bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of patients with stage III or inoperable WT treated on the second United Kingdom WT protocol (UKWT2); A United Kingdom Children's Cancer Study Group (UKCCSG) study
Authors: Grundy R.G. , Hutton C. , Middleton H. , Imeson J. , Pritchard J. , Kelsey A. , Marsden H.B. , Vujanic G.M. , Taylor R.E.
Published: February 2004

Background

The aims of UKWT2 included consolidating the results for stage III patients obtained in UKWT1 and improving the outcome for patients with inoperable tumours by giving vincristine, actinomycin‐D and doxorubicin in an intensive schedule (Intensive AVA).

Procedure

The second UK WT trial (UKWT2) ran between July 1986 and September 1991 accruing 448 patients. One hundred and six patients were diagnosed and treated for stage III disease. Six had clear cell sarcoma of the kidney (CCSK) and seven had rhabdoid tumours of the kidney (RTK) and are analysed separately. One other patient was excluded from overall analysis. Ninety‐two patients were followed for a median of 115 months. Seventy‐five received standard chemotherapy and abdominal radiotherapy according to protocol. Seventeen had stage III disease at immediate nephrectomy, but radiotherapy was omitted by physician choice. Thirty‐three patients had inoperable disease at diagnosis and received pre‐nephrectomy chemotherapy.

Results

Overall survival (OS) at 4 years for stage III favourable histology (FH) patients receiving abdominal RT was 83% (CI: 73–89). For children with stage III disease in whom RT was omitted the OS was 82% (CI: 59–97) and for inoperable disease 94% (CI: 78–98). The overall and event‐free survival (EFS) of children with stage III CCSK was 100% and was achieved with the majority of patients not receiving radiotherapy (CI: 48–100). Three of seven children with RTK are alive EFS and OS 43% (CI: 10–73). For patients treated by abdominal radiotherapy the overall local control rate was 94.4% (CI: 86.4–98.5*%), 96.7% (CI: 88.5–99.6%) for flank RT and 83.3% (51.6–98.0%) for whole abdominal radiotherapy (WRT).

Conclusions

The outcome for stage III FH disease was similar to that reported for UKWT1 and NWTS‐3. The combination of abdominal RT together with 3‐drug chemotherapy achieves a high abdominal tumour control rate. Flank RT is probably sufficient for localised tumour rupture. The high cure rates for children in this trial with ‘inoperable disease’ suggests that treatment should be modified according to their post‐chemotherapy stage in order to avoid over‐treatment. The high OS for stage III CCSK on this protocol suggests that treatment duration could be curtailed and the role of RT reviewed, though the numbers are small. The prognosis for older children with RTK seems to be better than for younger children although larger studies are required to confirm this. © 2003 Wiley‐Liss, Inc.
Prevalence of and risk factors for hydrocele in survivors of Wilms tumor
Authors: Ginsberg Jill P. , Hobbie Wendy L. , Ogle Susan K. , Canning Douglas A. , Meadows Anna T.
Published: February 2004

Background

The purpose of this study is to evaluate the prevalence of hydrocele as a complication of Wilms tumor (WT) therapy and nephrectomy and to determine whether radiation therapy to the flank increases the risk. We hypothesize that radiation increases the risk of hydrocele formation in patients treated for WT.

Methods

A retrospective, medical review of the chart was completed on 57 male patients with WT diagnosed between 1985 and 2000.

Results

There is an increased prevalence of hydrocele in males that had a nephrectomy as part of their WT therapy.

Conclusions

Male survivors of WT are at risk for development of a subsequent hydrocele that appears to be related to their prior surgery. © 2003 Wiley‐Liss, Inc.
Human parvovirus B19 DNA is not detected in Guthrie cards from children who have developed acute lymphoblastic leukemia
Authors: Isa Adiba , Priftakis Peter , Broliden Kristina , Gustafsson Britt
Published: February 2004

Background

There has been much speculation about the cause of childhood acute lymphoblastic leukemia (ALL). It has been suggested, on the basis of findings in epidemiological studies, that ALL may be initiated by an in utero infection of the fetus. The human parvovirus B19 (B19) is etiologically related to human diseases, including erythema infectiosum and aplastic crisis, but it has not yet been considered to be involved in the development of ALL. Therefore, the aim of this study was to investigate, whether prenatal B19 infection could still be indirectly correlated with the development of childhood ALL.

Procedures

Fifty‐four Guthrie cards, collected at 3–5 days of age, from Swedish children who subsequently developed ALL, as well as from 50 healthy controls, were investigated by nested PCR for the presence of B19 DNA.

Results

B19 DNA was not detected in any of the Guthrie cards from ALL patients or from healthy controls, although all tested samples had amplifiable cellular DNA as confirmed by an HLA DQ specific PCR.

Conclusion

B19 DNA was not found in any of the Guthrie cards from children who later developed ALL or in the healthy controls. These findings suggest that it is less likely that childhood ALL is associated with an in utero in fection with B19. © 2004 Wiley‐Liss, Inc.
Correlation of cerebrospinal fluid β‐glucuronidase activity with plasma methotrexate concentrations in leukemic children receiving high‐dose methotrexate
Authors: Vlacha Vasiliki , Eliopoulou Maria , Haidas Stavros , Beratis Nicholas G.
Published: February 2004

Background

The activity of lysosomal enzymes is increased in body fluids during inflammation, in which cellular malfunction and cellular death occurs. Because chemotherapy also causes cell malfunction and death, for identifying a neurologic effect, we studied the activity of β‐glucuronidase in the cerebrospinal fluid (CSF) of leukemic children during treatment.

