bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in Metabolic Response to TPN Are Influenced More by Sex Than by Light Exposure
Authors: Harrison Adele , Khashu Minesh , Friel James , Lavoie Jean‐Claude , Chessex Philippe
Published: March 2009

Background:

Failure to protect total parenteral nutrition (TPN) solutions from ambient light induces the generation of peroxides, which contributes to the oxidation of several amino acids. We hypothesized that photo‐protection improves the metabolic response to TPN.

Aim:

To study the effects of photo‐protecting TPN on urinary nitrogen and vitamin C excretion and to evaluate in premature infants the influence of sex.

Patients and Methods:

Premature infants were randomized to receive from birth light‐exposed (LE) or light‐protected (LP) TPN. Upon reaching full TPN, parenteral nutrient intakes were correlated with normalized urinary nitrogen and vitamin C concentrations.

Results:

No differences were observed between LE and LP. However, sex‐related differences were observed in nitrogen and vitamin C handling. In boys, 50% of the nitrogen loss was explained by parenteral amino acid intake, whereas in girls, no correlation was found. The inverse correlation observed between intake and urinary excretion only in girls suggests a state of greater vitamin C utilization in girls.

Conclusions:

These results demonstrate that sex‐related differences in nitrogen/protein metabolism reported during enteral nutrition are seen during TPN as well. Sex is an important variable that will need to be taken into account in future studies evaluating the potential clinical effects of photo‐protecting TPN.
Postnatal “Speed of Sound” Decline in Preterm Infants: An Exploratory Study
Authors: Roggero Paola , Giannì Maria Lorella , Orsi Anna , Piemontese Pasqua , Amato Orsola , Mora Stefano , Puricelli Valeria , Mosca Fabio
Published: March 2009

“Speed of sound” (SOS), measured by quantitative ultrasound, is a noninvasive method of assessing bone status. At expected term and 1, 2, and 3 months of corrected age, bone status and body fat mass were assessed by quantitative ultrasound and by an air‐displacement system in 53 preterm infants to explore whether longitudinal changes in bone health were influenced by body fat mass. SOS decreased within the first month of corrected age. Body fat mass increased significantly. No correlation between SOS and body fat mass was found. SOS was not influenced by changes in body fat mass. The decline in SOS may be ascribed to bone structure factors.
Effect of Calcium and Vitamin D Supplementation on Bone Mineral Density in Children With Inflammatory Bowel Disease
Authors: Benchimol Eric I , Ward Leanne M , Gallagher JC , Rauch Frank , Barrowman Nick , Warren Jaime , Beedle Susan , Mack David R
Published: March 2009

Objectives:

The purpose of this study was to evaluate the effect of calcium and vitamin D2 supplementation on bone mineral density (BMD) in children with inflammatory bowel disease (IBD).

Patients and Methods:

This was an open‐label, prospective study conducted over a 12‐month period. Seventy‐two patients were divided into 2 groups based on lumbar spine areal BMD (L2–4 aBMD). Patients with an L2–4 aBMD z score of −1 or higher were assigned to the control group (n = 33; mean age, 11.0 ± 3.5 years; 20 boys). Patients with an L2–4 aBMD of less than −1 (n = 39; mean age 11.8 ± 2.5 years; 25 boys) were allocated to the intervention group and received 1000 mg of supplemental elemental calcium daily for 12 months (n = 19) or supplemental calcium for 12 months and 50,000 IU of vitamin D2 monthly for 6 months (n = 20).

Results:

The 2 groups differed in L2–4 aBMD z scores (intervention, −1.9 ± 0.6; control, −0.2 ± 0.6; P < 0.001) and volumetric L2–4 BMD (vBMD; intervention, 0.29 ± 0.04; control, 0.33 ± 0.06; P < 0.001). After 1 year of therapy, the control and intervention groups had similar changes in height z scores, L2–4 aBMD, L2–4 vBMD (z score change, L2–4 aBMD: control 0.2 ± 0.6 [n = 21], intervention 0.4 ± 0.6; P = 0.4 [n = 26]; z score change, L2–4 vBMD: control 0.1 ± 0.4, intervention 0.2 ± 0.6; P = 0.74). The changes in these parameters were similar between patients who had received calcium only or calcium plus vitamin D.

Conclusions:

These results suggest that, in children with IBD, supplementation of calcium and vitamin D does not accelerate accrual in L2–4 BMD.
Growth Hormone Treatment in Prepubertal Children With Celiac Disease and Growth Hormone Deficiency
Authors: Giovenale Diletta , Meazza Cristina , Cardinale Giuliana M , Farinelli Edorado , Mastrangelo Costanzo , Messini Beatrice , Citro Giuseppe , Del Vecchio Maurizio , Di Maio Salvatore , Possenti Ilaria , Bozzola Mauro
Published: March 2009

Objective:

To evaluate the growth response to growth hormone (GH) replacement therapy during a gluten‐free diet in patients with celiac disease (CD) associated with GH deficiency (GHD).

Patients and Methods:

A total of 14 prepubertal children affected by CD and GHD with no catch‐up growth after ≥12 months of gluten‐free diet and a reversion to seronegativity for antiendomysium antibodies and 10 age‐matched prepubertal children with idiopathic GHD (IGHD) entered the study. All of the patients were treated with the same GH dosage (0.25 mg/kg subcutaneously each week). Height, growth rate, and body mass index were measured at the time of diagnosis of CD, at the time of endocrinological evaluation, and after the first, second, and third year of GH replacement therapy.

