[Stroke alarm-Arterial ischemic stroke as one of the most time-critical emergencies in children and adolescents]. / Notfall-Neuropädiatrie ­ Der arteriell ischämische Schlaganfall als einer der zeitkritischsten Notfälle bei Kindern und Jugendlichen.

Arterial ischemic stroke in childhood and adolescence is one of the most time-critical emergencies in pediatrics. Nevertheless, it is often diagnosed with a considerable time delay which may be associated with low awareness, the sometimes nonspecific clinical presentation with a wide variety of differential diagnoses, and less established 'acute care structures'. The revascularisation strategies in adult stroke care are also potential and promising treatment options for children, even if available evidence is still limited. In the post-acute phase, the etiological work-up is complex due to the multitude of risk factors to be considered. But it is essential to identify each child's individual risk profile as it determines secondary prevention, risk of recurrence and outcome. Long-term care in a multiprofessional, interdisciplinary team must take into account the bio-psycho-social aspects to integrate the child into its social and educational, and later professional environment.

Transient severe tricuspid regurgitation after transplantation of an extremely oversized donor heart in a child-Does size matter? A case report.

In pediatric heart transplantation, the size of the donor organ is an important criterion for organ allocation. Oversized donor hearts are often accepted with good results, but some complications in relation to a high donor-recipient ratio have been described. Our patient was transplanted for progressive heart failure in dilated cardiomyopathy. The donor-to-recipient weight ratio was 3 (donor weight 65 kg, recipient weight 22 kg). The intra-operative echocardiography before chest closure showed excellent cardiac function, no tricuspid valve regurgitation, and a normal central venous pressure. After chest closure, central venous pressure increased substantially and echocardiography revealed a severe tricuspid insufficiency. As other reasons for right ventricular dysfunction, that is, myocardial ischemia, pulmonary hypertension, and rejection, were excluded, we assumed that the insufficiency was caused by an alteration of the right ventricular geometry. After 1 week, the valve insufficiency regressed to a minimal degree. In pediatric heart transplant patients with a high donor-to-recipient weight ratio, the outlined complication may occur. If other reasons for right ventricular heart failure can be ruled out, this entity is most likely caused by an acute and transient alteration of the right ventricular geometry that may disappear over time.

Balloon-Atrioseptostomy in Small Children Using an Embolectomy Catheter: Preliminary Data.

Interventional treatment of restrictive atrial septal defects in complex heart disease is considered state-of-the-art therapy up to date. Nevertheless, dedicated balloons are lacking so far, as several products have been withdrawn from the market. We report on off-label use of a balloon embolectomy catheter used successfully in a preterm patient and discuss whether this device might be used in other patients as well as it seems to be promising due to its shape and versatility.

Microcatheter-assisted stenting of the tortuous vertical ductus arteriosus via femoral access in a duct-dependent pulmonary circulation.

BACKGROUND: Stenting of the patent ductus arteriosus (PDA) has been accepted as alternative option to surgical shunting to enable additional pulmonary blood flow or for palliation of patients with a truly duct-dependent pulmonary circulation. The procedure can be challenging given the variable and often tortuous anatomy of the PDA and various technical approaches are reported. OBJECTIVE: To report an alternative technique to treat tortuous ducts with microcatheter assistance and by transfemoral approach. METHODS: We applied this technique of PDA stenting in 5 consecutive patients (4/5 age < 1 week, weight 2,7-3,2 kg; 1/5 re-do PDA stenting at 6,5 month and 5,9 kg). A soft coronary guidewire was advanced by microcatheter assistance into the branch pulmonary arteries and thereafter replaced by an extrastiff guidewire to enable the placement of long coronary stents. RESULTS: Successful PDA stenting with this stepwise approach and with femoral access only could be achieved in all patients (n = 5/5). A single stent was used in 2 patients (one with re-do stenting and previous stents). 3/5 patients had 2 stents implanted by telescopic technique. Stent sizes used were 4,5 × 15 mm (n = 2) and 4,5 × 18 mm (n = 6). No guide wire or stent dislodgement appeared through all procedures with microcatheter assistance. CONCLUSIONS: This technique enables PDA stenting via transfemoral approach in complex and tortuous ducts and thereby offers an attractive addition to the interventional management of truly duct-dependent pulmonary circulation.

