Test and teach. Number 68. Diagnosis: Microvillus inclusion disease.
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Biomedical subjects
Publications and source records attributed to G P Davidson.
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Recently there has been much research effort directed towards the development of immunosensors. Optical technologies are currently proving very attractive for the construction of such sensors. The fluorescence capillary fill device (FCFD) has been designed to fulfil these needs. The development of an assay for human chorionic gonadotrophin (hCG) in the FCFD for a variety of body fluids (whole blood, serum, urine and saliva) demonstrates the versatility and assay performance of the device.
Optical immunosensors employing evanescent wave techniques have the potential to address the requirements of the 'alternative site' market; however, this potential has yet to be realised. The development of 'direct' sensors, such as those using surface plasmon resonance (SPR), has been hampered by problems of non-specific binding and poor sensitivity to small molecules. 'Indirect' sensors (for example, those employing a fluorescently labelled reagent) overcome many of the problems of direct sensors but require more sophisticated instrumentation because of the low light levels detected. In an attempt to combine the best features of the two techniques, an indirect SPR fluoroimmunoassay (SPRF) technique has been investigated. The surface field intensity enhancement produced by SPR is used to boost the emission from a fluorescently labelled immunoassay complex at a metal surface. The potential of the method is demonstrated by assaying for human Chorionic Gonadotrophin (hCG) in serum. Enhanced sensitivity over conventional total internal reflection fluorescence (TIRF) and SPR techniques was achieved.
In children technical limitations of upper oesophageal sphincter manometry have restricted investigation to the pull through technique under sedation. In this study we have used an adapted sleeve manometric technique for upper oesophageal sphincter monitoring in unsedated children and determined the influence of the state of arousal on upper oesophageal sphincter pressure. Twenty six children aged 3 to 42 months (median 17.5 months), who were referred for evaluation of oesophageal motor function, were studied with dual sleeve manometric assemblies which monitored upper and lower oesophageal sphincter pressures simultaneously. Pharyngeal, oesophageal body, and gastric pressures were also monitored with seven perfused side holes. Recordings were made for four hours after a meal and were technically successful in 24 children. The child's state of arousal was scored every 12th minute as follows: (A) resting, eyes closed, (B) resting, eyes open, (C) moving but comfortable, (D) restless and uncomfortable, (E) crying. In 67% of the 12 minute samples the children showed good adaptation to the procedure (arousal states A to C). There was a highly significant difference in upper oesophageal sphincter pressure between each of the arousal states (p less than 0.0001), being lowest in category A at (mean (SD) 18.1 (10.3) mmHg and highest in category D 55.7 (13.2) mm Hg. Abrupt changes in the state of arousal were associated with equally abrupt changes in upper oesophageal sphincter pressure. The state of arousal of unsedated children has an important influence on upper oesophageal sphincter pressure. It is essential that this factor is controlled for in any studies of upper oesophageal sphincter tone in children. The sleeve technique is capable of monitoring upper oesophageal sphincter motility for prolonged periods in unsedated children.
With the increase in the number of reported cases of child abuse it is important that medical practitioners should know the normal values for the size of the anus. Children aged 3 months to 15 years, attending a paediatric gastroenterology clinic for a routine examination, had a photographic record made of the anus 30 seconds after exposure of the anus as part of a standardised examination protocol. Anorectal disease, including Crohn's disease was present in eight children. Analysis of the 54 children without anorectal disease indicated that the anteroposterior diameter of the anus was less than 10.0 mm and the transverse diameter was less than or equal to 2.0 mm. Age, sex of the child, digital rectal examination, time since last defaecation and the capacity and contents of the rectum were unrelated to the size of the anus. In view of the difficulties which arise in suspected child abuse, medical practitioners should gain experience of the normal appearance and size of the anus. This can best be validated within a medicolegal framework if some form of standardised examination protocol is used. The key element of such an examination is not the position in which the child is examined but the time taken to observe the anus, to allow any dynamic changes to occur. An inspection time of 30 seconds in a cooperating conscious child is recommended.
