bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of the ductus venosus
Authors: Sothinathan Uma , Pollina Elena , Huggon Ian , Patel Shailesh , Greenough Anne
Published: August 2010

Absence of the ductus venosus is a rare vascular anomaly, but clinicians should be aware that it can be diagnosed antenatally and the prognosis is dependent on the type of associated malformation of the fetal vascular system. Antenatal detection of a single umbilical artery and unexplained cardiomegaly should prompt detailed examination of the umbilical and portal veins. Absent ductus venosus is associated with three main patterns of abnormal venous circulation, the worst prognosis being seen when the umbilical vein bypasses the liver and connects to the right atrium. Fetuses with absence of the ductus venosus are at risk of other congenital anomalies including facial clefts, hemivertebrae, cardiac, genitourinary, gastrointestinal anomalies; affected infants also have a poorer prognosis. In conclusion, fetuses with features suggestive of absence of ductus venosus require referral to a tertiary perinatal center.
Attention‐deficit/hyperactivity disorder: A plausible mouse model?
Authors: Granon Sylvie , Changeux Jean‐Pierre
Published: August 2010

Attention‐deficit/hyperactivity disorder (ADHD) is a multifactorial and heterogeneous disorder, highly prevalent in children and characterized by three main components: inattention, lack of inhibitory control and hyperactivity. Epidemiological evidence reveals that ADHD is associated with nicotine exposure, mostly, with prenatal cigarette smoking. Mice deleted for the β2‐subunit gene of the neuronal nicotinic receptor are proposed as a simple and reliable animal model for ADHD.

Conclusion: Nicotinic agonists targeting the α4β2 nicotinic receptors alleviate ADHD symptoms and may possibly contribute to an efficient therapy of ADHD children.
Alcohol consumption, smoking and breastfeeding in the first six months after delivery
Authors: Alvik Astrid , Haldorsen Tor , Lindemann Rolf
Published: August 2010

Aim: To study alcohol use and smoking after delivery, and to relate this to breastfeeding. Methods: A longitudinal questionnaire study, representative of pregnant women in Oslo. Ninety‐two per cent agreed to join the study. Non‐Norwegian speaking and/or immigrants from non‐western countries were not invited. Questionnaires were answered at 17 (T1) and 30 (T2) wk of pregnancy, and 6 mo after term (T3). They were completed by 93% (1749 women) at T1, 82% at T2, and 92% at T3. Results: Six months after delivery, 80% reported alcohol use. The mean alcohol consumption per week was less than half compared to the last 6 mo before pregnancy. The women with the highest pre‐pregnancy use reduced the most. Binge drinking (≥ 5 drinks) was also reported by half as many women (29%). However, 6% reported 12 or more drinks per occasion at least once. No demographic or mental health variables predicted binge drinking after pregnancy. Smoking 6 mo after pregnancy was reported by 18%, a reduction of 50% from before pregnancy. Women breastfeeding for at least 6 mo had higher education, less frequently reported binge drinking after delivery and less frequently suffered postnatal depression.

Conclusion: In this population‐based sample were 86% breastfed for at least 6 mo, the level of binge drinking is concerning.
Attitudes and feelings towards menstruation and womanhood in girls at menarche
Authors: Rembeck Gun I. , Möller Margareta , Gunnarsson Ronny K.
Published: August 2010

Aim: To elucidate early adolescent girls’ attitudes, thoughts and feelings towards menstruation and their bodies. Methods: 309 12‐y‐old girls answered questionnaires. One part of the questionnaire dealt with thoughts and feelings towards menstruation. The other part dealt with thoughts and feelings towards menstruation and sex and ability to communicate on aspects of womanhood. Results: Postmenarcheal girls were less positive towards menstruation than premenarcheal girls (p=1×10−6). Many girls (43%) did not reaffirm the statement “I like my body” and almost one quarter stated being teased for their appearance. Many of the girls claimed that they had been called “cunt” (38%) or “whore” (46%). If called “cunt” or “whore”, 17% stated that they felt alone, 76% felt anger and 50% were offended. Mothers were those with whom girls could most easily “chat” about their period. Sixty‐seven per cent received information about menstruation from school nurses.

