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Biomedical subjects

N J Spencer

Publications and source records attributed to N J Spencer.

At least 19 recordsLinked to original sources
PubMed2006

Effects of systemic fluoride and in vitro fluoride treatment on enamel crystals.

Systemically administered fluoride at a concentration of 75 ppm increases the surface roughness of developing enamel crystals in rats, which may be significant in advancing our understanding of the biological mechanism of fluorosis. Thus, the aim of this study was to investigate whether the increased surface roughness may be a result of surface restructuring by the direct action of fluoride at the crystal surface. We examined the fluoride dose-dependent roughening of enamel crystal surfaces in vivo, in the rat, and whether this roughening could be mimicked by the in vitro treatment of rat enamel crystals with neutral pH fluoride solutions. Our results showed that enamel crystal surface roughness increased after treatment with increasing fluoride ion concentrations, whether applied in vitro or administered systemically. This suggests a mechanism, alongside others, for the increased surface roughness of crystals in fluorotic enamel.

Administration, Oral↗
PubMed2005

Rates and social patterning of household smoking and breastfeeding in contrasting European settings.

OBJECTIVE: To compare rates and social patterning of household smoking and breastfeeding in families with newborn infants in birth cohorts in Coventry, UK and Veria, North Greece. METHODS: Infants born in 1996 in Coventry, 1999 in Veria were recruited into birth cohort studies using similar methodologies. In Coventry recruitment was by family health visitor at the primary visit; in Veria, hospital-based paediatricians enrolled infants at the neonatal examination. Data were collected at the initial contact on household smoking, type of feeding, and household socio-demographic characteristics. Rates of initial breastfeeding and household smoking with 95% confidence intervals were estimated and breastfeeding and household smoking regressed on parental education and housing tenure in logistic regression models. RESULTS: Data were available on 2612 Coventry infants and 773 Veria infants. Rates of household smoking and breastfeeding were higher in Veria compared to Coventry. In Coventry, living in rented accommodation and lower maternal and paternal education were associated with household smoking and bottle feeding. Logistic regression models fitted on initiation of breastfeeding failed to show social patterning in Veria but more educated mothers showed a longer duration of breastfeeding. Only low paternal education was associated with household smoking after adjustment for maternal education and housing tenure. CONCLUSIONS: Smoking and breastfeeding are more prevalent among households with young infants in Veria compared with Coventry. The social patterning of health-related behaviours noted in Coventry is less marked in Veria. The relevance of these findings for public health interventions in the contrasting settings is discussed.

Breast Feeding↗
PubMed2005

Systematic review of randomized controlled trials of atypical antipsychotics and selective serotonin reuptake inhibitors for behavioural problems associated with pervasive developmental disorders.

A systematic review of randomized controlled trials of the use of atypical antipsychotics and selective serotonin reuptake inhibitors in the treatment of behavioural problems associated with pervasive developmental disorders is reported. A search through both published and unpublished literature, including contacting drug companies and known experts in the field was undertaken. Six trials met the criteria for inclusion in the review. They largely suffer from methodological weaknesses; only two trials had satisfactory methodological quality. The heterogeneity in outcome measurements prevented from conducting a meta-analysis. There is yet no coherent body of data concerning the effects of these medications across all sub-classifications of pervasive developmental disorders, across all age categories, and concerning their medium- and long-term effects, and their effects on quality of life. Atypical antipsychotics and selective serotonin reuptake inhibitors may be of benefit for behavioural problems associated with pervasive developmental disorders. Risperidone has been the best studied among these medications. Atypical antipsychotics appear to have a low risk of extrapyramidal symptoms during short-term treatment. The reviewed trials cannot provide data on the use of selective serotonin reuptake inhibitors in the treatment of children with pervasive developmental disorders. No firm conclusions for clinical practice can be drawn. Larger, well-conducted randomized controlled trials with long-term follow-up are needed.

Adolescent↗
PubMed2004

Parental smoking and passive smoking in infants: fathers matter too.