The role of FDG-PET-CT in pediatric cardiac patients and patients with congenital heart defects.

AIM: Medical imaging by using FDG-PET/CT (PET-CT) can detect, confirm or eliminate with high sensitivity areas of suspected infections in case of persistent fever of unknown origin in combination with other bacteriological examinations. The aim of this study was to assess the potential role of PET-CT in detecting or excluding infections or other inflammatory processes in patients with congenital heart defects (CHD). In addition we wanted to evaluate the practical impact of PET-CT on the subsequent clinical management. METHODS: In this retrospective study we analyzed the data of all CHD patients who underwent PET-CT over a 5year period in our institution. The results were then evaluated with regard to the potential impact on clinical decision making. RESULTS: Between 2010 and 2015 PET-CT was performed in 30 patients. The mean age was 26years (SD 15years, range 1 to 66years). The diagnoses covered a large field of CHD. 11 patients (4/11 with assist device) were assessed before heart transplantation; suspected malignancies or infections were excluded and transplant listing was possible. In another 5/6 patients suspected assist device infection could be confirmed with PET/CT. Endocarditis was suspected in 13 patients, 2 of whom underwent previous MRI without confirmation and ECHO was inconclusive. Endocarditis was finally excluded in 5/13 patients but confirmed in 8/13 patients by PET-CT. CONCLUSION: In this study we could show a high sensitivity of PET-CT for specific localization of infections and with high impact on subsequent therapy. Based on this results clinical management could be targeted and adapted. We could demonstrate that PET-CT has a high impact on the subsequent clinical therapy.

Alpha-tubulin gene family of maize (Zea mays L.). Evidence for two ancient alpha-tubulin genes in plants.

Among 81 alpha-tubulin cDNA clones prepared from RNA from maize seedling shoot, endosperm and pollen, we identified six different alpha-tubulin coding sequences. The DNA sequence analysis of coding and non-coding regions from the clones showed that they can be classified into three different alpha-tubulin gene subfamilies. Genes within each subfamily encode proteins that are 99 to 100% identical in amino acid sequence. Deduced amino acid sequence identity between genes in different subfamilies ranges from 89 to 93%. The results of hybridizations of genomic DNAs to alpha-tubulin coding region probes and to 3' non-coding region probes constructed from six different alpha-tubulin cDNA clones indicated that the maize alpha-tubulin gene family contains at least eight members. Comparison of deduced alpha-tubulin amino acid sequences from maize and the dicot species Arabidopsis thaliana showed that alpha-tubulin isotypes encoded by genes in maize subfamilies I and II are more similar to specific Arabidopsis gene products (96 to 97% amino acid identity) than to isotypes encoded by genes in the other maize subfamilies. Phylogenetic analyses revealed that genes in these two subfamilies were derived from two ancient alpha-tubulin genes that predate the divergence of monocots and dicots. These same analyses revealed that the gene in maize subfamily III is more closely related to sequences from subfamily I genes than to those from subfamily II genes. However, the subfamily III gene has no close counterpart in Arabidopsis. We found evidence of a transposable element-like insertion in the subfamily III gene in some maize lines.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND: Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM: To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS: Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS: Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS: Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

Acute hemodynamic effects of post cardiotomy peritoneal dialysis in neonates and infants.

