Performance of a new oxygen delivery device for potentially infectious critically ill patients.

In patients with highly contagious diseases that are spread by respiratory droplets or air-borne particles, the use of high-flow oxygen may carry a significant risk of nosocomial transmission. We tested a new oxygen delivery device designed to address these problems by simulating 108 patients with sepsis and respiratory failure. The device being tested consisted of an airtight mask, a bacterial and viral filter, a T-shaped reservoir (50 and 100 ml) and oxygen delivery tubing connected directly to the mask. When tested with a 50-ml reservoir, a high fractional oxygen concentration was achieved: mean (SD) 0.83 (0.11) at a flow of 15 l.min(-1) oxygen. The 50-ml reservoir, when compared with the 100-ml reservoir, was associated with reduced carbon dioxide rebreathing (mean (SD) inspired fractional carbon dioxide concentration 2.5 (1.0) vs 3.0 (1.1), respectively, p = 0.009) and reduced inspiratory resistive work of breathing (mean (SD) 1.0 (0.6) J.l(-1) vs 1.2 (0.5) J.l(-1), respectively, p = 0.028). However, rebreathing and work of breathing were relatively high if a high respiratory rate was simulated. We conclude that the novel oxygen device we describe, equipped with the 50-ml T-shaped reservoir, is suitable for potentially infectious patients with type-1 respiratory failure but without marked tachypnoea.

A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to regulate accumulation of Fra-1 in tumour cells.

Fos-related antigen-1 (Fra-1) is a member of the Activator Protein-1 (AP-1) transcription factor superfamily that is overexpressed in a variety of cancers, including colon, breast, lung, bladder and brain. High Fra-1 levels are associated with enhanced cell proliferation, survival, migration and invasion. Despite its frequent overexpression, the molecular mechanisms that regulate the accumulation of Fra-1 proteins in tumour cells are not well understood. Here, we show that turnover of Fra-1, which does not require ubiquitylation, is cooperatively regulated by two distinct mechanisms-association with the 19S proteasomal subunit, TBP-1, and by a C-terminal degron, which acts independently of TBP-1, but is regulated by RAS-ERK (extracellular signal-regulated kinase) signalling. TBP-1 depletion stabilized Fra-1 and further increased its levels in tumour cells expressing RAS-ERK pathway oncogenes. These effects correlated with increased AP-1 transcriptional activity. We suggest that during Fra-1 degradation, association with TBP-1 provides a mechanism for ubiquitin-independent proteasomal recognition, while the C terminus of the protein regulates its subsequent proteolytic processing.

Newborn screening in Singapore.

Neonatal screening in Singapore for G6PD deficiency started in 1965. Screening for congenital hypothyroidism started in 1981 as a pilot research program and by 1990, it became nationwide. Screening for congenital hypothyroidism is by the measurement of TSH in the cord serum with recall of those exceeding the 99th percentile, by about 3-4 days of life. Treatment is usually started within a week of life. Over 400,000 newborns have been screened and the screening rate has been about 99.95%. The incidence rate is about 1 in 3,000. G6PD activity in the cord blood is measured using semi-quantitative rapid screening tests. Those identified are physically protected from environmental triggers by keeping them in hospital for a variable period of time. Parents are counseled. Data obtained from 22,830 newborns from the National University Hospital revealed incidence rates of 1.62% in all newborns, 3.15% in males and 0.11% in females. The Chinese and Malay males had a higher (3.94% and 2.95%) incidence respectively when compared to the Indian males with (0.66% incidence). The application of the preventive measures has resulted in no report of kernicterus in the last 20 years. Our efforts are now focused on minimizing the recall rate in the case of hypothyroidism screening, reducing the period of stay in hospital in those with G6PD deficiency and considering the introduction of a PKU screening program in Singapore.

Mass newborn screening for glucose-6-phosphate dehydrogenase deficiency in Singapore.

