bluuebunny/crossref_metadata_2025 huggingface dataset:
Limb Girdle Muscular Dystrophy: An Interval Study of Weakness and Functional Impairment
Authors: Stübgen Joerg-Patrick
Published: March 2009

Objective:

Prospective studies of the natural history of a myopathy are effective means of measuring the status and progression of disease. This 10-year interval study of progressive weakness and functional decline was aimed to document the natural course of clinically well-characterized limb girdle muscular dystrophy in South Africa.

Methods:

The manual muscle test (MMT) was used to evaluate limb strength; global strength was measured by the average muscle score (AMS). A nonlinear functional grading system was used to measure impairment of the arms and legs. An activities of daily living (ADL) scale was used to assess disability across multiple functional domains in a home environment.

Results:

The mean AMS deteriorated from 5.9 to 4.9 (on a 10-point scale) and was unrelated to patient age and disease duration. Most (78%) patients lost arm function. All patients maintained useful hand function. Two thirds of patients lost leg function. Half of the patients were wheelchair bound, and they reached this level of function around the end of their fourth decade of life. Every patient showed functional deterioration on the ADL scale. The mean score worsened from 65.6 to 77.2 (out of 156 points). The disability change was most pronounced in patients who became wheelchair bound.

Conclusion:

This interval analysis showed a significant decline of limb strength that was independent of patient age or duration of disease and was more rapid in stronger patients. A functional grading system detected decline and was a useful measure of deterioration when applied to patients over intervals. An ADL assessment ascertained a significant functional decline across multiple functional domains in a home environment and allowed us to advise patients on compensatory strategies to limit dependence.
Gustatory Impairment in Patients Undergoing Head and Neck Irradiation
Authors: Mirza Natasha , Machtay Mitchell , Devine Pamela A. , Troxel Andrea , Abboud Soo K. , Doty Richard L.
Published: March 2009

Objectives: To determine whether radiation alters taste function and structure.

Research Design: Prospective, longitudinal study.

Methodology: Testing prior to starting radiation, and 2 weeks, 2 months, and 6 months after completing radiation.

Results: Relative to controls, patients had lower taste identification test scores for bitter, salty, and sour tastes. Sour taste also showed a significant group‐by‐time interaction (P = .03). Taste pores were decreased in the irradiated group, with a significant group‐by‐time interaction (P = .03).

Conclusion: Head and neck cancer patients have decreased taste function, and radiation adversely affected sour taste and taste pores.
Clinical Features and Outcome of the Tall Cell Variant of Papillary Thyroid Carcinoma
Authors: Leung Alex Kwok‐Cheung , Chow Sin‐Ming , Law Stephen C. K.
Published: March 2009

Objectives: To study the clinical features and outcome of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC).

Study Design and Methods: A single‐institution retrospective analysis was performed to review patients with TCV and the usual type of PTC diagnosed from 1960 to 2000.

Results: Fourteen of 1,108 patients (median follow‐up, 8.9 yr) diagnosed with PTC had TCV. Ten were female, and four were male, with a mean age of 53.7 (33‐81) years. All were ethnic Chinese. Compared with the usual PTC cohort, TCV patients presented at an older age (mean, 53.7 vs. 45.2 yr; P = .015). They had a higher rate of extrathyroidal extension (78.6% vs. 43.4%, P = .009), tracheal invasion (28.6% vs. 9%, P = .034), and carotid vessel invasion (14.3% vs. 1.5%, P = .021). TCV patients had more frequent gross (42.9% vs. 17.2%) and microscopic (14.3% vs. 6%) postoperative locoregional residual disease (P = .008). They also had a higher percentage of stage III and IV disease (American Joint Committee on Cancer, 6th ed) (74.3% vs. 31.3%, P = .009). Ten‐year local failure‐free, regional failure‐free, and metastasis‐free survival were worse in the TCV group (78.6% vs. 88.8%. P = .017; 53.0% vs. 85.9%, P < .0001; 35.7% vs. 92.1%, P < .0001, respectively). The 10‐year cause‐specific survival was also lower in TCV patients (48.2% vs. 93.4%, P < .0001).

Conclusion: TCV presents at a higher stage with more advanced local disease. It has a higher risk of locoregional and distant relapse and a worse overall survival rate. Stratification by stage reveals that TCV has significantly higher mortality compared with PTC for stage IV disease. Aggressive treatment and close follow‐up of these patients is necessary.
The Use of Dexamethasone to Reduce Pain After Tonsillectomy in Adults: A Double‐Blind Prospective Randomized Trial
Authors: Lachance Marianne , Lacroix Yolène , Audet Nathalie , Savard Patrick , Thuot François
Published: March 2009

Objectives/Hypothesis: To determine the effectiveness of dexamethasone to reduce pain after tonsillectomy in adults by at least 13 mm on the visual analogue scale. The secondary objective was to reduce the use of narcotics by at least 20%.

Study Design: This multicentric study is a prospective double‐blind randomized controlled trial.

Methods: A total of 102 patients were enrolled and received a 4‐day trial either of dexamethasone in decreasing doses or placebo. The patients were asked to note the level of pain on the visual analogue scale daily for 7 days. They also had to record their consumption of analgesic and any eventual side effects.

Results: There were no statistically or clinically significant differences between the two groups for the level of pain noted on the visual analogue scale for the first 4 and 7 days. There were no statistical differences for the consumption of hydromorphone between the two groups.