OBJECTIVE: Evaluation of the acute hemodynamic changes during peritoneal dialysis in patients with low cardiac output syndrome and acute renal failure after open heart surgery. PATIENTS: Three newborns and three infants after corrective surgery of congenital heart disease with post cardiotomy dialysis. Five of these had an open thorax during dialysis. METHODS: Cardiac output measurements using the thermodilution technique on two consecutive days at four different times during the peritoneal dialysis cycle. RESULTS: We did not find a deterioration of the cardiac index or systemic vascular resistance measured over two cycles in each of the six patients. Pulmonary artery pressure rose slightly after instillation of the dialysate solution in all patients. Changes in central venous pressure and left atrial pressure were not clinically meaningful. In all patients fluid removal by peritoneal dialysis was effective. All five surviving patients recovered renal function. CONCLUSIONS: Peritoneal dialysis can be performed in newborns and infants following cardiac surgery without causing acute hemodynamic imbalances. An open chest may have a significant impact on hemodynamic stability during peritoneal dialysis by blunting any possible negative alterations of increased intraabdominal pressure.

Peritoneal dialysis after infant open heart surgery: observations in 27 patients.

BACKGROUND: The role of peritoneal dialysis (PD) in the management of infants after heart operation is under discussion. The aim of this study was to investigate the effect of PD on fluid balance and outcome. METHODS: Twenty-seven (33%) of 81 consecutive infants who underwent heart operation required PD. In 22 patients (81%), PD was started prophylactically at the end of the operation. We recorded hemodynamic data and fluid balance. Patients experiencing acute renal failure (ARF) were compared with the remaining infants. RESULTS: Eleven of 81 patients (14%) experienced ARF; 3 of them died (4% of all patients undergoing operation, 27% of those with ARF). Complications of PD, present in 33%, were transitory and of minor significance. Patients with ARF had decreased cardiac function compared with those without ARF but similar fluid balance. CONCLUSIONS: Peritoneal dialysis is an effective and safe method for the treatment of ARF in infants after open heart operation. As PD is helpful in modulating postoperative fluid balance, prophylactic use of PD can be recommended for selected patients who are at risk for low cardiac output syndrome.

Comparison of bile acid synthesis determined by isotope dilution versus fecal acidic sterol output in human subjects.

Fecal acidic sterol output has been found to be much lower than bile acid synthesis determined by isotope dilution (J. Lipid Res. 17: 17, 1976). Because of this confusing discrepancy, we compared these 2 measurements done simultaneously on 13 occasions in 5 normal volunteers. In contrast to previous findings, bile acid synthesis by the Lindstedt isotope dilution method averaged 16.3% lower than synthesis simultaneously determined by fecal acidic sterol output (95% confidence limit for the difference - 22.2 to -10.4%). When one-sample determinations of bile acid pools were substituted for Lindstedt pools, bile acid synthesis by isotope dilution averaged 5.6% higher than synthesis by fecal acidic sterol output (95% confidence limits -4.9 to 16.1%). These data indicate that the 2 methods yield values in reasonably close agreement with one another. If anything, fecal acidic sterol outputs are slightly higher than synthesis by isotope dilution.

Value of postmortem magnetic resonance imaging for fatal neonatal congenital heart disease: a case report.

Autopsies after neonatal death due to suspected or insufficient diagnosed cardiac malformations provide important information to parents and the involved obstetric and pediatric physicians. The autopsy rate, however, is declining. Postmortem magnetic resonance imaging may be an alternative option for selected cases, providing detailed morphologic information about the cardiovascular system. This case report demonstrates the beneficial use of postmortem magnetic resonance imaging in a newborn with a suspected complex cardiac malformation. The magnetic resonance imaging was able to complete the diagnosis of situs inversus totalis, with transposition of great arteries, and to provide valuable information about the underlying physiology.

Successful treatment of oleander intoxication (cardiac glycosides) with digoxin-specific Fab antibody fragments in a 7-year-old child: case report and review of literature.

