PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication.

PubMed

Dawson, Angelika J; Cox, Janice; Hovanes, Karine; Spriggs, Elizabeth

2015-01-01

The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin. This imprinting allows for diagnosis of PWS or AS based on methylation status using methylation sensitive (MS) multiplex ligation dependent probe amplification (MLPA). Maternally derived microduplications at 15q11.2-q13 have been associated with autism and other neuropsychiatric disorders. Multiple methods have been used to determine the parent-of-origin for 15q11.2-q13 microdeletions and microduplications. In the present study, a four-year-old nondysmorphic female patient with developmental delay was found to have a de novo ~5 Mb duplication within 15q11.2 by oligonucleotide genomic array. In order to determine the significance of this microduplication to the clinical phenotype, the parent-of-origin needed to be identified. The PWS/AS MS-MLPA assay is generally used to distinguish between deletion and uniparental disomy (UPD) of 15q11.2-q13, resulting in either PWS or AS. However, our study shows that PWS/AS MS-MLPA can also efficiently distinguish the parental origin of duplications of 15q11.2-q13.

Comparison of pulsed dye laser (PDL) and photodynamic therapy (PDT) for treatment of facial port-wine stain (PWS) birthmarks in pediatric patients.

PubMed

Zhang, Bin; Zhang, Tao-Hua; Huang, Zheng; Li, Qin; Yuan, Kai-Hua; Hu, Zhi-Qi

2014-12-01

Vascular-acting photodynamic therapy (PDT) might be an alternative approach for treating port wine stain (PWS) birthmarks, but the usefulness of PDT for pediatric patients has not been fully investigated. Medical records of pediatric patients (3-10 years old) with red and purple facial PWS were analyzed. Clinical outcomes after one session of PDL (585 nm, 4.8-6.5 J/cm(2)) and PDT (Hemoporfin - 3.5mg/kg, copper vapour laser - 120 J/cm(2)) were compared. The rate of excellent response in PDT group was significantly higher than that in PDL group (25.0% vs 10.9%). For red lesions there was no significant difference in overall response between PDL and PDT group, but for purple lesions the overall response rate of PDT group was significantly higher than that of PDL group (93.0% vs 75.6%). Lesions located at the forehead, cheek and jaw regions showed better responses to PDT. Incidences of pigmentation and scar formation in PDT group were significantly lower than PDL group (8.3% vs 21.1%). This study suggests that PDT is safe and effective for treating facial PWS of childhood patients. Copyright © 2014. Published by Elsevier B.V.

Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks.

PubMed

Yuan, Kai-Hua; Gao, Jian-Hua; Huang, Zheng

2012-12-01

Several Chinese studies suggest that Hemoporfin-mediated photodynamic therapy (PDT) is an alternative treatment for port-wine stain (PWS) birthmarks. To evaluate treatment responses and adverse effects associated with Hemoporfin PDT for the treatment of PWS and their management. The medical records of 700 patients who underwent PDT treatment in our center were retrospectively examined. Treatment-related reactions and adverse effects were reviewed. Different types of PWS lesions and different individuals showed different immediate responses (e.g. swelling, color change, pain). To certain extents these reactions were a useful indicator of the treatment endpoint. Edema and scabbing were the most common post-treatment responses. Short-term (e.g. blister, eczematous dermatitis, cutaneous photosensitivity) and long-term (e.g. pigmentation change, scar formation) adverse effects were generally caused by the phototoxicity associated with the combination of photosensitizer and light exposure. Although PDT is a safe treatment alternative for PWS birthmarks, treatment parameters must be selected for each individual patient and cutaneous changes must be monitored during light irradiation to minimize the risk of adverse effects. Over estimation of required light dosage or failure to recognize cutaneous changes associated with adverse effects can increase the risk of a poor outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

A study of the influence of different genotypes on the physical and behavioral phenotypes of children and adults ascertained clinically as having PWS.

PubMed

Webb, T; Whittington, J; Clarke, D; Boer, H; Butler, J; Holland, A

2002-10-01

A population-based cohort of people with a clinical diagnosis of Prader-Willi syndrome (PWS) was genetically assessed using molecular diagnostic methods and subsequently divided into the following genetic subtypes involving chromosome 15: 'deletion', 'disomy' and genetically negative (referred to as 'PWS-like'). The physical and behavioral characteristics of the three groups were compared in order to evaluate the unique characteristics of the phenotype resulting from loss of expression of imprinted genes at 15q11q13 (PWS vs. PWS-like cases), the possible effect of either haploid insufficiency of non-imprinted genes (deletion cases), or gain of function of imprinted genes (disomy cases) located within the PWS critical region at 15q11q13. In this study, the main differences between probands with either a deletion or disomy are considered, and the possible involvement of contributing genes discussed. The differences within the PWS group proved difficult to quantify. It would appear that haploid insufficiency or gain of function are more subtle contributors than gender-specific genomic imprinting in the production of the PWS phenotype.

Growth hormone therapy and respiratory disorders: long-term follow-up in PWS children.

PubMed

Berini, Jenny; Spica Russotto, Valeria; Castelnuovo, Paolo; Di Candia, Stefania; Gargantini, Luigi; Grugni, Graziano; Iughetti, Lorenzo; Nespoli, Luigi; Nosetti, Luana; Padoan, Giovanni; Pilotta, Alba; Trifirò, Giuliana; Chiumello, Giuseppe; Salvatoni, Alessandro

2013-09-01

Adenotonsillar tissue hypertrophy and obstructive sleep apnea have been reported during short-term GH treatment in children with Prader-Willi syndrome (PWS). We conducted an observational study to evaluate the effects of long-term GH therapy on sleep-disordered breathing and adenotonsillar hypertrophy in children with PWS. This was a longitudinal observational study. We evaluated 75 children with genetically confirmed PWS, of whom 50 fulfilled the criteria and were admitted to our study. The patients were evaluated before treatment (t0), after 6 weeks (t1), after 6 months (t2), after 12 months (t3), and yearly (t4-t6) thereafter, for up to 4 years of GH therapy. The central apnea index, obstructive apnea hypopnea index (OAHI), respiratory disturbance index, and minimal blood oxygen saturation were evaluated overnight using polysomnography. We evaluated the adenotonsillar size using a flexible fiberoptic endoscope. The percentage of patients with an OAHI of >1 increased from 3 to 22, 36, and 38 at t1, t4, and t6, respectively (χ(2) = 12.2; P < .05). We observed a decrease in the respiratory disturbance index from 1.4 (t0) to 0.8 (t3) (P < .05) and the central apnea index from 1.2 (t0) to 0.1 (t4) (P < .0001). We had to temporarily suspend treatment for 3 patients at t1, t4, and t5 because of severe obstructive sleep apnea. The percentage of patients with severe adenotonsillar hypertrophy was significantly higher at t4 and t5 than at t0. The OAHI directly correlated with the adenoid size (adjusted for age) (P < .01) but not with the tonsil size and IGF-1 levels. Long-term GH treatment in patients with PWS is safe; however, we recommend annual polysomnography and adenotonsillar evaluation.

A nonimprinted Prader-Willi Syndrome (PWS)-region gene regulates a different chromosomal domain in trans but the imprinted pws loci do not alter genome-wide mRNA levels.

PubMed

Stefan, Mihaela; Portis, Toni; Longnecker, Richard; Nicholls, Robert D

2005-05-01

Prader-Willi syndrome (PWS) is a complex neurobehavioral disorder that results from loss of function of 10 clustered, paternally expressed genes in a 1.5-Mb region of chromosome 15q11-q13. Many of the primary PWS region genes appear to have nuclear RNA regulatory functions, suggesting that multiple genetic pathways could be secondarily affected in PWS. Using a transgenic mouse model of PWS (TgPWS) with an approximately 4-Mb chromosome 7C deletion of paternal origin that models the neonatal phenotype of the human syndrome we compared by oligonucleotide microarrays expression levels of approximately 12,000 genes and ESTs in TgPWS and wild-type brain. Hybridization data were processed with two distinct statistical algorithms and revealed a dramatically reduced expression of 4 imprinted genes within the deletion region in TgPWS mice, with 2 nonimprinted, codeleted genes reduced twofold. However, only 3 genes outside the deletion were significantly altered in TgPWS mouse brain, with approximately 1.5-fold up-regulation of mRNA levels. Remarkably, these genes map to a single chromosome domain (18B3), and by quantitative RT-PCR we show that 8 genes in this domain are up-regulated in TgPWS brain. These 18B3 genes were up-regulated in an equivalent manner in Angelman syndrome mouse (TgAS) brain, which has the same deletion but of maternal origin. Therefore, the trans-regulation of the chromosome 18B3 domain is due to decreased expression of a nonimprinted gene within the TgPWS/AS mouse deletion in mouse chromosome 7C. Most surprisingly, since 48-60% of the genome was screened, it appears that the imprinted mouse PWS loci do not widely regulate mRNA levels of other genes and may regulate RNA structure.

Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development.

PubMed

Haqq, Andrea M; Grambow, Steven C; Muehlbauer, Michael; Newgard, Christopher B; Svetkey, Laura P; Carrel, Aaron L; Yanovski, Jack A; Purnell, Jonathan Q; Freemark, Michael

2008-12-01

Prader-Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyperghrelinaemia and increased insulin sensitivity. The role of ghrelin excess in the pathogenesis of obesity is unclear. To determine if high ghrelin levels precede the onset of obesity in young PWS children. A cross-sectional study of 33 infants with PWS and 28 healthy control subjects (C). Fasting ghrelin and other satiety hormones were measured. Median total serum ghrelin in young children with PWS trended higher, but did not differ significantly from those in C of similar age, weight-for-age z-score and sex. However, there was more variability in ghrelin concentrations of young PWS. Eleven of 33 PWS subjects had ghrelin levels greater than the 95th percentile for ghrelin values in the C subjects (> 2871 pg/ml). Six of the PWS subjects with high ghrelin levels had weight-for-age z-scores < 0. Ghrelin concentrations in PWS and C infants exceeded those in older children. In youngsters with PWS, leptin was higher, suggesting a relative excess of fat to lean body mass and plasma adiponectin was increased. Young infants with PWS who have not yet developed hyperphagia or obesity have median fasting ghrelin levels similar to controls. However, a subset (33%) of young PWS is hyperghrelinaemic; approximately one-half of those with hyperghrelinaemia have BMI z-score < 0. The age-related decline in ghrelin is blunted in PWS.

Mosaic isochromosome 15q and maternal uniparental isodisomy for chromosome 15 in a patient with morbid obesity and variant PWS-like phenotype.

PubMed

Wang, Jia-Chi; Vaccarello-Cruz, Mary; Ross, Leslie; Owen, Renius; Pratt, Victoria M; Lightman, Katherine; Liu, Yan; Hafezi, Katayoun; Cherif, Dhia; Sahoo, Trilochan

2013-07-01

Angelman and Prader-Willi syndromes are reciprocal imprinting disorders caused by loss of maternally or paternally expressed genes, respectively, within 15q11.2-q13. Angelman syndrome (AS; OMIM 105830) is a neurodevelopmental disorder and is due to the loss of maternally expressed UBE3A gene. Prader-Willi syndrome (PWS; OMIM 176270) is a clinically distinct disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13. Recently published data strongly suggest a role for the paternally expressed small nucleolar RNA (snoRNA) cluster, SNORD116, in PWS etiology. Uniparental disomy (UPD) 15 is one of the important causes of PWS and AS. Interestingly, balanced and unbalanced chromosomal aberrations in the form of Robertsonian translocation, isochromosomes, supernumerary marker chromosomes and copy number variations have been strongly linked with the occurrence of UPD. Here we report on a very unique case with a mosaic isochromosome for the entire long arm of 15, that is, i(15)(q10), resulting in mosaic uniparental isodisomy for 15q and with no copy number alterations. This is the first report of UPD15 constituted by a mosaic, but copy number neutral chromosomal rearrangement in a patient with a variant PWS-like phenotype. Copyright © 2013 Wiley Periodicals, Inc.

Quality of life in adults with facial port-wine stains

PubMed Central

Hagen, Solveig L.; Grey, Katherine R.; Korta, Dorota Z.; Kelly, Kristen M.

2018-01-01

Background Facial port-wine stains (PWS) are considered by some an aesthetic skin problem, yet impact on quality of life (QoL) has not been objectively documented. Objective We sought to (1) characterize the effect of PWS on QoL in adults, (2) to identify the clinical and demographic factors that affect QoL, and (3) to compare our results with QoL studies in other skin conditions. Methods In total, 244 adults with facial PWS completed an online QoL survey, which included the Skindex-29 instrument. Results QoL in adults with facial PWS was diminished, especially from an emotional perspective. Variables associated with reduced QoL in all Skindex-29 subdomains included comorbid depression, limited facial mobility, and presence of other skin conditions. Persons with hypertrophy had more emotional and symptomatic impairment. The composite dermatologic-specific QoL scores were similar to those of cutaneous T-cell lymphoma, rosacea, alopecia, and vitiligo. Limitations Selection bias was a potential limitation, as participants were primarily recruited from patient support groups. Conclusion Our analysis demonstrates that the presence of a facial PWS has a significant negative impact on QoL. Dermatologists caring for patients with PWS should inquire about QoL, provide appropriate support and resources, and consider QoL when discussing treatment options and obtaining authorization for these procedures. PMID:27955934

Body composition, adipokines, bone mineral density and bone remodeling markers in relation to IGF-1 levels in adults with Prader-Willi syndrome.

PubMed

van Nieuwpoort, I Caroline; Twisk, Jos W R; Curfs, Leopold M G; Lips, Paul; Drent, Madeleine L

2018-01-01

In patients with Prader-Willi syndrome (PWS) body composition is abnormal and alterations in appetite regulating factors, bone mineral density and insulin-like growth factor-1 (IGF-1) levels have been described. Studies in PWS adults are limited. In this study, we investigated body composition, appetite regulating peptides, bone mineral density and markers of bone remodeling in an adult PWS population. Furthermore, we investigated the association between these different parameters and IGF-1 levels because of the described similarities with growth hormone deficient patients. In this cross-sectional observational cohort study in a university hospital setting we studied fifteen adult PWS patients. Anthropometric and metabolic parameters, IGF-1 levels, bone mineral density and bone metabolism were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR) was calculated. Fourteen healthy siblings served as a control group for part of the measurements. In the adult PWS patients, height, fat free mass, IGF-1 and bone mineral content were significantly lower when compared to controls; body mass index (BMI), waist, waist-to-hip ratio and fat mass were higher. There was a high prevalence of osteopenia and osteoporosis in the PWS patients. Also, appetite regulating peptides and bone remodelling markers were aberrant when compared to reference values. Measurements of body composition were significantly correlated to appetite regulating peptides and high-sensitive C-reactive protein (hs-CRP), furthermore HOMA was correlated to BMI and adipokines. In adults with Prader-Willi syndrome alterations in body composition, adipokines, hs-CRP and bone mineral density were demonstrated but these were not associated with IGF-1 levels. Further investigations are warranted to gain more insight into the exact pathophysiology and the role of these alterations in the metabolic and cardiovascular complications seen in PWS, so these complications can be prevented or treated as

Postural strategies in Prader-Willi and Down syndrome patients.

PubMed

Cimolin, Veronica; Galli, Manuela; Grugni, Graziano; Vismara, Luca; Precilios, Helmer; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

Patients affected by Down (DS) and Prader-Willi syndrome (PWS) are characterised by some common clinical and functional features including gait disorders and reduced postural control. The aim of our study was to quantitatively compare postural control in adult PWS and DS. We studied 12 PWS and 19 DS adult patients matched for age, height, weight and body mass index. They were instructed to maintain an upright standing position on a force platform for 30s with open eyes (OE) and we calculated the range of center of pressure (CoP) displacement in the A/P direction (RANGE(AP)) and in the M/L direction (RANGE(ML)) and the total CoP trajectory length during quiet stance (Sway Path, SP). The range of oscillations in PWS and DS in both AP and ML direction were higher than in controls. PWS and DS were statistically different for RANGE(AP), with PWS showing higher mean values. Our results confirm a reduced capacity of both PWS and DS in maintaining postural stability. This appears to be in some respect different in PWS and DS, with PWS showing poorer control in AP. DS and, particularly, PWS should be encouraged to undergo specific balance training and strengthening of the ankle muscles as part of a comprehensive rehabilitation program to enhance daily functioning and quality of life. Copyright © 2010 Elsevier Ltd. All rights reserved.

Treatment of resistant port wine stains (PWS) with pulsed dye laser and non-contact vacuum: a pilot study.

PubMed

Kautz, Gerd; Kautz, Ingrid; Segal, Jenny; Zehren, Sabrina

2010-07-01

The blanching of resistant port wine stains (PWS) with a pulsed dye laser (PDL) requires a large number of treatments, resulting in substantial discomfort to patients, many of them children. Pneumatic skin flattening (PSF - Serenity Pro) is a new technology that generates a vacuum over the skin and reduces pain in laser-based treatments of the skin, while creating contact between the skin and an upper window. The same technology can be utilized to increase skin blood fraction while operated in a non-contact mode. The objective of this study was to test the enhancement in the efficacy of PWS treatment with PDL and Serenity Pro while vacuum is being utilized in the non-contact, blood-enrichment mode. Fifteen patients with resistant PWS underwent 1-4 treatments (interval of 5-20 weeks) under general anesthesia with a 595-nm PDL at 10-14 J/cm(2), 1.5-3 ms pulse duration, and 7-mm spot size. Lesion blanching with DCD chilling and with vacuum were photographed and compared. Better blanching of various degrees was observed on resistant PWS with the blood-enrichment technique in seven out of 11 patients who returned for follow-up. There were no cases of decrease in efficacy. Blood enrichment with the Serenity Pro non-contact vacuum technology has the potential of enhancing the capability of treating resistant port wine stains in over 50% of cases. Further studies will better quantify the number of treatments necessary for better lesion clearance. The vacuum-assisted technique may be of particular importance in view of the fact that achieving complete lesion clearance remains a challenge in PWS treatments.

Metabolic and adipose tissue signatures in adults with Prader-Willi syndrome: a model of extreme adiposity.