This study examines mothers' and fathers' smoking patterns in different kinds of smoking households, and assesses their relative contribution to infants' exposure to environmental tobacco smoke. It uses data from a cross-sectional survey of 314 smoking households (infants: mean age 10 weeks) in Coventry and Birmingham, England, examining reported tobacco consumption and objective measures of exposure: the study infant's urinary cotinine:creatinine ratios and their mother's salivary cotinine. The study shows that both mothers' and fathers' tobacco smoke make substantial contributions to infant exposure to tobacco smoke. Households were more likely to contain a smoking father than mother, with over two-thirds of households including a smoking father. In households where both parents smoke, fathers' tobacco consumption was found to be significantly higher than in households where only the father smokes. This suggests that the interaction between parents needs to be considered rather than focusing on mothers' or fathers' smoking behaviour in isolation. The implications for health promotion programmes are discussed, particularly the need to place more emphasis on tackling fathers' smoking. Currently, fathers' smoking receives far less research or health promotion attention than mothers' smoking. Protecting infants from fathers' as well as mothers' smoking is key to reducing environmental tobacco exposure in early infancy, when the risk of Sudden Infant Death is highest.

Cotinine↗
PubMed2003

Immunization with Haemophilus influenzae (Hib) conjugate vaccine following discharge from hospital.

BACKGROUND: This study was undertaken to ascertain Haemophilus influenzae type b (Hib) conjugate vaccination status following discharge from hospital and to determine the time taken to vaccinate with Hib conjugate vaccine following hospital discharge of unvaccinated children. MATERIALS AND METHODS: Population-based cross-sectional survey involving children aged 3-59 months admitted to a hospital with laboratory confirmed invasive H. influenzae disease. RESULTS: Of 51 eligible children, 42 (82%) had not received Hib conjugate vaccine prior to admission. No children were immunized prior to discharge. Vaccination following discharge took an average of 110 days (range 3-441 days). More than one quarter (28%) remained unvaccinated following discharge. If these children had been immunized, immunization coverage among this group of children would have increased significantly from 73% to 98% (p = 0.0017). CONCLUSION: In the immediate post-Hib conjugate vaccine period, delayed immunization after discharge was identified. This reduces the individual and community benefits of immunization.

Bacterial Capsules↗
PubMed2003

Changing socioeconomic risk factors for invasive H. influenzae disease after the introduction of conjugate vaccine.

OBJECTIVES: To determine socioeconomic risk factors for invasive Haemophilus influenzae (HI) disease before and after the introduction of HI type b (Hib) conjugate vaccine in the West Midlands, UK. METHODS: Study population consisted of children aged <5 years with laboratory confirmed invasive disease. Linear associations between disease rates and socioeconomic variables were examined 2-years before and 2-years after the introduction of conjugate vaccine. RESULTS: Pre-vaccine there were no trends in disease incidence. Post-vaccine there was an absolute reduction in disease incidence and significant disease differentials between affluent and deprived populations were identified for non-owner-occupancy (P=0.032) and car access (P=0.049). CONCLUSIONS: Our results suggest that changes in socioeconomic risk factor for invasive HI occurred after the introduction of conjugate vaccine. This may have implications for future immunisation strategies.

Child, Preschool↗
PubMed2002

Enteric nerve stimulation evokes a premature colonic migrating motor complex in mouse.

The effects of enteric nerve stimuli were investigated on spontaneously occurring colonic migrating motor complexes (CMMCs) in isolated mouse colon. Changes in circular smooth muscle tension were recorded simultaneously from the proximal, mid and distal regions of an in vitro preparation of whole mouse colon at 36 +/- 1 degrees C. The CMMCs were recorded from all preparations with a mean interval between contractions ranging from 135.2 +/- 9.3 to 163.3 +/- 22.4 s. The CMMCs migrated spontaneously from the proximal to distal colon and were abolished by tetrodotoxin (1 micromol L-1). In approximately half of all trials (57 of 103, n = 31), trains of stimuli (20 Hz, 2-5 s, 1 ms, 40-70 V) delivered to the mid or distal regions of colon, during the intervals between CMMCs, elicited a premature CMMC. However, similar trains of stimuli delivered to the proximal colon were without similar effects (33 trials, n = 13). It is suggested that in isolated whole mouse colon, CMMCs can be evoked prematurely by trains of electrical stimuli applied to the enteric nerves. The observation that nerve stimuli failed to evoke a premature CMMC from the proximal colon suggests that selective activation of functional ascending pathways may be required to initiate a premature CMMC.

