Immune signalling responses in intestinal epithelial cells exposed to pathogenic Escherichia coli and lactic acid-producing probiotics.

Enterohaemorrhagic Escherichia coli O157:H7 and adherent-invasive Escherichia coli are two groups of enteric bacterial pathogens associated with haemorrhagic colitis and Crohn's Disease, respectively. Bacterial contact with host epithelial cells stimulates an immediate innate immune response designed to combat infection. In this study, immune responses of human epithelial cells to pathogens, either alone or in combination with probiotic bacteria were studied. Industrially prepared Lactobacillus helveticus strain R0052 was first examined by microarray analysis and then compared to broth-grown strains of R0052 and Lactobacillus rhamnosus strain GG using quantitative realt-time polymerase chain reaction. Results showed host immune activation responses increased following pathogen exposure, which were differentially ameliorated using probiotics depending on both the preparation of probiotics employed and conditions of exposure. These findings provide additional support for the concept that specific probiotic strains serve as a promising option for use in preventing the risk of enteric bacterial infections.

Neonatology in Singapore: the way we were, the way forward.

Singapore has a maternity hospital since 1924, but for many decades the newborns could only receive basic care. Neonatal and perinatal mortality rates were high. Marked improvement in neonatal care began from the 1980s when many neonatal departments were set up to provide intensive care. Improved socioeconomic status, better healthcare facilities, effective infection control, immunisation programmes and availability of potent antibiotics contributed to the decline of perinatal and neonatal mortality. Following the implementation of the glucose-6-phosphate dehydrogenase (G6PD) deficiency screening programme, severe neonatal jaundice and kernicterus were largely reduced. Exchange blood transfusions initiated in the 1960s and phototherapy in the 1970s had saved many babies. Kernicterus is almost not seen now. With more neonatal-trained staff, organised resuscitation teams, advances in respiratory management and better monitoring equipment, more babies have survived. Closer cooperation between obstetricians and neonatologists was a great leap forward towards perinatal medicine. Physicians should endeavour to reduce the incidence and prevalence of birth defects and metabolic errors. Perinatal asphyxia should be promptly detected and managed effectively, including neuroprotective strategies. There should be markers to predict the outcome of asphyxiated babies for decision-making. Neonatologists should be mindful of safe introduction of new technologies and rapid diagnostic techniques for infections, including group B streptococcal screening and chemoprophylaxis when required. Other current issues include prevention of major morbidities, preservation of brain function, improved neurodevelopmental outcome of premature babies, use of blood substitutes, optimal nutrition, fetal surgery, evidence-based medicine, better information systems, avoidance of medication errors, adequate sedation and pain relief of the baby, and the use of nitric oxide. One should bear in mind the need to enhance the neonatal intensive care environment, improve non-invasive monitoring and minimise invasive procedures. Physicians should prioritise neonatal care for their country and utilise less costly neonatal care. Ethical issues in neonatology that arise following advancement in neonatal care deserve attention. Advances in life sciences, such as the completion of the human genome project, cloning of tissues and organs, human stem cell research and technology, gene therapy, deoxyribonucleic acid vaccines and nanomedicine, should benefit neonatology.

Decision-making: initiation and withdrawing life support in the asphyxiated infants in developing countries.

The issues of life support in the asphyxiated infant are not only whether cardiopulmonary resuscitation or CPR will be successful, but also whether if successful, the infant will be severely damaged. This is particularly important in the developing countries because the damaged infants may burden the society. The country has to allocate huge financial and human resources to look after them. When it comes to decisions in initiation and withdrawal of life support, there are differences between the East and the West. Physicians are searching for reliable predictors of outcome of term asphyxiated infants to enable early decision-making, initiation and withdrawal life support, as well as counselling and planning appropriate level of treatment including trials of cerebroprotective therapies. Markers commonly used to identify birth asphyxia are not good predictors of brain injury or death. There is a myriad of reports on clinical or laboratory tests, some using single parameter, to help determine neurological outcome of asphyxiated term infants. Much frequently used equipment in developed countries can be expensive and inaccessible to developing countries. There is an urgent need to look for relevant, simple and inexpensive methods. A combination of measurements may look promising in the early selection of at-risk neonates for decision and counselling. Recently measurement of urinary lactate: creatinine ratio to identify early newborn infants at risk for HIE was proposed. Withdrawal of life support is an ethical issue. In withdrawing life support of the severely asphyxiated infants, one must be aware of the differences of approach. There are differences in religion and culture; in beliefs and philosophies, between the East and West The importance of neonatal resuscitation should be emphasised. Some regions still adhere to obsolete resuscitation methods. Neonatal Resuscitation Program (NRP) should be promulgated and organised resuscitation should be introduced. There is an urgent need to train the trainers in CPR in the developing countries.