Conclusion: Wanting to be an adult and liking that their body develops seem to be associated with a more positive feeling towards menstruation. Furthermore, mothers’ timing and ability to communicate attitudes towards menstruation and the body are as important as those in a girl's immediate environment.
Health before and after adoption from Eastern Europe
Authors: Landgren Magnus , Andersson Grönlund Marita , Elfstrand Per‐Olof , Simonsson Jan‐Erik , Svensson Leif , Strömland Kerstin
Published: August 2010

Design: A population‐based study of pre‐adoption, arrival and post‐adoption health. Aim: To report prenatal and postnatal background factors, morbidity, growth and development in adoptees from Eastern Europe. Subjects and Methods: All 99 children born in Eastern Europe between 1990 and 1995 and adopted to western Sweden during 1993–1997 were invited to participate in the study. Altogether, 76 (77%) participated. Medical records from the birth countries, from the examination at arrival and from medical reports made during a mean post‐adoption period of 5 years were evaluated. Results: Low birth weight (≤2500 g) occurred in 48%. Congenital malformations were found in 22%. The biological mothers of 33% of the children had been considered alcoholics, and 16% of the children's mothers had been diagnosed with a psychiatric disability. A high incidence of infectious diseases, neurodevelopment disorders and growth retardation had been noted during the pre‐adoption period. Upon arrival in Sweden 75% were diagnosed with a medical condition, most often an infection. After a 5‐year post‐adoption period, small head circumference was associated with alcohol exposure during pregnancy and 46% had at least one neurodevelopment or behavioural disorder.

Conclusion: Adverse prenatal and perinatal factors, congenital malformations and post‐adoption neurodevelopment disorders were common. Adoptees and adopters have complex needs for health support and information.
Initial management of children with newly diagnosed idiopathic thrombocytopenic purpura in the Nordic countries
Authors: Treutiger Iris , Rajantie Jukka , Zeller Bernward , Elinder Göran , Rosthöj Steen ,   ON BEHALF OF THE NOPHO ITP WORKING GROUP
Published: August 2010

Aim: To describe the management practices of newly diagnosed childhood idiopathic thrombocytopenic purpura (ITP) in the Nordic countries. Methods: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0–14 years and at least one platelet count <30×109/L. Results: 506 children from 98 departments were registered. A diagnostic bone marrow aspiration was obtained within 14 days in 33%. Platelet and/or red blood cell transfusion was given in 11%. 287 children (57%) received platelet‐enhancing therapy with intravenous immune globulin (IVIG) or corticosteroids within 14 days of diagnosis, IVIG being the first line choice in over 90% of the cases. There were noticeable national differences in the management. The decision to start drug treatment within two days of diagnosis was influenced mainly by the platelet count. Neither early treatment nor response to treatment changed the risk of chronic disease.

Conclusion: This study has shown a great variation in the management practices of children with newly diagnosed ITP. Prospective studies are required to produce evidence‐based recommendations for this patient group.
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

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

Screening 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

Dirisamer 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

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

We 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

In 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

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

The 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

Fabry 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

This 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

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

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

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

Since 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

Human 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

Genetic 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.

Conclusion

These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.
Macrophage activation syndrome in juvenile idiopathic arthritis
Authors: Cortis Elisabetta , Insalaco Antonella
Published: August 2010

