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Biomedical subjects

K G Brownlee

Publications and source records attributed to K G Brownlee.

At least 19 recordsLinked to original sources
PubMed2001

Methicillin resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis.

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) infection is increasingly found in patients with cystic fibrosis (CF). AIMS: To determine whether MRSA infection has a deleterious effect on the clinical status of children with CF. METHODS: Children with MRSA in respiratory cultures during a seven year period were identified and compared with controls matched for age, sex, and respiratory function. Respiratory function tests, anthropometric data, Shwachman-Kulczycki score, Northern chest x ray score, intravenous and nebulised antibiotic therapy, and steroid therapy were compared one year before and one year after MRSA infection. RESULTS: From a clinic population of 300, 10 children had positive sputum or cough swab cultures for MRSA. Prevalence rose from 0 in 1992-1994 to 7 in 1998. Eighteen controls were identified. Children with MRSA showed significant worsening of height standard deviation scores and required twice as many courses of intravenous antibiotics as controls after one year. They had significantly worse chest x ray scores at the time of the first MRSA isolate and one year later, but showed no increase in the rate of decline in chest x ray appearance. There was a trend towards lower FEV(1) and FEF(25-75) in children with MRSA. There were no significant differences between the two groups with respect to change in weight, body mass index, or Shwachman score. There was no significant difference in prior use of steroids or nebulised antibiotics. CONCLUSION: MRSA infection in children with CF does not significantly affect respiratory function, but may have an adverse effect on growth. Children with MRSA require significantly more courses of intravenous antibiotics and have a worse chest x ray appearance than controls.

Adolescent↗
PubMed2000

Evaluation of fecal pancreatic elastase-1 as a measure of pancreatic exocrine function in children with cystic fibrosis.

Pancreatic elastase-1 (EL-1) is a specific human protease synthesised by the acinar cells. It is stable, unaffected by exogenous pancreatic enzyme treatment, and correlates well with stimulated pancreatic function tests. We report our experience of EL-1 measurements in 142 patients from a large cystic fibrosis (CF) clinic. The median patient age was 7.7 years (range, 0.1-20.8 years), 93 were homozygous and 38 heterozygous for DeltaF508, and 11 had other or unidentified mutations. There were 85 non-CF control subjects. Seven were pancreatic sufficient (PS). The median (quartile 1-quartile 3) fecal EL-1 of the 135 pancreatic insufficient (PI) patients was 10 microg/g stool (2.5-33); of the 7 PS patients, 698 microg/g stool (400.5-824.5), and of the non-CF controls, 615 microg/g stool (420-773). Using the Mann-Whitney U test, there was a statistically significant difference for fecal EL-1 activity between the PS and PI patients (P = 0.0001) and the PI and control group (P < 0.0001), but not between the control and PS groups (P = 0.63). Median (quartile 1-quartile 3) fecal EL-1 in the pancreatic insufficient DeltaF508 homozygotes was 10 microg/g stool (2-33), and in the heterozygotes 12 microg/g stool (4-39) (not significant, P = 0.62). We now use fecal EL-1 as evidence of PI in screened CF infants (reliable over the age of 2 weeks); in older CF patients at diagnosis; for confirming the need for pancreatic enzymes in patients referred to the clinic already taking enzymes; for annual monitoring of PS patients to detect the onset of PI; and as supporting evidence when excluding the diagnosis of CF in patients attending the pediatric gastroenterology clinic. The low values in the first 2 weeks in some normal and premature infants, and the persisting normal values in PS infants, make the fecal EL-1 test unsuitable for neonatal CF screening.

Adolescent↗
PubMed2000

Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.

OBJECTIVE: To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN: A multicentre randomised double blind placebo controlled trial. SUBJECTS: Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION: Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES: Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. RESULTS: 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). CONCLUSIONS: There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.

Acute Disease↗
PubMed1999

Acute bronchopulmonary infection due to Streptococcus milleri in a child with cystic fibrosis.

