Search PubMed⌕ Search

Biomedical subjects

T F Fok

Publications and source records attributed to T F Fok.

At least 163 records · Page 9Linked to original sources

Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants.

AIMS: To evaluate the commonly used markers--namely IL-6, TNF alpha, IL-1 beta, C-reactive protein and E-selection for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment. METHODS: Very low birthweight infants in whom clinical sepsis was suspected when they were > 72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined. RESULTS: One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNF alpha 17 pg/ml, IL-1 beta 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNF alpha on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection. CONCLUSIONS: Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNF alpha should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.

Biomarkers↗

Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits.

The deposition efficiency of three methods of aerosol delivery of salbutamol into lungs of ventilated rabbits was compared: 1) metered dose inhaler (MDI) with holding chamber (HC), 2) jet nebulizer (JN), and 3) ultrasonic (US) nebulizer. The latter system was tested using two different sized medication reservoirs, a large (20 mL) cup (US20) and a small (10 mL) cup (US10). After delivery of technetium-99m-labeled salbutamol aerosol, deposition in the lungs, trachea, and ventilator circuit were estimated by a gamma counter. Total pulmonary deposition [mean(SEM)] as a percentage of the prescribed drug was: MDI + HC 0.22(0.05)%; JN 0.48(0.05)%; US20 0.90(0.13)%; US10 3.05(0.49)%. Only the deposition from the US10 was statistically significantly higher than the other modes (p < 0.05). Dynamic scintigraphy showed that, among the nebulizers, the US10 continued to deliver medication for longer than either the JN or the US20. We conclude that the US10 appears to be more efficient in delivering aerosol to the lung in this rabbit model and merits further evaluation for clinical efficiency.

Administration, Inhalation↗

Pituitary-adrenal response in preterm very low birth weight infants after treatment with antenatal corticosteroids.

Antenatal corticosteroids have been widely used for the prevention of respiratory distress syndrome in preterm neonates, yet little is known about their effects on the hypothalamic-pituitary-adrenal axis in these infants. We prospectively evaluated pituitary-adrenal function in 61 preterm (< 32 gestational weeks), very low birth weight (< 1500 g) infants on days 7 and 14 of life using the human CRH stimulation test. The baseline and poststimulation plasma ACTH and serum cortisol concentrations did not differ significantly between infants whose mothers received no antenatal corticosteroids, and those whose mothers received 1-2 doses or > 2 doses (mean 7.2 doses) of prenatal dexamethasone (P = > 0.12). The number of doses of dexamethasone and the time intervals between the last dose of drug and delivery did not significantly affect the pituitary-adrenal responsiveness on days 7 and 14 of life. Among infants who did not require mechanical ventilation at the time of the human CRH test, significantly higher plasma ACTH (P < 0.014) and lower serum cortisol concentrations (P < 0.02) were found on day 14 than on day 7. In contrast, none of the poststimulation hormone concentrations were significantly different in ventilated infants between days 7 and 14. The relationship between the blood hormone concentrations in each time epoch (day 7 and day 14) and possible confounding factors including gestational and postconceptional age, birth weight, sex, Apgar scores, mode of delivery, single or higher order births, and mode of ventilation were determined. Plasma ACTH concentrations on day 7 were found to be significantly higher in ventilated than in nonventilated infants (P = 0.006). However, none of the aforementioned factors correlated significantly with plasma ACTH concentrations on day 14. Serum cortisol concentrations on day 7 were significantly higher in infants of greater gestational age (P = 0.039) and birth weight (P = 0.013), with lower Apgar scores at 1 and 5 min (P = 0.021 and P = 0.049, respectively), and in those delivered vaginally (P = 0.047). Similarly, serum cortisol concentrations on day 14 were found to be significantly higher in infants with lower Apgar scores at 1 and 5 min (P = 0.011 and P = 0.014, respectively) and in infants requiring mechanical ventilation (P = 0.014). Our results suggest that single or multiple courses of antenatal dexamethasone have no long-lasting suppressive effects on pituitary-adrenal function in preterm, very low birth weight infants. Maturation of pituitary function appears to be more advanced than adrenal function. The organ's ability to respond appropriately to various stressful stimuli indicates that the pituitary-adrenal axis is highly responsive at these early gestational ages.