The efficacy of a 10-day course of bovine colostrum with high antibody titre against the four known human rotavirus serotypes in protecting children against rotavirus infection was examined in patients admitted to hospital. Children aged 3 to 15 months were blocked in pairs according to ward accommodation (ie, isolation or open area). Each block contained 1 treated and 1 control child. The allocation to treatment or control (an artificial infant formula) was randomised. 9 of 65 control children but none of 55 treated children acquired rotavirus infection during the treatment period (p less than 0.001). The importance of protecting against rotavirus infection was highlighted by the fact that parents of symptomatic rotavirus-positive children sought medical attention seven times more often than did parents of symptomatic rotavirus-negative children (p less than 0.05).
The breath hydrogen test for carbohydrate malabsorption has been proved to be sensitive, specific and noninvasive. This study was performed to determine its applicability in the newborn period. Postprandial hydrogen excretion in the first 5 days of life was measured in 105 full-term normal newborns, who were either artificially or breast fed. Samples of expired air were collected via a nasopharyngeal catheter at 30 min intervals between feeds. Some babies showed no hydrogen production after 5 days, while others produced high (200 parts/10(6] levels. The incidence of hydrogen production increased postnatally--more than 80% of babies produced hydrogen by 5 days of age. None of the babies was unwell or developed frequent or loose stools suggestive of clinical carbohydrate malabsorption. It is therefore postulated that these high hydrogen levels reflect biochemical evidence of clinically insignificant carbohydrate malabsorption in this age group. This study shows clearly that an interfeed interval of 4 h in these babies is insufficient to cause breath hydrogen levels to fall in a predictable way. The ethical and practical difficulties in fasting these infants for longer periods suggest that conventional carbohydrate challenges with breath hydrogen estimations will be difficult in the neonate.
Hospital-acquired enteric infections, particularly those due to rotavirus, were investigated by studying 220 patients under 3 years of age who were admitted without gastroenteritis to two paediatric general medical wards during a 10 month period. Faecal specimens were collected within 48 h of admission and then daily until the patients were discharged. Samples were also collected after discharge if patients developed enteric symptoms within 2 days of discharge. Fourteen per cent (31 of 220) of patients acquired rotavirus infections while in hospital, 23% (seven of 30) excreted rotavirus only after discharge; 29% of patients infected with rotavirus were asymptomatic (nine of 31). Acquisition of rotavirus infection was most prevalent during the months May-August, with a prevalence of 34% (12 of 35) in May. Hospitalization was prolonged in those patients who acquired rotavirus (11.1 days compared with 8.0 days, P less than 0.05). This study highlights the importance of rotavirus as a cause of hospital cross-infection, particularly in the very young patient, and emphasizes the need for further assessment of factors involved in its acquisition. In order to determine correctly the incidence of hospital-acquired illness, it is essential to follow patients after discharge from hospital. This study reinforces the importance of developing preventive measures in order to reduce the frequency of this illness.
The use of overnight, nasogastric, nutritional supplementation during hospitalization of children with cystic fibrosis (CF) receiving antibiotic therapy for acute exacerbations of respiratory disease was evaluated in 11 children (mean age = 7.75 years). Supplementary feeding significantly increased inpatient energy intake from 116 +/- 30% to 165 +/- 30% (P less than 0.001) of recommended dietary allowance with minimal effect on oral intake. It also resulted in significantly improved weight gains but neither increased energy intakes nor weights were sustained at short-term (mean = 5.7 weeks) or long-term (mean = 21.6 weeks) follow-up. The notion that short bursts of nasogastric feeding for inpatients with CF improve growth status is not supported. However, the study did show that treatment of chest infections alone does not positively affect spontaneous oral energy intake.
Recent evidence suggests that malnutrition has a negative impact on pulmonary function in children with cystic fibrosis. In the past, dietary management has aimed at high energy low fat intake, but this has recently been shown to fall far short of the 120-150% of the recommended daily allowance for energy cystic fibrosis patients require. This paper outlines the current principles of nutritional management for children with cystic fibrosis. These include a high energy, high fat containing diet (within limits of individual tolerance); high carbohydrate intake; high salt intake; replacement of fat-soluble vitamins; appropriate use of pancreatic enzyme preparations; and supplemental feeding when indicated. It is vital that a nutrition education programme be established for each child and his or her family so that the emphasis shifts from treatment of malnutrition to prevention. The long-term aim must be to promote an independent, healthy lifestyle which incorporates good nutrition and other healthy pursuits such as exercise.