Conclusion: We cannot recommend the use of dexamethasone on a routine basis following tonsillectomy in adults for the reduction of pain or narcotics consumption.
Need for Intensive Histopathologic Analysis to Determine Lymph Node Metastases When Using Sentinel Node Biopsy in Oral Cancer
Authors: Bilde Anders , von Buchwald Christian , Therkildsen Marianne Hamilton , Mortensen Jann , Kirkegaard Jørgen , Charabi Birgitte , Specht Lena
Published: March 2009

Objective: To determine the predictive value of sentinel node biopsy (SNB)‐assisted neck dissection in patients with oral squamous cell carcinoma (SCC) stage T1 to 2N0M0 and to determine the incidence of subclinical metastases.

Study Design: Prospective cohort study.

Methods: Fifty‐one patients with clinically N0 neck underwent SNB‐assisted neck dissection. The localization of the sentinel node (SN) was determined using dynamic and planar lymphoscintigraphy and single photon emission computed tomography‐computed tomography. Histopathologic examination of the harvested SN was performed using step‐serial sectioning with hematoxylin‐eosin (H&E) and immunohistochemistry on formalin‐fixed, paraffin‐embedded tissue.

Results: A total of 181 SNs were excised with a median of 3 (range 1–7) SNs per patient. Four percent (2 of 51) of patients with subclinical (occult) lymph node metastasis would have been identified using routine H&E staining, whereas the 18% (9 of 49) were upstaged as a result of additional histopathology when the H&E evaluation was negative. Overall, the incidence of subclinical metastases was 22% (11 of 51).

Conclusion: In this study, SNB‐assisted neck dissection proved to be technically feasible in identifying subclinical metastasis, thus accurately staging the neck with a high degree of sensitivity in patients with oral SCC T1 to 2N0M0 when additional histopathology was performed. The vast majority of patients in this study would have been spared selective neck dissection had reliance on SNB been used and selective neck dissection performed only in the case of a positive SN. Future studies should focus on determining whether SNB alone reduces patient morbidity and whether this is as equally effective in the treatment of cervical nodal metastases as compared with selective neck dissection in patients with oral SCC.
Identification of Distant Metastases With Positron–Emission Tomography‐Computed Tomography in Patients With Previously Untreated Head and Neck Cancer
Authors: Gourin Christine G. , Watts Tammara L. , Williams Hadyn T. , Patel Vijay S. , Bilodeau Paul A. , Coleman Teresa A.
Published: March 2009

Objectives: To investigate the utility of positron–emission tomography‐computed tomography (PET‐CT) in identifying distant metastatic disease in patients with previously untreated head and neck squamous cell cancer (HNSCC) prior to definitive treatment.

Materials and Methods: Retrospective analysis of 27 consecutive patients with previously untreated HNSCC who underwent PET‐CT imaging in addition to chest radiography (CXR) as part of their metastatic workup.

Results: The majority of patients (89%) had TNM stage III or IV disease. PET‐CT was suspicious for pulmonary malignancy in four (15%) patients and indeterminate in one (4%) patient. CXR was suspicious for pulmonary malignancy in two (7%) patients. Pulmonary metastases or a new lung primary was present in 3 (11%) patients: 3 of 4 (75%) patients with positive PET‐CT scans and 0 of 23 (0%) patients with negative or indeterminate PET‐CT scans compared with 2 of 2 (100%) patients with positive CXR and 1 of 25 (4%) patients with negative CXR. The sensitivity and specificity of PET‐CT in predicting pulmonary malignancy was 100% and 96%, respectively, with a positive predictive value of 75% and a negative predictive value of 100%. The sensitivity and specificity of CXR in predicting pulmonary malignancy was 67% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 96%. Including nonpulmonary sites, the overall incidence of distant metastatic disease was 19% (5/27) with 11% (3/27) unsuspected prior to PET‐CT.

Conclusions: PET‐CT improves detection of metastatic disease in the high‐risk patient and should be performed as part of the routine pretreatment evaluation of patients with advanced stage HNSCC.
The Natural History of Idiopathic Unilateral Vocal Fold Paralysis: Evidence and Problems
Authors: Sulica Lucian
Published: March 2009

Objectives/Hypothesis: To identify clinical evidence regarding outcome and duration of unilateral idiopathic vocal fold paralysis (IVFP).

Study Design: Literature review.

Methods: Medline search using the terms “vocal fold paralysis,” “laryngeal paralysis,” “vagal paralysis,” and “recurrent nerve paralysis” was performed. Results were cross‐checked by substituting “palsy” and “paresis” in place of “paralysis,” “cord” in place of “fold,” and adding “idiopathic” to each term. Furthermore, papers antedating the period of time covered by Medline were identified in references of publications. Case series identified by means of these searches were examined for information regarding duration and outcome of IVFP.

Results: Seven hundred seventeen cases are reported. Complete recovery of motion occurred in 36 ± 22% (range, 13–83%) of individuals. Some recovery of motion (complete and partial) occurred in 39 ± 20% (range, 19–83%). Complete recovery of voice occurred in 52 ± 17% (range, 25–87%) of cases, some degree of recovery in 61 ± 22% (range, 25–87%). Most cases appear to recover in well under a year, with rare instances of markedly delayed recovery.

