bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteogenesis imperfecta: Anthropometric, skeletal and mineral metabolic effects of long‐term intravenous pamidronate therapy
Authors: Vallo Alfredo , Rodriguez‐Leyva Francisco , Rodríguez Soriano Juan
Published: August 2010

Background: Administration of bisphosphonates represents a beneficial therapy in children and adolescents with severe osteogenesis imperfecta (OI) because it significantly reduces the annual rate of bone fractures. Aim: To evaluate the anthropometric, skeletal and mineral metabolic effects of long‐term intravenous pamidronate therapy in OI. Methods: Ten patients, aged 5 mo to 25 y, with OI received cyclical intravenous pamidronate. The yearly dose of pamidronate was approximately 9 mg/kg/d at all ages. Duration of treatment varied from a minimum of 2 y to a maximum of 5 y. Growth, bone mass and mineral metabolic parameters were studied at baseline and repeated every year thereafter. Bone mass was assessed by calculation of bone mineral apparent density (L2–L4 BMAD). This represents the first study on the changes in size‐adjusted measures of bone mass observed with such therapy. Results: While on therapy, all children and adolescents grew normally but did not experience any manifest catch‐up growth. A significant decrease in the incidence of bone fractures was observed. In seven patients with severe forms, L2–L4 BMAD increased by 80% after the first 2 y of therapy but tended to stabilize or even decrease over the following years despite maintenance of therapy. A significant inverse correlation could be established between urinary Ca excretion and L2–L4 BMAD (r= − 0.30, p < 0.05).

Conclusion: Our results confirm that cyclical pamidronate infusions reduce the incidence of bone fractures and allow normal growth. The improvement in bone mass initially observed after the first 2 y of therapy is not always sustained over the following years despite maintenance of therapy.
Effects of sociodemographic factors on adherence to breastfeeding and other important infant dietary recommendations
Authors: Gudnadottir Maria , Sigurdur Gunnarsson Björn , Thorsdottir Inga
Published: August 2010

Aim: To examine in an affluent and healthy population the association between sociodemographic factors and the adherence to key infant dietary recommendations. Methods: In a longitudinal prospective study, healthy newborns were selected randomly in maternity wards around Iceland and their diet recorded every month for one year (n=124). In addition, a 48‐hour‐weighed‐record, including information on added sugar, fruits, vegetables and the use of A and D vitamin drops was completed by 91 (73%) mothers at 9 and 12 months. Information about the mothers’ education, smoking, age, parity, and family income was collected (n=98; 79%). Results: Regression analyses, including sociodemographic factors, showed exclusive breastfeeding to be positively associated with more education (P=0.022) and non‐smoking (P=0.013) explaining 22% of the variance, and total breastfeeding (exclusive + partial) with non‐smoking (P=0.006). Multiple regression also showed children's intake of added sugar from 9–12 months to be positively associated with mother's smoking (P=0.022) and negatively with age (P = 0.026), explaining 30% of variance. Sociodemographic factors were associated with children's fruit and vegetable consumption but not with the administration of AD‐vitamin drops. However, when tested for significance between groups, younger mothers with fewer children seemed less likely to give AD‐vitamin drops.

Conclusions: In a group of mothers getting regular antenatal care and giving birth to healthy infants, sociodemographic factors can predict which mothers need special guidance concerning recommendations about diet in infancy. These were mothers with less education, who smoked, were younger and were having their first or second child.
Phagocytosis of Giardia lamblia trophozoites by human colostral leukocytes
Authors: França‐Botelho Aline C. , Honório‐França Adenilda C. , França Eduardo L. , Aparecida Gomes Maria , Costa‐Cruz Julia M.
Published: August 2010

Aim: To determine the phagocytic activity of the polymorphonuclear and mononuclear cells present in human colostrum, and to verify the influence of opsonins in the adherence, ingestion and killing of Giardia lamblia trophozoites. Methods: Polymorphonuclear and mononuclear phagocytes were incubated with G. lamblia trophozoites, in the presence as well as the absence of supernatant of human colostrum (the source of opsonins) for 30, 60 and 120 min. The trophozoites/phagocytes ratio was 1:1, and the percentage of phagocytosed trophozoites was determined by microscopic examination of acridine orange‐stained cells. Results: The mononuclear phagocytes presented more functional activity than the polymorphonuclear. The highest indexes of adherence (77.6±5.1), ingestion (68.9±5.5) and killing (48.5±4.9) were obtained through the incubation of mononuclear cells in the presence of colostrum supernatant for 120 min.

Conclusion: The phagocytes of human colostrum were able to ingest G. lamblia trophozoites and presented microbicidal activity in vitro, suggesting that these phagocytes may act as an additional mechanism of protection against infant giardiasis through breastfeeding.
Asplenia syndrome in a pair of monozygotic twins
Authors: Hwang Mao‐Sheng , Su Wen‐Jen , Lin Ju‐Li
Published: August 2010

Asplenia syndrome is one of the heterotaxy syndromes, which many familial and animal studies suggest are caused by the loss of adequate genetic control of normal left–right asymmetry development. Moreover, there has not been any environmental factor documented to cause these syndromes. Asplenia syndrome occurring in a pair of monozygotic twins is reported. In view of the negative family history, a new germline mutant gene might be the aetiology of our patients. Both twins are associated with some degree of discordant complex heart defects within the context of a high degree of “mirror‐image” of the unpaired thoracoabdominal organs.