Children with advanced portal hypertension usually have splenomegaly (often associated with hypersplenism) which may lead to a decreased life span of circulating blood leukocytes. In a group of 6 children (age range 4-15 years; mean age 8.5 years) with portal hypertension, we examined peripheral blood mononuclear leukocytes for possible changes in their proportions, numbers and function. Compared to normal subjects, children with portal hypertension had a marked reduction in the percentages and absolute numbers of T lymphocytes (CD3+), T 'helper/inducer' (CD4+) and T 'suppressor/cytotoxic' (CD8+) cells. However, the percentages of B lymphocytes (FMC1+), natural killer cells (Leu 11+) and monocytes (morphological) were increased, and the absolute numbers of B cells were significantly increased in these patients. Lymphocyte responsiveness to phytohemagglutinin, pokeweed mitogen and concanavalin A were depressed in the patients, while the natural killer cell cytotoxicity was slightly increased. Thus, children with portal hypertension show changes in the relative proportions and absolute numbers of peripheral blood mononuclear blood leukocyte subpopulations as well as changes in mononuclear leukocyte function.
Acute diarrhoea is one of the commonest symptoms in paediatric practice. In most cases it will have an infectious cause. Acute diarrhoea in Australian children has a low mortality but significant morbidity. The major cause of death is unrecognised or underestimated dehydration.
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In 122 healthy newborn infants, we studied the relationship between breath hydrogen (H2) production after feedings containing lactose (human milk or commercial formula) in colicky and noncolicky infants at 6 weeks and 3 months. Eighty-three infants (68%) developed colic (mild, moderate, or severe) by 2.6 +/- 1.8 weeks of age (mean +/- SD). Zero time (baseline) breath H2 values were significantly higher in colicky compared with noncolicky infants at both 6 weeks (40.6 +/- 41.4 vs 14.8 +/- 32.9 ppm) and 3 months (27.7 +/- 38.1 vs 8.5 +/- 18.2 ppm). There were significantly more positive breath H2 tests in colicky compared with noncolicky infants at 6 weeks (78% vs 36%) and 3 months (89% vs 45%). Failure to produce H2 throughout the breath H2 test was significantly more frequent in noncolicky compared with colicky infants at 6 weeks (50% vs 18%) and 3 months (43% vs 4%). These findings remained significant even when infants with mild colic (at 6 weeks and 3 months) were included in the noncolicky group. We conclude that colicky infants produce more breath H2 in the fasting state and in response to feedings containing lactose than noncolicky infants produce. This may represent increased lactose malabsorption, differences in colonic bacterial fermentation conditions, or differences in the handling of colonic gas produced.
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We report the case of a 5 month old breast fed infant who presented with a history of vomiting, pallor, and failure to thrive. Investigations showed severe nutritional vitamin B12 deficiency with a megaloblastic pancytopenia. This deficiency was due to low vitamin B12 concentrations in the maternal breast milk, and subsequent investigations showed maternal pernicious anaemia. Treatment of the infant with vitamin B12 resulted in a rapid clinical and haematological improvement. This case represents an unusual presentation of pernicious anaemia.
The cause(s) of excessive fecal bile acid loss in cystic fibrosis (CF) has not yet been fully determined, but in vitro studies have suggested that a primary mucosal defect in ileal bile acid uptake may be of importance. To examine this mechanism in vivo, the terminal ileal uptakes of taurocholate and glycocholate were determined using a marker-perfusion technique in three CF infants and four controls. Normal and CF ileal conditions were stimulated by varying the taurocholate:glycocholate concentration ratio (normal 1:1, CF 1:4) and pH (normal 7.8, CF 6.0) of the perfusate. The mean bile acid uptake under normal perfusate conditions was not significantly different in CF subjects (taurocholate 0.124 mumol/min/cm ileum +/- SD 0.127, glycocholate 0.117 mumol/min/cm ileum +/- 0.114), and controls (0.142 +/- 0.164 and 0.115 +/- 0.120 respectively). Similarly, under CF conditions, bile acid uptake values in CF subjects and controls were similar. The results are not consistent with deranged ileal bile acid reabsorption being a major cause of fecal bile acid loss in CF.