Results:

Growth rate strikingly increased (P < 0.005) during the first year of therapy in a similar way in subjects with CD/GHD and IGHD (from a median standard deviation score [SDS] of −2.34 to an SDS of 3.25 and from an SDS of −1.29 to an SDS of 2.79, respectively). During the second and third years of GH treatment, the growth rate tended to decrease but the values at the third year were always positive (CD/GHD, median SDS, 1.10; IGHD, median SDS, 0.11), indicating continued catch‐up growth.

Conclusions:

In patients with CD with GH deficiency confirmed after ≥12 months of gluten‐free diet, GH replacement therapy should be started to allow complete catch‐up growth in children. In addition, the effect of GH treatment in patients who comply with a gluten‐free diet seems to be comparable to that observed in children with IGHD.
Liver Function Test Results Predict Nutritional Status Evaluated by Arm Anthropometric Indicators
Authors: Hurtado‐López Erika F , Larrosa‐Haro Alfredo , Vásquez‐Garibay Edgar M , Macías‐Rosales Rocío , Troyo‐Sanromán Rogelio , Bojórquez‐Ramos M Carmen
Published: March 2009

Objectives:

To compare the anthropometric indicators based on weight and height with the anthropometric indicators based on arm measurements and to predict the anthropometric nutritional status with liver function tests (LFTs) in children with chronic liver disease (CLD).

Patients and Methods:

A cross‐sectional study in a referral pediatric hospital enrolled 79 children with CLD (mean age 72.6 ± 61.8 months, 54% female). An independent variable of LFT was used to determine the outcome variable of nutritional status. Anthropometric indicators of height versus age, weight versus height, head circumference versus age, and arm indicators versus age were analyzed with Pearson correlation, the determination coefficient r2, and multiple regression.

Results:

A total of 44.3% of patients studied had growth impairment. The anthropomorphic indicator of weight for height identified malnutrition in 11.4%, compared with 43% identified by mid‐ to upper arm circumference (MUAC) and 40.5% identified with total arm area. MUAC (P < 0.001), total arm circumference (P < 0.001), arm muscle area (P = 0.009), and arm fat area (P = 0.023) identified more cases of z score less than −2 SD than weight/height. The presence of ascites misled weight‐for‐height measurements. Conjugated bilirubin and albumin had significant correlations with almost all of the anthropometric indicators. Alkaline phosphatase correlated significantly with all of the arm anthropometric indicators. A regression analysis led to 7 prediction models; the highest prediction of z score less than −2 SD was with triceps skinfold and conjugated bilirubin, albumin, and γ‐glutamyltransferase; height‐for‐age z score less than −2 SD was predicted by measurements of conjugated bilirubin, prothrombin time, and alanine aminotransferase.

Conclusions:

The data presented underline the correlation between the liver damage severity evaluated by LFT and the nutritional status estimated by anthropometric indicators. In our view these observations reflect the close relationship between liver function and the degree of liver damage to growth and current nutritional status.
Proton Pump Inhibitor Utilization Patterns in Infants
Authors: Barron John J , Tan Hiangkiat , Spalding James , Bakst Alan W , Singer Joseph
Published: March 2009

Objective:

Practice patterns regarding pediatric gastroesophageal reflux disease include acid suppression for infants meeting certain clinical criteria. This study aimed to examine the use of proton pump inhibitors (PPI) in infants and neonates.

Patients and Methods:

This retrospective observational study used data from 1999 to 2004 from 4 health care plans in the United States. Infants age <12 months with at least 1 pharmacy claim for a PPI were identified. Demographic information and PPI utilization patterns were assessed. Medical charts were reviewed in a subset of patients to gather dosing information.

Results:

Identified infants (N = 2469) were 58% male. PPI use rose 4‐fold from 2000 to 2003; lansoprazole and omeprazole were almost exclusively used. Treatment for almost half of the patients was initiated by their fourth month of life. The most common diagnoses identified through medical claims included gastroesophageal reflux (59%), problems feeding (23%), upper respiratory infections (23%), esophagitis (21%), and pain from gas (20%). Preindex H2 blockade was evident in 58% of the patients; preindex metoclopramide was used in 38% of the patients. Longer duration of PPI therapy was associated with patients who had more comorbidities. Through chart review of 388 patients, a subset of 272 patients with dosing information revealed that a median daily dosage in patients receiving lansoprazole was 1.74 mg · kg−1 · day−1 compared with 1.21 mg · kg−1 · day−1 for omeprazole.

Conclusions:

PPI use in the study population increased steadily from 1999 to 2004. These data offer valuable information on current PPI dosing patterns that may be used to design future clinical trials for assessment of gastroesophageal reflux disease regimens and clinical outcomes in the infant population.
Liver Stiffness Measurement in Children Using FibroScan: Feasibility Study and Comparison With Fibrotest, Aspartate Transaminase to Platelets Ratio Index, and Liver Biopsy
Authors: de Lédinghen Victor , Le Bail Brigitte , Rebouissoux Laurent , Fournier Céline , Foucher Juliette , Miette Véronique , Castéra Laurent , Sandrin Laurent , Merrouche Wassil , Lavrand Frédéric , Lamireau Thierry
Published: March 2009

Objective:

Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness in adult patients. The usefulness of FibroScan in children with chronic liver diseases is unknown. The aim of this prospective study was to evaluate the feasibility of liver stiffness measurement and to compare FibroScan, Fibrotest, and aspartate transaminase to platelets ratio index (APRI) with liver biopsy for the diagnosis of cirrhosis in children with chronic liver diseases.

Patients and Methods:

Between February 2004 and October 2005, 116 consecutive children with chronic liver diseases were prospectively included. All except 1 child (58 boys, mean age 10.7 years) could have noninvasive tests for fibrosis: FibroScan, Fibrotest, and APRI, and, when necessary, a liver biopsy (n = 33).