Procedure

The β‐glucuronidase activity in CSF was determined in 13 patients with B‐precursor acute lymphoblastic leukemia (ALL) treated with the medium risk arm of ALL Berlin‐Frankfurt‐Munster (BFM) 95 protocol. Plasma methotrexate (MTX) levels were determined at 24 and 48 hr after the infusion of high‐dose (5 g/m2/24 hr) MTX (MCA phase).

Results

The mean (SD) β‐glucuronidase activity prior to the onset of chemotherapy was 19.9 (5.6) nmoles/4‐methylumbelliferone/ml/hr. No significant changes in activity were noted during the phases of the protocol except of the MCA3. The activity was 24.4 (6.8) on MCA2, 28.4 (9.3) on MCA3, and 24.1 (9.5) on MCA4. The β‐glucuronidase activity was positively correlated with the plasma MTX levels at both 24 hr (r = 0.483, P = 0.006) and 48 hr (r = 0.676, P < 0.0001). No progressive changes were noted during the different phases of the protocol. The greatest β‐glucuronidase activity was measured in two patients with neurotoxicity.

Conclusions

The β‐glucuronidase activity is increased in the CSF of leukemic children receiving high‐dose MTX and particularly in neurotoxicity. It is positively correlated with plasma MTX levels. No cumulative effect of the chemotherapy was observed. The increased β‐glucuronidase activity is most likely due to enzyme leakage through the cell membranes caused mainly by a toxic effect of MTX on the cells of the central nervous system (CNS). © 2004 Wiley‐Liss, Inc.
Primary cardiac Burkitt lymphoma in a child
Authors: Meshref M. , Sassolas F. , Schell M. , Chalabreysse L. , Chassagne C. , Mialou V. , Marec Bérard P. , Di Filippo S. , Bergeron C.
Published: February 2004

Primary cardiac lymphoma (PCL) is a rare and usually fatal malignancy, seldom reported in children. This report describes the case of a 10‐year‐old boy who presented with multiple intracardiac masses which, when biopsied, proved to be small non‐cleaved cell (Burkitt's) lymphoma. The first two cycles of chemotherapy according to the LMB 96 protocol were given under close cardiological supervision, with good response. The treatment was then continued with full‐dose chemotherapy, without any cardiological complication. The patient who was treated by chemotherapy alone remains in complete remission 36 months after the end of treatment and can presently be considered as cured, without late cardiac effect. © 2004 Wiley‐Liss, Inc.
Effect of PM10 pollution in Bangkok on children with and without asthma
Authors: Preutthipan Aroonwan , Udomsubpayakul Umaporn , Chaisupamongkollarp Thitida , Pentamwa Prapat
Published: February 2004

This study aimed to investigate the effects of PM10 concentrations exceeding the Thai national standard (24‐hr average, >120 μg/m3) on daily reported respiratory symptoms and peak expiratory flow rate (PEFR) of schoolchildren with and without asthma in Bangkok. The 93 asthmatic and 40 nonasthmatic schoolchildren were randomly recruited from a school located in a highly congested traffic area. Daily respiratory symptoms and PEFR of each child were evaluated and recorded in the diary for 31 successive school days. During the study period, 24‐hr average PM10 levels ranged between 46–201 μg/m3. PM10 levels exceeded 120 μg/m3 for 14 days. We found that when PM10 levels were >120 μg/m3, the daily reported nasal irritation of asthmatic children was significantly higher than when PM10 levels were ≤120 μg/m3. In addition, when PM10 levels were >120 μg/m3, nonasthmatic children had a significantly higher daily reported combination of any respiratory symptoms. PEFR did not change with different ambient PM10 levels in both groups. This study suggests that elevated levels of PM10 concentrations in Bangkok affect respiratory symptoms of schoolchildren with and without asthma. Pediatr Pulmonol. 2004; 37:187–192. © 2004 Wiley‐Liss, Inc.
Upregulation of endothelial nitric oxide synthase and endothelin‐1 in pulmonary hypertension secondary to heart failure in aorta‐banded rats
Authors: Dai Zen‐Kong , Tan Mian‐Shin , Chai Chee‐Yin , Yeh Jwu‐Lai , Chou Shah‐Hwa , Chiu Chaw‐Chi , Jeng Arco Y. , Chen Ing‐Jun , Wu Jiunn‐Ren
Published: February 2004

This study assessed alterations in expression of pulmonary endothelial nitric oxide synthase (eNOS) and endothelin‐1 (ET‐1) in rats with pulmonary hypertension (PH) after the ascending aorta had been banded. Rats were studied 12 weeks after banding, which resulted in left heart failure with elevated pulmonary arterial pressure (banded: 31.3 ± 5.9 (mean ± SD) mmHg; sham: 20.0 ± 4.7 mmHg, P < 0.05). Competitive reverse transcription‐polymerase chain reaction demonstrated significant increases in pulmonary expression of preproET‐1 mRNA and eNOS mRNA. Western blot analysis indicated increased pulmonary eNOS protein. Radioimmunoassays indicated increased plasma ET‐1 concentrations in the pulmonary artery (banded: 12.4 ± 1.5 pg/ml; sham: 9.0 ± 1.3 pg/ml, P < 0.01) and increased ET‐1 content in lungs (banded: 240 ± 21 ng/g protein; sham: 203 ± 20 ng/g protein, P < 0.05). There was increased immunohistochemical staining of eNOS and ET‐1 in the pulmonary vascular endothelium of aorta‐banded rats. Even in the presence of increased eNOS expression, it was not clear how nitric oxide (NO) production (decreased, unchanged, or increased) was involved in the compensatory mechanism to offset pulmonary vasoconstriction. Increased ET‐1 expression may be important in mediating PH secondary to aortic banding, and may offer insights into the use of ET‐1 antagonists in treating patients with PH secondary to heart failure. Pediatr Pulmonol. 2004; 37:249–256. © 2004 Wiley‐Liss, Inc.
Pulmonary function in bronchopulmonary dysplasia
Authors: Robin Beverley , Kim Young‐Jee , Huth Jaimee , Klocksieben Jim , Torres Margaret , Tepper Robert S. , Castile Robert G. , Solway Julian , Hershenson Marc B. , Goldstein‐Filbrun Amy
Published: February 2004