PubMed

Lacroix, Delphine; Moutel, Sandrine; Coupaye, Muriel; Huvenne, Hélène; Faucher, Pauline; Pelloux, Véronique; Rouault, Christine; Bastard, Jean-Philippe; Cagnard, Nicolas; Dubern, Béatrice; Clément, Karine; Poitou, Christine

2015-03-01

Prader-Willi syndrome (PWS), the most frequent syndrome of obesity, is a model of early fat mass (FM) development, but scarce data exist on adipose tissue characteristics. The objective of the study was to compare metabolic, fat distribution, and transcriptomic signatures of sc adipose tissue (scAT) in PWS adults, with matched obese adults with primary obesities. Hormonal and metabolic assessments, systemic inflammation, and gene expression in scAT were compared between PWS patients and obese controls (OCs). Each 42nd PWS patient was matched with one randomly paired control with primary obesity. Matching factors were age, gender, fat mass (percentage), and diabetic status. Compared with OCs, the PWS group had a decreased percentage of trunk FM and a better metabolic profile with decreased insulin and homeostasis model assessment, an index of insulin-resistance, and increased concentrations of serum adiponectin and ghrelin. Adipocyte size relative to body fat was significantly higher in PWS vs OCs. scAT in PWS patients was characterized by a transcriptomic functional signature with enrichment of themes related to immunoinflammation, the extracellular matrix, and angiogenesis. A RT-PCR targeted study revealed that candidate genes encoding proinflammatory markers and remodeling molecules, CD68, CD3e, IL-1β, chemokine (C-C motif) ligand 5, collagen type 4-α, and lysyl oxidase, were down-regulated. Matched for FM, PWS subjects have a better metabolic profile, a phenotype that could be linked to changes in scAT remodeling and promotion of adipocyte growth.

Eating behavior and gastric emptying in adults with Prader-Willi syndrome.

PubMed

Hoybye, Charlotte; Barkeling, Britta; Naslund, Erik; Thorén, Marja; Hellstrom, Per M

2007-01-01

Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by distinctive physical, behavioral and psychiatric features. One cardinal symptom is excessive eating, often leading to extreme obesity. The etiology of the hyperphagia is unknown, but eating behaviors and gastrointestinal motility could play a pivotal role. In this pilot study, we therefore sought to give a closer description of the two. 12 PWS adults, 6 men and 6 women, 17-37 years of age with a median BMI of 34.9 were evaluated. Computerized monitoring of eating behavior and assessment of gastric emptying using paracetamol absorption were analyzed. Gastric emptying rate was compared to the rate in normal and obese controls. Eating behavior pattern was nonhomogeneous in the PWS patients, but they experienced both hunger and satiation. In PWS gastric emptying was similar to lean subjects (p > 0.05), but longer than in obese subjects (p < 0.05). Despite obesity, this group of adults with PWS did not display overeating in the test situation and gastric emptying rate was normal. Numbers are small, but the results are important for the treatment of obesity in this special group of patients. Copyright 2007 S. Karger AG, Basel.

Growth hormone treatment in adults with Prader-Willi syndrome: the Scandinavian study.

PubMed

Sode-Carlsen, Rasmus; Farholt, Stense; Rabben, Kai Fr; Bollerslev, Jens; Schreiner, Thomas; Jurik, Anne Grethe; Christiansen, Jens Sandahl; Höybye, Charlotte

2012-04-01

Prader-Willi syndrome (PWS) is characterized by short stature, muscular hypotonia, cognitive dysfunction, and hyperphagia usually leading to severe obesity. Patients with PWS share similarities with growth hormone deficiency (GHD). Few studies have dealt with growth hormone (GH) treatment in PWS adults. The purpose of the Scandinavian study was to evaluate the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety parameters in adults with PWS. Twenty-five women and 21 men with PWS were randomized to treatment with GH or placebo during 1 year followed by 2 years of open labeled GH treatment. At baseline 1/3 had normal BMI, six patients severe GHD, ten impaired glucose tolerance and seven diabetes. At 1 year insulin-like growth factor I (IGF-I) SDS had increased by 1.51 (P < 0.001) and body composition improved in the GH treated group. Visceral fat decreased by 22.9 ml (P = 0.004), abdominal subcutaneous fat by 70.9 ml (P = 0.003) and thigh fat by 21.3 ml (P = 0.013), whereas thigh muscle increased 6.0 ml (P = 0.005). Lean body mass increased 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). The positive effects on body composition were maintained after 2 years of GH treatment. Peak expiratory flow increased by 12% (P < 0.001) at 2 years of GH treatment. Lipid and glucose metabolism were unchanged, however, three patients developed diabetes at 2 years of GH treatment. In conclusion GH treatment had beneficial effects on the abnormal body composition without serious adverse events making it a logic treatment option in adults with PWS.

Relationship between antipsychotics and weight in patients with Prader-Willi syndrome.

PubMed

Elliott, Jennifer Padden; Cherpes, Gregory; Kamal, Khalid; Chopra, Ishveen; Harrison, Chelsea; Riedy, Mary; Herk, Brandon; McCrossin, Matt; Kalarchian, Melissa

2015-03-01

Individuals with Prader-Willi Syndrome (PWS) are at increased risk for developing behavioral and psychiatric disorders, often requiring antipsychotics (APs). Contrary to significant AP-associated weight gain observed in the general population, existing literature suggests weight loss in patients with PWS. To evaluate the relationship between AP use and body mass index (BMI) at admission, change in BMI during inpatient stay, and length of stay (LOS) in patients admitted to an inpatient PWS treatment program. Retrospective case-control study. Hospital-based, inpatient PWS treatment program serving nationally and internationally referred children and adults with PWS. Cases consisted of 52 pediatric patients with PWS who were taking APs at admission and during their stay, 97 adults with PWS who were taking APs at admission and during their stay, and 11 pediatric and adult patients with PWS who were AP naïve at admission and subsequently started an AP during their stay; all cases were matched with patients with PWS who were AP naïve at admission and during their stay by age (yrs), sex, and race-ethnicity (controls). Between- and within-group differences in admission BMI, BMI change from admission to discharge, and LOS were analyzed. Admission BMI was lower (mean ± SD 36.8 ± 11.9 kg/m(2) vs 46.7 ± 12.5 kg/m(2) , p<0.001) and LOS longer (mean ± SD 75.9 ± 38.5 days vs 57.8 ± 23.2 days, p=0.005) for pediatric cases with AP exposure at admission and during their stay compared with matched controls. All groups experienced significant decreases in BMI from admission to discharge (p≤0.001 for all comparisons), except for pediatric cases with AP exposure at admission and during their stay. Cases that were AP naïve at admission and subsequently started an AP during their inpatient stay experienced a significantly smaller decrease in BMI from admission to discharge than matched controls (-3.011 vs -7.288 kg/m(2) , p=0.027). No other comparisons between

Long-term echocardiographic and cardioscintigraphic effects of growth hormone treatment in adults with Prader-Willi syndrome.

PubMed

Marzullo, Paolo; Marcassa, Claudio; Minocci, Alessandro; Campini, Riccardo; Eleuteri, Ermanno; Gondoni, Luca Alessandro; Aimaretti, Gianluca; Sartorio, Alessandro; Scacchi, Massimo; Grugni, Graziano

2015-05-01

In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function compared to controls. The objective was to evaluate the cardiovascular response to a 4-year GH therapy in adult PWS patients. Study participants were nine severely obese PWS adults (three females, six males) and 13 age-, gender-, and body mass index-matched obese controls. In an open-label prospective study, assessment of endocrine parameters and metabolic outcome, whole-body and abdominal fat scans, echocardiography, and radionuclide angiography in unstimulated and dobutamine-stimulated conditions were conducted at baseline and after 1 and 4 years of GH treatment. GH treatment increased IGF-1 (P < .0001), decreased C-reactive protein levels (P < .05), improved visceral fat mass (P < .05), and achieved near-significant changes of fat and fat-free body mass in PWS patients. Left ventricle mass indexed by fat mass increased significantly after 1 and 4 years of GH therapy (P < .05) without evident abnormalities of diastolic function, while a trend toward a reduction of the ejection fraction was documented by echocardiography (P = .054). Radionuclide angiography revealed stable values throughout the study of both the left and right ventricle ejection fractions, although this was accompanied by a statistically nonsignificant reduction of the left ventricle filling rate. A positive association between lean body mass and left ventricle ejection fraction was evident during the study (P < .05). GH therapy increased the cardiac mass of PWS adults without causing overt abnormalities of systolic and diastolic function. Although the association between lean mass and left ventricle ejection fraction during GH therapy corroborates a favorable systemic outcome of long-term GH treatment in adults with PWS, subtle longitudinal modifications of functional parameters advocate appropriate cardiac monitoring in the long-term therapeutic strategy for PWS.

Central adrenal insufficiency in young adults with Prader-Willi syndrome.

PubMed

Grugni, Graziano; Beccaria, Luciano; Corrias, Andrea; Crinò, Antonino; Cappa, Marco; De Medici, Clotilde; Di Candia, Stefania; Gargantini, Luigi; Ragusa, Letizia; Salvatoni, Alessandro; Sartorio, Alessandro; Spera, Sabrina; Andrulli, Simeone; Chiumello, Giuseppe; Mussa, Alessandro

2013-09-01

A high prevalence (60%) of central adrenal insufficiency (CAI) has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. We have assessed CAI in adults with PWS using the low-dose short synacthen test (LDSST). Basal cortisol and ACTH, and 30-min cortisol after the administration of 1 μg synacthen, were determined in 53 PWS adults (33 females). A peak cortisol value of ≥500 nmol/l was taken as normal. Hormonal profiles were analysed in relation to gender, genotype and phenotype. Deficient patients were retested by high-dose short synachten test (HDSST) or a repeat LDSST. Mean ± SD basal cortisol and ACTH were 336·6 ± 140·7 nmol/l and 4·4 ± 3·7 pmol/l respectively. Cortisol rose to 615·4 ± 135·0 nmol/l after LDSST. Eight (15·1%) patients had a peak cortisol response <500 nmol/l, with a lower mean ± SD (range) basal cortisol of 184·9 ± 32·0 (138·0-231·7) compared with 364·1 ± 136·6 (149·0-744·5) in normal responders (P < 0·001). Seven of the eight patients underwent retesting, with 4 (7·5%) showing persistent suboptimal responses. Basal and peak cortisol correlated in females (r = 0·781, P < 0·001). Logistic regression revealed that only female gender and baseline cortisol were predictors of cortisol peaks (adjusted R square 0·505). Although CAI can be part of the adult PWS phenotype, it has a lower prevalence (7·5%) than previously reported. Clinicians are advised to test PWS patient for CAI. Our study also shows that basal cortisol is closely correlated with adrenal response to stimulation, indicating that its measurement may be helpful in selecting patients for LDSST. © 2013 John Wiley & Sons Ltd.

Clinical-etiologic correlation in children with Prader-Willi syndrome (PWS): an interdisciplinary study.

PubMed

Torrado, Maria; Araoz, Veronica; Baialardo, Edgardo; Abraldes, Karina; Mazza, Carmen; Krochik, Gabriela; Ozuna, Blanca; Leske, Vivian; Caino, Silvia; Fano, Virginia; Chertkoff, Lilien

2007-03-01

Prader-Willi syndrome (PWS) is a multisystemic disorder caused by the loss of expression of paternally transcribed genes within chromosome 15q11-q13. Most cases are due to paternal deletion of this region; the remaining cases result from maternal uniparental disomy (UPD) and imprinting defects. To better understand the phenotypic variability of PWS, a genotype-phenotype correlation study was performed in 91 children with PWS. Patients were diagnosed by Southern Blot Methylation assay and genetic subtypes were established using FISH and microsatellite analyses. Fifty-nine subjects with deletion (31/28 males/females; mean age 3.86 years), 30 with UPD (14/16 males/females; mean age 3.89 years) and 2 girls with a presumed imprinting defect (mean age 0.43 yrs) were identified. For correlation purposes patients were grouped as "deleted" and "non-deleted." An increased maternal age was found in the UPD group. Four of Holm's criteria were more frequently present in the deleted group: need for special feeding techniques, sleep disturbance, hypopigmentation, and speech articulation defects. Concerning cognitive assessments, only 9.52% of subjects with deletion had Full-Scale IQ (FSIQ) > or =70, while 61.53% of subjects without deletion had FSIQ > or =70. Similar results were found in behavioral measures. Sleep disorders and carbohydrate metabolism were systematically assessed. Polysomnoghaphic studies revealed a higher frequency of central events with desaturations > or =10% in the deleted group (P = 0.020). In summary, the phenotype was significantly different between both groups in certain parameters related to the CNS. These results might be related to the differences in brain gene expression of the genetic subtypes. (c) 2006 Wiley-Liss, Inc.

Utilization of powdered waste sludge (PWS) for removal of textile dyestuffs from wastewater by adsorption.

PubMed

Ozmihci, Serpil; Kargi, Fikret

2006-11-01

Acid pre-treated powdered waste sludge (PWS) was used for removal of textile dyestuffs from aqueous medium by adsorption as an alternative to the use of powdered activated carbon (PAC). The rate and extent of dysetuff removals were determined for four different dyestuffs at different PWS concentrations varying between 1 and 6 gl(-1). Biosorbed dyestuff concentrations at equilibrium decreased with increasing PWS concentration for all dyestuffs tested. PWS was more effective for adsorption of Remazol red RR and Chrisofonia direct yellow 12 as compared to the other dyestuffs tested. More than 80% percent dyestuff removal was obtained for all dyestuffs at PWS concentrations above 4 gl(-1) after 6h of incubation. Similar to percent dyestuff removal, the rate of adsorption was maximum at a PWS concentration of 4 gl(-1). Kinetics of adsorption of dyestuffs was investigated by using the first- and second-order kinetic models and the kinetic constants were determined. Second-order kinetics was found to fit the experimental data better than the first-order model for all dyestuffs tested. Adsorption isotherms were established for all dyestuffs used and the isotherm constants were determined by using the experimental data. Langmuir and the generalized adsorption isotherms were found to be more suitable than the Freundlich isotherm for correlation of equilibrium adsorption data. Acid pre-treated PWS was proven to be an effective adsorbent for dyestuff removal as compared to the other adsorbents reported in literature studies.

A model to characterize psychopathological features in adults with Prader-Willi syndrome.

PubMed

Thuilleaux, Denise; Laurier, Virginie; Copet, Pierre; Tricot, Julie; Demeer, Geneviève; Mourre, Fabien; Tauber, Maithé; Jauregi, Joseba

2018-01-01

High prevalence of behavioral and psychiatric disorders in adults with Prader-Willi Syndrome (PWS) has been reported in last few years. However, data are confusing and often contradictory. In this article, we propose a model to achieve a better understanding of the psychopathological features in adults with PWS. The study is based on clinical observations of 150 adult inpatients, males and females. Non-parametric statistics were performed to analyse the association of psychopathological profiles with genotype, gender and age. We propose a model of psychiatric disorders in adults with PWS based on cognitive, emotional and behavioural issues. This model defines four psychopathological profiles: Basic, Impulsive, Compulsive, and Psychotic. The Basic profile is defined by traits and symptoms that are present in varying degrees in all persons with PWS. In our cohort, this Basic profile corresponds to 55% of the patients. The rest show, in addition to these characteristics, salient features of impulsivity (Impulsive profile, 19%), compulsivity (Compulsive profile, 7%), or psychosis (Psychotic profile, 19%). The analysis of factors associated with different profiles reveals an effect of genotype on Basic and Psychotic profiles (Deletion: 70% Basic, 9% Psychotic; Non-deletion: 23% Basic, 43% Psychotic) and a positive correlation between male sex and impulsivity, unmediated by sex hormone treatment. This is a clinical study, based on observation proposing an original model to understand the psychiatric and behavioural disorders in adults with PWS. Further studies are needed in order to test the validity of this model. © 2017 Wiley Periodicals, Inc.

Management of hypogonadism in adolescent girls and adult women with Prader-Willi syndrome.

PubMed

Eldar-Geva, Talia; Hirsch, Harry J; Pollak, Yehuda; Benarroch, Fortu; Gross-Tsur, Varda

2013-12-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by an insatiable appetite, dysmorphic features, cognitive and behavioral difficulties, and hypogonadism. The heterogeneous reproductive hormone profiles indicate that some PWS women may have symptoms of hypoestrogenism, while others may potentially be fertile. We describe our experience in the assessment and treatment of hypogonadism in adolescents and adult females with PWS. The study population consisted of 20 PWS females, age ≥16 years (27.3 ± 7.9 years), followed in our clinic (12 deletion, 7 uniparental disomy, 1 imprinting-center defect). General physical examination, pubertal assessment, body mass index (BMI), gynecological examination, ultrasonography, bone densitometry, and hormonal profiles [FSH, LH, inhibin B, estradiol, prolactin, and TSH] were performed. The relevant assessed factors were: FSH and inhibin B, menstrual cycles (oligo/amenorrhea or irregular bleeding), ultrasound findings (endometrial thickness, uterine/ovarian abnormalities), BMI, bone densitometry, and patient/caregivers attitude. We classified seven women with inhibin B >20 ng/ml as potentially fertile. Following the assessment of the above factors, we recommended the individual-specific treatment; contraceptive pills, intra-uterine device, estrogen/progesterone replacement, and cyclic progesterone, in 3, 1, 4, and 1 patients, respectively. Four patients did not follow our recommendations due to poor compliance or family refusal. We recommended contraception pills for one 26-year-old woman with inhibin B and FSH levels 53 ng/ml and 6.4 IU/L; however, she refused treatment, conceived spontaneously and had an abortion. Guidelines for hormonal replacement therapy in PWS need to be tailored individually depending on physical development, hormonal profiles, bone density, and emotional and social needs of each PWS adolescent and adult. © 2013 Wiley Periodicals, Inc.

Behavioral phenotype in adults with Prader-Willi syndrome.