Results:

FibroScan, Fibrotest, and APRI were correlated with clinical or biological parameters of chronic liver diseases, but the FibroScan marker correlated most with all parameters. By histology, the METAVIR fibrosis category score was F1 in 7 cases, F2 in 8 cases, F3 in 6 cases, and F4 in 12 cases. FibroScan, Fibrotest, and APRI were significantly correlated with the METAVIR fibrosis score. For the diagnosis of cirrhosis, the area under the receiver operating characteristic curve was 0.88, 0.73, and 0.73 for FibroScan, Fibrotest, and APRI, respectively.

Conclusions:

These results indicate that liver stiffness measurement is feasible in children and is related to liver fibrosis. A specific probe dedicated to children and slender patients has thus been developed and is currently under evaluation. The FibroScan equipped with this specific probe could become a useful tool for the management of chronic liver diseases in children.
Ninety Percent of Celiac Disease Is Being Missed
Authors: Ravikumara M , Nootigattu VKT , Sandhu BK
Published: March 2009

Serological screening of 5470 children age 7.5 years from a cohort of 13,971 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) suggested the prevalence of celiac disease (CD) to be at least 1%. ALSPAC is an anonymous study, and hence seropositive children could not be individually identified or undergo biopsy. Inasmuch as all children within ALSPAC suspected of having CD are referred to just 1 center, we aimed to identify children with biopsy‐confirmed CD who were likely to be in this cohort and to estimate the magnitude of discrepancy between serology‐positive cases and biopsy‐confirmed cases. The results suggest that more than 90% of CD in children goes undiagnosed.
Probiotics for Necrotizing Enterocolitis: A Systematic Review
Authors: Barclay Andrew R , Stenson Ben , Simpson Judith H , Weaver Lawrence T , Wilson David C
Published: March 2009

Background:

Necrotizing enterocolitis (NEC) is the most commonly acquired neonatal intraabdominal emergency and causes significant morbidity and mortality. A proposed strategy for the prevention of NEC is the administration of oral probiotics. Probiotics have been shown to reduce NEC in experimental rat models and have been used in clinical trials. The authors aimed to review the existing data on the use of oral probiotics for the prevention of NEC in preterm infants (age <33 weeks) and those with very low birth weight (VLBW).

Materials and Methods:

Systematic review of randomized controlled trials (RCTs) and quasi‐RCTs was performed to find outcome measures of incidence, severity, need for surgery, and mortality in NEC. Electronic searches were performed on Medline and CINAHL databases using key word and subject headings with combinations of the terms “infant, preterm”; “infant, VLBW”; “enterocolitis, necrotizing”; and “probiotics.” In addition, citation searches were performed for all potential studies.

Results:

Six potential RCTs were identified for inclusion, but there were no systematic or Cochrane database reviews identified. One study was discounted because of the use of historical controls, so 5 studies were selected for analysis. Cumulatively, 640 infants were treated with probiotics and 627 were used as control subjects. All of the studies showed a trend toward less NEC in the treatment group. The heterogeneity of probiotic formulations and the timing and methods of interventions in the identified studies made synthesis and comparison of data inappropriate.

Conclusions:

The data appear to lend support to the use of oral probiotics for the prevention of NEC in preterm infants and those with VLBW. However, the data are insufficient to comment on their short‐ and long‐term safety. Type of probiotics used, as well as the timing and dosage, are still to be optimized. Further understanding of the pathogenesis of NEC and the mechanisms by which probiotics prevent it may lead to evidence‐based treatment strategies.
Evaluation of the Interleukin‐23 Receptor Gene Coding Variant R381Q in Pediatric and Adult Crohn Disease
Authors: Leshinsky‐Silver Esther , Karban Amir , Dalal Ilan , Eliakim Rami , Shirin Haim , Tzofi Tzipi , Boaz Mona , Levine Arie
Published: March 2009

Background:

Pediatric‐onset Crohn disease (CD) may differ in genotype or phenotype from adult‐onset CD. Genome‐wide screening recently identified a protective mutation (R381Q) in the interleukin‐23 (IL‐23) receptor gene located on chromosome 1. The aims of our study were to evaluate whether this mutation is associated with CD in our population and to find whether it may have an impact on age of onset or a specific location phenotype in a pediatric‐ and adult‐onset CD population.

Patients and Methods:

A total of 438 individuals (143 with pediatric‐onset CD [age <18 years], 139 with adult‐onset CD, and 157 control subjects) evaluated for age at onset and disease location were genotyped for the R381Q mutation in the IL‐23 receptor gene by pyrosequencing.

Results:

Mutant allele incidences were 5.7% in the normal cohort and only 2.28% in the CD cohort (P = 0.01). Carriers were found to constitute 8.9% of the normal cohort and only 4.6% of the CD cohort (P = 0.029). Homozygotes were found in only the control cohort. The mean age of onset for all of the patients with the mutation (including both age groups) was 17.8 ± 6.1 years versus 21.3 ± 12.4 years for patients without the mutation (P =0.08). The mutation was not associated with differences in sex, site of disease, or ethnicity. We did not find evidence of allelic interaction with CARD15.

