bluuebunny/crossref_metadata_2025 huggingface dataset:
FR167653, a potent suppressant of interleukin‐1 and tumor necrosis factor‐α production, ameliorates colonic lesions in experimentally induced acute colitis1
Authors: Blandino Ivan I Pacheco , Otaka Michiro , Jin Mario , Komatsu Koga , Odashima Masaru , Konishi Noriaki , Sato Toshihiro , Kato Sayuri , Watanabe Sumio
Published: March 2003

Background: Interleukin‐1 (IL‐1) and tumor necrosis factor‐α (TNF‐α) are believed to play a significant role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin‐1 and TNF‐α possess overlapping and synergetic activities inducing the production in cascade of other cytokines, adhesion molecules, arachidonic acid metabolites, as well as activating immune and non‐immune cells. FR167653 (C24H18FN5O2.H2SO4.H2O) is a newly synthesized organic compound with a potent inhibitory effect on IL‐1β and TNF‐α production. We hypothesized that the suppression of IL‐1 and TNF‐α induced by FR167653 could effectively attenuate experimentally induced colonic damage.

Methods: Colonic lesions were induced in male Sprague–Dawley rats (250–300 g) by intrarectal instillation of 4% acetic acid. The effect of FR167653 administration at 1.0, 1.5, 2.5 mg/kg per 6 h subcutaneously on acetic acid‐induced colonic damage was assessed. The lesion area, microscopic findings, colonic and serum levels of TNF‐α and IL‐1β were also evaluated.

Results: Treatment with FR167653 at 1.5 and 2.5 mg/kg per 6 h was able to ameliorate the gross macroscopic appearance of colonic lesions significantly, as well as ameliorate the lesion area induced by acetic acid. Colonic mucosal TNF‐α and IL‐1β levels of rats treated with FR167653 showed significant decrease in a dose‐dependent fashion compared with the control group. In the same manner, serum TNF‐α of rats treated with FR167653 was significantly lower than that of respective controls.

Conclusions: Subcutaneous administration of FR167653 was able to ameliorate the acute changes induced by acetic acid instillation in a dose‐dependent manner. This is the first report to evaluate the dual inhibition of the production of IL‐1 and TNF‐α, offered by FR167653, in acute experimental colitis. Further studies are necessary to evaluate FR167653's efficacy and safety on long‐term conditions.
A Japanese herbal medicine, Sho‐saiko‐to, prevents gut ischemia/reperfusion‐induced hepatic microvascular dysfunction in rats
Authors: Horie Yoshinori , Kajihara Mikio , Yamagishi Yoshiyuki , Kimura Hiroyuki , Tamai Hironao , Kato Shinzo , Ishii Hiromasa
Published: March 2003

Background and Aim:

We have reported that gut ischemia/reperfusion (I/R) causes hepatic microvascular dysfunction. Nitric oxide (NO) has been found to be a modulator of the adhesive interactions between leukocytes, platelets, and endothelial cells. Sho‐saiko‐to (TJ‐9), a Japanese herbal medicine, is reported to have protective effects against liver injury and to regulate NO production. The objective of this study was to determine whether TJ‐9 affects hepatic microvascular dysfunction elicited by gut I/R, and to investigate the role of NO.

Methods:

Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and the number of non‐perfused sinusoids (NPS). Plasma tumor necrosis factor (TNF)‐α and alanine aminotransferase (ALT) activities were measured. In another set of experiments, TJ‐9 (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered.

Results:

In control rats, gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma TNF‐α and ALT activities, and these changes were mitigated by the pretreatment with TJ‐9. Pretreatment with an NO synthase inhibitor diminished the protective effects of TJ‐9 on the increase in leukostasis in the pericentral region, NPS, and plasma TNF‐α levels, but not its effect on the increase in leukostasis in the midzonal region, total number of stationary leukocytes, or plasma ALT activities. Pretreatment with TJ‐9 increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST.

Conclusions:

These results suggest that TJ‐9 attenuates the gut I/R‐induced hepatic microvascular dysfunction and inflammatory responses such as TNF‐α production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti‐inflammatory effect like corticosteroid effect.
Endothelin‐3 induces both human and opossum gallbladder contraction mediated mainly by endothelin‐B receptor subtype in vitro
Authors: AL‐JIFFRY BILAL O , TOOULI JAMES , SACCONE GINO TP
Published: March 2003

Background: Endothelins are produced by gallbladder epithelial cells, suggesting a role in the regulation of gallbladder function.

Aims: To characterize the effect of endothelin‐3 (ET‐3) on human and Australian possum gallbladder contractility and identify the receptor(s) involved.

Methods: Human and possum gallbladder muscle strips were exposed to cumulative concentrations
of ET‐3 (10 pmol/L–100 nmol/L). Strips were pretreated with either tetrodotoxin
(TTX) (1 μmol/L), the selective ET receptor antagonists BQ‐123 (ETA),
BQ‐788 (ETB), alone or together, or the mixed ET antagonist tezosentan
(all 1 μmol/L). Maximal changes in tone were measured and expressed as percentage
of carbachol (100 μmol/L)‐induced tone. ANOVA was used for statistical analysis.

