bluuebunny/crossref_metadata_2025 huggingface dataset:
Japan's contribution to clinical pediatrics research in the last decade
Authors: Okamoto Shigeru , Rahman Mahbubur , Fukui Tsuguya
Published: January 2004

Abstract
Objective
: To determine Japan's contribution to research in clinical pediatrics over the last decade.

Methods
: Articles published in highly reputable pediatrics journals from 1991−2000 were accessed through the MEDLINE database. The number of articles which had an affiliation with a Japanese institution were counted for each of the journals and also summed in total. Proportions of randomized controlled trials (RCTs) and case‐control/cohort studies among the articles from Japan were also generated and compared with the average for the entirety. In addition, shares of the top‐ranking countries were presented along with their trend over time.

Results
: In total, 20 189 articles were published in the selected seven pediatric journals from 1991−2000. Japan contributed 3.0% of these articles and this contribution was ranked 7th in the world. A negative trend was noticed in Japan's contribution over time but it was not statistically significant (z = −0.40, P = 0.16). RCTs accounted for 7.3% of the total articles, but only 0.34% of those from Japan.

Conclusions
: Japan's share of articles in pediatrics research was smaller than that in basic science and some of the other clinical fields. The number of articles from Japan providing a high level of evidence was meager in this field.
Effect of caudal block on stress responses in children
Authors: Tuncer Sema , Yosunkaya Alper , Reisli Ruhiye , Tavlan Aybars , CICekci Faruk , Otelcioglu Seref
Published: January 2004

Abstract
Background
: The present study was performed during lower abdominal and genitourinary surgery, to assess the effects of caudal block on plasma cortisol, prolactin, insulin and glucose concentrations during and after surgery.

Methods
: Thirty male children aged 3−10 years who were scheduled for elective surgery, were selected for the study. The children were premedicated with oral midazolam 0.5 mg/kg. All children received induction with nitrous oxide in oxygen and sevoflurane. The children were randomly allocated into two groups: Group I, control group (n = 15) and group II, caudal group (n = 15). Anesthesia was maintained by face mask with the same agent in both groups. Caudal block was performed with 0.25% bupivacaine 2 mg/kg after induction of anesthesia in the caudal group. Blood samples were obtained after induction of anesthesia (T0) in order to measure baseline concentrations of cortisol, prolactin, glucose and insulin. Additional samples were obtained 30 min after the start of surgery (T1), and 60 min after the end of surgery (T2).

Results
: All of the basal values (T0) were within the normal ranges accepted by Meram Medical Faculty of Selcuk University for children of this age group and there were no differences between the groups (P > 0.05). In both groups, glucose concentration increased at T1, compared with T0 and T2 values (P < 0.05). However glucose concentration was lower in the caudal group than in the control group at T1 (P < 0.05). In both groups, prolactin concentration increased at T1, compared with T0 (P < 0.05). The mean plasma prolactin and cortisol concentration were lower in the caudal group than the control group at T1 and T2 (P < 0.05). The mean insulin concentration was lower in the caudal group than the control group at T2 (P < 0.05).

Conclusion
: These results indicate that caudal anesthesia suppresses the metabolic and endocrine responses to stress associated with lower abdominal and genitourinary surgery in children.
A randomized controlled trial of amantadine plus interferon‐α2a vs. interferon‐α2a alone in naive patients with chronic hepatitis C randomized according to the early virological response to interferon‐α2a monotherapy
Authors: Angelico M. , Cepparulo M. , Angelico F. , Francioso S. , Barlattani A. , Di Candilo F. , Della Vecchia R. , Demelia L. , De Sanctis G. , Gentile S. , Grieco A. , Parruti G. , Sabusco G. , Tarquini L. , Tosti A. , Zaru S. ,   THE SMIEC 1 GROUP
Published: January 2004

Background : An early virological response to interferon‐α treatment is a strong predictor of sustained response, but it has never been exploited to stratify patients in clinical trials.

Aim : To evaluate the efficacy of amantadine plus interferon‐α compared with interferon‐α alone in naive patients with chronic hepatitis C who were randomized on the basis of the early virological response to interferon‐α.

Methods : One hundred and eighty‐one patients received recombinant interferon‐α2a (3 MU three times weekly) for 2 months and 164 were evaluated for early (i.e. month 2) virological response. Hepatitis C virus (HCV) RNA‐negative patients (n = 66) were randomized to receive 3 MU of interferon‐α three times weekly, with or without amantadine (200 mg/day); HCV RNA‐positive patients (n = 98) were randomized to receive 6 MU of interferon‐α three times weekly, with or without amantadine (200 mg/day). HCV RNA‐positive patients at 6 months discontinued treatment, and all others completed 12 months.

Results : At month 6, HCV RNA‐negative patients made up 54.2% of the interferon + amantadine group and 42.0% of the monotherapy group (P = 0.07). At month 12, HCV RNA‐negative patients made up 38.5% of the interferon + amantadine group and 28.4% of the monotherapy group (N.S.). The sustained virological response rates were 21.6% and 20.9%, respectively (N.S.).