The purpose of this study was to examine lung function and bronchodilator responsiveness in infants with a history of prematurity and bronchopulmonary dysplasia (BPD), using the raised volume rapid thoracoabdominal compression technique as well as with whole‐body plethysmography. Spirometric measurements were obtained in 28 infants with a history of BPD, defined as preterm birth with O2 requirement at 36 weeks postmenstrual age (gestational age at birth, 26.4 ± 2.1 weeks, mean ± SD; birthweight, 898 ± 353 g; age at study, 68.0 ± 35.6 weeks). Fractional lung volumes were measured in 27 subjects. Values were expressed as percentage of predicted normal values. Compared to normal infants, those with a history of BPD exhibited decreases in forced expiratory flows including forced expiratory volume in 0.5 sec (76.3 ± 19.6%), forced expiratory flow at 75% of expired forced vital capacity (FEF75; 59.5 ± 30.7%), and FEF25–75 (74.0 ± 26.8%; P < 0.01 for all). Functional residual capacity (107.9 ± 25.3%), residual volume (RV, 124.5 ± 42.7%), and RV/total lung capacity (RV/TLC, 128.2 ± 35.3%) were increased in infants with a history of BPD (P < 0.05 for each). There was no difference in TLC between groups. Seventeen infants were studied both pre‐ and postalbuterol, and 6 (35%) demonstrated significant bronchodilator responsiveness. Infants with recurrent wheezing showed greater expiratory flow limitation, hyperinflation, and airways responsiveness, whereas those without wheezing showed only modest airway dysfunction. We conclude that infants with a history of BPD have pulmonary function abnormalities characterized by mild to moderate airflow obstruction and air trapping. Pediatr Pulmonol. 2004; 37:236–242. © 2004 Wiley‐Liss, Inc.
Use of a respiratory clinical score among different providers
Authors: Liu Lenna L. , Gallaher Margaret M. , Davis Robert L. , Rutter Carolyn M. , Lewis Toby C. , Marcuse Edgar K.
Published: February 2004

Respiratory assessment of children with asthma or bronchiolitis is problematic because both the components of the assessment and their relative importance vary among care providers. Use of a systematic standard assessment process and clinical score may reduce interobserver variation. Our objective was to determine observer agreement among physicians (MD), nurses (RN), and respiratory therapists (RT), using a standard respiratory clinical score. A clinical score was developed incorporating four physiologic parameters: respiratory rate, retractions, dyspnea, and auscultation. One hundred and sixty‐five provider pairs (e.g., MD‐MD, RN‐RT) independently assessed a total of 55 patients admitted for asthma, bronchiolitis, or wheezing at an urban tertiary‐care hospital. A weighted kappa statistic measured agreement beyond chance. Rater pairs had high observed agreement on total score of 82–88% and weighted kappas ranging from 0.52 (MD‐RN; 95% CI, 0.19, 0.79) to 0.65 (RN‐RN; 95% CI, 0.46, 0.87). Observed agreement on individual components of the score ranged from 58% (auscultation) to 74% (dyspnea), with unweighted kappas of 0.36 (respiratory rate; 95% CI, 0.26, 0.46) to 0.53 (dyspnea; 95% CI, 0.41, 0.65). In conclusion, this respiratory clinical score demonstrates good interobserver agreement between MDs, RNs, and RTs. Future research is needed to examine validity and responsiveness in clinical settings. By standardizing respiratory assessments, use of a clinical score may facilitate care coordination by physicians, nurses, and respiratory therapists and thereby improve care of children hospitalized with asthma and bronchiolitis. Pediatr Pulmonol. 2004; 37:243–248. © 2004 Wiley‐Liss, Inc.
Internal mandibular distraction to relieve airway obstruction in infants and young children with micrognathia
Authors: Chigurupati Radhika , Massie John , Dargaville Peter , Heggie Andrew
Published: February 2004

Micrognathia may cause upper airway obstruction requiring complex medical interventions and sometimes tracheostomy. The role of distraction techniques to lengthen the mandible is yet to be clarified. The aim of this paper is to present a series of five cases in which mandibular lengthening by osteotomy and internal distraction was used to relieve airway obstruction. Five patients whose ages ranged from 4–39 months (mean, 15 months) were managed at our center with internal distraction osteogenesis to relieve airway obstruction. Three patients had a tracheostomy, and two patients had refractory airway obstruction prior to distraction. Following osteotomy and insertion of internal distraction devices, the mandible was distracted a mean of 17 mm (range, 15–25 mm). The distraction devices were removed at the end of a consolidation period ranging from 3–10 weeks. Two of 3 patients with a tracheostomy were decannulated, while the third patient with tracheostomy is awaiting choanal atresia repair before being decannulated. The two patients who were not managed with a tracheostomy but who had persistent upper airway obstruction have not required further airway intervention after mandibular distraction. In conclusion, mandibular lengthening by distraction osteogenesis can relieve airway obstruction in infants and small children. This is a promising new technique that may avoid the need for tracheostomy in some infants with micrognathia, and facilitate early decannulation in those who have a tracheostomy. Pediatr Pulmonol. 2004; 37:230–235. © 2004 Wiley‐Liss, Inc.
Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat® Soft Mist™ Inhaler vs. a conventional metered dose inhaler plus spacer in children with asthma
Authors: von Berg Andrea , Jeena Prakash M. , Soemantri Peter A. , Vertruyen André , Schmidt Peter , Gerken Fronke , Razzouk Hassan
Published: February 2004

