Methylated hexachlorocyclohexane in blue mussels (Mytilus edulis) from the Mersey and Dee Estuaries.

Blue mussels (Mytilus edulis) from the Mersey and Dee Estuaries have been found to contain high concentrations of alpha-MHCH (methyl hexachlorocyclohexane) and gamma-MHCH (methyl lindane), and a series of other methylated isomers of MHCH. Mean values for SigmaMHCH in mussels declined serially from Rock Ferry (81.4 +/- 19.3 microg kg(-1)), the innermost site in the Mersey Estuary, to Egremont (49.0 +/- 8.6 microg kg(-1)) and New Brighton (11.1 +/- 3.8 microg kg(-1)); but the value for Crosby (67.0 +/- 10.2 microg kg(-1)) on the Liverpool shoreline was surprisingly high. Concentrations of alpha-HCH and gamma-HCH in M. edulis were consistently low, at <3.0 microg kg(-1). Comparisons between MHCH data for M. edulis and muscle tissue of both dab (Limanda limanda) and plaice (Pleuronectes platessa) give some evidence of food chain biomagnification of MHCH compounds, with adult plaice caught within the Mersey Estuary, where they feed on shellfish, showing very high levels of gamma-MHCH (18 +/- 9 microg kg(-1)) and MHCH (169 +/- 76 microg kg(-1)). Methylated analogues of HCH in biota are of potential regulatory interest and of substantial importance to the environmental management of the Mersey and Dee Estuaries.

Presence of secretory IgA antibodies to an enteric bacterial pathogen in human milk and saliva.

The concept of a common mucosal immune system in man was tested by examining the concurrent presence of specific-secretory IgA (SIgA) antibodies in human milk and saliva from three groups of subjects: 64 Sri Lankan women living in Sri Lanka; 20 immigrant Asian women living in Birmingham (median duration of residence in the United Kingdom five years); and 75 Caucasian women living in Birmingham (controls). Enzyme linked immunosorbent assays (ELISA) were developed to detect enterotoxigenic Escherichia coli (ETEC) colonisation factor/1 (CFA/1) specific SIgA antibodies in milk and saliva. ETEC CFA/1 specific SIgA antibody activity was detectable in milk (37.5% and 25%) and saliva (42.1% and 35%) of Sri Lankan and immigrant Asian women, respectively, but not in any of the Caucasian controls. Eighty five point two per cent of subjects who were positive had specific antibodies detectable in both milk and saliva; 5% of all Sri Lankan women and 10% of all immigrant Asian women had detectable antibody only in saliva. These observations lend further strong support to the idea that a common mucosal immune system exists in man. The continuing presence of specific SIgA antibodies in Asian immigrants to previously encountered antigens suggests that there may be an 'immunological memory' in the human secretory immune system.

Remission following an elemental diet or prednisolone in Crohn's disease.

The short- and long-term effects of an elemental diet in children with acute Crohn's disease were compared with those of prednisolone in historical controls. Clinical remission was induced in 25 of 30 and in 18 of 28 episodes treated for six weeks with an elemental diet and prednisolone. Patients with proximal disease had longer remission after treatment with an elemental diet (p < 0.05) than did patients with colonic disease after treatment with prednisolone (p < 0.01). Disease activity index score improved in both groups compared with the pretreatment scores (p < 0.05). However, the improvement in the elemental diet group was significantly better than in the prednisolone group (p < 0.001). Changes in linear growth were better after treatment with an elemental diet compared with steroids (p < 0.001). Serum albumin and haematocrit concentrations all improved significantly in the children treated with an elemental diet (p < 0.001) but not in those treated with steroids. Thus an elemental diet was better than prednisolone in proximal disease and confirmed improved growth and nutritional status.

IgA antibodies in human milk: epidemiological markers of previous infections?

The concept of an enteromammary link in secretory IgA (SIgA) antibody production was tested by hypothesising that specific SIgA antibody profiles in human milk might be an epidemiological marker for enteropathogens in a community. Milk from three subject groups was studied: 64 Sri Lankan women living in poor suburbs of Colombo, 20 Asian immigrant women domiciled in Birmingham, for a median period of five years (range 14 days-16 years), and 75 white women living in Birmingham. An enzyme linked immunosorbent assay (ELISA) was developed for the detection and measurement of SIgA antibodies to a panel of 14 crude O and 10 pure lipopolysaccharide antigens of diarrhoeagenic Escherichia coli strains well known to be endemic in the Indian subcontinent. The number of Sri Lankan and Asian immigrant women with SIgA antibodies to all 14 diarrhoeagenic E coli antigens (except O127 in Asian women) was significantly higher than in the white controls. The amount of E coli O antigen specific SIgA antibody activity as a percentage of total SIgA also gave significantly higher median values in Sri Lankan (6%) and in Asian immigrant (4%) women than in white controls (0.7%). SIgA antibodies were highly O serogroup specific and showed excellent concordance between crude O and the corresponding purified lipopolysaccharide antigens. These results suggest that milk antibody profiles represent an epidemiological marker of exposure to enteral pathogens. The continuing specific milk antibody response in Asian women who have been domiciled in the United Kingdom for many years may indicate 'memory' in the human secretory immune system.