Results: Endothelin‐3 induced a concentration‐dependent increase in tone in both human and
pos‐sum strips (P < 0.05) and at 100 nmol/L represented 44.2 ± 4.5%
and 40.3 ± 4.6% of carbachol‐induced tone, respectively. The effect
on human strips was TTX insensitive, whereas the possum concentration–response
curve was shifted to the right. Individually, BQ‐123 and BQ‐788 shifted the human
concentration‐response curve to the right, but a greater inhibition by BQ‐788 was
achieved in the possum (P < 0.05). However, BQ‐123 plus BQ‐788 further
reduced the ET‐3 effect (P < 0.001) to a level comparable to that observed in the presence of tezosentan in both human and possum strips.

Conclusion: Endothelin‐3 produces potent gallbladder contraction in vitro, acting mainly
via ETB receptors and also interacting with ETA receptors. The receptors are located on the smooth muscle, but in possum gallbladder, neural receptors may also be involved. These findings suggest that ET‐3 may regulate motility of possum and human gallbladder.

© 2002 Blackwell Science Asia Pty Ltd
Management of peptic ulcer disease not related to Helicobacter
Authors: Yeomans Neville D
Published: March 2003

Abstract  Most peptic ulcers not due to Helicobacter pylori are caused by non‐steroidal anti‐inflammatory drugs (NSAID), among which an important subset are due to vascular protective (‘low‐dose’) aspirin therapy. Non‐steroidal anti‐inflammatory drugs ulcers heal quite quickly when treated with a proton pump inhibitor (PPI), even though the NSAID is continued. If the NSAID can be stopped, the ulcers heal readily with either a PPI or a histamine H2‐receptor antagonist (H2‐RA). If anti‐inflammatory treatment is still needed after ulcers are healed, prophylactic co‐therapy with a PPI or misoprostol will reduce the risk of ulcer recurrence by about 60–80%. The alternative of switching to a highly selective cyclooxygenase‐2 inhibitor has been shown to reduce the risk of a complicated ulcer by about 50–60%, unless low‐dose aspirin treatment needs to be given as well for vascular disease. Idiopathic ulcers are becoming more frequent as H. pylori prevalence falls. Some may be sequelae of previous NSAID ulceration even though the NSAID has been ceased and the original ulcer had healed. These are best treated with an H2‐RA or a PPI, followed by long‐term maintenance with either of these (often in half the healing dosage) to prevent recurrence. Ulcers due to Zollinger–Ellison syndrome and other hypergastrinemia syndromes are rare, and largely beyond the scope of this review.

© 2002 Blackwell Publishing Asia Pty Ltd
Advances in the management of irritable bowel syndrome
Authors: Kellow John E
Published: March 2003

Abstract  Recent advances in different aspects of irritable bowel syndrome have led to a need to reassess the overall management of this common, complex disorder. Important areas include: first, the heterogeneity of symptom patterns and the role of specific diagnostic symptom criteria for use in both clinical practice and in clinical research; second, the growing interest in the potential interaction between ‘peripheral’ and ‘central’ pathophysiological mechanisms; and third, the development of novel and effective drugs designed to target specific receptor systems in the enteric nervous system. This review covers each of these aspects and emphasizes an approach to management of patients based on pathophysiological considerations.

© 2002 Blackwell Publishing Asia Pty Ltd
Suppression of Helicobacter pylori‐induced interleukin‐8 production in gastric cancer cell lines by an anti‐ulcer drug, geranylgeranylacetone
Authors: Yoshimura Naoki , Suzuki Yasuo , Saito Yasushi
Published: March 2003

Background:
Geranylgeranylacetone (GGA) is an antigastritis and anti‐ulcer agent, with as yet an unknown mechanism of action. In this study, we investigated the effect of GGA on Helicobacter pylori‐induced interleukin (IL)‐8 production and IL‐8 mRNA expression in KATOIII cells, an established gastric cell line.

Methods:
Interleukin‐8 production in H. pylori‐infected KATOIII cells was measured by using enzyme‐linked immunoassay. The cytotoxicity of H. pylori on KATOIII cells was measured by a 51Cr release assay. The effect of GGA on H. pylori‐induced IL‐8 mRNA expression was measured by using northern blotting.

Results:
Interleukin‐8 production increased with time and H. pylori dose; the most significant increase was seen within 6–24 h of coculture with H. pylori. A dose of 0.1 mmol GGA suppressed IL‐8 production (P = 0.0077) and inhibited H. pylori‐induced IL‐8 mRNA expression (P = 0.0019). Furthermore, H. pylori‐induced gastric mucosal cell injury associated with IL‐8 and neutrophil activation was enhanced by NH3, and this enhancement was suppressed by GGA (P = 0.0043).

Conclusions:
Helicobacter pylori‐
infected gastric mucosal cells produce IL‐8, which can promote neutrophil activation, thus contributing to mucosal tissue injury associated with
H. pylori
infection. Agents like GGA, which can suppress IL‐8 production may have a protective role in the treatment of mucosal tissue damage seen in
H. pylori infection.

© 2002 Blackwell Publishing Asia Pty Ltd
Non‐alcoholic fatty liver disease: An overview
Authors: Mulhall Brian P , Ong Janus P , Younossi Zobair M
Published: March 2003

Non‐alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non‐alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of ‘burned‐out’ NASH. Although NAFL and NASH are associated with insulin‐resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure.

© 2002 Blackwell Publishing Asia Pty Ltd
Effects of insulin‐like growth factors‐IR and ‐IIR antisense gene transfection on the biological behaviors of SMMC‐7721 human hepatoma cells
Authors: YANG JIAN‐MIN , CHEN WEN‐SHENG , LIU ZHI‐PENG , LUO YUAN‐HUI , LIU WEI‐WEN
Published: March 2003

Background and Aims: Insulin‐like growth factors (IGFs) are closely related to hepatocellular carcinoma growth. The study aim was to investigate the effects of IGF‐IR and IGF‐IIR antisense gene transfection on the biological behaviors of SMMC‐7721 human hepatoma cells.