The objective of this study was to compare the efficacy and safety of ipratropium bromide/fenoterol hydrobromide (IB/FEN; Berodual®) delivered from the novel propellant‐free Respimat® Soft Mist™ Inhaler (SMI) with that from a chlorofluorocarbon (CFC) metered‐dose inhaler (MDI) plus spacer in children with asthma. The study followed a multicenter, randomized, double‐blind (within Respimat® SMI), parallel‐group design. During the 2‐week run‐in period, patients received two actuations of CFC‐MDI tid (IB 20 μg/FEN 50 μg per actuation) via a spacer (Aerochamber®) (MDI 40/100). Patients (n = 535) were then randomized to: Respimat® SMI containing IB 10 μg/FEN 25 μg (Respimat® SMI 10/25), IB 20 μg/FEN 50 μg (Respimat® SMI 20/50), one actuation tid or CFC‐MDI containing IB 20 μg/FEN 50 μg per actuation (in total 1B 40 μg/FEN 100 μg), or two actuations tid via Aerochamber® (MDI 40/100), for 4 weeks. The primary endpoint was the change in forced expiratory volume in 1 second (FEV1) during the first 60 min after dosing (area under the curve from 0–1 h [AUC0–1 h]) on day 29. Analysis of the primary endpoint demonstrated that the efficacy of Respimat® SMI 10/25 and 20/50 was equivalent to or greater than that of MDI 40/100. Similar results indicating that Respimat® SMI 10/25 and 20/50 were not inferior to MDI 40/100 were also found on days 1 and 15. Analyses of other secondary endpoints supported these results. The safety profile of Respimat® SMI was comparable to that of the CFC‐MDI plus spacer. In conclusion, IB/FEN delivered via Respimat® SMI is at least as effective as, and is as safe as, when delivered via CFC‐MDI plus Aerochamber® in children with asthma. Use of Respimat® SMI thus enables a 2–4‐fold reduction in the nominal dose of IB/FEN, and obviates the need for a spacer. Pediatr Pulmonol. 2004; 37:264–272. © 2004 Wiley‐Liss, Inc.
Repeatability of sodium and chloride in exhaled breath condensates
Authors: Zacharasiewicz Angela , Wilson Nicola , Lex Christiane , Li Albert , Kemp Michael , Donovan Jacqueline , Hooper James , Kharitonov Sergei A. , Bush Andrew
Published: February 2004

Exhaled breath condensate (EBC) has been proposed as a noninvasive tool to study airway inflammation. The reproducibility of breath condensates was recently questioned. We therefore measured sodium and chloride concentrations in EBC and assessed the repeatability of these measurements in healthy adults and children with airway disease. We investigated technical repeatability and within‐day repeatability in five healthy adults, and compared these results with those of 10 asthmatic children and 9 children with cystic fibrosis (CF). We also assessed within‐period repeatability in the healthy controls. We report that the variability of measurements was similar for within sample, within day, and between visits, for both normals and children with asthma and CF, and that the major source of variability of sodium and chloride measurements is restricted by the reproducibility of the measurement assay method used. The wide use of EBC is more likely to depend on the development of highly sensitive and reproducible assays, rather than further refinements of the collection technique. Pediatr Pulmonol. 2004; 37:273–275. © 2004 Wiley‐Liss, Inc.
Is clinical wheezing reliable as the endpoint for bronchial challenges in preschool children?
Authors: Godfrey Simon , Uwyyed Kamal , Springer Chaim , Avital Avraham
Published: February 2004

The present study was designed to compare the clinical finding of wheeze by auscultation with an objective evaluation by acoustic means at the endpoint of a bronchial challenge in preschool children. Challenges were undertaken using a tidal breathing method in 51 preschool children as part of the investigation of possible asthma. An electronic stethoscope was used for auscultation of each lung and for the simultaneous recording of the acoustic sonogram for analysis. In 24 children, the pediatrician determined that the challenge was positive, and in 22 of these, he heard wheezing at the endpoint of the challenge. In 2 children the challenge was considered positive, based on a modest fall in saturation. The acoustic record was scanned manually for presence of wheeze defined in terms of duration, and power spectrum without reference to auscultatory findings. In positive challenges, the mean wheeze rate was 28.1% (95% CI, 19.5–36.8%), while no wheeze was detected acoustically in negative challenges. Using a cutoff wheeze rate (duration of wheeze/duration of breath phase ×100) of 10% for the whole group, clinical wheezing detected by the pediatrician had a sensitivity of 100% (no false negatives) and a specificity of 91%. In conclusion, the clinical observation of wheeze agrees very well with its detection by acoustic measurement at the endpoint of a bronchial challenge in preschool children. Pediatr Pulmonol. 2004; 37:193–200. © 2004 Wiley‐Liss, Inc.
Perceptions of value of routine care among patients with cystic fibrosis and their families
Authors: Byczkowski Terri L. , Kotagal Uma R. , Britto Maria T. , Wilmott Robert W.
Published: February 2004