Conclusions:

We confirmed the findings that the IL‐23 receptor gene coding variant allele R381Q appears to decrease susceptibility to CD in an Israeli Jewish population. We found a trend toward earlier age of onset, but no interactions with CARD15 or modifying effect on disease location.
Celiac Disease Screening by Immunochromatographic Visual Assays: Results of a Multicenter Study
Authors: Baviera Luis Carlos Blesa , Aliaga Ester Donat , Ortigosa Luis , Litwin Néstor , Peña‐Quintana Luis , Méndez Virginia , González Ma Victoria , López‐Manzanares Javier Manzanares , Méndez Enrique , Koninckx Carmen Ribes
Published: March 2009

Objective:

To assay the efficiency for celiac disease (CD) screening of 2 immunochromatographic visual stick assays based on human recombinant tissue transglutaminase (tTG). One was the antitissue transglutaminase antibodies (AtTGA) stick for IgA/G antibodies to tTG detection, the other was the AtTGA/antigliadin antibodies (AGA) stick for IgA antibodies for tTG and/or gliadins.

Patients and Methods:

In a prospective multicenter study, 4 pediatric gastroenterology units from Spain and 2 from Latin America enrolled 72 control children with a normal small bowel mucosa and 113 untreated patients with CD with Marsh type 3 lesions.

Results:

Evaluation of results by the gastroenterologists and by 2 independent observers at the coordination center showed a remarkably low interobserver variability. For the AtTGA stick, sensitivity was 96.5% and specificity was 98.6%. The AtTGA/AGA stick displayed a sensitivity of 94.5% and a specificity of 98.6% for AtTGA and a sensitivity of 63.1% and a specificity of 95.2% for AGA. The highest efficiency and positive likelihood ratio was obtained for the AtTGA stick, higher than for IgA AtTGA by enzyme‐linked immunosorbent assay. One additional advantage was that previous investigation of total serum IgA levels could be eluded. The IgA AtTGA/AGA stick, with an efficiency of 95.1%, compared with 89.2% when the combined results of the 2 enzyme‐linked immunosorbent assays were considered, turned out to be an excellent diagnostic tool for infants with no IgA deficiency.

Conclusion:

These 2 assays are extremely efficient for CD screening, by combining a high diagnostic accuracy with the simplicity and rapidity of visual methods.
A Neonatal Mouse Model of Intestinal Perforation: Investigating the Harmful Synergism Between Glucocorticoids and Indomethacin
Authors: Gordon Phillip V , Herman Andrew C , Marcinkiewicz Marek , Gaston Benjamin M , Laubach Victor E , Aschner Judy L
Published: March 2009

Background:

Early postnatal steroids and indomethacin in combination have been shown to increase the risk of spontaneous intestinal perforation (SIP) in infants with extremely low birth weight (ELBW), but the mechanism behind this synergistic effect is unknown.

Materials and Methods:

Based on literature in a variety of models suggesting that glucocorticoids and nonsteroidal antiinflammatory agents diminish complementary isoforms of nitric oxide synthase (NOS), we hypothesized that perturbations in NO metabolism contribute to SIP.

Results:

Our results using newborn wild‐type (WT) and endothelial NOS‐knockout (eNOS KO) mice treated with dexamethasone and/or indomethacin indicate that indomethacin treatment diminishes ileal eNOS abundance; dexamethasone treatment diminishes ileal inducible NOS and neuronal NOS (nNOS); 100% of dexamethasone‐treated eNOS KO mice die after 3 days; eNOS KO mice treated for 2 days with dexamethasone develop acute pyloric stenosis in association with reduced expression of pyloric nNOS; and isolated ileum from eNOS KO mice treated for 2 days with dexamethasone exhibit a significant decrease in spontaneous peristalsis, decreased circumference, and decreased capacitance for forced volume before ileal perforation compared with ileum from untreated controls.

Conclusions:

Our findings suggest that eNOS and nNOS display functional overlap in the newborn mouse gastrointestinal tract and that simultaneous reduction in the activity of both NOS isoforms may be a risk factor for neonatal ileal perforation. If this holds true in human infants, then it provides a plausible etiologic explanation for the strong temporal association between SIP and the simultaneous treatment of ELBW infants with glucocorticoids and indomethacin.
Meta‐analysis: octreotide prevents post‐ERCP pancreatitis, but only at sufficient doses
Authors: ZHANG Y. , CHEN Q.‐B. , GAO Z.‐Y. , XIE W.‐F.
Published: March 2009

Background  Effects of octreotide on post‐endoscopic retrograde cholangiopancreatography pancreatitis have been studied in many clinical trials. These trials have yielded inconclusive results. Results of more recent studies using larger doses, however, seem to be more optimistic.

Aim  To examine effects of octreotide at different doses on PEP.

Methods  A comprehensive search of relevant databases, including Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library and Science Citation Index yielded 18 randomized controlled trials (RCTs). Trials were divided into two groups according to the total dosage of octreotide: <0.5 mg (OCT1), ≥0.5 mg (OCT2). The rate of PEP was analysed using a fixed effect model.

Results  At doses of ≥0.5 mg, octreotide reduced the rate of PEP. In the OCT2 group, analysis revealed a statistically significant difference on PEP between the octreotide group and the controls (3.4% vs. 7.5%, pooled OR = 0.45; 95% CI: 0.28–0.73; P = 0.001, NNT = 25). In the OCT1 group, the rate of PEP was similar between patients receiving octreotide and the controls (7.2% vs. 6.0%, pooled OR = 1.23; 95% CI: 0.80–1.91; P = 0.35).

Conclusion  Octreotide is effective in preventing PEP, but only at sufficient doses (≥0.5 mg).
Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten‐free diet
Authors: LANZINI A. , LANZAROTTO F. , VILLANACCI V. , MORA A. , BERTOLAZZI S. , TURINI D. , CARELLA G. , MALAGOLI A. , FERRANTE G. , CESANA B. M. , RICCI C.
Published: March 2009

Background  Expected benefits of gluten‐free diet (GFD) in coeliac patients include healing of small intestinal mucosa, but it remains unclear to what extent this benefit is achieved in adults.