PubMed

Sinnema, Margje; Einfeld, Stewart L; Schrander-Stumpel, Constance T R M; Maaskant, Marian A; Boer, Harm; Curfs, Leopold M G

2011-01-01

Prader-Willi syndrome (PWS) is characterized by temper tantrums, impulsivity, mood fluctuations, difficulty with change in routine, skinpicking, stubbornness and aggression. Many studies on behavior in PWS are limited by sample size, age range, a lack of genetically confirmed diagnosis of PWS and inconsistent assessment of behavior. The aim of this study was to explore systematically the relation between behavioral problems and age groups, genetic subtypes and BMI categories in an adult PWS population. Participants were contacted via the Dutch Prader-Willi Parent Association and through physicians specialized in persons with ID. Behaviors were studied using the Developmental Behavior Checklist for Adults (DBC-A). The forms were completed by the main caregivers of 98 adults with a genetically confirmed diagnosis of PWS. Differences between age groups were statistically significant (ANOVA, p=0.03). DBC-A total scores were higher in the consecutive age groups, with the most behavioral problems in the oldest age groups. Differences between genetic subtypes were also statistically significant (ANOVA, p<0.01). Persons with mUPD had higher total scores on the DBC-A than persons with a deletion. Those with a Type I deletion showed higher total DBC-A scores than persons with a Type II deletion. There were no statistically significant differences in DBC-A total scores between the different BMI categories. Individuals with a BMI<25 had higher scores on the self-absorbed subscale compared to persons with a BMI between 25 and 30. Unlike previous descriptions of the behavioral phenotype in adults with PWS, we did not find a reduction in behavioral problems in older adults. Therefore, special attention should be paid to behavioral problems as part of general management of adults with PWS. Longitudinal studies are warranted to gain more insight into the natural history and course of behavioral problems in adults and older people with PWS over the long term and possible risk and

Corticospinal physiology in patients with Prader-Willi syndrome: a transcranial magnetic stimulation study.

PubMed

Civardi, Carlo; Vicentini, Roberta; Grugni, Graziano; Cantello, Roberto

2004-10-01

Prader-Willi syndrome (PWS) is a genetic developmental disorder, mostly caused by a deletion on the paternal chromosome 15 or by a maternal uniparental disomy 15. Some PWS clinical and neurochemical features suggest an involvement of the corticospinal motor structures. To explore the corticospinal physiology of PWS by transcranial magnetic stimulation. A community-based hospital. We studied motor evoked potentials in the first dorsal interosseous muscle of 21 young-adult patients with PWS. Thirteen patients had a deletion at chromosome 15; 8 had a uniparental disomy. We measured the following variables: relaxed motor threshold, central motor conduction time, duration of the central silent period, and short-interval intracortical inhibition and facilitation. We also recorded F waves in the first dorsal interosseous muscle. We had 11 normal controls. In the whole PWS group, motor threshold was higher as compared with controls (P<.05). The central motor conduction time, central silent period, and F waves were normal. Intracortical facilitation was reduced significantly (P<.001). Patients with PWS and a deletion had a weaker intracortical inhibition as compared with patients with PWS and a uniparental disomy (P<.05). Transcranial magnetic stimulation changes in patients with PWS suggested a hypo-excitability of the motor cortical areas. Defective neurogenesis of the cortical tissue and multiple transmitter alterations are the putative causes. Impaired intracortical inhibition might represent an electrical marker for a deletion defect.

18 years long-term results of facial port-wine stain (PWS) after photodynamic therapy (PDT)--a case report.

PubMed

Yu, Wenxin; Ma, Gang; Qiu, Yajing; Chen, Hui; Jin, Yunbo; Yang, Xi; Hu, Xiaojie; Chang, Lei; Wang, Tianyou; Zhou, Henghua; Li, Wei; Lin, Xiaoxi

2015-03-01

Port-wine stain (PWS) is still a challenging condition for clinician to treat, because in the majority of cases, the stains are not lifted fully by treatment with laser therapy. Photodynamic therapy (PDT) was considered recently as a promising alternative treatment for PWS. We report here long-term follow-up measures 18 years on PWS lesion treated with PDT and the histological data of residual PWS. Copyright © 2014 Elsevier B.V. All rights reserved.

Behavioral profile of adults with Prader-Willi syndrome: correlations with individual and environmental variables.

PubMed

Jauregi, Joseba; Laurier, Virginie; Copet, Pierre; Tauber, Maithé; Thuilleaux, Denise

2013-08-06

Maladaptive behavior has been reported as a phenotypical feature in Prader-Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was related to a lower severity of symptoms. Some

Behavioral profile of adults with Prader-Willi syndrome: correlations with individual and environmental variables

PubMed Central

2013-01-01

Background Maladaptive behavior has been reported as a phenotypical feature in Prader–Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. Methods The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. Results Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. Conclusions Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was

Forecasting near-surface weather conditions and precipitation in Alaska's Prince William Sound with the PWS-WRF modeling system

NASA Astrophysics Data System (ADS)

Olsson, Peter Q.; Volz, Karl P.; Liu, Haibo

2013-07-01

In the summer of 2009, several scientific teams engaged in a field program in Prince William Sound (PWS), Alaska to test an end-to-end atmosphere/ocean prediction system specially designed for this region. The "Sound Predictions Field Experiment" (FE) was a test of the PWS-Observing System (PWS-OS) and the culmination of a five-year program to develop an observational and prediction system for the Sound. This manuscript reports on results of an 18-day high-resolution atmospheric forecasting field project using the Weather Research and Forecasting (WRF) model.Special attention was paid to surface meteorological properties and precipitation. Upon reviewing the results of the real-time forecasts, modifications were incorporated in the PWS-WRF modeling system in an effort to improve objective forecast skill. Changes were both geometric (model grid structure) and physical (different physics parameterizations).The weather during the summer-time FE was typical of the PWS in that it was characterized by a number of minor disturbances rotating around an anchored low, but with no major storms in the Gulf of Alaska. The basic PWS-WRF modeling system as implemented operationally for the FE performed well, especially considering the extremely complex terrain comprising the greater PWS region.Modifications to the initial PWS-WRF modeling system showed improvement in predicting surface variables, especially where the ambient flow interacted strongly with the terrain. Prediction of precipitation on an accumulated basis was more accurate than prediction on a day-to-day basis. The 18-day period was too short to provide reliable assessment and intercomparison of the quantitative precipitation forecasting (QPF) skill of the PWS-WRF model variants.

The effects of muscle hypotonia and weakness on balance: a study on Prader-Willi and Ehlers-Danlos syndrome patients.

PubMed

Galli, Manuela; Cimolin, Veronica; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

Prader-Willi syndrome (PWS) and Ehlers-Danlos syndrome (EDS) are two different genetical disorders both characterized, among other features, by muscular hypotonia. Postural control seems to be impaired in both conditions. The aim of the present study was to quantitatively compare postural control in adult PWS and EDS using stabilometric platform to unveil possible common determinants of impaired balance. We enrolled 11 PWS and 21 EDS adult patients and 20 age-matched controls. They were instructed to maintain an upright standing position for 30s with open eyes (OEs) focusing on a 6 cm black circle positioned at a distance of 1.5m. Both PWS and EDS patients were characterized by higher RANGEML, RANGEAP and trajectory length of CoP values as compared to CG. No statistically differences were found between PWS and EDS in terms of any of these parameters. The results demonstrated that both PWS and EDS are characterized by a severe postural instability. Muscle hypotonia and weakness may account for reduced balance capacity. Quantitative characterization of instability is important to identify, develop and enhance rehabilitation interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prevalence and Phenotype of Sleep Disorders in 60 Adults With Prader-Willi Syndrome.

PubMed

Ghergan, Adelina; Coupaye, Muriel; Leu-Semenescu, Smaranda; Attali, Valérie; Oppert, Jean-Michel; Arnulf, Isabelle; Poitou, Christine; Redolfi, Stefania

2017-12-01

Excessive sleepiness is a common symptom in Prader-Willi syndrome (PWS), and it negatively impacts the quality of life. Obstructive sleep apnea and narcolepsy phenotypes have been reported in PWS. We characterized sleep disorders in a large cohort of adults with PWS. All consecutive patients with genetically confirmed PWS unselected for sleep-related symptoms, underwent a clinical interview, polysomnography, and multiple sleep latency tests (MSLT, n = 60), followed by long-term (24 hours) polysomnography (n = 22/60). Among 60 adults evaluated (57% female, aged 25 ± 10 years, body mass index: 39 ± 12 kg/m2), 67% reported excessive sleepiness. According to the sleep study results, 43% had a previously unrecognized hypersomnia disorder, 15% had an isolated sleep breathing disorder, 12% had combined hypersomnia disorder and untreated breathing sleep disorder, and only 30% had normal sleep. Isolated hypersomnia disorder included narcolepsy in 35% (type 1, n = 1, and type 2, n = 8), hypersomnia in 12% (total sleep time >11 hours, n = 2, and MSLT <8 minutes, n = 1), and borderline phenotype in 53% (≥2 sleep onset in REM periods and MSLT >8 minutes, n = 10, and 8 minutes < MSLT < 10 minutes, n = 4). Sleep breathing disorders, isolated and combined, included obstructive sleep apnea (n = 14, already treated in seven), sleep hypoxemia (n = 1) and previously undiagnosed hypoventilation (n = 5). Modafinil was taken by 16 patients (well tolerated in 10), resulting in improved sleepiness over a mean 5-year follow-up period. Sleepiness affects more than half of adult patients with PWS, with a variety of hypersomnia disorder (narcolepsy, hypersomnia, and borderline phenotypes) and breathing sleep disorders. Earlier diagnosis and management of sleep disorders may improve sleepiness, cognition, and behavior in these patients. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society]. All rights reserved. For permissions, please

Testosterone replacement therapy to improve secondary sexual characteristics and body composition without adverse behavioral problems in adult male patients with Prader-Willi syndrome: an observational study.

PubMed

Kido, Yasuhiro; Sakazume, Satoru; Abe, Yoshiko; Oto, Yuji; Itabashi, Hisashi; Shiraishi, Masahisa; Yoshino, Atsunori; Tanaka, Yuriko; Obata, Kazuo; Murakami, Nobuyuki; Nagai, Toshiro

2013-09-01

Prader-Willi syndrome (PWS), a complex genetic disorder, arises from suppressed expression of paternally inherited imprinted genes on chromosome 15q11-q13. Characteristics include short stature, intellectual disability, behavioral problems, hypogonadism, obesity, and reduced bone and muscle mass. Testosterone replacement (TR) remains controversial due to concerns regarding behavioral problems. To evaluate the effects of TR on secondary sexual characteristics, body composition, and behavior in adult males with PWS, 22 male PWS patients over the age of 16 with behavioral scores of less than grade 4 on the Modified Overt Aggression Scale (MOAS) underwent monthly intramuscular TR (125 mg). Pubertal change, body composition and behavior were evaluated before and after 24 months of therapy. Serum testosterone, LH, and FSH did not change. Increased pubic hair was observed in 16 of 22 patients (72.7%). Percent body fat decreased from 47.55 ± 2.06% to 39.75 ± 1.60% (n = 18) (P = 0.018). Bone mineral density increased from 0.8505 ± 0.0426 g/cm(2) to 0.9035 ± 0.0465 g/cm(2) (n = 18) (P = 0.036), and lean body mass increased from 18093.4 ± 863.0 g to 20312.1 ± 1027.2 g (n = 18) (P = 0.009). The MOAS was unchanged, from 4.5 ± 2.0 at the beginning of the study to 3.0 ± 1.7 at the end of study indicating no increase in aggression. No behavioral problems were observed. Based on this pilot study, TR with 125 mg monthly is a potentially safe and useful intervention for adult males with PWS. Copyright © 2013 Wiley Periodicals, Inc.

Maladaptive behaviour in Prader-Willi syndrome in adult life.

PubMed

Clarke, D J; Boer, H; Chung, M C; Sturmey, P; Webb, T

1996-04-01

Thirty adults with Prader-Willi syndrome (PWS) were compared with 30 adults with non-specific learning disability matched for age, sex and severity of mental retardation. Maladaptive behaviour was assessed with the Aberrant Behavior Checklist (ABC), a 58-item structured interview which rates behaviours from 0 (not a problem) to 3 (severe problem) and which yields five factors (I) irritability, agitation; (II) lethargy, withdrawal; (III) stereotypic behavior; (IV) hyperactivity, non-compliance; and (V) inappropriate speech). The PWS sample had significantly higher factor I (P < 0.001) and factor V (P < 0.05) scores. The PWS sample had mean scores above 1 for 17 ABC items; the contrast subjects had no mean scores above 1. The factor I scores for the PWS sample were similar to those of inpatients in hospital facilities for adults with mental retardation and mental illness or severely challenging behaviour. The results support previous work, and extend it by suggesting that temper tantrums, self-injury, impulsiveness, lability of mood, inactivity and repetitive speech are characteristic behaviours in PWS in adult life. Studies of the reasons for heterogeneity in behaviour are now needed.

Exploring patterns of unwanted behaviours in adults with Prader-Willi syndrome.

PubMed

Pignatti, Riccardo; Mori, Ileana; Bertella, Laura; Grugni, Graziano; Giardino, Daniela; Molinari, Enrico

2013-11-01

Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. The behaviour of 31 PWS adults was investigated via the Symptom Checklist-90-Revised (SCL-90-R), the Yale-Brown Obsessive Compulsive Scale Symptom Checklist (Y-BOCS-SC), and the Prader-Willi Behavioural Checklist (PBC). The PBC is a quick screening questionnaire prompted specifically for the investigation on adults with PWS. Statistical clustering revealed two patterns of unwanted behaviours from the PBC. Behaviours belonging to the first cluster (e.g., Excessive food intake, Skin picking) appear to be linked to the usual phenotypic manifestation of PWS. By contrast, many other behaviours (e.g., some O-C symptoms and aggressive actions) could show a relationship also to individual psychopathologies. Both internal (Anxiety and Depression) and external (Hostility) difficulties in managing impulses should account for individually distinct behaviours in adults with PWS. © 2013 John Wiley & Sons Ltd.

Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome

PubMed Central

Bueno, Marta; Esteba-Castillo, Susanna; Novell, Ramon; Giménez-Palop, Olga; Coronas, Ramon; Gabau, Elisabeth; Corripio, Raquel; Baena, Neus; Viñas-Jornet, Marina; Guitart, Míriam; Torrents-Rodas, David; Deus, Joan; Pujol, Jesús; Rigla, Mercedes

2016-01-01

Context Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis. Objectives To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS. Design Experimental study. Setting University hospital. Subjects 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls. Interventions Subjects ingested a liquid meal after fasting ≥10 hours. Main Outcome Measures Leptin and BDNF levels in plasma extracted before ingestion and 30’, 60’, and 120’ after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60’ and 120’ after ingestion. Results Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05). Leptin was higher in PWS patients than in controls at all time points (p<0.001). PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65–0.94). In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13–0.9). Postprandial leptin patterns did no differ among genetic subtypes. Conclusions Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors. PMID:27685845

Combination of PDT and topical angiogenic inhibitor for treatment of port wine stain (PWS) birthmarks: a novel approach

NASA Astrophysics Data System (ADS)

Yuan, Kaihua; Huang, Qiaobing; Huang, Zheng

2009-06-01

Port wine stain (PWS) birthmarks are a congenital cutaneous vascular malformation involving ecstatic post-capillary venules. Current standard treatment for PWS is the pulsed dye laser (PDL). Vascular-targeted photodynamic therapy (PDT) has been used for the treatment of PWS in China since the early 1990's. Both can achieve a certain degree of color blanching in various types of PWS lesions. However, the majority of PWS lesions require multiple treatments. Some PWS lesions can recur or become darker after successful treatment. Recently, it has been proposed that this phenomenon might be initiated by neoangiogenesis that can be caused by treatment via wound healing response. The combined use of photothermolysis and a topical application of an angiogenic inhibitor such as Imiquimod and Rapamycin, were evaluated in several pilot studies. It is well-known that PDT can induce various host immune responses VEGF overexpression. Recent clinical data also show that improved clinical outcomes are obtained through the combination of ocular PDT and anti-VEGF therapy. This article will discuss rationales and implications of using such a combination modality and highlight recent progress based on our clinical experience and published data.

Elimination of Cu(II) toxicity by powdered waste sludge (PWS) addition to an activated sludge unit treating Cu(II) containing synthetic wastewater.

PubMed

Pamukoglu, M Yunus; Kargi, Fikret

2007-09-05

Copper(II) ion toxicity onto activated sludge organisms was eliminated by addition of powdered waste sludge (PWS) to the feed wastewater for removal of Cu(II) ions by biosorption before biological treatment. The synthetic feed wastewater containing 14 or 22 mgl(-1) Cu(II) was mixed with PWS in a mixing tank where Cu(II) ions were adsorbed onto PWS and the mixture was fed to a sedimentation tank to separate Cu(II) containing PWS from the feed wastewater. The activated sludge unit fed with the effluent of the sedimentation tank was operated at a hydraulic residence time (HRT) of 10h and sludge age (SRT) of 10 days. To investigate Cu(II), COD and toxicity removal performance of the activated sludge unit at different PWS loadings, the system was operated at different PWS loading rates (0.1-1 gPWSh(-1)) while the Cu(II) loading rate was constant throughout the operation. Percent copper, COD and toxicity removals increased with increasing PWS loading rate due to increased adsorption of Cu(II) onto PWS yielding low Cu(II) contents in the feed. Biomass concentration in the aeration tank increased and the sludge volume index (SVI) decreased with increasing PWS loading rate due to elimination of Cu(II) from the feed wastewater by PWS addition. PWS addition to the Cu(II) containing wastewater was proven to be effective for removal of Cu(II) by biosorption before biological treatment. Approximately, 1 gPWSh(-1) should be added for 28 mgCuh(-1) loading rate for complete removal of Cu(II) from the feed wastewater to obtain high COD removals in the activated sludge unit.

Social/economic costs and health-related quality of life in patients with Prader-Willi syndrome in Europe.

PubMed

López-Bastida, Julio; Linertová, Renata; Oliva-Moreno, Juan; Posada-de-la-Paz, Manuel; Serrano-Aguilar, Pedro; Kanavos, Panos; Taruscio, Domenica; Schieppati, Arrigo; Iskrov, Georgi; Baji, Petra; Delgado, Claudia; von der Schulenburg, Johann Matthias Graf; Persson, Ulf; Chevreul, Karine; Fattore, Giovanni

2016-04-01

The aim of this study was to determine the economic burden from a societal perspective and health-related quality of life (HRQOL) of patients with Prader-Willi syndrome (PWS) in Europe. We conducted a cross-sectional study of patients with PWS from Spain, Bulgaria, Hungary, Germany, Italy, the UK, Sweden and France. Data on demographic characteristics, healthcare resource utilisation, informal care, labour productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. A total of 261 patients completed the questionnaire. The average annual costs ranged from € 3937 to € 67,484 between countries; the reference year for unit prices was 2012. Direct healthcare costs ranged from € 311 to € 18,760, direct non-healthcare costs ranged from € 1269 to € 44,035, and loss of labour productivity ranged from € 0 to € 2255. Costs were also shown to differ between children and adults. The mean EQ-5D index score for adult PWS patients ranged between 0.40 and 0.81 and the mean EQ-5D visual analogue scale score ranged between 51.25 and 90.00. The main strengths of this study lie in our bottom-up approach to costing and in the evaluation of PWS patients from a broad societal perspective. This type of analysis is very scarce in the international literature on rare diseases in comparison with other illnesses. We conclude that PWS patients incur considerable societal costs and experience substantial deterioration in HRQOL.

