bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporary amelioration of bilirubin conjugation defect in Gunn rats by transplanting conditionally immortalized hepatocytes
Authors: KIM BYUNG‐HO , HAN YO SEB , DONG SEOK HO , KIM HYO JONG , CHANG YOUNG WOON , LEE JOUNG IL , CHANG RIN
Published: March 2003

Abstract Background: Conditionally immortalized hepatocytes (CIH) have been used in hepatocyte transplantation as an alternative to primary hepatocytes to cope with the shortage of donor organs. However, CIH are known to undergo apoptosis at body temperature and survive in vivo for a short period. In the present study, we investigated whether CIH function or not and how long their function is maintained in vivo.

Methods: Various CIH cell lines that were established with temperature‐sensitive Simian virus 40 large T antigen were transplanted into the spleen of Gunn rats, which are defective in bilirubin uridine diphosphate glucuronoside transferase (BUGT). Then, we measured biological changes over 3 months.

Results: Serum bilirubin of the syngeneic CIH recipients decreased by 30%, which was maintained for 8 weeks. Thereafter, it began to rise to basal levels. The recipients of allogeneic CIH showed a minor reduction of bilirubin, although this was not statistically significant. However, there was no significant change in the bilirubin level in recipients of BUGT‐defective congeneic CIH throughout the study period. Bilirubin monoglucuronides in the bile were not detected in the recipients of BUGT‐defective CIH. However, they appeared in recipients of non‐defective CIH and made up approximately 41% of total bile pigments.

Conclusions: Conditionally immortalized hepatocytes expressed hepatocyte function in vivo as well as in vitro, but the function lasted for a couple of months. According to our previous study, the limited functional duration may be related to the inevitable occurrence of apoptosis of these cells at body temperature. These data suggest that CIH can be used in hepatocyte transplantation only for temporary hepatic support.

© 2002 Blackwell Publishing Asia Pty Ltd
Clinical implications of hepatogenous diabetes in liver cirrhosis
Authors: Holstein A , Hinze S , THIEßEn E , Plaschke A , Egberts E‐H
Published: March 2003

Background: Hepatogenous diabetes is a common complication of liver cirrhosis. The aim of the present study was to examine the clinical and therapeutic implications and the prognostic significance of hepatogenous diabetes in patients with liver cirrhosis.

Methods: The prospective cohort study was conducted in 52 patients with histologically confirmed liver cirrhosis (44% Child A, 37% Child B, 19% Child C). The examination included a history, determination of basal C‐peptide and glycosylated hemoglobin (HbA1c) and, in some cases, a 3 h oral glucose tolerance test with 100 g glucose. Patients were also examined for signs of diabetic retinopathy and information on the further course of illness was obtained.

Results: Seventy‐one percent of patients with liver cirrhosis had manifest diabetes, 25% had impaired glucose tolerance and only 4% had normal glucose tolerance. In most cases, the hepatogenous diabetes was clinically asymptomatic. Sixteen percent of patients with hepatogenous diabetes had a family history of diabetes; only 8% had retinopathic complications. Within 5.6 ± 4.5 years after diagnosis of liver cirrhosis, 52% of the diabetics had died, mainly of complications of the cirrhosis. There were no diabetes‐associated or cardiovascular deaths.

Conclusions: Hepatogenous diabetes differs from type 2 diabetes in that there is less often a positive family history and that the cardiovascular and retinopathic risk is low. The prognosis of cirrhotic patients with diabetes is more likely to be negatively affected by the underlying hepatic disease and its complications than by the diabetes. Antihyperglycemic treatment of hepatogenous diabetes should always be carefully weighed up in each individual case.
Non‐cirrhotic portal fibrosis: Current concepts and management
Authors: SARIN SK , KAPOOR D
Published: March 2003

Abstract 
Non‐cirrhotic portal hypertension (NCPH) comprises diseases having an increase in portal pressure (PP) due to intraheptic or prehepatic lesions, in the absence of cirrhosis. The lesions are generally vascular, either in the portal vein, its branches or in the perisinusoidal area. Because the wedged hepatic venous pressure is near normal, measurement of intravariceal or intrasplenic pressure is needed to assess PP. The majority of diseases included in the category of NCPH are well‐characterized disease entities where portal hypertension (PHT) is a late manifestation and, hence, these are not discussed. Two diseases that present only with features of PHT and are common in developing countries are non‐cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO). Non‐cirrhotic portal fibrosis is a syndrome of obscure etiology, characterized by ‘obliterative portovenopathy’ leading to PHT, massive splenomegaly and well‐tolerated episodes of variceal bleeding in young adults from low socioeconomic backgrounds, having near normal hepatic functions. In some parts of the world, NCPF is called idiopathic portal hypertension (IPH) or ‘hepatoportal sclerosis’. Because 85–95% of patients with NCPF and EHPVO present with variceal bleeding, treatment involves management with endoscopic sclerotherapy (EST) or variceal ligation (EVL). These therapies are effective in approximately 90–95% of patients. Gastric varices are another common cause of upper gastrointestinal bleeding in these patients and these can be managed with cyanoacrylate glue injection or surgery. Other indications for surgery include failure of EST/EVL, and symptomatic hypersplenism. The prognosis of patients with NCPF is good and 5 years survival in patients in whom variceal bleeding can be controlled has been reported to be approximately 95–100%.