Methods: 7721‐IGF‐IR‐AS cells (human hepatoma SMMC‐7721 cells transfected with IGF‐IR antisense gene in our previous study) were transfected with a plasmid vector expressing IGF‐IIR cDNA in the antisense orientation by DOTAP liposome.7721‐IGF‐R‐AS cells were obtained by selection with G418 and hygromycin. Morphological changes of the cells were observed with optic and electron microscopes. In vitro growth of the 7721‐IGF‐R‐AS cells was observed with a soft agar test, MTT test and with naked mice inoculation test in vivo.

Results: The following changes were found in the SMMC‐7721 cells after being transfected with the IGF‐IR and IGF‐IIR antisense genes: (i) the degree of malignancy of the tumor cells as revealed by cell morphology was ameliorated; (ii) the growth capability of the tumor cells in soft agar and their tumorigenicity in naked mice were significantly depressed. However, in the control groups, the SMMC‐7721 cells transfected both with IGF‐IR and IGF‐IIR sense cDNA and SMMC‐7721 cells transfected without any external genes, had no such changes. However, the cell growth curves had no significant differences among these three groups.

Conclusion: IGF‐IR and IGF‐IIR antisense genes could significantly restrain the malignant behavior of human hepatoma cells and might be useful in investigating a potential route for hepatocellular carcinoma gene therapy.
Colonic mucosa in patients with portal hypertension
Authors: MISRA VATSALA , MISRA SRI PRAKASH , DWIVEDI MANISHA , SINGH PREMALA A , KUMAR VINEETA
Published: March 2003

Background and Aims: To do a histomorphometric study of vascular changes in colonic mucosa of patients with portal hypertension (PHT) and to find their association with clinical and upper and lower gastrointestinal endoscopic observations.

Methods: Full length colonoscopy was carried out in 55 patients with portal hypertension and 25 controls. Hemorrhoids, anorectal varices and colopathy were carefully looked for and recorded. Two biopsies each were taken from the caecum, ascending colon, transverse colon, descending colon and rectum. Sections from all the five sites were examined for histopathological changes with special reference to changes in mucosal capillaries. Morphometric assessment of the diameter of the capillary and thickness of the capillary wall was performed. These histomorphometric changes were correlated with clinical parameters and findings of upper and lower gastrointestinal endoscopic findings.

Results: Dilated and congested capillaries as well as capillaries with irregular thickening of the wall were seen in a significantly higher number of sections from patients than controls in biopsies from all the five sites from caecum to rectum. On morphometry, the diameter of the capillaries and the thickness of the capillary wall in biopsies from all the five sites in patients was significantly higher than that in the control group. Apart from vascular changes, edema and inflammatory infiltrate in lamina propria were the other significant histological features noted. No significant association between clinical and endoscopic features and histomorphometric assessment was found.

Conclusion: Dilated tortuous mucosal capillaries with irregular thickening of wall, edema of lamina propria and mild chronic inflammatory infiltrate are the major histopathological changes seen in colonic biopsies of patients with PHT, showing that PHT produces changes in the colonic mucosa similar to those seen in the mucosa of upper GI tract. However, the histological changes had no correlation with the clinical or endoscopic findings except that the thickness of the capillary wall was higher in patients who had undergone endoscopic sclerotherapy as opposed to those who had not received sclerotherapy.
Effects of blood transfusion on left ventricular output in premature babies
Authors: YU CW , SUNG RYT , FOK TF , WONG EMC
Published: March 2003

Objective: To investigate the acute effects of red blood cell transfusion on haemodynamics in preterm babies.

Setting: A neonatal unit in a University Hospital.

Patients: Preterm babies whose postnatal age was less than four weeks and who required red blood cell transfusion.

Measurement: Cardiac output and left ventricular systolic function was determined using Doppler echocardiography before, one hour and 24 h after red blood cell transfusion. Blood pressure and haematocrit were also recorded at the same time. Mixed‐effects regression model was used to analyse the effect of blood transfusion on left ventricular function and cardiac output.

Results: 57 preterm babies were recruited. Univariate analysis showed that cardiac index decreased significantly 24 h after transfusion (P<0.05). Systemic red cell transport increased by an average of 11.1% 24 h after transfusion (P<0.05). Multivariate analysis showed that the cardiac index was negatively associated with haematocrit and the index was higher in male babies.

Conclusion: There was a significant drop in cardiac index and an increase in systemic red cell transport 24 h after transfusion in premature babies.
Filling the gap: Weaning practices of children aged 0–2 years in western metropolitan Melbourne
Authors: GRAHAM VA , GIBBONS K , MARRAFFA C , HENRY L , MYERS J
Published: March 2003

Objective:

To investigate weaning practices of children aged 0–2 years in Melbourne’s western metropolitan region (WMR).

Methodology:

The study group comprised children aged 0–2 years attending six maternal and child health centres in the City of Brimbank in Melbourne’s WMR. One hundred and nineteen parents were asked to complete a questionnaire about their child. Interpreters were used as required. In total, 115 questionnaires were completed representing a response rate of 97%. All maternal and child health nurses working in the target region were asked to complete a questionnaire. Of these, five were selected randomly to participate in follow‐up indepth interviews. Weaning was defined as the addition of food/fluids other than breast milk or formula.