Routine quarterly visits are an integral part of effective disease management for patients with cystic fibrosis (CF), regardless of the patient's age. The objective of this study was to explore the relationship between perceptions of the value of routine visits and perceived overall quality of care. The population in this study consisted of 194 patients at a single CF center. Telephone interviews were completed with 162 parents of children or adult patients (response rate, 84%) in May–June 2000. Among other satisfaction‐related questions, respondents were asked to rate: 1) overall quality of care, 2) importance of routine clinic visits in providing good preventative care, and 3) helpfulness of routine clinic visits in providing knowledge for CF care. They were also asked open‐ended questions concerning the reasons for their ratings. Perceived helpfulness and importance of routine visits were negatively associated with patient age and positively associated with perceived overall quality of care, especially for parents of teenage patients. The most common reason for low importance ratings was that the patient's health is perceived to be good, making routine clinic visits unnecessary. The most common reasons for low helpfulness ratings were that the visits are too repetitive or routine, and the family learns nothing new from them. In conclusion, tailoring routine visits to respond to different age‐based needs and making routine visits less repetitive may add value to routine visits, which could result in increased perceived overall quality of care, especially for parents of teenage patients. Pediatr Pulmonol. 2004; 37:210–216. © 2004 Wiley‐Liss, Inc.
Epidemiologic survey of 196 patients with congenital central hypoventilation syndrome
Authors: Vanderlaan Mary , Holbrook Cheryl R. , Wang Mei , Tuell Andrew , Gozal David
Published: February 2004

This study examined the cross‐sectional medical and social characteristics of children diagnosed with congenital central hypoventilation syndrome (CCHS). A detailed questionnaire was mailed to all families with a child with CCHS who are affiliated with a family network or support group. The questionnaire response rate was >75% (n = 196). Mean age was 10.22 years ±6.6 years (SD) (range, 0.4–38 years), with a 1:1 sex ratio. Multisystem involvement was almost universal among the cohort, with Hirschsprung's disease (HD) present in 16.3%; 61.7% of the children had a tracheotomy, but 14.3% were never tracheotomized, with 77 subjects (39.3%) not having a tracheostomy tube at time of survey. Respiratory support approaches varied but clearly reflected the trend towards earlier and more widespread transition to noninvasive ventilatory modalities. Significant developmental problems were noted, but attendance in regular classes occurred in the majority. Significant deficiencies in routine periodic evaluation and management were reported. In addition, the presence of CCHS was associated with a significant financial and psychosocial burden to the families. In conclusion, a comprehensive survey of 196 CCHS children and their families revealed a cross‐sectional picture of substantial medical and psychosocial complexities associated with this disorder, and pointed out substantial inadequacies in routine preventive care that appear to impose stress on the families. The emerging trend of earlier transition to noninvasive ventilatory support warrants future studies. Implementation of recommended guidelines for diagnosis and multidisciplinary follow‐up of CCHS should ultimately ameliorate the long‐term outcome of this lifelong condition. Pediatr Pulmonol. 2004; 37:217–229. © 2004 Wiley‐Liss, Inc.
Aortic hiatus gastric hernia
Authors: Spivey John F. , Ramachandran Venkataraman , Graff Gavin R.
Published: February 2004

Congenital diaphragmatic hernias are a relatively common anomaly that can present with significant respiratory morbidity and mortality. We report on a case of an aortic‐hiatal gastric hernia that initially presented with repeated episodes of respiratory distress, which was diagnosed as asthma. The diagnosis of a diaphragmatic hernia was made at 18 months of age. In the operating room, it was noted that it was an aortic hiatal hernia, which was surgically repaired. Subsequently, there has been improvement in daily respiratory symptoms. Pediatr Pulmonol. 2004; 37:279–282. © 2004 Wiley‐Liss, Inc.
Thoracic wall lesions in children
Authors: Wong Kin‐Sun , Hung Iou Jih , Wang Chao Ran , Lien Reyin
Published: February 2004

Our objective was to review the clinical features and radiographic manifestations of chest wall lesions in a pediatric chest unit. Twenty‐five patients (11 males and 14 females, aged 14 months to 15 years) were suspected of having a chest wall lesion on the basis of clinical examination and chest radiograph. A retrospective review of clinical characteristics and radiographic findings was performed in order to define the pathology and extent of lesions and outcomes of chest wall diseases in children. Thirty‐six percent of pediatric patients studied for thoracic abnormalities had anatomical variations of the thoracic cage such as sternal titling, bifid ribs, and costal cartilage convexities. Tuberculous infections of the sterum and ribs were seen in 4 cases. Osteochondromas were seen in 4 patients, and were especially noted in patients with a history of familial exostosis. Other malignant thoracic wall tumors included in this study included chondrosarcoma (n = 1), Ewing's sarcoma (n = 1), and primitive neuroectodermal tumor (n = 2). In conclusion, the protruding lesions arising from the chest wall demonstrate a wide range of normal, congenital variant, and pathologic lesions arising from the soft tissues and bony components. Those with life‐threatening lesions (less likely located in the parasternal region) are more prone to have chest pains and dyspneic respirations; in most cases, plain chest radiographs tend to have a high rate of bony or pleural involvement as well as thoracic deformities. In an endemic area of tuberculosis, costal tuberculosis should be considered in undiagnosed bony lesions; a chest CT scan could be diagnostically useful. Pediatr Pulmonol. 2004; 37:257–263. © 2004 Wiley‐Liss, Inc.
Risk factors for an intensive care unit admission in children with asthma
Authors: Belessis Yvonne , Dixon Susan , Thomsen Amanda , Duffy Barry , Rawlinson William , Henry Richard , Morton John
Published: February 2004