Conclusions: Review of available evidence reveals a highly variable rate of return of motion in IVFP. The rate of return of normal voice is consistently higher, although similarly variable. The marked differences in rates of recovery among reports appears to be the result of variable definitions of recovery, oversimplified all‐or‐none notions of paralysis and recovery, and inconsistent reporting of time elapsed from onset of paralysis to evaluation. All of these factors should be addressed in future prospective studies to shed further light on the natural history of vocal fold paralysis.
Pathology of Paediatric Gastrointestinal Neuromuscular Disease
Authors: Smith Virpi V
Published: March 2009

Congenital and acquired disorders of the enteric neuromusculature are relatively uncommon in childhood, with the exception of Hirschsprung disease. Despite this, a number of histologically well‐defined phenotypes of enteric neuromuscular disease are now recognised in paediatric populations, essentially comprising enteric neuropathies and enteric myopathies. This classification is briefly discussed.
Cost and Consultation Patterns of Abdominal Pain in Uruguayan Children
Authors: Saps Miguel , Bolioli Pablo , Espana Magali , Marshall Beth M , Di Lorenzo Carlo
Published: March 2009

Background:

Children with abdominal pain (AP) have worse quality of life and poorer social functioning and school attendance than their healthy peers. This is the first investigation of consultation patterns and costs of AP in South American children.

Patients and Methods:

All data were collected from Unidad Coronaria Movil in Montevideo, Uruguay. Diagnoses of all house calls during a 4‐year period (January 2002 through December 2005) were analyzed. Variances in consultation patterns based on sex and age were investigated. Supply and personnel costs were analyzed and prorated to obtain an accurate estimate of the cost per house call and outpatient visit.

Results:

A total of 125,945 in‐home visits and 1588 outpatient consultations were analyzed. Consultation rates for AP peaked among patients 7 to 9 years of age. Female subjects 9 to 14 years of age consulted significantly more frequently for AP than male subjects in the same age group. The average AP consultation accounted for approximately 3.8% of the per capita health care spending in Uruguay in 2005.

Conclusions:

AP is a global health problem that is present across ethnicities, nationalities, and geographic locations and is associated with significant health care expenditure.
Gastrointestinal Complications of Inherited Epidermolysis Bullosa: Cumulative Experience of the National Epidermolysis Bullosa Registry
Authors: Fine Jo‐David , Johnson Lorraine B , Weiner Madeline , Suchindran Chirayath
Published: March 2009

Background:

Portions of the gastrointestinal (GI) tract may be severely involved in patients with inherited epidermolysis bullosa (EB). Evidence‐based data are lacking as to the frequency and time of onset of these complications.

Patients and Methods:

Cross‐sectional and longitudinal data were analyzed on 3,280 and 450 patients with EB, respectively, who were followed from 1986–2002 as part of the National EB Registry, an epidemiological study that attempted to identify, enroll, and collect data on every EB patient residing within the continental United States. Frequencies of abnormalities arising within the esophagus, stomach, small and large intestines, rectum, and anus were determined for each major EB subtype. Cumulative risks were similarly calculated for esophageal stenoses or strictures, and for severe growth retardation.

Results:

Esophageal strictures and growth retardation were commonly seen among the more severe EB subtypes, most notably Hallopeau‐Siemens recessive dystrophic EB, and occurred as early as within the first year of life. EB subtype‐specific differences were also observed in the frequency of occurrence of other GI complications.

Discussion:

A variety of GI complications arise in patients with inherited EB, varying across the major EB subtypes in their relative severity, frequency, and time of onset.

Conclusions:

Data generated by the National EB Registry should provide a sound basis whereby evidence‐based strategies can be implemented for more effective surveillance and treatment of specific GI complications.
12‐Month Follow‐up After Successful Infliximab Therapy in Pediatric Crohn Disease
Authors: Wynands Jan , Belbouab Reda , Candon Sophie , Talbotec Cécile , Mougenot Jean‐François , Chatenoud Lucienne , Schmitz Jacques , Cézard Jean‐Pierre , Goulet Olivier , Hugot Jean‐Pierre , Ruemmele Frank M
Published: March 2009

Aim:

Infliximab (IFX) therapy is highly efficacious for the induction and maintenance of remission in pediatric Crohn disease (CD). However, to date it is unclear how long patients should be given IFX. Given the increasing safety concerns about the concomitant and prolonged use of IFX and azathioprine in CD, we wanted to address the clinical outcome in pediatric CD patients who responded to IFX medication, once IFX was stopped.

Patients and Methods:

Upon induction therapy with 3 IFX infusions, 36 of 38 patients with CD were in clinical remission at 3 months. These 36 responders were separated into 2 groups: 16 patients received no further IFX infusions, whereas 20 patients received scheduled maintenance therapy with IFX for 12 months.

Results:

Among the 16 patients who received no further IFX infusions, 12 experienced relapse during the 12‐month follow‐up interval after IFX was stopped. In the group receiving maintenance therapy, 11 of 20 patients remained in clinical remission at 12 months of therapy, whereas 8 patients required adjustment of IFX doses or intervals. Among the 11 children who were in clinical remission and receiving maintenance therapy without dose adjustment, 8 experienced relapse within 12 months after IFX maintenance therapy was stopped. Overall, the relapse rates after IFX induction or maintenance therapy was stopped were 75% and 72%, respectively.