© 2002 Blackwell Publishing Asia Pty Ltd
β ‐Catenin expression in hepatocellular carcinoma: A possible participation of β ‐catenin in the dedifferentiation process
Authors: Suzuki Tetsuya , Yano Hirohisa , Nakashima Yutaka , Nakashima Osamu , Kojiro Masamichi
Published: March 2003

Background: β‐Catenin is known as a multifunctional protein acting as a regulator of the cadherin‐mediated cell–cell adhesion system and in the Wingless/Wnt signal transduction pathway. Recent studies reported mutation of the β‐catenin gene in some tissues of hepatocellular carcinoma (HCC).

Methods: ‘Nodule‐in‐nodule’ appearance is a feature of well‐differentiated HCC containing a distinct nodule of less‐differentiated cancer tissue inside, and it is presumed to be a morphological expression of the dedifferentiation process. The present study immunohistochemically investigated the β‐catenin expression according to the dedifferentiation process of HCC, that is, in small well‐differentiated HCC with indistinct margins, HCC with a ‘nodule‐in‐nodule’ appearance, moderately differentiated HCC, which does not have a ‘nodule‐in‐nodule’ appearance, and sarcomatous HCC.

Results: The expression of β‐catenin was observed in approximately 70% of small well‐differentiated HCC with indistinct margins. In HCC with a ‘nodule‐in‐nodule’ appearance, membranous expression of β‐catenin was higher in the well‐differentiated cancer tissues than in the less‐differentiated cancer tissues (P < 0.01), cytoplasmic expression was higher in the less‐differentiated cancer tissues (P < 0.01), and nuclear expression was higher in the less‐differentiated cancer tissues (P < 0.001). In moderately differentiated HCC, tumors with membranous expression of β‐catenin had more frequent intrahepatic metastasis than those without having the expression (P < 0.001).

Conclusions: Accumulation of β‐catenin was already present in the early stage of HCC, and in less‐differentiated cancer tissue the membranous expression of β‐catenin could be related to intrahepatic metastasis.

© 2002 Blackwell Publishing Asia Pty Ltd
Cholangiocarcinoma: Recent progress. Part 2: Molecular pathology and treatment
Authors: Okuda Kunio , Nakanuma Yasuni , Miyazaki Masaru
Published: March 2003

Part 2 of this review discusses DNA damage in biliary epithelial cells in the development of cholangiocarcinoma, alterations in cell kinetics of biliary epithelial cells, biliary epithelial mitoinhibition, and apoptosis that includes the role of Bcl‐2, transforming growth factor‐β, telomerase activities and deregulation of Ras and p53, cancer‐associated antigens in cholangiocarcinoma, precancerous lesions, stroma formation and angiogenesis, cancer invasion, cell–cell and cell–matrix interactions, and the mechanism of evasion from immune surveillance. These discussions are followed briefly by treatments such as photodynamic therapy, and surgical approaches comparing resection and liver transplantation.
Changes in autonomic nervous activity during endoscopic retrograde cholangiopancreatography: A possible factor in cardiac complications
Authors: Ochi Yoshie , Nomura Masahiro , Okamura Seisuke , Yano Mitsuyasu , Saito Ken , Nakaya Yutaka , Ito Susumu
Published: March 2003

Background and Aims: The changes of autonomic nervous activity during endoscopic retrograde cholangiopancreatography (ERCP) are closely related to the development of cardiovascular complications, such as arrhythmias and acute coronary syndrome. In the present study, the correlation between changes in hemodynamics and autonomic nervous activity during ERCP procedures was evaluated by analyzing heart rate variability and blood catecholamine levels.

Methods: Twenty‐three patients who underwent ERCP (ERCP group) and 15 control subjects who were only premedicated (C group) were studied. Ambulant ECG, blood pressure, arterial oxygen saturation, and blood level of catecholamine were measured. Autonomic nervous function was assessed by analyzing the spectral analysis and 1/f fluctuation. The low frequency power (LF power; 0.04–0.15 Hz), high frequency power (HF power; 0.15–0.40 Hz, indicator of parasymapathetic tone), the ratio of LF power to HF power (LF/HF ratio, indicator of sympathetic tone), and 1/f fluctuation (indicator of pleasant mood) were calculated.

Results: Blood pressure and heart rate were increased and arterial oxygen saturation was decreased in the ERCP group during the endoscopic procedure. Changes in the parameters of autonomic nervous function (LF power, HF power, LF/HF ratio, and 1/f fluctuation) were significantly greater in the ERCP group than in the C group, especially during cholangiography. Moreover, blood levels of catecholamines were significantly increased during the ERCP procedure. In the C group, however, blood levels of catecholamines did not significantly change except directly after premedication.

Conclusions: Autonomic nervous activity varied greatly during cholangiography, demonstrating that ERCP has more than a little influence on the cardiovascular system. The results of the present study indicated that attention should be focused on changes in hemodynamics in patients with cardiovascular complications by monitoring the aforementioned hemodynamic parameters during ERCP.

© 2002 Blackwell Publishing Asia Pty Ltd
Expression of mRNA for glucocorticoid receptors in peripheral blood mononuclear cells of patients with Crohn's disease
Authors: Hori Takashiro , Watanabe Kouichi , Miyaoka Masaaki , Moriyasu Fuminori , Onda Kenji , Hirano Toshihiko , Oka Kitaro
Published: March 2003

Background: The amount of glucocorticoid (GC) receptors (GR) in immune cells might be critical for successful GC treatment of patients with Crohn's disease (CD). However, little is known about the expression of GR in CD; therefore, we carried out quantitative analyses for GR messenger (m)RNA expression in peripheral‐blood mononuclear cells (PBMC) of CD.