Macrophage activation syndrome (MAS) is a rare and potentially lethal complication of chronic rheumatic diseases of childhood, in particular of systemic‐onset juvenile idiopathic arthritis (s‐JIA), resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. The onset, acute and dramatic, may mimic a flare of the underlying disease or a severe sepsis. Diagnosis is difficult and, until now, no specific criteria have been developed. Laboratory data show pancytopenia, coagulopathy, low ESR and low concentrations of serum albumin, and high levels of ferritin, liver enzymes and triglycerides. Activated macrophages are found in various organs, particularly in bone marrow. Most hypotheses on the mechanism underlying MAS are based on the data obtained in primary haemophagocytic lymphohistiocytosis (HLH), a genetic disease very similar to MAS. Prompt diagnosis is essential because prognosis is highly related to early treatment. The first approach was to use intravenous methylprednisolone pulse therapy; cyclosporin A was proposed in patients resistant to steroids. We describe nine patients affected by haemophagocytosis: seven patients developed MAS and two patients developed HLH. A child with s‐JIA developed three episodes of MAS. After the third episode, as there was no improvement with pulses of methylprednisolone and cyclosporine, he was successfully given etanercept.

Conclusion: Our data, together with a similar, published observation, suggest that the TNF inhibitor etanercept is potentially useful for obtaining remission in children not responding to steroids and cyclosporin A.
ZUR SEROLOGIE DES I‐ANTIGENS IN DER SALMONELLA‐GRUPPE.
Authors: Kauffmann. F.
Published: August 2010

Die Entwicklung des I‐Antigens ist bei den meisten Salmonella‐Stämmen, die das I‐Antigen enthalten, verschieden. Mit Hilfe der Objektglasagglutination kann man innerhalb desselben Stammes zwischen Kolonien unterscheiden, die entweder eine sehr starke (++ Form), eine mässig starke (+ Form) oder eine negative resp. sehr schwache (++ Form) I‐Objektglasagglutination ergeben.

Bei Weiterzüchtung von Einzelkolonien der I++ Form, der I+ Form oder der I++ Form kommt es in der Regel zu Abspaltungen anderer Formen, sodass man von einem » I‐Formenwechsel « sprechen kann. Die I++ Form ist we niger stabil als die I± Form, sodass also die Stämme mit I‐Antigen eine deutliche Neigung haben, yon der I++ Form in die I ++ Form überzugehen.

Immunisiert man Kaninchen mit der I++ Form, so erhält man Immunseren mit hohem I‐Titer, während die Immunisierung von Kaninchen mit der I± Form Seren mit niedrigem I‐Titer ergibt. Ausserdem reagieren jedoch die einzelnen Kaninchen auf die Antigenzufuhr verschieden.

In der praktischen Diagnose müssen zur Bestimmung des I‐Antigens zahlreiche Einzelkolonien untersucht werden, um nach Möglichkeit die I++ Form zu finden.

Unter Berücksichtigung des I‐Formenwechsels konnte das I‐Antigen bei folgenden weiteren Salmonellatypen nachgewiesen werden: S. bispebjerg, S. budapest, S. enteritidis var. danysz, S. dublin, S. rostock und S. eastbourne.
KOMPLEMENTBINDUNGSVERSUCHE BEI MAULUND KLAUENSEUCHE.
Authors: Reyn. Alice
Published: August 2010

Meerschweinchenseren, die Maul‐ und Klauenseuche (MK) ‐Rekonralescenten von Typen O und A entnommen worden waren, gaben typspezifische Komplementbindung, wenn wässrige, formalinhaltige Antigene benutzt wurden. Es wurden insgesamt 300 Meerschweinchenseren geprüft. Ein einziges Serum von einem Tier, das mit Aluminiumhydroxydvakzin behandelt worden war, gab ebenfalls spezifische Komplementbindung. Eine »KäItebindungstechnik«, die sich als geeignet erwiesen hat, wird beschrieben.

Rinderseren
20) von MK‐Rekonvaleszenten verhielten sich ganz anders als Meerschweinchenseren, da die Typspezifizität aufgehoben zu sein schien, solange formalinisierte Antigene (Typ O und A) angewandt wurden. Es wurden nämlich auch positive Reaktionen mit formolisierten, nichtvirushaltigen Antigenen (Meerschweinchennieren‐ und Rindernierenantigene, welche in formalinisiertem Puffersalzwasser suspendiert waren), erzielt. Bei Verwendung von formalinfreien Antigenen waren die Reaktionen mit den virusfreien Kontrollantigenen negativ. Es erwies sich als unmöglich, mit dem vorhandenen Material die Frage zu lösen, ob die erzielten Kornplementbindungen mit Rinderseren spezifisch, eventuell typspezifisch seien.