UNLABELLED: A 7-year-old girl presented six hours after ingestion of a yellow oleander seed (Thevetia peruviana) with severe emesis, change in colour vision and complete heart block. Initial treatment with phenytoin and isoprenalin infusion led to intermittent supraventricular and ventricular tachycardia. The patient was then treated with two intravenous doses of 190 mg of digoxin-specific Fab antibody fragments (Digibind). Subsequently the patient's rhythm reverted to sinus rhythm and the symptoms resolved within 2 hours. CONCLUSION: administration of digoxin-specific Fab antibody fragments in an otherwise healthy child after oleander intoxication is safe and without adverse reactions.

Initial experience using the NuMED Cheatham Platinum (CP) stent for interventional treatment of coarctation of the aorta in children and adolescents.

We report the immediate results in a group of selected patients with native or recurrent coarctation of the aorta who underwent endovascular stent implantation using the newly designed Cheatham-Platinum (CP)-stent. The balloon-expandable stents were implanted in 6 patients (mean age 12.7 years) with coarctation of the aorta (5 native, 1 recurrent). The maximal systolic peak pressure gradient was decreased from 49 to 3 mmHg (p <0.001). There was a 350% increase in the mean diameter at the original coarctation site (3.8 to 13.8 mm, p <0.01). Although the maximal diameter varied from 8 to 18 mm, there was only a minor reduction in the length of the CP-stents used (max. 11%). The dilatation was successful in all patients and there were no complications during balloon dilatation or stent implantation. All patients were hypertensive prior to stent implantation, with three of them requiring antihypertensive drug therapy. In 2 patients only a moderate dilatation diameter was chosen initially due to the extremely small coarctation site (1 mm) and repeat dilatation after 12 months was performed in order to obtain a maximal aortic diameter. At a mean of 18 months of follow-up, 5 of 6 patients are normotensive. There is no recurrence of coarctation, aortic dissection or aneurysm formation and no stent displacement. These findings suggest that the implantation of CP-stents for coarctation of the aortamay cover a wide spectrum of aortic diameters and consequently hereby offer an effective alternative approach to surgery or ballon dilatation alone even in infancy and childhood. The potential for redilatation of CP-stents in a wide range of diameters without significant shortening adds to the benefit of this device in growing children.

[Difficulties in diagnosing Marfan's syndrome in childhood and adolescence]. / Diagnostische Schwierigkeiten bei Patienten mit Marfan-Syndrom im Kindes- und Jugendalter.

BACKGROUND: The diagnosis of Marfan's syndrome in childhood and adolescence is made by the criteria of the Gent nosology, which evaluates genetic data, family history and a spectrum of clinical criteria. Due to the age dependent manifestations of the clinical symptoms, combined with the extreme heterogeneity of Marfan's syndrome diagnosis in early childhood remains sometimes difficult. PATIENTS: Prospectively, we analyzed the clinical symptoms of all patients where Marfan's syndrome was suspected. We evaluated those patients between January 1997 and April 2002 by an interdisciplinary approach. METHODS: We compared the clinical datas of the patients by using the Gent nosology and the Berlin nosolgy. RESULTS: 34 patients underwent full follow-up. The median age was 10,32 years with a range of 0,01 to 37,31 years, 19 patients were male, 15 patients were female. In eight patients Marfan's syndrome could be rouled out, 9 of 26 patients (34,6 %) fullified the criteria of the Gent nosology, in 17 of 26 patients (65,4 %) Marfan's syndrome remained just suspected, but was not fullified by the criteria of the Gent nosology. Concerning the Berlin nosology 14 of 26 patients (53,8 %) fullified the criteria, 12 of 26 patients (46,2 %) failed. Due to the criteria of the Gent nosology 14 patients (53,8 %) fullified the criteria of skeletal involvement, 21 patients (80,8 %) fullified cardiovascular major manifestation, 6 patients (23,1 %) had an ophthalmic major manifestation, and 9 patients (34,6 %) had an affected first degree relative or were genetically determined. CONCLUSIONS: On the basis of the data of our patients the diagnosis of Marfan's syndrome in childhood and adolescence can be made more sensitive by the criteria of the Berlin nosology compared to the Gent nosology. This seems to be caused by the age dependent manifestations of the symptoms. Until diagnostic algorhythms of Marfan's syndrome in childhood remain suboptimal, continuous clinical follow-up for all cases even those only in the case of suspected Marfan's syndrome are necessary to exclude complicated course and to improve outcome.