Methods: Seventeen patients with CD and 33 healthy subjects entered into this study. We measured the GRα mRNA level in the PBMC of these subjects by a reverse transcription‐competitive polymerase chain reaction procedure. Relative amounts for GRβ mRNA were obtained semiquantitatively.

Results: The amounts of GRα‐mRNA in the CD patients and healthy subjects were 0.053 ± 0.052 and 0.130 ± 0.108 (copies/copies of β‐actin mRNA), respectively. The former value was significantly lower than that of the latter (P < 0.01). The rates of the CD patients and healthy subjects expressing GRβ‐mRNA in PBMC were 41.2% and 45.5%, respectively, and there was no significant difference in the rates between the two groups (P = 0.339). However, the relative amounts of GRβ‐mRNA in the PBMC were estimated to be 1.053 × 10−5 ± 2.540 × 10−5 for the CD patients, and 1.872 × 10−5 ± 3.252 × 10−5 (fluorescence intensity/copies of β‐actin mRNA) for the healthy subjects, and the former was significantly smaller than the latter (P < 0.05). Moreover, there was an inverse correlation between the duration of disease (year) and the amounts of GRα‐mRNA in the PBMC of the CD patients (P < 0.05).

Conclusions: The amounts of GRα‐mRNA and GRβ‐mRNA in the PBMC of the CD patients were lower than those of the healthy subjects. The duration of disease correlated with decreased amounts of GRα‐mRNA in the PBMC. Furthermore, the clinical significance of the GR‐mRNA status in the PBMC remains to be elucidated.
Is delayed normalization of alanine aminotransferase a poor prognostic predictor in chronic hepatitis C patients treated with a combined interferon and ribavirin therapy?
Authors: HUNG CHAO‐HUNG , LEE CHUAN‐MO , LU SHENG‐NAN , WANG JING‐HOUNG , TUNG HUNG‐DA , CHEN TSUNG‐MING , CHEN CHIEN‐HUNG , CHANGCHIEN CHI‐SIN
Published: March 2003

Background and Aims
: Decreased alanine aminotransferase (ALT) level is the accepted basic indicator of an interferon (IFN) therapeutic effect in chronic hepatitis C. This study assessed whether delayed normalization of ALT predicts a poor response to a combined therapy of IFN and ribavirin in patients with chronic hepatitis C virus (HCV) infection.

Methods:
Patients were treated with IFN‐α 2b three times weekly and oral ribavirin for 24 weeks. The ALT values were assessed monthly and patterns of changes in ALT activity were analyzed. Serum HCV‐RNA was checked at weeks 0, 12, 24, and 48.

Results:
A total of 103 patients completed therapy and 69 (67%) of them achieved a sustained viral response (SVR). There was no significant difference in the SVR between patients with or without early normalization (week 12) of ALT level (69 vs 56%). Of the sustained responders, nine patients (13%) with delayed ALT normalization had a SVR. Nine of the 12 patients (75%) with abnormal ALT and negative HCV‐RNA at week 12 had a SVR compared with none of four patients who had positive HCV‐RNA at week 12 (P = 0.0192).

Conclusions:
Lack of normalization of the ALT level at week 12 does not preclude successful virological outcome in hepatitis C patients receiving a combined therapy of IFN and ribavirin. Hepatitis C virus RNA at week 12 may be a useful predictor of treatment outcome in patients without early biochemical response.

© 2002 Blackwell Publishing Asia Pty Ltd
Renal tract abnormalities detected in Australian preschool children
Authors: HOGG RJ , HARRIS S , LAWRENCE DM , HENNING PH , WIGG N , JUREIDINI KF
Published: March 2003

Objective:

To quantify the incidence of abnormalities in urinalysis and blood pressure from preschool children and their predictive value in detecting renal disease within an Australian community.

Methodology:

Urine samples, blood pressure and height measurements and parental reports of significant medical problems were collected from a total of 9355 South Australian preschool children. Seven hundred and forty‐three children with abnormal results were investigated in a nephrology outpatient clinic. A control group of 357 children with no detectable abnormality were also recalled, examined and, where appropriate, investigated.

Results:

Nine thousand, three hundred and fifty‐five children were tested. Of these, 0.81% were shown to have a clinically significant renal tract abnormality. The findings included children with urinary tract infections, vesico‐ureteric reflux, glomerular disease, renal calculi, essential hypertension and a renal neoplasm. While dipstick‐based methods were the most specific indicators of renal tract abnormalities, measurement of blood pressure and urinary β2‐microglobulin were also important in detecting abnormalities. Screening for glycosuria did not result in the detection of significant undiagnosed abnormalities. In the control group with no abnormality detected at testing, there was one case each of aortic coarctation, polycystic kidney disease and vesico‐ureteric reflux diagnosed.

