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Biomedical subjects

P C Ng

Publications and source records attributed to P C Ng.

At least 19 recordsLinked to original sources

Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.

AIM: To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome. METHODS: Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications. RESULTS: More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects. CONCLUSION: These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.

Administration, Inhalation

Effect of multiple courses of antenatal corticosteroids on pituitary-adrenal function in preterm infants.

AIM: To evaluate the pituitary-adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS: The pituitary-adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 microg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS: The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = -0.59, p = 0.04 and r = -0.60, p = 0.039, respectively). CONCLUSIONS: The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary-adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve.

Adrenal Cortex Function Tests

Massive subdural haematoma: an unusual complication of septicaemia in preterm very low birthweight infants.

Non-traumatic massive subdural haematoma is a rare condition in newborn infants and is usually associated with hereditary coagulation disorders or congenital vascular malformation. Its occurrence in preterm very low birthweight infants secondary to systemic bacterial infection has not been reported. We describe two extremely preterm neonates who developed massive subdural haematoma as a result of gram-negative septicaemia and disseminated intravascular coagulation. Both infants suffered severe parenchymal cerebral injury and hydrocephalus. Clinicians should be aware of this unusual and catastrophic complication if a very low birthweight infant with severe sepsis and disseminated intravascular coagulation suddenly deteriorates despite successful treatment with antibiotics. Radiological imaging by cranial ultrasound or computed tomography scanning should be routinely considered in all such infants for the detection of intracranial bleeding.

Bacteremia

Clinical prediction of post-extubation radiological changes of the chest in newborn infants.

OBJECTIVE: Whether a chest radiograph should be performed routinely in all infants after extubation, or selectively only in those with clinical deterioration, is a controversy in neonatal unit practice. This study tested the hypothesis that most cases of post-extubation radiological deterioration in the lungs could be detected by clinical assessment. METHODS: A chest radiograph was performed at 8 h post-extubation in 100 episodes of extubation in 85 newborn infants ventilated for a variety of lung diseases. Each infant was assessed at the same time by a neonatologist blinded to the radiological findings, to determine whether a chest radiograph would have been requested based on clinical judgement. The infants were continuously monitored for their respiratory and oxygenation status before and after extubation. RESULTS: Compared to the pre-extubation chest radiographs, 23 of the 100 post-extubation chest radiographs showed either deterioration of the pre-existing lung pathologies or appearance of significant new pathologies. The clinicians' assessment failed to detect most of the deterioration, with a sensitivity of only 21.7%. Systematic analysis of the infants' clinical parameters showed that the development of significant intercostal/subcostal retraction, and an increase in inspired oxygen concentration by > or = 7% after extubation, were the best predictors of post-extubation radiological deterioration (sensitivity 82.6%, specificity 62.3%, positive predictive value 39.6%, and negative predictive value 92.3%). Serial blood gas in contrast had little predictive value. CONCLUSION: We conclude that most cases of radiological deterioration of the lungs after extubation are clinically predictable, provided the correct clinical criteria are used.

Blood Gas Analysis

Is homozygous alpha-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous alpha-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous alpha-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.

Fatal Outcome

Risk factors for Enterobacter septicemia in a neonatal unit: case-control study.

Thirty cases of Enterobacter aerogenes or Enterobacter cloacae septicemia diagnosed over a 32-month period in a tertiary care neonatal unit were enrolled in a case-control study. Each case patient was matched with two controls (patients occupying the cots nearest the case patient when the latter developed septicemia). Of the 32 perinatal characteristics evaluated, 11 were identified by univariate analysis to be significantly associated with the infection. These included parents being residents of the Vietnamese refugee camps, respiratory distress syndrome, necrotizing enterocolitis, umbilical arterial catheterization, umbilical venous catheterization, bladder catheterization, mechanical ventilation, antibiotic treatment, peripheral venous catheterization, nasogastric intubation, and parenteral nutrition. Multivariate analysis, however, showed that preceding bladder catheterization and ongoing parenteral nutrition were the only independent risk factors for enterobacter septicemia. Strict aseptic technique in the preparation of parenteral nutrition fluid and avoidance of bladder catheterization are measures that may reduce the risk of enterobacter sepsis for newborns.

Bacteremia

Randomised crossover trial of salbutamol aerosol delivered by metered dose inhaler, jet nebuliser, and ultrasonic nebuliser in chronic lung disease.

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.

Administration, Intranasal

Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants.

