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Biomedical subjects

L M Harrison

Publications and source records attributed to L M Harrison.

At least 19 recordsLinked to original sources

Extra-classical receptive field effects measured in striate cortex with fMRI.

The aim of this study was to measure the contextual influence of globally coherent motion on visual cortical responses using functional magnetic resonance imaging. Our motivation was to test a prediction from representational theories of perception (i.e. predictive coding) that primary visual responses should be suppressed by top-down influences during coherent motion. We used a sparse stimulus array such that each element could not fall within the same classical receptive field of primary visual cortex neurons (i.e. precluding lateral interactions within V1). This enabled us to attribute differences, in striate cortex responses, to extra-classical receptive field effects mediated by backward connections. In accord with theoretical predictions we were able to demonstrate suppression of striate cortex activations to coherent relative to incoherent motion. These results suggest that suppression of primary visual cortex responses to coherent motion reflect extra-classical effects mediated by backward connections.

Adult↗

Encoding uncertainty in the hippocampus.

The medial temporal lobe may play a critical role in binding successive events into memory while encoding contextual information in implicit and explicit memory tasks. Information theory provides a quantitative basis to model contextual information engendered by conditional dependence between, or conditional uncertainty about, consecutive events in a sequence. We show that information theoretic indices characterizing contextual dependence within a sequential reaction time task (SRTT) predict regional responses, measured by fMRI, in areas associated with sequence learning and navigation. Specifically, activity of a distributed paralimbic system, centered on the left hippocampus, correlated selectively with predictability as measured with mutual information. This is clear evidence that the brain is sensitive to the probabilistic context in which events are encountered. This is potentially important for theories about how the brain represents uncertainty and makes perceptual inferences, particularly those based on predictive coding and hierarchical Bayes.

Adult↗

Postmortem bacteriology: a re-evaluation.

AIM: To assess the value of postmortem bacteriology in necropsy practice, with specific emphasis on bacterial invasion of blood and cerebrospinal fluid (CSF). METHODS: A review of published articles on postmortem bacteriology. Studies were selected to cover the full range of necropsy practice including adults, the perinatal period, and infancy. The review covers over 5000 necropsies, mainly in adults, but including 1108 perinatal cases and 468 cases of sudden unexpected death in infancy. Data are available on 4992 blood cultures, 1168 specimens of CSF, and 743 cultures of spleen. RESULTS: Studies in which careful precautions have been taken to reduce contamination show that approximately two thirds of blood cultures are negative, two in nine yield a single isolate, and one in nine have a mixed growth. The postmortem interval has only a small effect on the isolation rate. A pure growth of a known pathogen has a more than 50% likelihood of being found in association with genuine infection in adults and in the perinatal period. CONCLUSIONS: The main postmortem artefact is contamination, but this can be considerably reduced by careful technique. Agonal spread is less common than is often assumed. Postmortem translocation is not a problem if the body is appropriately stored. A pure growth of a pathogen in blood or CSF should be regarded as a possible contributing factor to death at all ages.

Artifacts↗

Rhes, the Ras homolog enriched in striatum, is reduced under conditions of dopamine supersensitivity.

Striatal dopamine receptors become supersensitive when dopaminergic input is removed through either surgical denervation or pharmacological depletion. Although alterations such as increased D2 receptor binding and increased receptor-G protein coupling have been described in supersensitive striatal tissue, their roles in the mechanism of supersensitivity remain uncertain. The Ras Homolog Enriched in Striatum (Rhes) is expressed in brain areas that receive dopaminergic input, and here we test whether alterations in its expression accompany treatments that promote dopamine receptor supersensitivity in rats. Removal of dopamine input to the striatum by surgical denervation with 6-hydroxydopamine resulted in a decrease in rhes mRNA expression throughout striatum, as measured with quantitative in situ hybridization. The decrease was detected as early as two weeks and as late as seven months after surgery. Furthermore, a decrease in rhes mRNA was evident after repeated or acute reserpine treatment. Chronic daily injection of rats with the D2 antagonist eticlopride, which is known to up-regulate D2 receptors without inducing profound receptor supersensitivity, did not alter the expression of rhes mRNA in striatum. Thus, changes in rhes mRNA expression are strictly correlated with receptor supersensitivity, perhaps as a result of continuous removal of dopaminergic input. These findings suggest that rhes mRNA expression is maintained by dopamine and may play a role in determining normal dopamine receptor sensitivity.