Adrenal Cortex Hormones↗

The pituitary-adrenal responses to exogenous human corticotropin-releasing hormone in preterm, very low birth weight infants.

To evaluate the pituitary-adrenal reserve and to standardize the methodology of performing the human CRH (hCRH) stimulation test, we performed the hCRH test on 14 preterm (< 32 gestational weeks), very low birth weight infants, who did not receive antenatal or postnatal corticosteroid treatment, on days 7 and 14 of life. Blood samples were obtained 0 (baseline), 15, 30, and 60 min after an iv dose of hCRH (1 microgram/kg). The plasma ACTH concentration rose from a basal value of 5.7 +/- 0.6 pmol/L (mean +/- SEM) to 11.9 +/- 2.1 pmol/L (P < 0.005), 9.2 +/- 1.2 pmol/L (P < 0.005), and 7.7 +/- 0.8 pmol/L (P < 0.005) at 15, 30, and 60 min, respectively. The corresponding rises in serum cortisol from a basal concentration of 396 +/- 67 nmol/L were 509 +/- 71 nmol/L (P < 0.0001), 647 +/- 62 nmol/L (P < 0.0001), and 578 +/- 60 nmol/L (P < 0.0001). The plasma ACTH concentration consistently peaked early at 15 min, whereas the maximum cortisol response occurred 30 min post-hCRH stimulation. No significant differences were detected between the hCRH tests performed on days 7 and 14 (P > 0.15). Mechanical ventilation, infant gender, and mode of delivery did not significantly influence the hormonal responses (P > 0.25). We have defined in this study the pattern, the magnitude of the pituitary-adrenal response, and the timing of the peak concentrations of plasma ACTH and serum cortisol in relation to a standard iv dose of hCRH. The hCRH test in very low birth weight infants appears to be safe and reproducible, and produces a pituitary-adrenal response comparable to that seen in older children and adults, indicating that pituitary-adrenal function is mature at these early stages of gestation.

Adrenocorticotropic Hormone↗

Pituitary-adrenal suppression and recovery in preterm very low birth weight infants after dexamethasone treatment for bronchopulmonary dysplasia.

High dose dexamethasone is frequently used for the treatment of neonatal respiratory conditions and to facilitate weaning from mechanical ventilation in preterm, very low birth weight infants. However, very little is known about the severity, site, and duration of steroid-induced hypothalamic-pituitary-adrenal axis suppression in this category of patients. Twenty-three preterm, very low birth weight infants who received a full 3-week dose-tapering course of dexamethasone were prospectively studied, with a human CRH stimulation test performed at three different times: before the start of steroid treatment (week 0), immediately after the course (week 3), and 4 weeks after stopping dexamethasone (week 7). Plasma ACTH and serum cortisol concentrations were measured at 0 (baseline), 15, 30, and 60 min. Immediately after the steroid course (week 3), both basal and poststimulation plasma ACTH and serum cortisol concentrations were markedly suppressed. The hormone concentrations at 0, 15, 30, and 60 min in week 3 were significantly lower than their corresponding levels in week 0 (P < 0.0001 for both ACTH and cortisol) and week 7 (P < 0.0001 and P < 0.005 for ACTH and cortisol, respectively). In contrast, when the hormone levels in week 7 were compared to their corresponding concentrations in week 0, only the 60 min serum cortisol concentration in week 7 was significantly lower (P = 0.02). The currently used dosage of dexamethasone caused severe pituitary-adrenal suppression immediately after treatment, but substantial recovery of the endocrine axis was observed 4 weeks after discontinuation of therapy. Although the recovery appeared to be earlier with the pituitary center, both pituitary and adrenal glands were capable of mounting a biochemically adequate response to exogenous human CRH stimulation at this stage. Steroid replacement therapy may be desirable at a time of stress in the immediate posttreatment period, but it would seem unnecessary 1 month after stopping dexamethasone treatment.

Adrenal Gland Diseases↗

Lower gastrointestinal tract perforation in preterm infants treated with dexamethasone for bronchopulmonary dysplasia.