Aim  To assess factors affecting histological outcome of GFD in a large cohort of adult coeliac patients.

Methods  We extracted information on 465 consecutive coeliac patients studied before and during GFD.

Results  Duodenal biopsies at diagnosis were classified as Marsh I in 11, II in 25 and III in 429 cases. After a median 16 months GFD, 38 (8%) patients had histological ‘normalization’, 300 (65%) had ‘remission’ with persistent intraepithelial lymphocytosis, 121(26%) had ‘no change’ and 6 (1%) had ‘deterioration’. Coeliac disease related serology was negative in 83% of patients with Marsh III lesion during GFD. Male gender and adherence to GFD were independently associated with histological ‘normalization’ and ‘remission’. Persistence of intraepithelial lymphocytosis was not associated with human lymphocyte antigen gene dose or with Helicobacter pylori infection.

Conclusions  Complete normalization of duodenal lesions is exceptionally rare in adult coeliac patients despite adherence to GFD, symptoms disappearance and negative CD related serology. Control biopsies are mandatory to identify lack of response to gluten‐free diet.
TPMT*26 (208F→L), a novel mutation detected in a Chinese
Authors: Kham Shirley Kow Yin , Soh Chin Kok , Aw Derrick Chen Wee , Yeoh Allen Eng Juh
Published: March 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• More than 27 mutations in the TPMT gene causing decreased TPMT activity have been reported in various races.

• Decreased TPMT activity is associated with increased myelosuppression from azathioprine or thioguanine treatment.

• TPMT*3C is the most common genetic variant found in Asian populations.

WHAT THIS STUDY ADDS

• TPMT*26 (208F→L) is a novel mutation, previously not reported, which is associated with reduced TPMT activity in three siblings in an Asian Chinese family.

• This mutation is associated with increased sensitivity to azathioprine clinically.

AIMS

Azathioprine, mercaptopurine and thioguanine are commonly used to treat autoimmune disorders, leukaemia and solid organ transplantation. However, azathiopurine and its metabolites can also cause adverse reactions such as myelosuppression. These manifestations may be attributed to polymorphisms or mutations in the thiopurine methyltransferase (TPMT) gene that might result in low TPMT enzyme activity. Our aim was to investigate if azathioprine‐related myelosuppression is associated with TPMT polymorphism, which in turn affects its enzyme activity.

METHODS

A 61‐year‐old Chinese man with severe atopic eczema developed moderate myelosuppression with standard doses of azathioprine. His TPMT activity was measured using radiochemical assay. Genotyping of TPMT *3C, *3A and *6 were screened using polymerase chain reaction‐restriction fragment length polymorphism. Novel mutation was detected by sequencing. Family studies of his three other siblings were performed.

RESULTS

After 4 weeks of azathioprine treatment, the patient's white blood cells and absolute neutrophil count dropped by 40–45%. He was then taken off azathioprine, and blood counts returned to normal. TPMT activity test showed intermediate levels of 9.1 nmol h−1 ml−1 peripheral red blood cells (pRBC). Resequencing of the TPMT gene revealed a missense mutation Phe→Leu at 208 aa position in exon 9 (ss105107120). Two of his three siblings were heterozygous for 208F→L, which accounts for the decreased enzyme activity (brother 8.9 nmol h−1 ml−1 pRBC, sister 8.8 nmol h−1 ml−1 pRBC). The remaining sibling had wild‐type allele with normal enzyme activity. Screening of 100 normal healthy Chinese subjects did not reveal any individual with this mutation.

CONCLUSION

We report a novel mutation TPMT*26 (208F→L) associated with a decrease in TPMT enzyme activity.
Foraging activity and dietary spectrum of wood ants (Formica rufagroup) and their role in nutrient fluxes in boreal forests
Authors: DOMISCH TIMO , FINÉR LEENA , NEUVONEN SEPPO , NIEMELÄ PEKKA , RISCH ANITA C. , KILPELÄINEN JOUNI , OHASHI MIZUE , JURGENSEN MARTIN F.
Published: March 2009

Abstract1. We monitored three different‐sized wood ant (Formica aquiloniaYarrow) mounds over a 3‐year period in Finnish boreal forests dominated by Norway spruce (Picea abiesKarst.), to assess the seasonal temperature dependency of ant activity. Additionally, we also monitored Norway spruce trees around the mounds for descending honeydew foragers.

2. The amount of collected honeydew and prey and its composition, as well as the carbon (C), nitrogen (N), and phosphorus (P) in honeydew and invertebrate prey was also investigated.

3. The number of warm days (average temperature above 20 °C) and the amount of precipitation differed among the years. Ant activity at the mounds (but not on the trees) was highly correlated with air temperature throughout the ant‐active season (May–September), but ant activity in spring and autumn was lower than in summer at similar temperatures. During all 3 years, honeydew played a major role in wood ant nutrition (78–92% of dry mass). Invertebrate prey was mainly Diptera (on average 26.2%), Coleoptera (12.5%), Aphidina (9.3%), and Arachnoida (8.5%).

