Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany

The lack of epidemiological data on the frequency and/or burden of organic acidurias (OA) and mitochondrial fatty acid transport and oxidation disorders (mtFATOD) is one reason for hesitation to expand newborn screening (NBS) by tandem mass spectrometry (MS-MS). From 1999 to 2000, the frequency of ten potentially treatable OA and mtFATOD was assessed by active nation-wide surveillance on cases presenting with clinical symptoms using the German Paediatric Surveillance Unit (ESPED) system. Case ascertainment was complemented by a second independent source: 3-monthly inquiries in the metabolic laboratories performing secondary selected screening for OA and mtFATOD. Frequency estimates for clinically symptomatic cases older than 7 days in a birth cohort of 844,575 conventionally screened children was compared to the frequency found in a cohort of 382,247 screened by MS-MS in Bavaria and Baden-Württemberg. The overall frequency of the ten conditions considered was 1:8,000 (95% CI 1:11,000–1:6,000) by MS-MS as compared to 1:23,000 (95% CI 1:36,000–1:17,000) in symptomatic cases presenting mainly with metabolic crisis. The contributions of medium-chain acyl-CoA dehydrogenase deficiency (MCADD), other mtFATOD and OA were 29, 4 and 13 among the 46 cases identified by MS-MS, and 19, 1 and 13 among the 33 clinically symptomatic cases, respectively. Acute metabolic crisis, with a lethal outcome in four patients, was reported for 22/33 clinically symptomatic cases. No clinically symptomatic cases were reported from cohorts with screened by MS-MS. Conclusion: ten potentially treatable organic acidurias and mitochondrial fatty acid transport and oxidations disorders were more common than phenylketonuria with organic acidurias accounting for 28% of the cases detected by newborn screening and 39% of the cases identified on high risk screening. These conditions were related to considerable morbidity and mortality. Considerations for their inclusion in expanded newborn screening programmes might be warranted.Abbreviations ESPED Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) - MCADD medium-chain acyl-CoA dehydrogenase deficiency - MS-MS tandem mass spectrometry - mtFATOD mitochondrial fatty acid transport and oxidation disorders - NBS newborn screening - OA organic acidurias     

Childhood factors associated with asthma remission after 30 year follow up

BACKGROUND: Factors contributing to either "complete" or "clinical" remission of asthma are important to know since there is no cure for the disease. METHODS: A cohort of 119 allergic asthmatic children was examined three times with a mean follow up of 30 years. They were aged 5-14 years at visit 1 (1966-9), 21-33 years at visit 2 (1983-6), and 32-42 years at visit 3 (1995-6). Complete remission of asthma at visit 3 was defined as no asthma symptoms, no use of inhaled corticosteroids, normal lung function (FEV1 >90% predicted), and no bronchial hyperresponsiveness (PC10 >16 mg/ml). Clinical remission was defined as no asthma symptoms and no use of inhaled corticosteroids. RESULTS: 22% of the group was in complete remission of asthma at visit 3 and a further 30% was in clinical remission (total 52%); 57% of subjects in clinical remission had bronchial hyperresponsiveness and/or a low lung function. Logistic regression analyses showed that a higher FEV1 in childhood and more improvement in FEV1 from age 5-14 to 21-33 were associated with both complete and clinical asthma remission at age 32-42. CONCLUSIONS: Complete remission of asthma was present in a small subset of asthmatics while half the subjects showed clinical remission. Both complete and clinical remission were associated with a higher lung function level in childhood and a higher subsequent increase in FEV1. These results support the view that defining remission only on the basis of symptoms and medication use will overlook subjects with subclinical active disease and possibly associated airway remodelling.     

Doppler sonography of uterine arteries at 20-23 weeks: risk assessment of adverse pregnancy outcome by quantification of impedance and notch