Adrenergic Uptake Inhibitors↗

Stochastic models of neuronal dynamics.

Cortical activity is the product of interactions among neuronal populations. Macroscopic electrophysiological phenomena are generated by these interactions. In principle, the mechanisms of these interactions afford constraints on biologically plausible models of electrophysiological responses. In other words, the macroscopic features of cortical activity can be modelled in terms of the microscopic behaviour of neurons. An evoked response potential (ERP) is the mean electrical potential measured from an electrode on the scalp, in response to some event. The purpose of this paper is to outline a population density approach to modelling ERPs. We propose a biologically plausible model of neuronal activity that enables the estimation of physiologically meaningful parameters from electrophysiological data. The model encompasses four basic characteristics of neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by stochastic forces, (iii) organized into populations with similar biophysical properties and response characteristics and (iv) multiple populations interact to form functional networks. This leads to a formulation of population dynamics in terms of the Fokker-Planck equation. The solution of this equation is the temporal evolution of a probability density over state-space, representing the distribution of an ensemble of trajectories. Each trajectory corresponds to the changing state of a neuron. Measurements can be modelled by taking expectations over this density, e.g. mean membrane potential, firing rate or energy consumption per neuron. The key motivation behind our approach is that ERPs represent an average response over many neurons. This means it is sufficient to model the probability density over neurons, because this implicitly models their average state. Although the dynamics of each neuron can be highly stochastic, the dynamics of the density is not. This means we can use Bayesian inference and estimation tools that have already been established for deterministic systems. The potential importance of modelling density dynamics (as opposed to more conventional neural mass models) is that they include interactions among the moments of neuronal states (e.g. the mean depolarization may depend on the variance of synaptic currents through nonlinear mechanisms).Here, we formulate a population model, based on biologically informed model-neurons with spike-rate adaptation and synaptic dynamics. Neuronal sub-populations are coupled to form an observation model, with the aim of estimating and making inferences about coupling among sub-populations using real data. We approximate the time-dependent solution of the system using a bi-orthogonal set and first-order perturbation expansion. For didactic purposes, the model is developed first in the context of deterministic input, and then extended to include stochastic effects. The approach is demonstrated using synthetic data, where model parameters are identified using a Bayesian estimation scheme we have described previously.

Bayes Theorem↗

Abnormal cortex-muscle interactions in subjects with X-linked Kallmann's syndrome and mirror movements.

X-linked Kallmann's (XKS) subjects, who display mirror movements, have abnormal corticospinal tracts which innervate motoneurons of the left and right distal muscles of the upper limb. The size of the abnormal ipsilateral projection is variable. We have used coherence and cumulant analysis between EEG and first dorsal interosseous muscle (1DI) EMG to explore mechanisms underlying mirror movements in three XKS subjects. Results are compared with those of three normal subjects. We argue that significant coherence is functionally relevant when associated with a negative cumulant at an appropriate lag. Given this, normal subjects showed coherence at approximately 22 Hz between the EEG recorded over the sensori-motor cortex contralateral to the voluntarily moved hand and the 1DI EMG of this hand. No significant coherence was seen between 1DI EMG and the sensori-motor cortex ipsilateral to the muscle activity. In contrast, two of the XKS subjects (K2 and K4) had significant coherence at 22 Hz, together with a negative cumulant at an appropriate lag, between the ipsilateral cortical EEG and the 1DI EMG of the voluntarily activated hand. This implies that activity in the abnormal ipsilateral corticospinal projection can contribute to the voluntary drive. For these two subjects, the ipsilateral corticospinal projection was greater than the contralateral projection, as revealed using magnetic brain stimulation. In one of these subjects, K4, significant 22 Hz coherence and negative cumulant was also seen between the EMG of the voluntarily activated hand and the cortex contralateral to this hand. In the third subject, K4a, coherence and negative cumulant was detected between the EMG of the voluntary side and the cortical activity contralateral to this hand. The contralateral cortico spinal projection of this subject was greater than the ipsilateral projection. Regarding the mirroring hand of the XKS subjects, coherence (with negative cumulant at an appropriate lag) was seen in all three subjects between the EMG recorded from the mirroring hand and cortical EEG ipsilateral to this hand. This provides evidence that activity in the aberrant ipsilateral projection is involved in producing the drive that results in mirror movements. In one subject, K4, coherence and negative cumulant was also seen between the EMG of the mirroring hand and motor cortical activity contralateral to this hand. Thus, in this subject, activity in the corticospinal projection contralateral to the mirroring hand also contributed to the mirror movements. In conclusion, this study has provided further evidence that the 22 Hz coherence seen between EEG and EMG is dependent upon corticospinal activity and has furthered our understanding of mechanisms underlying mirror movements.