Understanding traditional Chinese medicine--a doctor's viewpoint.

Singapore is a cosmopolitan country and its population comprises the Chinese, Malays, Indians, and others such as the Eurasians. In this heterogeneous, multi-racial, multi-lingual and multi-cultural society, medical treatment is also varied. People can seek modern (mainstream, western) medicine or traditional medicine when they are sick. Usually they first seek modern medicine. Some turn to traditional medicine as complementary treatment or alternative treatment. Traditional medicine is here to stay in this country. In November 2000, the Traditional Chinese Medicine (TCM) Practitioners Bill was passed in the Singapore Parliament. Health care providers, including doctors, would benefit from a good knowledge of both modern and traditional medicine. Practitioners in traditional medicine should also learn modern medicine.

Combination cyclopentolate and phenylephrine for mydriasis in premature infants with heavily pigmented irides.

PURPOSE: This study examined whether safe and effective mydriasis can be achieved in premature infants with heavily pigmented irides using combination cyclopentolate 0.2% and phenylephrine 1% eyedrops. METHODS: A prospective, randomized double-blind study was performed to compare combination cyclopentolate 0.2% and phenylephrine 1% eye-drops with triple instillation of tropicamide 0.5% and phenylephrine 2.5%. Twenty-eight consecutive babies with dark irides and birthweight <1600 g referred for screening for retinopathy of prematurity comprised the study population. Infants' eyes were randomly dilated twice with both regimens within a 2-week period. Blood pressure, heart rate, and pupil size were measured. RESULTS: Good mydriasis was achieved in both groups with no significant differences in pupil size or blood pressure (systolic, diastolic, or mean arterial pressures) over starting baseline values. Pulse rates decelerated below the baseline values in both groups, but these differences were not large. CONCLUSION: The single combination eyedrop of cyclopentolate 0.2% and phenylephrine 1% is as effective and safe a mydriatic for infants with dark irides as both tropicamide 0.5% and phenylephrine 2.5%.

Perinatal infections--problems in developing countries.

The transmission of infections from the biologic mother to her offspring is popularly known as perinatal infection (PI). It is not synonymous to infections during the perinatal or neonatal period. Physicians should avoid focusing attention only on the TORCH agents in the evaluation of suspected PI. Perinatal period begins from 28 weeks of gestation. Would one consider in utero infections in the first or second trimester of pregnancy as PIs? Developing countries have difficulty in collecting reliable and accurate data of PIs. These data are useful to define the magnitude of the problems, to monitor the trends, to recognise the mode of spread, and to find a solution of PIs. Most PIs are asymptomatic and diagnosis is extremely difficult. Developing countries need rapid, easy-to-operate, simple, and cheap diagnostic tools urgently. Access to health care in the remote city is limited. Newer drugs are too expensive and very few patients can benefit from these. Each developing country should prioritize its PI problems and tackle those that have serious public health problems and socio-economic impact. Most developing countries should focus on HIV (human immunodeficiency virus) and HBV (hepatitis B virus) infections. Other countries where ophthalmia, malaria or tuberculosis are prevalent or endemic, should focus on these. Developing countries are more willing to allocate the budget for prevention of diseases than for treatment. There may be problem of promulgating the information on prevention of diseases because of illiteracy, multi-lingual community. Vaccines where available, should be affordable. Other effective prevention guidelines should be workable in poorer nations. The government should play an important role in enforcing immunisation program by intensive promotion program or by legislation.

Reduction of nosocomial infection in a neonatal intensive care unit (NICU).