An admission to an intensive care unit (ICU) with asthma is a marker of asthma severity and may be a precursor of asthma death. The aim of this study was to investigate risk factors for acute severe asthma needing an ICU admission. We hypothesized that children admitted to the ICU represent a severe phenotype with identifiable premorbid clinical features. The study was case‐control in design. One hundred and forty‐one children were studied. Seventy children admitted to the ICU and 71 children admitted to the general medical ward served as cases and controls, respectively. Children were aged between 1–16 years. They underwent skin prick allergy testing, and had a nasopharyngeal aspirate and serology performed to screen for respiratory pathogens. Their parents completed an asthma and allergy symptom questionnaire and the Newcastle Asthma Knowledge Questionnaire (NAKQ). On univariate analysis, an admission to the ICU was more likely in children with 1) “frequent episodic” or “persistent” background asthma; 2) three or more previous admissions for asthma; 3) one or more asthma admissions in the previous 12 months; 4) three or more presentations to the Emergency Department (ED) in the preceding 12 months; 5) three or more positive responses on skin prick allergy testing; 6) an elevated IgE level; 7) oxygen saturation on presentation ≤91%; 8) longer duration of asthma; 9) lower level of maternal education; 10) an admission during autumn; 11) three or more siblings; and 12) being prescribed antibiotics. Risk factors that remained significant on multivariate analysis were three or more presentations to the ED in the preceding 12 months (P = 0.003), an elevated IgE level (P = 0.01), oxygen saturation on presentation ≤91% (P = 0.003), and longer asthma duration (P = 0.02). ICU patients took longer to see a doctor and to commence oral steroids. No differences were found between cases and controls in the proportion taking preventer therapy (58% vs. 52%), provided with a written asthma action plan (32% vs. 25%), or in whom spirometry or peak flow was measured (28% vs. 42%). However, rates were low in both groups. Parental asthma knowledge was generally poor. This study identified risk factors for an ICU admission in children with asthma. A potentially preventable risk factor is a history of multiple ED presentations in the past year. Specialist referral of children with multiple ED presentations may improve asthma control and reduce the risk of an ICU admission. Background asthma management remains suboptimal in children needing hospitalization. Pediatr Pulmonol. 2004; 37:201–209. © 2004 Wiley‐Liss, Inc.
Late presentation of congenital cystic adenomatoid malformation of lung in ten‐year‐old girl
Authors: Hugger Kenessa , Maupin Kevin D.
Published: February 2004

Congenital cystic adenomatoid malformation of the lung (CCAML) is uncommon, and usually presents in children with respiratory distress. We describe a girl presenting with pneumonia at age 10 years. She had been previously healthy and active, and with no previous hospitalizations or X‐rays. A chest CT scan showed right lower lobe cystic lesions suggestive of CCAML. Pediatr Pulmonol. 2004; 37:276–278. © 2004 Wiley‐Liss, Inc.
The novel Ras antagonist, farnesylthiosalicylate, suppresses growth of prostate cancer in vitro
Authors: McPherson Robert A. , Conaway Mark C. , Gregory Chris W. , Yue Wei , Santen Richard J.
Published: February 2004

BACKGROUND

The majority of men with advanced prostate cancer (PCa) respond to androgen deprivation therapy (ADT) with objective evidence of tumor regression. However, these tumors will regrow in the presence of low‐androgen levels after 12–18 months. Regrowth after ADT is associated with upregulation of growth factor (GF) mediated pathways. The compound farnesylthiosalicylate (FTS), a specific antagonist of the 21 kDa Ras protein, suppresses GF signaling and it might be a useful therapy against advanced PCa.

METHODS

We measured androgen and GF dependent growth of androgen dependent LNCaP and androgen hypersensitive CWR‐R1 PCa cells in response to specific inhibitors of GF pathways, including FTS. Inhibition of GF mediated signaling and cell‐cycle pathways was confirmed by Western blotting of extracts from treated cells.

RESULTS

Both LNCaP and CWR‐R1 cells were dependent on GF signaling pathways for cell growth. FTS, as well as suppressing cell growth, inhibited GF signaling pathway activity and reduced the levels of E2F1, p‐Rb, and p‐cdc2, all GF dependent mediators of cell‐cycle progression.

CONCLUSIONS

These data suggest that FTS might be a useful agent against PCa that has relapsed after ADT. © 2004 Wiley‐Liss, Inc.
Separation of enzymatically active and inactive prostate‐specific antigen (PSA) by peptide affinity chromatography
Authors: Wu Ping , Stenman Ulf‐Håkan , Pakkala Miikka , Närvänen Ale , Leinonen Jari
Published: February 2004

BACKGROUND

Prostate‐specific antigen (PSA) is a serine protease with highly prostate‐specific expression and an important marker for prostate cancer. We have previously identified novel PSA‐binding peptides that enhance the enzymatic activity of PSA when produced as fusion proteins.

METHOD

PSA‐binding peptides and derivatives with a spacer were chemically synthesized and used to prepare an affinity column, which was used to fractionate PSA in seminal plasma, serum, and LNCap cell culture medium.

RESULTS

Approximately 67% of seminal plasma PSA bound to the peptide affinity column and was eluted under mild conditions. Eluted PSA was intact and enzymatically active while the unbound fraction mainly contained various nicked forms. ProPSA from LNCap cells bound to the peptide column only after activation by trypsin.

CONCLUSIONS

PSA‐binding peptides can be used to separate enzymatically active and inactive forms of PSA. Thus the peptides are potentially useful as ligands for development of methods for specific detection of active free PSA. © 2003 Wiley‐Liss, Inc.
Cell specific expression of CD10/neutral endopeptidase 24.11 gene in human prostatic tissue and cells
Authors: Song Jian , Aumüller Gerhard , Xiao Fei , Wilhelm Beate , Albrecht Martin
Published: February 2004

BACKGROUND

Neutral endopeptidase (NEP/CD10) is a cell surface zinc metalloproteinase that functions as part of a regulatory loop controlling local concentrations of peptide substrates and associated peptide‐mediated signal transduction processes. In contrast to the encouraging data dealing with NEP activity and regulation in prostate epithelial cells, only a few studies are available on the cellular expression and localization of neutral endopeptidase in the prostatic stromal and cancer cells. Here, we describe the cellular localization of NEP in human prostatic tissue and cells using in situ RT‐PCR as a novel molecular biological approach.