Conclusion : The addition of amantadine does not enhance the sustained virological response to interferon‐α in naive patients with chronic hepatitis C; however, an additive effect of amantadine occurs in the first 6 months, mainly in patients without an early response to monotherapy. Early response to interferon‐α is a strong predictor of sustained virological response.
Viral clearance in HCV viraemic patients with normal alanine aminotransferase after combination therapy: a controlled, open‐labelled study
Authors: Mangia A. , Spinzi G. , Vuturo O. , Pazienza V. , Iacobellis A. , Piattelli M. , Giacobbe A. , Leandro G. , Piermanni V. , Minoli G. , Montalto G. , Andriulli A.
Published: January 2004

Background : In patients with chronic hepatitis C virus infection and persistently normal alanine aminotransferase levels, liver fibrosis has been reported in 0–22% of cases and advanced liver disease in 5–10% of cases.

Aim : To determine whether patients with persistently normal alanine aminotransferase levels clear infection after anti‐viral therapy at equal or different rates from infected patients with raised alanine aminotransferase levels.

Methods : Thirty‐five hepatitis C virus RNA‐positive patients with fibrosis at liver histology (Group 1) were matched for genotype, sex, age and histology with patients with raised alanine aminotransferase levels (Group 2). Both groups were treated with 3 MU interferon‐α2b plus ribavirin (1000–1200 mg) for 12 months.

Results : End‐of‐therapy response was achieved in 71.4%[95% confidence interval (CI), 56.4–86.3] of patients in Group 1 and in 52.3% (95% CI, 42.8–61.9) of those in Group 2 (P = 0.04). At week 72, 22 patients (62.8%; 95% CI, 46.8–78.1) in Group 1 and 50 patients (47.5%; 95% CI, 38.0–57.1) in Group 2 showed a sustained virological response (P = 0.11). Non‐1 genotype was the only independent predictor of sustained response (P = 0.002), with an odds ratio of 3.45 (95% CI, 1.58–7.50). At month 3 of therapy, the positive predictive values for non‐response were 100% and 96% in Groups 1 and 2, respectively.

Conclusions : Interferon and ribavirin induce comparable sustained virological response in patients with persistently normal or raised alanine aminotransferase levels. Stage 1 fibrosis, rather than alanine aminotransferase levels, may be the criterion on which to decide whether or not to treat patients with persistently normal alanine aminotransferase levels.
Combining infliximab and methotrexate in fistulizing Crohn's disease resistant or intolerant to azathioprine
Authors: Schröder O. , Blumenstein I. , Schulte‐Bockholt A. , Stein J.
Published: January 2004

Background : Crohn's disease is complicated by fistulas in 20–40% of patients at some time during the course of their illness. Azathioprine has been reported to heal fistulas in 30–40% of cases. Long‐lasting effects by the anti‐tumour necrosis factor‐α antibody infliximab most often require repeated infusions. Methotrexate has been shown to be an effective drug in maintaining remission in Crohn's disease.

Aim : To evaluate the combination of infliximab and methotrexate as therapy for fistulas in patients with Crohn's disease.

Methods : Twelve consecutive patients (mean age, 29.5 years) with fistulizing Crohn's disease resistant or intolerant to azathioprine were followed prospectively. Patients received three infusions of infliximab (5 mg/kg) and long‐term methotrexate (20 mg/week). Therapy success was defined as sustained closure of fistulas ≥ 6 months after fistula closure.

Results : In four of the 12 patients, complete closure of fistulas that persisted for ≥ 6 months (median follow‐up, 13.25 months) was observed. In three further patients, a partial response was noted. In five patients, persistent therapy success could not be achieved or therapy had to be stopped due to side‐effects.

Conclusions : A combination of infliximab with long‐term methotrexate may be a promising concept in fistulizing Crohn's disease. Our data indicate the need for larger controlled trials.
Clopidogrel plus omeprazole compared with aspirin plus omeprazole for aspirin‐induced symptomatic peptic ulcers/erosions with low to moderate bleeding/re‐bleeding risk — a single‐blind, randomized controlled study
Authors: Ng F.‐H. , Wong B. C.‐Y. , Wong S.‐Y. , Chen W.‐H. , Chang C.‐M.
Published: January 2004

Background : Clopidogrel causes significantly less symptomatic peptic ulcer disease and gastrointestinal bleeding than low‐dose aspirin in average‐risk patients. The gastrotoxicity of clopidogrel in patients with active peptic ulcer disease is unknown.

Aim : To compare the incidence of unhealed ulcers in patients receiving clopidogrel or aspirin.

Methods : Patients with aspirin‐induced peptic ulcer disease treated with omeprazole (20 mg/day) were randomized to receive clopidogrel (75 mg/day) or to continue with low‐dose aspirin. Success was defined as ulcer/erosion healing at the eighth week.

Results : One hundred and twenty‐nine patients were recruited (69 received clopidogrel and 60 continued with aspirin). Thirty‐one (45%) in the clopidogrel group and 25 (42%) in the aspirin group had a minor gastrointestinal bleed. No ulcer showed an adherent clot or visible vessel. The distributions of peptic ulcer disease were similar in the clopidogrel and aspirin groups (gastric ulcer: 41% vs. 40%; duodenal ulcer: 10% vs. 12%; gastric ulcer + duodenal ulcer: 6% vs. 3%; gastritis: 32% vs. 37%; duodenitis: 4% vs. 7%; gastritis + duodenitis: 0% vs. 2%). Clopidogrel and aspirin were re‐started after 0.86 ± 1.79 and 0.44 ± 1.60 days, respectively (P = 0.170). Three (4%) patients stopped clopidogrel due to drug rash. Using per protocol analysis, the treatment success rates of clopidogrel and aspirin were 94% (62/66) and 95% (57/60), respectively.