Results:

The mean age for the introduction of solids was 4.3 months. Of the children already introduced to solids, 67% had commenced between4 and 6 months whilst 29% of the infants were taking solids by 3 months of age. Of the children already having juice, 85% had done so by the age of 6 months. The mean age for the introduction of cow’s milk as the main drink was 10.7 months (S.D. 2.8). For English speaking families the mean age was 11.3 months (S.D. 1.8) whilst for families speaking languages other than English the mean age was 9.7 months (S.D. 4.1).

Conclusions:

Most parents in this group were following the recommended guidelines for weaning. Some parents had poor knowledge of appropriate weaning time, use of fruit juice and introduction of cow’s milk as the main drink. Additional information and education is required in these areas. Further investigation is required in relation to use of cow’s milk and ethnicity.
Arthrogryposis multiplex congenita in Western Australia
Authors: SILBERSTEIN EP , KAKULAS BA
Published: March 2003

Objective:

Determination of the prevalence of arthrogryposis multiplex congenita in Western Australia as well as the causes of the condition. Overseas reports varied considerably and no such survey had been conducted in Western Australia.

Methodology:

Case names were obtained from various registers and records as well as from private practitioners covering the 14 years birth cohort between 1980 and 1993. The records, and where possible the patients, were seen by one of the authors. Diagnosis was further established through relevant investigation where possible.

Results:

Thirty cases were identified, giving a birth prevalence of ≈1 in 12 000. In nine cases there were significant abnormalities of the central nervous system, in seven cases anterior horn cell and/or peripheral nervous involvement was the cause and in three there was primary muscle disease. The remaining 11 had various syndromes for which no definite neuropathological lesions could be demonstrated, but most of these had syndromes such as distal arthrogryposis or amyoplasia. Mortality was 37%. Talipes occurred in 23 of 30 cases. Early intervention and, in more severe cases, radical surgical intervention was the management adopted in most cases.

Conclusion:

The birth prevalence of arthrogryposis in Western Australia is somewhat less than that reported in Canada and Finland but somewhat greater than the Edinburgh figures, which appear to be the extremes quoted in the literature. Prognosis is worse in cases with serious central nervous system involvement and/or chest involvement, and better in cases of localised arthrogryposis (e.g. distal), as well as in the specific syndrome of amyoplasia as described by Hall.
Growth failure in cystic fibrosis
Authors: McNaughton SA , Stormont DA , Shepherd RW , Francis PWJ , Dean B
Published: March 2003

Objective: The aim of this study was to describe and compare the nutritional status of children aged 0–18 years attending the cystic fibrosis (CF) clinic at the Royal Children's Hospital, Brisbane, Australia, as outpatients in 1986 and 1996.

Methodology: The heights, weights and pulmonary function of children attending the CF clinic as outpatients in 1986 (n = 97) and 1996 (n = 227) were retrospectively analysed using a computerized database maintained by the CF clinic. The heights and weights were analysed in terms of z scores for height for age (HAZ), weight for age (WAZ) and weight for height (WHZ). Pulmonary function data is not available for all children. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced mid expiratory flows (FEF) were expressed as a percentage of predicted and are presented here.

Results: The 1986 sample consisted of 41 males (age range 0.18–14.59 years, mean age 6.52 (4.33)) and 56 females (age range 0.15–14.97 years, mean age 7.75 (3.70)). The 1996 sample consisted of 111 males (age range 0.09–17.97 years, mean age 8.80 (5.49)) and 114 females (age range 0.12–17.98 years, mean age 8.49 (5.26)). In 1986, males were shorter than females (P = 0.0096) and females had a lower mean FVC than males (P = 0.0438). In 1996, males were shorter, lighter and more wasted than females (P = 0.0357, P = 0.0034 and P = 0.0273, respectively) and females had a lower mean FEV1 and mean FVC than males (P = 0.0176 and P = 0.0079, respectively). Males in 1996 were lighter and more wasted than males in 1986 (P = 0.0023 and P = 0.0139, respectively) and had a lower mean FEV1, mean FVC and mean FEF (P < 0.0001, P = 0.0012 and P = 0.0069, respectively). Females in 1996 were shorter and lighter than females in 1986 (P = 0.0273 and P = 0.0405, respectively) and had a lower mean FEV1, mean FVC and mean FEF (P < 0.0001, P < 0.0001 and P < 0.0001, respectively). When subjects were classified according to FEV1 (FEV1≥ 75% or FEV1 < 75%), there were no significant differences in z scores between the 1986 group and 1996 group. Similarly, when the 1986 group were matched for gender and FEV1 with the 1996 group, there were no significant differences in z scores for males or females.

Conclusions: It is suggested that the apparent worsening of nutritional status among the 1996 group of CF patients is in fact due to an effect of increased survival of patients with more severe clinical symptoms. The findings from this study highlight the continuing, and in fact, worsening problem of growth failure in children with CF.
The evolving role of community‐based general paediatricians: The Barwon experience
Authors: Hewson PH , Anderson PK , Dinning AH , Jenner BM , McKellar WJD , Weymouth RD , Gollan And Ra
Published: March 2003

Objective: To detail the acute and chronic paediatric service and community‐orientated activities and responsibilities of community‐based general paediatricians.

Methodology: Data were collected over the 12 months July 1996 to June 1997 relevant to (i) acute neonatology and paediatrics, (ii) the different community paediatric service organizations with which the paediatricians were involved, and (iii) the quantification of the amount of time spent in non‐consulting paediatric work.