Diarrhoea and growth faltering in rural Zimbabwe.

OBJECTIVE: To assess the evidence that diarrhoea is an important cause of growth faltering in young children in developing countries. DESIGN: Prospective, longitudinal cohort study. SETTING: Worker's compounds on commercial farms in Shamva, rural Zimbabwe. SUBJECTS: 204 children < 12 months old were enrolled, 73 from birth. The median age at enrolment was 4 months. Eleven children died and 39 were lost to follow-up. INTERVENTIONS: Prospective weekly diarrhoea surveillance by farm health workers and monthly anthropometry. RESULTS: Growth faltering was severe, but there was little difference in average rates of growth between children with frequent diarrhoea and infrequent diarrhoea. The results of an interval-based data analysis were consistent with there being only a transient effect of diarrhoea on weight gain. Estimation of weight faltering following episodes of diarrhoea and the rate of return to the trend in the 9-14 month age range, indicated that weight loss associated with each episode was small (approximately 2%) and return to the child's trend was 90% complete within a month. At older ages than this, weight loss appeared to be less, and estimates were not statistically significant. CONCLUSIONS: These observations lend weight to the hypothesis that recurrent episodes of diarrhoea are not a potent cause of growth faltering in early childhood except in a small minority of largely catastrophic cases. Inadequate food intake is a more plausible explanation.

PIP: In Zimbabwe, health workers collected data on diarrhea incidence every week and anthropometric data once a month from 204 children aged less than 12 months to examine the association between diarrhea and growth faltering. 73 children were enrolled at birth. 148 children were followed throughout the entire study. 11 children died (8 because of diarrhea or protein-energy malnutrition). 39 children were lost to follow-up. The children's parents were farm laborers who lived on large-scale commercial farms in Shamva district. Diarrhea incidence peaked between 13 and 18 months. In 91% of attacks, the diarrhea was watery rather than bloody. 31 children had more than 9 diarrhea episodes (high diarrhea frequency). 25 had no more than 4 diarrhea episodes (low diarrhea frequency). There was little difference in the children's mean weight and mean length from 1 to 30 months of age between high and low diarrhea frequency subjects. The average loss of overall growth per diarrhea episode in the age range 9-23 months was 51 g and 0.18 cm. In the age range of 9-14 months, weight loss after the diarrhea episode was 2.3% of body weight, and 90% of the sudden weight decline below the child's trend was recovered in 30 days. Weight loss was less than 2.3% among older children. A 2.3% weight loss in an 8 kg child is 180 g. Assuming that diarrhea is responsible for the entire weight loss (about 66 g/episode), the reduction in overall growth is about 120 g (1.5%). The total energy needed to accumulate 120 g is 480 kcal; thus, a child would require an additional 2-3 kcal/kg/day (a small amount) to gain 120 g. These findings support the hypothesis that recurrent diarrhea episodes do not induce growth faltering except in a few cases. Inadequate food intake is a more plausible explanation.

Abnormal gut blood flow velocities in neonates at risk of necrotising enterocolitis.

Duplex pulsed Doppler ultrasound was used to determine blood flow velocities in the coeliac axis and superior mesenteric artery in three groups of neonates: a group at high risk of developing necrotising enterocolitis (n = 27) and two control groups, i.e., a nonasphyxiated, appropriately grown group of preterm infants (n = 18) and a group of nonasphyxiated term infants (n = 14). Subjects were studied on the first, second, and fourth days of life. The median peak systolic velocities in the superior mesenteric artery were between 20 and 51% lower in the at-risk group than in the term control group on all 3 days of measurement (p less than 0.05-p less than 0.002). The ratio of peak systolic velocity in the coeliac axis to that in superior mesenteric artery, an index of relative downstream vascular resistance in the superior mesenteric artery, was 42-65% greater in the at-risk group compared with the other two groups on days 1 and 2 (p less than 0.05-p less than 0.001) and significantly greater than the term group on day 4 (73%, p less than 0.002). These data demonstrate that neonates at risk of developing necrotising enterocolitis have abnormal gut blood flow velocities. Furthermore, they provide evidence that an alteration in the splanchnic circulation may be an important factor in the final common pathway that links diverse risk factors for necrotising enterocolitis with clinical disease.

Doppler assessment of human neonatal gut blood flow velocities: postnatal adaptation and response to feeds.