UNLABELLED: New measures aimed at reducing nosocomial infection in our neonatal intensive care unit (NICU) were introduced over a 3-month period from 1 July to 30 September 1994. OBJECTIVE: The aim of this study was to evaluate the impact of these measures on the incidence of nosocomial infection in our NICU. METHODS: The new measures introduced were: 1. grouping of all blood investigations to allow for fewer blood samplings per baby per day; 2. reduction of routine blood investigations after the acute illness has stabilised, and 3. a system of aseptic delivery of drugs through a central venous catheter, thereby reducing the need for peripheral intravenous lines. Nosocomial infections were defined according to the criteria spelt out in the Centres for Disease Control (CDC) guidelines. Data for the study was obtained from the ongoing surveillance carried out by the hospital's infection control team. Period 1 (1 year duration) was prior to the implementation of the new measures. Period 2 (1 year duration) was after implementation of the new measures. RESULTS: The overall nosocomial infection patient rates (expressed as number of infections per 100 intensive care unit patients) were 17.6 for Period 1 and 7.5 for Period 2. The overall nosocomial infection patient-day rates (expressed as number of infections per 1000 patient-days) were 13.5 and 6.1 respectively (p < 0.01). When the infants' birth weights were stratified as < 1500 g, 1500-2500 g, and > 2500 g, the greatest decline in both the overall nosocomial infection patient rate and nosocomial infection patient-day rate was seen in infants weighing < 1500 g. There was also a significant decline in the rates of blood-stream infections in infants weighing < 1500 g (from 7.5 to 2.8 per 1000 patient-days) (p < 0.05). Ventilator associated pneumonias also showed a decline from 3.3 to 1.0 pneumonia per 1000 ventilator days. The organisms responsible for the majority of blood stream infections in Period 1 were methicillin-resistant Staphylococci Aureus (MRSA), coagulase-negative staphylococci, gram-negative bacilli and candida. In Period 2, coagulase-negative staphylococci was the predominant organism. CONCLUSION: We conclude that there was a reduction in nosocomial infection rates. The new measures introduced may have contributed to this reduction.

De novo interstitial deletion of chromosome 1p with absent corpus callosum--a case report.

Deletion of short arm of chromosome 1 is a rare clinical entity and there are no clearly defined phenotype. We report a case of deletion of the short arm of chromosome 1, which is believed to be the first case among the Chinese population. This baby was also found to have some Robinow Syndrome-like features as well as absent corpus callosum which have never been reported in deletion of chromosome 1p.

Proteus syndrome.

This female Asian (Malay) baby had clinical features of Proteus syndrome. She had a large right facial lipolymphangioma with hyperpigmentation of the overlying skin. There was a smaller lymphangioma over the left side of her neck with excess nuchal folds, macrodactyly and bilateral talipes equinovarus. Despite the extensive hemifacial swelling, there was no evidence of upper respiratory tract obstruction. Generalized seizures developed on the sixth day of life which were controlled with phenobarbital. The lymphangiomas were excised without recurrence.

Traditional Chinese medicine and treatment of neonatal jaundice.

OBJECTIVE: Treatment with herbs may increase the risk of neonatal jaundice (NNJ). It is logical to look into the current practice in some hospitals in China where herbs are being used in the treatment of NNJ. It is also the purpose of this study to find out the chemical constituents and actions of the herbs, and the rationale of the treatment. METHODS: Twenty reports, from 1973 to 1989, from different parts of China, come in a published book and the paediatric journals written in the Chinese language. The Zhong Yao Da Zi Dian, an encyclopedia of Chinese materia medica, and other books on the pharmacology and applications of Chinese materia medica were also referred to in the study. FINDINGS: Yin-chen (oriental wormwood or Artemisia) was the most commonly used herbs for NNJ (95%). Others were Da-huang (rhubarb or Rheum officinale), Huang-qin (skullcap root or Scutellaria), Gan-cao (licorice or glycyrrhiza) and Huang-lian (goldthread rhizome or Copts chinesis). Huang-lian, which contains the alkaloid berberine, was used in 4 centers (20%). Berberine can cause severe acute hemolysis in babies with G6PD deficiency. Currently, Yin-chen comes as a decoction Artemisia composita and an intravenous preparation. These preparations have potential central nervous system and cardiovascular toxicities. CONCLUSIONS: Chinese herbs have many pharmacological substances and therefore multiple actions. In recent years, Chinese herbs are used in conjunction with "Western" drugs, rendering the study of the effects of herbs on NNJ extremely difficult. The efficacy and safety of phototherapy for NNJ have been firmly established, thus diminishing the need for drug treatment. What is the present day role, therefore, of herbal medicine for NNJ? Is there a place for further research of these herbal medicines?

