be with a third generation cephalosporin. Judicious antibiotic use, which avoids over-prescribing and unnecessary use of broad-spectrum agents, improved living standards in underprivileged communities and introduction of an effective conjugate vaccine, able to reduce the rates of pneumococcal infection and hopefully colonization, may limit the spread of resistant strains.     

Ocular sequelae in extremely premature infants at 5 years of age

Objective To report long-term ophthalmological sequelae in extremely premature infants at 5 years and to determine the relationship between neonatal variables (including retinopathy of prematurity; ROP) and the 5 year ophthalmological outcome of these infants.
Methodology The study cohort comprised 84 surviving infants born with a birthweight <1000 g or gestational age <28 weeks from June 1985 to December 1989. All infants had an ophthalmological assessment between 34 and 40 weeks post conceptional age to document grade of ROP and were assessed at 5 years of age for fundoscopy, visual acuity, refractive error and ocular mobility.
Results Of the 84 long-term survivors 69 (82%) were formally assessed at 5 years. Overall, 30 (43%) had some form of ocular disorder. Nineteen (27%) had reduced visual acuity of <6/6 and three of these were blind. Myopia > −0.5 dioptre was noted in eight (12%), hypermetropia ≥2.0 dioptre in five (8%), astigmatism in seven (11%) and strabismus was present in nine (14%) of the cohort. There was a significant relationship ( P <0.0001) between the incidence of ocular disorders and ROP. However, even those premature children without ROP had a 31% incidence of ocular disorder at 5 years.
Conclusion Long-term ophthalmological follow-up is recommended in all extremely premature infants regardless of the presence of ROP in the neonatal period.     

Seasonality of sudden infant death syndrome in mainland Britain and Ireland 1985-95

AIM: To compare an ultrasonic height measuring device (Gulliver) with mechanical stadiometry and the classical "book and tape measure" method. METHODS: Blinded duplicate measurements of height were made on each of 14 children by a pair of observers using a stadiometer (H) and Gulliver (G). Height was measured on a further 18 children by parents and an auxologist using Gulliver and the book and tape method (TM), and the results were compared with those obtained with a single stadiometry measurement. Finally, measurement of a rigid metal box was made on 10 occasions by the three methods. RESULTS: In the group of 14 children, the mean difference (range) in height (H minus G) was +2.8 cm (+0.5 to +4.55 cm), with H giving a systematically higher value in 276 of 280 individual measurements. In the group of 18 children, height by H was greater than by G or TM in 47 of 52 individual measurements. The mean (SD) height of the box by H (61.60 (0.07) cm) was greater than by G (60.96 (0.15) cm; p < 0.001) but not TM (61.4 (0.16) cm; p > 0.05). G and TM produced three times less reliable estimations of height than H, but with a large difference in cost, and there was evidence of systematic underrecording of height by 0.5 cm with G. CONCLUSIONS: Stadiometry is precise and reproducible, and can detect true changes in height over one month periods in mid-childhood, and should remain the standard way of observing growth. The book and tape method can produce clinically acceptable quarterly estimations of height that can be performed in the home.