Assessment of physical function in adults with Prader-Willi syndrome.

PubMed

Sode-Carlsen, Rasmus; Farholt, Stense; Rabben, Kai Fr; Bollerslev, Jens; Sandahl Christiansen, Jens; Höybye, Charlotte

2009-01-01

To evaluate implementation of at test battery for assessing physical function in adults with Prader-Willi syndrome (PWS). Forty-three adults with PWS, 20 men and 23 women, mean age 29 +/- 9 years. Body mass index (BMI) and body composition were measured. A test battery a.m. Guralnik for standing balance, 2.4 m and 10 m walk and repeated rising from a chair was scored and evaluated. Mean BMI was 29.4 +/- 9.1 kg/m(2), body fat mass (FM) 26.0 +/- 16.1 kg. The adults with PWS managed the test battery well, and high scores were achieved for standing balance and 2.4 m walk. In contrast, only 13 managed maximum score in the repeated rising from a chair and 31 to walk 10 m for 6 s or faster. Significant correlations were seen between 2.4 m walk and FM ( p = 0.041) and between 10 m walk and BMI ( p = 0.001) and FM ( p = 0.019). Repeated rising from a chair and 10 m walk are useful assessments in clinical practice to identify adults with PWS with reduced physical function. Reduced performance was related to higher BMI and FM emphasising the importance of efforts to keep normal body weight and body composition in adults with PWS. These measures might be useful in monitoring effects of intervention.

Early diagnosis and multidisciplinary care reduce the hospitalization time and duration of tube feeding and prevent early obesity in PWS infants.

PubMed

Bacheré, N; Diene, G; Delagnes, V; Molinas, C; Moulin, P; Tauber, M

2008-01-01

To describe and evaluate the impact of very early diagnosis and multidisciplinary care on the evolution and care of infants presenting with Prader-Willi syndrome (PWS). 19 infants diagnosed with PWS before the second month of life were followed by a multidisciplinary team. Median age at the time of analysis was 3.1 years [range 0.4-6.5]. The data were compared with data collected in 1997 from 113 questionnaires filled out by members of the French PWS Association. The patients from this latter data set were 12.0 years [range 4 months to 41 years] at the time of analysis, with a median age of 36 months at diagnosis. The duration of their hospitalization time was significantly reduced from 30.0 [range 0-670] to 21 [range 0-90] days (p = 0.043). The duration of gastric tube feeding was significantly reduced from 30.5 [range 0-427] to 15 [range 0-60] days (p = 0.017). Growth hormone treatment was started at a mean age of 1.9 +/- 0.5 years in 10 infants and L-thyroxine in 6 infants. Only 1 infant became obese at 2.5 years. Early diagnosis combined with multidisciplinary care decreases the hospitalization time, duration of gastric tube feeding and prevents early obesity in PWS infants. (c) 2007 S. Karger AG, Basel.

Motor performance in Prader-Willi syndrome patients and its potential influence on caregiver's quality of life.

PubMed

Chiu, Valeria Jia-Yi; Tsai, Li-Ping; Wei, Jang-Ting; Tzeng, I-Shiang; Wu, Hsin-Chi

2017-01-01

Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by a variety of physical, cognitive, and behavioral impairments. PWS is a unique sarcopenia model characterized by an abnormal increase in body fat mass and a decrease in muscle mass that predisposes patients to reduced physical activity, functional limitations, and disability. These manifestations may require both symptomatic and supportive management, thus negatively influencing their lifelong family caregiver's quality of life. The aim of this study was to examine the functional motor performance of adults with PWS in Taiwan and to measure the quality of life of their primary family caregivers. The functional motor tests consisted of the following: (1) 30-s sit-to-stand test, (2) timed up-and-go test, (3) hand grip and lateral pinch strength tests, and (4) Berg Balance Scale. The World Health Organization Quality of Life-short form (WHOQOL-BREF) and the Short-Form 36 Health Survey Questionnaire (SF-36) were used to evaluate health-related quality of life, and the parenting stress index was used to assess the magnitude of stress within the parent-child system. The participants included seven adults (two females and five males) with genetically confirmed PWS and their respective main caregivers. The mean age of the adults with PWS was 25.28 years; range 18-31 years, SD 5.10; the mean BMI was 29.2 kg/m 2 , SD 6.43. All adults with PWS showed lower hand grip and lateral pinch strengths, fewer sit-to-stand cycles during the 30-s chair stand test, and greater average time during the timed up-and-go test when compared to the normative data on healthy adults. Balance was negatively correlated with the caregiver's health concepts of social functioning ( r s -0.879, P  = 0.009) and with role limitations due to physical problems ( r s -0.899, P  = 0.006) and emotional problems ( r s -0.794, P  = 0.033); hand grip strength was negatively correlated with bodily pain ( r s -0.800, P �

Exploring Patterns of Unwanted Behaviours in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Pignatti, Riccardo; Mori, Ileana; Bertella, Laura; Grugni, Graziano; Giardino, Daniela; Molinari, Enrico

2013-01-01

Background: Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. Methods: The behaviour of 31 PWS adults was…

Beneficial Effects of GH in Young Adults With Prader-Willi Syndrome: A 2-Year Crossover Trial.

PubMed

Kuppens, Renske J; Bakker, Nienke E; Siemensma, Elbrich P C; Tummers-de Lind van Wijngaarden, Roderick F A; Donze, Stephany H; Festen, Dederieke A M; van Alfen-van der Velden, Janielle A E M; Stijnen, Theo; Hokken-Koelega, Anita C S

2016-11-01

Patients with Prader-Willi syndrome (PWS) are severely at risk to develop morbid obesity, diabetes mellitus type 2, and cardiovascular disease, leading to high mortality. They have an increased fat mass (FM) and decreased lean body mass (LBM). During childhood, GH treatment counteracts the natural course of increasing obesity. Discontinuation of GH treatment at attainment of adult height (AH) might deteriorate their improved clinical condition, whereas continuation might benefit them. To investigate the effects of GH versus placebo on body composition in young adults with PWS who were GH treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled crossover study with stratification for gender and body mass index in 27 young adults with PWS. PWS Reference Center in The Netherlands. Crossover intervention with GH (0.67 mg/m 2 · d) and placebo, both during 1 year. Body composition, measured by dual-energy x-ray absorptiometry. During placebo, FM increased (relative change +21.5%; P < .001). Compared with placebo, GH treatment resulted in lower FM (-2.9 kg; P = .004) and higher LBM (+1.5 kg; P = .005), representing relative changes of -17.3% FM and +3.5% LBM. Both limb and trunk FM percentage were lower during GH versus placebo (relative change +17.3% and +15.6%; P < .001 and P = .007, respectively). No GH-related adverse events occurred. GH-treated young adults with PWS who have attained AH benefit from continuation of GH treatment. FM increases during placebo, whereas GH versus placebo results in lower FM and higher LBM. Thus, GH treatment maintains the improved body composition without safety concerns.

Analysis of Circulating Mediators of Bone Remodeling in Prader-Willi Syndrome.

PubMed

Brunetti, G; Grugni, G; Piacente, L; Delvecchio, M; Ventura, A; Giordano, P; Grano, M; D'Amato, G; Laforgia, D; Crinò, A; Faienza, M F

2018-06-01

We tested the hypothesis that the levels of bone remodeling mediators may be altered in Prader-Willi syndrome (PWS). We assessed RANKL, OPG, sclerostin, DKK-1 serum levels, and bone metabolism markers in 12 PWS children (7.8 ± 4.3 years), 14 PWS adults (29.5 ± 7.2 years), and 31 healthy controls matched for sex and age. Instrumental parameters of bone mineral density (BMD) were also evaluated. Lumbar spine BMD Z-scores were reduced in PWS children (P < 0.01), reaching osteopenic levels in PWS adults. PWS patients showed lower 25(OH)-vitamin D serum levels than controls (P < 0.001). Osteocalcin was increased in PWS children but reduced in adults respect to controls (P < 0.005 and P < 0.01, respectively). RANKL levels were higher in both pediatric and PWS adults than controls (P < 0.004), while OPG levels were significantly reduced (P < 0.004 and P < 0.006, respectively). Sclerostin levels were increased in children (P < 0.04) but reduced in adults compared to controls (P < 0.01). DKK-1 levels did not show significant difference between patients and controls. In PWS patients, RANKL, OPG, and sclerostin significantly correlated with metabolic and bone instrumental parameters. Consistently, with adjustment for age, multiple linear regression analysis showed that BMD and osteocalcin were the most important predictors for RANKL, OPG, and sclerostin in children, and GH and sex steroid replacement treatment in PWS adults. We demonstrated the involvement of RANKL, OPG, and sclerostin in the altered bone turnover of PWS subjects suggesting these molecules as markers of bone disease and new potential pharmacological targets to improve bone health in PWS.

Growth Hormone Therapy in Adults with Prader-Willi Syndrome.

PubMed

Vogt, Karen S; Emerick, Jill E

2015-04-16

Prader-Willi syndrome (PWS) is characterized by hyperphagia, obesity if food intake is not strictly controlled, abnormal body composition with decreased lean body mass and increased fat mass, decreased basal metabolic rate, short stature, low muscle tone, cognitive disability, and hypogonadism. In addition to improvements in linear growth, the benefits of growth hormone therapy on body composition and motor function in children with PWS are well established. Evidence is now emerging on the benefits of growth hormone therapy in adults with PWS. This review summarizes the current literature on growth hormone status and the use of growth hormone therapy in adults with PWS. The benefits of growth hormone therapy on body composition, muscle strength, exercise capacity, certain measures of sleep-disordered breathing, metabolic parameters, quality of life, and cognition are covered in detail along with potential adverse effects and guidelines for initiating and monitoring therapy.

Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients.

PubMed

Tauber, Maïthe; Mantoulan, Carine; Copet, Pierre; Jauregui, Joseba; Demeer, Genevieve; Diene, Gwenaëlle; Rogé, Bernadette; Laurier, Virginie; Ehlinger, Virginie; Arnaud, Catherine; Molinas, Catherine; Thuilleaux, Denise

2011-06-24

Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder with hypothalamic dysfunction, early morbid obesity with hyperphagia, and specific psychiatric phenotypes including cognitive and behavioural problems, particularly disruptive behaviours and frequent temper outbursts that preclude socialization. A deficit in oxytocin (OT)-producing neurons of the hypothalamic paraventricular nucleus has been reported in these patients. In a double-blind, randomised, placebo-controlled study, 24 adult patients with PWS received a single intranasal administration of 24 IU of OT or placebo and were tested 45 min later on social skills. Behaviours were carefully monitored and scored using an in-house grid as follows: over the two days before drug administration, on the half-day following administration, and over the subsequent two days. All patients were in a dedicated PWS centre with more than ten years of experience. Patients are regularly admitted to this controlled environment. Patients with PWS who received a single intranasal administration of OT displayed significantly increased trust in others (P = 0.02) and decreased sadness tendencies (P = 0.02) with less disruptive behaviour (P = 0.03) in the two days following administration than did patients who received placebo. In the half-day following administration, we observed a trend towards less conflict with others (p = 0.07) in the OT group compared with the placebo group. Scores in tests assessing social skills were not significantly different between the two groups. This study needs to be reproduced and adapted. It nevertheless opens new perspectives for patients with PWS and perhaps other syndromes with behavioural disturbances and obesity. ClinicalTrials.gov: NCT01038570.

De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature.

PubMed

Kitsiou-Tzeli, Sophia; Tzetis, Maria; Sofocleous, Christalena; Vrettou, Christina; Xaidara, Athena; Giannikou, Krinio; Pampanos, Andreas; Mavrou, Ariadne; Kanavakis, E

2010-08-01

The 15q11-q13 PWS/AS critical region involves genes that are characterized by genomic imprinting. Multiple repeat elements within the region mediate rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Recently, duplications of maternal origin concerning the same critical region have been implicated in autism spectrum disorders (ASD). We present a 6-month-old girl carrying a de novo duplication of maternal origin of the 15q11.2-q14 PWS/AS region (17.73 Mb in size) [46,XX,dup(15)(q11.2-q14)] detected with a high-resolution microarray-based comparative genomic hybridization (array-CGH). The patient is characterized by severe hypotonia, obesity, microstomia, long eyelashes, hirsutism, microretrognathia, short nose, severe psychomotor retardation, and multiple episodes of drug-resistant epileptic seizures, while her brain magnetic resonance imaging (MRI) documented partial corpus callosum dysplasia. In our patient the duplicated region is quite large extending beyond the Prader-Willi-Angelman critical region (PWACR), containing a number of genes that have been shown to be involved in ASD, exhibiting a severe phenotype, beyond the typical PWS/AS clinical manifestations. Reporting of similar well-characterized clinical cases with clearly delineated breakpoints of the duplicated region will clarify the contribution of specific genes to the phenotype.

The use of medical care and the prevalence of serious illness in an adult Prader-Willi syndrome cohort.

PubMed

Sinnema, Margje; Maaskant, Marian A; van Schrojenstein Lantman-de Valk, Henny M J; Boer, Harm; Curfs, Leopold M G; Schrander-Stumpel, Constance T R M

2013-08-01

Adults with Prader-Willi syndrome (PWS) have an increased occurrence of several medical conditions. We report on the consequences of high morbidity rates such as prevalence rate of hospital admissions, medication use and surgery in a Dutch cohort of adults with PWS. Special attention is paid to causes and symptoms of serious illness. Participants were contacted via the Dutch Prader-Willi Parent Association and through physicians specializing in persons with ID. The persons with PWS and their main caregivers were visited at home. Information was collected through semi-structured interviews on 102 adults with PWS. The need for medical care in the neonatal period is associated with hypotonia and feeding problems. Hospital admissions for respiratory tract infections are frequent. During childhood most hospital admissions were due to PWS syndrome specific surgery. During adolescence hospital admissions occurred for scoliosis surgery and endocrine evaluations. At adult age, hospitalization was associated with inguinal hernia surgery, diabetes mellitus, psychosis, erysipelas, water and drug intoxications. In the older group, respiratory infections were again the main reason for hospital admissions. Frequently used medications at adult age included psychotropics, laxatives, anti-diabetics and dermatologic preparations. Abnormal drinking patterns, problems with anesthesia, decreased ability to vomit, abnormal pain awareness and unpredictable fever responses were frequent and often lead to delayed diagnoses of serious conditions. People with PWS are frequent users of medical-care. Reasons for hospitalization and medication use are age specific. Knowledge on the different presentation of symptoms in people with PWS is needed. In case of unexplained illness, disturbances of consciousness and behavioral changes in people with PWS, an infection should be ruled out in the first place. Information from this study may help in preventing conditions and recognizing conditions in an

Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients

PubMed Central

2011-01-01

Background Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder with hypothalamic dysfunction, early morbid obesity with hyperphagia, and specific psychiatric phenotypes including cognitive and behavioural problems, particularly disruptive behaviours and frequent temper outbursts that preclude socialization. A deficit in oxytocin (OT)-producing neurons of the hypothalamic paraventricular nucleus has been reported in these patients. Methods In a double-blind, randomised, placebo-controlled study, 24 adult patients with PWS received a single intranasal administration of 24 IU of OT or placebo and were tested 45 min later on social skills. Behaviours were carefully monitored and scored using an in-house grid as follows: over the two days before drug administration, on the half-day following administration, and over the subsequent two days. All patients were in a dedicated PWS centre with more than ten years of experience. Patients are regularly admitted to this controlled environment. Results Patients with PWS who received a single intranasal administration of OT displayed significantly increased trust in others (P = 0.02) and decreased sadness tendencies (P = 0.02) with less disruptive behaviour (P = 0.03) in the two days following administration than did patients who received placebo. In the half-day following administration, we observed a trend towards less conflict with others (p = 0.07) in the OT group compared with the placebo group. Scores in tests assessing social skills were not significantly different between the two groups. Conclusions This study needs to be reproduced and adapted. It nevertheless opens new perspectives for patients with PWS and perhaps other syndromes with behavioural disturbances and obesity. Trial registration number ClinicalTrials.gov: NCT01038570 PMID:21702900

Cognitive profile in a large French cohort of adults with Prader-Willi syndrome: differences between genotypes.