Results: Findings revealed decreasing hospital admissions, infrequent severe neonatal resuscitation requirements, extensive involvement in community organizations and a great deal of time spent in non‐consulting paediatric work.

Conclusions: Ongoing training and upgrading in acute paediatric diagnostic and procedural skills, rationalization of resuscitation expertise, training in management and administrative skills and models of care for the chronically ill should become part of the training of community‐based general paediatricians.
The successful containment of Coxsackie B4 infection in a neonatal unit
Authors: Austin BJ , Croxson MC , Powell KFP , Gunn TR
Published: March 2003

This report describes the containment of a potential enterovirus epidemic in a neonatal intensive care unit.

A case of neonatal enterovirus meningitis and myocarditis was identified. Polymerase chain reaction (PCR) was used to assist in appropriate cohorting of contacts. One further infant became cross‐infected with Coxsackie B4. Serum PCR was accurate in detecting the infection in the early stages in this asymptomatic neonate. Neonatal enterovirus infection is relatively rare but has the potential to cause outbreaks in neonatal wards. PCR can be used to diagnose and monitor for cross infection.
Varicella vaccine in non‐immune household contacts of children with cancer or leukaemia
Authors: Kappagoda C , Shaw PJ , Burgess MA , Botham SJ , Cramer LD
Published: March 2003

Objective: To assess the immunogenicity and reactogenicity of a new formulation of live attenuated varicella vaccine (Oka strain) in non‐immune household contacts of children with cancer or leukaemia.

Methodology: This was an open study with one group. Healthy varicella‐susceptible adults and children living in the same household as children with cancer or leukaemia were vaccinated with a new live attenuated varicella vaccine (Oka strain) which is stable when stored at 2–8°C (refrigerator temperature) for at least 24 months (Varilrix). Children less than 13 years of age received one dose (0.5 mL containing at least 103.3 plaque forming units) by subcutaneous injection and those aged over 13 years received two doses 8 weeks apart. Adverse reactions following vaccination were recorded daily by the vaccinees. Post‐vaccination antibody estimation was determined using indirect immunofluorescence 6 weeks after vaccination.

Results: Thirty‐five seronegative subjects (28 children and 7 adults and adolescents) were vaccinated. All subjects tested (34) had seroconverted after vaccination. Local injection site reactions were experienced by 15/35. Other adverse reactions were uncommon (rash 2/35, fever (≥ 37.5°C) 3/35). No cases of clinical varicella occurred amongst the high–risk household contacts of the vaccine.

Conclusion: This is the first study of this formulation of varicella vaccine in household contacts of children with cancer or leukaemia. The vaccine was found to be safe and immunogenic, but further follow‐up is needed to document duration of immunity.
How well are we doing? – Metabolic control in patients with diabetes
Authors: Thomsett MJ , Shield GJ , Batch JA , Cotterill AM
Published: March 2003

Objective: To compare the present level of metabolic control in children and adolescents with insulin‐dependent diabetes mellitus (IDDM) attending Brisbane paediatric diabetes clinics with published overseas data.

Methodology: Blood HbA1c concentrations, population characteristics, current treatment practices and short‐term complications were recorded in all patients, aged 19 years and under, attending the diabetes clinics of the two Brisbane Children’s Hospitals or the private practice of one of the authors (MJT) in the first quarter of 1998.

Results: Two hundred and sixty‐eight patients were assessed (M/F 142/126). Ages ranged from 1 to 19 years (mean 11.2 years); duration of IDDM was 0–16 years (mean 4.4 years); and 141 (53%) were pubertal. Of those aged less than 13 years, only 4% had more than two injections daily. Insulin doses (U/kg/day) rose with increasing age. Larger doses were required in regimens involving more than two injections per day than those involving one to two injections per day. Ketoacidosis or severe hypoglycaemia in the last 3 months were reported in eight (2.7%) and 17 (6.3%) of patients, respectively. Mean HbA1c (Â± SD) was 8.6 Â± 1.4% (range 5.2–14.0%), with 33% of children having a HbA1c concentration < 8%. HbA1c concentrations were significantly related (P < 0.05) to insulin dose and to duration of diabetes, but not to severe hypoglycaemia, ketoacidosis, age, frequency of injections, or number of clinic visits per year. Mean HbA1c concentration was significantly higher (P < 0.05) in those children in puberty (8.7 Â± 1.5%) than in those not in puberty (8.5 Â± 1.2%).

Conclusions: Only 33% of patients had a HbA1C concentration less than 8% and 6.3% had a severe hypoglycaemic episode in the 3 months. These results are similar to published overseas data.
Tetracycline‐induced benign intracranial hypertension
Authors: Nagarajan L , Lam GC
Published: March 2003

Abstract: We report on a young adolescent with benign intracranial hypertension which we attribute to the use of minocycline for acne.
Elevated plasma bile acid concentrations in two sisters with tyrosinaemia type I
Authors: Sass JO , Skladal D
Published: March 2003

Abstract: A 21‐month‐old girl suffering from tyrosinaemia type I and undergoing treatment with 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC) presented with pruritus which rapidly ceased with administration of high doses of ursodeoxycholic acid. Determination of plasma bile acids revealed clearly elevated levels both in samples taken before and after the onset of NTBC therapy, thus indicating, that the increase was not related to the administration of this drug. This result is corroborated by data from the first patient’s newborn sister, diagnosed with the same disease, who showed elevated plasma bile acid concentrations in all samples examined, except for the cord plasma. This is the first report on altered bile acid concentrations in tyrosinaemia type I, and underlines the need for thorough investigation of bile acid metabolism in this disease.
Invasive Haemophilus influenzae type b infections in Singapore children: A hospital‐based study
Authors: Lee Ys , Kumarasinghe G , Chow C , Khor ESH , Lee Bw
Published: March 2003

Objective: A 6‐year (1990–95) hospital‐based retrospective study was carried out to investigate the pattern of invasive Haemophilus influenzae type b (Hib) disease.

