Prevalence Estimation of Williams Syndrome Strømme, Petter; Bjømstad, Per G.; Ramstad, Kjersti
Journal of child neurology,
04/2002, Letnik:
17, Številka:
4
Journal Article
Recenzirano
There are limited population-based data on the occurrence of Williams syndrome. We estimated its prevalence combining data from two investigations. One was an epidemiologic study originally designed ...to assess the prevalence and etiology of mental retardation among 30,037 Norwegian children born between 1980 and 1985 and living in Akershus County on January 1, 1993. The other investigation was a national survey of Williams syndrome. In the first study, 213 children were referred for evaluation, whereas the second study comprised 57 cases with Williams syndrome born between 1970 and 1992, who were referred for evaluation from all Norwegian counties. The epidemiologic study revealed three children with Williams syndrome, whereas one additional case complying with our demographic criteria was identified in the national survey, thus giving a prevalence of 1 in 7500. In all cases, a typical chromosome 7q11.23 deletion was detected. We also conclude that Williams syndrome is not an uncommon cause of mental retardation, with a prevalence of approximately 6% of patients with genetic etiology. (J Child Neurol 2002;17:269-271).
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•We established a fibroblast cell cultures from killer whale skin biopsies.•We exposed the fibroblasts with environmentally relevant concentrations of POPs.•POP exposure led to ...altered transcription of a low number of genes in the fibroblasts.•The genes were related to lipid metabolism, myogenesis and glucocorticoid action.•The information is important for management of chemicals and a data-deficient species.
Populations of killer whale (Orcinus orca) contain some of the most polluted animals on Earth. Yet, the knowledge on effects of chemical pollutants is limited in this species. Cell cultures and in vitro exposure experiments are pertinent tools to study effects of pollutants in free-ranging marine mammals. To investigate transcriptional responses to pollutants in killer whale cells, we collected skin biopsies of killer whales from the Northern Norwegian fjords and successfully established primary fibroblast cell cultures from the dermis of 4 out of 5 of them. Cells from the individual with the highest cell yield were exposed to three different concentrations of a mixture of persistent organic pollutants (POPs) that reflects the composition of the 10 most abundant POPs found in Norwegian killer whales (p,p’-DDE, trans-nonachlor, PCB52, 99, 101, 118, 138, 153, 180, 187). Transcriptional responses of 13 selected target genes were studied using digital droplet PCR, and whole transcriptome responses were investigated utilizing RNA sequencing. Among the target genes analysed, CYP1A1 was significantly downregulated in the cells exposed to medium (11.6 µM) and high (116 µM) concentrations of the pollutant mixture, while seven genes involved in endocrine functions showed a non-significant tendency to be upregulated at the highest exposure concentration. Bioinformatic analyses of RNA-seq data indicated that 13 and 43 genes were differentially expressed in the cells exposed to low and high concentrations of the mixture, respectively, in comparison to solvent control. Subsequent pathway and functional analyses of the differentially expressed genes indicated that the enriched pathways were mainly related to lipid metabolism, myogenesis and glucocorticoid receptor regulation. The current study results support previous correlative studies and provide cause-effect relationships, which is highly relevant for chemical and environmental management.
Aims
The purpose of this paper was to present the results of a simple modification of the suture technique for pulmonary artery banding (PAB), which allows for stepwise debanding by use of balloon ...catheter.
Methods and results
During the period 1985-2007, PAB operations were performed in 227 children at Rikshospitalet. Of these children, 14.5% (n = 33) were treated by balloon dilatation of the PAB. Nine were treated twice. The intention of the procedure was total debanding in 17 and palliative treatment by stepwise dilatation of the PAB in 16 patients. Median follow up time was 59 months. The mean reduction of the gradient was more pronounced in the first group (37.0 ± 19.0 vs. 14.5 ± 10.3 mmHg, P < 0.001). The average mean oxygen saturation improved, however, significantly within the palliated group. The median time for reintervention after stepwise dilatation was 9 months. Serious, procedure-related complications occurred in 2 of 42 catheterizations (4.8%). Debanding by catheter replaced surgery in 8 of the 17 patients (47%).