Two cases of ileal perforation in preterm infants treated with high-dose dexamethasone for bronchopulmonary dysplasia are described. Corticosteroid-induced gastroduodenal haemorrhage or perforation has been well documented, but less known to most clinicians is that the lower gastrointestinal tract can also be involved. Unlike previous reported cases in which affected infants deteriorated rapidly and became moribund within hours of onset of symptoms, "silent" perforations detected on routine radiograph or escaping clinical recognition until at an advanced stage can be the initial presentation. The need for greater vigilance and a low threshold for abdominal investigations are emphasised in preterm infants treated with dexamethasone.

Anti-Inflammatory Agents↗

Cloverleaf skull--when should one operate?

Cloverleaf skull or kleeblattschadel usually occurs as a result of premature closure of the cranial sutures, with accompanying hydrocephalus, proptosis, cranial base and midface hypoplasia. The incidence of this abnormality is rare, with less than 130 reported cases in the literature, and is associated with various congenital syndromes. Conventional surgical management advocates shunting prior to definitive craniotomy and bone remodeling. We report an unusual case of Pfeiffer syndrome with associated cloverleaf skull deformity, in which early surgery was vital for decompression of raised intracranial pressure and shunt independence for the first six months. A secondary craniofacial procedure was performed at nine months of age to improve cosmesis. In such cases, good outcome can be achieved if aggressive surgery is combined with good paediatric anaesthesia and intensive care.

Acrocephalosyndactylia↗

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Aerosols↗

Varicella exposure in a neonatal intensive care unit: emergency management and control measures.

We describe an exposure of varicella zoster virus in our neonatal intensive-care unit and the emergency procedures instituted to prevent an outbreak. Fifty-seven infants and 129 staff members were exposed but none developed chickenpox. The measures included rapid identification of varicella antibody status in all neonates and those staff members with uncertain history of varicella infection; cohorting of exposed infants according to immune status; and prompt administration of varicella zoster immunoglobulin to susceptible patients. The recommendation of the American Academy of Pediatrics did not accurately predict the immune status of preterm infants, as only one of the eight susceptible infants would have qualified for immunoglobulin prophylaxis if their guidelines had been followed. Mass screening of all exposed infants using the varicella zoster enzyme linked immunosorbent assay (ELISA) test was the only reliable means of determining the immune status. Of the four risk factors evaluated for the prediction of antibody status: gestational age, postnatal age, birthweight and episodes of blood transfusion, only postnatal age was found to independently predict the immune status of our patients. Because varicella zoster susceptible staff members are difficult to identify on the basis of history, we suggest that prospective screening of staff in high-risk units be undertaken and vaccination with live varicella vaccine be offered to susceptibles.

Antibodies, Viral↗

Neonatology in the 'Pearl of the East'.

Clinicians practising in different regions of the world are often impressed at marked differences in disease patterns witnessed. The bases of most obvious differences are usually socio-economic and genetic, but culture and environment can be equally important. Documenting and assessing such differences is more than just a passing interest. Globalization has resulted in significant movement of people from one area to another. During the past decade, many young Chinese families have emigrated to Australia, Europe and North America for social and political reasons. Clinicians in these regions will need to be aware of the "Chinese disease patterns'. This overview highlights some of the more striking differences seen in neonatal medicine between the East (Hong Kong) and the West (Australia/Europe/North America). In addition to the immediate clinical relevance, it is hoped that this review can provide a background from which fruitful research ideas may emerge and to stimulate interest for trainee neonatologists who wish to seek sabbatical experience in Hong Kong.

China↗

Isolated congenital tricuspid valve dysplasia: a rare condition mimicking persistent pulmonary hypertension of the newborn.

Isolated congenital tricuspid valve dysplasia is a rare and potentially lethal congenital heart disease that can be easily confused with persistent pulmonary hypertension of the newborn. We describe a neonate with isolated congenital tricuspid valve dysplasia who did not respond to mechanical ventilation but improved by tolazoline. Clinicians should be aware that the initial fulminant course of this condition may be reversed by reducing the pulmonary vascular resistance, thereby allowing time for spontaneous recovery.

Diagnosis, Differential↗

Hepatic haemangioendothelioma presenting with early heart failure in a newborn: treatment with hepatic artery embolization and interferon.

We report our management of a newborn presenting in utero with congestive heart failure secondary to a giant hepatic haemangioendothelioma. Control of heart failure was achieved by transcatheter hepatic artery embolization, and rapid regression of the tumor was observed after a course of alpha 1 interferon. The combination of hepatic artery embolization and interferon may be a useful approach in the management of this rare, potentially fatal condition.