Recognition of kernicterus as a significant contributor to newborn mortality and morbidity in G6PD deficient babies and the ease with which G6PD deficiency could be detected and kernicterus prevented by avoidance of triggers, led to the establishment of mass newborn screening for G6PD deficiency in 1965. G6PD deficient newborns are identified within a day of birth by measuring the enzyme activity in cord blood. They are then physically protected from triggers by keeping them in the hospital for the first 2 weeks of life after their parents are counseled. Enzyme activity is measured using Wong's in-house modification of the Bernstein's technique or the BM G6PD Deficiency Screening test based on the Beutler assay. Close to 1.6 million newborns, representing practically 100% of all births have been screened. Analysis of data from 22,830 newborns at the National University Hospital reveals an incidence of 1.62% in all newborns. 3.15% in males and and 0.11% in females. A distinct racial variation in the incidence of deficiency was observed in males: Chinese 3.94%, Malays 2.95% and Indians 0.66%. Intermediate deficiency was most frequently identified (1.83%) in Chinese females. With the preventive measures. the incidence of kernicterus has dropped dramatically and there has been, over the last 20 years, no reported cases of kernicterus in newborns with G6PD deficiency. We are now looking at issues like comparing different assay techniques and determining a shorter period of stay in hospital. We believe that all Asians, especially Chinese babies, should be screened for G6PD deficiency, irrespective of which country the child is born.

Value of abdominal sonography in the assessment of children with abdominal pain.

PURPOSE: We retrospectively evaluated the usefulness of sonography in the diagnostic assessment of children with abdominal pain. METHODS: From July 1988 to October 1996, 676 children who had abdominal pain and were referred for sonography underwent abdominal and pelvic sonographic examination. Of these, 644 children had recurrent abdominal pain (RAP) and 32 children had acute or subacute abdominal pain (ASAP). The mean ages and relative risks of underlying abnormalities were calculated for children with RAP and ASAP. RESULTS: Abdominal abnormalities were sonographically detected in 10 children with RAP (2%), a significantly lower incidence than in children with ASAP (56%, p < 0.0001), with a relative risk of 0.028 (95% CI, 0.014-0.055). In the RAP group, an underlying abnormality was more likely (p < 0.001) to be sonographically detected in children who had atypical clinical features (5 of 46%; 11%) than in those with typical clinical features (5 of 598; 1%), with a relative risk of 12.94 (95% CI, 3.90-43.30). Children with RAP were found to have hydronephrosis (3), urinary cystitis (2), duplex kidney (1), hypoplastic low-lying kidney (1), choledochal cyst (1), ovarian teratoma (1), and gross gaseous distention with fecal masses (1). Children with ASAP had urinary cystitis (4), intussusception (2), appendicitis (2), appendiceal abscess (1), perforated gut with ascites (1), gut duplication (1), thickened gut wall with fluid from severe gastroenteritis (1), gross gaseous distention with fecal masses (1), hepatosplenomegaly (1), cholecystitis (1), gross hydronephrosis (1), Wilms' tumor (1), and abdominal neuroblastoma (1). CONCLUSIONS: Abdominal sonography is useful in children with ASAP. Although an underlying abnormality was rarely found in children with RAP, children who have RAP with atypical clinical features should have sonographic screening. If no abnormalities are found, the normal sonograms may be reassuring to parents.

Risk factors for birth defects in Singapore: a case control study.

To explore possible risk factors for birth defects, a matched case-control study was carried out at Kandang Kerbau Hospital in Singapore from January 1986 to December 1988. Cases and controls were selected from livebirths born in that hospital during that period. Cases were babies who were clinically detected as having defects at birth and the diagnosis reconfirmed at 6 weeks post partum. Each case was matched to a control by maternal age, ethnic background of mother, the same class of maternity ward and time of delivery. Five hundred and seventy-two matched pairs were accrued for the study. The parents of both cases and controls were interviewed at 6 weeks post partum. Information on the medical and birth history of both mother and baby was obtained from medical records. Using conditional logistic regression analysis to adjust for potential confounders, the strongest risk factors for birth defects were family history of birth defects (OR 3.3; 95% CI 1.8-6.4) and parents having a previous abnormal baby (OR 2.4; 95% CI 1.1-5.3). Other notable risk factors included drug history during pregnancy (OR 1.2; 95% CI 0.8-2.0), the ingestion of traditional medicine during pregnancy (OR 1.4; 95% CI 1.0-2.0), injuries or accidents during pregnancy (OR 2.2; 95% CI 1.5-3.2) and maternal diabetes mellitus (OR 1.3, 95% CI 0.3-7.1). Mothers in professional occupations (OR 1.4, 95% CI 0.7-2.6) and those in production occupation (OR 1.2, 95% CI 0.9-1.7) had an increased risk for birth defects compared to housewives.(ABSTRACT TRUNCATED AT 250 WORDS)