Conclusions : In patients with aspirin‐associated peptic ulcer disease of low to moderate grade, both early conversion from aspirin to clopidogrel and continuation of aspirin are safe.
Economic evaluation of Helicobacter pylori eradication in the CADET‐Hp randomized controlled trial of H. pylori‐positive primary care patients with uninvestigated dyspepsia
Authors: Chiba N. , Veldhuyzen Van Zanten S. J. O. , Escobedo S. , Grace E. , Lee J. , Sinclair P. , Barkun A. , Armstrong D. , Thomson A. B. R.
Published: January 2004

Background : Adult Helicobacter pylori‐positive patients by 13C‐urea breath test with uninvestigated dyspepsia symptoms were randomized to 1‐week eradication treatment with omeprazole, metronidazole and clarithromycin (OMC) vs. omeprazole and placebo antimicrobials (OPP) in the Canadian Adult Dyspepsia Empiric Treatment—H. pylori‐positive (CADET‐Hp) study.

Aim : To perform an economic evaluation of this 1‐year study.

Methods : Following blind eradication treatment, family practitioners managed patients according to their usual practices. Health resource utilization information was collected prospectively. From the mean costs of the health resources consumed and the treatment outcomes, the incremental cost‐effectiveness ratios and incremental net benefits of eradication treatment vs. OPP were determined.

Results : Eradication therapy significantly improved dyspepsia symptoms (treatment success: OMC, 50%; OPP, 36%; P = 0.02). The incremental cost‐effectiveness ratio of OMC vs. OPP was − 387 Canadian dollars (CAD$) per treatment success (90% CI, – CAD$1707, CAD$607), indicating a lower cost with treatment success. The incremental net benefit analysis showed that H. pylori eradication was cost‐effective if the willingness‐to‐pay value exceeded a nominal figure of CAD$100 from a health service perspective or CAD$607 from the societal perspective.

Conclusion : In uninvestigated patients presenting with dyspepsia at the primary care level, eradication of H. pylori in those who are H. pylori positive leads to a cost‐effective improvement in dyspepsia symptoms compared with a strategy of not eradicating H. pylori in these patients.
Hereditary non‐polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations
Authors: Thompson E , Meldrum CJ , Crooks R , McPhillips M , Thomas L , Spigelman AD , Scott RJ
Published: January 2004

Hereditary non‐polyposis colorectal cancer (HNPCC) is an autosomal dominant, inherited condition that is characterized primarily by the development of early‐onset colorectal cancer and a number of other epithelial malignancies. The underlying genetic basis of the disease is associated with a breakdown of DNA‐mismatch repair. There are many genes involved in DNA‐mismatch repair, and five of them have been implicated in HNPCC. Two of the genes (hMSH2 and hMLH1) account for the majority of HNPCC families (approximately 60%), and it is not known what the exact contributions of the remaining three genes (hPMS1, hPMS2, and hMSH6) are in relation to this condition. In addition, a sixth gene (hEXO1) has been associated with a disease phenotype that is consistent with HNPCC. Current estimates suggest that all four of these genes, combined, may account for up to 5% of families. In this report, we examine the contribution of hPMS2 and hEXO1 to a well‐defined set of families that fulfill the diagnostic criteria for HNPCC. The genes, hPMS2 and hEXO1, were studied by denaturing high performance liquid chromatography (DHPLC) analysis in 21 families that have previously been determined not to have mutations in hMSH2 or hMLH1. hPMS2 accounts for a small proportion of HNPCC families, and none were deemed to be associated with hEXO1. Mutations in hPMS2 appear to account for a small proportion of families adhering to the Amsterdam II criteria, whereas hEXO1 does not appear to be associated with HNPCC.
A trial for induction of supernumerary primordial germ cells in Xenopus tadpoles by injecting RNA of Xenopus vasa homologue into germline cells of 32‐cell embryos
Authors: Ikenishi Kohji , Yamakita Shinya
Published: January 2004

Whether overexpression of Xenopus vasa homologue or Xenopus vasa‐like gene 1 (XVLG1) in germline cells of Xenopus embryos can induce supernumerary primordial germ cells (PGC) at tadpole stage was investigated. XVLG1 RNA (0.1–2.0 ng) and β‐gal RNA (0.5 ng) were injected into one of, usually, four germ plasm‐bearing cells (GPBC) of 32‐cell embryos, with the β‐gal RNA (2.0 ng) serving as both lineage tracer and control for XVLG1 RNA. The total number of PGC, including X‐gal‐stained and unstained PGC of injected and uninjected GPBC origins respectively, was examined in the experimental tadpoles developed from the injected embryos. The injected RNA, XVLG1 and β‐gal RNA, were translated, resulting in a large amount of corresponding proteins in presumptive PGC (pPGC) as well as in somatic cells derived from the injected GPBC. Nevertheless, the average number of total PGC per tadpole found in the experimental tadpoles from the XVLG1 RNA‐injected embryos was not significantly different from that of β‐gal RNA‐injected ones, irrespective of the injected dose of XVLG1 RNA. This indicates that the extra XVLG1 protein in pPGC is not sufficient to increase the number of PGC in the tadpoles.
Inhibition of mitogen activated protein kinase signaling affects gastrulation and spiculogenesis in the sea urchin embryo
Authors: Kumano Maya , Foltz Kathy R.
Published: January 2004