Conclusion:

Undiagnosed renal tract abnormalities are present in many Australian preschool children. Most are detectable by a thorough history, examination and urinalysis.
A Chinese girl with Leigh syndrome: Effect of botulinum toxin on dystonia
Authors: LEUNG TF , HUI J , YEUNG WL , GOH K
Published: March 2003

Leigh syndrome is a form of neurodegenerative disease which is associated with intracranial infarcts. The diagnosis is made by finding hyperlactacidaemia together with cerebral infarcts on neuroimaging. We report a 4‐year‐old Chinese girl with Leigh syndrome who had several atypical features. She presented with generalized dystonia and developmental regression. In addition, she suffered from an unusual feature of bladder dystonia. This patient appeared to be suffering from respiratory chain complex I deficiency from studies on cultured skin fibroblasts. Assays for respiratory chain enzymes as well as mitochondrial DNA point mutations and major deletions in muscle were normal. Dystonia persisted despite treatments with muscle relaxants and a ketogenic diet. Intramuscular botulinum toxin resulted in significant relief of dystonia.
Deflazacort treatment in progressive diaphyseal dysplasia (Camurati–Engelmann disease)
Authors: Baş F , Darendeliler F , Petorak İ , Sadikoğlu B , Bilir A , Bundak R , Saka N , Günöz H
Published: March 2003

Abstract: Progressive diaphyseal dysplasia (PDD), a rare disorder of bones, in recent years has been accepted as a systemic disease within the spectrum of connective tissue disorders associated with immunological abnormalities. Steroids have been used in the treatment of PDD with variable success. In this report PDD is described in a 5‐year‐old boy who presented with leg pain, fatigue, headache and anorexia with an onset in infancy. Physical examination revealed a waddling gait, thorax deformity and thickening in the upper extremities. The diagnosis was made by radiologic demonstration of cortical thickening and a narrowed medullary cavity of the long bones of extremities. Bone scintigraphy showed areas of increased osteoblastic activity in the diaphyseal part of the long bones of extremities and the skull. Electron microscopic examination revealed myopathic and vascular changes. Serum immunoglobulin A, G and M levels were elevated and CD4 positive T cell numbers were low. Deflazacort, a steroid with a similar anti‐inflammatory effect to prednisolone but with fewer adverse effects, was started in a dose of 1.2 mg/kg/day. Deflazacort treatment resulted in clinical and radiological improvement within 12 months with no side effects. In conclusion, steroids may be recommended as an effective method of treatment in PDD and deflazacort may be a safe alternative steroid.
Rett syndrome: Clinical update and review of recent genetic advances
Authors: Ellaway C , Christodoulou J
Published: March 2003

Abstract: Rett syndrome, a severe neurodevelopmental disorder occurring almost exclusively in females, is thought to be the second most common cause of profound mental retardation in females after Down syndrome. Recent genetic advances suggest the gene for Rett syndrome to be located on the distal arm of the X chromosome, Xq28. This manuscript reviews the clinical phenotype, natural history and current genetic understanding of the disorder.
Difference in susceptibilities of different cell lines to bilirubin damage
Authors: Ngai K‐C , Yeung C‐Y , Leung C‐S
Published: March 2003

Objective: To investigate if there are differences in susceptibilities to bilirubin toxicity of different cell lines.

Methodology: A modified 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method was adopted to study the cytotoxic effect of bilirubin on several commercially available cell lines including human glioblastoma (ATCC CRL 1690, T98G), human neuroblastoma (ATCC HTB‐10, SK‐N‐MC), human liver (ATCC CCL 13, Chang Liver, HeLa markers) and a mouse fibroblast (ATCC CCL‐1, NCTC Colon 929).

Results: Cytotoxicity was observed when certain bilirubin:albumin molar ratios were exceeded in the medium of a cell line in culture. Different cells exhibited different susceptibilities to the cytotoxic effects of bilirubin; neuroblastoma and glioblastoma were most susceptible, fibroblasts were the least vulnerable.

Conclusions: Our findings have confirmed the clinical impression that different cells sustain different degrees of cytotoxicities caused by bilirubin.
Prevalence of childhood asthma, allergic rhinitis and eczema in Urumqi and Beijing
Authors: Zhao T.B , Wang AJ , Chen YZ , Xiao ML , Duo LK , Liu G , Lau YL , Karlberg J
Published: March 2003

Objective: To assess the prevalence of asthma and other allergies in children in Urumqi and Beijing, compared with that in Hong Kong.

Methods: A total of 7754 primary school students were randomly selected to participate in the study. Data were collected in 1995–96 using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol for 6‐ and 7‐year‐olds. The study design and data quality assurance in all aspects followed the protocol, including the double entry of data.

Results: The questionnaire response rate was high (98.9%). Beijing children reported significantly more asthma than those living in Urumqi in three categories: wheezing or whistling in the chest in the past year (6.0%, 95% confidence interval (CI): 5.1–6.9%vs 2.9%, 2.3–3.5%, P < 0.001), sleeping disturbed due to wheezing (1.3%, 0.9–1.7%vs 0.6%, 0.3–0.9%, P < 0.03) and having experienced asthma ever (10.7%, 9.6–11.8%vs 7.6%, 6.6–8.6%, P < 0.001). The prevalence of allergic rhinitis (30.0%vs 31.1% estimated as 12‐month nasal symptoms in Beijing and Urumqi, respectively) and eczema (2.8%vs 2.0% recorded as 12‐month itchy rash) in the two cities were not significantly different. A similar study was also performed in Hong Kong in 1995 using the same ISAAC protocol. The children in Urumqi and Beijing had fewer (P < 0.05) allergic symptoms compared to those living in Hong Kong (n = 3618). The 12‐month prevalence of wheezing, nasal symptoms and itchy rash found in Hong Kong were 9.2% (95% CI: 8.2–10.2%), 35.1% (33.5–36.7%) and 4.2% (3.5–4.9%), respectively.