[The clinical diagnosis of aortic isthmus stenosis]. / Klinische Diagnostik der Aortenisthmusstenose.

BACKGROUND AND OBJECTIVE: Unfortunately, congenital coarctation of the aorta (CoA) is in many cases not diagnosed until adulthood., even though this defect is known to cause serious complications if treated too late. This retrospective study of patients was undertaken to ascertain whether early, exclusively clinical, diagnosis would have been possible. PATIENTS AND METHODS: The case notes of 61 patients with native CoA (n = 45) or restenosis in adulthood after earlier surgical repair (n = 16) were analysed with regard to the findings on physical examination and the patients' symptoms. RESULTS: The patients' age ranged from 15 to 54 years (mean 23 +/- 15.5 years). 48 of 58 patients (83%; incomplete data excluded three patients) had hypertension in the brachial arteries and 50 of 58 (86%) had a pressure difference between the arms. 51 of 53 patients (96%) had a heart murmur, while a pressure gradient between the arms and legs was recorded in in 49 of 51 patients (96%). Notching of the ribs was noted in the chest radiogram of 47 of the 58 patients in whom it was taken. 35 patients had reported one, 23 more than one symptom. CONCLUSION: In all patients (with native CoA or restenosis after surgical repair) it would have been possible to make the correct diagnosis of CoA on the basis of hypertension in the arms, a difference in pulse amplitude and/or a pressure gradient between arms and legs, as well as a cardiac murmur. Normal pressures in ten patients could be explained by marked collateral circulation (rib notching), but even in these patients their symptoms plus at least two other main signs could have provided the correct diagnosis at an earlier time.

The small genome of Arabidopsis contains at least nine expressed beta-tubulin genes.

The small genome of Arabidopsis contains at least nine expressed beta-tubulin (TUB) genes, in contrast to the large genomes of vertebrate animals, which contain a maximum of seven expressed beta-tubulin genes. In this study, we report the structures of seven new TUB genes (TUB2, TUB3, TUB5, TUB6, TUB7, TUB8, and TUB9) of Arabidopsis. The sequences of TUB1 and TUB4 had been reported previously. Sequence similarities and unique structural features suggest that the nine TUB genes evolved by way of three branches in the plant beta-tubulin gene evolutionary tree. Two genes (TUB2 and TUB3) encode the same beta-tubulin isoform; thus, the nine genes predict eight different beta-tubulins. In contrast to the alpha-tubulin (TUA) genes with their divergent intron patterns, all nine TUB genes contain 2 introns at conserved positions. Noncoding 3' gene-specific hybridization probes have been constructed for all nine TUB genes and used in RNA gel blot analyses to demonstrate that all nine genes are transcribed. Two-dimensional protein immunoblot analyses have resolved at least seven different beta-tubulin isoforms in Arabidopsis, indicating that most, if not all, of the TUB transcripts are translated.

Characterization of four new beta-tubulin genes and their expression during male flower development in maize (Zea mays L.).

