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Biomedical subjects

T F Fok

Publications and source records attributed to T F Fok.

At least 145 records · Page 8Linked to original sources

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↗

Hyperoxia-induced lung injury in premature rat: description of a suitable model for the study of lung diseases in newborns.

OBJECTIVE: To provide suitable animal model (hyperoxia-induced premature rat lung damage) for research of bronchopulmonary dysplasia (BPD) and to better understand pathogenesis of BPD and look for effective drugs to prevent and treat BPD. METHODS: Rat litters delivered prematurely at 21-day gestation by hysterotomy. Vigorous resuscitation at birth resulted in a high survival rate. Surfactant and antioxidant enzyme (AOE) system were measured. The model was tested in an experiment of hyperoxia-induced lung injury. RESULTS: Compared to litters delivered spontaneously at term (gestation 22 days), these preterm rats had immature pulmonary surfactant composition with low total phospholipid (x +/- s: 10.09 +/- 1.49 micrograms/mg wet weight vs 12.04 +/- 1.31 micrograms/mg wet weight; P = 0.0367) and phostidylcholine (5.06 +/- 1.82 micrograms/mg wet weight vs 8.28 +/- 2.35 micrograms/mg wet weight; P = 0.0238) levels. The concentrations of AOE enzymes, superoxide dismutase (11.40 +/- 2.04 mu/mg DNA vs 15.78 +/- 1.84 mu/mg DNA; P < 0.01) and catalase (92.81 +/- 62.25 mu/mg DNA vs 412.24 +/- 117.50 mu/mg DNA; P < 0.01) were also significantly lower. Animals exposed to hyperoxia had a significantly higher mortality. Pulmonary edema and histological features of lung damage were observed in the pups exposed to hyperoxia. CONCLUSIONS: The premature rat model is relatively cheap, readily available and has a high survival rate. Pulmonary surfactant and AOE systems are immature. These properties make them a suitable model for the study of acute and chronic lung damage related to prematurity and O2 toxicity.

Animals↗

Biochemical investigation of young hospitalized Chinese children: results over a 7-year period.

During the seven years from January 1989 to December 1995, we investigated 2,269 Chinese infants and young children for metabolic disorders in Hong Kong. These young patients, all aged under 4 years and originated from southern China, were ill with no apparent cause and had clinical manifestations suggestive of inherited metabolic diseases. A spot urine and a plasma sample were obtained from each patient for biochemical analysis, including urinary organic acid identification and plasma amino acid analysis. Six cases of mucopolysaccharidosis, four multiple carboxylase deficiency, three 2-methylacetoacetyl CoA thiolase deficiency, two methymalonic aciduria, one glutaric aciduria type I, one glutaric aciduria type II, one a-oxoglutaric aciduria, and one case of orotic aciduria were detected. There were also single suspected cases of medium-chain acyl-CoA dehydrogenase deficiency and isovaleric aciduria. No primary amino acid disorder, such as phenylketouria and maple syrup urine disease, has been detected. Our results suggest that a different pattern of inherited metabolic diseases exists in the southern Chinese when compared with the Chinese in other regions of China.

Child, Preschool↗

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↗

Eye protection for newborns under phototherapy: comparison between a modified headbox and the conventional eyepatches.

In a randomized trial comparing a modified oxygen headbox with conventional eye patches for protecting the eyes of newborn infants undergoing phototherapy, the use of the headbox did not interfere with phototherapy treatment and was preferred by the nursing staff, as shown by an opinion survey. This, plus our previously reported finding that the headbox was associated with less eye infection, less periorbital skin irritation and less accidental exposure of the eyes due to displacement of the protective devices, suggests that the headbox provides a convenient and inexpensive alternative method of eye protection. The device may be particularly useful in busy and under-staffed neonatal units where vigilant eye care of infants undergoing phototherapy may be difficult.

Attitude of Health Personnel↗

Delivery of metered dose inhaler aerosols to paralyzed and nonparalyzed rabbits.