Adult↗

Finger movement is associated with attenuated cutaneous reflexes recorded from human first dorsal interosseous muscle.

Cutaneomuscular reflexes (CMR) have been recorded from the first dorsal interosseous muscle (1DI) of the preferred hand, somatosensory evoked potentials (SEP) were recorded from the contralateral sensory cortex and the sensory nerve action potential (SNAP) was recorded from the median nerve of 15 adult subjects whilst electrically stimulating the digital nerves of the index finger. Subjects performed the following tasks (a) a sustained abduction of the index finger against resistance at 10-20 % maximum voluntary contraction (MVC), and (b) abduction of the index finger as in (a) whilst performing self paced low amplitude tapping of the (i) index finger, (ii) thumb, (iii) middle finger, (iv) little finger and (v) ipsilateral foot. The E2 component of the CMR and the N20/P25 components of the SEP were significantly reduced during finger tapping (P < 0.05). This reduction was independent of which finger was tapping (P > 0.05). There was a significant (qualitative) relationship between the decrease in the size of the E2 component of the CMR and the N20/P25 components of the SEP ((2) test; P < 0.05). There were no significant changes in E1 and I1 (P > 0.05). The size of the SNAP was independent of task (P > 0.05). The size of the E1, I1, E2 components of the CMR, and the N20/P25 components of the SEP were unaltered during foot tapping (P > 0.05, n = 4). We conclude that the decrease in size of the E2 component associated with finger tapping results from gating of the digital nerve input.

Adolescent↗

Physiological tremor in human subjects with X-linked Kallmann's syndrome and mirror movements.

Human physiological tremor consists of mechanical-reflex and neurogenic components. The origin of the neurogenic component, classically detected in the frequency range 7-12 Hz, has been much debated. We have studied six subjects with X-linked Kallmann's syndrome (XKS) and mirror movements. In these subjects unilateral magnetic brain stimulation results in abnormal bilateral EMG responses. Furthermore, abnormal sharing of central nervous inputs between the left and right motoneurone pools results in both abnormal motor unit synchronisation between left and right EMGs and abnormal sharing of long but not short-latency cutaneomuscular reflexes. XKS subjects with mirror movements thus provide a model for studying the central origin of physiological tremor. During sustained co-extension of the left and right index fingers, simultaneous finger tremor and extensor indicis (EI) EMGs were recorded and cross-correlated. The tremor and EMG signals were also subjected to time and frequency domain analysis.Results of frequency domain analysis between ipsilateral finger tremor and EI EMG were similar for both control and XKS subjects. However, in contrast to the controls, short-term synchronisation of left and right EI motor unit activity and significant coherence between left and right EMG, left and right tremor, left EMG and right tremor and right EMG and left tremor were found in XKS subjects. The frequency range (6-40 Hz) and coherence values between left and right were similar to ipsilateral coherence values of rectified EMG and tremor. These data provide strong evidence to support the hypothesis that the neurogenic component of physiological tremor is supraspinal in origin and ranges from 6 to 40 Hz.

Adult↗

Ancylostoma caninum anticoagulant peptide-5: immunolocalization and in vitro neutralization of a major hookworm anti-thrombotic.

Hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia in the developing world. Recently two major anticoagulant serine protease inhibitors have been identified and cloned from adult Ancylostoma caninum hookworms. One of these, A. caninum anticoagulant peptide 5 (AcAP5), is a potent and specific inhibitor of human coagulation factor Xa. A polyclonal IgG has been purified from rabbits immunized with recombinant AcAP5 using affinity chromatography. Using immunohistochemistry, the polyclonal alpha-rAcAP5 IgG localized to the cephalic or amphidial glands, confirming previous biochemical studies that had identified this secretory gland as the primary source of anticoagulant activity in the adult worm. This polyclonal IgG also neutralized the inhibitory activity of recombinant and native AcAP using a single stage chromogenic assay of coagulation factor Xa activity. In addition, the polyclonal IgG also neutralized the anticoagulant activity of native and recombinant AcAP5 as measured by the activated partial thromboplastin time clotting assay. Importantly, this neutralizing activity is species specific, as the polyclonal IgG failed to neutralize the anticoagulant activity of A. ceylanicum. Taken together, these data suggest that the hookworm anticoagulant AcAP5 represents a viable target for future immunization strategies aimed at inhibiting the ability of the adult hookworm to feed on blood in vivo.

Ancylostoma↗

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

Amino Acid Sequence↗

A broad spectrum Kunitz type serine protease inhibitor secreted by the hookworm Ancylostoma ceylanicum.

Although blood-feeding hookworms infect over a billion people worldwide, little is known about the molecular mechanisms through which these parasitic nematodes cause gastrointestinal hemorrhage and iron deficiency anemia. A cDNA corresponding to a secreted Kunitz type serine protease inhibitor has been cloned from adult Ancylostoma ceylanicum hookworm RNA. The translated sequence of the A. ceylanicum Kunitz type inhibitor 1 (AceKI-1) cDNA predicts a 16-amino acid secretory signal sequence, followed by a 68-amino acid mature protein with a molecular mass of 7889 daltons. Recombinant protein (rAceKI-1) was purified from induced lysates of Escherichia coli transformed with the rAceKI-1/pET 28a plasmid, and in vitro studies demonstrate that rAceKI-1 is a tight binding inhibitor of the serine proteases chymotrypsin, pancreatic elastase, neutrophil elastase, and trypsin. AceKI-1 inhibitory activity is present in soluble protein extracts and excretory/secretory products of adult hookworms but not the infective third stage larvae. The native AceKI-1 inhibitor has been purified to homogeneity from soluble extracts of adult A. ceylanicum using size exclusion and reverse-phase high pressure liquid chromatography. As a potent inhibitor of mammalian intestinal proteases, AceKI-1 may play a role in parasite survival and the pathogenesis of hookworm anemia.

Amino Acid Sequence↗

Reactive control of precision grip does not depend on fast transcortical reflex pathways in X-linked Kallmann subjects.

It has been shown that subjects maintain grasp stability by automatically regulating grip force in response to loads applied tangentially to a manipulandum held using a precision grip. Signals from cutaneous mechanoreceptors convey the information necessary for both the initiation and scaling of responses. The central neural pathways that support these grip reactions are unknown. However, the latency of the increase in force is similar to that of 'long-latency' transcortical reflexes recorded from muscles following muscle stretch or electrical stimulation of digital nerves. This study assessed the importance of fast transcortical pathways for reactive grip responses by examining these responses in subjects with X-linked Kallmann's syndrome (XKS). Subjects were selected whose corticospinal projection, as assessed by magnetic brain stimulation, is essentially ipsilateral, and in whom the long-latency reflex components following digital nerve stimulation are only found contralateral to the stimulated side. Despite this anomaly of the fast corticospinal pathway, these XKS subjects responded in the same way as control subjects; grip response latencies were similar and responses were appropriately scaled. However, the non-operating hand of these XKS subjects often mirrored the grip force changes of the operating hand. Reflex force mirroring was most marked during the first 50 ms and the force output was always less than 20 % of that of the operating hand. We conclude, firstly, that somatosensory driven precision grip responses that support grasp stability do not depend on fast conducting corticospinal pathways in these subjects and, secondly, that such responses do not use those 'long-latency' reflex pathways probed by cutaneomuscular reflexes elicited by electrical stimulation of digital nerves.