PubMed

Copet, P; Jauregi, J; Laurier, V; Ehlinger, V; Arnaud, C; Cobo, A-M; Molinas, C; Tauber, M; Thuilleaux, D

2010-03-01

Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of expression of maternally imprinted genes situated in the 15q11-13 chromosome region. The origin is a 'de novo' deletion in the paternal chromosome in 70% of the cases and a maternal uniparental disomy in 25%. The two main genotypes show differences, notably regarding cognitive and behavioural features, but the mechanisms are not clear. This study assessed cognitive impairment in a cohort of adults with genetically confirmed PWS, analysed their profiles of cognitive strengths and weaknesses, and compared the profiles in terms of genotype. Ninety-nine male and female adults participated, all inpatients on a specialised unit for the multidisciplinary care of PWS. The Wechsler Adult Intelligence Scale (WAIS-III) was administered to all patients in identical conditions by the same psychologist. Eighty-five patients were able to cope with the test situation. Their scores were analysed with non-parametric statistical tools. The correlations with sex, age and body mass index were explored. Two genotype groups were compared: deletion (n = 57) and non-deletion (n = 27). The distribution of intelligence quotients in the total cohort was non-normal, with the following values (medians): Full Scale Intelligence Quotient (FSIQ): 52.0 (Q1:46.0; Q3:60.0), Verbal Intellectual Quotient (VIQ): 53.0 (Q1:48; Q3:62) and Performance Intellectual Quotient (PIQ): 52.5 (Q1:48; Q3:61). No correlation was found with sex, age or body mass index. Comparison between groups showed no significant difference in FSIQ or VIQ. PIQ scores were significantly better in the deletion group. The total cohort and the deletion group showed the VIQ = PIQ profile, whereas VIQ > PIQ was

Motor performance in Prader-Willi syndrome patients and its potential influence on caregiver’s quality of life

PubMed Central

Chiu, Valeria Jia-Yi; Tsai, Li-Ping; Wei, Jang-Ting; Tzeng, I-Shiang

2017-01-01

Background Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by a variety of physical, cognitive, and behavioral impairments. PWS is a unique sarcopenia model characterized by an abnormal increase in body fat mass and a decrease in muscle mass that predisposes patients to reduced physical activity, functional limitations, and disability. These manifestations may require both symptomatic and supportive management, thus negatively influencing their lifelong family caregiver’s quality of life. The aim of this study was to examine the functional motor performance of adults with PWS in Taiwan and to measure the quality of life of their primary family caregivers. Methods The functional motor tests consisted of the following: (1) 30-s sit-to-stand test, (2) timed up-and-go test, (3) hand grip and lateral pinch strength tests, and (4) Berg Balance Scale. The World Health Organization Quality of Life-short form (WHOQOL-BREF) and the Short-Form 36 Health Survey Questionnaire (SF-36) were used to evaluate health-related quality of life, and the parenting stress index was used to assess the magnitude of stress within the parent-child system. Results The participants included seven adults (two females and five males) with genetically confirmed PWS and their respective main caregivers. The mean age of the adults with PWS was 25.28 years; range 18–31 years, SD 5.10; the mean BMI was 29.2 kg/m2, SD 6.43. All adults with PWS showed lower hand grip and lateral pinch strengths, fewer sit-to-stand cycles during the 30-s chair stand test, and greater average time during the timed up-and-go test when compared to the normative data on healthy adults. Balance was negatively correlated with the caregiver’s health concepts of social functioning (rs −0.879, P = 0.009) and with role limitations due to physical problems (rs −0.899, P = 0.006) and emotional problems (rs −0.794, P = 0.033); hand grip strength was negatively correlated with

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice.

PubMed

Rozhdestvensky, Timofey S; Robeck, Thomas; Galiveti, Chenna R; Raabe, Carsten A; Seeger, Birte; Wolters, Anna; Gubar, Leonid V; Brosius, Jürgen; Skryabin, Boris V

2016-02-05

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5'HPRT-LoxP-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p-/m5'LoxP)), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p-/m5'LoxP) mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases.

Medical, psychological and social features in a large cohort of adults with Prader-Willi syndrome: experience from a dedicated centre in France.

PubMed

Laurier, V; Lapeyrade, A; Copet, P; Demeer, G; Silvie, M; Bieth, E; Coupaye, M; Poitou, C; Lorenzini, F; Labrousse, F; Molinas, C; Tauber, M; Thuilleaux, D; Jauregi, J

2015-05-01

Prader-Willi syndrome (PWS) is a developmental genetic disorder characterised by a variable expression of medical, cognitive and behavioural symptoms. In adulthood, the prevalence and severity of these symptoms determine the quality of life of the affected persons. Because of their rare disease condition, data on health and social problems in adults with PWS are scarce. In this research, we present medical, psychological and social features of a large cohort of adults admitted to a specialised PWS centre in France and analyse the differences according to genotype, gender and age. Data from 154 patients (68 men/86 women), with a median age of 27 years (range 16-54), were collected during their stay in our centre. Clinical histories were completed using information from parents or main caregivers, and the same medical team performed the diagnosis of different clinical conditions. Statistical analyses were performed to determine the influence of factors such as genotype, age or gender. Paternal deletion genotype was the most frequent (65%) at all ages. Most patients had mild or moderate intellectual disability (87%). Only 30% had studied beyond primary school and 70% were in some special educational or working programme. Most of them lived in the family home (57%). The most prevalent somatic comorbidities were scoliosis (78%), respiratory problems (75%), dermatological lesions (50%), hyperlipidaemia (35%), hypothyroidism (26%), Type 2 diabetes mellitus (25%) and lymph oedema (22%). Some form of psychotropic treatment was prescribed in 58% of subjects, and sex hormones in 43%. Patients with deletion had a higher body mass index (44 vs. 38.9 kg/m(2)) and displayed higher frequency of sleep apnoeas. Non-deletion patients received insulin treatment (19% vs. 4%) and antipsychotic treatment (54.8% vs. 32.7%) more frequently. No difference was observed in the prevalence of Type 2 diabetes between the two genotype groups. Patients >27 years of age had a higher rate of

[Prader Willi syndrome patients: study of 77 patients].

PubMed

Poyatos, David; Camprubí, Cristina; Gabau, Elisabeth; Nosas, Ramón; Villatoro, Sergi; Coll, María Dolores; Guitart, Miriam

2009-11-07

The Prader-Willi syndrome (PWS) is a disease of genetic origin. It is characterized by neonatal hypotonia, hypogonadism, hiperfagia leading to obesity, low stature, developmental delay, moderate mental retardation, abnormal behavior and characteristic facial appearance. It is caused by the loss or the inactivation of paternal genes of the imprinted region 15q11-13. There are different genetic causes: paternal 15q11-q13 deletion in 70% of patients, maternal uniparental disomy in the 20-25% and less than 5% have an imprinting defect. We present the results obtained in the transverse clinical - genetic study of 77 PWS patients. There has been realized the study of 374 suspected PWS patients. Cytogenetics studies of bands G and hybridization in situ fluorescent (FISH) and molecular genetics analysis of microsatellites, Southern blot, MS-PCR and sequenciation were carried out. Holm's criteria use for the correlation phenotype - genotype in 48 patients. PWS was confirmed in 77 patients, 46 deletion, 16 uniparental disomy, two imprinting defect and 13 only PWS methylation pattern. Significant differences do not observe in the correlation phenotype - genotype. The frequencies of the molecular alterations, 71.87 % deletion, 25 % UPD and 3.12 % DI, they are similar to described in the literature. It presents the algorithm of diagnosis used with the MS-PCR as rapid technology to confirm PWS.

Irisin and the Metabolic Phenotype of Adults with Prader-Willi Syndrome

PubMed Central

Pollak, Yehuda; Eldar-Geva, Talia

2015-01-01

Context Hyperphagia, low resting energy expenditure, and abnormal body composition contribute to severe obesity in Prader Willi syndrome (PWS). Irisin, a circulating myokine, stimulates “browning” of white adipose tissue resulting in increased energy expenditure and improved insulin sensitivity. Irisin has not been previously studied in PWS. Objectives Compare plasma and salivary irisin in PWS adults and normal controls. Examine the relationship of irisin to insulin sensitivity and plasma lipids. Design and Study Participants A fasting blood sample for glucose, lipids, insulin, leptin, adinopectin, and irisin was obtained from 22 PWS adults and 54 healthy BMI-matched volunteers. Saliva was collected for irisin assay in PWS and controls. Results Fasting glucose (77±9 vs 83±7mg/dl, p = 0.004), insulin (4.1±2.0 vs 7.9±4.7μU/ml, p<0.001), and triglycerides (74±34 vs 109±71mg/dl, p = 0.007) were lower in PWS than in controls. Insulin resistance (HOMA-IR) was lower (0.79±0.041 vs 1.63±1.02, p<0.001) and insulin sensitivity (QUICKI) was higher (0.41±0.04 vs 0.36±0.03, p<0.001) in PWS. Plasma irisin was similar in both groups, but salivary irisin (64.5±52.0 vs 33.0±12.1ng/ml), plasma leptin (33.5±24.2 vs 19.7±19.3ng/ml) and plasma adinopectin (13.0±10.8 vs 7.6±4.5μg/ml) were significantly greater in PWS (p<0.001). In PWS, plasma irisin showed positive Pearson correlations with total cholesterol (r = 0.58, p = 0.005), LDL-cholesterol (r = 0.59, p = 0.004), and leptin (r = 0.43, p = 0.045). Salivary irisin correlated negatively with HDL-cholesterol (r = -0.50, p = 0.043) and positively with LDL-cholesterol (r = 0.51, p = 0.037) and triglycerides (r = 0.50, p = 0.041). Conclusions Salivary irisin was markedly elevated in PWS although plasma irisin was similar to levels in controls. Significant associations with plasma lipids suggest that irisin may contribute to the metabolic phenotype of PWS. PMID:26334732

Irisin and the Metabolic Phenotype of Adults with Prader-Willi Syndrome.

PubMed

Hirsch, Harry J; Gross, Itai; Pollak, Yehuda; Eldar-Geva, Talia; Gross-Tsur, Varda

2015-01-01

Hyperphagia, low resting energy expenditure, and abnormal body composition contribute to severe obesity in Prader Willi syndrome (PWS). Irisin, a circulating myokine, stimulates "browning" of white adipose tissue resulting in increased energy expenditure and improved insulin sensitivity. Irisin has not been previously studied in PWS. Compare plasma and salivary irisin in PWS adults and normal controls. Examine the relationship of irisin to insulin sensitivity and plasma lipids. A fasting blood sample for glucose, lipids, insulin, leptin, adinopectin, and irisin was obtained from 22 PWS adults and 54 healthy BMI-matched volunteers. Saliva was collected for irisin assay in PWS and controls. Fasting glucose (77 ± 9 vs 83 ± 7 mg/dl, p = 0.004), insulin (4.1 ± 2.0 vs 7.9 ± 4.7 μU/ml, p<0.001), and triglycerides (74 ± 34 vs 109 ± 71 mg/dl, p = 0.007) were lower in PWS than in controls. Insulin resistance (HOMA-IR) was lower (0.79 ± 0.041 vs 1.63 ± 1.02, p<0.001) and insulin sensitivity (QUICKI) was higher (0.41 ± 0.04 vs 0.36 ± 0.03, p<0.001) in PWS. Plasma irisin was similar in both groups, but salivary irisin (64.5 ± 52.0 vs 33.0 ± 12.1ng/ml), plasma leptin (33.5 ± 24.2 vs 19.7 ± 19.3 ng/ml) and plasma adinopectin (13.0 ± 10.8 vs 7.6 ± 4.5μg/ml) were significantly greater in PWS (p<0.001). In PWS, plasma irisin showed positive Pearson correlations with total cholesterol (r = 0.58, p = 0.005), LDL-cholesterol (r = 0.59, p = 0.004), and leptin (r = 0.43, p = 0.045). Salivary irisin correlated negatively with HDL-cholesterol (r = -0.50, p = 0.043) and positively with LDL-cholesterol (r = 0.51, p = 0.037) and triglycerides (r = 0.50, p = 0.041). Salivary irisin was markedly elevated in PWS although plasma irisin was similar to levels in controls. Significant associations with plasma lipids suggest that irisin may contribute to the metabolic phenotype of PWS.

Psychiatric Illness in a Cohort of Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Sinnema, Margje; Boer, Harm; Collin, Philippe; Maaskant, Marian A.; van Roozendaal, Kees E. P.; Schrander-Stumpel, Constance T. R. M.; Curfs, Leopold M. G.

2011-01-01

Previous studies have suggested an association between PWS and comorbid psychiatric illness. Data on prevalence rates of psychopathology is still scarce. This paper describes a large-scale, systematic study investigating the prevalence of psychiatric illness in a Dutch adult PWS cohort. One hundred and two individuals were screened for psychiatric…

Determination of model parameters for zinc (II) ion biosorption onto powdered waste sludge (PWS) in a fed-batch system.

PubMed

Kargi, Fikret; Cikla, Sinem

2007-12-01

Biosorption of zinc (II) ions onto pre-treated powdered waste sludge (PWS) was investigated using a completely mixed tank operating in fed-batch mode instead of an adsorption column. Experiments with variable feed flow rate (0.05-0.5 L h(-1)), feed Zn(II) ion concentrations (37.5-275 mg L(-1)) and amount of adsorbent (1-6 g PWS) were performed using fed-batch operation at pH 5 and room temperature (20-25 degrees C). Break-through curves describing variations of aqueous (effluent) zinc ion concentrations with time were determined for different operating conditions. Percent zinc removal from the aqueous phase decreased, but the biosorbed (solid phase) zinc ion concentration increased with increasing feed flow rate and zinc concentration. A modified Bohart-Adams equation was used to determine the biosorption capacity of PWS (q'(s)) and the rate constant (K) for zinc ion biosorption. Biosorption capacity (q'(s)=57.7 g Zn kg(-1) PWS) of PWS in fed-batch operation was found to be comparable with powdered activated carbon (PAC) in column operations. However, the adsorption rate constant (K=9.17 m(3) kg(-1) h(-1)) in fed-batch operation was an order of magnitude larger than those obtained in adsorption columns because of elimination of mass transfer limitations encountered in the column operations. Therefore, a completely mixed tank operated in fed-batch mode was proven to be more advantageous as compared to adsorption columns due to better contact between the phases yielding faster adsorption rates.

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice

PubMed Central

Rozhdestvensky, Timofey S.; Robeck, Thomas; Galiveti, Chenna R.; Raabe, Carsten A.; Seeger, Birte; Wolters, Anna; Gubar, Leonid V.; Brosius, Jürgen; Skryabin, Boris V.

2016-01-01

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5′HPRT-LoxP-NeoR cassette (5′LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScrp−/m5′LoxP), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScrp−/m5′LoxP mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScrp−/m5′LoxP mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. PMID:26848093

Postural adaptations to long-term training in Prader-Willi patients.

PubMed

Capodaglio, Paolo; Cimolin, Veronica; Vismara, Luca; Grugni, Graziano; Parisio, Cinzia; Sibilia, Olivia; Galli, Manuela

2011-05-15

Improving balance and reducing risk of falls is a relevant issue in Prader-Willi Syndrome (PWS). The present study aims to quantify the effect of a mixed training program on balance in patients with PWS. Eleven adult PWS patients (mean age: 33.8 ± 4.3 years; mean BMI: 43.3 ± 5.9 Kg/m2) attended a 2-week training program including balance exercises during their hospital stay. At discharge, Group 1 (6 patients) continued the same exercises at home for 6 months, while Group 2 (5 patients) quitted the program. In both groups, a low-calorie, well-balanced diet of 1.200 kcal/day was advised. They were assessed at admission (PRE), after 2 weeks (POST1) and at 6-month (POST2). The assessment consisted of a clinical examination, video recording and 60-second postural evaluation on a force platform. Range of center of pressure (CoP) displacement in the antero-posterior direction (RANGEAP index) and the medio-lateral direction (RANGEML index) and its total trajectory length were computed. At POST1, no significant changes in all of the postural parameters were observed. At completion of the home program (POST2), the postural assessment did not reveal significant modifications. No changes in BMI were observed in PWS at POST2. Our results showed that a long-term mixed, but predominantly home-based training on PWS individuals was not effective in improving balance capacity. Possible causes of the lack of effectiveness of our intervention include lack of training specificity, an inadequate dose of exercise, an underestimation of the neural and sensory component in planning rehabilitation exercise and failed body weight reduction during the training. Also, the physiology of balance instability in these patients may possibly compose a complex puzzle not affected by our exercise training, mainly targeting muscle weakness.

Postural adaptations to long-term training in Prader-Willi patients

PubMed Central

2011-01-01

Background Improving balance and reducing risk of falls is a relevant issue in Prader-Willi Syndrome (PWS). The present study aims to quantify the effect of a mixed training program on balance in patients with PWS. Methods Eleven adult PWS patients (mean age: 33.8 ± 4.3 years; mean BMI: 43.3 ± 5.9 Kg/m2) attended a 2-week training program including balance exercises during their hospital stay. At discharge, Group 1 (6 patients) continued the same exercises at home for 6 months, while Group 2 (5 patients) quitted the program. In both groups, a low-calorie, well-balanced diet of 1.200 kcal/day was advised. They were assessed at admission (PRE), after 2 weeks (POST1) and at 6-month (POST2). The assessment consisted of a clinical examination, video recording and 60-second postural evaluation on a force platform. Range of center of pressure (CoP) displacement in the antero-posterior direction (RANGEAP index) and the medio-lateral direction (RANGEML index) and its total trajectory length were computed. Results At POST1, no significant changes in all of the postural parameters were observed. At completion of the home program (POST2), the postural assessment did not reveal significant modifications. No changes in BMI were observed in PWS at POST2. Conclusions Our results showed that a long-term mixed, but predominantly home-based training on PWS individuals was not effective in improving balance capacity. Possible causes of the lack of effectiveness of our intervention include lack of training specificity, an inadequate dose of exercise, an underestimation of the neural and sensory component in planning rehabilitation exercise and failed body weight reduction during the training. Also, the physiology of balance instability in these patients may possibly compose a complex puzzle not affected by our exercise training, mainly targeting muscle weakness. PMID:21575153

A descriptive study of colorectal function in adults with Prader-Willi Syndrome: high prevalence of constipation.

PubMed

Kuhlmann, Louise; Joensson, Iben Moeller; Froekjaer, Jens Broendum; Krogh, Klaus; Farholt, Stense

2014-04-04

Some patients with Prader-Willi Syndrome (PWS) have symptoms of constipation, but bowel function in PWS has never been systematically evaluated. The aim of the present study was to describe colorectal function in PWS by means of validated techniques. Twenty-one patients with PWS (14 women, age 17-47 (median = 32)) were evaluated with the Rome III constipation criteria, stool diary, digital rectal examination, rectal diameter assessed from transabdominal ultrasound, and total gastrointestinal transit time (GITT) determined with radio-opaque markers. Results were compared with those of healthy controls. Among PWS patients able to provide information for Rome III criteria, 8/20 (40%) fulfilled the criteria for constipation. Most commonly reported symptoms were a feeling of obstructed defecation (8/19, 42%), <3 defecations per week (8/17, 47%), straining during defecation (7/19, 37%) and lumpy or hard stools (6/19, 32%). Rectal diameter did not differ between PWS (median 3.56 centimeters, range 2.24-5.36) and healthy controls (median 3.42 centimeters, range 2.67-4.72) (p = 0.96), but more PWS patients (13/20; 65%) than healthy controls (3/25; 12%) (p < 0.001) had fecal mass in the rectum. Median GITT was 2.0 days (range 0.5-4.4) in PWS versus 1.6 (range 0.7-2.5) in the control group (p = 0.26). However, GITT was >3 days in 5/21 (24%) of PWS and none of the controls (p = 0.047). Constipation is very common in PWS. Patients with PWS have an increased prevalence of prolonged GITT and palpable stools in the rectum at digital rectal examination.