The mitogen activated protein (MAP) kinase signaling cascade has been implicated in a wide variety of events during early embryonic development. We investigated the profile of MAP kinase activity during early development in the sea urchin, Strongylocentrotus purpuratus, and tested if disruption of the MAP kinase signaling cascade has any effect on developmental events. MAP kinase undergoes a rapid, transient activation at the early blastula stage. After returning to basal levels, the activity again peaks at early gastrula stage and remains high through the pluteus stage. Immunostaining of early blastula stage embryos using antibodies revealed that a small subset of cells forming a ring at the vegetal plate exhibited active MAP kinase. In gastrula stage embryos, no specific subset of cells expressed enhanced levels of active enzyme. If the signaling cascade was inhibited at any time between the one cell and early blastula stage, gastrulation was delayed, and a significant percentage of embryos underwent exogastrulation. In embryos treated with MAP kinase signaling inhibitors after the blastula stage, gastrulation was normal but spiculogenesis was affected. The data suggest that MAP kinase signaling plays a role in gastrulation and spiculogenesis in sea urchin embryos.
Differentiation of chondrocytes and scleroblasts during dorsal fin skeletogenesis in flounder larvae
Authors: Suzuki Tohru , Haga Yutaka , Takeuchi Toshio , Uji Susumu , Hashimoto Hisashi , Kurokawa Tadahide
Published: January 2004

In teleosts, the embryonic fin fold consists of a peridermis, an underlying epidermis and a small number of mesenchymal cells. Beginning from such a simple structure, the fin skeletons, including the proximal and distal radials and lepidotrichia (finrays), develop in the dorsal fin fold at the larval stage. Their process of skeletogenesis and embryonic origin are unclear. Using flounder larvae, we report the differentiation process for chondrocytes and scleroblasts prior to fin skeletogenesis and the effects of retinoic acid (RA) on it. In early larvae, the mesenchymal cells grow between the epidermis and spinal cord to form a line of periodical condensations, which are proximal radial primordia, to produce chondrocytes. The prescleroblasts, which ossify the proximal radial cartilages, differentiate in the mesenchymal cells remaining between the cartilages. Then, mesenchymal condensations occur between the distal ends of the proximal radials, forming distal radial primordia, to produce chondrocytes. Simultaneously, condensations occur between the distal radial primordia and peridermis, which are lepidotrichia primordia, to produce prescleroblasts. Exogenous RA specifically inhibits the mesenchymal condensation prior to the proximal radial formation together with the down‐regulation of sonic hedgehog (shh) and patched (pta) expression, resulting in the loss of proximal radials. Thus, it was indicated that differentiation of the precursor cells of radials and lepidotrichia begins in the proximal part of the fin fold and that the initial mesenchymal condensation prior to the proximal radial formation is highly susceptible to the effects of RA. Lepidotrichia formation does not occur where proximal radials are absent, indicating that lepidotrichia differentiation requires interaction with the radial cartilages. To examine the suggestion that neural crest cells contribute to the medial fin skeletons, we localized the HNK‐1 positive cells in flounder embryos and slug and msxb‐positive cells in pufferfish, Fugu rubripes, embryos. That the positive cells commonly arrive at the proximal part of the fin fold does not contradict the suggestion, but their final destiny as radial chondrocytes or lepidotrichia scleroblasts, should be further investigated.
Hoxa‐11 and Hoxa‐13 are involved in repression of MyoD during limb muscle development
Authors: Yamamoto Masakazu , Kuroiwa Atsushi
Published: January 2004

Under the influence of the limb mesenchyme, Hoxa‐11 is expressed in migrating and proliferating premyoblasts in the limb field and Hoxa‐13 is induced in subdomains of congregated limb muscle masses. To evaluate the roles of Hoxa‐11 and Hoxa‐13 in myogenesis of the limb, we performed electroporation in ovo to force expression of these Hox genes in limb muscle precursors. In the presence of ectopic Hoxa‐11, expression of MyoD was blocked transiently. In C2C12 myoblasts, transfection of Hoxa‐11 also repressed the expression of endogenous MyoD. Forced expression of Hoxa‐13 resulted in more pronounced repression of MyoD in both limb and C2C12 myoblasts. In contrast, targeted disruption of Hoxa‐13 gave rise to enhanced expression of MyoD in the flexor carpi radialis muscle, a forearm muscle that normally expressed Hoxa‐13. These results suggest that Hoxa‐11 and Hoxa‐13 are involved in the negative regulation of MyoD expression in limb muscle precursors.
Molecular identification of the skin transformation center of anuran larval skin using genes of Rana adult keratin (RAK) and SPARC as probes
Authors: Ishida Yuji , Suzuki Ken‐ichi , Utoh Rie , Obara Masanobu , Yoshizato Katsutoshi
Published: January 2004

