bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori infection, histopathological gastritis and gastric epithelial cell apoptosis in children
Authors: Singh Manisha , Prasad Kashi N. , Krishnani Narendra , Saxena Ashish , Yachha Surender K. 
Published: August 2010

Abstract Aim: Features of gastritis and gastric epithelial cell apoptosis in children infected with Helicobacter pylori genotypes are seldom studied. Therefore, we investigated the relationship between vacA genotypes and the severity of gastritis, and gastric epithelial cell apoptosis in H. pylori‐infected children. Methods: Antral biopsies from 52 children infected with H. pylori vacA genotypes (s1a/m1 = 17, s1a/m2 = 21 and s2/m2 = 14) were analysed for severity of gastritis on histopathology. Fifteen biopsies infected with different vacA genotypes were studied for gastric epithelial cell apoptosis by terminal uridine deoxynucleotidyl nick‐end labelling. Results: Children infected with the s1a/m1 and s1a/m2 vacA genotypes had higher severity of chronic inflammation than the s2/m2 genotype (s1 a/m1 vs s2/m2, p=0.05; s1a/m2 vs s2/m2, p=0.01). The vacA s1a allele was more independently associated with severe chronic inflammation than the s2 allele (p=0.02). Children infected with the s1a/m1 and s1a/m2 strains had higher gastric epithelial cell apoptosis than the s2/m2 strain (s1a/m1 or s1a/m2 vs s2/m2, p<0.0001). Conclusion: The s1a/m1 and s1a/m2 H. pylori vacA genotypes have significantly higher association with severe chronic gastritis and gastric epithelial cell apoptosis than the s2/m2 genotype in children. The role of H. pylori vacA genotypes and their allelic subtypes in relation to pathogenicity and disease potential in children needs further studies.
Time to screen for proteinuria?
Authors: Tullus Kjell 
Published: August 2010

AbstractScreening for proteinuria in childhood is performed in some countries but remains a controversial subject. During the last decade, a greater understanding of the importance of proteinuria for the long‐term prognosis of children with renal diseases has been gained. Exciting new data also show that proteinuria is a prognostic factor for long‐term cardiovascular outcome. Conclusion: In my opinion, there are still not strong enough reasons to support the routine screening of healthy children for proteinuria.
ApoB‐100 and ApoB/ApoA‐1 ratio in children and adolescents from families with very early myocardial infarction
Authors: Dirisamer Albert , Stadler Alfred , Bucek Robert. A. , Widhalm Kurt 
Published: August 2010

AbstractDirisamer A, Stadler A, Bucek RA, Widhalm K. ApoB‐100 and ApoB/ApoA‐1 ratio in children and adolescents from families with very early myocardial infarction. Acta Paediatrica 00. Stockholm. ISSN 0803–525. Aim: The relationship between apolipoprotein B, LDL/ApoB, ApoB/ApoA‐1, lipids and a family history of very early myocardial infarction (parent and/or grandparent <45 years) was studied in 46 children compared with 64 controls. Methods: 19 children came out of families with a myocardial infarction (MI) of the father and 27 children with MI of a grandparent. Results: In the whole risk group LDL‐C, ApoB and ApoB/ApoA‐1 ratio showed the most significant relationship, whereas in children from families with MI of the father ApoB level showed the strongest association with family history of MI. No relationship could be found for ApoA1, HDL‐C and LDL/ApoB. Conclusion: Our results show that levels of ApoB, LDL‐C and ApoB/ApoA‐1 might be better predictors in children from families of very early MI as compared with ApoA‐1, HDL‐C and LDL/ApoB.
pH and nitric oxide synthase activity and expression in bovine aortic endothelial cells
Authors: Nagy Sandor , Harris Michael B. , Ju Hung , Bhatia Jatinder , Venema Richard C. 
Published: August 2010