Adult↗

Habituation of cutaneomuscular reflexes recorded from the first dorsal interosseous and triceps muscle in man.

Cutaneomuscular reflexes have been recorded from the first dorsal interosseous muscle during a sustained abduction of the index finger of 20 subjects (25 recordings) following stimulation of the digital nerves at the following frequencies: 2 Hz, 3 Hz, 5 Hz, 7 Hz and 9 Hz, presented in random order. Five hundred stimuli were given at each frequency. EMG was rectified and consecutive batches of 100 sweeps of each set of 500 responses were averaged time locked to the stimulus. All reflex components, E1, I1 and E2, exhibit habituation with the E1 component habituating the most and the I1 component the least. There was considerable variation in the rate of habituation between subjects. The rate of habituation was independent of the frequency of stimulation. Reflex responses were recorded from the triceps brachii muscle in eight subjects; this reflex response habituated at a faster rate than the E2 component recorded from the first dorsal interosseous muscle. These results are discussed in relation to the choice of stimulus parameters for the clinical testing of cutaneous reflexes. We conclude that it is important to consistently average the same number of responses.

Adolescent↗

Nociceptin/orphanin FQ (N/OFQ) induces a quasi-morphine abstinence syndrome in the rat.

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that exerts antiopiate effects under some circumstances, and there is evidence that it contributes to opiate tolerance. This raises the question, might N/OFQ also contribute to opiate dependence and abstinence? Twenty-two male Sprague-Dawley rats were cannulated in the third ventricle and challenged 7 days later by third ventricle injection of 50, 200 or 1,000 ng N/OFQ or saline alone. Each rat was observed under "blind" conditions for 30 min beginning 15 min after onset of the third ventricle injection. There was a significant positive linear trend of signs as a function of N/OFQ dose. Subjects receiving saline had 18.0+/-2.0 (mean+/-SEM) overall abstinence-like signs, whereas subjects receiving 50, 200 or 1000 ng N/OFQ had 35.2+/-3.6, 49.8+/-2.6 and 63.5+/-9.7 signs, respectively. In 16 additional rats, abstinence-like signs induced by 1000 ng N/OFQ were significantly attenuated by low SC doses of morphine or clonidine. These results raise the possibility that N/OFQ might contribute to opiate dependence and subsequent abstinence syndrome. On the other hand, N/OFQ over a wide dose range induced abstinence signs with similar potency in morphine dependent and non-dependent rats.

Animals↗

Acquisition of a new motor skill is accompanied by changes incutaneomuscular reflex responses recorded from finger muscles in man.

Cutaneomuscular reflex (CMR) responses and motor unit synchronisation have been recorded to investigate possible reorganisation of central nervous pathways in six healthy adults learning a novel skill with the non-dominant hand. Multi-unit surface EMG signals were recorded from first dorsal interosseous (1DI) and abductor digiti minimi (ADM) muscles during sustained flexion of the index finger and abduction of the little finger (flex/ab) and during bilateral controlled finger abduction (ab/ab). CMR responses were elicited by concomitant stimulation of the digital nerves of the index finger at 2.5 times threshold for perception. For training purposes the subject practised the novel flex/ab task phasically at a rate of 1 Hz for 10 min daily for 12 days. Cortically mediated components of the CMR responses recorded from 1DI and ADM were significantly larger in both muscles during training. Taking the data for all subjects together, when subjects performed sustained flex/ab (novel task), the size of the I1 and E2 components were increased by 25 and 55% in IDI and 192 and 167% in ADM (Mann-Whitney U-test, P<0.05). Corresponding values for sustained ab/ab were more modest: 31 and 16% in 1DI and 88 and 54% in ADM. Changes in the size of the spinal E1 component were not the same in each muscle: values for sustained flex/ab and ab/ab were 33 and 31% smaller in 1DI and 89 and 59% larger in ADM. No significant changes were found in the amount of synchrony of motor unit firing between 1DI and ADM when subjects performed either task during training. These results suggest that learning a new motor skill produces changes which take place predominantly in the cortical pathways of the CMR and these may be due to changed connectivity within motor and/or sensory cortex which has previously been shown in the monkey.

Adult↗

Opiate modulating properties of nociceptin/orphanin FQ.