An 8 year old girl with cystic fibrosis had severe respiratory disease associated with chronic Pseudomonas aeruginosa bronchopulmonary infection. Despite regular courses of intravenous antipseudomonal antibiotics, she continued to deteriorate over 18 months with persistent productive cough, worsening respiratory function, and increasing oxygen dependence. During her 11th admission Streptococcus milleri was isolated from sputum cultures in addition to P aeruginosa. She failed to respond to antipseudomonal antibiotics but improved dramatically with the addition of intravenous benzylpenicillin. Although S milleri is considered a normal mouth commensal and its isolation from sputum of cystic fibrosis patients is of uncertain significance, it was associated with clinically significant infection in this child. S milleri was eradicated with antibiotic treatment and clinical improvement has been maintained.

Acute Disease↗
PubMed1999

Plasma creatinine rises dramatically in the first 48 hours of life in preterm infants.

OBJECTIVE: Published data show that plasma creatinine falls steadily during the first 28 days of life and that creatinine levels in the neonatal period are higher in more premature infants. However, the best reference data commence on day 2 of life. The objective of this study was to document how plasma creatinine changes in the first 48 hours of life and to examine the reason for the apparently high levels of creatinine in preterm infants, compared with maternal levels. DESIGN: A prospective observational study on a regional neonatal intensive care unit. PATIENTS: A total of 42 preterm infants, mean gestational age of 29.4 weeks (range: 23-35), mean birth weight of 1.42 kg (.55-2.77), divided into 4 gestation groups: 23 to 26 weeks (n = 9), 27 to 29 weeks (n = 13), 30 to 32 weeks (n = 12), and 33 to 35 weeks (n = 8). INTERVENTIONS: Measurement of plasma creatinine and urea concentration in cord blood and in serial samples taken for routine arterial blood gas analysis. OUTCOME MEASUREMENTS: Changes in creatinine concentration with time and relationship to gestational age, birth weight, and illness severity. RESULTS: Mean creatinine at birth was 73 micromol/L (95% confidence interval [CI]: 68-79 micromol/L). Plasma creatinine rose significantly over the first 48 hours. Mean peak creatinine in the most preterm infants (23-26 weeks) was 221 micromol/L (CI: 195-247 micromol/L). Peak plasma creatinine was inversely related to gestation (Spearman's coefficient: -.73) and birth weight (Spearman's coefficient: -.76). Significant differences in creatinine concentration were seen among different gestational groups at 24 and 48 hours of life. Peak creatinine correlated with a high Clinical Risk Index for Babies score (Spearman's coefficient:. 64). The fall in creatinine began later in more premature infants. All 38 surviving infants had normal renal function; their mean plasma creatinine at discharge was 52 micromol/L (CI: 46-58 micromol/L). CONCLUSIONS: Rather than falling steadily from birth, creatinine rises dramatically in the first 48 hours of life, especially in infants of <30 weeks' gestation. Even large rises in creatinine in the first 48 hours may be expected and should not be used in isolation to diagnose renal failure.

Birth Weight↗
PubMed1997

Role of epidermal growth factor and transforming growth factor alpha in the developing stomach.

AIMS: To determine whether epidermal growth factor (EGF) or the related transforming growth factor alpha (TGF alpha) may have a role in the developing human stomach; to substantiate the presence of EGF in human liquor in the non-stressed infant and whether EGF in amniotic fluid is maternally or fetally derived. METHODS: The temporal expression and localisation of EGF, TGF alpha, and their receptors during fetal and neonatal life were examined in 20 fetal and five infant stomachs. Simultaneously, samples of amniotic fluid and fetal urine from 10 newborn infants were collected and assayed for EGF by radioimmunoassay. RESULTS: EGF immunoreactivity was not noted in any of the specimens examined. In contrast, TGF alpha immunoreactivity was shown in mucous cells from 18 weeks of gestation onwards. EGF receptor immunoreactivity was seen on superficial mucous cells in gastric mucosa from 18 weeks of gestation onwards. The median concentration of EGF was 30 and 8.5 pg/ml in amniotic fluid and fetal urine, respectively, suggesting that EGF is not produced by the fetus. CONCLUSIONS: This study adds weight to the hypothesis that swallowed EGF, probably produced by the amniotic membranes, and locally produced TGF alpha, may have a role in the growth and maturation of the human stomach.