Conclusions:

These data indicate that IFX is efficacious in controlling severe pediatric CD; however, to induce and maintain clinical remission, repeated IFX infusions are required, with a need for dose adjustment in a substantial number of patients.
Safety and Efficacy of Granulocyte and Monocyte Adsorption Apheresis in Paediatric Inflammatory Bowel Disease: A Prospective Pilot Study
Authors: Martín de Carpi Javier , Vilar Pere , Prieto Gerardo , Novo María Dolores García , Ribes Carmen , Varea Vicente
Published: March 2009

Objective:

Selective granulocyte‐monocyte adsorption (GMA) apheresis is a safe technique that has shown efficacy in inflammatory bowel disease (IBD), especially in adult steroid‐dependent and steroid‐refractory ulcerative colitis. GMA apheresis is performed with Adacolumn, a direct blood perfusion system that selectively adsorbs circulating granulocytes and monocytes. Studies on efficacy of GMA apheresis in paediatric IBD are scarce. Our aim was to evaluate efficacy, safety, and tolerability of GMA apheresis in paediatric IBD patients followed for 1 year.

Patients and Methods:

Nine patients with a mild to moderate flare‐up (6 boys, 3 girls; 5 ulcerative colitis [UC], 4 Crohn disease [CD]) were included. Mean age at inclusion was 13 years and 9 months, and mean disease duration before inclusion was 28 months. All of our patients with UC were steroid‐dependent; patients with CD had been unsuccessfully treated with other therapies. GMA apheresis consisted of 5 consecutive weekly sessions lasting 60 minutes each.

Results:

After the 5 sessions, 4 of 5 patients with UC and 1 of 4 patients with CD achieved remission. This remission was maintained in 2 of 4 patients with UC and in the single patients with CD. Patients taking steroids could begin to taper their daily doses after the second apheresis, and 3 of 5 of these patients reached the end of the study steroid‐free. GMA apheresis was well tolerated and no severe side effects related to the technique were observed.

Conclusions:

GMA apheresis is a safe, well‐tolerated technique in paediatric IBD. As previously reported, we have observed a better efficacy in promoting and maintaining remission, and reducing conventional drugs in patients with UC than in patients with CD.
Clinical Response to 2 Dosing Regimens of Lansoprazole in Infants With Gastroesophageal Reflux
Authors: Khoshoo Vikram , Dhume Pooja
Published: March 2009

Proton pump inhibitors such as lansoprazole are used in the treatment of gastroesophageal reflux disease (GERD), but dosing guidelines for infants have not been determined. The objective of this study was to assess the clinical efficacy of 2 dosing regimens of lansoprazole in infants with GERD using the revised infant gastroesophageal reflux questionnaire scores (I‐GERQ‐R). Thirty consecutive infants (3–7 months) with GERD, whose conditions were diagnosed by I‐GERQ‐R scores of ≥16, were randomly assigned to receive 1 of 2 lansoprazole dosing regimens: 15 mg given once per day (group A) or approximately 7.5 mg given 2 times per day (group B). Matched infants in a control group were treated with an extensively hydrolyzed formula (group C). Daily I‐GERQ‐R scores were gathered, and the scores after 1 and 2 weeks of treatment were used for analysis. The mean pretreatment scores were similar in groups A, B, and C (26.6, 26.9, and 25.9, respectively). After treatment there was a similar drop in the mean scores in groups A and B (20.6 and 20.0, respectively), but not in group C (25.8). At the end of the first week of treatment, in group A, 5 of 15 infants (33%) had a significant reduction in their I‐GERQ‐R scores, whereas in group B, 10 of 15 infants (67%) had a significant reduction in their I‐GERQ‐R scores (P < 0.05). At the end of the second week of treatment, groups A and B had similar numbers of patients with significant improvement (60% and 67%), which was higher than in group C (3/15, 20%). Overall, there was no difference in the symptom response, as measured by I‐GERQ‐R scores, between 15 mg of lansoprazole given once per day and 7.5 mg given twice per day in infants with GERD, but the twice‐daily regimen produced a faster symptom response. Both regimens were significantly better than treatment of infants with an extensively hydrolyzed formula.
Breast Development in the First 2 Years of Life: An Association With Soy‐based Infant Formulas
Authors: Zung Amnon , Glaser Tamar , Kerem Zohar , Zadik Zvi
Published: March 2009

Objective:

To evaluate the estrogenic effect of soy‐based formulas in female infants. These formulas contain significant amounts of phytoestrogens, compounds with structural similarity to estradiol.

Patients and Methods:

A cross‐sectional study consisting of 694 female infants ages 3 to 24 months that consecutively attended 10 general pediatric clinics, none of them having been referred for breast development. The presence of breast buds served as a marker for the endocrine effect of soy‐derived phytoestrogens.

Results:

Of the participants, 92 had consumed soy formulas for more than 3 months. Breast tissue was more prevalent in the second year of life in infants fed soy‐based formula vs those that were breast‐fed and those fed dairy‐based formula (22.0% vs 10.3%; P = 0.02) with an odds ratio of 2.45 (95% confidence interval 1.11–5.39). No differences in breast bud prevalence were observed during the first year of life. Unlike infants on dairy‐based formulas and breast‐feeding, infants fed a soy‐based formula did not demonstrate a decline in the prevalence of breast during the second year of life.