Conclusion: This report implies that sporadic asplenia syndrome might associate with new mutations and further genetic study may be indicated. These monozygotic twins' discordant phenotypes imply that some unidentified factors play an important role in their ultimate development of the same genetically determined abnormalities.
Neonatal omphalitis: A review of its serious complications
Authors: Fraser Nia , Davies Brian W. , Cusack Jonathan
Published: August 2010

Until the advent of aseptic deliveries and aseptic umbilical cord care, many deaths occurred from umbilical infections. Omphalitis is a localized infection of the umbilical cord stump, most commonly caused by a single organism, which usually responds well to appropriate antibiotics. Umbilical sepsis is relatively uncommon in the developed world but is endemic in less‐developed regions. Complications of omphalitis are exceedingly rare, but potentially catastrophic. Many of these babies will require surgical intervention. This paper aims to review the serious complications of omphalitis and how these should be managed.

Conclusion: It is important to be aware of the rare but potentially lethal complications of omphalitis. Prompt recognition of serious sequelae is crucial for survival.
Transient and chronic neutropenias detected in children with different viral and bacterial infections
Authors: Karavanaki K. , Polychronopoulou S. , Giannaki M. , Haliotis F. , Sider B. , Brisimitzi M. , Dimitriou C. , Scordias G. , Marangou F. , Stamatiadou A. , Avlonitis S.
Published: August 2010

Aim: The aim of the study was to identify the relationship of acquired neutropenias with infections in childhood and to assess their course, complications, short and long‐term outcome. Method: During a two‐year period, all children admitted to the pediatric ward with neutropenia were investigated for underlying infections with indices of infection, cultures of body fluids and serological tests. Results: Sixty‐seven previously healthy children, aged (median, 25–75%) 0.7 years (0.2–1.5), were identified with neutropenia (frequency: 2.0%). An infectious agent was identified in 34/67 cases (50.7%) (viral infection: n=24, bacterial: n=10). In 50/67 (74.6%) children, neutropenia recovered within 2 months (transient neutropenia, TN), while in 17/67 (25.4%) of them it persisted for more than two months. Two years after diagnosis 50/67 children (74.6%) accepted to be reassessed. Of these children, 8/50 (16%) remained neutropenic (neutropenic children, NC), while 42/50 had recovered completely. Conclusion: Neutropenia during childhood is usually transient, often following viral and common bacterial infections, does not present serious complications and in the majority, it resolves spontaneously. However, in a significant percentage of patients, neutropenia is discovered during the course of an infection, on a ground of a preceding chronic neutropenic status.
Glucocorticoid receptor and vascular endothelial growth factor in nephrotic syndrome
Authors: Wasilewska Anna , Zoch‐Zwierz Walentyna
Published: August 2010

Aim: The aim of the study was to assess plasma and urine concentrations of vascular endothelial growth factor (VEGF) in nephrotic syndrome children (NS) depending on the total dose of glucocorticoids (GC) and the percentage of lymphocytes with glucocorticoid receptor expression (CD3/GCR). Methods: We examined 51 children (2–15 years), allocated to three groups: group I: 13 children with the first NS onset, group II: 13 children with NS relapse, group C: 25 healthy children. The NS patients were examined: (A) before treatment and (B) 4–5 weeks after prednisone administration at a dose of 60 mg/m2/24 h. Plasma and urinary VEGF levels were determined using the immunoenzymatic ELISA method. Flow cytometry was applied to assess CD3/GCR expression. Results: Higher plasma and urinary VEGF concentrations were noted in NS children before treatment (A), as compared to control subjects (C). Following prednisone therapy (B), VEGF level was reduced but it was still higher than in the control group. Positive correlation was observed between VEGF and protein in the urine (group I r = 0.660, P < 0.05, group II r = 0.818, P<0.01) and a weak positive correlation between VEGF in plasma and urine (group I r = 0.531, P<0.05, group II – r = 0.581, P<0.05). CD3/GCR expression was lower in group II. In both groups, the correlation between plasma VEGF and CD3/GCR was positive (P<0.05). Conclusions: 1. Plasma and urinary VEGF levels increase during nephrotic syndrome onset. 2. Glucocorticoid treatment reduces plasma and urinary VEGF levels in NS children.
Rheumatic fever‐mimicking carditis as a first presentation of chronic active Epstein‐Barr virus infection
Authors: Toubo Taikai , Ohga Shouichi , Takada Hidetoshi , Suga Naohiro , Nomura Akihiko , Ohno Takurou , Hara Toshiro
Published: August 2010