Conclusion
We consider catheter debanding a valuable alternative in selected cases. Combination with additional interventional techniques may extend the future indications.
During progression to heart failure (HF), myocardial extracellular matrix (ECM) alterations and tissue inflammation are central. Lumican is an ECM‐localized proteoglycan associated with inflammatory ...conditions and known to bind collagens. We hypothesized that lumican plays a role in the dynamic alterations in cardiac ECM during development of HF. Thus, we examined left ventricular cardiac lumican in a mouse model of pressure overload and in HF patients, and investigated expression, regulation and effects of increased lumican in cardiac fibroblasts. After 4 weeks of aortic banding, mice were divided into groups of hypertrophy (AB) and HF (ABHF) based on lung weight and left atrial diameter. Sham‐operated mice were used as controls. Accordingly, cardiac lumican mRNA and protein levels were increased in mice with ABHF. Similarly, cardiac biopsies from patients with end‐stage HF revealed increased lumican mRNA and protein levels compared with control hearts. In vitro, mechanical stretch and the proinflammatory cytokine interleukin‐1β increased lumican mRNA as well as secreted lumican protein from cardiac fibroblasts. Stimulation with recombinant glycosylated lumican increased collagen type I alpha 2, lysyl oxidase and transforming growth factor‐β1 mRNA, which was attenuated by costimulation with an inhibitor of the proinflammatory transcription factor NFκB. Furthermore, lumican increased the levels of the dimeric form of collagen type I, decreased the activity of the collagen‐degrading enzyme matrix metalloproteinase‐9 and increased the phosphorylation of fibrosis‐inducing SMAD3. In conclusion, cardiac lumican is increased in experimental and clinical HF. Inflammation and mechanical stimuli induce lumican production by cardiac fibroblasts and increased lumican altered molecules important for cardiac remodeling and fibrosis in cardiac fibroblasts, indicating a role in HF development.
Lumican was increased in the failing heart of mice and men. In vitro cyclic mechanical stretch and inflammation induced lumican expression and protein secretion from cardiac fibroblasts. Moreover, increased lumican in cardiac fibroblasts induced expression of molecules important for cardiac remodeling and fibrosis, suggesting a role for lumican in heart failure development.
Increased astrocytic Ca
2+
signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca
2+
signaling in such mice. Here, ...we employ an event-based algorithm to assess astrocytic Ca
2+
signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca
2+
response to locomotion and an uncoupling of pupil responses and astrocytic Ca
2+
signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRAB
NE
, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca
2+
responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca
2+
activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease.
Neurodegenerative conditions such as Parkinson’s or Alzheimer’s disease are characterized by neurons dying and being damaged. Yet neurons are only one type of brain actors; astrocytes, for example, are star-shaped ‘companion’ cells that have recently emerged as being able to fine-tune neuronal communication. In particular, they can respond to norepinephrine, a signaling molecule that acts to prepare the brain and body for action. This activation results, for instance, in astrocytes releasing chemicals that can act on neurons.
Certain cognitive symptoms associated with Alzheimer’s disease could be due to a lack of norepinephrine. In parallel, studies in anaesthetized mice have shown perturbed astrocyte signaling in a model of the condition. Disrupted norepinephrine-triggered astrocyte signaling could therefore be implicated in the symptoms of the disease. Experiments in awake mice are needed to investigate this link, especially as anesthesia is known to disrupt the activity of astrocytes.
To explore this question, Åbjørsbråten, Skaaraas et al. conducted experiments in naturally behaving mice expressing mutations found in patients with early-onset Alzheimer’s disease. These mice develop hallmarks of the disorder. Compared to their healthy counterparts, these animals had reduced astrocyte signaling when running or being startled. Similarly, a fluorescent molecular marker for norepinephrine demonstrated less signaling in the modified mice compared to healthy ones.
Over 55 million individuals currently live with Alzheimer’s disease. The results by Åbjørsbråten, Skaaraas et al. suggest that astrocyte–norepinephrine communication may be implicated in the condition, an avenue of research that could potentially lead to developing new treatments.