Abstract Aim: Nitric oxide (NO) plays an important role in the transition from intrauterine to extrauterine life. If this transition fails, a condition called persistent pulmonary hypertension of the neonate (PPHN) may develop. The current treatment modalities for this disease include induction of alkalosis by hyperventilation or alkali infusion, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation. There is evidence from animal studies that the elevated pH, not the low pCO2 is responsible for the resultant pulmonary vasodilatation. In this study, we examined the effect of pH on the activity and expression of endothelial nitric oxide synthase (eNOS) in cultured bovine aortic endothelial cells (BAEC) as a possible explanation for the pH dependent drop in pulmonary vascular resistance. Methods: BAEC were exposed to a pH gradient of 7.1–7.6 for 4 h (short‐term) and 16 h (long‐term). Standard Western blotting technique was used to detect expression of eNOS. Activity was measured by an indirect assay using bovine aortic smooth muscle cells (BASM) as reporter cells and measuring cGMP levels as a marker of NO production. The cells were exposed to the pH gradient for a total of 4 h and measurement were made at 30, 60 and 90 min, and 2, 3 and 4 hours. Results: eNOS activity and expression remained unchanged during the four and sixteen hours of exposure. Conclusion: In this in vitro experiment, we could not demonstrate an alkalosis‐induced increase in eNOS activity and expression. The clinically observed pH dependent vasodilatation does not appear to be directly mediated through the induction of eNOS.
Partial cerebellar hypoplasia in a patient with Prader‐Willi syndrome
Authors: Titomanlio Luigi , De Brasi Daniele , Romano Alfonso , Genesio Rita , Diano Alvaro A. , Giudice Ennio DEL 
Published: August 2010

AbstractWe report a 3‐y‐old male infant with Prader‐Willi syndrome (PWS) caused by a de novo interstitial deletion of 15q11‐q13. Additional features included a right cerebellar hemisphere hypoplasia. The extent of deletion was determined by FISH analysis using an SNRPN PW/AS probe that maps in the PWS/AS critical region (CR) and with specific 15q BACs. We unravelled an interstitial 15q11.2‐q13.1 deletion spanning about 3 Mb. Conclusion: To date only a few other PWS patients—including autopsy cases—with CNS structural anomalies have been described. Our case report adds knowledge to the issue of brain involvement in Prader‐Willi syndrome. Further MRI studies of PWS patients will be helpful to clarify a correlation between PWS and brain abnormalities.
Identification of the 5T‐12TG allele of the cystic fibrosis transmembrane conductance regulator gene in hypertrypsinaemic newborns
Authors: Padoan Rita , Corbetta Carlo , Bassotti Alessandra , Seia Manuela 
Published: August 2010

AbstractIn order to increase knowledge of the pathogenic effect of the 5T‐12TG allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, we evaluated its presence in 24 hypertrypsinaemic newborns with borderline sweat tests. Among 20 CFTR‐identified alterations, the 5T‐12TG haplotype was the second most frequent mutation (14.6%) over F508del. Conclusion: Our study suggests the need for searching for this allele in hypertrypsinaemic infants with inconclusive sweat tests.
Assessment of differences in linear growth among populations in the WHO Multicentre Growth Reference Study
Authors:   WHO MULTICENTRE GROWTH REFERENCE STUDY GROUP, de Onis Mercedes 
Published: August 2010

Abstract Aim: To assess differences in length/height among populations in the WHO Multicentre Growth Reference Study (MGRS) and to evaluate the appropriateness of pooling data for the purpose of constructing a single international growth standard. Methods: The MGRS collected growth data and related information from 8440 affluent children from widely differing ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the USA). Eligibility criteria included breastfeeding, no maternal smoking and environments supportive of unconstrained growth. The study combined longitudinal (birth to 24 mo) and cross‐sectional (18–71 mo) components. For the longitudinal component, mother–infant pairs were enrolled at delivery and visited 21 times over the next 2 y. Rigorous methods of data collection and standardized procedures were applied across study sites. We evaluate the total variability of length attributable to sites and individuals, differences in length/height among sites, and the impact of excluding single sites on the percentiles of the remaining pooled sample. Results: Proportions of total variability attributable to sites and individuals within sites were 3% and 70%, respectively. Differences in length and height ranged from −0.33 to +0.49 and −0.41 to +0.46 standard deviation units (SDs), respectively, most values being below 0.2 SDs. Differences in length on exclusion of single sites ranged from −0.10 to +0.07, −0.07 to +0.13, and −0.25 to +0.09 SDs, for the 50th, 3rd and 97th percentiles, respectively. Corresponding values for height ranged from −0.09 to +0.08, −0.12 to +0.13, and −0.15 to +0.07 SDs. Conclusion: The striking similarity in linear growth among children in the six sites justifies pooling the data and constructing a single international standard from birth to 5 y of age.
X‐chromosome inactivation: role in skin disease expression
Authors: Happle Rudolf 
Published: August 2010