Obsessive-compulsive symptoms in Prader-Willi and "Prader-Willi-Like" patients.

PubMed

State, M W; Dykens, E M; Rosner, B; Martin, A; King, B H

1999-03-01

To compare obsessive-compulsive (OC) symptoms in patients with Prader-Willi syndrome (PWS) and symptoms in a group of patients presenting with "Prader-Willi-like" features but without the genetic abnormalities associated with PWS. 16 patients aged 4 through 20 years were evaluated in a clinic specializing in the assessment and management of behavioral and food-related problems in PWS. Eight patients were found to have key features of the syndrome but did not have a PWS genotype. These PWS-like subjects were matched to 8 clinic patients with a confirmed deletion of the PWS critical region of the paternally derived chromosome 15. All subjects were evaluated for obesity, IQ, food-related problems, maladaptive behaviors, and non-food-related OC symptoms. There were no differences between the 2 groups with respect to measures of obesity, IQ, food-related difficulties, or overall maladaptive behaviors. The PWS group showed significantly greater numbers of OC symptoms and greater symptom severity. Patients with PWS have elevated numbers of OC symptoms and significant symptom-related impairment which are not explained by developmental delay, food-related difficulties, or obesity. OC symptoms are part of a behavioral phenotype that accompanies deletions on the proximal long arm of chromosome 15 in PWS.

Evaluation of patient wristbands and patient identification process in a training hospital in Turkey.

PubMed

Cengiz, Canan; Celik, Yusuf; Hikmet, Neset

2016-10-10

Purpose The purpose of this paper is to evaluate the utilisation of patient wristbands (PWs) and patient identification (PI) process in a training hospital in Ankara, Turkey. Design/methodology/approach This descriptive and cross-sectional study was conducted in a training hospital with 640 beds, accreditied by Joint Commission International. The views of 348 patients and 419 hospital personnel on the implementation of patient wristbands and identification process were evaluated. Findings The results indicated that lack of information among patients about the importance of PWs and the misknowledge among staff participants on when, where, and by whom PWs should be put on and verified were the weakest points in this hospital. Research limitations/implications PI process must be strictly implemented according to the standard procedures of patient safety. Both patients and hospital personnel should be trained continuously, and training sessions must be held to increase their awareness about the importance of PWs and identification process. Practical implications Finding new ways and using new methods for increasing knowledge about PI and PWs are necessary. Hospital management should prepare a written PI and PW policy and procedure documents by taking the views of patients and hospital personnel and share these with them. Originality/value This study incorporates the views and attitudes of patients and health care personnel in improving health care quality by increasing awareness about PI and wristbands.

Characterisation of Balance Capacity in Prader-Willi Patients

ERIC Educational Resources Information Center

Capodaglio, Paolo; Menegoni, Francesco; Vismara, Luca; Cimolin, Veronica; Grugni, Graziano; Galli, Manuela

2011-01-01

Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). This explorative study aims to characterise balance capacity in PWS as compared to non-genetically obese patients (O) and to a group of normal-weight individuals (CG). We enrolled 14 PWS patients: 8 females and 6 males (BMI = 41.3 [plus or minus] 7.3…

Effect of Genotype and Previous GH Treatment on Adiposity in Adults With Prader-Willi Syndrome.

PubMed

Coupaye, Muriel; Tauber, Maithé; Cuisset, Laurence; Laurier, Virginie; Bieth, Eric; Lacorte, Jean-Marc; Oppert, Jean-Michel; Clément, Karine; Poitou, Christine

2016-12-01

Adults with Prader-Willi syndrome (PWS) have an increased proportion of sc fat mass compared with body mass index (BMI)-matched controls, but whether the genotype influences body composition and metabolic profile remains controversial. To assess body composition and metabolic features in adults with PWS, according to genetic subtype. In addition, the effect of previous GH treatment was assessed. Main Outcomes and Measures: Body composition (Dual Energy X-ray Absorptiometry) and metabolic parameters were compared in PWS adults (mean age, 25.5 ± 8.9 y) with deletion (n = 47) or uniparental disomy (UPD) (n = 26), taking into account GH treatment in childhood and/or adolescence. In subgroups, adipocyte size, fasting total ghrelin levels, and resting energy expenditure were measured, and hyperphagia was assessed by the Dykens Hyperphagia Questionnaire. Body composition (Dual Energy X-ray Absorptiometry) and metabolic parameters were compared in PWS adults (mean age, 25.5 ± 8.9 y) with deletion (n = 47) or uniparental disomy (UPD) (n = 26), taking into account GH treatment in childhood and/or adolescence. In subgroups, adipocyte size, fasting total ghrelin levels, and resting energy expenditure were measured, and hyperphagia was assessed by the Dykens Hyperphagia Questionnaire. In the whole sample, the deletion group had a higher BMI compared with UPD (40.9 ± 11.5 vs 34.6 ± 9.6 kg/m 2 , P = .02), but there was no difference between groups in percent body fat, metabolic profile, adipocyte size, resting energy expenditure, hyperphagia score, or ghrelin levels. In subjects previously treated with GH, BMI was not different between UPD and deletion groups (33.0 ± 9.7 vs 33.5 ± 11.1 kg/m 2 ). In addition, previous GH treatment was associated with decreased percent body fat and adipocyte volume only in the deletion group. A deletion genotype in adults with PWS is associated with increased BMI. GH treatment in childhood and/or adolescence limits this deleterious phenotypic

Cognitive, emotional, physical and social effects of growth hormone treatment in adults with Prader-Willi syndrome.

PubMed

Höybye, C; Thorén, M; Böhm, B

2005-04-01

Prader-Willi syndrome (PWS) is a multisystem genetic disorder characterized by short stature, muscular hypotonia, hyperphagia, obesity, maladaptive behaviour, hypogonadism and partial growth hormone (GH) deficiency (GHD). Severe GHD of other aetiologies has been shown to affect mood and quality of life negatively, and there are reports of improvements with GH replacement. We have studied cognitive, emotional, physical and social parameters in PWS adults at baseline, during and after GH treatment. Nineteen patients, 9 females and 10 males, median age 25 years, mean BMI 35 kg/m2 participated in this study. Approximately half of the group had GHD. All patients fulfilled the clinical criteria for PWS and 13 had a positive genotype. The patients were randomized to 6 months of treatment with either GH [1.6 IU/day (0.53 mg/day)] or placebo, followed by 12 months of active GH treatment. Treatment was then stopped, and the patients were followed for an additional period of 6 months. A test battery for general cognitive evaluation and a computer-based measurement of reaction time, motor speed and fluency were employed at baseline, after 6 months and at the end of GH treatment. At the same time intervals, a self-evaluation questionnaire was answered at the end of each test session. Other questionnaires reflecting the patients' cognitive, emotional, physical and social status were answered by relatives/caretakers at baseline and at 3 and 6 months following cessation of GH treatment. Baseline cognitive level was estimated to be moderately to mildly impaired; IQ range was 40-90. The results from some of the cognitive and the motor performance tests improved significantly after 6 and 18 months of GH treatment. According to the questionnaires, both the patients and the relatives/caretakers evaluated physical status rather negatively at baseline, but still, impairments in both physical and social status and overall functioning were observed when GH treatment was discontinued. The

Brain activity in adults who stutter: Similarities across speaking tasks and correlations with stuttering frequency and speaking rate

PubMed Central

Ingham, Roger J.; Grafton, Scott T.; Bothe, Anne K.; Ingham, Janis C.

2012-01-01

Many differences in brain activity have been reported between persons who stutter (PWS) and typically fluent controls during oral reading tasks. An earlier meta-analysis of imaging studies identified stutter-related regions, but recent studies report less agreement with those regions. A PET study on adult dextral PWS (n = 18) and matched fluent controls (CONT, n = 12) is reported that used both oral reading and monologue tasks. After correcting for speech rate differences between the groups the task-activation differences were surprisingly small. For both analyses only some regions previously considered stutter-related were more activated in the PWS group than in the CONT group, and these were also activated during eyes-closed rest (ECR). In the PWS group, stuttering frequency was correlated with cortico-striatal-thalamic circuit activity in both speaking tasks. The neuroimaging findings for the PWS group, relative to the CONT group, appear consistent with neuroanatomic abnormalities being increasingly reported among PWS. PMID:22564749

Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of life.

PubMed

Vaiani, Elisa; Herzovich, Viviana; Chaler, Eduardo; Chertkoff, Lilien; Rivarola, Marco A; Torrado, Maria; Belgorosky, Alicia

2010-10-01

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20-30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. To evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. Eighteen patients with PWS, aged 0.16-2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. In 13 of 18 patients with PWS (72.2%), serum TT4 and/or FT4 levels were below the 2.5th percentile of the reference population, while in only one PWS patient serum T3 was below this cut-off. The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infant PWS patients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development. © 2010 Blackwell Publishing Ltd.

Physical activity and maximal oxygen uptake in adults with Prader-Willi syndrome.

PubMed

Gross, Itai; Hirsch, Harry J; Constantini, Naama; Nice, Shachar; Pollak, Yehuda; Genstil, Larry; Eldar-Geva, Talia; Tsur, Varda Gross

2017-03-16

Prader-Willi Syndrome (PWS) is the most common genetic syndrome causing life-threatening obesity. Strict adherence to a low-calorie diet and regular physical activity are needed to prevent weight gain. Direct measurement of maximal oxygen uptake (VO 2 max), the "gold standard" for assessing aerobic exercise capacity, has not been previously described in PWS. Assess aerobic capacity by direct measurement of VO 2 max in adults with PWS, and in age and BMI-matched controls (OC), and compare the results with values obtained by indirect prediction methods. Seventeen individuals (12 males) age: 19-35 (28.6 ± 4.9) years, BMI: 19.4-38.1 (27.8 ± 5) kg/m 2 with genetically confirmed PWS who exercise daily, and 32 matched OC (22 males) age: 19-36 (29.3 ± 5.2) years, BMI: 21.1-48.1 (26.3 ± 4.9) kg/m 2 . All completed a medical questionnaire and performed strength and flexibility tests. VO 2 max was determined by measuring oxygen consumption during a graded exercise test on a treadmill. VO 2 max (24.6 ± 3.4 vs 46.5 ± 12.2 ml/kg/min, p < 0.001) and ventilatory threshold (20 ± 2 and 36.2 ± 10.5 ml/kg/min, p < 0.001), maximal strength of both hands (36 ± 4 vs 91.4 ± 21.2 kg, p < 0.001), and flexibility (15.2 ± 9.5 vs 26 ± 11.1 cm, p = 0.001) were all significantly lower for PWS compared to OC. Predicted estimates and direct measurements of VO 2 max were almost identical for the OC group (p = 0.995), for the PWS group, both methods for estimating VO 2 max gave values which were significantly greater (p < 0.001) than results obtained by direct measurements. Aerobic capacity, assessed by direct measurement of VO 2 max, is significantly lower in PWS adults, even in those who exercise daily, compared to OCs. Indirect estimates of VO 2 max are accurate for OC, but unreliable in PWS. Direct measurement of VO 2 should be used for designing personal training programs and in clinical studies of exercise

Evaluating the frequency and characteristics of seizures in 142 Japanese patients with Prader-Willi syndrome.

PubMed

Takeshita, Eri; Murakami, Nobuyuki; Sakuta, Ryoichi; Nagai, Toshiro

2013-08-01

Prader-Willi syndrome (PWS) has not been widely regarded as a disorder with a risk factor for seizures. We retrospectively investigated the frequency and characteristics of seizures and examined genotype-phenotype correlations with respect to seizures in PWS. We analyzed 142 patients with PWS and identified 31 (22%) with seizures. The most common seizure type was febrile convulsion (12%, 17/142). Epilepsy occurred in 6% of the patients in our cohort (9/142). The frequencies of febrile seizure and epilepsy in PWS were higher than those in the general population. Our study suggested that the frequency of seizures was not associated with genotypes of PWS (P = 0.35). In our study patients with PWS, 68% of the patients with seizures experienced initial episodes before they were 2 years old, and the seizures were relatively easier to manage. Copyright © 2013 Wiley Periodicals, Inc.

Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader-Willi syndrome.

PubMed

Kuppens, R J; Diène, G; Bakker, N E; Molinas, C; Faye, S; Nicolino, M; Bernoux, D; Delhanty, P J D; van der Lely, A J; Allas, S; Julien, M; Delale, T; Tauber, M; Hokken-Koelega, A C S

2015-12-01

Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may be involved in the underlying mechanisms of the switch. The purpose of this study is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS and investigate their associations with hyperphagia. This is a cross-sectional clinical study conducted in three PWS expert centers in the Netherlands and France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients with PWS (0.2-29.4 years) and compared with 50 age-matched obese subjects (4.3-16.9 years) and 39 healthy controls (0.8-28.6 years). AEBSF was used to inhibit deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml, resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p = 0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16). The reason for the higher AG/UAG ratio in PWS and obese was, however, completely different, as PWS had a high AG and obese a very low UAG. PWS patients without weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG ratio. The switch to excessive weight gain in PWS seems to coincide with an increase in the AG/UAG ratio, even prior to the start of hyperphagia.

Speech Situation Checklist-Revised: Investigation With Adults Who Do Not Stutter and Treatment-Seeking Adults Who Stutter.

PubMed

Vanryckeghem, Martine; Matthews, Michael; Xu, Peixin

2017-11-08

The aim of this study was to evaluate the usefulness of the Speech Situation Checklist for adults who stutter (SSC) in differentiating people who stutter (PWS) from speakers with no stutter based on self-reports of anxiety and speech disruption in communicative settings. The SSC's psychometric properties were examined, norms were established, and suggestions for treatment were formulated. The SSC was administered to 88 PWS seeking treatment and 209 speakers with no stutter between the ages of 18 and 62. The SSC consists of 2 sections investigating negative emotional reaction and speech disruption in 38 speech situations that are identical in both sections. The SSC-Emotional Reaction and SSC-Speech Disruption data show that these self-report tests differentiate PWS from speakers with no stutter to a statistically significant extent and have great discriminative value. The tests have good internal reliability, content, and construct validity. Age and gender do not affect the scores of the PWS. The SSC-Emotional Reaction and SSC-Speech Disruption seem to be powerful measures to investigate negative emotion and speech breakdown in an array of speech situations. The item scores give direction to treatment by suggesting speech situations that need a clinician's attention in terms of generalization and carry-over of within-clinic therapeutic gains into in vivo settings.

Imprinting center analysis in Prader-Willi and Angelman syndrome patients with typical and atypical phenotypes.

PubMed

Camprubí, Cristina; Coll, Maria Dolors; Villatoro, Sergi; Gabau, Elisabeth; Kamli, Amine; Martínez, Maria Jesus; Poyatos, David; Guitart, Miriam

2007-01-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are genetic disorders caused by a deficiency of imprinted gene expression from the paternal or maternal chromosome 15, respectively. This deficiency is due to the deletion of the 15q11-q13 region, parental uniparental disomy of the chromosome 15, or imprinting defect (ID). Mutation of the UBE3A gene causes approximately 10% of AS cases. In this present study, we describe the molecular analysis and phenotypes of two PWS patients and four AS patients with ID. One of the PWS patients has a non-familial imprinting center (IC) deletion and displayed a severe phenotype with an atypical PWS appearance, hyperactivity and psychiatric vulnerability. The other PWS and AS patients did not present genetic abnormalities in the IC, suggesting an epimutation as the genetic cause. The methylation pattern of two AS patients showed a faint maternal band corresponding to a mosaic ID. One of these mosaic patients displayed a mild AS phenotype while the other displayed a PWS-like phenotype.

Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults.

PubMed

Manning, Katherine E; Tait, Roger; Suckling, John; Holland, Anthony J

2018-01-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19-27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of myelin content using

Gait Pattern in Two Rare Genetic Conditions Characterized by Muscular Hypotonia: Ehlers-Danlos and Prader-Willi Syndrome

ERIC Educational Resources Information Center

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

This study aimed to quantify and compare the gait pattern in Ehlers-Danlos (EDS) and Prader-Willi syndrome (PWS) patients to provide data for developing evidence-based rehabilitation strategies. Twenty EDS and 19 PWS adult patients were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters…

Gait patterns in Prader-Willi and Down syndrome patients

PubMed Central

2010-01-01

Background Prader-Willi (PWS) and Down Syndrome (DS) are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies. Methods 19 PWS patients (17.7-40 yr) and 21 DS patients (18-39 yr) were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls (Control Group: CG; 33.4 + 9.6 yr). Results and Discussion The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p < 0.05) in all joints than CG and PWS. As for ankle kinetics, both PWS and DS showed a significantly lower push-off during terminal stance than CG, with DS yielding the lowest values. Stiffness at hip and ankle level was increased in DS. PWS showed hip stiffness values close to normal. At ankle level, stiffness was significantly decreased in both groups. Conclusions Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern. PMID:20565926

Gait patterns in Prader-Willi and Down syndrome patients.

PubMed

Cimolin, Veronica; Galli, Manuela; Grugni, Graziano; Vismara, Luca; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2010-06-21

Prader-Willi (PWS) and Down Syndrome (DS) are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies. 19 PWS patients (17.7-40 yr) and 21 DS patients (18-39 yr) were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls (Control Group: CG; 33.4 + 9.6 yr). The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p < 0.05) in all joints than CG and PWS. As for ankle kinetics, both PWS and DS showed a significantly lower push-off during terminal stance than CG, with DS yielding the lowest values. Stiffness at hip and ankle level was increased in DS. PWS showed hip stiffness values close to normal. At ankle level, stiffness was significantly decreased in both groups. Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern.

Disobedience and driving in patients with epilepsy.