Conclusions:

We suggest that phytoestrogens impose a preserving effect on breast tissue that is evolved in early infancy, leading eventually to a slower waning of infantile breast tissue.
α‐Defensin Expression in the Gastric Tissue of Children with Helicobacter pylori–Associated Chronic Gastritis: An Immunohistochemical Study
Authors: Soylu Ozlem Bekem , Ozturk Yesim , Ozer Erdener
Published: March 2009

In this study, we evaluated the expression of α‐defensin and its correlation with histological criteria in children with and without Helicobacter pylori–associated gastritis. Forty‐five children were included. Immunohistochemical staining was performed and the relationship between α‐defensin immunoscoring and H pylori status and histological criteria was evaluated. Expression of α‐defensin was significantly higher in the H pylori–positive group (P < 0.001) and it was significantly associated with higher grades of chronic inflammation and neutrophil density (P < 0.001 for both). Our data show that α‐defensin expression is increased in H pylori infection in childhood and is associated with inflammatory tissue damage.
CDDUX: A Disease‐specific Health‐related Quality‐of‐life Questionnaire for Children With Celiac Disease
Authors: van Doorn Roesja K , Winkler Lex MF , Zwinderman Koos H , Mearin M Luisa , Koopman Hendrik M
Published: March 2009

Objective:

The development of a disease‐specific, health‐related, quality‐of‐life questionnaire for children ages 8 to 18 with celiac disease (CD), together with a parent‐as‐proxy version.

Materials and Methods:

We used a focus‐group method (bottom‐up approach) to investigate the impact of CD on children's everyday lives and selected 24 items to create a preliminary disease‐specific questionnaire. This questionnaire, together with the complementary generic quality‐of‐life questionnaire DUX‐25, was sent to 756 children with CD in the Netherlands and was returned by 530 of them. With the help of statistical analyses (Cronbach α, factor analysis, Pearson correlation, Student t test, paired samples t test, and item response theory), we tested the psychometric performance of the 24 items.

Results:

We reduced the questionnaire to 12 items: the Celiac Disease DUX (CDDUX). The CDDUX has 3 subscales: “Communication” (3), “Diet” (6), and “Having CD” (3). This questionnaire proved to be reliable, valid, and feasible and able to discriminate between perception of severity in cases of CD as assessed by parents.

Conclusions:

Children with a better perception of their own health status have a higher score on the CDDUX questionnaire. The whole group seems to have a lower quality of life than the healthy reference group on all domains of the DUX‐25. The new disease‐specific questionnaire CDDUX provides information about how children with CD think and feel about their illness. The questionnaire may enable researchers and clinicians to determine the consequences of this illness and the effects of clinical interventions on several aspects of daily living.
Chubby Face and the Biochemical Parameters for the Early Diagnosis of Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency
Authors: Chen Hung‐Wen , Chen Huey‐Ling , Ni Yen‐Hsuan , Lee Ni‐Chung , Chien Yin‐Hsiu , Hwu Wuh‐Liang , Huang Yuan‐Te , Chiu Pao‐Chin , Chang Mei‐Hwei
Published: March 2009

Objectives:

To identify facial and biochemical characteristics as early clinical features of neonatal intrahepatic cholestasis due to citrin deficiency (NICCD).

Patients and Methods:

Ten patients with diagnoses of NICCD by SLC25A13 mutation analysis in Taiwan were recruited. A “Chubby Index” was developed for objective measurement of their facial characteristics. Liver function profiles were analyzed and compared with data on neonatal hepatitis and biliary atresia.

Results:

Chubby face was observed in early infancy in all 5 patients whose serial photographs were taken. A significant difference in the Chubby Index was seen between NICCD infants and healthy infants (1.331 ± 0.07 vs 1.068 ± 0.059; P < 0.05). NICCD is characterized by an aspartate aminotransferase–to–alanine aminotransferase ratio of 2 or greater, a direct bilirubin–to–total bilirubin ratio under 0.67, and a standard deviation score for α‐fetoprotein of 4 or greater, with respect to neonatal hepatitis and biliary atresia. Although chubby face, abnormal liver function profiles, and multiple amino acidemia gradually disappeared after age 1 year, an increase in hepatic echogenicity was observed in most patients in long‐term follow‐up.

Conclusions:

Our Chubby Index is an informative measurement of the facial characteristics of infants with NICCD. The chubby face features, along with an aspartate aminotransferase–to–alanine aminotransferase ratio of 2 or greater, a direct bilirubin–to–total bilirubin ratio under 0.67, and a standard deviation score for α‐fetoprotein of 4 or greater, may serve as useful clinical indicators for diagnosing NICCD early in infancy.
Safety and Efficacy of Adalimumab in Pediatric Patients With Crohn Disease
Authors: Wyneski Matthew J , Green Alex , Kay Marsha , Wyllie Robert , Mahajan Lori
Published: March 2009

Objectives:

Adalimumab has recently become available for adult patients with Crohn disease (CD) as a viable alternative tumor necrosis factor‐α inhibitor to infliximab. To our knowledge, there have been no studies reviewing the use of adalimumab in pediatric patients with CD. Our aim was to examine the safety and efficacy of adalimumab therapy in pediatric patients with CD.

Patients and Methods:

We performed a retrospective chart review of 15 pediatric patients with CD who received adalimumab at a single institution between January 2003 and March 2007. All of the patients had a history of an attenuated response or anaphylaxis to infliximab. Each patient's chart was reviewed for age at diagnosis, sex, extent of disease, age at start of adalimumab therapy, course of therapy, side effects noted during therapy, concurrent medications, and response to adalimumab. Clinical response to adalimumab was classified as complete, partial, or no response based on the patients' ability to be weaned from steroids, increased or decreased need for steroids, or need for surgery during the course of treatment. This study was approved by the Cleveland Clinic Institutional Review Board.