Menschenseren verhielten sich ziemlich gleich wie Rinderseren, wenn sie auch eine genngere Tendenz, mit forrnalinhaltigen Antigenen stärker zu binden als mit formalinfreien, verrieten. Es wurden schwache positive Reaktionen mit Meerschweinchenantigen Typ O in ca. 60% der MK‐verdächtigen Fälle (im ganzen 15), wovon nur einer mit verifizierter MK, nachgewiesen. Von etwa 200 Seren von Krankenhauspatienten und 16 Seren, die gesunden Personen entnornmen worden waren, gaben 44% ebenfalls schwache positive Reaktion mit Meerschweinchenantigen Typ 0.

Die Seren von 2 Patienten, die unter dem Verdacht standen, MK kontrahiert zu haben, reagierten sowohl mit Typ O‐Antigen als auch mit Typ A‐Antigen: ähnliche Reaktionen gaben einige Kontrollseren.

Somit gelang es uns nicht, spezifische Komplementbindung niit Menschenseren aufzuzeigen.

Typ C (Waldmann) haben wir nicht geprüft.

Für zukünftige Versuche mit Menschen‐ und Rinderseren sind wässrige, formalinfreie, eventuell durch Gradocolfilter filtrierte Antigene zu empfehlen.
DIE DIMENSIONEN DER ZOTTENOBERFLÄCHE DER VOLLGETRAGENEN MENSCHLICHEN PLAZENTA.
Authors: Christoffersen Aage Krogh
Published: August 2010

L'ouvrage présent contient la description d'une série de mesurages de la superficie villeuse de 61 placentas humains nés à terme. La technique est celle proposée par Dodds: D'après une section histologique de grosseur connue les contours des villosités sont dessinés en un agrandissement connu dans un nombre convenable de champs visuels. La longeur des contours est mesurée, divisée par l'agrandissement des dessins et multipliée par la grosseur de la tranche. De cette maniere est trouvée la superficie villeuse dans les champs visuels mesurés. Le volume de ceux‐ci étant connu, il est possible de multiplier les résultats de mesurage correspondant au volume de la quantité totale de tissu villeux dans chacun des placentas examinés. On corrige pour les erreurs s'ensuivant de la section oblique des tranches des villosités des‐sinées.

De cet examen il résulte que la superficie villeuse de 1 mm3 de tissu placentaire typique est de 34 mm2 environ, avec une dissémination moyenne d'à peu près 3 mm2 seulement. Dans les 61 cas examinés la superficie villeuse totale variait entre 10 m2 et 20 m2 environ.

D'un examen particulier de la paroi villeuse il résulta que sa grosseur s'élève à 7 μ environ.

Une calculation approximative montre que ces dimensions sont compatibles avec l'idée du caractère mécanique de l'échange de substances materno‐foetal.
ÜBER DEN α‐β PHASENWECHSEL IN DER SALMONELLAGRUPPE.
Authors: Kauffmann F.
Published: August 2010

Auf Grund serologischer Untersuchungen wurde die »Chester‐Gruppe« in 2 verschiedene Typen eingeteilt: S. Chester = IV.[V]. e, h ? e, n, x … und S. san diego = IV.[V]. e, h ? e, n, z15…

Untersuchungen über die β‐Phasen ergaben das Vorliegen von 4 serologisch verschiedenen β‐Phasen, deren For‐meln für praktisch‐diagnostische Zwecke gekürzt wurden, so‐dass sie mit Hilfe von 2 absorbierten Seren (x und z15) be‐stimmt werden können.

Die heute bekannten 20 Salmonellatypen mit α‐β Phasenwechsel werden in einer Antigentabelle angegeben.