PubMed

Tatum, W O; Worley, A V; Selenica, M L B

2012-01-01

Motor vehicle accidents direct legislators to ensure pubic safety. We attempted to characterize and quantify driving risk in patients with seizures (PWS). We delivered 12-question surveys to 287 consecutive PWS at an epilepsy clinic in Florida. Illegal and disobedient driving practices were analyzed. Eighty-three of 236 (35.2%) PWS were eligible to drive and 62.3% were ineligible with a seizure in <6 months (P<0.001, 95% CI: 0.57-0.70). Among the ineligible responders, 23.8% (35/147) of ineligible responders were illegally driving (14.83% of cohort); 11.86% (28/236) of PWS were disobedient refusing to obey the law, and 8.9% (21/236) of PWS were defiant and knew the law. Sadness (75/236, 31.8%) was the most common reaction to restriction, but disobedient PWS were angry (10/28, 35.7%). Overall, a small number of PWS are disobedient and illegally driving. A targeted approach to high-risk drivers with repeated verbal and supplemental driving information may help avoid unnecessary universal physician reporting for PWS. Copyright © 2011 Elsevier Inc. All rights reserved.

Outcomes of adenotonsillectomy in patients with Prader-Willi syndrome.

PubMed

Meyer, Stacy L; Splaingard, Mark; Repaske, David R; Zipf, William; Atkins, Joan; Jatana, Kris

2012-11-01

To assess the efficacy of upper airway surgical intervention in patients with Prader-Willi syndrome (PWS). Due to reports of sudden death in children undergoing treatment with growth hormone for PWS, detection of sleep-disordered breathing by polysomnography (PSG) has been recommended. Retrospective study. Multidisciplinary PWS Center at a tertiary care children's hospital. Thirteen pediatric patients with PWS who underwent adenotonsillectomy (T&A) with pre-PSG and post-PSG. Comparison of PSG results before and after T&A. Six of our patients were girls (46%); 8 had genetic characteristics consistent with deletion (61%), and the remaining 5 had genetic characteristics consistent with uniparental disomy (39%). The median age at T&A was 3 years (age range, 6 months to 11 years), and the median age at start of growth hormone treatment was 8.5 months (range, 2 months to 6 years). Nine of the 13 patients had mild to moderate obstructive sleep apnea (OSA) or obstructive hypoventilation (69%); in 8 of these 9, breathing normalized after T&A. Four children had severe OSA prior to surgery (31%). Breathing normalized in 2 of these after surgery, but 2 had PSG findings of residual combined obstructive and central apneas postoperatively. Adenotonsillectomy, while effective in most children with PWS who demonstrate mild to moderate OSA, may not be curative in children with severe OSA. An increase in central apneas can occur in some children with PWS postoperatively, and it is important to repeat PSG after surgery. Further studies are necessary to determine optimal treatment for some children with PWS and sleep-disordered breathing.

Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saitoh, S.; Cassidy, S.B.; Conroy, J.M.

Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprintingmore » mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences. 49 refs., 4 figs., 3 tabs.« less

Glaucoma in Patients with Eyes Close to Areas Affected by Port-wine Stain has Lateral and Gender Predilection.

PubMed

Wu, Yue; Yu, Ru-Jing; Chen, Di; Xu, Li; Li, Mao; Zhu, Li; Guo, Chun-Yu; Guo, Wen-Yi

2017-12-20

The location of facial port-wine stain (PWS) may be helpful for predicting some associated anomalies; high glaucoma incidence is found in patients with eyes close to PWS-affected areas (V1, ophthalmic branch area of the trigeminal nerve). This study aimed to investigate the characteristics of glaucoma in V1-affected PWS. A total of 569 patients with V1 area-affected PWS were reviewed in the study. The large series was based on the referral system between the Department of Plastic and Reconstructive Surgery and the Department of Ophthalmology. All patients were screened for glaucoma with assessments of intraocular pressure, cup-to-disc ratio, corneal diameter (only for infants), and axial length. Of the 569 patients, 110 (19.3%) patients had glaucoma. Among the patients, 18.1% (76/420) had early-onset glaucoma (under 4-year-old group). In the 4 to 18-year-old age group, 29.3% (29/99) of the patients had glaucoma. Compared with right lateral and bilateral PWS, left-sided PWS had a lower risk of glaucoma in this study (odds ratio = 0.432 [95% confidence interval, 0.264-0.706], P = 0.01). The under 4-year-old group showed a slight predominance of males (61.8%) in glaucoma. High glaucoma incidence was observed in patients with eyes close to PWS. More attention should be paid to glaucoma screening for right lateral and bilateral PWS patients. The predominance of males in Sturge-Weber syndrome (SWS) early-onset glaucoma patients might be due to the limitation of the case number; however, it might also provide us a new clue of potential relationship between SWS and PCG.

Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels.

PubMed

Tan, Wenbin; Chernova, Margarita; Gao, Lin; Sun, Victor; Liu, Huaxu; Jia, Wangcun; Langer, Stephanie; Wang, Gang; Mihm, Martin C; Nelson, J Stuart

2014-11-01

Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues. Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels. Infantile PWS sample size was small. Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in the most advanced stage of PWS and may participate in nodular formation. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Biological effects of diethylene glycol (DEG) and produced waters (PWs) released from offshore activities: a multi-biomarker approach with the sea bass Dicentrarchus labrax.

PubMed

Stefania, Gorbi; Maura, Benedetti; Claudia, Virno Lamberti; Barbara, Pisanelli; Ginevra, Moltedo; Francesco, Regoli

2009-11-01

Diethylene glycol (DEG) is largely used during oil and gas exploitation by offshore platforms. The aim of this work was to investigate if this compound induces direct molecular/cellular effects in marine organisms, or indirectly modulate those of produced waters (PWs). Sea bass (Dicentrarchus labrax) were exposed to DEG dosed alone or in combination with PWs from an Adriatic platform. A wide array of analysed biomarkers included cytochrome P450-dependent enzymatic activity, bile metabolites, glutathione S-transferases, acetylcholinesterase, peroxisomal proliferation, antioxidant defences (catalase, glutathione reductase, glutathione peroxidases, glutathione), total oxyradical scavenging capacity, malondialdehyde and DNA integrity (single strand breaks and frequency of micronuclei). Results did not reveal marked effects of DEG, while PWs influenced the biotransformation system, the oxidative status and the onset of genotoxic damages. Co-exposures caused only limited differences of biomarker responses at some experimental conditions, overall suggesting a limited biological impact of DEG at levels normally deriving from offshore activities.

Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial.

PubMed

Mogul, Harriette R; Lee, Phillip D K; Whitman, Barbara Y; Zipf, William B; Frey, Michael; Myers, Susan; Cahan, Mindy; Pinyerd, Belinda; Southren, A Louis

2008-04-01

GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies. Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults. We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods. The study was conducted at outpatient treatment facilities at four U.S. academic medical centers. Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations. Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated. Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry. Lean body mass increased from 42.65 +/- 2.25 (se) to 45.47 +/- 2.31 kg (P < or = 0.0001), and percent fat decreased from 42.84 +/- 1.12 to 39.95 +/- 1.34% (P = 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6-12 months of GH. Mean fasting glucose of 85.3 +/- 3.4 mg/dl, hemoglobin A1c of 5.5 +/- 0.2%, fasting insulin of 5.3 +/- 0.6 microU/ml, area under the curve for insulin of 60.4 +/- 7.5 microU/ml, and homeostasis model assessment of insulin resistance of 1.1 +/- 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T(3) increased 26.7% from 127.0 +/- 7.8 to 150.5 +/- 7.8 ng/dl (P = 0.021) with normalization in all subjects, including six (20%) with baseline T(3) values at least 2 sd below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients). This multicenter study demonstrates that GH improves body composition, normalizes T(3), and is well tolerated without glucose impairment in PWS genotype adults.

Characterisation of balance capacity in Prader-Willi patients.

PubMed

Capodaglio, Paolo; Menegoni, Francesco; Vismara, Luca; Cimolin, Veronica; Grugni, Graziano; Galli, Manuela

2011-01-01

Being severely overweight is a distinctive clinical feature of Prader-Willi Syndrome (PWS). This explorative study aims to characterise balance capacity in PWS as compared to non-genetically obese patients (O) and to a group of normal-weight individuals (CG). We enrolled 14 PWS patients: 8 females and 6 males (BMI = 41.3 ± 7.3 kg/m(2), age = 32.86+4.42 years), 44 obese individuals, 22 males and 22 females (BMI = 40.6 ± 4.6 kg/m(2), age = 34.2 ± 10.7 years) and 20 controls (CG: 10 females and 10 males; BMI: 21.6 ± 1.6 kg/m(2); age: 30.5 ± 5.3 years). Postural acquisitions were conducted by means of a force platform from which the COP pattern vs time was analysed. The participants were required to stand barefoot on the platform with eyes open and heels at standardized distance and position for 60s. All of the analysed parameters were statistically different from O and CG groups. PWS individuals showed greater displacements in both the A/P and M/L direction (RMS, RANGE and MV indices). Analysis of the overall planar movement of the CoP showed that the PWS patients were characterised by higher RMS distance from the centre (RMS(CoP) index) and area of confidence ellipse (AREA(CoP) index) when compared both to obese and healthy individuals. PWS patients showed a poorer balance capacity than their non-genetically obese counterparts and healthy individuals, with greater differences in both the A/P and M/L direction than O. Rehabilitation programs for PWS should take this finding into account. In addition to weight loss, strengthening of ankle flexors/extensors, and balance training, tailored interventions aimed at improving A/P control should be given particular consideration. Copyright © 2010 Elsevier Ltd. All rights reserved.

An 18-year-old patient with Prader-Willi syndrome: a case report on dental management under sedation and general anesthesia.

PubMed

Song, Ki Un; Nam, Ok Hyung; Kim, Mi Sun; Choi, Sung Chul; Lee, Hyo-Seol

2015-12-01

Prader-Willi syndrome (PWS) is a rare genetic disorder reported rarely in dentistry. Dental practitioners should know the features of PWS because affected patients have a variety of dental symptoms. The current report describes a case of PWS. An 18-year-old male patient presented with traumatic injuries. Initial emergency treatments were performed under sedation, and further treatments were conducted under general anesthesia. After adequate healing, periodic follow-up and dietary management according to the patient's age and nutritional phase were recommended. Dental management of PWS patients consists of active preventive measures in addition to dietary consultation according to age and nutritional phase.

Gait strategy in genetically obese patients: a 7-year follow up.

PubMed

Cimolin, V; Vismara, L; Galli, M; Grugni, G; Cau, N; Capodaglio, P

2014-07-01

The aim of this study was to quantitatively evaluate the change in gait and body weight in the long term in patients with Prader-Willi Syndrome (PWS). Eight adults with PWS were evaluated at baseline and after 7 years. During this period patient participated an in- and out-patient rehabilitation programs including nutritional and adapted physical activity interventions. Two different control groups were included: the first group included 14 non-genetically obese patients (OCG: obese control group) and the second group included 10 age-matched healthy individuals (HCG: healthy control group). All groups were quantitatively assessed during walking with 3D-GA. The results at the 7-year follow-up revealed significant weight loss in the PWS group and spatial-temporal changes in gait parameters (velocity, step length and cadence). With regard to the hip joint, there were significant changes in terms of hip position, which is less flexed. Knee flexion-extension showed a reduction of flexion in swing phase and of its excursion. No changes of the ankle position were evident. As for ankle kinetics, we observed in the second session higher values for the peak of ankle power in terminal stance in comparison to the first session. No changes were found in terms of ankle kinetics. The findings demonstrated improvements associated to long-term weight loss, especially in terms of spatial-temporal parameters and at hip level. Our results back the call for early weight loss interventions during childhood, which would allow the development of motor patterns under normal body weight conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Deficits in voice and multisensory processing in patients with Prader-Willi syndrome.

PubMed

Salles, Juliette; Strelnikov, Kuzma; Carine, Mantoulan; Denise, Thuilleaux; Laurier, Virginie; Molinas, Catherine; Tauber, Maïthé; Barone, Pascal

2016-05-01

Prader-Willi syndrome (PWS) is a rare neurodevelopmental and genetic disorder that is characterized by various expression of endocrine, cognitive and behavioral problems, among which a true obsession for food and a deficit of satiety that leads to hyperphagia and severe obesity. Neuropsychological studies have reported that PWS display altered social interactions with a specific weakness in interpreting social information and in responding to them, a symptom closed to that observed in autism spectrum disorders (ASD). Based on the hypothesis that atypical multisensory integration such as face and voice interactions would contribute in PWS to social impairment we investigate the abilities of PWS to process communication signals including the human voice. Patients with PWS recruited from the national reference center for PWS performed a simple detection task of stimuli presented in an uni-o or bimodal condition, as well as a voice discrimination task. Compared to control typically developing (TD) individuals, PWS present a specific deficit in discriminating human voices from environmental sounds. Further, PWS present a much lower multisensory benefits with an absence of violation of the race model indicating that multisensory information do not converge and interact prior to the initiation of the behavioral response. All the deficits observed in PWS were stronger for the subgroup of patients suffering from Uniparental Disomy, a population known to be more sensitive to ASD. Altogether, our study suggests that the deficits in social behavior observed in PWS derive at least partly from an impairment in deciphering the social information carried by voice signals, face signals, and the combination of both. In addition, our work is in agreement with the brain imaging studies revealing an alteration in PWS of the "social brain network" including the STS region involved in processing human voices. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effects of Muscle Hypotonia and Weakness on Balance: A Study on Prader-Willi and Ehlers-Danlos Syndrome Patients

ERIC Educational Resources Information Center

Galli, Manuela; Cimolin, Veronica; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

Prader-Willi syndrome (PWS) and Ehlers-Danlos syndrome (EDS) are two different genetical disorders both characterized, among other features, by muscular hypotonia. Postural control seems to be impaired in both conditions. The aim of the present study was to quantitatively compare postural control in adult PWS and EDS using stabilometric platform…

Analysis of quality of life and influencing factors in 197 Chinese patients with port-wine stains

PubMed Central

Wang, Juan; Zhu, Yu-you; Wang, Zhong-ying; Yao, Xiu-hua; Zhang, Lan-fang; Lv, Hong; Zhang, Si-ping; Hu, Bai

2017-01-01

Abstract Port-wine stains (PWS) are congenital capillary malformations, usually occurring on the face, neck, and other exposed parts of the skin, that have serious psychological and social impact on the patient. Most researchers focus on the treatment of PWS, but the quality of life (QoL) of PWS patients is seldom researched. The objective of this study is to evaluate the QoL of patients with PWS on exposed parts and explore the factors influencing the QoL of PWS patients. The QoL of 197 cases with PWS on exposed parts were prospectively studied using the Dermatology Life Quality Index questionnaire (DLQI), and the factors influencing the patients’ QoL were analyzed by single-factor analysis and multiple-factor logistic regression analysis. The reliability and validity of the QoL of PWS patients were then assessed by DLQI. A total of 197 valid questionnaires were collected. The DLQI scores in PWS cases ranged from 2 to 16, with 2 to 5 in 52.29% (103/197), 6 to 10 in 42.13% (83/197), and 11 to 20 in 5.58% (11/197). The main score elements of the DLQI focused on symptoms and feelings, daily activities, and social entertainment. Single-factor analysis and multiple-factor logistic regression analysis showed that the main influencing factors were female sex, skin hypertrophy, and lesion area >30 cm2. The inter-item correlation averaged 47.46% and the Cronbach α was 0.740, indicating high internal consistency. Correlation of the 6 dimensions of the DLQI questionnaires with the total scores showed that the Spearman correlation coefficient r ranged from 0.550 to 0.782 (P < .001), with symptoms and feelings having a correlation coefficient of 0.782 and a high correlation with total scores. This study shows that PWS has mild to moderate influence on the QoL of most patients, mainly on daily activities, social entertainment, and feelings. PMID:29390578

Effectiveness of a 6-month home-based training program in Prader-Willi patients.

PubMed

Vismara, Luca; Cimolin, Veronica; Grugni, Graziano; Galli, Manuela; Parisio, Cinzia; Sibilia, Olivia; Capodaglio, Paolo

2010-01-01

In addition to hypotonia and relative sarcopenia, patients with Prader-Willi syndrome (PWS) show reduced spontaneous physical activity and gait disorders. Scant evidence exists that daily muscle training increases their lean mass and physical activity levels. Whether adequate long-term physical training is feasible and effective in improving muscle function and gait in PWS is still unknown. Eleven adult PWS patients (mean age: 33.8±4.3 years; mean BMI: 43.3±5.9 kg/m(2)) admitted to our hospital were enrolled in this study. During their hospital stay they attended a 2-week rehabilitation program which included supervised exercise sessions. At discharge, Group 1 (6 patients) continued the same exercises at home for 6 months, while Group 2 (5 patients) did not continue home-based training. They were assessed at admission (PRE), at 2 weeks (POST1) and at 6 months (POST2). The assessment consisted of a clinical examination, 3D gait analysis and muscle strength measurement with an isokinetic dynamometer. After 2 weeks of supervised training (POST1), no significant changes in spatial-temporal gait parameters were observed, although significant improvements in ankle dorsal flexion during stance and swing and knee flexor strength were evidenced by 3D gait analysis and dynamometry in all patients. Following 6 months of home training (POST2), Group 1 had showed significant improvements in cadence and reduced knee hyperextension in mid-stance. Ankle plantar and dorsal flexors isokinetic strength had improved significantly at 120° s(-1), whereas Group 2 showed no changes in their spatial-temporal and kinematic parameters. The present study reinforces the idea that even in participants with PWS who present with a distinctive psychological profile, long-term group interventions are feasible and effective in improving their overall physical functioning. Providing an effective and simple home-based training program represents a continuum of the rehabilitation process outside the

Physical health problems in adults with Prader-Willi syndrome.

PubMed

Sinnema, Margje; Maaskant, Marian A; van Schrojenstein Lantman-de Valk, Henny M J; van Nieuwpoort, I Caroline; Drent, Madeleine L; Curfs, Leopold M G; Schrander-Stumpel, Constance T R M

2011-09-01

Prader-Willi syndrome (PWS) is a genetic disorder which is characterized by severe hypotonia and feeding problems in early infancy. In later childhood and adolescence, this is followed by hyperphagia and extreme obesity if the diet is not strictly controlled. Data on physical health problems in adults with PWS are scarce. We report on the prevalence of physical health problems in a Dutch cohort of adults with PWS in relation to age, BMI, and genetic subtype. Participants (n = 102) were retrieved via the Dutch Prader-Willi Parent Association and through physicians specializing in persons with intellectual disabilities (ID). Details regarding physical health problem spanning the participants' lifespan were collected from caretakers through semi-structured interviews. Cardiovascular problems included diabetes mellitus, hypertension, and cerebrovascular accidents. Respiratory infections were frequent in adulthood. In males, cryptorchidism was almost universal, for which 28/48 males had a history of surgery, mostly orchidopexy. None of the women had a regular menstrual cycle. Sixteen individuals had a diagnosis of osteoporosis. Spinal deformation, hip dysplasia, and foot abnormalities were common. Skinpicking, leg edema, and erysipelas were frequent dermatological problems. The findings in our group support the notion that the prevalence of physical health problems is underestimated. This underscores the importance of developing monitoring programs which would help to recognize physical health problems at an early stage. Copyright © 2011 Wiley-Liss, Inc.