Results:

Fifteen pediatric patients with CD received adalimumab for a 33‐month period. Of those, 14 patients had adequate follow‐up, and 1 patient was lost to follow‐up. The mean age at initiation of therapy was 16.6 years (median 17.9 years, range 10.3–21.8 years, SD 3.1 years). The majority of patients received an 80‐mg loading dose administered subcutaneously and 40‐mg doses subsequently every 2 weeks. The median duration of therapy was 6.5 months (range 1–31 months). A total of 272 injections were given. Of the 14 patients with sufficient data for follow‐up, 7 (50%) had a complete response, 2 (14%) had a partial response, and 5 (36%) had no response to adalimumab. Complete response was achieved after a median of 5 injections (range 3–11). Of the 14 patients with adequate follow‐up, 5 had fistulizing disease; 3 of these maintained fistula closure, 1 had temporary closure, and 1 required surgery to assist with closure. Twenty‐six adverse events occurred during therapy. Eight (57%) patients had at least 1 adverse effect. The most common events were abdominal pain and nausea. No serious adverse events were reported, no serious infections occurred, and no adverse events required discontinuation of adalimumab.

Conclusions:

Adalimumab was well tolerated in pediatric patients with CD. Complete or partial response was observed in 64% of patients. No serious adverse events occurred during therapy. Additional studies are needed to evaluate the efficacy and to determine optimal dosing of adalimumab in the pediatric population with CD.
Comparison of Epidermal Growth Factor and Heparin‐binding Epidermal Growth Factor–like Growth Factor for Prevention of Experimental Necrotizing Enterocolitis
Authors: Dvorak Bohuslav , Khailova Ludmila , Clark Jessica A , Hosseini Dania Molla , Arganbright Kelly M , Reynolds Charity A , Halpern Melissa D
Published: March 2009

Background:

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurely born infants. Epidermal growth factor (EGF) and heparin‐binding EGF‐like growth factor (HB‐EGF) have protective effects against intestinal injury. The aim of this study was to compare the effect of oral administration of HB‐EGF, EGF, or both on the incidence of NEC in a neonatal rat model.

Materials and Methods:

Premature rats were fed by hand and exposed to asphyxia and cold stress to develop NEC. Four diets were used: formula (NEC), formula supplemented with 500 ng/mL HB‐EGF (HB), 500 ng/mL EGF (EGF), or a combination of both (E+HB). Ileal injury, endogenous HB‐EGF production, expression of EGF receptors, goblet cell density, and expression of apoptotic proteins were evaluated.

Results:

Oral administration of either EGF or HB‐EGF significantly reduced the incidence of NEC; however, EGF provided better protection in physiologically relevant doses. Simultaneous administration of both growth factors did not result in any synergistic protective effect against NEC. There were no significant differences between treatment groups in ileal gene expression of EGF receptors or HB‐EGF. However, the balance of apoptotic proteins in the ileum was shifted in favor of cell survival in EGF‐treated rats. This mechanism may be responsible for the higher efficiency of EGF protection against NEC.

Conclusions:

These data suggest that a physiological dosage of EGF or a pharmacological dosage of HB‐EGF could be used for prevention of NEC.
Overview of Pediatric Short Bowel Syndrome
Authors: Duro Debora , Kamin Daniel , Duggan Christopher
Published: March 2009

Short bowel syndrome (SBS) is a malabsorptive state occuring as a result of surgical resection or congenital disease of a significant portion of the small intestine (1). The amount of resection or remaining bowel generally dictates the degree of malabsorption and consequentely the need for specialized enteral nutrition or parenteral nutrition (PN). Intestinal failure in the context of SBS is defined as a dependence on PN to maintain minimal energy and fluid requirement for growth in children. Common causes of SBS in infants and children include necrotizing enterocolitis, midgut volvulus, intestinal atresia, and gastroschisis. Early identification of patients at risk for long‐term PN dependency is the first step toward avoiding severe complications. Close monitoring of nutritional status, steady and early introduction of enteral nutrition, and aggressive prevention, diagnosis, and treatment of infections such as central venous catheter sepsis and bacterial overgrowth can significantly improve the prognosis. Intestinal transplantation is an emerging treatment that may be considered when intestinal failure is irreversible and children are experiencing serious complications related to TPN administration.
Omega‐3 LC‐PUFA Supply and Neurological Outcomes in Children With Phenylketonuria (PKU)
Authors: Koletzko Berthold , Beblo Skadi , Demmelmair Hans , Hanebutt Fabienne L
Published: March 2009

Children with phenylketonuria (PKU) follow a diet with very low intakes of natural protein, which is devoid of food sources of the omega‐3 docosahexaenoic acid (DHA). A resulting DHA depletion has been demonstrated in PKU children and may account for detectable subtle neurological deficits that are not explained by variation in plasma phenylalanine concentrations. We supplemented 36 children with PKU ages 1 to 11 years for 3 months with encapsulated fish oil providing a daily dose of 15 mg DHA/kg body weight. DHA supplementation resulted in significantly faster visual evoked potential latencies, indicating more rapid central nervous system information processing. In addition, DHA significantly improved outcomes in a test of motor function and coordination. No changes over time were seen in age‐matched healthy controls. Because the PKU children had a good supply of the omega‐3 precursor alpha‐linolenic acid, these observations lead us to conclude that endogenous conversion of alpha‐linolenic acid is not sufficient to provide adequate amounts of DHA that support optimal function, and hence DHA appears to be a conditional essential substrate for children with PKU. Because early treated PKU children are healthy, with normal fatty acid turnover, these data may indicate a need to supply some DHA to children in general. Further studies are ongoing aiming at establishing quantitative DHA requirements in children.
Early Flavor Learning and Its Impact on Later Feeding Behavior
Authors: Beauchamp Gary K , Mennella Julie A
Published: March 2009