OBJECTIVE: To assess whether paralysis alters pulmonary deposition of albuterol delivered by metered dose inhaler and spacer to small animals. DESIGN: A parallel group study of intubated and ventilated rabbits. INTERVENTIONS: Animals in group 1 (n = 7) were paralyzed with intravenous pancuronium, and ventilated at a rate of 30 breaths/ min. The animals in group 2 (n = 6) were ventilated at a rate of 10 breaths/min under light anesthesia without paralysis. In this latter group, spontaneous respiration continued at a rate of 40 to 50 breaths/min. Both groups were maintained at PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and other ventilatory settings were identical. MEASUREMENTS AND MAIN RESULTS: Technetium-99m labeled albuterol aerosol was delivered by metered dose inhaler via a spacer device to both groups. Pulmonary deposition of the aerosol, determined by measuring the radioactivity in the lung tissues at autopsy, was expressed as percent of the total radioactivity dispensed by the metered dose inhaler. Group 2 showed significantly greater lung deposition than group 1 (0.510 +/- 0.076 [SEM]% vs. 0.226 +/- 0.054%, p = .0094). Deposition in the airway, the endotracheal tube, and the ventilator circuit did not differ significantly. CONCLUSION: Metered dose inhaler delivery of aerosolized medications to ventilated rabbits is significantly enhanced if respiration is not controlled. This observation might have implications for the delivery of therapeutic aerosols to newborns and young infants receiving slow, intermittent, mandatory ventilation.

Aerosols↗

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↗

High frequency oscillatory ventilation in infants with increased intra-abdominal pressure.

AIMS: To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated. METHODS: Eight infants (25 to 38 gestational weeks, birthweight 600-3200 g, postnatal age 1 to 190 days) with a variety of intra-abdominal pathologies, resulting in severe abdominal distension and failure of conventional ventilation, were studied. RESULTS: The oxygenation status of all infants significantly improved within an hour of changing from conventional to high frequency oscillatory ventilation. Infants who were hypercapneic on conventional ventilation also showed a reduction in PaCO2. As a group, the mean (SD) PaO2/FIO2 improved from 4.99 (0.98) kpa to 11.55 (3.8) kpa (P = 0.002), and the PaCO2 from 6.48 (2.12) kpa to 4.89 (1.22) kpa (P = 0.028). These improvements were sustained throughout the next 48 hours. CONCLUSION: High frequency oscillatory ventilation seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure.

Abdomen↗

Randomised controlled trial: comparison of colloid or crystalloid for partial exchange transfusion for treatment of neonatal polycythaemia.

AIM: To compare the efficacy of using isotonic saline (crystalloid) or 5% albumin (colloid) as replacement fluid in partial exchange transfusion (PET) for the treatment of neonatal polycythaemia. METHODS: One hundred and two polycythaemic full term infants were randomly allocated to receive PET with either isotonic saline or 5% albumin. The criteria for PET were: (a) venous haematocrit > or = 0.7; or (b) venous haematocrit 0.65-0.69 with symptoms or signs attributable to polycythaemia. RESULTS: PET with either saline (n = 53) or 5% albumin (n = 50) resulted in a significant and sustained decline in haematocrit up to 24 hours after PET. Although the immediate haemodilution effect of isotonic saline was statistically smaller than that of 5% albumin (decline in haematocrit 19.3% vs 22.8% of pre-PET value), the difference was too small to be of any clinical significance, and the haematocrit at 4 or 24 hours after PET did not differ significantly between the two groups. PET with either replacement fluid was not associated with any complication. The serum sodium and potassium concentrations were not significantly affected by the PET in either group. CONCLUSIONS: Both isotonic saline and 5% albumin are effective when used as replacement fluid in PET for the treatment of neonatal polycythaemia. Isotonic saline, which is cheaper and free of infection, should be the replacement fluid of choice.

Albumins↗