A 7‐y‐old girl presented with prolonged fever, arrhythmia and cardiomegaly during the treatment course of group A β‐haemolytic streptococcal pharyngitis. The isolated rheumatogenic strain M1 suggested the diagnosis of rheumatic fever. However, serous pericardial effusion contained high levels of Epstein‐Barr virus (EBV) DNA. Clonally proliferating EBV+ T cells were determined in the circulation. The atypical carditis without valvitis was then complicated by coronary artery dilatations. Four months after the start of prednisolone plus antiviral/bacterial therapy, EBV+ T‐cell lymphoma developed in the thigh. Conclusion: Atypical carditis may be a notable and life‐threatening presentation of chronic active EBV infection to be differentiated from rheumatic fever.
A boy with coeliac disease and obesity
Authors: Oso Olumuyiwa , Fraser Neil C.
Published: August 2010

Aim: To report the case of a 14‐y‐old boy with coeliac disease and obesity. Methods and results: A 14‐y‐old boy presented with episodic diarrhoea associated with eating spaghetti. His body mass index (BMI) at presentation was 37.2 kg/m2 (>99.9th centile). Both antigliadin and anti‐endomysial antibodies were positive, and coeliac disease was diagnosed by jejunal biopsy. His diarrhoea ceased and the gliadin and endomysial antibodies disappeared after starting gluten‐free diet. At 17 y, his BMI increased to 42.7 kg/m2 despite dietary support. Conclusion: Obesity in a child does not exclude the diagnosis of coeliac disease, especially if presenting with suggestive symptoms.
Prenatal and postnatal maternal smoking as risk factors for preschool children's mental health
Authors: Höök Börje , Cederblad Marianne , Berg Roland
Published: August 2010

Aim: To identify maternal prenatal and postnatal smoking as risk factors for psychosocial behaviour problems in Swedish preschool children. Methods: This prospective, longitudinal population study compared mothers’ self‐reported smoking during pregnancy and when the child was 3 mo old with behaviour problems according to Achenbach's Child Behavior Checklist at 3 y (1428 children) and 5.5 y of age (677 of the children). Results: 16% of the mothers smoked during pregnancy and the same number after the birth of the child. Controlling for possible confounding variables, maternal smoking was significantly related to externalizing problems, aggressive behaviour, and destructive/delinquent behaviour both at 3 y and 5.5 y. The effect was as strong for girls as for boys. Length and weight were lower for children of smoking mothers than for children of non‐smoking mothers.

Conclusion: Our study supports the importance of preventing maternal smoking during pregnancy and the infant years. Even a few cigarettes per day have negative consequences for the child. The goal must be total abstinence from smoking both pre‐ and postnatally.
Effects of parental smoking and level of education on initiation and duration of breastfeeding
Authors: Di Napoli Anteo , Di Lallo Domenico , Pezzotti Patrizio , Forastiere Francesco , Porta Daniela
Published: August 2010

Aim:To evaluate the effects of parental smoking and level of education on the initiation and duration of breastfeeding in a prospective cohort study on mother–infant pairs.Methods:We studied 543 mother–infant pairs enrolled after delivery at a hospital in Rome. Information about parents’ characteristics were obtained from a questionnaire administered in hospital; the outcome of the study was the infant's feeding habits in the preceding 24 h, assessed by telephone every 2 wk. The effects of parental smoking and level of education on initiation and duration of breastfeeding were evaluated through multivariate logistic regression models and time‐dependent Cox models.Results:After controlling for confounding factors, we found a negative effect for mothers’ smoking both on breastfeeding initiation (odds ratio 2.19, 95% CI 1.05–4.55) and duration (hazard ratio 3.37, 95% CI 1.85–6.13) when at least one parent had a low level of education.

Conclusion:Our study shows that maternal smoking, particularly when one of the parents has a low level of education, determines a negative effect on the initiation and duration of breastfeeding. Public health policy should promote educational programmes for both parents focused on quitting smoking, which could have positive effects on the initiation and duration of breastfeeding.
Cigarette smoking during pregnancy and hyperactive‐distractible preschooler's: A follow‐up study
Authors: Markussen Linnet Karen , Obel Carsten , Bonde Else , Hove Thomsen Per , Jørgen Secher Niels , Wisborg Kirsten , Brink Henriksen Tine
Published: August 2010

Aim:To study the association between intrauterine exposure to tobacco smoke and behavioural disorders in preschool children, primarily symptoms of inattention, hyperactivity and impulsivity but also hostile‐aggressive and anxious‐fearful symptoms.Methods:We conducted a follow‐up study in 1355 singletons born to Danish‐speaking mothers. Information on smoking habits during pregnancy and other lifestyle factors was obtained from self‐administered questionnaires filled in during second and third trimester. Approximately 3.5 years later, the parents provided information on their child's behaviour using the self‐administered Preschool Behaviour Questionnaire. The children were categorized into three not mutually exclusive behaviour groups: hyperactive – distractible (13.6%), hostile–aggressive (4.6%), and anxious‐fearful (6.4%) children.Results:Compared with children of non‐smokers, children born to women who smoked 10 or more cigarettes per day had a 60% increased risk of hyperactivity and distractibility perceived by the parents (OR 1.6; 95% CI 1.0–2.3; P < 0.05). The results were adjusted for maternal lifestyle factors and socioeconomic characteristics. Additional adjustment for perinatal factors and parental psychiatric hospitalization did not change the results substantially (OR 1.7; 95% CI 1.1–2.6). We found no statistically significant association between maternal smoking in pregnancy and hostile–aggressive and anxious‐fearful behaviour in the offspring.