METHODS

Immunofluorescence and Western blot experiments were performed to control the expression and distribution of the NEP in normal and malignant human prostatic tissues and cell lines. NEP gene expression was monitored by RT‐PCR, NEP mRNA was detected in paraffin tissue sections and cultured cells of human prostate by the highly sensitive method of one step‐in situ reverse transcriptase‐polymerase chain reaction (RT‐PCR).

RESULTS

NEP mRNA was detected in human prostatic tissue and in cultured cells by means of in situ RT‐PCR. Prostatic tissue showed strong signals in the glandular epithelium and weak signals in the stroma, cultured cells displayed strong signals in prostate cancer cells (LNCaP) and weak signals in stromal cells (hPCPs). Western blot experiments were performed using whole cell extracts to proof the presence of NEP protein in LNCaP and hPCPs. The experiments confirm the expression of NEP by both cell types, however, the experiment with hPCPs cells showed two bands. NEP‐immunofluorescence was strong in normal prostatic epithelium and confined to the apical plasma membrane. In dedifferentiated prostate cancer specimens, immunofluorescence of apical plasma membranes was lost, and both the cytoplasm and portions of the plasma membrane were immunoreactive for NEP. Prostate cancer cells (LNCaP) showed a strong immunoreaction of the plasma membrane and the cytoplasm. In comparison with LNCaP cells, only a weak cytoplasmic immunofluorescence was found in some stromal cells (hPCPs).

CONCLUSIONS

In normal prostatic tissue and specimens derived from human prostate cancer, NEP mRNA and protein are expressed mainly by the epithelial cells and to a minor extent by the stromal cells of human prostate glands. In situ RT‐PCR is a powerful and straightforward approach for the routine and rapid detection of cellular specific expression of low copy genes. © 2003 Wiley‐Liss, Inc.
Clinical understaging in patients with prostate adenocarcinoma submitted to radical prostatectomy: Predictive value of serum chromogranin A
Authors: Sciarra Alessandro , Voria Giuseppe , Monti Salvatore , Mazzone Luigi , Mariotti Gianna , Pozza Mariangela , D'Eramo Giuseppe , Silverio Franco Di
Published: February 2004

PURPOSE

To evaluate whether the pretreatment determination of serum chromogranin A (CgA) can provide information beyond that obtained with serum prostate specific antigen (PSA) and Gleason score at biopsy as a predictive factor of clinical understaging (T2‐pT3) of prostate adenocarcinoma.

MATERIALS

In this prospective study, we analyzed 83 consecutive patients with clinical T2N0M0 prostate adenocarcinoma submitted to radical prostatectomy (RRP). On the same day of RRP, before surgery, a blood sample for the determination of serum total PSA and CgA levels (RIA) was obtained.

RESULTS

After RRP, 27 of the 83 cases (32.5%) showed extracapsular disease extension (pT3) at the final pathological examination and were considered clinically understaged. A significant association between serum CgA and pathological stage (r = 0.3830; P = 0.0004) was found. At the multivariate analysis, serum CgA and PSA, but not biopsy Gleason score, were found to be significant pretreatment independent predictors of pT3 at RRP (P = 0.00004 and P = 0.0018, respectively). The relative risk of clinical understaging significantly varied according to serum CgA levels. Using a CgA cut‐off value of 60 ng/ml, PPV and NPV for clinical understaging were 0.5161 and 0.7885, respectively (P = 0.0072).

CONCLUSIONS

Serum CgA could be incorporated into risk assessment models of newly diagnosed prostate cancer. © 2003 Wiley‐Liss, Inc.
Molecular characterization of the commonly used human androgen receptor expression vector, pSG5‐AR
Authors: Litvinov Ivan V. , Chang Chawnshang , Isaacs John T.
Published: February 2004

BACKGROUND

pSG5‐AR is a commonly used androgen receptor (AR) expression vector. However, a detailed molecular characterization of this construct has not been published. In this study, we describe the molecular organization of the above plasmid and analyze the AR transcript coded by the above construct.

METHODS

pSG5‐AR was sequenced by the standard dideoxy sequencing method. The obtained sequence was analyzed by the DS Gene software.

RESULTS

A molecular map of the pSG5‐AR plasmid as well as a map of the AR insert is provided. The AR transcript from pSG5‐AR is lacking significant portions of the 5′‐ and 3′‐untranslated region (UTR) and contains shorter than average CAG and GGC repeats.

CONCLUSIONS

The above characteristics of the pSG5‐AR are significant and may result in different regulation pattern of expression of the expressed AR in comparison to the endogenous gene. Such a conclusion is based on the knowledge that post‐transcriptional regulation plays an important role in controlling the levels of AR in a cell. Such regulation is controlled by the regulatory elements within the 5′‐ and 3′‐UTRs of the AR transcript. In addition, this vector might be coding for an AR with a different transactivational capacity than the endogenous AR gene. The transactivational activity of AR was shown to be affected by the size of the trinucleotide‐repeat‐regions (CAG and GGC) within the gene. © 2004 Wiley‐Liss, Inc.
Effects of transforming growth factor‐β1 on parathyroid hormone‐related protein mRNA expression and protein secretion in canine prostate epithelial, stromal, and carcinoma cells
Authors: Sellers Rani S. , LeRoy Bruce E. , Blomme Eric A.G. , Tannehill‐Gregg Sarah , Corn Stephanie , Rosol Thomas J.
Published: February 2004

BACKGROUND

Bone metastases of prostate carcinoma are associated with osteoblastic metastases. Tumor‐derived factors, such as parathyroid hormone‐related protein (PTHrP), may promote the development of osteoblastic metastases. We examined the effect of transforming growth factor‐β1 (TGFβ1) on PTHrP mRNA expression and PTHrP secretion in normal canine prostate epithelial cells (PEC) and stromal cells (PSC), and in canine prostate carcinoma cells (PCC).