Es wird eine Zusammenstellung über die serologische Variation in der Salmonellagruppe gegeben.
ÜBER DIE BÖSARTIGEN HÄMANGIOME IN DER MILZ UND LEBER.
Authors: Siirala Urpo , Näätänen. Esko
Published: August 2010

Im obigen ist über einen Fall berichtet, in dem bei einer 20jährigen Frau eine bösartige Blutgefässgeschwulst sowohl in der Milz als in der Leber festgestellt wurde. Der obere Teil des Bauches der früher gesunden Patientin beginnt allmäh‐lich anzuschwellen und empfindlich zu werden. Nach 7 1/2 Monate dauernder Krankheit stirbt sie an Kachexie und einer durch Ruptur des Lebertumors verursachten inneren Blutung. Pathologisch‐anatomisch wurde in der stark vergrösserten Milz und Leber ein in bezug auf den histologischen Bau wech‐selndes, aber meist ziemlich stark anaplastisches, malign wachsendes Hämangiom nachgewiesen. Es scheint offenbar, dass die Milzgeschwulst primär und das in der Leber kon‐statierte Tumorwachstum metastatischer Natur ist. Fälle wie der oben beschriebene sind ausserordentlich selten. An ähn‐lichen Fällen sind unseres Wissens nur vier veröffentlicht worden (Langhans, Theile, Jores und Wright).
ÜBER MEHRERE NEUE SALMONELLA‐TYPEN.
Authors: Kauffmann F.
Published: August 2010

Es werden serologische und kulturelle Untersuchungen an mehreren neuen Salmonella‐Typen mitgeteilt.
ÜBER DIE STRUKTUR DER SCHILDDRÜSE NACH HYPOPHYSENSTIELDURCHTRENNUNGEN BEIM KANINCHEN.*
Authors: Westman Von A. , Jacobsohn D. , Okkels H.
Published: August 2010

Nach Durchtrennung des Hypophysenstiels beim Kaninschen, die sowohl bei erwachsenen wie juvenilen Tieren ausgeführt wurde, findet sich bei 11 von 14 Fällen ein mikroskopisches Schilddrüsenbild, dass von einer herabgesetzten Funktion zeugt. Bei den übrigen 3 Fällen scheint die Funktion normal gewesen zu sein. Alle Fälle hatten eine hochgradige Genitalatrophie. Es scheint, als ob die thyreotrope Funktion des Vorderlappens nicht so abhängig von dem Vorhandensein einer normalen Verbindung zwischen der Hypophyse und dem Hypothalamus ist, wie es sich für die gonadotropen Funktionen gezeigt hat.
ZUR SEROLOGIE DER DYSENTERIE‐GRUPPE.
Authors: Kauffmann. Von F.
Published: August 2010

Von Antigenbeziehungen zwischen der Dysenterie‐ und Salmonella‐Gruppe ausgehend, wurden serologische Untersuchungen speziell innerhalb der Flexner‐Gruppe durchgeführt, um zu einer praktisch brauchbaren Typendiagnose zu gelangen. Dieses Ziel konnte erreicht werden, da zwischen den einzelnen Typen (A, D, H, W und WX) deutliche qualitative Antigendifferenzen festgestellt wurden. Mit Hilfe bestimmter Faktoren‐Seren war die Typenbestimmung schon in der Objektglas‐Agglutination möglich.

Es wurde festgestellt, dass die Kulturen Stansfield VZ zum A‐Typ, Hiss‐Russell Y zum D‐Typ und Whittington Z zum H‐Typ gehören. Dagegen stellen die Kulturen Mountain WX, Oxford W und wahrscheinlich auch Hughes X weitere selbständige Typen der Flexner‐Gruppe dar.

Zwischen den einzelnen Typen der Flexner‐Gruppe einerseits und den Typen I (= Schmitz), E (= Sonne) und Shiga andererseits bestehen unter Berücksichtigung der Glattformen keine Antigenbeziehungen.