The recently discovered peptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOR share many structural similarities with the opioid peptides and their receptors. The anatomical distributions of N/OFQ and NOR are similar to those of opioid peptides and receptors. In addition, NOR and opiate receptors couple via the same G-proteins to similar effectors, such as Ca(2+) channels, K(+) channels, adenylyl cyclase, and several protein kinases. Thus, the behavioral effects of N/OFQ have been investigated in the context of known opiate effects, and a possible connection has been sought between the effects of these two homologous signaling systems. Originally characterized as a nociception-producing peptide, N/OFQ has now been shown to have diverse effects on nociception, as well as effects on many other behaviors. With regard to nociception, the peptide has been reported to produce hyperalgesia, reversal of opioid-mediated analgesia, analgesia, and allodynia. N/OFQ also has effects on other behaviors, such as locomotion, feeding, anxiety, spatial attention, reproductive behaviors, and opiate tolerance. The relationship between opiates and N/OFQ is strengthened by the fact that opiates also affect these behaviors. However, the exact nature of the relationship of N/OFQ with opiates-opiate-like versus antiopiate-remains controversial. This review will detail the diverse effects of N/OFQ and suggest that this peptide, like other putative antiopiate peptides, can be described as 'opiate modulating. '

Amino Acid Sequence↗

The nasopharyngeal bacterial flora in infancy: effects of age, gender, season, viral upper respiratory tract infection and sleeping position.

The aim of the investigation was to determine the effect of age, gender, viral upper respiratory tract infection (URTI), season and sleeping position on the composition of the nasopharyngeal bacterial flora in infancy. Seventy-two babies, 38 male and 34 female, whose birthdates were evenly spread throughout the year were followed from birth to 18 months of age. From 0 to 6 months nasopharyngeal swabs were obtained once a month in periods without URTI and daily for 3 days during episodes of URTI. From 12 to 18 months of age nasopharyngeal swabs were obtained in the early morning alter an overnight sleep and later in the day after the baby had been up for over 2 h. Swabs were obtained in prone and supine sleepers with and without infection. In infants aged 0-6 months URTI had little effect on the nasopharyngeal bacterial flora, but there was a marked effect of age and less marked effect of season and gender. In particular Staphylococcus aureus carriage decreased with age, was most common in the winter months and the density of colonisation was greater in males than females. In infants aged 12-18 months the combination of prone sleeping with URTI and an early morning swab led to increased carriage of staphylococci, streptococci. Haemophilus influenzae and Gram-negative bacilli which are not normally part of the nasopharyngeal flora. These results are relevant to sudden infant death syndrome (SIDS). The combination of prone sleeping and URTI reproduces the nasopharyngeal flora seen in SIDS. Gram-negative bacilli isolated from SIDS cases should not be dismissed as post-mortem contaminants. The features of S. aureus make it a prime candidate for a pathogenic role in SIDS.

Aging↗

Sleeping position in infants over 6 months of age: implications for theories of sudden infant death syndrome.

The aim of this study was to determine the prevalence of prone and supine sleeping in infants aged 0-12 months and relate this to changes in the number of cases of sudden infant death syndrome (SIDS) since 1985. Seventy-two babies, 38 male and 34 female, were followed for the first 18 months of life with regular home visits and sleeping position was recorded. In addition, data on the number of cases of SIDS in England and Wales between 1985 and 1995 were analysed. All babies slept supine for the first 5 months of life, but once they could turn over in their cots (mean age 7.34 months, range 5-11 months) the majority slept prone. By 11 months of age, 53 regularly slept prone (73%), 95% CI +/- 19.8%), while 11 slept supine, three adopted the side position and five varied from night to night. The number of cases of SIDS in infants aged 7-11 months has fallen significantly (P<0.0001) in a period in which the prevalence of prone sleeping, in that age group, has not changed. The most plausible explanation for this paradoxical result is that supine sleeping in the first 5 months of life reduces the absolute risk of SIDS in the second 6 months of life even though most babies are then sleeping prone. It is suggested that reduced exposure to nasopharyngeal bacterial superantigens in babies sleeping prone might explain this effect.

Adult↗