In this review, we first outline the role and mechanisms of the chemical senses (taste, smell, and chemical irritation) in the perception of the flavor of a food or beverage. We then describe research findings, much of them from our laboratories, on the ontogeny of flavor perception and the interacting roles of innate responses and learning in the establishment of flavor preference of infants and children. Broadly, taste (sweet, sour, salty, bitter, umami, or savory) preferences have a strong innate component. Sweet, umami, and salty substances are innately preferred, whereas bitter and many sour substances are innately rejected. Nevertheless, these innate tendencies can be modified by pre‐ and postnatal experiences. Volatile components of flavor, detected by the olfactory system, are strongly influenced by early exposure and learning beginning in utero and continuing during early milk (breast milk or formula) feedings. These experiences set the stage for later food choices and are important in establishing life‐long food habits. As many of the diseases plaguing developed and developing societies involve excess consumption of some foods, an understanding of factors that determine choice and ingestion, particularly an understanding of the early factors, is important in designing strategies to enhance the health of the infant, child, and adult.
NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control
Authors: Wang Bin , Hurov Kristen , Hofmann Kay , Elledge Stephen J.
Published: March 2009

The ability to sense and respond to DNA damage is critical to maintenance of genomic stability and the prevention of cancer. In this study, we employed a genetic screen to identify a gene, NBA1 (new component of the BRCA1 A complex), that is required for resistance to ionizing radiation. The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. NBA1 is required to maintain BRE and Abra1 abundance and for the recruitment of BRCA1 to sites of DNA damage. In depth bioinformatics analysis revealed that the BRCA1 A complex bears striking similarities to the 19S proteasome complex. Furthermore, we show that four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability, thus forming a complex that might facilitate the deubiquitinating activity of the deubiquitination enzyme BRCC36 or the E3 ligase activity of the BRCA1/BARD1 ligase. These findings provide a new perspective from which to view the BRCA1 A complex.
Mosaic retroposon insertion patterns in placental mammals
Authors: Churakov Gennady , Kriegs Jan Ole , Baertsch Robert , Zemann Anja , Brosius Jürgen , Schmitz Jürgen
Published: March 2009

One and a half centuries after Charles Darwin and Alfred Russel Wallace outlined our current understanding of evolution, a new scientific era is dawning that enables direct observations of genetic variation. However, pure sequence-based molecular attempts to resolve the basal origin of placental mammals have so far resulted only in apparently conflicting hypotheses. By contrast, in the mammalian genomes where they were highly active, the insertion of retroelements and their comparative insertion patterns constitute a neutral, virtually homoplasy-free archive of evolutionary histories. The “presence” of a retroelement at an orthologous genomic position in two species indicates their common ancestry in contrast to its “absence” in more distant species. To resolve the placental origin controversy we extracted ∼2 million potentially phylogenetically informative, retroposon-containing loci from representatives of the major placental mammalian lineages and found highly significant evidence challenging all current single hypotheses of their basal origin. The Exafroplacentalia hypothesis (Afrotheria as the sister group to all remaining placentals) is significantly supported by five retroposon insertions, the Epitheria hypothesis (Xenarthra as the sister group to all remaining placentals) by nine insertion patterns, and the Atlantogenata hypothesis (a monophyletic clade comprising Xenarthra and Afrotheria as the sister group to Boreotheria comprising all remaining placentals) by eight insertion patterns. These findings provide significant support for a “soft” polytomy of the major mammalian clades. Ancestral successive hybridization events and/or incomplete lineage sorting associated with short speciation intervals are viable explanations for the mosaic retroposon insertion patterns of recent placental mammals and for the futile search for a clear root dichotomy.
Nitric Oxide Is Involved in Cadmium-Induced Programmed Cell Death in Arabidopsis Suspension Cultures
Authors: De Michele Roberto , Vurro Emanuela , Rigo Chiara , Costa Alex , Elviri Lisa , Di Valentin Marilena , Careri Maria , Zottini Michela , Sanità di Toppi Luigi , Lo Schiavo Fiorella
Published: March 2009

Exposure to cadmium (Cd2+) can result in cell death, but the molecular mechanisms of Cd2+ cytotoxicity in plants are not fully understood. Here, we show that Arabidopsis (Arabidopsis thaliana) cell suspension cultures underwent a process of programmed cell death when exposed to 100 and 150 μ  m CdCl2 and that this process resembled an accelerated senescence, as suggested by the expression of the marker senescence-associated gene12 (SAG12). CdCl2 treatment was accompanied by a rapid increase in nitric oxide (NO) and phytochelatin synthesis, which continued to be high as long as cells remained viable. Hydrogen peroxide production was a later event and preceded the rise of cell death by about 24 h. Inhibition of NO synthesis by N  G-monomethyl-arginine monoacetate resulted in partial prevention of hydrogen peroxide increase, SAG12 expression, and mortality, indicating that NO is actually required for Cd2+-induced cell death. NO also modulated the extent of phytochelatin content, and possibly their function, by S-nitrosylation. These results shed light on the signaling events controlling Cd2+ cytotoxicity in plants.
The Phloem-Delivered RNA Pool Contains Small Noncoding RNAs and Interferes with Translation
Authors: Zhang Shoudong , Sun Li , Kragler Friedrich
Published: March 2009