METHODS

Primary cultures of PEC, PSC, and PCC were produced. The effect of TGFβ1 on PTHrP mRNA expression was measured by Northern blot, and secretion of PTHrP into culture medium was measured by immunoradiometric assay (IRMA). Degradation of recombinant‐human PTHrP (rhPTHrP) (1–84) inoculated in prostrate cell cultures was measured over 24 hr. Arginine esterase (AE) activity in tissue and conditioned medium was also measured.

RESULTS

TGFβ1 increased PTHrP mRNA expression in a time‐ and dose‐dependent manner in PEC and in PCC. TGFβ1 decreased PTHrP mRNA in PSC. TGFβ1 significantly increased PTHrP secretion (P ≤ 0.05) into PEC but not PSC conditioned medium. rhPTHrP was significantly (P ≤ 0.05) degraded in PEC conditioned medium as compared to PSC conditioned medium. AE activity was present in prostate and prostate carcinoma tissue, but not in conditioned medium from PEC or PSC.

CONCLUSIONS

TGFβ1 increased PTHrP mRNA expression in canine PEC and PCC, and decreased expression in PSC. This regulatory pathway may be important in the pathogenesis of osteoblastic metastases. © 2004 Wiley‐Liss, Inc.
The regulation of clinical trials in South Africa
Authors: Baird Debbie , van Niekerk Diederik
Published: February 2004

In South Africa the Medicines Control Council (MCC) is a statutory body responsible for the regulation of all clinical trials undertaken for both non‐registered and registered medicines. In this article, we first take a brief look at the legislative background and its development over the last 30 years. We then introduce you to the current regulatory environment, including the structure of the MCC and the clinical trials approvals process. Finally, we look briefly to the future of clinical trials regulation and the progress made by the successful collaboration between the MCC and the clinical trials industry. Copyright © 2004 John Wiley & Sons, Ltd.
The Myth of the SOP
Authors: Blackmore Aliah
Published: February 2004

The analysis in this paper is based on the assumption that the standard operating procedure (SOP) is a product of the implicit tension between the driving forces of innovation and regulation. In this context, the current and potential capacity of the SOP in the modern organisation is examined with regard to the continually, evolving interaction between the organisational workflow and the know‐how of the employees within the organisation. This paper concentrates on the discrepancy between the process to which the SOP refers and the know‐how implemented by the process participant. It is argued that this deviation from ‘reality’ indicates that the SOP currently has the impact of an organisational myth. The paper concludes by outlining some strategies for reducing this deviation. Copyright © 2004 John Wiley & Sons, Ltd.
A revised guideline for medical device clinical investigations: ISO 14155 Part 1 and 2: 2003
Authors: Giroud Danielle
Published: February 2004

The international standard (International Organization for Standardization (ISO)) ISO 14155:1996 ‘Clinical Investigation of Medical Devices for Human Subjects’ has been updated in 2003. The revised ISO 14155:2003 focuses on general requirements for clinical studies (Part 1) and the clinical investigation plan (Part 2). The documents provide manufacturers with significantly improved guidelines for the conduct of clinical investigations with medical devices. This article highlights the main differences between the previous version of 1996 and the new version of 2003. The article also points out some areas in the new ISO 14155 which may still need further improvement. Copyright © 2004 John Wiley & Sons, Ltd.
Constrained stabilization problems for discrete‐time linear plants
Authors: Saberi Ali , Shi Guoyong , Stoorvogel Anton A. , Han Jian
Published: February 2004

In this paper we study discrete‐time linear systems with full or partial constraints on both input and state. It is shown that the solvability conditions of stabilization problems are closely related to important concepts, such as the right‐invertibility of the constraints, the location of constraint invariant zeros and the order of constraint infinite zeros. The main results show that for right‐invertible constraints the order of constrained infinite zeros cannot be greater than one in order to achieve global or semi‐global stabilization. This is in contrast to the continuous‐time case. Controllers for both state feedback and measurement feedback are constructed in detail. Issues regarding non‐right invertible constraints are discussed as well. Copyright © 2004 John Wiley & Sons, Ltd.
A new non‐linear sliding‐mode torque and flux control method for an induction machine incorporating a sliding‐mode flux observer
Authors: Chen Fang , Dunnigan Matthew W.
Published: February 2004

In this paper a novel sliding‐mode control algorithm, based on the differential geometry state‐co‐ordinates transformation method, is proposed to control motor torque directly. Non‐linear feedback linearization theory is employed to decouple the control of rotor flux magnitude and motor torque. The advantages of this method are: (1) The rotor flux and the generated torque can be accurately controlled. (2) Robustness with respect to matched and mismatched uncertainties is obtained. Additionally, a varying continuous control term is proposed. As a result, chattering is eliminated without sacrificing robustness and precision. The control strategy is based on all motor states being available. In practice the rotor fluxes are not usually measurable, and a sliding‐mode observer is derived to estimate the rotor flux. The observer is designed to possess invariant dynamic modes which can be assigned independently to achieve the desired performance. Furthermore, it can be shown that the observer is robust against model uncertainties and measurement noise. Simulation and practical results are presented to confirm the characteristics of the proposed control law and rotor flux observer. Copyright © 2004 John Wiley & Sons, Ltd.