To judge whether an Amplatzer Septal Occluder can be used as standard therapy instead of surgery for closure of atrial septal defects we report our experiences in 200 patients. Of these patients, 127 ...had an atrial septal defect with haemodynamically significant left-to-right shunt, 68 patients a persistent oval foramen after presumed paradoxical embolism, and 5 had a fenestration after Fontan-repair. Mean age was 29.8 years (0.8 to 77.7 years). Body weight ranged from 6.9 to 120.0 kg (mean 51.5 kg). After diagnostic cardiac catheterization, and balloon-sizing of the defect, we implanted Amplatzer Septal Occluders with stents of 4 to 28 mm diameter. Follow-up studies were obtained after 48 hours, and one, six, and twelve months. Transcatheter closure of the atrial septal defect proved successful in all without any relevant residual shunts. In particular, complete closure was achieved in all patients after presumed paradoxical embolism. The mean period of follow-up is 9.5 months, with a range from 0.4 to 23.5 months, giving a total of 1898 patient months. The occlusion rate after three month was 98.1%. A trivial haemodynamically insignificant residual shunt remained in 1.9% of the patients. Fluoroscopy times ranged from 0 to 43.5 minutes, with a median of 8.7 minutes. The excellent results in the short and medium term in children and adults have resulted in using this device routinely at the present time for closure of central atrial septal defects up to a diameter of 28 mm. Final judgement, however, is only possible after long-term follow-up.
The cardiac findings in eight patients, two of whom were female, with total lipodystrophy (Berardinelli-Seip's disease) are reported. One of them had the acquired form of the disease. Four patients ...died at a mean age of 32 years. As far as we know, at least three of them most likely died for cardiac reasons, one shortly after recovering from an attempted suicide. All eight patients had hypertrophic hearts, mostly with deranged diastolic, but also systolic, function. One had pulmonary hypertension. We conclude that generalized lipodystrophy is a serious disease with cardiac affection leading to cardiac dysfunction and early death. There is no specific cardiac treatment, and the treatment should be according to the general guidelines for patients with hypertrophic, dysfunctioning hearts.
Twenty-six adolescents, aged 13-18 years, with severe congenital heart disease were matched for sex, age and living area with 26 adolescents with repaired atrial septal defect and regarded as ...physically fit. These two groups were compared according to somatic condition, psychopathology, psychosocial functioning and chronic family difficulties. A higher rate of psychiatric problems in the complex group, an association between psychosocial functioning and physical capacity, as well as an association between psychosocial functioning and chronic family difficulties were observed. These findings suggest that physical capacity is of crucial importance for mental health and functioning of adolescents with congenital heart disease. The association with chronic family difficulties also suggests that a comprehensive biopsychosocial approach is necessary in the treatment and rehabilitation of these patients.
Cardiovascular remodelling in the conditioned athlete is frequently associated with physiological ECG changes. Abnormalities, however, may be detected which represent expression of an underlying ...heart disease that puts the athlete at risk of arrhythmic cardiac arrest during sports. It is mandatory that ECG changes resulting from intensive physical training are distinguished from abnormalities which reflect a potential cardiac pathology. The present article represents the consensus statement of an international panel of cardiologists and sports medical physicians with expertise in the fields of electrocardiography, imaging, inherited cardiovascular disease, cardiovascular pathology, and management of young competitive athletes. The document provides cardiologists and sports medical physicians with a modern approach to correct interpretation of 12-lead ECG in the athlete and emerging understanding of incomplete penetrance of inherited cardiovascular disease. When the ECG of an athlete is examined, the main objective is to distinguish between physiological patterns that should cause no alarm and those that require action and/or additional testing to exclude (or confirm) the suspicion of an underlying cardiovascular condition carrying the risk of sudden death during sports. The aim of the present position paper is to provide a framework for this distinction. For every ECG abnormality, the document focuses on the ensuing clinical work-up required for differential diagnosis and clinical assessment. When appropriate the referral options for risk stratification and cardiovascular management of the athlete are briefly addressed.
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