Anesthetics, Local↗
PubMed2002

The treatment of parental height as a biological factor in studies of birth weight and childhood growth.

Parental height is frequently treated as a biological variable in studies of birth weight and childhood growth. Elimination of social variables from multivariate models including parental height as a biological variable leads researchers to conclude that social factors have no independent effect on the outcome. This paper challenges the treatment of parental height as a biological variable, drawing on extensive evidence for the determination of adult height through a complex interaction of genetic and social factors. The paper firstly seeks to establish the importance of social factors in the determination of height. The methodological problems associated with treatment of parental height as a purely biological variable are then discussed, illustrated by data from published studies and by analysis of data from the 1958 National Childhood Development Study (NCDS). The paper concludes that a framework for studying pathways to pregnancy and childhood outcomes needs to take account of the complexity of the relation between genetic and social factors and be able to account for the effects of multiple risk factors acting cumulatively across time and across generations. Illustrations of these approaches are given using NCDS data.

Birth Weight↗
PubMed2001

Spatial and temporal coordination of junction potentials in circular muscle of guinea-pig distal colon.

1. In isolated, stretched, flat-sheet preparations of guinea-pig distal colon, simultaneous intracellular recordings were made from pairs of circular muscle (CM) cells to map the region of smooth muscle at which spontaneous junction potentials (sJPs) were coordinated in both space and time. 2. Spontaneous inhibitory junction potentials (sIJPs) and excitatory junction potentials (sEJPs) were recorded from all animals with varying frequencies and amplitudes (up to 25 mV). 3. Large amplitude (> or = 9 mV) sIJPs or sEJPs with near-identical amplitudes and time courses were recorded synchronously from two CM cells, even when the two electrodes were separated by up to 11 mm in the circumferential axis and < or = 4 mm in the longitudinal axis. However, smaller (< 9 mV) sIJPs or sEJPs were less coordinated and exhibited greater variability in their times to peak. 4. The standard deviation (S.D.) for the time difference between the peaks of sJPs was related to the amplitude of the events and the distance between the electrodes. The S.D. for large amplitude JPs (approximately 30 ms), which was less than that for small JPs (approximately 150 ms), remained constant across the circumferential axis (at least up to 6 mm), but declined rapidly for distances > or = 2 mm in the longitudinal axis. 5. Current injection (up to 8 nA) into a single CM cell elicited electrotonic potentials in neighbouring CM cells, only when the two electrodes were separated by less than 100 microm circumferentially. Beyond 50 microm electronic potentials were rarely detected. 6. Tetrodotoxin (TTX; 1 microM) abolished all sJPs, whereas hexamethonium (300 microM) either abolished, or substantially reduced all sJPs. 7. Nitro-L-arginine (L-NA; 100 microM) abolished the slow repolarisation phase of sIJPs without any apparent effect on the amplitude of sIJPs. Apamin abolished the fast, initial component of sIJPs, suggesting synchronous release of two inhibitory neurotransmitters during the sIJP. Atropine (1 microM) abolished sEJPs. 8. No sJPs were recorded from the CM layer when it was separated from the myenteric plexus. 9. In conclusion, sIJPs and sEJPs in colonic CM occur synchronously over large regions of the smooth muscle syncitium. The results are discussed in relation to the idea that spontaneous junction potentials in colonic CM are not monoquantal events, but are generated by the simultaneous release of transmitter from many release sites, due to the synchronous activation of many enteric motor neurons.

Animals↗
PubMed2001

Simultaneous intracellular recordings from longitudinal and circular muscle during the peristaltic reflex in guinea-pig distal colon.