Four different beta-tubulin coding sequences were isolated from a cDNA library prepared from RNA from maize seedling shoots. The four genes (designated tub4, tub6, tub7 and tub8) represented by these cDNA clones together with the tub1 and tub2 genes reported previously encode six beta-tubulin isotypes with 90-97.5% amino acid sequence identity. Results from phylogenetic analysis of 17 beta-tubulin genes from monocot and dicot plant species indicated that multiple extant lines of beta-tubulin genes diverged from a single precursor after the appearance of the two major subfamilies of alpha-tubulin genes described previously. Hybridization probes from the 3' non-coding regions of six beta-tubulin clones were used to quantify the levels of corresponding tubulin transcripts in different maize tissues including developing anthers and pollen. The results from these dot blot hybridization experiments showed that all of the beta-tubulin genes were expressed in most tissues examined, although each gene showed a unique pattern of differential transcript accumulation. The tub1 gene showed a high level of transcript accumulation in meristematic tissues and almost no accumulation in the late stages of anther development and in pollen. In contrast, the level of tub4 transcripts was very low during early stages of male flower development but increased markedly (more than 100 times) during the development of anthers and in pollen. Results from RNAse protection assays showed that this increased hybridization signal resulted from expression of transcripts from one or two genes closely related to tub4. The tub4-related transcripts were not present in shoot tissue. Transcripts from the tub2 gene accumulated to very low levels in all tissues examined, but reached the highest levels in young anthers containing microspore mother cells. RNAse protection assays were used to measure the absolute levels of alpha- and beta-tubulin transcripts in seedling shoot and in pollen. The alpha-tubulin gene subfamily I genes (tua1, tua2, tua4) contributed the great majority of alpha-tubulin transcripts in both shoot and pollen. Transcripts from the beta-tubulin genes tub4, tub6, tub7, and tub8 were predominant in shoot, but were much less significant than the tub4-related transcripts in pollen.

[Is transcatheter occlusion of a persistent foramen ovale a possibility for the avoidance of a paradoxical embolism?]. / Transkatheterverschluss des persistierenden Foramen ovale als Möglichkeit zur Vermeidung paradoxer Embolien?

BACKGROUND AND OBJECTIVE: Cerebral embolism may have different causes with sometimes serious consequences. If no specific reason can be found, paradoxical embolization through a persistent foramen ovale (PFO) is increasingly as a cause of the cerebral ischaemia. This study was undertaken to ascertain whether in patients with cerebral embolism occlusion of a PFO with a transcatheter technique can prevent further cerebral emboli. PATIENTS AND METHODS: Indications for transcatheter occlusion were based on neurological signs (ischaemic stroke), cardiovascular diagnosis, and coagulation tests. Between August 1991 and July 1996, transcatheter occlusion of a PFO was performed in 28 fully anticoagulated patients (median age 37.8 [15.4-65.4] years). The mean PFO diameter was 9.5 mm (3-17), mean duration of fluoroscopy 18.3 (8.7-43.1) min. The Rashkind device was implanted in three patients, the Sideris buttoned device in 25. During the follow-up period (2-64 months; mean 13 months) renewed neurological symptoms occurred in only one patient. Transoesophageal echocardiography excluded thrombi on the implanted device or in the left atrium, and a residual PFO. The cause of the one neurological episode is therefore not clear. All other patients have remained free of symptoms and recurrence without anticoagulation after placement of the device. CONCLUSIONS: Transcatheter occlusion of a PFO is a relatively simple and safe procedure. Our results suggest that it can at least lower the incidence of further cerebral embolizations. The clinical value of the method in comparison with anticoagulation requires further study.

Renal impairment in patients with long-standing cyanotic congenital heart disease.

Nephropathy is known to occur in patients with long-standing cyanotic congenital heart disease (CCHD). In order to assess the incidence, nature and degree of the problem among such patients, discriminating urine analyses were performed in 26 patients with CCHD, with a mean age of 22 (10-42) y. Ten patients showed reduced glomerular function, six of whom also had advanced glomerulopathy. Glomerular filtration rates were below normal in half of the patients and occurred with glomerular-type proteinuria in five, with tubular-type proteinuria in one and without pathological proteinuria in four. An elevated haematocrit and duration of cyanosis were identified as the main risks factors for the development of glomerulopathy. The risk of developing glomerular lesions rose sharply during the second decade of life. Nephropathy in CCHD is common and the dominant feature is glomerular damage, which is related to the duration of cyanosis and the extent to which the haematocrit is elevated.