Descriptive profile of birth defects among livebirths in Singapore.

A case-control study of birth defects was carried out in Kandang Kerbau Hospital in Singapore for a three-year period from January 1986 until December 1988. This paper presents the descriptive profile of birth defects among livebirths seen in that hospital. Out of 44,842 livebirths, 678 babies were found to have birth defects, giving a prevalence of 15.13 per 1000 livebirths (95% CI 14.0-16.2). The musculoskeletal system was the most frequently affected system accounting for 161 cases with a prevalence of 3.59 per 1,000 livebirths (95% CI 3.06-4.19), followed by 111 cases with defects of the gastrointestinal system (2.47 per 1,000 livebirths 95% CI 2.04-2.98), 88 cases of chromosomal disorders (prevalence of 1.96 per 1,000 livebirths 95% CI 1.57-2.42), 78 cases with defects of the cardiovascular system (1.74 per 1,000 livebirths 95% CI 1.38-2.17), 73 cases with defects of the urogenital system (1.63 per 1,000 livebirths 95% CI 1.28-2.05), and 52 cases with defects of the central nervous system (1.16 per 1,000 livebirths 95% CI 0.87-1.52). The prevalence of cleft lip, cleft palate in isolation, and cleft lip and palate combined was 1.72 per 1,000 livebirths and the occurrence of Down's syndrome was 1 in 700 livebirths. When reviewed 6 weeks postpartum, the rate of false positives at birth was 4%. In a control group of 709 "normal" cases at birth, the rate of cases not detected at birth but detected at 6 week follow-up, false negatives was 0.84%.

PIP: A case-control study of birth defects was carried out in Kerdang Kerbau Hospital in Singapore over a 3-year period from January 1986 to December 1988. This paper presents the descriptive profile of birth defects among live births seen in that hospital. Of 44,842 live births, 678 babies were found to have birth defects, which gives a prevalence of 15.13/1000 live births (95% CI 14.0-16.2). The musculoskeletal system was the most frequently affected system, accounting for 161 cases with a prevalence of 3.59/1000 live births (95% CI 3.06-4.19), followed by 111 cases with gastrointestinal system defects (2.47/1000 live births, 95% CI 2.04-2.98), 88 cases of chromosomal disorders 1.96/1000 live births, 96% CI 1.57-2.42), 78 cases with cardiovascular system defects (1.74/1000 live births, 95% CI 1.38-2.17), 73 cases with urogenital system defects (1.63/1000 live births, 95% CI 1.28-2.05), and 52 cases with central nervous system defects (1.16/1000 live births, 95% CI 0.87-1.52). The prevalence of cleft lip, cleft palate in isolation, and cleft lip an palate combined was 1.72/1000 live births and the occurrence of Down's syndrome was 1 in 700 live births. When reviewed 6 weeks postpartum, the rate of false positives at birth was 4%. Among a control group of 709 normal cases at birth, the rate of cases not detected at birth but at the 6-week followup showed a rate of 0.84% false negatives.

Phototherapy and the brain-stem auditory evoked response in neonatal hyperbilirubinemia.

The latencies of peak V and interpeaks I-V and III-V in the brain-stem auditory evoked response of infants with hyperbilirubinemia before phototherapy were significantly greater than those in a control group of infants. These values of the brain stem auditory-evoked response improved significantly during phototherapy and correlated significantly with the declining bilirubin levels. Improvement continued after phototherapy, despite a rebound of serum bilirubin concentrations.