4. The total amounts of C, N, and P input brought into the ant mounds in the form of food (both honeydew and prey) on the stand level were 12.6–39.0, 1.6–4.6 and 0.1–0.4 kg ha−1 year−1, respectively, which is equivalent to 2–6%, 12–33% and 27–58% of the fluxes in annual needle litterfall in typical boreal Norway spruce forests. Thus, wood ants can play a significant role in short term and local N and P cycling of boreal forest ecosystems.
Current status of the Antarctic herb tundra formation in the Central Argentine Islands
Authors: PARNIKOZA I. , CONVEY P. , DYKYY I. , TROKHYMETS V. , MILINEVSKY G. , TYSCHENKO O. , INOZEMTSEVA D. , KOZERETSKA I.
Published: March 2009

Changes in the higher plant populations of the Argentine Islands over the last four to five decades have been central to developing an understanding of the likely biological responses to the globally exceptional rates of regional climate change, in particular warming, experienced along the western Antarctic Peninsula over the same period. In this study, we reassessed local populations and distribution of the two indigenous flowering plants on two islands in this archipelago, the grass Deschampsia antarctica and the pearlwort Colobanthus quitensis, in order to compare with previous partial and detailed surveys carried out by the British Antarctic Survey between 1963 and 1990. Our major finding was that the strong trend of recent increase in population size documented in 1990 has not continued, with current population sizes of both higher plants now being slightly lower than but still comparable with those recorded in the last survey in 1990. We discuss reasons underlying this, including possible limits imposed by the suitability of available habitat, and a recent plateauing of the local climate warming trend in comparison with that seen before the 1990 survey, with no significant short‐term warming apparent in annual or seasonal meteorological data since 1990.
From introduction to equilibrium: reconstructing the invasive pathways of the Argentine ant in a Mediterranean region
Authors: ROURA‐PASCUAL NÚRIA , BAS JOSEP M. , THUILLER WILFRIED , HUI CANG , KRUG RAINER M. , BROTONS LLUÍS
Published: March 2009

Determining the geographical range of invasive species is an important component of formulating effective management strategies. In the absence of detailed distributional data, species distribution models can provide estimates of an invasion range and increase our understanding of the ecological processes acting at various spatial scales. We used two complementary approaches to evaluate the influence of historical and environmental factors in shaping the distribution of the Argentine ant (Linepithema humile), a widespread, highly invasive species native to South America. Occurrence data were combined with environmental data at incremental spatial scales (extent and resolution) to predict the suitable range of the ant invasion using ecological niche models. In addition, we also used a spread model that simulated the jump dispersal of the species to identify the most plausible scenarios of arrival ofL. humilein the NE Iberian Peninsula at local scales. Based on the results of both modelling practices, we suggest thatL. humilemight have reached its maximum geographic range at regional scales in the NE Iberian Peninsula. However, the species does not appear in equilibrium with the environment at small spatial scales, and further expansions are expected along coastal and inland localities of the Costa Brava. Long‐distance jumps are ultimately responsible for the spread of the Argentine ant in the area. Overall, our study shows the utility of combining niche based models with spread models to understand the dynamics of species' invasions.
Evaluation of potassium permanganate against an experimental subacute infection of Flavobacterium columnare in channel catfish, Ictalurus punctatus (Rafinesque)
Authors: Darwish A M , Mitchell A J , Straus D L
Published: March 2009

An experiment was performed to evaluate the efficacy of potassium permanganate (KMnO4) as a prophylactic and therapeutic treatment of an experimental subacute infection of Flavobacterium columnare in channel catfish, Ictalurus punctatus. Fish were cutaneously abraded and divided into five treatment groups: (i) challenged by waterborne exposure to F. columnare and not treated with KMnO4 (positive control), (ii) challenged and simultaneously treated with KMnO4, (iii) challenged and treated with KMnO4 at 1, 6 and 9 days post‐challenge, (iv) not challenged and treated with KMnO4 at 1, 6 and 9 days post‐challenge (first negative control) and (v) not challenged and not treated (second negative control). The dosing of KMnO4 was 2.0 mg L−1 above the potassium permanganate demand for 2 h duration. The survival of the group challenged and simultaneously treated with KMnO4 (99%) was significantly higher than the positive control (78%) and was not significantly different from the negative control groups. The challenged fish treated with KMnO4 post‐challenge had 7% higher survival than the positive control (85% compared with 78%), but that difference was not statistically significant. The results demonstrate that KMnO4 has a clear prophylactic value but probably a marginal therapeutic value once the infection has established.
A review of mycobacteriosis in marine fish
Authors: Jacobs J M , Stine C B , Baya A M , Kent M L
Published: March 2009

Mycobacteriosis is a serious and often lethal disease of fish, affecting a wide range of species globally both in culture and wild settings. Caused by several species of the genus Mycobacterium, the disease has received considerable attention in recent years because of the discovery of new species in piscine hosts, epizootics in wild fisheries, and the ability of a few species to infect humans. The impact of this disease in aquaculture and the aquaria trade has been well reported and there is currently no widely accepted cure other than depopulation and facility disinfection. However, the impact on wild fisheries is poorly understood and may relate to species‐specific interactions (host–pathogen) and possibly environmental stressors. In this review, much of what is known about mycobacteriosis in marine fish is summarized with particular attention to an epizootic in striped bass, Morone saxatilis, (Walbaum), in Chesapeake Bay, USA.
Protection conferred against viral nervous necrosis by simultaneous inoculation of aquabirnavirus and inactivated betanodavirus in the sevenband grouper, Epinephelus septemfasciatus (Thunberg)
Authors: Yamashita H , Mori K , Nakai T
Published: March 2009

