Association of ambient air‐pollution levels with acute asthma exacerbation among children in Singapore

BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges.     

Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly

In a double-blind, randomized, crossover study, the H1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 +/- SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 +/- 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 +/- 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 +/- 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 +/- 13% to 60 +/- 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 +/- 15% to 78 +/- 13% from 4 to 8 hours. The mean serum-elimination half-life of chlorpheniramine was 22.6 +/- 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 +/- 11% to 37 +/- 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 +/- 14% to 46 +/- 19% at 2, 5, and 6 hours (p less than 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H1-receptor-antagonist ingestion.     

Synectin/syndecan-4 regulate coronary arteriolar growth during development.

Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin (-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 microm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin.     

Egg-sharing in assisted conception: ethical and practical considerations

The present acute shortage of eggs for donation cannot be overcomeunless adequate guidelines are set to alleviate the anxietiesregarding payments, in cash or kind, to donors. The currentHuman Fertilisation and Embryology Authority (HFEA) guidelinesdo not allow direct payment to donors but accept the provisionof lower cost or free in-vitro fertilization (IVF) treatmentto women in recognition of oocyte donation to anonymous recipients.Egg-sharing achieved in this way enables two infertile couplesto benefit from a single surgical procedure. However, the practicalguidelines related to this approach are ill-defined at the presenttime leading to some justifiable uncertainty. A pilot studywas therefore undertaken in order to establish the place ofegg-sharing in an assisted conception programme. The currentHFEA guidelines on medical screening of patients, counselling,age and rigid anonymity between the donor and recipient werefollowed. The study involved 55 women (25 donors and 30 recipients)in 73 treatment cycles involving fresh and frozen-thawed embryos.Donors were previous IVF patients who, regardless of their abilityto pay, shared their eggs equally with matched anonymous recipients.They paid only for their consultations and tests right up tothe point of being matched with a recipient The sole recipientpaid the cost applicable in egg donation of a single egg collection,although both received embryo transfers. The results indicatethat although the recipients were older than the donors (41.4± 0.9 versus 31.6 ± 0.5 years), and there wasno difference in the mean number of eggs allocated, the percentagefertilization rates, or the mean number of embryos transferred,there were more births per patient amongst recipients than amongstdonors (30 versus 20%). We conclude that providing the donorsare selected carefully, this scheme whereby a sub-fertile donorhelps a sub-fertile recipient is a very constructive way ofsolving the problem of the shortage of eggs for donation. Thereare also the advantages of including a group of women who wouldotherwise be denied treatment Problems related to ‘patientcoercion’ can, in our view, be fully overcome by the applicationof strict common-sense safeguards. The ideal of pure altruismis not without its medical and moral risk. The success of egg-sharingdepends on shared interests and a degree of altruism betweenthe donor, the recipient and the centre. The current HFEA guidelinesshould be applauded for enabling a highly effective conceptof mutual help to develop.     

Allergen-stimulated interleukin-4 and interferon-gamma production in primary culture: responses of subjects with allergic rhinitis and normal controls.

The balance of interleukin-4 (IL-4) to interferon-gamma (IFN-gamma) production that is induced following exposure to common environmental antigens is believed to be instrumental in determining whether hypersensitivity or clinical unresponsiveness results to that antigen. To date, evaluation of cytokine (protein) production has been based predominantly on allergen-reactive CD4 T-cell clones or activation of fresh unselected peripheral blood mononuclear cell (PBMC) populations with non-physiological stimuli such as phorbal myristate acetate (PMA) and calcium ionophore, phytohaemagglutinin (PHA), anti-CD3 or anti-CD2/anti-CD28 monoclonal antibodies (mAb). Here, ultrasensitive IL-4 and IFN-gamma assays were optimized to allow direct analysis of antigen-stimulated cytokine production by fresh human PBMC. Primary cultures of cells from grass pollen-sensitive allergic rhinitis subjects and non-atopic controls were stimulated using a range of grass pollen allergen concentrations in the absence of exogenous cytokines or polyclonal activators. The majority of subjects (45 of 52) exhibited chloroquine-sensitive, CD4-dependent cytokine production in allergen-stimulated, short-term primary culture. Median IL-4 production was substantially greater among atopics (13.0 pg/ml versus < 1 pg/ml, Mann-Whitney U test, P < 0.0000001) and IFN-gamma was lower (P = 0.008), providing direct evidence for an imbalance in both IL-4 and IFN-gamma production among circulating, pollen-reactive cells in individuals with seasonal allergic rhinitis. The distinction in the allergen-driven cytokine responses elicited from normal and atopic donors was underscored by examination of the ratios of IFN-gamma:IL-4 synthesis. Non-atopic individuals exhibited intense IFN-gamma dominance of the T-cell response, in marked contrast to that observed among grass pollen-sensitive individuals (median IFN-gamma:IL-4 ratios of 14.0 versus 0.096, P = 0.000002). The observation that essentially all individuals produced IFN-gamma (+/- IL-4) following antigen stimulation in vitro argues that the most relevant consideration in determining susceptibility to immediate hypersensitivity versus clinical tolerance to environmental allergens is not a genetically defined capacity to recognize the antigen (i.e. if allergen-reactive T cells are present in that individual) but the nature of the cytokine response.     