Antineoplastic Agents↗

Fatal haemorrhagic gastritis associated with oral sulindac treatment for patent ductus arteriosus.

We report the first case in a preterm infant given oral sulindac for treatment of symptomatic patent ductus arteriosus who subsequently developed severe acute haemorrhagic gastritis leading to disseminated intravascular coagulation, massive pulmonary haemorrhage and death. The postmortem examination suggested that the mechanism was likely a direct irritant insult causing ischaemia on the gastric mucosa. Although sulindac is supposed to be a renal-sparing non-steroidal anti-inflammatory prodrug associated with minimal renal and gastrointestinal adverse effects, clinicians should be alerted to this potential life-threatening complication in preterm infants. Until the question of safety could be adequately addressed, the use of sulindac for ductal closure should remain experimental.

Cyclooxygenase Inhibitors↗

Use of eyepatches in phototherapy: effects on conjunctival bacterial pathogens and conjunctivitis.

We conducted a randomized controlled trial to determine the effects of eye occlusion on the risk of eye infection in full term newborn infants receiving phototherapy. Among 102 infants whose eyes were occluded with eyepatches, pathogens were isolated from 50 eyes of 33 infants. The positive isolation rate was significantly higher than that of a group of control infants (n = 101) whose eyes were protected by a headbox made of light-proof plastics. Among the latter group pathogens were detected in 22 eyes of 14 infants. In addition significantly more infants in the eyepatches group had purulent eye discharge (23 of 102 vs. 9 of 101, P = 0.013) and clinical conjunctivitis (13 of 102 vs. 2 of 101, P = 0.004) than the controls. Proper eye care is imperative when eyepatches are used on infants receiving phototherapy, and alternative methods of eye protection should be considered.

Bacteria↗

Isolated congenital tuberculosis otitis in a preterm infant.

We report an unusual case of localized congenital tuberculosis otitis in a preterm infant. Unlike disseminated congenital cases, the manifestations of localized otitis are associated with a triad of signs: (i) regional lymphadenopathy in the absence of typical systemic features of tuberculosis; (ii) delayed onset of presentation; and (iii) refractory otitis unresponsive to conventional antimicrobial agents. The need for greater diligence in looking for neonatal tuberculosis is emphasized, especially in an ethnic or socioeconomic environment where the disease is prevalent.

Antibiotics, Antitubercular↗

Chest position and pulmonary deposition of surfactant in surfactant depleted rabbits.

AIMS: To investigate the correlation between chest position and the distribution of surfactant in the lungs of surfactant depleted rabbits, to corroborate current guidelines on the intratracheal instillation of exogenous surfactant in newborns. METHODS: Twelve tracheotomised rabbits, depleted of pulmonary surfactant by saline bronchoalveolar lavage, were given intratracheal 99m Technetium labelled Exosurf in three positions (prone, right side down, and left side down) (n = 4 in each group). They were monitored for 10 minutes using dynamic gamma scintigraphy monitoring. Instillation completed, the lateral lying animals were turned to the opposite side to determine whether redistribution of the surfactant had taken place. The amount of radiolabelled surfactant deposited at the peripheral, central, dorsal and ventral parts of the lungs was then estimated by gamma counting of the lung sections at necropsy. RESULTS: Both gamma scintigraphy and gamma counting showed similar rates and total amount of surfactant accumulation in both lungs of the prone animals. In the lateral lying animals surfactant accumulated at a significantly faster rate in the dependent lungs: the amount of surfactant deposition was three to 14-fold that in the raised lungs (p = 0.017; nested ANOVA). Changing the chest position immediately after instillation did not redistribute the surfactant. In all three groups of animals there was no significant difference in deposition between the peripheral, central, ventral and dorsal parts of the lungs. CONCLUSIONS: Pulmonary distribution of intratracheally instilled surfactant is largely determined by gravity, and changing the chest position after instillation does not result in any redistribution of the surfactant. During the instillation of exogenous surfactant to newborn infants, keeping the chest in the horizontal position may therefore result in the most even distribution of the surfactant in the two lungs. Further deposition studies are required to evaluate the validity of the current recommendations on surfactant administration.

Animals↗