Priorities in neonatal care in developing countries.

Lower perinatal and neonatal mortality have been achieved in the developed countries following advancement of neonatal care, introduction of high technologies, and better knowledge of pathophysiology of the newborn infants. Other contributing factors are organised delivery room care with skillful resuscitative techniques as well as risk identification and efficient transport of the sick infants including in utero transfer of the fetus, etc. It cannot be assumed that similar results can be attained in developing countries where financial and human resources are the problems. With limited resources, it is necessary to prioritize neonatal care in the developing countries. It is essential to collect minimum meaningful perinatal data to define the problems of each individual country. This is crucial for monitoring, auditing, evaluation, and planning of perinatal health care of the country. The definition and terminology in perinatology should also be uniform and standardised for comparative studies. Paediatricians should be well trained in resuscitation and stabilisation of the newborn infants. Resuscitation should begin in the delivery room and a resuscitation team should be formed. This is the best way to curtail complication and morbidity of asphyxiated births. Nosocomial infections have been the leading cause of neonatal deaths. It is of paramount importance to prevent infections in the nursery. Staff working in the nursery should pay attention to usage of sterilised equipment, isolation of infected babies and aseptic procedures. Paediatricians should avoid indiscriminate use of antibiotics. Most important of all, hand-washing before examination of the baby is mandatory and should be strictly adhered to. Other simpler measures include warming devices for maintenance of body temperature of the newborn babies, blood glucose monitoring, and antenatal steroid for mothers in premature labour. In countries where neonatal jaundice is prevalent, effective management to prevent kernicterus is essential. Simple assisted ventilatory device such as nasal continuous positive airway pressure (nCPAP) is also useful.

PIP: Levels of perinatal and neonatal mortality have declined in the developed countries following advances in neonatal care, the introduction of high technology, and better knowledge of the pathophysiology of newborn infants. Organized and skilled delivery room care together with risk identification and the efficient transport of sick infants, including in utero fetal transfer, also contribute to the reduction in mortality. However, in developing countries constrained by limited financial and human resources, the nature and delivery of neonatal care must be prioritized. Meaningful perinatal data must first be collected to define the problems of each country related to the monitoring, auditing, evaluation, and planning of perinatal health care services. Definitions and terminology in perinatology should be standardized to facilitate comparative study. Pediatricians should be well trained in the resuscitation and stabilization of newborn infants, infections should be prevented in the nursery, warming devices must be made available to maintain the body temperature of newborns, blood glucose should be monitored, and antenatal corticosteroids provided to women in premature labor. In countries where neonatal jaundice is prevalent, proper and effective management to prevent kernicterus is essential. Finally, a simple assisted ventilatory device such as nasal continuous positive airway pressure is also useful.

Detection of quinolone-resistant Neisseria gonorrhoeae.

The present National Committee for Clinical Laboratory Standards (NCCLS) guideline for testing Neisseria gonorrhoeae quinolone susceptibility defines only a susceptible category for ciprofloxacin, enoxacin, lomefloxacin, and ofloxacin, while susceptible, intermediate, and resistant categories are defined for fleroxacin. To further define the criteria for detection of quinolone resistance in gonococci, by standard disk diffusion and agar dilution methodologies recommended by the NCCLS, we tested 29 strains of quinolone-resistant N. gonorrhoeae (QRNG) recently isolated from ofloxacin-treated patients who were considered clinical failures. Regression analyses were performed on these results together with those of another 20 strains showing reduced susceptibility and 13 fully susceptible strains (ofloxacin MICs of < or = 0.25 microgram/ml). With 5-micrograms ofloxacin disks, resistance in 27 (93.1%) of the QRNG strains (MICs of > 1 microgram/ml) was detected by the criterion of a zone diameter of < 22 mm, while in the remaining 2 (6.9%), the disks failed to detect resistance. A cluster of 15 highly resistant strains showed ofloxacin MICs of > 4 micrograms/ml and zone diameters of < 13 mm. When tested with 5-micrograms ciprofloxacin disks, the corresponding values for resistance and high-level resistance of these QRNG strains were < 25 mm (MICs of > 0.5 micrograms/ml) and < 15 mm (MICs of > 2 micrograms /ml), respectively. Six strains for which ofloxacin MICs were > or = 8 micrograms/ml showed no zones at all with both 5-micrograms ofloxacin and 5-micrograms ciprofloxacin disks. These QRNG strains are now firmly established in the Southeast Asia region, and it is important for clinical laboratories to recognize these clinically resistant strains and to monitor their spread.