Conclusion:Exposure to tobacco smoke in utero was associated with hyperactive‐distractible behaviour in preschool children.
Unmet education and training needs in adolescent health of health professionals in a UK children's hospital
Authors: McDonagh Janet E. , Minnaar Gregory , Kelly Karen , O'Connor David , Shaw Karen L.
Published: August 2010

Aim: To determine the perceived education and training needs in adolescent health of health professionals.Design:Cross‐sectional survey Setting and subjects: Hospital staff in a UK children's hospital.Outcome measures:perceived barriers, confidence, knowledge, skill and prior teaching in key adolescent health subject areas.Results:The hospital survey was completed by 159/1400 professionals representing a completion rate of 11%. Doctors and staff from ‘Professions allied to medicine’ rated ‘lack of training’, ‘lack of teaching materials’ and ‘lack of community resources’ as the main barriers to providing developmentally appropriate care. Sixty per cent of hospital respondents had received no prior specific training in adolescent health. All but four topics were perceived to be of very high or high importance by the majority of respondents (54–90%). Low scores in perceived knowledge, confidence and/or skill were reported in nine key subject areas (including adolescent mental health and substance use). Differences between doctors and professions allied to medicine were observed in a minority of areas.

Conclusion:Unmet education and training needs of a range of professionals working in a paediatric setting were identified in key areas of adolescent health and they provide useful directions for the development of future multidisciplinary training programmes.
Angiotensin‐converting enzyme DD genotype is preventive against circulatory failure in very‐low‐birthweight neonates
Authors: Nobilis András , Szabó Miklós , Kocsis István , Sulyok Endre , Tulassay Tivadar , Vásárhelyi Barna
Published: August 2010

We studied the association between genetic polymorphisms of the renin‐angiotensin system and the risk for circulatory failure (CF) during the first three postnatal days in 104 very‐low‐birthweight preterm infants.

Conclusion: Infants with angiotensin‐converting enzyme DD genotype were protected against CF (adjusted OR 0.41, 95% CI 0.19–0.89).
Nasal continuous positive airway pressure for neonatal back transfer
Authors: Ofoegbu Bibian N , Clarke Paul , Robinson Michael J
Published: August 2010

We report the use of nasal continuous positive airway pressure (nCPAP) for neonatal back transfer of 51 babies. nCPAP may be used to provide safe respiratory support during back transportation of infants. Babies transferred on nCPAP were significantly smaller and of younger postmenstrual age than historical comparators who had to wait for transfer until independent of nCPAP. nCPAP transferred babies spent significantly less time on the intensive care unit.
Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants
Authors: Mihatsch Walter A. , Hoegel Josep , Pohlandt Frank
Published: August 2010

Aim: To investigate whether a mixture of prebiotic non‐digestible oligosaccharides (GosFos; referring to galacto‐ and fructo‐oligosaccharides) would improve feeding tolerance in preterm infants on full enteral formula feeding. We hypothesized that GosFos would: (1) reduce stool viscosity and (2) accelerate gastrointestinal transport. Methods: In a placebo‐controlled double‐blind trial 20 preterm infants on full enteral nutrition (gestational age 27 (24–31) weeks, postnatal age 42 (11–84) days, and weight at study entry 1570 (1080–2300) g were randomly allocated to have their feedings supplemented with either GosFos (1 g/100 mL) or placebo for 14 days. Stool viscosity was measured by high‐pressure capillary rheometry. Gastrointestinal transport time was assessed as the time from feeding carmine red to its appearance in the diaper. The hypotheses were tested as a priori ordered hypotheses. Data are shown as median (range). Results: Birth weight, gestational age, postnatal age, and weight at study entry did not differ between groups. GosFos significantly reduced both stool viscosity, as measured by extrusion force (32 (2–67) versus 158 (24–314) N), and gastrointestinal transit time (12 (4–33) versus 26 (5–52) h). No adverse effects were observed.