Conclusion: Urumqi, Beijing and Hong Kong represent communities at different stages of westernization and the results from these three cities reflect a worldwide trend for an increasing prevalence of allergies along with westernization. These three cities could assist in identifying risk factors involved in the increase in asthma, allergic rhinitis and eczema.
Methaemoglobinaemia secondary to topical lignocaine/ prilocaine in a circumcised neonate
Authors: Couper Rtl
Published: March 2003

Abstract: The use of topical lignocaine/prilocaine (EMLA®, Astra Pharmaceuticals, North Ryde, NSW, Australia) for pain relief for neonatal circumcision is becoming more prevalent. Because of immaturity of the methaemoglobin reductase pathway, the neonate is vulnerable to methaemoglobinaemia which is a recognized complication of prilocaine therapy. This is the second report of methaemoglobinaemia due to the use of EMLA® in associateion with circumcision during the newborn period.
Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment
Authors: Harris M , Hauser S , Nguyen TV , Kelly PJ , Rodda C , Morton J , Freezer N , Strauss BJG , Eisman JA , Walker JL
Published: March 2003

Objective: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids.

Methodology: A cross‐sectional comparison of lumbar spine‐bone mineral density (LS‐BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid.

Results: Weight was the only independent predictor of LS‐BMD (r2 = 0.38). Children receiving greater than 800 μg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight‐adjusted LS‐BMD than children treated with 400–800 μg/day of inhaled corticosteroid (mean difference: 0.06 g/cm2, 95% confidence interval (CI): – 0.02 to – 0.10). A significant difference in weight‐adjusted LS‐BMD persisted when all children receiving greater than 800 μg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400–800 μg/day of inhaled corticosteroid (mean difference: – 0.05 g/cm2, 95%CI interval: –0.02 to – 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400–800 μg/day of inhaled corticosteroid.

Conclusions: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.
Review of the outcome of management of Graves’ disease in children and adolescents
Authors: Bergman P , Auldist AW , Cameron F
Published: March 2003

Objective: To review our recent experience in the management of paediatric Graves’ disease, the leading cause of hyperthyroidism in childhood, in view of ongoing international debate regarding therapy.

Methodology: Retrospective medical record review of patients with Graves’ disease, treated between 1985 and 1999, at the Royal Children’s Hospital, Melbourne.

Results: Forty patients, aged at diagnosis between 2.9 and 17.6 years (median age 11 years; 31 females), were treated. Thirty‐three patients received either definitive therapy or at least 24 months medical therapy and follow up at the time of the study. Six patients experienced successful remission upon withdrawal of medication (median medication duration 3.2 years; four females; median follow up 4.1 years). Children successfully achieving remission were younger at presentation than those requiring surgery (9.5 vs 12.9 years, respectively; P = 0.01). Ten patients were treated surgically, leaving 4–6 g residual thyroid tissue. Surgical indications included failed initial medical therapy, relapse after medication cessation, non‐compliance and significant medication side effects. During a median follow up of 1.7 years (range 0.2–5 years), three of 10 patients have subsequently relapsed and four of 10 patients are receiving postoperative thyroxine replacement. Transient hypocalcaemia occurred in five patients and temporary recurrent laryngeal nerve palsy occurred in two patients.

Conclusions: Fewer than 20% of children experienced successful sustained remission at median follow up of 3.2 years. Medication remains a well‐tolerated therapeutic option. Surgery is a reasonable alternative when there are specific indications. In order to decrease the likelihood of surgical relapse, less than 4 g thyroid tissue should be left postoperatively.
A 10‐year serogroup B meningococcal disease epidemic in New Zealand: Descriptive epidemiology, 1991–2000
Authors: Baker MG , Martin DR , Kieft CEM , Lennon D
Published: March 2003

Objective: New Zealand has experienced an epidemic of meningococcal disease since 1991. This paper describes the characteristics of this epidemic during its first 10 years (1991–2000), current control measures, and potential future interventions.

Methodology: Meningococcal disease surveillance in New Zealand uses combined notification and laboratory data. Population census data from 1991 and 1996 were used to calculate disease rates.

Results: The annual incidence of meningococcal disease increased from 53 cases (1.6 per 100 000 population) in the pre‐epidemic year of 1990 to a peak of 613 (16.9 per 100 000) in 1997, followed by consistently raised rates. Over the 1996–2000 period, there was an average of 502 cases per year (13.9 per 100 000). The epidemic has resulted in 3547 cases since 1991; approximately 3000 in excess of the number expected based on pre‐epidemic disease incidence. Of the total cases, 158 (4.5%) were fatal. A disproportionately large number of cases have been in Maori and Pacific Islands children in the northern part of the North Island of New Zealand. Since 1991, the epidemic has increasingly been dominated by serogroup B meningococci with subtype P1.7b,4, which by 2000 accounted for 84.6% of all cases for whom this testing was carried out. The majority of these organisms were characterised as B:4:P1.7b,4.