Methodology: Cases with Hib isolated from sterile sites (blood, cerebrospinal fluid, or joint aspirate) were identified from the hospital’s microbiological records, and their reviewed case records. Patients with pyogenic meningitis in the same study period were also identified to estimate the incidence of Hib meningitis.

Results: Twelve patients had positive cultures from sterile sites, of whom nine children were less than 5 years of age. These included seven cases of meningitis, one patient with acute epiglottitis, and one case of pneumonia. Three of the seven patients with meningitis had significant long‐term sequelae. Our data also suggests a relatively low proportion of ethnic Chinese children with invasive disease. It was estimated that 18.4% to 41.1% of pyogenic meningitis in children admitted to the National University Hospital were due to Hib. The estimated annual attack rate of invasive Hib disease was at most 3.3 per 100 000 children aged less than 5 years (95% confidence interval: 2.6–3.5/100 000).

Conclusion: Invasive Hib infections are relatively uncommon in our community. This justifies the need for a cost effectiveness study before a universal Hib vaccination program is implemented.
Toxic shock syndrome associated with newly diagnosed type I diabetes
Authors: Couper J J , Kallincos N , Pollard A , Honeyman M , Prager P , Harrison L C , Rischmueller M
Published: March 2003

Abstract: Studies of two post‐mortem pancreata of children at the onset of type I diabetes have suggested activation and expansion of islet infiltrating T cells by a superantigen. We present the first reported case of a superantigen mediated disease, toxic shock syndrome (TSS), occurring at the diagnosis of type I diabetes. A 12‐year‐old girl presented with TSS and newly diagnosed diabetes with ketoacidosis. At presentation she was unconscious, febrile and hypotensive, with a desquamating erythematous rash and Kussmaul breathing. During resuscitation, her renal impairment, diarrhoea, thrombocytopaenia and ketoacidosis resolved. Vaginal discharge and blood cultures grew Staphylococcus aureus. T cell studies at 2 weeks after diagnosis detected a high level of spontaneous and islet antigen‐specific proliferation with associated interleukin‐10 production compared to human leucocyte antigen DR matched controls.
Hepatitis C infection in children: A Melbourne perspective
Authors: Karim B , Alex G , Smith Al , Hardikar W
Published: March 2003

Objective: To examine the clinical spectrum of hepatitis C virus (HCV) infected children in our care by determining presentation, mode of acquisition, degree of co‐infection, biochemical evidence of persisting hepatitis and treatment outcome.

Methodology: A retrospective review of the medical records of all children attending the Royal Children’s Hospital, Melbourne, between 1990 and 1998, who had antibodies to HCV infection detected. Detailed clinical information, investigations and the results of treatment were extracted from the clinical notes.

Results: A total of 94 children (age range 2 weeks to 19.7 years) were identified, of whom nine had passive transfer of maternal antibodies from HCV‐positive mothers and were excluded from analysis. Sixty‐seven children (79%) were infected by transfusion of blood or blood products. Perinatal transmission occurred in 11 children (13%), and six children (7%) had a history of i.v. drug abuse. The majority of children were asymptomatic at presentation. Of the 65 patients tested for HCV‐ribonucleic acid, 43 (66%) were positive. Fifty‐seven cases had serial alanine aminotransaminase (ALT) measurements over a mean of 28 months. Of these, 38 (67%) had an abnormal ALT. Ten cases (12%) were co‐infected with hepatitis B virus, HIV or both. Of 12 patients treated with interferon, four responded with normalisation of ALT from 3 to 12 months post‐commencement of therapy.

Conclusions: Although HCV was largely an asymptomatic condition in our clinic population, more than half the patients had biochemical evidence of ongoing liver damage. Given the chronicity of this infection in the majority of patients and the long‐term risks of cirrhosis and hepatocellular carcinoma, children with HCV infection represent a high‐risk group worthy of regular follow up.
Family data in Rett syndrome: Association with other genetic disorders
Authors: Leonard H , Fyfe S , Dye D , Hockey A , Christodoulou J
Published: March 2003

Background: Rett syndrome is a neurological disorder, almost exclusively affecting girls.

Methodology: Between 1993 and 1995 pedigree data were obtained from families of girls registered with the Australian Rett syndrome database.

Results: Although 21 individual disorders were reported to be present in family members of affected girls, there was no apparent clustering of the same disorder in different families. However it was certain that a geneticist had been involved in only 10.9% of cases.

Conclusions: Mutations in the MECP2 gene have now been reported in a proportion of sporadic cases. Thus, it will be important to examine this phenotype–genotype correlation in the Australian cohort. Where a mutation is found, prenatal diagnosis in a subsequent pregnancy will be a possibility. Using the Australian population database and in conjunction with the clinical genetic services in each state it is planned to contact families with an affected girl to offer testing and counselling.
Neonatal outcome of gastroschisis and exomphalos: A 10‐year review
Authors: Kitchanan S , Patole Sk , Muller R , Whitehall Js
Published: March 2003

Objective: To study neonatal outcomes associated with gastroschisis and exomphalos in a regional neonatal unit.