Quinolone-resistant Neisseria gonorrhoeae in Hong Kong.

OBJECTIVE: To study the serologic characters and antibiotic susceptibilities of quinolone-resistant Neisseria gonorrhoeae in Hong Kong. STUDY DESIGN: Sixty-nine strains of Neisseria gonorrhoeae isolated from clinical failure cases after treatment with ofloxacin during the period January 1, 1992, to January 1, 1995, were studied. A panel of 14 monoclonal antibodies against protein I classified these strains into 21 serovars. The pattern of serovar distribution against varying minimum inhibitory concentrations of ofloxacin was compared with 143 strains isolated from a cohort of quinolone-susceptible, clinically responsive cases. Antibiotic susceptibilities tests were performed on quinolone-resistant strains to penicillin, tetracycline, ciprofloxacin, spectinomycin, and ceftriaxone. Epidemiologic information on location of contact was collected. RESULTS: Serologic characterization showed that Bop and Bpy were the dominant serovars among quinolone-resistant strains. Most IA and other IB serovars had declined in the selection process for quinolone resistance. Antibiotic susceptibility tests showed that 81.2%, 89.9%, and 78.3% of quinolone-resistant Neisseria gonorrhoeae strains were resistant to penicillin, tetracycline, and both, respectively, whereas 10 of 69 (14.5%) of such strains displayed high-level quinolone resistance (ofloxacin minimum inhibitory concentration > 8 micrograms/ml). The quinolone-resistant strains remained fully susceptible to spectinomycin and ceftriaxone. CONCLUSIONS: Quinolone-resistant strains have become firmly established in Hong Kong. Serovar determination has documented shifts in the gonococcal population during the selection process for quinolone resistance. Places that use quinolones in the treatment of sexually transmitted diseases should be alert to the emergence of high-level quinolone-resistant Neisseria gonorrhoeae.

Ethical issues in neonatal paediatrics--the Singapore perspective.

In Singapore, formulating ethical guidelines for people who live in a multiracial, multilingual, multicultural and multi-religious community can be difficult. The "individualised prognostic" strategy in the management of critically ill infants has been followed. Our neonatal paediatricians encounter the following ethical problems: extremely premature babies whose viability is doubtful, babies born with severe congenital malformations, babies born with signs of life in legal or therapeutic termination of pregnancy, the asphyxiated babies or babies with severe or extensive brain damage, and babies who are chronically sick and have no chance of recovery or leaving the hospital. Good ethical decisions require medical facts. The infant's diagnosis and prognosis must be accurate. There should also be detailed information that continuation of any form of medical treatment for the infant is futile, will do more harm than good and is inhumane. Ethical decisions should be made in the best interests of the infant. Dating of the infant's gestational age should be accurate and reliable, and there should also be unanimous definitions such as fetal viability, abortions and lethal malformations. Ethical guidelines and the law must also keep pace with changes in medical practice.

Outcome of the extremely low birth weight infants (less than 999 grams): what messages are we getting?