Conclusion: Meningococcal disease rates are likely to remain elevated in New Zealand for at least several more years. A vaccine which could induce immunity to the P1.7b,4 PorA subtype may have a role in controlling this epidemic. Efforts are underway to obtain and trial such a vaccine. Measures are also underway to reduce overcrowded living conditions which are contributing to the epidemic. Early recognition and antibiotic treatment of cases improves outcomes and should continue to be promoted. Integrated notification and laboratory‐based surveillance of meningococcal disease provides relatively complete surveillance of this disease in New Zealand and has supported the development of public health interventions.
Maternal transmission of infectious pathogens in breast milk
Authors: Jones CA
Published: March 2003

Abstract: Breast milk provides a superior source of nutrition and many other health benefits to the newborn infant. However, breastfeeding has also been recognized as a route of transmission to the newborn of some important pathogens that may result in disease. In the present article, up‐to‐date research and recommendations on the maternal transmission of infectious pathogens in breast milk or by breastfeeding are discussed in the context of local epidemiology and in the setting of an industrialized country.
Clinical risk factors but not bone density are associated with prevalent fractures in prepubertal children
Authors: Ma DQ , Jones G
Published: March 2003

Objective:  The aim of this study was to investigate the association of clinical risk factors and bone density with prevalent fractures in prepubertal children.

Methods:  Bone mineral density (BMD) in lumbar spine, femoral neck and total body bone was assessed by dual‐energy X‐ray absorptiometry. Clinical data on risk factors were collected by measurement and questionnaires.

Results:   Of 324 children, 32 (10%) had a prevalent fracture (upper limb 69%). Most fractures were due to low‐energy falls at home (69%). Children with fractures were older (P = 0.04), had higher levels of sports participation (P = 0.03), lower levels of breastfeeding (P = 0.05) and tended towards higher usage of inhaled corticosteroids in the previous year (P = 0.05). However, both BMD and apparent BMD did not differ between those with and without prevalent fracture. No differences were observed in the proportion of maternal fractures, maternal smoking during pregnancy, asthma history and oral prednisolone in last year (all P > 0.05). A final model incorporating age, weight, height, breastfeeding history, sports participation and inhaled corticosteroid usage accounted for 10% of the variability in the odds of fracture (P = 0.03).

Conclusion:  These results suggest that BMD may be less important than clinical risk factors for total fracture risk in prepubertal children. However, sample size limitations mean that further investigation in larger populations with less heterogeneity in fracture types is warranted.
Paediatric narcolepsy: Complexities of diagnosis
Authors: Hood BM , Harbord MG
Published: March 2003

Abstract:  Narcolepsy is a sleep disorder that is characterized by excessive daytime sleepiness and the inappropriate intrusion of aspects of rapid eye movement sleep into wakefulness. While the disorder emerges from an interplay of genetic and environmental factors, recent findings suggest that abnormalities in the neurotransmission of hypocretin may be implicated in its pathogenesis. Although narcolepsy has typically been associated with adulthood, there is a growing evidence base for the emergence of the disorder in childhood. We report suspected narcolepsy in early infancy, highlighting both the complexities of presentation and subsequent diagnosis associated with paediatric narcolepsy, and the significant psychosocial difficulties experienced by children and families managing this disorder.
Sepsis in neonatal intensive care in the late 1990s
Authors: Mehr SS , Sadowsky JL , Doyle LW , Carr J
Published: March 2003

Aim:  To determine the incidence and clinical characteristics of sepsis in ventilated infants from an Australian neonatal intensive care unit (NICU) in the late 1990s.

Methods:  Demographic data was collected from babies requiring assisted ventilation (AV) over the 6‐month period from 1 July to 31 December 1998. Sepsis was divided into early onset sepsis (EOS; ″ 72 h of age) and late onset sepsis (LOS; >72 h of age), including both definite (culture‐proven + abnormal markers) and probable (culture negative + abnormal markers) episodes.

Results:  Two hundred and eleven babies required AV over this period. Of these, 64 (30.3%) had at least one infection, with 85 episodes of sepsis (40.3 episodes per 100 admissions requiring AV). There were 22 babies with 22 episodes of EOS, and 45 with 63 episodes of LOS. Three babies had both EOS and LOS. The rate of EOS was 10.4 infected infants (10.4 infections per 100 admissions requiring AV). The rate of LOS was 21.3 infected infants (29.9 infections per 100 admissions requiring AV). The rates of both EOS and LOS were higher than previously reported by Australian studies in the early 1990s. In both EOS and LOS, risk factors for infection were common. Group B streptococcus was the commonest cause of definite EOS. The mortality rate from sepsis in the EOS group was 14% (3/22). Coagulase‐negative staphylococci were the commonest cause of LOS. The mortality rate from sepsis in the LOS group was 11% (5/45).

Conclusions:  EOS and LOS are significant problems in ventilated NICU infants in the late 1990s.
Variation in mortality and intraventricular haemorrhage in occupants of Pacific Rim nurseries
Authors: Martinez A , Taeusch HW , Yu V , Tan KW , Yeung C‐Y , Lu J‐H , Nishida H , Boo N‐Y
Published: March 2003

Objective:  A network of neonatal intensive care units in Pacific Rim countries was formed to compare infant risk factors, clinical practices, and outcomes for very low birthweight infants.

Methodology:  A multicentre, prospective study compared outcomes for infants born smaller than 1501 g or at less than 31 weeks gestation.