Anuran larval skin undergoes a process of metamorphosis into preadult and adult skin. Basal skein, larval basal and adult basal cells are basement membrane‐attaching cells in the larval, preadult and adult epidermis, respectively, and are identified as cells expressing genes of RLK (Rana larval keratin), both RLK and RAK (Rana adult keratin), and RAK. Larval to preadult skin conversion takes place in the histological entity called the skin transformation center (STC). The present study performed a cDNA subtractive gene screening on cDNA of the larval and the preadult skin, and cloned the secreted protein acidic and rich in cysteine (SPARC) gene as an upregulated gene in the larva to preadult skin conversion. RAK gene‐positive basal skein cells and fibroblasts in and around the STC were weakly and strongly sparc‐positive, respectively. Using sparc and rak, we redefined the STC and visualized it on a histological section as an approximately 150 µm‐long region that contained about 20 rak‐negative and weakly sparc‐positive basal cells. Intense sparc expression was observed in basal skein cells, but not in larval basal cells, suggesting that SPARC acts as a suppressor of rak during epidermal differentiation. This suggestion was tested by investigating the effect of SPARC on cultured larval basal cells. We observed that SPARC suppressed the expression of rak, but not rlk.
Analysis of gene expression in rabbit nuclear transfer embryos: Use of single‐embryo mRNA differential display
Authors: Li Wen Yong , Yu Wei Dong , Qi Bing , He Xin , Wang Yu Ge , Liu Gui Sheng , Du Miao , Chen Qing Xuan
Published: January 2004

Lack of or abnormal expression of developmentally important genes is believed to hamper early development of the nuclear transfer (NT) embryo. To identify stage‐specific genes in rabbit NT embryo development, mRNA differential display was used to compare the mRNA content of rabbit NT embryos at different developmental stages, from Metaphase II oocytes to 8–16‐cell stage embryos. Thirty‐four zygotic transcripts, which abruptly appeared at the 8–16‐cell stage in rabbit NT embryos, were isolated; 11 of these were potential novel genes with no matches in the current databases. Of the remaining 23, 12 were matched with established sequence tags with functions uncharacterized and the other 11 were homologous to those in the European Molecular Biology Laboratory (EMBL) and GenBank databases. The differential expression of eight of the 34 amplicons were confirmed by reverse Northern blotting, and four positive clones were validated. Previous studies and present data indicated that these three genes were probably related to preimplantation rabbit embryo development.
Management for fistula‐in‐ano with Ginseng and Tang‐kuei Ten Combination
Authors: Ohya Toshiki , Usui Yoshiko , Okamoto Kentaro , Inoue Yumi , Arii Shigeki , Iwai Takehisa
Published: January 2004

Abstract
Background
: Non‐operative management for patients with fistula‐in‐ano in infancy using a traditional herbal medicine Ginseng and Tang‐kuei Ten Combination (GTTC) is described.

Methods
: A total of 22 patients with peri‐anal abscess or fistula‐in‐ano were treated with GTTC. Eighteen patients showed no improvement using the conventional non‐operative management (frequent curettage of abscess cavity), after which administration of GTTC was commenced. The other four patients received GTTC from the beginning of their treatment. A dose of 0.1−0.2 g/kg of GTTC was given orally twice a day. The period between onset of peri‐anal abscess and the commencement of GTTC (pre‐GTTC period) was compared to the period until remission after administration of GTTC (post‐GTTC period). The relationship between the GTTC dose, age at onset of peri‐anal abscess, post‐GTTC period, and relapse rates were investigated.

Results
: Twenty‐one patients reached remission, but a 4‐year‐old boy failed to reach remission and he required fistelectomy. Pre‐GTTC periods were from 11 days to 3 years (median 50 days) and statistically longer than post‐GTTC periods (4−65 days, median 7 days). There was a reverse correlation between the age at onset of peri‐anal abscess and post‐GTTC period (r = −044, P < 0.05). There was no statistical correlation between the dose of GTTC and post‐GTTC period. Five patients showed relapse after discontinuing GTTC, all of them could be resolved with augmentation of the dose. The onset of peri‐anal abscess in patients who relapsed were all < 3 months of age.

Conclusion
: Ginseng and Tang‐kuei Ten Combination seemed to accelerate the recovery of patients with fistula‐in‐ano in infancy.
Determination of total homocysteine in dried blood spots using high performance liquid chromatography for homocystinuria newborn screening
Authors: Febriani Andi Dwi Bahagia , Sakamoto Akiko , Ono Hiroaki , Sakura Nobuo , Ueda Kazuhiro , Yoshii Chiyoko , Kubota Miho , Yanagawa Junko
Published: January 2004

Abstract
Background
: The most widely used method for newborn screening for homocystinuria (HCU) is a semi­quantitative bacterial inhibition assay for measuring methionine concentration in dried blood spots (DBS). Because this method has resulted in a number of missed cases due to many factors, we developed a high performance liquid chromatography (HPLC) method with fluorescence detection to measure total homocysteine (tHcy) in DBS which might be useful for newborn screening for HCU.

Methods
: One disk of DBS 3 mm in diameter was sonicated in 10 min. The extract was reduced with dithioerythritol and was derivatized with 4‐aminosulfonyl‐7fluoro‐2,1,3‐benzoxadiazole before injection into HPLC.

Results
: This method showed good linearity (r = 0.996), precision (coefficient of variation range 2.7−5%), and excellent correlation coefficient between DBS and serum tHcy, both in control (r = 0.932) and patient samples (r = 0.952). By this method, the mean tHcy concentration in DBS of preterm newborns, full‐term newborns, and adults was 1.4 ± 1.0, 2.5 ± 1.6, and 4.9 ± 1.5 µmol/L, respectively. The mean tHcy DBS concentration in two cases of cystathionine‐β‐synthase deficiency and one case of 5,10‐methylentetrahydrofolate reductase deficiency was 22.7 ± 2.88, 29.3 ± 1.90, and 41.3 µmol/L, respectively.