AbstractThe occurrence of X inactivation in mammals has the consequence that all women are functional mosaics. In X‐linked skin disorders, Lyonization usually gives rise to a mosaic pattern, as manifest by the appearance of the lines of Blaschko. This arrangement of lesions is observed in male‐lethal X‐linked traits, such as incontinentia pigmenti, focal dermal hypoplasia, Conradi–Hünermann–Happle syndrome, oral–facial–digital syndrome type 1 and MIDAS (microphthalmia, dermal aplasia and sclerocornea) syndrome, as well as in various X‐linked non‐lethal phenotypes, such as hypohidrotic ectodermal dysplasia of Christ–Siemens–Touraine, IFAP (ichthyosis follicularis–alopecia–photophobia) syndrome and X‐linked dyskeratosis congenita. Analogous X‐inactivation patterns have been documented in human bones, teeth, eyes and, possibly, the brain. Patterns that are distinct from the lines of Blaschko are also seen, such as the lateralization observed in CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, and the chequerboard pattern seen in women heterozygous for X‐linked congenital hypertrichosis. Exceptional cases of either severe or absent involvement in a woman heterozygous for an X‐linked trait can be explained by skewing of X inactivation. Some X‐linked skin disorders are caused by genes that escape inactivation, which is why heterozygous female ‘carriers’ of these disorders do not show mosaicism. A well‐known example is X‐linked recessive ichthyosis due to steroid sulphatase deficiency, the locus for which is situated at the tip of the short arm of the X chromosome and does not undergo Lyonization. On the other hand, in the case of Fabry disease, the gene encoding α‐galactosidase A is subject to inactivation. Remarkably, however, the skin lesions of women do not show a mosaic pattern. Conclusion: In the various X‐linked skin disorders, affected women show quite dissimilar degrees of involvement and forms of manifestation because X inactivation may give rise to different patterns of functional mosaicism. Paradoxically, no such pattern is observed in women with Fabry disease. Like many X‐linked diseases, Fabry disease should neither be called recessive nor dominant, because these dichotomous terms are obscured by the mechanism of X inactivation.
The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease
Authors: Beck Michael 
Published: August 2010

AbstractFabry disease is a rare lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A. The resultant storage of undegraded glycolipids leads to the progressive development of potentially life‐threatening manifestations affecting multiple organ systems in the body. This paper describes the development of the Mainz Severity Score Index (MSSI), a scoring system for patients with Fabry disease. Conclusion: The MSSI score has been proven to be representative in patients with ‘classic’ Fabry disease and may be useful for monitoring clinical improvement in patients receiving enzyme replacement therapy.
Inhibition and reversibility of renal changes: lessons from diabetic kidney disease
Authors: Flyvbjerg Allan 
Published: August 2010