Results:  Gestational age‐specific survival and incidence of intracranial haemorrhage varied for infants born in these nurseries. We found differences in infant risk factors among the nurseries. There were also significant differences in the use of antenatal steroids, but similar rates for Caesarean section and surfactant treatment. The factor most predictive of neonatal death and severe intracranial abnormality was an elevated Clinical Risk Index for Babies (CRIB) score. Antenatal steroid treatment (>24 h prior to delivery) was associated with improved survival and decreased incidence of severe intracranial abnormalities. Antenatal steroid treatment for less than 24 h prior to delivery was not associated with improved survival. Caesarean delivery was associated with improved survival, but showed no benefit regarding the incidence of severe intracranial abnormality.

Conclusions:  Our Pacific Rim nursery network found differences in neonatal outcomes that correlated best with measures of neonatal risk at birth, antenatal steroid treatment, and Caesarean delivery. These data emphasize the importance of obstetric care to improve postnatal outcomes in premature infants, and highlight the usefulness of CRIB scores in these patients.
Customer focus: Patient, organization and EQuIP in collaboration
Authors: Sheahan M
Published: March 2003

Abstract The Australian Council on Healthcare Standards (ACHS) Evaluation and Quality Improvement Program (EQuIP) calls on healthcare organizations to increase their focus on patients by using leadership to coordinate, and continuous improvement to guide, care delivery. At a large acute care private facility in Melbourne, a program has been developed to create a ‘care partnership’, characterized by shared decision making, collaboration and conciliation. This program enhances patient care through the coordination of three strategies, a patient communication strategy, an evaluation strategy and a quality improvement strategy. The program has resulted in patient guided reforms such as redesign of a patient information booklet, a hospital‐wide discharge planning improvement initiative and a hospital‐wide strategy to improve pain management. Through the creation of a care partnership, this program helps an acute care hospital focus its services and processes on one of its key customer groups, patients.
A prospective, physician self‐reported adverse incident audit on a general medical unit
Authors: Witham Miles D , Kendall Peter A
Published: March 2003

Abstract There is some evidence that physician self‐reporting is an efficient and effective way of collecting data on adverse incidents in health care. This study tested a simple prospective adverse incident audit, self‐reported by physicians, on a general medical unit. A total of 158 reports were collected over a 6‐month period covering a wide range of quality issues, including, but not limited to, safety issues. One‐third of reported incidents occurred within 48 h of hospitalization. One‐half of incidents were associated with harm or inconvenience to patients. Reported incidents fell into easily classifiable groups, and the data was used as a platform for a coordinated approach to quality improvement within the department. It is concluded that this technique is an easily implementable addition to the more traditional methods used for quality improvement within general medicine.
Use of clinical audit for revalidation: Is it sufficiently accurate?
Authors: Jutley Rajwinder S , Mckinley Aileen , Hobeldin Mohammed , Mohamed Anies , Youngson George G
Published: March 2003

Abstract In order to provide better patient care, clinicians will be subject to revalidation and re‐certification. This may be partially based on existing and ongoing data collection, yet many units fail to incorporate mechanisms that validate the data that may be used. The accuracy of audit data was evaluated in a unit that has been using commercially available audit software for over 10years. A total of 655 consecutive surgical admissions were documented over a 6‐month period and errors in data collection and entry were gathered and analyzed. An overall accuracy of 90.5% was confirmed but examination of the data found them to be open to misinterpretation. Moreover, 13% of errors were made during a single week when locum staff were involved. The study highlights the fallibility of data collection during audit, and urges caution if using such data when judging performance‐related issues as part of the process of appraisal.
Facilitating best practice: Transferring the lessons of the Clinical Support Systems Program
Authors: Long Paul W , Larkins Richard G , Patterson Craig Glenroy , Hyde Jim
Published: March 2003

Abstract The Clinical Support Systems Program (CSSP) includes the management of clinical practice using clinical and consumer pathways, outcome and performance indicators, clinical measurement and review in a continuous improvement cycle using the best available extant evidence. The Royal Australasian College of Physicians is testing the CSSP model through four consortia around Australia. There are 17 project sites in three States. The funded projects address major clinical problems including congestive heart failure and acute coronary syndromes, acute stroke management, and colorectal cancer care. There is some early evidence of the CSSP influencing change in areas beyond the bounds of the project settings and the College has developed a plan to promote wider adoption of best practice. This approach recognises the College’s role in providing Fellows with the practical tools of quality improvement, the means to collect data and compare their practice to other clinicians, while traversing the appropriate educational framework.
Assessment of critical loading of lakes as a basis for remedial measures: A review of fundamental concepts
Authors: Håkanson Lars
Published: March 2003