Conclusion: Formula supplementation with GosFos reduced stool viscosity and accelerated gastrointestinal transport. Further trials are required to investigate whether GosFos facilitates enteral feeding advancement and early enteral nutrition thereby eventually reducing the incidence of catheter‐related nosocomial infections and improving long‐term outcome.
Analysis of renal biopsies performed in children with abnormal findings in urinary mass screening
Authors: Lee Young‐Mock , Baek Seoung‐Yon , Hong Kim Ji , Soo Kim Dong , Seung Lee Jae , Kim Pyung‐Kil
Published: August 2010

Background: School urinary mass screening tests are performed to make early diagnosis and provide proper treatment for chronic renal diseases. However, very few systemic analyses or studies have been reported regarding final diagnosis made on children with abnormal urinary screening results. Aim: To study the cases of renal biopsy in children detected in urinary screening. Methods: We retrospectively analysed 461 cases of renal biopsy performed on children referred to us with abnormal school urinary mass screening results who satisfied indications for renal biopsy. Results: Pathologically abnormal findings were observed in 285 (61.8%) patients. Thin glomerular basement membrane disease was detected in 127 (27.5%) cases and IgA nephropathy in 121 (26.2%) cases. Among those 461 children, microscopic haematuria was observed in 289 (62.7%) patients, proteinuria in nine (2.0%), and both in 163 (35.4%). In addition, a statistically higher rate of pathological abnormalities on renal biopsy was noted in the group with microscopic haematuria combined with proteinuria and also in cases with more severe haematuria.

Conclusion: School urinary mass screening has greatly contributed to diagnosing chronic renal diseases. Continuous medical observation is required when abnormal urinalysis is observed, and a more aggressive medical approach such as renal biopsy should also be performed if necessary.
Effects of cyclosporine A in hyperzincaemia and hypercalprotectinaemia
Authors: Sugiura Tokio , Goto Kenji , Ito Kouichi , Ban Kyoko , Okada Shoji , Moriyama Akihiko , Togari Hajime
Published: August 2010

Introduction: Hyperzincaemia and hypercalprotectinaemia with systemic inflammation, recurrent infections, hepatosplenomegaly, arthritis, anemia, cutaneous inflammation, and failure to thrive is an extremely rare disease and no therapy is reported. Aim: To evaluated the effects of cyclosporine A in hyperzincaemia and hypercalprotectinaemia in terms of serum cytokine level changes before and after treatment. Methods: A 10‐year‐old girl was admitted suffering from pyoderma gangrenosum, hepatosplenomegaly, anemia that was unresponsive to iron supplementation, persistent inflammation, arthritis, and increased serum zinc. The level of serum calprotectin was extremely high; therefore, we diagnosed hyperzincaemia and hypercalprotectinaemia and started cyclosporine A treatment. Twelve cytokines in serum were measured before and one year after treatment. Results: Cyclosporine A was very effective. Her skin lesion and joint pain were alleviated and quality of life was markedly improved. C‐reactive protein had decreased and anemia had improved. While zinc levels had fallen, calprotectin remained at an extremely high level. Of the cytokines examined, interleukin ‐6 serum levels had fallen and interleukin ‐8 showed a marked reduction after treatment.

Conclusion: Cyclosporine A is effective for hyperzincaemia and hypercalprotectinaemia. Serum interleukin ‐8 may be useful in assessing the therapeutic effects of cyclosporine A in hyperzincaemia and hypercalprotectinaemia.
The anal position index: A simple method to define the normal position of the anus in neonate
Authors: Davari Heidar Ali , Hosseinpour Mehrdad
Published: August 2010

Aim: The purpose of this study was to determine the normal position of anus using anal position index (API) and the modified measurement method and to emphasize the importance of ectopic anus. This cross‐sectional study was performed on 400 neonates equally, boys and girls who were all delivered at full term without any malformations. Anal position index, which is the ratio of anus‐fourchette distance in girls and anus‐scrotum distance in boys to the distance between coccyx and fourchette/scrotum, was calculated in all cases. To make correct measurements, transparent adhesive tape was used longitudinally on midperinum in a way that it covered the anus. Then fourchette/scrotum, anus center and the lower margin of coccyx were marked on it. Distances marked on each tape were then measured with the standard ruler. Mean±SD of API in girls was 0.45±0.08 (95% CI: 0.44–0.46) and in boys 0.54±0.07 (95% CI: 0.53–0.55). Mean±2 SD was considered as the normal range for an anus position. Six female and five male neonates who had abnormal APIs were investigated further.

Conclusions: Our findings suggested a simple method for determination of normal position of anus in children, especially those who are referred for chronic constipation. API can never be considered as the sole indication for the surgical intervention.
Complementary feeding in the WHO Multicentre Growth Reference Study
Authors:   WHO MULTICENTRE GROWTH REFERENCE STUDY GROUP, de Onis Mercedes
Published: August 2010

Aim: To describe complementary feeding practices in the Multicentre Growth Reference Study (MGRS) sample.

Methods: Food frequency questionnaires and 24‐h dietary recalls were administered to describe child feeding throughout the first 2 y of life. This information was used to determine complementary feeding initiation, meal frequency and use of fortified foods. Descriptions of foods consumed and dietary diversity were derived from the 24‐h recalls. Compliance with the feeding recommendations of the MGRS was determined on the basis of the food frequency reports. Descriptive statistics provide a profile of the complementary feeding patterns among the compliant children.