An aquabirnavirus (ABV) and a formalin‐inactivated betanodavirus [redspotted grouper nervous necrosis virus (RGNNV)] were investigated for their potential to prevent RGNNV‐induced viral nervous necrosis (VNN) in the sevenband grouper, Epinephelus septemfasciatus (Thunberg). Three groups of fish were injected intramuscularly with ABV, intraperitoneally with inactivated RGNNV (iRGNNV) or with both ABV and iRGNNV. At 3, 7, 14, 21 and 28 days post‐injection (p.i.), fish were challenged by intramuscular injection of RGNNV. Control fish, which received neither ABV nor iRGNNV, showed high mortalities in all RGNNV challenges. Fish that received only ABV exhibited relative percent survival (RPS) of >60 against RGNNV challenges at 3, 7, 14 and 21 days p.i., but not at 28 days p.i., while fish that received only iRGNNV showed significantly higher protection against RGNNV challenges only at 21 and 28 days p.i. In contrast, fish that received both ABV and iRGNNV showed 60 or higher RPS against all RGNNV challenges. Fish inoculated with iRGNNV with or without ABV exhibited similar high titres of neutralizing antibodies to RGNNV at 14, 21 and 28 days p.i. These results indicate that combined inoculation with iRGNNV and ABV conferred both rapid non‐specific and delayed specific protection against VNN.
Age‐ and Hormone‐Regulation of N‐Methyl‐d‐Aspartate Receptor Subunit NR2b in the Anteroventral Periventricular Nucleus of the Female Rat: Implications for Reproductive Senescence
Authors: Maffucci J. A. , Noel M. L. , Gillette R. , Wu D. , Gore A. C.
Published: March 2009

Glutamate, acting through its N‐methyl‐d‐aspartate (NMDA) and non‐NMDA receptors in the hypothalamus, regulates reproductive neuroendocrine functions via direct and indirect actions upon gonadotrophin‐releasing hormone (GnRH) neurones. Previous studies indicate that the NMDA receptor subunit NR2b undergoes changes in protein and gene expression in the hypothalamus in general, and on GnRH neurones in particular, during reproductive ageing. In the present study, we examined whether the NR2b‐expressing cell population, both alone and in association with the NR1 subunit (i.e. the latter subunit is necessary for a functional NMDA receptor), is altered as a function of age and/or steroid hormone treatment. Studies focused on the anteroventral periventricular (AVPV) nucleus of the hypothalamus, a region critically involved in the control of reproduction. Young (3–5 months), middle‐aged (9–12 months), and aged (approximately 22 months) female rats were ovariectomised and, 1 month later, they were treated sequentially with oestradiol plus progesterone, oestradiol plus vehicle, or vehicle plus vehicle, then perfused. Quantitative stereologic analysis of NR2b‐immunoreactive cell numbers in the AVPV showed an age‐associated decrease in the density of NR2b‐immunoreactive cells, but no effect of hormone treatment. In a second study, immunofluorescent double labelling of NR2b and NR1 was analysed by confocal microscopy of fraction volume, a semi‐quantitative measure of fluorescence intensity. No effect of ageing was detected for immunofluorescent NR1 or NR2b alone, whereas the NR2b fraction volume increased in the oestradiol plus vehicle group. With ageing, the fraction volume of the NR2b/NR1‐colocalised subunits increased. Together with the stereology results, this suggests that, although fewer cells express the NR2b subunit in the ageing AVPV, a greater percentage of these subunits are co‐expressed with NR1. Our results suggest that the subunit composition of NMDA receptors in the AVPV undergo both age‐ and hormonal‐regulation, which may be related to previous observations of changes in functional responses of reproductive neuroendocrine systems to NMDA receptor modulators with ageing.
Loss of Hypothalamic Response to Leptin During Pregnancy Associated with Development of Melanocortin Resistance
Authors: Ladyman S. R. , Tups A. , Augustine R. A. , Swahn‐Azavedo A. , Kokay I. C. , Grattan D. R.
Published: March 2009

Hypothalamic leptin resistance during pregnancy is an important adaptation that facilitates the state of positive energy balance required for fat deposition in preparation for lactation. Within the arcuate nucleus, pro‐opiomelanocortin (POMC) neurones and neuropeptide Y (NPY)/agouti‐related gene protein (AgRP) neurones are first‐order leptin responsive neurones involved in the regulation of energy balance. The present study aimed to investigate whether the regulation of these neuropeptides is disrupted during pregnancy in association with the development of leptin resistance. As measured by quantitative in situ hybridisation, POMC and AgRP mRNA levels were not significantly different during pregnancy, whereas NPY mRNA levels increased such that, by day 21 of pregnancy, levels were significantly higher than in nonpregnant, animals. These data suggest that these neurones were not responding normally to the elevated leptin found during pregnancy. To further characterise the melanocortin system during pregnancy, double‐label immunohistochemistry was used to quantify leptin‐induced phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in POMC neurones, using α‐melanocyte‐stimulating hormone (MSH) as a marker. The percentage of α‐MSH neurones containing leptin‐induced pSTAT3 did not significantly differ from nonpregnant animals, indicating that there was no change in the number of POMC neurones that respond to leptin during pregnancy. Treatment with α‐MSH significantly reduced food intake in nonpregnant rats, but not in pregnant rats, indicating resistance to the satiety actions of α‐MSH during pregnancy. The data suggest that multiple mechanisms contribute to leptin resistance during pregnancy. As well as a loss of responses in first‐order leptin‐responsive neurones in the arcuate nucleus, there is also a downstream disruption in the melanocortin system.
Thyroid Hormone Receptor β Mediates Acute Illness‐Induced Alterations in Central Thyroid Hormone Metabolism
Authors: Boelen A. , Kwakkel J. , Chassande O. , Fliers E.
Published: March 2009