AbstractThis review describes the clinical characteristics of kidney disease in patients with diabetes in terms of functional and morphological changes, and summarizes the risk factors for progression of disease and the knowledge available today on various treatment modalities. New insights into the pathogenesis of kidney disease in diabetic patients are also reviewed in the context of the nephropathy of Fabry disease. Newly recognized pathways that play a role in the development/progression of kidney disease in patients with diabetes include metabolic factors, (e.g. advanced glycation end products), intracellular signalling proteins (e.g. protein kinase C) and growth factors/cytokines (e.g. growth hormone, insulin‐like growth factors, transforming growth factor β and vascular endothelial growth factor). As classic examples of progress in our understanding of the pathogenesis of kidney disease in patients with diabetes, the relationship between two growth factor/cytokine‐systems and the development of diabetic kidney disease is reviewed, including a description of well‐known or potential therapeutic strategies targeting the two systems. Conclusion: It is hoped that the new pathogenetic insights into diabetic kidney disease may facilitate the development of new drugs for the treatment of this and related kidney diseases.
Extracellular matrix turnover and disease severity in Anderson–Fabry disease
Authors: Shah J. S. , Hughes D. , Tayebjee M. , MacFadyen R. , Mehta A. , Elliott P. M. 
Published: August 2010

Abstract Background: Anderson–Fabry disease (AFD) is an inherited metabolic disease associated with premature death from cardiovascular and renal disease. Recent studies have shown that patients with AFD develop progressive left‐ventricular (LV) remodelling. We hypothesized that patients with AFD have abnormal extracellular matrix (ECM) turn over compared with normal controls. Methods and Results: Twenty‐nine (mean age (±SD), 44.1±11.7 years; 15 male) consecutive patients with AFD and 21 age‐ and gender‐matched controls (mean age, 39.7±11.3 years; 10 male) had serum analysed for matrix metalloproteinase‐9 (MMP‐9), tissue inhibitor of metalloproteinases‐1 (TIMP)‐1 and ‐2 levels using an in‐house enzyme‐linked immunosorbent assay. MMP‐9 levels were significantly elevated in patients compared with controls (mean difference from controls, 427.1 ng/ml, 95% CI, 252.1 – 602.2 ng/ml, p<0.001). There was a negative correlation between MMP‐9 and fractional shortening (r = − 0.5, p=0.01). There were no differences in TIMP levels between patients and controls. There was no correlation between LV mass or maximal LV wall thickness and MMP‐9 levels. There was a positive correlation between MMP‐9 levels and the Mainz Severity Score Index (r = 0.5, p=0.01). These relationships remained significant, independently of gender and age‐using stepwise linear regression analysis. Conclusion: Patients with AFD have higher levels of MMP‐9 compared with controls. MMP‐9 levels correlated with clinical markers of disease severity suggesting that abnormal ECM turnover plays an important role in the pathogenesis of AFD. This in turn suggests that MMP‐9 levels may be a useful circulating marker for disease severity and a surrogate marker for the response to enzyme replacement therapy.
Cardiac evaluation of myocardial involvement in Anderson–Fabry disease by cardiac magnetic resonance imaging: a study of five patients
Authors: Bacchion F. , Russo N. , Cacciavillani L. , Corbetti F. , Tognana G. , Burlina A. , Burlina A. , Sarais C. , Angelini A. , Razzolini R. 
Published: August 2010

Abstract Background: Anderson–Fabry disease (AFD) is an X‐linked inborn error of glycosphingolipid metabolism due to a deficiency of the lysosomal hydrolase α‐galactosidase A associated with multisystemic involvement subsequent to deposition of neutral glycosphingolipid in many organs. Over time, microvascular disease of the kidneys, heart and brain progresses leading to premature death. Aim: To evaluate cardiac involvement in patients with AFD using gadolinium‐enhanced cardiovascular magnetic resonance imaging (MRI). Methods: We studied five patients (age range, 23–53 years two males and three females belonging to two different families) with a diagnosis of AFD made by low plasma α‐galactosidase activity and molecular analysis of mutations. Four of them had been treated with recombinant human α‐galactosidase A replacement therapy for at least 14 months. Clinical manifestations were assessed and an electrocardiogram and echocardiography (ECG) were performed in all patients for a preliminary evaluation of the cardiac involvement before initiating therapy. Coronary angiography and endomyocardial biopsy were performed in one patient. All patients finally underwent cine and late‐phase gadolinium‐enhanced cardiovascular MRI. Results: ECG and echocardiogram showed left ventricular hypertrophy in two patients and mitral insufficiency in three. Cine‐MRI confirmed these findings. Angiography showed the coronary artery to be free from lesions and histology revealed hypertrophic myocytes and the presence of fibrosis. Gadolinium‐enhanced MRI revealed hyperenhancement, mainly in the basal inferolateral wall, both in the subendocardial and mid‐wall layer, in the three older patients. Conclusion: These observations suggest that myocardial fibrosis occurs in Anderson–Fabry disease and may contribute to the hypertrophy and the natural history of the disease. The characteristic patterns of hyperenhancement differ from those seen in other myocardial pathologies (myocardial infarction, hypertrophic cardiomyopathy) and this may help in the differential diagnosis of the late‐onset forms (cardiac variant). Mitral valve insufficiency was also present in three patients, and this could be due to dysfunction of the inferolateral wall.
GAUCHER DISEASE AND MISCELLANEOUS
Authors: Wendt S. , Mengel E. , Beck M. 
Published: August 2010