In plants, the vascular tissue contains the enucleated sieve tubes facilitating long-distance transport of nutrients, hormones, and proteins. In addition, several mRNAs and small interfering RNAs/microRNAs were shown to be delivered via sieve tubes whose content is embodied by the phloem sap (PS). A number of these phloem transcripts are transported from source to sink tissues and function at targeted tissues. To gain additional insights into phloem-delivered RNAs and their potential role in signaling, we isolated and characterized PS RNA molecules distinct from microRNAs/small interfering RNAs with a size ranging from 30 to 90 bases. We detected a high number of full-length and phloem-specific fragments of noncoding RNAs such as tRNAs, ribosomal RNAs, and spliceosomal RNAs in the PS of pumpkin (Cucurbita maxima). In vitro assays show that small quantities of PS RNA molecules efficiently inhibit translation in an unspecific manner. Proof of concept that PS-specific tRNA fragments may interfere with ribosomal activity was obtained with artificially produced tRNA fragments. The results are discussed in terms of a functional role for long distance delivered noncoding PS RNAs.
Case of lupus vulgaris diagnosed 50 years after onset
Authors: UTTAWICHAI Pattanawadee , IGARASHI Tsukasa , KAWANA Seiji
Published: March 2009

Cutaneous tuberculosis is an infrequent form of extrapulmonary tuberculosis, but is a symptom that can lead to diagnosis of tuberculosis. We describe a case of lupus vulgaris in a 79‐year‐old woman who had a 50‐year history of a slowly growing plaque on her right cheek. She visited many hospitals without resolution and the plaque gradually enlarged. Recently, she was misdiagnosed with eczema and prescribed topical steroids that had no effect, and she subsequently visited our outpatient clinic. A diagnosis of lupus vulgaris was made based on histopathology, culture and polymerase chain reaction, and isoniazid, rifampicin and ethambutol were administered as antituberculosis treatment. Although the incidence of cutaneous tuberculosis has decreased significantly in developed countries, knowledge and awareness of the disease are still of importance for proper diagnosis and treatment.
Genetic mapping of quantitative trait loci for resistance to Haemonchus contortus in sheep
Authors: Marshall K. , Maddox J. F. , Lee S. H. , Zhang Y. , Kahn L. , Graser H.‐U. , Gondro C. , Walkden‐Brown S. W. , Van Der Werf J. H. J.
Published: March 2009

This paper presents results from a mapping experiment to detect quantitative trait loci (QTL) for resistance to Haemonchus contortus infestation in merino sheep. The primary trait analysed was faecal worm egg count in response to artificial challenge at 6 months of age. In the first stage of the experiment, whole genome linkage analysis was used for broad‐scale mapping. The animal resource used was a designed flock comprising 571 individuals from four half‐sib families. The average marker spacing was about 20 cM. For the primary trait, 11 QTL (as chromosomal/family combinations) were significant at the 5% chromosome‐wide level, with allelic substitution effects of between 0.19 and 0.38 phenotypic standard deviation units. In general, these QTL did not have a significant effect on faecal worm egg count recorded at 13 months of age. In the second stage of the experiment, three promising regions (located on chromosomes 1, 3 and 4) were fine‐mapped. This involved typing more closely spaced markers on individuals from the designed flock as well as an additional 495 individuals selected from a related population with a deeper pedigree. Analysis was performed using a linkage disequilibrium–linkage approach, under additive, dominant and multiple QTL models. Of these, the multiple QTL model resulted in the most refined QTL positions, with resolutions of <10 cM achieved for two regions. Because of the moderate size of effect of the QTL, and the apparent age and/or immune status specificity of the QTL, it is suggested that a panel of QTL will be required for significant genetic gains to be achieved within industry via marker‐assisted selection.
Historical biogeography of the endemic Campanulaceae of Crete
Authors: Cellinese Nicoletta , Smith Stephen A. , Edwards Erika J. , Kim Sang‐Tae , Haberle Rosemarie C. , Avramakis Manolis , Donoghue Michael J.
Published: March 2009

Aim  The clade Campanulaceae in the Cretan area is rich in endemics, with c. 50% of its species having restricted distributions. These species are analysed in the context of a larger phylogeny of the Campanulaceae. Divergence times are calculated and hypotheses of vicariance and dispersal are tested with the aim of understanding whether Cretan lineages represent remnants of an older continental flora.

Location  The Cretan area: Crete and the Karpathos Islands (Greece).

Methods  We obtained chloroplast DNA sequence data from rbcL, atpB and matK genes for 102 ingroup taxa, of which 18 are from the Cretan area, 11 are endemics, and two have disjunct, bi‐regional distributions. We analysed the data using beast, a Bayesian approach that simultaneously infers the phylogeny and divergence times. We calibrated the tree by placing a seed fossil in the phylogeny, and used published age estimates as a prior for the root.

Results  The phylogenetic reconstruction shows that all Campanula species fall within a well‐supported campanuloid clade; however, Campanula is highly polyphyletic. The Cretan endemics do not form a monophyletic group, and species are scattered throughout the campanuloid clade. Therefore, the Cretan taxa did not evolve following a single vicariance or dispersal event. Most Cretan lineages represent remnants of an older continental flora, with the exception of one clade that radiated in situ after island isolation, and one lineage that appears to have arrived by dispersal.

Main conclusions  Most Cretan species were present in the islands at the time of their isolation, and very little long‐distance dispersal to Crete and diversification within Crete has occurred since then. Endemism is probably driven by loss of species on the mainland after island isolation. Species on the islands may have been more widespread in the past, but they are now restricted to often inaccessible areas, probably as a result of human pressure.