Conclusions
: The present method, which is rapid, user friendly and reliable, seems applicable to newborn screening of HCU in place of methionine measurement.
Renal resistive indexes and some renal functions in liver cirrhotic children
Authors: AydoĞdu Sema , Akil Ipek , Akil Talha , Kabasakal Caner , Killi Refik , Mir Sevgi , YaĞci RaŞit
Published: January 2004

Abstract
Background
: The aim of the present study was to investigate renal vascular resistive changes in children with different stages of liver cirrhosis without obvious renal failure.

Methods
: Twenty‐nine children (14 girls, 15 boys, mean age 11.6 years) with cirrhosis and 20 healthy children (mean age 10.3 years) were investigated for renal vascular resistance with Doppler ultrasonography, urinary sodium, N‐acetyl‐beta‐D glucosaminidase (NAG) and microalbuminuria excretion.

Results
: The measurements of renal resistive indexes (RRI) were significantly higher in cirrhotic patients than the control group (0.69 ± 0.07 vs 0.62 ± 0.02, P < 0.0001). RRI measurement was found to be increased in decompensated cirrhotic patients than in compensated cirrhotic patients (0.73 ± 0.05 vs 0.67 ± 0.08, P < 0.0001). A significant positive relationship was observed between RRI and child score (r = 0.53). Urine NAG/Cr ratio was significantly higher in cirrhotic patients than in the control subjects (P < 0.001). Microalbumin concentrations were increased in the patients with decompensated cirrhosis than in the controls (P = 0.02). Patients with ascites and portal hypertension showed increased RRI values.

Conclusions
: We conclude that patients with cirrhosis are at risk of renal deterioration, which can not be detected by serum urea, creatinine, and glomerular filtration rate. The increase of RRI is associated with the progress of hepatocellular disease, and also the development of ascites and portal hypertension. Elevated urinary sodium excretion, elevated urinary NAG/Cr ratio and microalbuminuria might have a prognostic value especially in patients with Child scores> 6. Hence, monitoring RRI is a non‐invasive means of studying early renal hemodynamic alteration in childhood cirrhosis.
Child abuse as a result of enuresis
Authors: Can Gamze , Topbas Murat , Okten Aysenur , Kizil Melahat
Published: January 2004

Abstract
Background
: Enuresis is a frequent manifestation with important psychological and social consequences. The aim of the present study was to describe the types of child abuse as a result of enuresis, and to investigate the association of child abuse.

Methods
: A cross‐sectional field study was conducted between March 2001 and August 2001 in the 5−17‐year‐old age group, to identify risk factors and prevalence of enuresis in the province of Trabzon, Turkey. A face‐to‐face interview with 889 mothers was carried out. In the questionnaire, the existence, frequency, and risks factors of enuresis were questioned in detail and the parental reactions to the child's enuresis were widely investigated.

Results
: The prevalence of nocturnal enuresis was 17.9% in the 5−17‐year‐old age group. It was also found out that of 154 mothers, 86.4% (n = 133) were involved in child abuse of different types. It was found that 40.6% of children who were abused as a result of their enuresis were neglected medically, 42.1% were spanked and 12.8% were beaten.

Conclusions
: The high prevalence of enuresis among Turkish children leads to a high frequency of neglect. The high frequency of other types of child abuse in Turkey can be taken as being punishment.
Sucking behavior at breast during the early newborn period affects later breast‐feeding rate and duration of breast‐feeding
Authors: Mizuno Katsumi , Fujimaki Koichiro , Sawada Madoka
Published: January 2004

Abstract
Background
: One of the objectives of health‐workers is to help increase the rate and duration of breast‐feeding. It could become a helpful tool if babies sucking behavior at breast in the early neonatal period could predict babies at risk of short‐term breast‐feeding. The aims of this study are: to determine the prevalence of a range of sucking behaviors at breast in the early neonatal period in Japan; to determine if sucking behavior in the early neonatal period affects the later breast‐feeding rate; and to clarify reasons for ceasing breast‐feeding for each sucking behavior.

Methods
: A total of 1582 mothers of infants aged 6−12 months were surveyed. The questionnaire asked mothers their interpretation from memory of the sucking behavior of their infants in the early neonatal period. Mothers were asked to choose one out of five defined types (barracudas, excited ineffectives, procrastinators, gourmets and resters) and others. The study also included questions about the type of feeding (i.e. full, partial). Finally mothers were questioned about the time of and reasons for ceasing breast‐feeding.

Results
: Sufficient responses to the questionnaires were given by 1474 mothers (93.2%). The remainder of mothers questioned (108, 6.8%) did not provide appropriate answers. The babies whose mothers selected ‘Barracudas’ as the sucking behavior which best described their babies breast‐feeding showed the largest number of full breast‐feeding. These babies also displayed the highest breast‐feeding rate all the time. The ‘Procrastinators’ type showed the lowest overall rate of breast‐feeding. The Chi‐square test revealed that sucking behavior in the early neonatal period affects the breast‐feeding rate at 3 and 6 months of age (P < 0.001). The reasons for ceasing breast‐feeding observed in all subtypes were perceived shortage of milk volume and elder children's anger and jealousy.