Amniotic Fluid↗
PubMed1994

To PEEP or not to PEEP?

It is well recognised that reducing positive end expiratory pressure (PEEP) leads to an increase in the tidal volume and minute volume in ventilated neonates. The magnitude of this effect is perhaps not commonly appreciated, however. Effectively, PEEP is four times as potent as peak inflation pressure (PIP) in bringing about changes in tidal volume. The influence of changes in PEEP and PIP on tidal volume and the relative magnitude of each are considered. Twenty one preterm infants were studied on 38 separate occasions. All were sedated, paralysed, and ventilated, 19 for hyaline membrane disease. A 1 cm H2O reduction in PEEP was twice as potent as a 2 cm H2O increase in PIP in achieving an increase in tidal volume (14 v 7%). Similarly, increasing PEEP by 1 cm H2O was twice as effective as a 2 cm H2O decrease in PIP in reducing tidal volume (13 v 6%). Small (0.5-1 cm H2O) changes in PEEP can often be used to improve ventilation and carbon dioxide elimination. Levels of PEEP of 4-5 cm H2O may, at times, impair gas exchange and contribute to overdistension.

Humans↗
PubMed1993

Gastric acid secretion in preterm infants.

Little is known about the ontogeny of gastric acid secretion in the very preterm infant. In order to study this we recorded intragastric pH continuously for 24 h on 71 occasions in 22 enterally starved preterm infants. Infants ranged from 24 to 29 weeks' gestation and were studied in the first 5 days, and in the third week, of life. As the infants became more mature, both in terms of gestation and postnatal age, there was a decrease in intragastric pH from median (range) 3.7, 2.5 (0.6-3.9) and 1.8 (1.3-2.6) for infants of 24-25, 26-27 and 28-29 weeks' gestation, respectively on the first day of life to 1.8 (1.7-1.9), 2.0 (1.8-2.3) and 1.7 (1.5-2.0) on day 16. All the infants were able to maintain a gastric pH of below 4 from the first day of life. Our data lay to rest the suggestion that the preterm infant is incapable of hydrogen ion secretion. Gastric acid secretion in the newborn preterm infant should allow normal proteolytic activity and the well recognised clinical problems of intragastric bleeding, gastritis or oesophagitis may be attributable to intragastric acid.

Gastric Acid↗
PubMed1993

The effect of intravenous ranitidine on the intragastric pH of preterm infants receiving dexamethasone.

Gastric perforation is a catastrophic, albeit uncommon, side effect of steroid treatment for premature infants with bronchopulmonary dysplasia (BPD). A reduction of intragastric acidity may protect against peptic ulceration. The effect of different doses of ranitidine, given as intravenous infusions, on intragastric acidity in premature neonates was therefore examined. Ten consecutive, enterally starved, infants receiving dexamethasone (0.6 mg/kg) for BPD were enrolled. Intragastric pH was continuously monitored on the day before steroid treatment and on the four following days, initially without H2 blockade and then using a continuous intravenous infusion of ranitidine at 0.031, 0.0625, and 0.125 mg/kg/hour. An infusion of 0.0625 mg/kg/hour of ranitidine was sufficient to increase and maintain gastric pH above 4; the authors therefore use this infusion during dexamethasone administration as possible prevention of gastric perforation.

Bronchopulmonary Dysplasia↗
PubMed1993

Early or late parenteral nutrition for the sick preterm infant?