Results: Complementary feeding in the compliant group began at a mean age of 5.4 mo (range: 4.8 (Oman)–5.8 mo (Ghana)). Complementary food intake rose from 2 meals/d at 6 mo to 4–5 meals in the second year, in a reverse trend to breastfeeding frequency. Total intake from the two sources was 11 meals/d at 6–12 mo, dropping to 7 meals/d at 24 mo. Inter‐site differences in total meal frequency were mainly due to variations in breastfeeding frequency. Grains were the most commonly selected food group compared with other food groups that varied more by site due to cultural factors, for example, infrequent consumption of flesh foods in India. The use of fortified foods and nutrient supplements was also influenced by site‐variable practices. Dietary diversity varied minimally between compliance groups and sites.

Conclusion: Complementary diets in the MGRS met global recommendations and were adequate to support physiological growth.
Reliability of anthropometric measurements in the WHO Multicentre Growth Reference Study
Authors:   WHO MULTICENTRE GROWTH REFERENCE STUDY GROUP, de Onis Mercedes
Published: August 2010

Aim: To describe how reliability assessment data in the WHO Multicentre Growth Reference Study (MGRS) were collected and analysed, and to present the results thereof.

Methods: There were two sources of anthropometric data (length, head and arm circumferences, triceps and subscapular skinfolds, and height) for these analyses. Data for constructing the WHO Child Growth Standards, collected in duplicate by observer pairs, were used to calculate inter‐observer technical error of measurement (TEM) and the coefficient of reliability. The second source was the anthropometry standardization sessions conducted throughout the data collection period with the aim of identifying and correcting measurement problems. An anthropometry expert visited each site annually to participate in standardization sessions and provide remedial training as required. Inter‐ and intra‐observer TEM, and average bias relative to the expert, were calculated for the standardization data.

Results: TEM estimates for teams compared well with the anthropometry expert. Overall, average bias was within acceptable limits of deviation from the expert, with head circumference having both lowest bias and lowest TEM. Teams tended to underestimate length, height and arm circumference, and to overestimate skinfold measurements. This was likely due to difficulties associated with keeping children fully stretched out and still for length/height measurements and in manipulating soft tissues for the other measurements. Intra‐ and inter‐observer TEMs were comparable, and newborns, infants and older children were measured with equal reliability. The coefficient of reliability was above 95% for all measurements except skinfolds whose R coefficient was 75–93%.

Conclusion: Reliability of the MGRS teams compared well with the study's anthropometry expert and published reliability statistics.
Assessment of sex differences and heterogeneity in motor milestone attainment 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 the heterogeneity of gross motor milestone achievement ages between the sexes and among study sites participating in the WHO Multicentre Growth Reference Study (MGRS). Methods: Six gross motor milestones (sitting without support, hands‐and‐knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone) were assessed longitudinally in five of the six MGRS sites, namely Ghana, India, Norway, Oman and the USA. Testing was started at 4 mo of age and performed monthly until 12 mo, and bimonthly thereafter until all milestones were achieved or the child reached 24 mo of age. Four approaches were used to assess heterogeneity of the ages of milestone achievement on the basis of sex or study site. Results: No significant, consistent differences in milestone achievement ages were detected between boys and girls, nor were any site–sex interactions noted. However, some differences among sites were observed. The contribution of inter‐site heterogeneity to the total variance was <5% for those milestones with the least heterogeneous ages of achievement (hands‐and‐knees crawling, standing alone, and walking alone) and nearly 15% for those with the most heterogeneous ages of achievement (sitting without support, standing with assistance, and walking with assistance). 

Conclusion: Inter‐site differences, most likely due to culture‐specific care behaviours, reflect normal development among healthy populations across the wide range of cultures and environments included in the MGRS. These analyses support the appropriateness of pooling data from all sites and for both sexes for the purpose of developing an international standard for gross motor development.
Skewed X inactivation in healthy individuals and in different diseases
Authors: Helene Ørstavik Karen
Published: August 2010

In female mammalian cells, one of the two X chromosomes is inactivated in early embryonic life. Females are mosaics for two cell populations, one with the maternal and one with the paternal X as the active chromosome. Skewed X inactivation is arbitrarily defined, often as a pattern where 80% or more of the cells show a preferential inactivation of one X chromosome. Inactivation is presumed to be permanent for all descendants of a cell; however, after about 55 years of age, the frequency of skewed X inactivation in peripheral blood cells increases, probably through selection. Unfavourable skewing of X inactivation, where the X chromosome carrying a mutant allele is the predominantly active X, has been found in affected female carriers of several X‐linked disorders; however, for many X‐linked disorders, a consistent relationship between the pattern of X inactivation and clinical phenotype has been difficult to demonstrate. One reason for this may be that peripheral blood cells are not a representative or relevant tissue in many disorders. In some severe X‐linked disorders, post‐inactivation selection takes place against the X chromosome carrying the mutant allele, leading to a completely skewed X‐inactivation pattern. Skewed X inactivation has also been reported in young females with breast cancer, and may indicate an effect of X‐linked genes on the development of this condition.