Duplex pulsed Doppler ultrasound was used to study changes in gut blood flow velocities during the first week of life in a group of 14 term babies. There was a significant increase in fasting peak systolic velocity in the superior mesenteric artery between days 1 and 2 with a further upward trend until day 5; no such changes were seen in the coeliac axis. Fasting velocities were 20% lower in breast-fed babies than bottle-fed babies. Following feeds, there was a significant increase in velocity in the superior mesenteric artery that was 35% greater in the bottle-fed than breast-fed babies. Changes in the coeliac axis were qualitatively similar but substantially smaller. The peak velocity in both vessels occurred 50 min after a feed. We conclude that Doppler ultrasound can be readily used to measure gut blood flow velocities in the human newborn. It provides a noninvasive technique for investigating adaptive postnatal changes in the splanchnic circulation, and, in particular, the response to feeds.

The nature of small bowel luminal fluid lactase.

The evidence indicating a mucosal source for the jejunal fluid lactase activity of children is so far inconclusive. Samples of jejunal mucosa and the adjacent fluid were obtained simultaneously from 15 children. Lactase activity was measured at pH 5.9 in mucosa and fluid. Fluid activities showed a significant positive correlation with the activity of the corresponding mucosal homogenate but a stronger correlation was found with an enterocyte microvillous membrane fraction prepared from the same homogenate (r = 0.807 and 0.889, respectively). Kinetic and pH optima studies were consistent with a microvillous membrane origin. Fluid activity and pH optimum were not changed detectably when measured in the presence of an enterocyte lysosomal acid lactase inhibitor. Jejunal fluid lactase activity and its properties closely reflect the microvillous membrane enzyme. Lysosomal acid lactase does not contribute measurably to the total lactase activity of jejunal fluid.

Recurrent and persistent diarrhoea in a rural Zimbabwean community: a prospective study.

Prospective surveillance of patterns of diarrhoeal disease was conducted in a cohort of 204 young children living in a rural community in Zimbabwe. Trained field assistants recorded morbidity data obtained by weekly recall of mothers. Diarrhoea was defined by a commonly used local word, and a diarrhoea-free gap of three or more days was taken to signify a new attack. Diarrhoea was common in this study population with a peak incidence between 6 and 18 months of age. There was, however, wide individual variability in diarrhoea attack rates (range 0 to 20 attacks) during the 22 month study period. Whilst only 6 per cent of the recorded diarrhoea episodes were persistent (lasting longer than 14 days), a high proportion (26 per cent) of subjects had at least one attack of persistent diarrhoea (PD) during follow up. Children who had frequent attacks of acute diarrhoea also tended to have PD; PD was rare in those with few attacks. Thus, within this uniformly deprived African community, there were individuals who had a much higher susceptibility to diarrhoea compared to others. An understanding of this variability may point the way towards more effective interventions in the control of diarrhoeal disease.

Risk factors for high diarrhoea frequency: a study in rural Zimbabwe.

Diarrhoea morbidity data were collected prospectively over 22 months from a cohort of young children living in a deprived community in rural Zimbabwe. Despite the general high prevalence of diarrhoeal disease, there was considerable individual variability in attack rates. Risk factors associated with high diarrhoea frequency were therefore sought by a questionnaire study on feeding, environmental, educational and socio-economic factors. This was supported by observation of living conditions, and water and sanitation facilities. Surprisingly, no association was found between diarrhoeal morbidity and any of these factors, suggesting that other factors such as individual hygiene behaviour or individual susceptibility to diarrhoea may play a role in determining the observed differences in diarrhoea rates in this community.

Early growth faltering in rural Zimbabwean children.

Longitudinal data on weight and height were collected during the first 30 months of life from children living in a deprived rural community in Zimbabwe. All were breast-fed for up to a mean of 21 months; maize porridge being introduced from three months onwards. During the first 6 months, growth was similar to, or even exceeded, that of the NCHS reference population. Thereafter, growth faltering was common. By the age of 30 months, there was a mean deficit in weight of 2,0 kg in girls and 2,3 kg in boys, and a mean deficit in height of 8 cm in boys and 9 cm in girls. No seasonal variation in growth pattern was found. The substantially better growth of more privileged children in Zimbabwe and elsewhere in Africa, would suggest that these children were failing to realise their full genetic potential for growth because of adverse environmental factors.

Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin.

The effects on gut blood flow velocities of parenteral indomethacin (0.2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent--or in some cases even retrograde--diastolic flow. In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fall in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7.4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantially less (22% compared with 47%) and later (median time to maximum fall 37.3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus. These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus.

Understanding non-attendance in outpatient paediatric clinics.