1. Simultaneous intracellular recordings were made from longitudinal muscle (LM) and circular muscle (CM) cells of guinea-pig distal colon during the peristaltic reflex. 2. Spontaneous rhythmical depolarizations with superimposed action potentials (mean amplitude: 19 +/- 2 mV) were regularly recorded from the LM (mean interval: 7 +/- 1 s). In contrast, in the CM layer, spontaneous action potentials occurred with an irregular frequency. Although spontaneous action potentials in LM were rarely correlated in time with those in CM, spontaneous inhibitory junction potentials (sIJPs) were found to occur synchronously in both muscles (5 out of 27 animals; 19 %). 3. Graded inflation of an intra-luminal balloon or mucosal stimulation oral to the recording electrodes elicited gradeable compound IJPs synchronously in both LM (mean amplitude: 6 +/- 1 mV) and CM (mean amplitude: 9 +/- 1 mV) (descending inhibitory reflex). Evoked IJPs were often followed by action potentials in both muscle layers. 4. Mucosal stimuli applied anal to the recording electrodes elicited compound excitatory junction potentials (EJPs) synchronously in both muscles layers that were often associated with the generation of action potentials. In the LM, evoked EJP amplitudes ranged from 3 mV (subthreshold) to 31 mV (including the action potential) and in the CM from 4 mV (subthreshold) to 44 mV (including the action potential). 5. Apamin (500 nM) reduced the evoked IJP in the CM by 55 % (from 11 +/- 2 to 5 +/- 1 mV), but caused no significant reduction in the LM layer (from 8 +/- 1 to 6 +/- 1 mV). Apamin-resistant IJPs in both muscle layers were likely to be due to nitric oxide, since they were abolished by L-NA (100 microM). 6. Atropine (1 microM) abolished the ascending excitatory reflex in both muscles. 7. Injection of neurobiotin into the LM and CM confirmed that simultaneous intracellular recordings were made from different muscle layers. 8. In conclusion, during the peristaltic reflex, the LM and CM layers receive synchronous inhibitory neuromuscular inputs during descending inhibition and synchronous excitatory neuromuscular inputs during ascending excitation. No evidence was found to support reciprocal innervation.

Action Potentials↗
PubMed2001

Role of muscle tone in peristalsis in guinea-pig small intestine.

We investigated the involvement of muscle tone and circular muscle (CM) contraction in peristalsis in isolated guinea-pig small intestine. A segment of jejunum (approximately 13 cm) was mounted into a three chambered partitioned bath. Peristaltic waves were initiated in the oral chamber either by: (1) infusing fluid into the oral end of the jejunum; the ejected fluid was diverted via a cannula from reaching the intermediate and anal chambers, or by (2) intraluminal balloon distension of the empty oral segment. Tension of the circular muscle was measured in all three chambers. Peristaltic waves elicited by fluid infusion were evoked at an abrupt threshold. In contrast, peristaltic waves elicited by distension could be graded in amplitude according to stimulus intensity. Peristaltic waves evoked in an empty intestine exhibited similar propagation velocities to peristaltic waves associated with fluid propulsion. Nifedipine (200-400 nM) added to the intermediate chamber to block muscle contraction did not prevent peristaltic waves elicited by either stimulus from propagating into the anal chamber, although their amplitude was attenuated. Nifedipine to the site of stimulation (oral chamber) abolished peristaltic waves generated by either stimulus. Tetrodotoxin (1-2 microM), or a low Ca2+-high Mg2+ solution to the intermediate chamber abolished the propagation of peristalsis from the oral to anal chambers. In conclusion, graded peristaltic waves can occur in an empty intestine. Therefore peristalsis is not necessarily an "all-or-none" phenomenon. Peristalsis depends on the spread of nervous activity along the bowel, rather than the reactivation of neural circuits caused by displacement of fluid in the lumen. However, local muscle tone and contraction are important for the initiation and maintenance of peristaltic propagation.

Animals↗
PubMed2001

Control of migrating motor activity in the colon.