AIMS: To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis in preterm, very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit. The babies were randomly allocated to receive oral vancomycin (15 mg/kg every 8 hours for 7 days) or an equivalent volume of placebo solution. Prophylaxis was started 24 hours before the start of oral feeds. All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs. Necrotising enterocolitis was diagnosed and staged according to modified Bell's criteria. RESULTS: Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis (p = 0.035). Infants with necrotising enterocolitis were associated with a significant increase in mortality (p = 0.026) and longer duration of hospital stay (p = 0.002). CONCLUSIONS: Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm, very low birthweight infants and was associated with a 50% reduction in the incidence. However, widespread implementation of this preventive measure is not recommended, as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms. Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients.

Administration, Oral

Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer.

To identify the most efficient device for the delivery of bronchodilator aerosol to nonventilated preterm infants with chronic lung disease, we compared the metered dose inhaler (MDI) used in conjunction with a non-valved spacer, an ultrasonic nebulizer with a small medication cup, and two jet nebulizers. The subjects were enrolled in two double-blind randomized crossover studies. In study A (n=10), each infant was given a nominal dose of 200 microg of salbutamol by a MDI (Ventolin) at 4 h intervals, and in random sequence via an Aerochamber (Neonatal Aerochamber) with its one-way valve removed, an ultrasonic nebulizer with a small cone-shaped medication cup (Siemens Electronics), and a jet nebulizer (Side-stream). Their functional residual capacity (FRC) and static respiratory system mechanics were measured before, and at 15, 30, 60, and 120 min after aerosol delivery. Study B (n=10) was carried out in an identical manner, but with a different jet nebulizer (Hudson). In both studies, administration of salbutamol aerosol via the MDI Aerochamber or ultrasonic nebulizer resulted in a significantly greater reduction in respiratory system resistance than via jet nebulizers. Furthermore, the use of MDI Aerochamber or ultrasonic nebulizer was associated with a greater degree of post-treatment tachycardia and improvement in FRC. The bronchodilating effect of salbutamol delivered via the ultrasonic nebulizer appeared to be slightly greater than that via the MDI-Aerochamber, receiving significance only in Study B. We conclude that both the metered-dose inhaler used with a nonvalved Aerochamber and the ultrasonic nebulizer with a small medication cup are both more efficient than the jet nebulizers in preterm infants.

Albuterol

Pituitary-adrenal suppression in preterm, very low birth weight infants after inhaled fluticasone propionate treatment.

Systemic corticosteroids prescribed for treatment of pulmonary diseases in preterm, very low birth weight infants caused severe suppression of the hypothalamic-pituitary-adrenal axis and produced serious physiological and metabolic disturbances. However, the effect of inhaled corticosteroids on their pituitary-adrenal functions is not known. We prospectively evaluate the pituitary-adrenal function using the human CRH stimulation test in a cohort of very low birth weight infants at risk for hypothalamic-pituitary-adrenal axis suppression in a double blind, randomized pilot study designed for assessing the efficacy and adverse effects of inhaled fluticasone propionate in newborn preterm infants who required mechanical ventilation for treatment of respiratory distress syndrome. Twenty-five preterm (< 32 gestational weeks), very low birth weight (< 1500 g) infants were randomized to receive inhaled fluticasone propionate (n = 13) or a placebo inhaler (n = 12). The medication was given every 12 h (fluticasone propionate, 1,000 micrograms/day) for 14 days. All surviving infants had their pituitary-adrenal functions assessed by human CRH test on the following morning immediately after completion of the 2-week course. All basal (0 min) and post-stimulation (15, 30, and 60 min) plasma ACTH and serum cortisol concentrations were significantly suppressed in the inhaled fluticasone group compared to their corresponding levels in the placebo group [basal plasma ACTH concentrations (F = 6.0; P = 0.02), poststimulation plasma ACTH concentrations (F > 8.6; P < 0.01), basal serum cortisol concentrations (F = 5.6; P = 0.03), and poststimulation serum cortisol concentrations (F > 15.6; P < 0.001)]. This is the first study in very low birth weight infants that demonstrates unequivocally that cumulative high dose inhaled corticosteroids can induce moderately severe suppression of both the pituitary and adrenal glands. The systemic bioactivity is probably associated with pulmonary vascular absorption, which effectively circumvents the hepatic first pass metabolism. Until the question of safety can be adequately addressed, inhaled fluticasone propionate should be used with cautionin preterm infants.

Administration, Inhalation

Aerosol delivery to non-ventilated infants by metered dose inhaler: should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 micrograms/dose) of MDI albuterol through a neonatal Aerochamber 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber: 51.2 +/- 3.1% vs. 35.0 +/- 2.8%, P < 0.0001; Babyhaler: 38.8 +/- 2.3% vs. 19.2 +/- 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used.

Aerosols

Preparation and characterization of the F (ab)2 fragments of an aromatase activity-suppressing monoclonal antibody.