High-resolution computed tomography study of the cranium of a fossil anthropoid primate, Parapithecus grangeri: new insights into the evolutionary history of primate sensory systems

Extant anthropoids have large brains, small olfactory bulbs, and high-acuity vision compared with other primates. The relative timing of the evolution of these characteristics may have important implications for brain evolution. Here computed tomography is used to examine the cranium of a fossil anthropoid, Parapithecus grangeri. It is found that P. grangeri had a relatively small brain compared with living primates. In addition, it had an olfactory bulb in the middle of the range for living primates. Methods for relating optic foramen area and other cranial measurements to acuity are discussed. Multiple regression is used to estimate retinal ganglion cell number in P. grangeri. Given currently available comparative data, P. grangeri seems to have had retinal ganglion cell counts intermediate for living primates, overlapping with the upper end of the range for strepsirrhines and possibly with the lower end for anthropoids.     

Semantic knowledge and episodic memory for faces in semantic dementia

Previous studies have documented poor recognition memory for faces in patients with semantic dementia. Preserved face recognition memory was found in this study, however, so long as atrophy was confined predominantly to the left temporal lobe. Patients with structural damage to the right temporal lobe were typically impaired, with the status of the hippocampus and parahippocampal gyrus (including the perirhinal cortex) on the right being critical. Two single-case studies of patients with predominantly left temporal lobe pathology confirmed good recognition memory for famous faces, even if semantic knowledge about the celebrities depicted was severely degraded. An effect of semantic knowledge on recognition memory became apparent only when perceptually different photographs of the famous people were used at study and test. These results support the view that new episodic learning typically draws on information from both perceptual and semantic systems.     

On the ERN and the significance of errors

The error-related negativity (ERN) is an event-related brain potential observed when subjects commit errors. To examine whether the ERN is sensitive to the value of errors, the motivational significance of errors was manipulated in two experiments. In Experiment 1, low and high monetary value errors were compared to evaluate the effect of trial value on the ERN. In Experiment 2, subjects performed a flanker task both while their performance was being evaluated and during a control condition. Consistent with the notion that the error-detection system is sensitive to the significance of errors, the ERN was significantly larger on high-value trials in Experiment 1 and during evaluation in Experiment 2. There were no corresponding effects on the correct response negativity, and no behavioral differences between conditions were evident in either experiment. These results are discussed in terms of the functional role of the ERN in response monitoring.     

Whisker trimming begun at birth or on postnatal day 12 affects excitatory and inhibitory receptive fields of layer IV barrel neurons

In rats, whisker trimming during development leads to persistent alterations in the function of cortical barrel circuits and to behavioral deficits later in life. Here we examined how whisker trimming begun either at birth (P0) or on postnatal day 12 (P12), around the onset of whisking behavior, affects receptive fields of layer IV barrel neurons. All whiskers on the left face were trimmed for 40-45 days and then allowed to regrow fully. Extracellular single-unit recordings and controlled deflections of principal and adjacent whiskers (PW and AW, respectively), individually or in paired combinations, were used to assess excitatory and suppressive effects of neighboring whiskers on barrel neurons. Results indicate that whisker trimming both from P0 and P12 leads to enlarged excitatory and weakened inhibitory receptive fields in layer IV neurons. PW- and AW-evoked responses are larger in magnitude in trimmed than in control animals; AW-evoked responses are disproportionately affected, decreasing the spatial focus of barrel neurons. Deprivation after P12 accounts for approximately 50% of the total effect observed in P0 trimmed animals. Suppressive interactions, evoked by two whiskers deflected in succession, are weaker in trimmed than in control animals. Suppressive caudal/rostral and ventral/dorsal gradients, however, seem unaffected by sensory deprivation. Thus the developmental period during which experience persistently modifies maturing barrel circuitry extends up to and likely beyond the onset of whisking behavior. Sensory deprivation during this time affects development of both excitatory and inhibitory receptive fields of barrel neurons and likely impairs cortical integration of sensory information from multiple whiskers.