Acute illness in mice profoundly affects thyroid hormone metabolism in the hypothalamus and pituitary gland. It remains unknown whether the thyroid hormone receptor (TR)‐β is involved in these changes. In the present study, we investigated central thyroid hormone metabolism during lipopolysaccharide (LPS)‐induced illness in TRβ−/− mice compared to wild‐type (WT) mice. We administered a sublethal dose of LPS or saline to TRβ−/− and WT mice. TRβ−/− mice displayed higher basal levels of serum triiodothyronine (T3) and thyroxine (T4) compared to WT, reflecting thyroid hormone resistance. In the periventricular area of the hypothalamus, we observed a marked decrease in thyrotrophin‐releasing hormone (TRH) mRNA expression in TRβ−/− and WT mice at t = 4 h, coinciding with the peak in plasma corticosterone. The decrease in TRH mRNA persisted in WT, but not in TRβ−/− mice at t = 24 h. By contrast, the increase of type 2 deiodinase (D2) mRNA already present at 4 h after LPS remained significant at 24 h in TRβ−/−, but not in WT mice. LPS decreased pituitary thyroid‐stimulating hormone β mRNA expression in WT at 24 h but not in TRβ−/− mice. The peak in pituitary D2 expression at t = 4 h in WT was absent in TRβ−/− mice. The relative decrease in plasma T3 and T4 upon LPS treatment was similar in both strains, although, at t = 24 h, plasma T3 tended to be restored in TRβ−/− mice. Our results suggest that TRβ is involved in suppression of the central component of the hypothalamic‐pituitary‐thyroid axis in acute illness.
The Trophic Effects of Oestrogen on Male Rat Anterior Pituitary Lactotrophs
Authors: Nolan L. A. , Levy A.
Published: March 2009

Rapid but often transient changes in mitotic and apoptotic activity are important components of the pituitary response to changes in the hormonal environment. For example, bilateral adrenalectomy and orchidectomy each result in a wave of increased mitosis lasting approximately 1 week, mediated by the same population of trophically active and, to a large extent, endocrinologically inactive cells. By contrast to these tonic inhibitors of pituitary trophic activity, reports of a progressive increase in lactotroph numbers during pregnancy suggest that oestrogen is a potent and persistent pituitary mitogen. By comparing the amplitude and duration of male rat anterior pituitary mitotic responses to oestrogen treatment, to adrenalectomy, and to a combination of the two, the present study aimed to further clarify the characteristics of the oestrogen‐induced trophic response, in particular whether lactotrophs are the predominant cell type involved. Adrenalectomy produced a wave of increased mitotic activity, which resolved within 7 days as expected, whereas oestrogen induced a significant increase in mitotic activity, which was sustained for the 14‐day duration of the study. The trophic effects of combining adrenalectomy and oestrogen treatment were not additive in that the statistically insignificant upward trend in mitotic index during the first few days compared to oestrogen treatment alone was entirely abolished by oestrogen pre‐treatment. The increase in mitotic activity in lactotrophs induced by oestrogen either with or without adrenalectomy did not result in an increase in the relative size of the prolactin‐positive compared to prolactin‐negative pituitary parenchymal cell numbers by the end of the study. Despite the marked increase in the lactotroph population that is reported during pregnancy, these data indicate that at least the early (i.e. within 2 weeks) mitotic response to pharmacological doses of oestrogen increases mitotic activity in the lactotroph subpopulation by only 5–8% relative to other cellular subpopulations. Unexpectedly, the mitotic response to oestrogen principally occurs in non‐prolactin‐containing cells and results in the recruitment, amongst other trophically responsive populations, of the entire subpopulation of prolactin‐, adrenocorticotrophic hormone‐ and luteinising hormone‐negative cells that respond mitotically to adrenalectomy. Oestrogen therefore has a previously unrecognised non‐cell type‐specific trophic effect in the pituitary that obscures the relative expansion of the lactotroph population by inducing concurrent increases in numbers of prolactin‐negative cells, the nature of which at least in part remains to be determined.
A Single Episode of Restraint Stress Regulates Central Corticotrophin‐Releasing Hormone Receptor Expression and Binding in Specific Areas of the Mouse Brain
Authors: Greetfeld M. , Schmidt M. V. , Ganea K. , Sterlemann V. , Liebl C. , Müller M. B.
Published: March 2009

The importance of restraining stress‐induced activation of the hypothalamic‐pituitary‐adrenocortical (HPA) system within tolerable limits requires efficient mechanisms for feedback inhibition. Recently, central corticotrophin‐releasing hormone (CRH) receptor type 1 (CRHR1) has been shown to mediate HPA system feeback inhibition. To date, most of the data regarding stress‐associated expression changes of CRHR1 and CRHR2 mRNA and their ligand CRH have been generated in rats. Taken considerable species differences into consideration, and with the growing importance of transgenic mice, a systematic analysis of the time course of expression changes of CRH and its two receptors in the mouse brain is needed to provide more insight into the regulation of the HPA system, both under physiological and pathophysiological conditions in this species. We analysed in detail the time course of expression changes of CRH, CRHR1 and CRHR2 mRNA after of restraint stress in mice in stress‐relevant brain regions (paraventricular nucleus, hippocampus, neocortex). We could show a rapid, strong and long‐lasting decrease in cortical and hippocampal CRHR1 mRNA expression after stress, whereas CRHR2 mRNA increased in the same neuroanatomical areas. In situ hybridisation analyses could be further confirmed at the protein level by CRH receptor autoradiography with changes in CRH binding that persisted even 7 days after a single episode of restraint stress. Our observation that stress has opposing effects on CRHR1 and CRHR2 neuronal systems supports the idea that regulation of the relative contribution of the two CRH receptors to brain CRH pathways may be essential in coordinating physiological responses to stress. We further hypothesise that the sustained alteration of CRH receptor expression and binding after a single episode of stress could mediate the long‐term effects of stress on neuroendocrine function and emotional regulation.