Outpatient clinic appointments are often not kept. There has been little study of the reasons for this, but failure to attend may affect future health. Our study was based on the children's outpatient department of a large inner city district general hospital. The parents of 34 children who had failed to keep appointments and of 12 who did attend were interviewed in depth and the appointment systems of the hospital and of a nearby regional referral centre for children were reviewed. At the district general hospital 23% of first appointments and 35% of subsequent appointments were not kept. We found that parents usually made a conscious decision about attending, balancing the perceived advantages and disadvantages of doing so. Their assessment of the severity of the child's illness was crucial in this. Twenty one of the 34 children who had not attended were assessed at the time of interview as still needing to attend. Of these, 16 subsequently kept an appointment and 11 underwent further investigation or treatment. We conclude that children who are not brought for outpatient appointments may be at risk of avoidable ill health and that ways of either ensuring attendance at outpatient clinics or providing alternative means of health supervision are needed.

Adhesion and ultrastructural properties of human enterotoxigenic Escherichia coli producing colonization factor antigens III and IV.

Human enterotoxigenic Escherichia coli (ETEC) producing colonization factor antigen III (CFA/III) and coli surface antigens 4, 5, and 6 (CS4, CS5, and CS6) of CFA/IV were examined ultrastructurally and for ability to adhere to human small intestinal enterocytes and to cultured human intestinal mucosa. Strains of serotypes O25:H-, O25:H42, and O167:H5 producing CFA/III plus CS6, CS4 plus CS6, and CS5 plus CS6, respectively, showed good adhesion to human enterocytes (1.8 to 4.2 bacteria per brush border) and cultured human intestinal mucosa, whereas variants lacking these antigens or producing only CS6 were nonadherent (0 to 0.03 bacterium per brush border). By electron microscopy, CFA/III, CS4, and CS5 appeared as morphologically distinct rodlike fimbriae: CFA/III was 7 to 8 nm in diameter, CS4 was 6 to 7 nm in diameter, and CS5 was 5 to 6 nm in diameter. CS5 was unusual in that it appeared to be composed of two fine fibrils arranged in a double-helical structure. CS6 was difficult to characterize morphologically but possibly has a very fine fibrillar structure. By specific fimbrial staining and immunoelectron microscopy. CS4 and CS5 were shown to promote mucosal adhesion of ETEC; a similar adhesion role for the CS6 antigen could not be confirmed. ETEC strains of serotypes O27:H7, O27:H20, O148:H28, and O159:H20 which produced CS6 showed good adhesion to human enterocytes (1.6 to 3.0 bacteria per brush border), whereas variants which lacked CS6 were nonadherent (0 to 0.01 bacterium per brush border). These strains, however, also produced fimbrial or fibrillar surface antigens, in addition to CS6, which probably represent additional coli surface antigens responsible for the observed adhesive properties of these ETEC serotypes.

Does mechanical ventilation precipitate gastro-oesophageal reflux during enteral feeding?

The influence of intermittent positive pressure ventilation on gastro-oesophageal reflux in preterm infants is not known. In many neonatal units, however, concern that ventilation may increase gastro-oesophageal reflux (and therefore aspiration) leads to avoidance of enteral feeding during ventilation. We have therefore performed a crossover study of gastrooesophageal reflux by monitoring lower oesophageal pH in a group of nine enterally fed, very low birthweight infants both during assisted ventilation and normal breathing. All infants had less reflux during intermittent positive pressure ventilation (mean (SEM) reflux index 2.3 (0.6%)) than during normal breathing (mean (SEM) reflux index 6.1 (1.1%)). Assisted ventilation was associated with a significant reduction in the gastro-oesophageal pressure gradient, an effect which may be related to the use of positive and end expiratory pressure during ventilation. These data show that fear of gastro-oesophageal reflux should not preclude the use of enteral feeding in preterm infants receiving ventilation.

Intestinal permeability as a measure of small intestinal mucosal integrity: correlation with jejunal biopsy.

The permeability of the small intestine was measured and jejunal biopsy performed in 39 children with gastrointestinal disorders. Intestinal permeability was measured using orally administered mannitol and lactulose as probe molecules in an isotonic solution (274 mOs/l), and the results were expressed as the ratio of the urinary excretion of the two sugars over 5 h. Urine samples were analysed for mannitol and lactulose content by high performance liquid chromatography. Children with small intestinal mucosal damage, irrespective of the cause, had a significantly lower (P less than 0.001) mannitol excretion (mean recovery 1.21% of ingested dose) than those with a normal mucosa (mean recovery 5.3%), while lactulose excretion did not differ (P greater than 0.05). The mean value of the lactulose:mannitol urinary excretion ratios was significantly higher (P less than 0.001) in subjects with an abnormal mucosa (0.98) compared to those with a normal mucosa (0.2). Using the mean plus two standard deviations of the normal mucosa group to define the upper limit of normal, all lactulose: mannitol excretion ratios from the abnormal mucosa group were above this limit. The results of this study show that the sugar permeability test is a sensitive, non-invasive screening test for jejunal mucosal damage in children and shows good correlation with jejunal biopsy results.