The preparation and characterization of the Fab and F(ab')2 fragments of a murine monoclonal antibody specific for aromatase cytochrome P-450 and which is suppressive of estrogen biosynthesis are described. This monoclonal antibody, MAb3-2C2, was purified from murine ascites using protein A affinity chromatography and digested with immobilized papain to produce antibody fragments. The Fab and F(ab')2 fragments were then purified using protein A affinity chromatography and S-200 HR size exclusion chromatography. The Fab fragment was further purified using S-100 HR size exclusion chromatography. Both the Fab and F(ab')2 fragments of the MAb3-2C2 suppressed aromatase activity in a dose-dependent manner. While the F(ab')2 fragment (110 kDa) maintained potent suppressive activity, the Fab fragment (42 kDa) required a higher concentration to suppress aromatase activity as compared to the IgG.

Antibodies, Monoclonal

Single-puncture laparoscopic-assisted gastrostomy.

This is a description of an original method of performing gastrostomy using an operating laparoscope through a single puncture under direct vision. It is accessible to any surgeon with basic laparoscopic skills who has a basic laparoscopic instrument set and an operating laparoscope. No other special equipment or disposables are required.

Enteral Nutrition

Erythromycin treatment for gastrointestinal dysmotility in preterm infants.

OBJECTIVE: To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants. METHODOLOGY: A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre. RESULTS: All responded favourably without adverse effects and tolerated full enteral feeding within 1-2 weeks of the commencement of the drug. CONCLUSIONS: As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.

Erythromycin

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants.

OBJECTIVES: A prospective study comparing the efficacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (< 1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus. METHODOLOGY: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (+/-1 week) and birthweight (+/-100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group. RESULTS: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment (P > 0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups (P < 0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group. CONCLUSIONS: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.

Administration, Oral

Central diabetes insipidus in a newborn with deletion of chromosome 7q.

We report an infant with midline craniofacial defects and holoprosencephaly due to chromosome 46, XY, del (7) (pter-->q34) who presented at 1 week of age with central diabetes insipidus. The importance of hypothalamic-pituitary endocrine investigation in patients with this syndrome, and more generally, in patients with midline craniofacial malformation or holoprosencephaly is emphasized. As infants with chromosome 7q deletion bear close phenotypic resemblance to infants of Trisomy 13, chromosomal confirmation and karyotype banding is mandatory to establish an accurate diagnosis and for genetic counselling of their parents.

Abnormalities, Multiple

Vascular air embolism: a rare complication of nasal CPAP.

A preterm infant developed bilateral tension pneumothoraces and extensive vascular air embolism 6 h after being commenced on nasal continuous positive airway pressure (CPAP). Neonatal clinicians should be aware that catastrophic vascular air embolism could occur in infants receiving nasal CPAP, a modality of respiratory support conventionally considered non-invasive and 'safe'.

Embolism, Air

Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants.

AIM: To compare the efficacy of a colloid (5% albumin) and a crystalloid (isotonic saline) solution for treating hypotension in mechanically ventilated preterm infants. METHODS: Sixty three preterm infants weighing 540 to 1950 g at birth and with gestational ages of 23 to 34 weeks, who developed hypotension (mean arterial pressure < 25, 30, and 35 mm Hg for infants with birthweight < 1, 1-1.49, and 1.5-1.99 kg, respectively) within the first 2 hours of life, were randomly allocated to receive intravenous infusions at 10 ml/kg of either 5% albumin (group 1, n = 32) or isotonic (0.9%) saline (group 2, n = 31). Inotropic support with dopamine infusion was given if the infants remained hypotensive after a total of three infusions (30 ml/kg). Subsequent extra doses of volume expander in the form of 5% albumin was given, depending on the infant's blood pressure. RESULTS: There was no difference in the volume of the test solutions required between the two groups. Outcome, as assessed by the number of infants requiring inotropic support and death or chronic lung disease, did not differ between the groups. After inotropic support, however, group 1 required significantly more volume expander to maintain normal blood pressure (median: 27.5 ml/kg vs 10 ml/kg; P = 0.0187) and had a higher mean (SEM) percentage weight gain within the first 48 hours of life (at 24 hours: 6.3(1.3)% vs 3.3(0.8)%; P = 0.049; at 48 hours: 5.9(1.9)% vs 0.9(1.7)%; P = 0.045). The difference in weight gain was significant at 48 hours even when only those infants not requiring inotropic support or extra 5% albumin were compared (group 1: 1.5(1.5)%, group 2: -4.2(1.1)%; P = 0.027). CONCLUSIONS: Isotonic saline is as effective as 5% albumin for treating hypotension in preterm infants, and it has the additional advantage of causing less fluid retention in the first 48 hours.

Albumins