Lake ecosystems throughout the world are threatened by numerous chemicals. Most people have heard about the major chemical threats to aquatic systems, such as mercury, radionuclides, sulphur and acid rain, and nutrients causing eutrophication effects. How are these threats manifested in ecosystems? What is threatened and why? What can be done for remediation? The complexity of ecosystems has often led to the predictive failure of ecosystems models, and a decade ago these models were rightly regarded with suspicion. At that time, many lake models predicted target variables, such as mean concentrations of toxins in water, sediments and fish, within a factor of 10. There has been very rapid development in predictive modelling for water pollutants during recent years. Today, lake models for water pollutants predict as well as can be measured (i.e. within a factor of 0.25–0.5). One major reason for this rapid development is the Chernobyl accident. Large quantities of radiocaesium were released in a pulse during April–May 1986. In order to follow the radiocaesium along ecosystem pathways, the identification of fundamental transport processes and the structuring of models has been developed. To obtain a high predictive power in ecosystem models, it is crucial to include only the key processes (the optimal size problem). Effect‐load‐ sensitivity (ELS) models play a paramount role in the environmental sciences and lake management. The aim of ELS models is to provide quantitative predictions relating operationally defined ecological effect variables to load and environmental sensitivity variables. Validated ELS models provide a tool to simulate practically feasible remedial measures, and important concepts like critical load, natural load and guideline limits/values can be defined from ELS models. The first objective of this paper is to discuss some basic structures, principles and components of ELS models. Empirical (static) and dynamical (time‐dependent) ELS models exist for mercury, radiocaesium and phosphorus in lakes. These models have high predictive powers for a wide range of validation lakes. The second objective of this paper is to demonstrate what can actually be done in water management in terms of remediation of the effects asociated with acidification (lake liming), eutrophication and contamination by mercury and radiocaesium.
Optical and biological properties of Lake Ülemiste, a water reservoir of the city of Tallinn II: Light climate in Lake Ülemiste
Authors: Reinart A. , Arst H. , Erm A. , Trei T. , Hussainov M.
Published: March 2003

Underwater light climate in strongly eutrophic Lake Ülemiste was studied by applying in situ measurements and model calculations. The attenuation of light in the waters of Lake Ülemiste is rather high, with a diffuse attenuation coefficient of photosynthetically active radiation, spectral region 400–700 nm (PAR) being 1.0–3.3 m–1. From the subsurface irradiance, only 3–13% reaches the depth of 1 m. However, in most cases, 1% from the irradiance just under the surface of water is available at the average depth (2.5 m) of the lake. A simple model is used for an approximate description of the temporal variation of underwater PAR at different depths. The initial data are the episodically determined values of the diffuse attenuation coefficient of PAR, Kd,PAR and the values of continuously recorded incident irradiance. Light is limiting phytoplankton growth in Lake Ülemiste only for a very short time each year: in early spring and late summer. The study should be continued to investigate the effect of artificially regulated influx and outflow of water and nutrients to toxic cyanobacteria blooms in this lake.
Trophic state, fish community and intensive production of salmonids in Alicura Reservoir (Patagonia, Argentina)
Authors: Temporetti P. F. , Alonso M. F. , Baffico G. , Diaz M. M. , Lopez W. , Pedrozo F. L. , Vigliano P. H.
Published: March 2003

The Governments of the Provinces located in Patagonia, Argentina, promote the intensive breeding of salmonids in the Andean Patagonian region. Although annual production is low (450 ton ha–1 year–1), some effects are significant. Waste produced by salmonid breeding (feed losses, faeces and excretion) increases nutrient and organic matter concentrations, which cause modifications of water quality, sediments and biota. A consequent risk is the elevation of eutrophication levels. Possible changes in water composition, sediments, algae and wild fish populations were studied. Sites affected by fish farming showed increased nutrient concentration, and phytoplankton and periphyton biomass. Chlorophyll a was similar at both sites (affected and unaffected by fish farm sites). Sediments clearly reflect fish farm waste inputs: total phosphorus and organic matter increased 12‐fold and fourfold, respectively. The species present in the gill‐net catches were the autochthonous Percichthys trucha, Odontesthes hatcheri, Diplomystes viedmensis, and the introduced salmonids Oncorhynchus mykiss, Salmo trutta, Salmo salar sebago and Salvelinus fontinalis. About 50% of the total catch was salmonids. A major portion of the catch per unit weight was composed of rainbow trout, followed by perch. The catch per unit weight obtained for this reservoir agrees with the range of values previously determined (Quiros 1990) for Patagonian reservoirs. Compared with previous studies by Freyre et al. (1991), a variation in catch composition exists. This consists mainly of an increase in the numbers and condition of O. mykiss and a decrease in P. trucha. Presence of fish that escaped from hatcheries, recognizable by their eroded fins, was observed; particularly in a sampling station near the fish cage systems. Variations in catches could be caused by cyclical changes in fish populations (Wooton 1991), by direct and indirect effects of intensive fish farming, or by a combination of both events, and can only be understood through long‐term studies of catch variation.
Application of integrated environmental management through the preparation of an environmental action programme: Case study from the Songkhla Lake Basin in southern Thailand
Authors: Chufamanee Pakawan , Lønholdt Jens
Published: March 2003

The concepts and principles for integrated environmental management (IEM), which is based on a strategic and participatory approach to environmental and regional planning, has been successfully applied to a large lake system in the southern region of Thailand. The application was achieved through the Danish Cooperation for Environment and Development funded project ‘Environmental Management in the Songkhla Lake Basin’ (EmSong Project) in the Office of Environmental Policy and Planning within the Ministry of Science, Technology and Environment. Through the application of the methods and tools for IEM, including the use of a participatory and strategic planning approach, and the establishment of a comprehensive database and an integrated surface water model for the lake system, an environmental action programme (EAP) has been developed. This action programme, which is based on a broad consensus at the local and regional level, includes vision and mission statements, resource objectives and strategies for management from an economically and ecologically important lake system in Thailand. The operational part of the EAP is a project catalogue, which contains immediately needed projects described to an international pre‐feasibility level. The former is the tangible output of the EmSong Project. A more intangible output from the EmSong Project is committed and informed local and regional government and community‐based organizations.