The outcome of the extremely low birth weight (less than 1,000g or ELBW) babies continues to improve. More ELBW babies are surviving, though some of them may have various degrees of impairment or disability. The chance of dying or surviving with a major disability or cerebral palsy declines significantly in recent years in the developed countries. The implication of these findings is that application of neonatal care does not increase the risk of disabled survival as has been often feared but promoted normal survival. Great effort has been put in to achieve good results and better outcome. Developing countries however, will face a problem of achieving similar results because of limited resources or priority of allocation of limited resources, inadequate facilities, lower socio-economic status, poor home environment and lack of follow-up services, training and rehabilitation set-ups or intervention programme. What is the relevance of these good results in relation to the developing or third world countries? The limit of viability may have to be redefined. Nevertheless, it should be the aim to lower the mortality of these high risk babies and to reduce complications and morbidity of the survivors. Maintenance and control of body temperature, control of infections, blood sugar monitoring, antenatal steroids for the mother in premature labour, resuscitation at birth or even simple nasal continuous positive airway pressure (CPAP) should come a long way in fulfilling these goals. Those ELBW children who survive without neurological damage may have learning difficulties. It is necessary to find out the reasons for that such as the impact of the home environment on mental development. Do the children have a good background conducive for learning? Are there establishments for intervention programme in the community for these high risk children? The ratio of neonatal beds per 1,000 deliveries may have to be reviewed now that more ELBW infants are staying in the hospital for a longer period, and surviving.

Outbreak of Vibrio cholerae 01 in Hong Kong related to contaminated fish tank water.

An outbreak of 12 cholera cases, caused by Vibrio cholerae eltor inaba, occurred in Hong Kong during a three week period in June-July 1994. Only adults of both sexes were affected. Epidemiological investigations showed linkage in all cases with consumption of seafood, including shellfish, mantis shrimps and crabs. Microbiological findings demonstrated that contaminated seawater in fish tanks used for keeping alive these seafoods is the most likely vehicle of transmission. Aggressive control measures, promptly instituted, included prohibition of use of contaminated typhoon shelter water in fish tanks, use of seawater with E. coli counts below 610 organisms/100 ml, and the banning of unlicensed food sampans in typhoon shelters. These measures, coupled with public announcements and an active health education campaign on food safety and personal hygiene, abruptly terminated the outbreak. Places which practise the use of seawater, from probable contaminated sources, to keep alive their seafood for human consumption should be alerted to the possibility of transmission of Vibrio cholerae through this route.

Rapid decline in penicillinase-producing Neisseria gonorrhoeae in Hong Kong associated with emerging 4-fluoroquinolone resistance.

OBJECTIVE--To study the changes in penicillinase-producing (PPNG) and high-level tetracycline resistant (TRNG) Neisseria gonorrhoeae isolated in Hong Kong associated with emerging quinolone resistance (QRNG) over a two year period from November 1992 to October 1994. MATERIALS AND METHODS--Four thousand and eighty-six strains of Neisseria gonorrhoeae isolated, of which 432 were PPNG, were examined for susceptibilities to penicillin and tetracycline by an agar dilution method using the breakpoint minimum inhibitory concentrations (MICs) of 1 and 10 mg/1 respectively. Ofloxacin susceptibility was done using 0.1 and 1 mg/l. Penicillinase production was detected by performing the chromogenic cephalosporin nitrocefin test on all penicillin resistant (MIC > 1 mg/l) strains. RESULTS--Three thousand and eighty (75.4%) and 79 (1.9%) strains were found to be penicillin resistant and TRNG (MIC > 10 mg/l) respectively. Sixty-nine strains (1.7%) were resistant to both, of which 54 (1.3%) were PPNG. Three strains were multiply-resistant to penicillin, tetracycline and ofloxacin; however, none was PPNG. While the percentage of penicillin resistant strains remained stable (mean 75.5%, SD 7.0), TRNG decreased from 4.5% to 2.1%. The most dramatic change was the sharp decline of PPNG from 25.5% in January 1993 to 4.3% in October 1994, concurrent with a linear increase in strains with ofloxacin MIC > 0.1 mg/l. Significant clinical failure was seen in strains having ofloxacin MIC > 1 mg/l (QRNG), which increased drastically from 0.5% to 10.4% during the study period. Selection against PPNG and TRNG strains appeared to occur only when fully quinolone-susceptible strains first become less susceptible (MIC > 0.1 mg/l), but not when these less susceptible strains become fully resistant (MIC > 1 mg/l). CONCLUSION--PPNG is now no longer hyperendemic in Hong Kong. Emergence of QRNG is associated with rapid decline of both PPNG and TRNG. This is the first report of plasmid-curing effect of the 4-fluoroquinolones occurring on an ecological scale.