Methods: A retrospective (1988–97) data analysis to study the effect of the type of defect/surgery, mode/place of delivery and associated anomalies on time to start and reach full feeds, duration of total parental nutrition (TPN) support and total hospital stay. Exact bivariate test procedures were used for data analysis.

Results: Twenty‐one cases of gastroschisis (17 inborn) and five cases (four inborn) of exomphalos were identified. Of these, 23.8% cases of gastroschisis and 60% of cases of exomphalos had associated gut anomalies. The survival rates for gastroschisis and exomphalos were 91 and 100%, respectively. The median time to start and reach full enteral feeds in outborn neonates was longer than in inborn neonates (9 vs 25 days, respectively, P = 0.01; and 16 vs 49 days, respectively, P = 0.01), as was the duration of TPN support (14 vs 42 days, respectively; P = 0.02). Neonates with gastroschisis had significant delays in starting and reaching full feeds compared with neonates with exomphalos (median 13 vs 4.5 days, respectively, P = 0.03; and 24 vs 8, respectively, P = 0.02) and they required prolonged support with TPN (median 23 vs 6 days, respectively; P = 0.01). Antenatal detection was significantly more frequent in inborn compared with outborn neonates (100 vs 67%, respectively; P = 0.03). The severity of associated gut anomalies and the delivery to surgery interval did not differ significantly to explain the increased morbidity in outborn neonates. Outcome was not significantly different after analysis by type of surgery and mode of delivery.

Conclusions: Increased morbidity in outborn neonates may be related to factors such as temperature, care, hydration status, care of the defect and vascular compromise of prolapsed gut during prolonged transportation.
A randomized trial of enteral feeding volumes in infants born before 30 weeks’ gestation
Authors: Kuschel C A , Evans N , Askie L , Bredemeyer S , Nash J , Polverino J
Published: March 2003

Objective: To compare the effect of two volumes of enteral feeds on postnatal growth in infants born before 30 weeks gestation.

Methodology: Fifty‐four infants, less than 30 weeks gestational age, who reached full enteral feeds were randomized to remain on 150 mL/kg per day (150 group) or increase to 200 mL/kg per day (200 group). The primary outcome measure was growth at 35 weeks corrected gestational age (CGA).

Results: There were no statistically significant differences in demographic or clinical parameters between the study groups at commencement of the study, although there was a trend for infants in the 150 group to be lighter (895 g vs 1020 g, P = 0.27). Milk intakes were increased in 43% of the infants in the 150 group, whereas 54% of the infants in the 200 group required reduced intakes. Infants in the 200 group had greater daily weight gains (16.7 g/kg per day vs 15.2 g/kg per day, P = 0.047) and at 35 weeks CGA were heavier (2020 g vs 1885 g, P = 0.014) and had a greater arm fat area (282 mm2vs 218 mm2, P = 0.009). There was no difference in length or head circumference at 35 weeks CGA, and no difference in any growth parameter at 1 year of age. Morbidity was not different between the groups.

Conclusions: The individual milk volume requirements for adequate weight gain without significant adverse effects vary between 150 and 200 mL/kg per day in extremely premature infants. For many infants in both groups, the assigned target volume was not appropriate. Increased milk intakes (and therefore higher caloric and mineral intakes) are associated with increased daily weight gains and a greater weight at 35 weeks CGA. The weight gain may be due to an increase in fat deposition.
Choice of formula and human milk supplement for preterm infants in Australia
Authors: Simmer K
Published: March 2003

Abstract: Human milk (HM) is considered to be the optimal feed of choice for neonates, however, for preterm infants, HM fortifiers are often added to increase growth. If HM is unavailable, preterm formula is the next best option for preterm infants. Choosing which fortifier, if any, to use or which formula can be confusing. In this paper, the composition of milk feeds available in Australia and New Zealand is reviewed with the aim of assisting paediatricians to decide which feed is most appropriate for their patients.
Alveolar capillary dysplasia with antenatal anomalies mimicking trisomy 21
Authors: McGaughran J. , Souter DJ , Kuschel CA
Published: March 2003

Abstract: Alveolar capillary dysplasia (ACD) has been described in conjunction with a number of congenital abnormalities. The case reported here was noted in utero to have duodenal atresia and a partial atrioventricular canal defect and a provisional diagnosis of trisomy 21 was considered. A fetal blood sample showed a normal karyotype. The diagnosis of ACD was made at post‐mortem following a neonatal death on the tenth day. This case further highlights the range of congenital abnormalities that may be present in cases of ACD that may mimic other conditions, including trisomy 21, on antenatal scan. However, the absence of congenital anomalies, even in the same family, would not exclude the diagnosis of ACD.
Hepatitis in children hospitalized with measles: The experience acquired after a Greek epidemic
Authors: Papadopoulou AL , Theodoridou M , Syriopoulou V , Mostrou G , Kattamis CH
Published: March 2003

Objective: In childhood, hepatitis is an uncommon and ill‐defined complication of measles. We studied prospectively the prevalence of hepatitis in 189 children with measles, admitted to hospital during a measles epidemic in Greece.

Methodology: Diagnosis of measles was based on clinical features and a fourfold rise of the haemagglutination inhibiting antibody titre, while liver impairment was based on a twofold or greater increase in liver enzymes.