Die Antigenbeziehungen zwischen der Dysenterie Flexner‐ und Salmonella‐Gruppe spielen praktisch keine Rolle und treten nur dann in Erscheinung, wenn man mit sehr starken Salmonella O‐Seren (z. B. von S. senftenberg) arbeitet.

Innerhalb der Dysenterie‐Glattformen kommt ein Formenwechsel vor, der einer näheren Untersuchung bedarf; ferner können Verlustvarianten auftreten.

Die Typeneinteilung in der Dysenterie‐Gruppe muss — ebenso wie in der Salmonella‐Gruppe — in erster Linie auf serologischen Methoden beruhen, sodass die weitere Unterteilung der Serotypen in Vergärungstypen mit Hilfe kultureller Methoden ein sekundärer Vorgang ist. Die serologischen Dysenterie‐Typen sind praktisch als konstant zu betrachten und haben daher epidemiologische Bedeutung.

Die serologischen Dysenterie‐Typen müssen sowohl bei der Widal‐Reaktion als auch bei der Vaccine‐Herstellung berücksichtigt werden.
ÜBER ANTIGENBEZIEHUNGEN ZWISCHEN PNEUMOKOKKEN UND SALMONELLABAKTERIEN.
Authors: Kauffmann Von F. , Nielsen A. Langvad
Published: August 2010

Zwischen den verschiedenen Pneumokokken‐ und Salmonella‐Typen bestehen im allgemeinen keine oder nur sehr geringe Antigenbeziehungen. Eine Ausnahme hiervon bilden die Pneumokokken‐Seren der 35‐Gruppe (35, 35 A und 35 B), die S. kirkee stark agglutinieren. Diese übergreifenden Reaktionen beruhen wahrscheinlich auf gemeinsamen Partialantigenen, die bei den Pneumokokken‐Typen in der Kapsel und bei den Salmonella‐Bakterien im Körper enthalten sind.
ANWENDUNG VON MUCIN‐INFEKTIONEN BEI CHEMOTHERAPEUTISCHEN UNTERSUCHUNGEN.
Authors: Hansen V. Sindbjerg
Published: August 2010

Mit Hilfe von Schweinemagenmucin a. m. Miller wurden experimentelle Infektionen mit Bakterien erzeugt, welche sonst apathogen oder sehr wenig pathogen für Mäuse sind. Diese Infektionen wurden mit Chemotherapeutika behandelt, und es wurde eine gute therapeutische Wirkung von Sulfapyridin, Sulfathiazol und Sulfamethylthiazol gegenüber Meningokokken, B. coli, B. paradysenteriae Flexner sowie B. typhi beobachtet.
RECHERCHES SUR LA FERMENTATION MUTATIVE DES BACTÉRIES
Authors: Kristensen. Par Martin
Published: August 2010

1. Les particularités les plus importantes du cours de la mutation de la Salmonella dublin que nous avons décrites dans le mémoire précédent (vol. 17, p. 193) par l'examen d'une seule souche, se retrouvent aussi chez les 4 autres souches typiques de Salmonella dublin, mais seulement en partie chez 2 souches, atypiques au point de vue fermentatif.

2. Il est à supposer que la mutation fermentative ait pour règle que le logarithme de la fraction du nombre de réceptables de culture, dans lesquels, à une époque donné aucune mutation ne s'est produite, est proportionnel à la quantité de culture. Cependant ceci est seulement valable, si les conditions générales de culture sont comparables.

3. En se guidant d'après cette règle algébrique on a établi des comparaisons entre les expériences de mutation avec Salmonella dublin envers l'arabinose sous des conditions différentes de culture, partie sur la base d'expériences antérieures de Schmit‐Jensen, partie sur la base d'expériences personelles. Dans la plupart des cas on a trouvé la mutabilité plus grande dans les tubes ordinaires que sous des circonstances moins aérobes, p. ex. des tubes capillaires.

4. On a indiqué une méthode simple pour la mise en oeuvre des réactions de fermentation dans une volume de culture de 0, 1 c. c. environ.