Abstract Introduction: The most common subtype of Gaucher disease is the non‐neuronopathic form with only visceral symptoms. At the opposite end of the spectrum is chronic neuronopathic Gaucher disease with severe neurological symptoms and typically a decreased life span. Methods: We report 15 patients (median age at manifestation, 1.2 years) with chronic neuronopathic Gaucher disease and 20 patients with non‐neuronopathic Gaucher disease (median age at manifestation, 3.0 years). Results: In most patients with chronic neuronopathic Gaucher disease (12 out of 15), the 1448T‐C mutation was found, whereas in 18 out of 20 patients with non‐neuronopathic Gaucher disease the mutation identified was N370S. At initial presentation, patients with chronic neuronopathic Gaucher disease had significantly higher chitotriosidase levels (median, 21 307 versus 5611 nmol/ml/hour). Thirteen of these patients had a strabismus, all patients suffered from saccade initiation failure, and eight of the nine patients assessed showed abnormal brainstem auditory evoked response (BAER) (none of these were found in patients with non‐neuronopathic disease). Three of the patients with neuronopathic disease had multifocal myoclonic epilepsy. Additionally, in ten of these patients pulmonary manifestation was seen (versus three of the patients with non‐neuronopathic Gaucher disease). After treatment with enzyme replacement therapy (60–120 IU/kg) for between 18 months and 8 years, three of the children with chronic neuronopathic Gaucher disease experienced an improvement in BAER. Eight out of the nine patients with bone pain before enzyme replacement therapy had no pain. The patients with non‐neuronopathic Gaucher disease received 60 IU/kg or less to maintain their therapy response and were observed for 3–13 years. Conclusion: Neurological manifestations are often associated with chitotriosidase activities greater than 20 000. In patients with chronic neuronopathic Gaucher disease, a higher dose between 60 and 120 IU/kg bodyweight may be required to reduce the visceral manifestations of disease.
Growth hormone therapy—established uses in short children
Authors: Schwenk W. Frederick 
Published: August 2010

AbstractSince the first reported efficacious use of human growth hormone in 1958, numerous children have been treated with this hormone. This review discusses the five indications for use of human growth hormone in children that have been approved to date by the United States Food and Drug Administration. Conclusion: Further, long‐term studies will be needed to address the optimal use of this hormone in each of these conditions.
Non‐conventional use of growth hormone therapy
Authors: Cappa Marco , Ubertini Graziamaria , Colabianchi Diego , Fiori Rossana , Cambiaso Paola 
Published: August 2010

AbstractHuman growth hormone therapy is allowed in certain clinical conditions according to national healthcare criteria. Growth hormone, however, produces a wide spectrum of effects. Linear growth is only one of the many expected results, and there are interesting possibilities to explore which could provide additional means of improving the quality of life for the ever‐increasing numbers of chronic paediatric patients. Conclusion: In this review, we discuss the rationale for and possibility of using growth hormone therapy in some conditions not strictly related to growth hormone deficiency.
Stones, bones, and heredity
Authors: Milliner Dawn S. 
Published: August 2010

AbstractGenetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN‐5 gene with impaired kidney‐specific CLC‐5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low‐molecular‐weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine–glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined.ConclusionThese disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.