One of the most significant developments in our approach to studying gastrointestinal motility over the past few years has been in the advent of genetic manipulation and the development of knockout animals. This means that it is possible to study motility patterns of specific regions of the gastrointestinal tract in which the development or synthesis of particular neurotransmitter substances or receptors has been prevented. The mouse has emerged as the model species for investigating the effects that genetic knockouts may have on gastrointestinal motility; therefore, an understanding of the mechanisms underlying the control of motility patterns of unaffected mice is crucial before we can apply this knowledge to knockout models. Major advances have been made in the past few years regarding the mechanisms underlying the generation of migrating motor complexes in the large bowel, particularly in the mouse colon.

Acetylcholine↗
PubMed2001

The care and health needs of children in residential care in the Maltese Islands.

OBJECTIVES: To survey the health needs of children in residential care in the Mediterranean Islands of Malta and Gozo. SETTING: Thirteen children's Residential Homes in the Maltese Islands. STUDY DESIGN: Cross-sectional interview survey. METHODS: Carers at the Residential Homes were interviewed using a semistructured questionnaire between June and November 1996. Data related to all the children resident in the homes at the time of the interview were collected including socio-demographic factors, reasons for admission to care, medical needs and medical services received. RESULTS: In all, 309 children, aged birth-16 years-equivalent to 4.2/1000 Maltese children-were in residential care at the time of the study. Fifty-three per cent were boys and 52% were < 8 years of age. The most common reasons for admission into residential care were single parenthood (25%), separated parents and parents unable to offer adequate care (19% each). Admission 'medicals' rarely included a developmental assessment or use of growth charts. Medical and developmental examinations were not carried out on a regular basis and children were medically examined only when required. Dental check-ups were performed more regularly; 30% of the children had a dental check-up every 6 months. Behavioural problems were common affecting 20.7% of all children, followed by chronic bronchial asthma which was present in 7.4%. Developmental delay (global or specific) was reported in 23.3% of children under the age of 4. CONCLUSIONS: Residential care is the predominant form of substitute care for disadvantaged children in Malta and Gozo. The demography of the child population in Residential Homes in these Islands is different from that in other countries, in that 52% of children in residential care are < 8 years of age compared to proportionately more adolescents in other countries. Medical supervision is minimal. A standardised medical and developmental assessment should be established as an essential part of this form of substitute care.

Adolescent↗
PubMed2001

Effects of alosetron on spontaneous migrating motor complexes in murine small and large bowel in vitro.

Alosetron (Lotronex) is a serotonin subtype 3 (5-HT3) receptor antagonist that alleviates symptoms of irritable bowel syndrome (IBS) in female patients. Alosetron may act centrally, involve the alteration of ascending pain sensation, or modulate peristaltic, secretory, or sensory function. To investigate further the mechanisms underlying its action and gender selectivity we recorded the effect of increasing concentrations of alosetron or ondansetron on spontaneous migrating motor complexes (MMCs) from isolated terminal ileum or colon from C57BL/6 mice. Both antagonists inhibited MMC frequency before affects on duration or amplitude. The threshold of inhibition for alosetron was 100-fold less in small intestine from females (20 nM) than from males. The opposite effect of gender was observed with ondansetron in the colon. All MMCs were abolished by either drug at 10 microM. Our results demonstrate that alosetron selectively inhibits MMC frequency in isolated preparations of murine bowel. Because contractile events in the ileum correlate with symptoms of IBS in humans, the gender selectivity of alosetron may be caused by a direct action within the small intestine.

Animals↗
PubMed2000

Spontaneous migrating motor complexes occur in both the terminal ileum and colon of the C57BL/6 mouse in vitro.

We have studied migrating motor complexes (MMCs) in the isolated terminal ileum or colon (IMMCs and CMMCs respectively) of the C57BL/6 mouse. Periodic contractions occurred spontaneously in both preparations in the absence of intraluminal stimulation. After an initial period, complexes became synchronized between the oral and anal ends of the tissue, and could be observed for in excess of 7 h. The propagation velocity was 3.1+/-1.0 and 3.9+/-0.6 mm s(-1) in the ileum and colon respectively. IMMCs occurred every 6.01+/-0.39 min and had a duration of 86.3+/-10.4 s. The interval between CMMCs was smaller (3.52+/-0.31 min) and contractions were shorter in duration (30.7+/-3.6 s). In both preparations, these motor events were dependent on cholinergic transmission: blocked by hexamethonium (500 microM) and attenuated or blocked by atropine (1 microM). This study is the first demonstration of spontaneous migrating contractions in the isolated ileum or colon of the C57BL/6 mouse, the strain of choice for neurological transgenic and targeted mice.