Results: Nine children (4.8%) had increased liver enzymes. Hepatitis was not related to the duration and severity of fever or the coexistence of other complications, and in all children but one, was subclinical and resolved rapidly. One child with mental retardation who was being treated with anti‐epileptic therapy and had normal liver enzymes prior to measles, developed hepatic coma from which he recovered 1 month later.

Conclusions: Liver involvement in childhood measles is rare and transient but it may be severe in children receiving hepatotoxic drugs.
Normal pulse oximeter reading in a cyanotic infant
Authors: Li AM , Wong W , Chan MHM , Ma KC , Law LK , Van Zwieten R , Lam CWK , Fok TF
Published: March 2003

Abstract: A newborn infant who presented with central cyanosis was found to have hereditary methaemoglobinaemia. The pulse oximeter readings and physical findings were incompatible. Clinical assessment remains an important part in the management of such cases.
Rhabdomyolysis following status asthmaticus
Authors: Li AM , Li CK , Chik KW , Shing MMK , Fok TF
Published: March 2003

Abstract: A 15‐year‐old Chinese boy developed rhabdomyolysis with myoglobinuria and marked elevation of serum creatine phosphokinase following a prolonged and severe attack of asthma. He recovered after vigorous hydration and supportive treatment. Clinicians should be aware of this potentially fatal, albeit rare, complication of status asthmaticus.
Paediatric melioidosis in the Northern Territory of Australia: An expanding clinical spectrum
Authors: Edmond KM , Bauert P , Currie BJ
Published: March 2003

Objective: The objective of this study was to present the laboratory and clinical features of the six cases of paediatric melioidosis diagnosed from 1997–;2000.

Methodology: All cases of melioidosis confirmed by the pathology department of Royal Darwin Hospital were prospectively identified by culture and/or serology.

Results: Four children were Aboriginal and all six cases presented during the rainy season (November–;April) in rural areas in the tropical Top End of the Northern Territory. Delay in diagnosis ranged from 5 and 11 days. Two cases had localized melioidosis, two cases had underlying disease and were likely to be colonized with Burkholderia pseudomallei (B. pseudomallei). Two cases had neurological melioidosis with major residual disability. No deaths occurred.

Conclusions: Melioidosis remains an unusual disease in children in the tropical Northern Territory. The average annual incidence since 1997 is 5.48 per 100 000. This series demonstrates that children in Australia can have serious neurological complications from B. pseudomallei infection. All children living in or visiting tropical Australia are at risk, especially those residing in rural areas in the rainy season. Melioidosis remains a difficult disease to manage, and expert opinion should be sought if B. pseudomallei is cultured from any site.
Glycopeptide prescribing in an Australian tertiary paediatric hospital
Authors: Jones DA , Pulver L , Tai B , Nourse C
Published: March 2003

Objective: To assess the extent and appropriateness of glycopeptide use in a tertiary Australian Paediatric hospital.

Methodology: A retrospective analysis of prescriptions during a six‐month period between July 1999 and January 2000. Medical records were examined and prescribing practices compared with the recommendations of the Hospital Infectious Control Practices Advisory Committee (HICPAC) and the Infectious Diseases Society of America (IDSA).

Results: Fifty‐one patients were identified who received a total of 98 glycopeptide prescriptions. The Haematology/ Oncology unit prescribed 71/98 (72.4%). 68/98 (69.4%) patients received vancomycin, 9/98 (9.2%) received teicoplanin and 21/98 (21.4%) a combination of both. 81/98 (82.7%) had central venous catheters and 69/98 (70.4%) were immunocompromised. 48/98 (49%) prescriptions were for empiric treatment with 38/98 (38.8%) for prophylaxis and 11/98 (12.2%) therapeutic. 19/98 (19.4%) prescriptions were deemed appropriate, 6 (6.1%) by HICPAC criteria, and a further 13 (13.3%) by IDSA or other criteria. Of 19 prescriptions started appropriately, only 7/17 (41.1%) were continued appropriately beyond 48 h. Appropriate cultures were taken before prescription in 93.3% of cases. Dose was appropriate in 91/98 (92.9%) and frequency appropriate in all cases. The cost of inappropriate prescribing was approximately $9500.

Discussion: A high rate of inappropriate glycopeptide prescribing was evident in this paediatric population. Inappropriate prescribing existed across all subspecialties. Use was primarily for empiric therapy and prophylaxis in young children with an oncology diagnosis. A number of situations existed where glycopeptide prescription was felt appropriate despite not being included in HICPAC/IDSA guidelines. Areas with high rates of inappropriate prescribing were identified and will be targeted for education and intervention. Audit of practice continues.
Carbohydrate‐deficient glycoprotein syndrome 1b: A new answer to an old diagnostic dilemma
Authors: Kelly DF , Boneh A , Pitsch S , Gold H , Fietz M , Nelson P , Oliver MR
Published: March 2003

Abstract: A patient with carbohydrate‐deficient glycoprotein syndrome type 1b (CDGS1b) is reported. The patient presented at 5 months of age with failure to thrive, prolonged diarrhoea, hepatomegaly and elevated serum liver transaminases. Liver biopsy showed steatosis. A low serum albumin and elevated serum liver transaminases persisted throughout childhood during which he had repeated infectious illnesses. From the age of 10 years he had oesophageal and duodenal ulceration together with recurrent bacterial cholangitis. Liver biopsy demonstrated hepatic fibrosis. CDGS1b was suspected, supported by the finding of a protein‐losing enteropathy and finally confirmed by showing a reduced phosphomannoseisomerase activity. This case illustrates a rare condition with a wide range of presentations.