Bronchopulmonary dysplasia in very low birthweight infants.

The incidence, clinical presentation and severity of bronchopulmonary dysplasia (BPD) in 110 consecutive very low birthweight (VLBW) infants admitted to the National University Hospital Neonatal Intensive Care Unit between October 1985 and January 1989 is reviewed. Thirty-two infants died, giving an overall survival rate of 70.9%. Sixty infants (54.4%) required mechanical ventilation in the first week of life; 24 (40%) of these infants died. Of the 36 survivors, 23 required oxygenation at 28 days of life and 21 fulfilled the criteria for BPD (35% of the 60 ventilated and 58% of the survivors). The incidence of BPD in all VLBW infants is 19% and of VLBW survivors 27%. Birthweight and gestational age appear to be important determinants. All the survivors in the 501-750 g birthweight group developed BPD compared to 6.25% in those above 1250 g. None of those greater than 30 weeks gestation developed BPD. Two forms of BPD were observed; the 'severe' group presented radiologically with chest radiographs characteristic of Stage IV BPD, while the 'mild' group with small or normal sized lungs demonstrated irregular strands of radio-densities alternating with areas of normal or increased lucency. The duration of mechanical ventilation and oxygen dependency were significantly longer in the 'severe' group, with the mean maximum peak inspiratory pressure, mean airway pressure, and FiO2 required in the first week of life being also significantly higher. Hyaline membrane disease was the main cause of respiratory failure requiring ventilation. The other causes were persistent pulmonary hypertension (1) and apnoea of prematurity (3); all of the latter developed only mild BPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoxygenation in parturients: a comparison of 4, 6 and 8 vital capacity breaths to 5 minutes of tidal volume breathing.

We compared the difference in denitrogenation (by intermittent measurement of arterial tension, PaO2) in 45 parturients at term when preoxygenated with 4, 6 or 8 rapid vital capacity breaths and 5 minutes of tidal volume breathing. Oxygen, at 8 litres min-1, was delivered through a facemask via a circle absorber with a 2 litre reservoir bag. Higher PaO2 was produced with 5 minutes of tidal volume breathing. This differed significantly from the PaO2 produced by 4, 6 or 8 rapid vital capacity breaths (p less than 0.01).

A multivariate analysis of factors predictive of parenteral nutrition-related cholestasis (TPN cholestasis) in VLBW infants.

To identify the factors predictive of development of TPN-related cholestasis, we conducted a historical cohort analysis of 62 VLBW infants who received TPN of which 17 developed cholestasis (27.4%). In the cholestatic group, the mean duration of TPN administration was significantly longer (25.7 days vs 8 days, p less than 0.001), the maximum daily amino-acids and lipids in the TPN infusate was significantly higher (amino-acids 2.25 vs 1.25 gm/kg/day, p less than 0.001; lipids 2.0 gm/kg/day vs 1.25 gm/kg/day, p less than 0.01), the duration of fasting was significantly longer (20.7 days vs 6.3 days, p less than 0.001) and the incidence of necrotizing enterocolitis was significantly higher (58.8% vs 15.5%, p 0.02). Using a linear discriminant analysis model with development of cholestasis as the dependent variable, the duration of TPN (p 0.0000) and the maximum daily amino-acid in infusate (p 0.0000) were found to be independent variables predictive of development of cholestasis. This model may serve to identify VLBW infants who will develop cholestasis during TPN.

Haematological status of fullterm healthy infants in the first week of life.

The haematological status of 105 healthy fullterm neonates was studied daily during the first week of life. Hb, MCV, RBC, PCV and WBC were determined with a Coulter 5 Counter, white cell differential reticulocyte and platelet counts manually, and ESR by a micromethod on free flowing capillary blood from heel stabs. A decline in Hb, PCV, MCV, RBC values and reticulocyte count was observed over the 7 days. The platelet count however rose slightly. The white cell count initially declined. The polymorphs initially predominant declined as the lymphocytes increased; by 7 days, both were about equal in proportions and together accounted for about 85% of the white cell population. The micro-ESR was very low, rising only slightly over the week.