5. Le bacille typhique du type de fermentation II possède primairement une capacité faible de fermentation de xylose. Par une mutation généralement survenue vite cette capacité de fermentation disparaît, peut‐être, dans quelques cas, seulement en partie. La mutation provoquant une capacité de fermentation augmentée ne se produit généralement qu'à une époque ultérieure.
PERIARTERIITIS NODOSA DER PULMONAL‐ARTERIE UND PRIMÄRE PULMONAL‐SKLEROSE.
Authors: Eskelund Viggo
Published: August 2010

Ein 11‐jähriger Knabe, der 4 Jahre hindurch an Mittelohrenentzündung gelitten hatte, wurde wegen dauernder Eiterung des rechten Ohres in der Universitätsohrenklinik in Kopenhagen aufgenommen, wo die Resektion des Warzenfortsatzes ausgeführt wurde.

Vom Ohrenleiden abgesehen, war er bei der Aufnahme gesund und hatte früher ausser Influenza keine Krankheiten durchgemacht.

6 Wochen nach der Aufnahme und vor der Operation wurde er von einem akuten katarrhalischen Leiden, welches mit Husten, Fieber und follikulärem Belag der Gaumenmandeln einherging, befallen. Ausserdem bestand leichte Cyanose des Antlitzes. Da die Symptome nach wenigen Tagen abgeklungen waren, nahm man in leichter Äthernarkose die oben erwahnte Operation vor.

Im Laufe der 2 darauffolgenden Wochen erschlaffte der Pat. allmählich, wurde matt und cyanotisch und starb plötzlich in tiefer Cyanose.

Die Autopsie zeigte starke Hypertrophie der rechten Herzhälfte, Erweiterung des Hauptstammes der Pulmonalarterie und Sklerose der auf der Schnittfläche hervortretenden feineren Verzweigungen derselben.

Der Sektionsbefund deutete am ehesten auf eine primäre Sklerose der Pulmonalarterie; bei der mikroskopischen Untersuchung der Arteriolae pulmonalis wurde jedoch festgestellt, dass das Wesentlichste des Gefässleidens in nekrotischen Veränderungen der Media und Adventitia, starker Verdickung der Adventitia mit lymphozytärer Infiltration der Randzonc und Intimaproliferation, besonders der kleineren Arterienzweige, bestand. Schliesslich wurden sowohl knotenförmige, fibröse Adventitiaverdickungen, als kleine Aneurysmen beobachtet.

Im Mittelpunkt des Krankheitsbildes steht somit eine chronische Periarterütis nodosa arteriae pulmonalis, die durch eine obliterierende Intimaproliferation die Hypertrophìe der rechten Herzhälfte bedingt (Cor pulmonale) und hierdurch eine primäre Pulmonalsklerose vortäuscht.

Aus dem Studien der Literatur geht hervor, dass dieses Leiden in den meisten Fällen als ein primär obliterierendes Leiden der feineren Pulmonaläste aufgefasst werden muss, welches durch verschiedene Ursachen heravorgerufen wird und sekundär arteriosklerotische Veränderungen im Hauptstamm und den grösseren Verästelungen zur Folge hat.
EXPERIMENTELLE UNTERSUCHUNG ÜBER KALBSHYPOPHYSENTRANSPLANTATE BEI DER RATTE.*
Authors: Westman A. , Jacobsohn D.
Published: August 2010

In die vorderen Augenkammern erwachsener und juvenil hypophysektomierter und normaler erwachsener Ratten wurden Kalbshypophysenvorderlappen transplantiert. Bei sämtlichen Tieren kam es zu einer Nekrose und folgenden Resorbtion der Transplantate. Die Ovarien und Nebennieren der hypophysenlosen Ratten mit den Transplantaten wiesen eine hochgradige Atrophie auf, und das Wachstum der juvenil operierten Tiere blieb gehemmt. Die Transplantate haben, wie aus diesen Beobachtungen hervorgeht, keine dauerhafte hormonale Wirkung.