Conclusion
: Based on the sucking behavior at breast in the early neonatal period, it is possible to predict babies at risk for short‐term breast‐feeding.
Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease
Authors: Nakamura Yosikazu , Yashiro Mayumi , Uehara Ritei , Watanabe Makoto , Tajimi Morihiro , Oki Izumi , Ojima Toshiyuki , Sonobe Tomoyoshi , Yanagawa Hiroshi
Published: January 2004

Abstract
Background
: Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut‐off point to predict aneurysm formation is not clear.

Methods
: One hundred and five patients with giant coronary aneurysms were selected from the 15th and 16th nationwide surveys of Kawasaki disease in Japan. A total of 2936 patients without Kawasaki disease were recruited from a single hospital as a control group. Odds ratios were calculated for six laboratory data with specific values as cut‐off points. Receiver operating characteristic (ROC) curves were observed to determine the most appropriate laboratory tests and cut‐off points.

Results
: Hematocrit, leukocyte count, neutrophil proportion, and hemoglobin had one or more peaks of odds ratio for specific cut‐off points, but they did not have a clear cut‐off point for the predictor according to the receiver operating characteristic curves. Alanine aminotransferase (ALT) increased the risk of giant coronary aneurysms continuously so no clearly appropriate cut‐off point was identified. Serum sodium concentration of 135 mEq/L had a peak of odds ratio, and those with <135 mEq/L had the highest odds ratio (4.78). This value seemed appropriate with a sensitivity of 78% and specificity of 57%, although the predictive positive value was as small as 5%.

Conclusion
: The author's propose that a serum sodium concentration of <135 mEq/L at the patient's first visit to hospital may be a predictor of giant coronary aneurysms due to Kawasaki disease.
Nitric oxide inhalation therapy in very low‐birthweight infants with hypoplastic lung due to oligohydramnios
Authors: Uga Naoki , Ishii Tetsuya , Kawase Yasuhiro , Arai Hiroko , Tada Hiroshi
Published: January 2004

Abstract
Background
: Although nitric oxide inhalation (iNO) therapy improves arterial oxygenation and reduces the rate of extracorporeal membrane oxygenation in term neonates, the efficacy of this therapy in premature infants is controversial. The objective of the present study was to determine whether iNO therapy improves the survival of very low‐birthweight infants with pulmonary hypoplasia due to prolonged rupture of membrane.

Methods
: A retrospective comparative study of very low‐birthweight infants with pulmonary hypoplasia due to oligohydramnios who had or had not been treated with iNO therapy, was performed (iNO‐treated group, eight infants; control group, 10 infants). A neonate was considered to have pulmonary hypoplasia due to oligohydramnios if the following conditions were satisfied: (i) artificial surfactant treatment did not improve the respiratory distress; (ii) prolonged rupture of membrane (PROM) continued for more than 5 days with oligohydramnios; and (iii) sufficient arterial oxygenation did not occur even after giving 100% oxygen, and more than 8 cm H2O of mean airway pressure was needed to maintain arterial oxygenation.

Results
: Nitric oxide inhalation improved arterial oxygenation rapidly and consistently in all eight infants with pulmonary hypoplasia. All eight iNO‐treated infants survived longer than 28 days, while five of the 10 control infants died within 24 h of birth (P < 0.05). Before starting iNO, seven of the eight treated infants had shown persistent pulmonary hypertension, which was confirmed by echocardiography. No iNO‐treated infant had IVH greater than grade 1, while one control infant had grade 2 IVH. All six long‐term survivors in the iNO‐treated group are developing normally, while only two of the control infants are developing normally as of February 2002.

Conclusions
: The majority of the infants with pulmonary hypoplasia due to oligohydramnios had persistent pulmonary hypertension. iNO improved the arterial oxygenation and significantly improved the survival rate. A controlled study to determine whether iNO therapy improves the survival rate of preterm infants with pulmonary hypoplasia due to oligohydramnios is necessary.
Video‐fluoroscopic study of swallowing in children with neurodevelopmental disorders
Authors: Fung Cheuk‐Wing , Khong Pek‐Lan , To Raymond , Goh Winnie , Wong Virginia
Published: January 2004

Abstract
Background
: Children with neurodevelopmental disorders can have feeding problems. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Video‐fluoroscopic study of swallowing (VFSS) is essential in understanding the pathological mechanisms involved during swallowing.

Methods
: The aim of the present study was to assess the role of VFSS in assessment and management of four children with various neurodevelopmental disorders in a multidisciplinary feeding team. We describe the team approach, with the participation of child neurologist, radiologist with the rehabilitation team including the speech therapist, occupational therapist and dietician, in the assessment and plan of management.

Results
: Video‐fluoroscopic study of swallowing had been useful in assessing the type of swallowing problems with treatment goals targeted to the basic underlying pathophysiological mechanism.