Conclusion: The process of X inactivation and the resultant degree of skewing is clearly important for the expression of genetic diseases. It is also important to consider, however, that under normal conditions the frequency of skewed X inactivation increases with age in peripheral blood cells. Analysis of the expression of a large proportion of the genes on the X chromosome has revealed that X‐chromosome inactivation is more heterogeneous than previously thought.
Disease manifestations and X inactivation in heterozygous females with Fabry disease
Authors: Maier Esther M. , Osterrieder Stephanie , Whybra Catharina , Ries Markus , Gal Andreas , Beck Michael , Roscher Adelbert A. , Muntau Ania C.
Published: August 2010

Aim: Fabry disease is an X‐linked lysosomal storage disorder characterized by an accumulation of neutral glycosphingolipids in multiple organ systems caused by α‐galactosidase A deficiency due to mutations in the GLA gene. The majority of heterozygous females show the characteristic signs and symptoms of the disease, and some of them are severely affected. The current hypothesis for the occurrence of disease manifestations in females is skewed X inactivation favouring the mutant GLA allele.

Method: We analyzed the patterns of X inactivation in the leukocytes of 28 biochemically and genetically characterized symptomatic Fabry disease heterozygotes and their correlation with clinical and biochemical disease expression.

Results: X inactivation patterns in symptomatic females who are heterozygous for Fabry disease did not differ from those of female controls of the same age (p = 0.669). Thirteen (46%) of the 28 females with Fabry disease showed random X inactivation, ten (36%) moderate skewing, and five (18%) highly skewed X inactivation. Segregation analysis was performed in the families of six females who had highly or moderately skewed X inactivation. In four of these females, skewing favoured the wild‐type GLA allele and in the other two skewing favoured the mutant allele. Patterns of X inactivation or the extent of skewing were not related to the severity of clinical manifestations or to residual enzyme activity.

Conclusion: In this study we provide evidence that heterozygous females with Fabry disease show random X inactivation. Our data do not support the hypothesis that the occurrence and severity of disease manifestations in the majority of Fabry heterozygotes are related to skewed X inactivation.
Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease
Authors: Barbey Frédéric , Brakch Noureddine , Linhart Aleš , Jeanrenaud Xavier , Palecek Thomas , Bultas Jan , Burnier Michel , Hayoz Daniel
Published: August 2010

Aim:Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima–media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.

Methods:The common carotid artery intima–media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high‐definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age‐matched healthy individuals (83 men, 37 women).

Results:The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706±211 µm and 749±395 µm, respectively) compared with that of the control population (614±113 µm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non‐homogeneous intima–media thickening greater than 1.2 mm.

Conclusion:This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.
Fabry disease and vascular risk factors: future strategies for patient‐based studies and the knockout murine model
Authors: Moore David F. , Gelderman Monique P. , Fuhrmann Steven R. , Schiffmann Raphael , Brady Roscoe O. , Goldin Ehud
Published: August 2010

Fabry disease is secondary to deficiency of the lysosomal enzyme α‐galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non‐clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.

Conclusion: Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.
Gaucher disease: multiple lessons from a single gene disorder
Authors: Beutler Ernest
Published: August 2010

Gaucher disease is the most common lysosomal storage disease. It is caused by a deficiency in the lysosomal enzyme glucocerebrosidase, a β‐glucosidase, which results in the accumulation of the lipid glucocerebroside in macrophages throughout the body. Gaucher disease is most common in the Ashkenazi Jewish population, and three mutations of the gene encoding glucocerebrosidase (GBA) have been shown to be prevalent in this population (c.1226 A > C [N370S], 84GG and IVS2[+1]). In non‐Jewish patients, the most common mutation is c.1448 G > C (L444P). Until 15 years ago, treatment has been restricted to symptomatic interventions, such as splenectomy or hip replacement. However, there are now specific treatment options – enzyme replacement therapy and substrate reduction therapy. Future developments may include the use of chaperone therapy.

Conclusion: The lessons that we have learned from Gaucher disease may well be applicable to the development of therapies for some of the other less common lysosomal storage diseases.
What makes the heart fail? New insights from defective genes
Authors: Olson Timothy M.
Published: August 2010

Dilated cardiomyopathy (DCM) is an idiopathic, genetically heterogeneous disorder characterized by heart failure and arrhythmia. Over the past decade, the molecular basis for DCM has been partially uncovered by discovery of mutation in genes encoding cystoskeletal, sarcomeric, nuclear membrane, and sarcoplasmic reticulum proteins. These findings have implicated pathogenic mechanisms whereby structural integrity, contractile force dynamics, and calcium regulation within the cardiac myocyte are perturbed. Recognition of dilated and hypertrophic cardiomyopathies as allelic disorders has provided the opportunity to identify genotype‐phenotype relationships and to gain new insight into pathways leading to cardiac failure and hypertrophy.