Animals↗
PubMed2000

Purinergic and cholinergic neuro-neuronal transmission underlying reflexes activated by mucosal stimulation in the isolated guinea-pig ileum.

1. We present evidence that adenosine triphosphate (ATP) plays a major role in excitatory neuro-neuronal transmission in ascending and descending reflex pathways to the longitudinal (LM) and circular muscle (CM). 2. A partitioned bath was used for the pharmacological isolation of a segment of guinea-pig ileum ( approximately 6 cm in length), allowing drugs to be selectively applied to an intermediate region between the region where mucosal stimulation was applied and that where mechanical recordings were made. 3. Brush stroking the mucosa (3 strokes) elicited a synchronous contraction of the LM and CM both above (ascending excitation) and below (descending excitation) the site of stimulation. All reflexes were abolished when tetrodotoxin (1 microM) was applied to the intermediate chamber. 4. Hexamethonium (300 microM) added to the intermediate chamber abolished the ascending contraction in 15 % of oral preparations (from 26 preparations, 18 animals) and the descending contraction in 13% of anal preparations studied (from 53 preparations, 48 animals). In the remaining 85% of oral preparations, hexamethonium usually attenuated the oral contraction of the LM and CM. However, in the remaining 87% of anal preparations, hexamethonium had no effect on the anal contraction of the LM and CM. 5. Oral and anal reflexes that were hexamethonium resistant were either abolished or attenuated by the further addition of the P2 purinergic receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) or alpha,beta-methylene ATP (50-100 microM) to the intermediate chamber. 6. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP, 20 microM) or alpha,beta-methylene ATP (50-100 microM) stimulated both ascending and descending excitatory pathways, when applied to the intermediate chamber. 7. In conclusion, ascending and descending neuro-neuronal transmission in excitatory nervous pathways to the LM and CM is complex and clearly involves neurotransmitter(s) other than acetylcholine (ACh). We suggest mucosal stimulation releases ACh and ATP in both ascending and descending excitatory reflex pathways that synapse with excitatory motoneurons to the LM and CM.

Acetylcholine↗
PubMed2000

Validation of the Warwick Child Health and Morbidity profile in routine child health surveillance.

OBJECTIVE: To further validate a simple instrument for the measurement of parent-reported health and morbidity in infancy and childhood when used in routine child health surveillance as part of a whole year birth cohort study. Setting The socially and ethnically diverse city of Coventry. METHODS: Health visitors administered the Warwick Child Health and Morbidity profile (WCHMP), incorporated into the Parent Held Record (PHR), to the parents of infants born in 1996 and enrolled in the Coventry Cohort study as part of routine child health surveillance at 8 weeks and 8 months. Criterion validity was estimated for Hospital admission status and immunization status against health records and validity against medically plausible constructs was tested by comparing responses between domains and between the two data collection points for the whole cohort. RESULTS: Criterion validity for parental reporting of immunization status (Kappa 0.824 [95% CIs, 0.708, 0.940]) and hospital admission (Weighted Kappa 0.987 [95% CIs, 0.977, 0.997]) were high. There was a high level of concordance between parental responses to related domains and the medically plausible constructs. The proportion of parents reporting chronic illness, acute significant illness, chronic illness and accidents increased as expected between 8 weeks and 8 months. As expected, adverse outcomes at 8 weeks were associated with an increased risk of the same outcomes at 8 months. CONCLUSIONS: The WCHMP is a simple measure of parent-reported health and illness which was shown to be reliable and valid with low inter-observer variation on initial field-testing. Further validation of the WCHMP, incorporated into the PHR, in a routine child health surveillance programme demonstrates its suitability for use in infancy to collect cross-sectional and longitudinal health and morbidity data for research and service planning purposes.

Child Health Services↗