Conclusion
: A child neurologist should be involved in the multidisciplinary oromotor rehabilitation program for neurologically impaired children with feeding problems.
Trapping intensities for sampling ants in Australian rangelands
Authors: JAMES CRAIG D.
Published: January 2004

Abstract  I investigated the relationship between species richness and composition of ant faunas, and sampling intensity in two regions with different long‐term histories of grazing intensity in mulga (Acacia aneura) woodlands in northern New South Wales. There were two aims: (i) to examine the relationship between sampling intensity and species richness and composition; and (ii) to explore the differences in ant assemblages from two regions of markedly different grazing intensity when sampled at different intensities (i.e. when a higher proportion of the local ant fauna were collected). Ants were sampled in pit traps (120‐mm diameter) at densities of two, four, six and nine pits per 100 m2. Each sampling‐intensity treatment was replicated three times within each region. Pit traps filled with preservative were opened for 3 days. Species richness was higher with each successive increase in sampling intensity but was not different between regions for a given trapping intensity. There was no obvious asymptote of the curve relating trapping intensity to cumulative species richness suggesting that even greater trap densities than those used in the present study would be needed to collect most of the species of ants using a patch of ground over a few days. Spatial replication of a low‐intensity sampling design did not capture as many species as one higher‐intensity sampling array with the same total number of pit traps. This result can be explained by aggressive numerically dominant species of ants monopolizing access to a greater proportion of the traps in low‐density arrays. Ordination reveals that regions and sampling‐intensity treatments could be discriminated and that differences between regions with different grazing histories were less apparent with high‐intensity sampling arrays than they were with low‐intensity sampling arrays. This suggests that differences between locations in space (or potentially samples in time) could be exaggerated by incomplete sampling of the patch‐scale fauna. Comparison of the present study with other studies suggests that most studies to date have used sampling intensities that would not give a thorough assessment of the patch‐scale ground‐dwelling fauna if sampled only by pit traps. The implications of the results for programmes of ant monitoring in rangelands are discussed.
Characteristics of Australia's rangelands and key design issues for monitoring biodiversity
Authors: SMYTH ANITA K. , JAMES CRAIG D.
Published: January 2004

Abstract  We explored the key issues that are most likely to influence any set of guiding principles for developing biodiversity monitoring programmes in Australia's rangelands. We defined the Australian rangelands and came up with an overview of their climate extremes, land‐use pressures and biodiversity loss, and then focussed on issues underpinning the design phase of any monitoring programme. Using Noss's 1990 framework of compositional, structural and functional attributes of biodiversity and its new revisions by others, we showed how the elusive, abstract concept of biodiversity can be used to identify many measurable attributes that can form a minimum and necessary set of indicators for any biodiversity monitoring task. We then described the steps in the monitoring process, with a particular focus on the reasons for monitoring biodiversity as they strongly influence the selection of indicators. We concluded by compiling a table of key issues as background information for developing guiding principles (Table 4). The list is by no means an exhaustive list for the design phase but it does indicate that considerable attention needs to be given to this phase when developing monitoring programmes. We have intentionally not addressed the equally important issues associated with the planning and delivery phases of developing a monitoring programme, as Wallace et al. and Watson and Novelly cover these in their papers in the present issue of Austral Ecology.
Weeds and the monitoring of biodiversity in Australian rangelands
Authors: GRICE A. C.
Published: January 2004

Abstract Monitoring the biodiversity of Australian rangelands has been identified as a means of informing policy and supporting funding decisions in relation to the conservation of biodiversity. Australian rangelands are subject to invasion by alien plants that have the potential to have major impacts on ecosystem function and biodiversity, although there has been little quantitative documentation of these effects. Research is needed to improve our understanding of how and to what extent alien plants affect biodiversity in Australian rangelands so that this relationship can be considered when developing and implementing programmes to monitor biodiversity. It is also important to consolidate existing efforts to quantify the extent of alien plant invasions and monitor their progress, thus documenting a process that threatens biodiversity. Information on the presence and abundance of alien plant species should be considered for inclusion as a component of biodiversity monitoring programmes that are undertaken. Monitoring components of biodiversity can itself provide a basis for evaluating weed management strategies.
Correlations between steroids concentration in follicular fluid, pronuclear morphology and embryo qualities in in vitro fertilization
Authors: Hasegawa Junichi , Iwasaki Shinji , Yanaihara Atsushi , Negishi Momoko , Tahara Ryuzo , Okai Takashi
Published: January 2004

Background:  Several parameters of early embryo development are known as predictors of implantation success. Recently, zygote or embryo morphological assessments are thought to be a major method of selection in embryo transfer. We expected that the concentrations of the steroids in follicular fluid (FF) were associated with oocyte maturation and embryo quality. In the present paper, we evaluated the relationship of several parameters.

Methods:  We investigated 105 samples of FF from 22 subjects by in vitro fertilization (IVF). We evaluated the correlations between the FF concentrations of estradiol (E2) and progesterone (P4), the diameter of the ovarian follicles, fertilization, and zygote assessment based on pronuclear morphology and day 3 embryo qualities (i.e. number of blastomeres and fragmentation rate).

Results:  There was a positive correlation between the E2 concentrations in FF and serum (r = 0.273, P < 0.01), but there was no correlation between follicular diameter and the FF concentration of each steroid. The concentration of E2 in FF containing fertilized oocytes was not significantly different from that in FF containing unfertilized oocytes. At the pronuclear stage, the concentration of either steroid in FF did not differ among the morphological groups. The concentration of P4 in FF was significantly lower in the group in which pronuclei were detected at 20 h after insemination than in the group in which pronuclei were not detected. The concentration of E2 in FF was significantly related to the number of blastomeres (r = 0.271, P < 0.05) and furthermore, was significantly higher in FF from which morphologically good embryos were obtained at day 3 (P < 0.05).

Conclusions:  The FF concentrations of the steroids did not affect the pronuclear pattern, but P4 production may play a role in reducing the potential of the oocyte to develop pronuclei and the concentration of E2 may predict the cleavage capability of the oocyte. (Reprod Med Biol 2003; 2: 171–176)