OBJECTIVE: To assess the diagnostic value of Doppler sonography of the uterine arteries (DSUA) at 20-23 gestational weeks as screening procedure in a low risk population. PATIENTS AND METHODS: The study group consisted of 7508 singleton low-risk pregnancies. Doppler sonography of both uterine arteries was performed as routine part of anomaly scan. Impedance of both uterine arteries was registered using the mean PI of the two uterine arteries. In case of notch, "Notch-Index" was defined as (C-D)/C with D = post-systolic nadir and C = following zenith of the waveform. Outcome variables were placental abruption, pre-eclampsia, intrauterine growth retardation, intrauterine/neonatal death and preterm delivery before 32 completed gestational weeks. To discriminate normal and pathological waveform, incidence of adverse pregnancy outcome was related to four different definitions of pathological waveform. To describe the severity of impairment of perfusion, the frequency of adverse pregnancy outcome was related to different classes of impedance. RESULTS: To find a simple discrimination between normal and pathological uterine perfusion, best diagnostic performance was reached by a definition using a combination of high impedance and notch (no notch and mean PI > P'95 or unilateral notch and mean PI > P'90 or bilateral notch and mean PI > P'50). The prevalence of notch in nulliparae (8.5%) was higher than in parae (4.7%) and decreased with increasing gestational age (20 weeks: 8.6%-23 weeks: 5.4%). We found a clear relation between elevation of impedance, depth of notch and frequency of adverse pregnancy outcome with a frequency of complications varying from 3.2% (mean PI < or = 0.8, mean NI = 0.1) to 38.4% (mean PI > 2.0, mean NI > 0.1). CONCLUSION: Doppler sonography of the uterine arteries at 20-23 weeks has the capacity to predict at least a part of severe forms of adverse pregnancy outcome and to assess the probability of complications by quantification of the impairment of the uterine blood flow.     

Carbon Dioxide in the Aortic Arch: Coronary Effects and Implications in a Swine Study

Purpose: CO₂ angiography is considered dangerous in the aortic arch where bubbles may cause critical cerebral and cardiac ischemia. We investigated CO₂ distribution, physiologic effects in the heart, methods of detection and treatments. Methods: Eight pigs had CO₂ and iodinated contrast arch angiograms in supine and both lateral decubitus positions. An electrocardiogram, physiologic data and cardiac ultrasound were obtained. Therapies included precordial thumps and rolls to lateral decubitus positions. Results: Supine high descending aorta CO₂ injections floated retrograde up the arch during diastole and preferentially filled the right coronary artery (RCA): mean score 3.5 (of 4), innominate artery 2.4, left coronary artery 1.2; n = 17; p = 0.0001. Aortic root injections preferentially filled the RCA when the animal was supine, left coronary in the right decubitus position, and showed a diffuse pattern in the left decubitus position. Right decubitus rolls filled both coronaries causing several lethal arrhythmias. Precordial thumps successfully cleared CO₂. Ultrasound is a sensitive detector of myocardial CO₂. Conclusion: Arch distribution of CO₂ primarily involves the RCA. Diagnostic ultrasound detects cardiac CO₂ well. Precordial thumps are an effective treatment.     

Pet sensitivities in asthmatic children

A history of pet contact and/or apparent clinical sensitivity was obtained in 65 (55%) of 118 unselected asthmatic children. These 65 children were skin tested and their sera examined for specific IgE using the radioallergosorbent test. Those children who had apparent clinical sensitivities had larger skin test reactions and were more likely to have positive specific IgE results than those without apparent sensitivities. Positive skin tests were very common (80%), but the larger the skin test reaction (weal diameter greater than 4 mm diameter) the more likely was there to be a positive history or a positive specific IgE result. Hence a large skin test reaction can provide a helpful pointer to animal allergy of clinical importance. Commercially available animal extracts have limitations for diagnostic tests. A questionnaire survey of 150 day schools emphasized the potential opportunities for contact with animal allergens at school.     

A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection

A rapid microagglutination test has been developed which can be performed in 30 minutes. Ninety-seven percent of 96 patients diagnosed as having Legionella pneumophila (serogroup 1) infection by indirect immunofluorescence were also detected by the rapid microagglutination test.     

Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes

Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin lymphoma (HL) secrete factors that interact with inflammatory background cells and may serve as biomarkers for disease activity. To detect new proteins related to pathogenesis, we analyzed the secretome of HRS cells. Proteins in cell culture supernatant of 4 HL cell lines were identified using 1DGE followed by in-gel trypsin digestion and LC-MS/MS. In total, 1290 proteins, including 368 secreted proteins, were identified. Functional grouping of secreted proteins revealed 37 proteins involved in immune response. Sixteen of the 37 proteins (ie, ALCAM, Cathepsin C, Cathepsin S, CD100, CD150, CD26, CD44, CD63, CD71, Fractal-kine, IL1R2, IL25, IP-10, MIF, RANTES, and TARC) were validated in HL cell lines and patient material using immunohistochemistry and/or ELISA. Expression of all 16 proteins was confirmed in HL cell lines, and 15 were also confirmed in HL tissues. Seven proteins (ALCAM, cathepsin S, CD26, CD44, IL1R2, MIF, and TARC) revealed significantly elevated levels in patient plasma compared with healthy controls. Proteomics analyses of HL cell line supernatant allowed detection of new secreted proteins, which may add to our insights in the interaction between HRS cells and infiltrating lymphocytes and in some instances might serve as biomarkers.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.