Conclusion: Collectively, family‐based studies of DCM provide the rationale for clinical screening in first‐degree relatives, regardless of family history or age of the index case.
Cystinuria
Authors: Strologo Luca Dello , Rizzoni Gianfranco
Published: August 2010

Cystinuria is an autosomal recessive disorder characterized by impaired transport of cystine, lysine, ornithine and arginine in the proximal renal tubule and in the epithelial cells of the gastrointestinal tract. Following recent progress in the genetic understanding of the disease, the traditional classification, based on the excretion of cystine and dibasic amino acids in obligate heterozygotes, may no longer be considered valid. A new classification is therefore needed: type A due to two mutations of SLC3A1 on chromosome 2, and type B due to two mutations of SLC7A9 on chromosome 19. The possibility of a third type, AB, with one mutation on each of the above‐mentioned genes, is left open, but is unlikely. Clinical data show that cystinuria is more severe in males than in females in terms of stone production and early age of onset. The two types of cystinuria (A and B) have a similar outcome. A mild renal failure is present in 17% of patients. Medical treatment of this disorder is possible, but requires a composite approach: urine dilution and alkalization, and the use of drugs to form chemical bonds with the sulphydryl domains of the cystine molecule, which lower the amount of free cystine in the urine.

Conclusion: Following new achievements in the genetics of cystinuria, a new classification has been proposed. Cystinuria is more severe in males than in females, but only rarely leads to renal insufficiency. The two types of cystinuria have a similar clinical outcome. A combined medical treatment may be effective in reducing renal stone incidence.
DEPOT DE METHYLCHOLANTHRENE DANS QUELQUES‐UNS DES ORGANES DE LA SOURIS.
Authors: Esmarch Ole
Published: August 2010

Les expériences effectuées portent sur un matériel quin'est pas suffisamment grand pour en tirer des conclusions certaines. Cependant il pourrait sembler que le tissu mamellaire n'ait pas tendance à réagir par la formation de carcinomes au contact direct avec du méthylcholanthrène.M

On n'a pas réussi à provoquer, par le méthylcholanthrène, des tumeurs hépathiques sur le petit nombre d'animaux d'expérience.

Les observations de principe que j'ai réussi à faire sont les suivantes:

la dégénration maligne d'un bout de peau arraché de ses alentours et déposé dans le tissu sous‐cutané avec du methylcholanthréne

la production d'un plasmocytome dans le tissu pulmonaire sous I'influence directe du méthylcholanthrène. La tumeur se répand le long des vaisseaux et des bronches en měme temps qu'a lieu un amas de cellules plasmatiques dans une glande lymphatique

la formation intratesticulaire d'un épithélioma pavimenteux transplantable qui a produit des métastases.
FINGERABDRÜCKE VON WESTGRÖNLÄNDERN.
Authors: Hnsen. Vibeke Fabricius
Published: August 2010

Es wurden Fingerabdrucke von 184 Westgronlandern gemischter Abstammung genommen. Die Verteilung der Mustertypen an allen Fingern wird gezeigt und mit fruheren Untersuchungen verglichen. Es findet sich eine Ahnlichkeit mit St. Lawrence‐ und Point Barrow‐Eskimos, die auch mischrassiger Abstammung sind; bei Ostgronlandern findet man bedeutend mehr Wirbel und weniger Bogen und Schleifen, wahrend man bei der rein europaischen Bevolkerung das umgekehrte Verhaltnis antrifft.
ÜBER EINEN NEUEN SALMONELLA‐TYPUS (S. UGANDA)*.
Authors: Kauffmann. F.
Published: August 2010

Es wird ein neuer Salmonella‐Typus (S. Uganda) beschrie‐ben, dessen Antigenformel III, X, XXVI. l, z13? 1,5… lautet, und der aus der Milz eines tödlich verlaufenen, fieberhaften Krankheitsfalles in Uganda isoliert wurde.
ÜBER SERUMFÄLLE.
Authors: Gammelgaard. Von Arne
Published: August 2010

Nach Erwähnung der in der Literatur beschriebenen, tödlich verlaufenden Shocks nach Seruminjektion und deren Ähnlichkeitspunkte, sowohl klinisch als pathologisch‐anatomisch mit dem anaphylaktischen Shock bei Tieren, und nach einer kurzen Erwähnung des Symptomkomplekses, der Serumkrankheit, wird ein tödlich verlaufender Serumfall nach prophylaktischer Tetanusantitoxin‐Injektion bei einem 42‐jährigen. früher gesunden Mann berichtet, der weder je Symptome von Überempfindlichkeit aufgewiesen, noch früher Seruminjektion erhalten hat.

Bei der Obduktion wurden kapillare Hyperämie in den Organen, perivasculäres ödem und perivasculäre Blutungen überall im Gehirn, besonders in der Medulla oblongata und Pons, kleine Blutungen in den Nieren und kleinere Blutaustritte in der Herzmuskulatur nachgewiesen. Da man eine Viertelstunde vor dem Eintritt des Todes klinisch noch keine deutlichen schockartigen Symptome beobachtet hat, hat man die Möglichkeit hervorgehoben, dass die nachgewiesenen perivasculären Hirnblutungen eine wesentliche Ursache zum Eintritt des Todes gewesen sind.