No one doubts that good nutrition is an important component of neonatal intensive care, nor that this can only be accomplished by the use of intravenous fat. With regard to the effects of nutrition on bronchopulmonary dysplasia, however, we are facing a dilemma. On the one hand there is the suggestion that inadequate nutrition increases the severity of bronchopulmonary dysplasia and on the other that the use of intravenous fat predisposes to it. In an attempt to narrow the area of uncertainty we randomly allocated 129 infants of less than 1750 g birth weight to receive either early or late lipid containing parenteral nutrition. The median duration of ventilation support in the 'early' group was 8.5 days and in the 'late' group eight days; this was not significantly different.

Bronchopulmonary Dysplasia↗
PubMed1993

When is the fetus first capable of gastric acid, intrinsic factor and gastrin secretion?

Little data exist regarding the activity of gastric parietal and G cells in the very immature infant. Therefore, we have examined the developing human stomach for the presence and location of parietal and G cells, by using both standard histological methods and antibodies to the H+/K(+)-ATPase (proton pump), intrinsic factor and gastrin in 25 fetuses (ranging from 13-28 weeks) and in 5 infants (2-21 weeks). Parietal cell activity was noted in the body, antrum and pyloric regions in all the fetal specimens examined. However, this activity was much more limited in the infant specimens. Gastrin immunoreactivity was noted in all specimens from 18 weeks of gestation onwards; this activity was located solely in the antral and pyloric region. These results indicate that the human fetus has the potential to produce gastric acid, intrinsic factor and gastrin from the middle of the second trimester.

Enterochromaffin Cells↗
PubMed1992

Gastric secretory function in the developing human stomach.

Little data exists regarding the activity of gastric parietal cells in the very immature infant. Therefore we have examined the developing human stomach for the presence and location of parietal cells, using both standard histological methods and antibodies to the H+/K+ ATPase (proton pump) and intrinsic factor, in 35 fetuses (ranging from 13-28 weeks) and in five infants (2-21 weeks). Parietal cell activity was noted in the body, antrum and pyloric regions in all the fetal specimens examined. However, this activity was much more limited in the infant specimens. We have noted that from the end of the first trimester parietal cells are present in a mature, functional form with the potential to secrete both gastric acid and intrinsic factor.

Embryonic and Fetal Development↗
PubMed1992

Changes in the plasma aminogram of parenterally fed infants treated with dexamethasone for bronchopulmonary dysplasia.

A substantial increase in the plasma concentration of most amino acids was observed in 59 preterm infants with chronic lung disease soon after the initiation of dexamethasone therapy. The size of increase appeared to be dose related. This phenomenon is likely to be the result of steroid induced protein catabolism. Interestingly, neither phenylalanine nor tyrosine concentrations were significantly increased.

Amino Acids↗
PubMed1992

Catabolic effect of dexamethasone in the preterm baby.

Most babies treated with dexamethasone for bronchopulmonary dysplasia exhibit an appreciable rise in the blood urea concentration, from a mean of 2.3 mmol/l before steroid to a mean of 7.1 mmol/l after. In order to discover whether this was primarily the result of increased protein catabolism, nitrogen balance studies before and after the start of dexamethasone were performed and a mean deficit in nitrogen retention of 158 mg/kg/24 hours was found. Similarly the urinary 3-methylhistidine (3MH):creatinine ratio before and after the commencement of dexamethasone treatment in a group of preterm babies was measured. It was found that there was a substantial increase in 3MH excretion after dexamethasone: from a mean 3MH:creatinine ratio of 46 in the week before steroids to a mean ratio of 77 in the week after. As 3MH emanates almost exclusively from the breakdown of actin in skeletal muscle cell, this finding implies the loss of muscle tissue. It was also found that the babies were in less positive nitrogen balance after dexamethasone, to a degree which is significant relative to their protein reserves. The long term consequences of a period of increased catabolism are not yet known but the authors suggest caution in the use of dexamethasone, at least in babies with milder degrees of bronchopulmonary dysplasia in whom the ratio of benefit to risk may be less favourable.

Bronchopulmonary Dysplasia↗