[Sturge-Weber syndrome in port-wine stain patients: a retrospective study on the clinical features and screening strategy].

PubMed

Wu, Y; Yu, R J; Lin, X X; Guo, W Y

2017-10-11

Objective: To investigate the clinical characteristics of Sturge-Weber syndrome (SWS) in the patients with Port-wine stain (PWS). Methods: A total of 279 PWS patients, 164 males, 115 females with a median age of first visit 17.00 (4.75, 56.00) months. Most of the PWS patients were referred to the Ophthalmology Department for screening eye problems when the cutaneous angiomas involved the ophthalmic division of the trigeminal nerve distribution. The intraocular pressure (IOP), cup to disk ratio (C/D), corneal condition and other essential measurements were examined to screen glaucoma or choroidal hemangioma. The differences of age, gender and vascular ectasia in the ipsilateral eyes were compared among PWS and SWS patients with chi-square test. The differences about the first visit time, IOP, C/D and corneal diameters were evaluated with independent-sample T test or nonparametric test followed by Mann-Whitney U test. Results: A total number of 66 out of 279 PWS patients (23.7%) were confirmed as SWS with glaucoma. The IOP of the ipsilateral eye with vascular ectasia in PWS and SWS was 13.00 mmHg (1 mmHg=0.133 kPa) (IQR: 9.75, 17.00) and 23.00 mmHg (20.00, 32.00), respectively ( Z=- 8.212, P< 0.001); the IOP differences between the ipsilateral and contralateral eye in PWS and SWS was 1mmHg (0, 2) and 7 mmHg (3, 11) respectively; the C/D in the ipsilateral eye and the contralateral eye was 0.30 (0.30, 0.35) and 0.7 (0.6, 0.8) respectively in SWS cases with secondary glaucoma. Conclusions: There is a high proportion of SWS with glaucoma in ophthalmic division affected PWS patients. Fundus examinations were necessary for this type of patients. (Chin J Ophthalmol, 2017, 53:753-757) .

Scoliosis in patients with Prader Willi Syndrome - comparisons of conservative and surgical treatment.

PubMed

Weiss, Hans-Rudolf; Goodall, Deborah

2009-05-06

In children with Prader Willi syndrome (PWS), besides growth hormone (GH) therapy, control of the food environment and regular exercise, surgical treatment of scoliosis deformities seems the treatment of choice, even though the risks of spinal surgery in this specific population is very high. Therefore the question arises as to whether the risks of spinal surgery outweigh the benefits in a condition, which bears significant risks per se. The purpose of this systematic review of the Pub Med literature was to find mid or long-term results of spinal fusion surgery in patients with PWS, and to present the conservative treatment in a case study of nine patients with this condition. Types of studies included; all kinds of studies; retrospective and prospective ones, which reported upon the outcome of scoliosis surgery in patients with PWS.Types of participants included: patients with scoliosis and PWS.Type of intervention: surgery.Search strategy for identification of the studies; Pub Med; limited to English language and bibliographies of all reviewed articles.Nine patients with PWS from our data-base treated conservatively have been found, being 19 years or over at the time this study has been performed. The results of conservative management are described and related to the natural history and treatment results found in the Pub Med review. From 2210 titles displayed in the Pub Med database with the key word being "Prader Willi syndrome", 5 different papers were displayed at the date of the search containing some information on the outcome of surgery and none appeared to contain a mid or long-term follow-up. The PWS patients treated conservatively from our series all stayed below 70 degrees and some of which improved. If the curve of scoliosis patients with PWS can be kept within certain limits (usually below 70 degrees) conservatively, this treatment seems to have fewer complications than surgical treatments. The results of our retrospective study of nine patients

The effect of vision on postural strategies in Prader-Willi patients.

PubMed

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Priano, Lorenzo; Capodaglio, Paolo

2011-01-01

The aim of this study was to quantify the role of visual contribution in patients with Prader-Willi syndrome (PWS) on balance maintenance using a force platform. We enrolled 14 individuals with PWS free from conditions associated with impaired balance, 44 obese (OG) and 20 healthy controls (CG). Postural sway was measured for 60s while standing on a force platform (Kistler, CH; acquisition frequency: 500 Hz) integrated with a video system. Patients maintained an upright standing position with Open Eyes (OE) and then with Closed Eyes (CE). The ratio between the value of the parameter under OE and CE conditions was measured. Under OE condition PWS and OG were characterized by higher postural instability than CG, with the PWS group showing poorer balance capacity than OG. The Romberg ratio showed that while OG and CG had lower balance without vision, PWS maintained the same performance changing from OE to CE. The integration of different sensory inputs appears similar in OG and CG with higher postural stability under OE than CE. Balance in PWS is not influenced by the elimination of visual input. Copyright © 2011 Elsevier Ltd. All rights reserved.

Scoliosis in patients with Prader Willi Syndrome – comparisons of conservative and surgical treatment

PubMed Central

Weiss, Hans-Rudolf; Goodall, Deborah

2009-01-01

In children with Prader Willi syndrome (PWS), besides growth hormone (GH) therapy, control of the food environment and regular exercise, surgical treatment of scoliosis deformities seems the treatment of choice, even though the risks of spinal surgery in this specific population is very high. Therefore the question arises as to whether the risks of spinal surgery outweigh the benefits in a condition, which bears significant risks per se. The purpose of this systematic review of the Pub Med literature was to find mid or long-term results of spinal fusion surgery in patients with PWS, and to present the conservative treatment in a case study of nine patients with this condition. Types of studies included; all kinds of studies; retrospective and prospective ones, which reported upon the outcome of scoliosis surgery in patients with PWS. Types of participants included: patients with scoliosis and PWS. Type of intervention: surgery. Search strategy for identification of the studies; Pub Med; limited to English language and bibliographies of all reviewed articles. Nine patients with PWS from our data-base treated conservatively have been found, being 19 years or over at the time this study has been performed. The results of conservative management are described and related to the natural history and treatment results found in the Pub Med review. From 2210 titles displayed in the Pub Med database with the key word being "Prader Willi syndrome", 5 different papers were displayed at the date of the search containing some information on the outcome of surgery and none appeared to contain a mid or long-term follow-up. The PWS patients treated conservatively from our series all stayed below 70° and some of which improved. If the curve of scoliosis patients with PWS can be kept within certain limits (usually below 70 degrees) conservatively, this treatment seems to have fewer complications than surgical treatments. The results of our retrospective study of nine patients

Metabolic cost of over ground gait in younger stroke patients and healthy controls.

PubMed

Platts, Marina M; Rafferty, Daniel; Paul, Lorna

2006-06-01

Locomotor impairment, such as that which may occur following a stroke, results in increased energy expenditure during walking. Previous research quantifying this increased metabolic demand has focused on older people; thus, the aim of this study was to investigate the physiological cost of walking in younger patients following stroke. Thirteen stroke patients (mean age of 40.7+/-10.0 yr) and 13 age- and sex-matched controls participated. Each subject walked for 5 min around an elliptical course (two cones set 9.5 m apart) at their own preferred walking speed (PWS). The percentage of expired oxygen was measured using a portable gas analyzer. Following a 5-min rest, the control subjects repeated the procedure, but at the PWS of the patient to whom they were matched. The PWS of the stroke patients was significantly lower than that of the controls (P<0.001); however, there was no significant difference in terms of oxygen uptake (P=0.403). When the distance walked was considered, there was a statistically significant difference in oxygen uptake per unit of distance between the two groups (P<0.001) and also between the patients PWS and the controls walking at the PWS of the patients. The high metabolic cost of walking would suggest that, even for younger stroke patients, early rehabilitation should consider aerobic evaluation and training with the aim of optimizing functional independence.

The transition to increased automaticity during finger sequence learning in adult males who stutter.

PubMed

Smits-Bandstra, Sarah; De Nil, Luc; Rochon, Elizabeth

2006-01-01

The present study compared the automaticity levels of persons who stutter (PWS) and persons who do not stutter (PNS) on a practiced finger sequencing task under dual task conditions. Automaticity was defined as the amount of attention required for task performance. Twelve PWS and 12 control subjects practiced finger tapping sequences under single and then dual task conditions. Control subjects performed the sequencing task significantly faster and less variably under single versus dual task conditions while PWS' performance was consistently slow and variable (comparable to the dual task performance of control subjects) under both conditions. Control subjects were significantly more accurate on a colour recognition distracter task than PWS under dual task conditions. These results suggested that control subjects transitioned to quick, accurate and increasingly automatic performance on the sequencing task after practice, while PWS did not. Because most stuttering treatment programs for adults include practice and automatization of new motor speech skills, findings of this finger sequencing study and future studies of speech sequence learning may have important implications for how to maximize stuttering treatment effectiveness. As a result of this activity, the participant will be able to: (1) Define automaticity and explain the importance of dual task paradigms to investigate automaticity; (2) Relate the proposed relationship between motor learning and automaticity as stated by the authors; (3) Summarize the reviewed literature concerning the performance of PWS on dual tasks; and (4) Explain why the ability to transition to automaticity during motor learning may have important clinical implications for stuttering treatment effectiveness.

Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial.

PubMed

Kuppens, R J; Mahabier, E F; Bakker, N E; Siemensma, E P C; Donze, S H; Hokken-Koelega, A C S

2016-11-16

Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m 2 /day), both during 1 year. Total (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

Successful early dietary intervention avoids obesity in patients with Prader-Willi syndrome: a ten-year follow-up.

PubMed

Schmidt, H; Pozza, S Bechtold-Dalla; Bonfig, W; Schwarz, H P; Dokoupil, K

2008-07-01

Hyperphagia is a frequent symptom in patients with Prader-Willi syndrome (PWS) and results in marked obesity with the risk of metabolic and cardiovascular complications. To investigate whether early diagnosis of PWS and strict dietary intervention prevents excessive weight gain in patients with PWS. A strict fat reduced and modified carbohydrate diet consisting of 10 kcal/ cm height was provided to nine patients (seven female, two male) diagnosed early with PWS (group A). Patients were prospectively followed at our center with follow-up visits every three months. Eight patients with late diagnosis of PWS served as controls (group B). Body mass index (BMI) SDS and height SDS were compared between these two groups over a ten-year period. At the age of two years height SDS and BMI SDS were significantly lower in group A (-2.9 vs -1.2, p <0.05, and BMI SDS -0.1 vs +1.8, p < 0.05). After ten years BMI SDS increased significantly to +1.2 SDS in group A, but was still significantly lower than in group B (BMI SDS +2.4), p <0.005. Patients without restrictive diet were significantly taller than patients on the diet (height SDS group A -2.8 vs group B -1.3, p < 0.05). Early dietary treatment starting at the second year of life and continued until the age of ten years is effective in avoiding excessive weight gain in patients with PWS, but results in shorter stature. Therefore growth hormone may be a useful additional treatment in these patients.

Psychiatric Adverse Effects of Rimonobant in Adults with Prader-Willi syndrome

PubMed Central

Motaghedi, Roja; Lipman, Elizabeth G; Hogg, Jeannette E.; Christos, Paul J.; Vogiatzi, Maria G.; Angulo, Moris A.

2010-01-01

Background Prader Willi syndrome (PWS) without strict environmental modifications can lead to obesity associated with significant morbidity and mortality. In addition to increased appetite, these individuals have decreased energy expenditure with lower insulin like growth factor 1 (IGF-1), which contributes to adiposity. No effective treatment is available for this condition. Endocannabinoid receptor CB1 antagonist, rimonobant, has been effective for treatment of obesity in adult subjects. Rimonabant promotes weight loss by multiple proposed mechanisms, including decreased appetite and lipogenesis, and increased energy expenditure. Therefore, we conducted this pilot study to evaluate the effect of rimonabant on body weight and composition of adults with PWS. Method This was a double blind placebo controlled study. Body weight, total fat mass, fasting ghrelin, leptin, IGF1 and insulin like growth factor binding protein (IGFBP3) were collected at baseline, and after 90 and 180 days of treatment with placebo or 20 mg of rimonabant. Results Due to psychiatric adverse effects, 50% of subjects in the rimonabant group withdrew, and the study was terminated early (N=10) for safety concerns. There was a trend for weight loss, lower fat mass and higher IGF1 level at the end of study in this group. Leptin followed the fat mass and decreased with rimonabant treatment. Conclusion Rimonabant administration may be efficacious for weight loss in adults with PWS; unfortunately it is associated with an unacceptably high risk of psychiatric side effects. Future CB1 antagonists will need a better psychiatric profile before considered in the treatment of obesity in this genetic condition. PMID:20965292

Diagnosis and treatment of GH deficiency in Prader-Willi syndrome.

PubMed

Grugni, Graziano; Marzullo, Paolo

2016-12-01

Prader-Willi syndrome (PWS) results from under-expression of the paternally-derived chromosomal region 15q11-13. Growth failure is a recognized feature of PWS, and both quantitative and qualitative defects of the GH/IGF-I axis revealing GH deficiency (GHD) have been demonstrated in most children with PWS. In PWS adults, criteria for GHD are biochemically fulfilled in 8-38% of the studied cohorts. Published data support benefits of early institution of GH therapy (GHT) in PWS children, with positive effects on statural growth, body composition, metabolic homeostasis, and neurocognitive function. Like in pediatric PWS, GHT also yields beneficial effects on lean and body fat, exercise capacity, and quality of life of PWS adults. Although GHT has been generally administered safely in PWS children and adults, careful surveillance of risks is mandatory during prolonged GH replacement for all PWS individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

In adults with Prader-Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels.

PubMed

Purtell, Louise; Sze, Lisa; Loughnan, Georgina; Smith, Ellie; Herzog, Herbert; Sainsbury, Amanda; Steinbeck, Katharine; Campbell, Lesley V; Viardot, Alexander

2011-08-01

Prader-Willi syndrome (PWS) is a leading genetic cause of obesity, characterized by hyperphagia, endocrine and developmental disorders. It is suggested that the intense hyperphagia could stem, in part, from impaired gut hormone signaling. Previous studies produced conflicting results, being confounded by differences in body composition between PWS and control subjects. Fasting and postprandial gut hormone responses were investigated in a cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched for percentage body fat and central abdominal fat, and 10 healthy normal weight subjects. PYY[total], PYY[3-36], GLP-1[active] and ghrelin[total] were measured by ELISA or radioimmunoassay. Body composition was assessed by dual energy X-ray absorptiometry. Visual analog scales were used to assess hunger and satiety. In contrast to lean subjects (p<0.05), PWS and obese subjects were similarly insulin resistant and had similar insulin levels. Ghrelin[total] levels were significantly higher in PWS compared to obese subjects before and during the meal (p<0.05). PYY[3-36] meal responses were higher in PWS than in lean subjects (p=0.01), but not significantly different to obese (p=0.08), with an additional non-significant trend in PYY[total] levels. There were no significant differences in self-reported satiety between groups, however PWS subjects reported more hunger throughout (p=0.003), and exhibited a markedly reduced meal-induced suppression of hunger (p=0.01) compared to lean or obese subjects. Compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response. Elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

Impact of transitional care on endocrine and anthropometric parameters in Prader–Willi syndrome

PubMed Central

Paepegaey, A C; Coupaye, M; Jaziri, A; Ménesguen, F; Dubern, B; Polak, M; Oppert, J M; Tauber, M; Pinto, G; Poitou, C

2018-01-01

Context The transition of patients with Prader–Willi syndrome (PWS) to adult life for medical care is challenging because of multiple comorbidities, including hormone deficiencies, obesity and cognitive and behavioral disabilities. Objective To assess endocrine management, and metabolic and anthropometric parameters of PWS adults who received (n = 31) or not (n = 64) transitional care, defined as specialized pediatric care followed by a structured care pathway to a multidisciplinary adult team. Patients and study design Hormonal and metabolic parameters were retrospectively recorded in 95 adults with PWS (mean ± s.d. age 24.7 ± 8.2 years, BMI: 39.8 ± 12.1 kg/m²) referred to our Reference Center and compared according to transition. Results Among the entire cohort, 35.8% received growth hormone (GH) during childhood and 16.8% had a GH stimulation test after completion of growth. In adulthood, 14.7% were treated with GH, 56.8% received sex-hormone therapy, whereas 91.1% were hypogonadic and 37.9% had undergone valid screening of the corticotropic axis. The main reason for suboptimal endocrine management was marked behavioral disorders. Patients receiving transitional care were more likely to have had a GH stimulation test and hormonal substitutions in childhood. They also had a lower BMI, percentage of fat mass, improved metabolic parameters and fewer antidepressant treatments. Transitional care remained significantly associated with these parameters in multivariate analysis when adjusted on GH treatment. Conclusion A coordinated care pathway with specialized pediatric care and transition to a multidisciplinary adult team accustomed to managing complex disability including psychiatric troubles are associated with a better health status in adults with PWS. PMID:29666169

Assessment of Efficacy of the 595-nm Pulsed Dye Laser in the Treatment of Facial Port-Wine Stains in Indian Patients.

PubMed

Khandpur, Sujay; Sharma, Vinod K

2016-06-01

Pulsed dye lasers have revolutionized treatment of port-wine stains (PWS). The authors' previous study with a 585-nm/0.45-millisecond pulsed dye laser (PDL) showed 25% to 75% improvement in 60% of facial PWS. The authors analyzed data on facial PWS treated with a 595-nm tunable PDL in Indian patients. Response was assessed subjectively on a scale of -1 to 5 (Investigator Global Assessment) by comparing pretreatment and posttreatment photographs. Patients' perception of change in PWS was also noted on a visual analog scale from 0 to 10 (Patient Global Assessment). Side effects were recorded. A total of 74 flat and 24 hypertrophic PWS in skin Types IV and V with a median lesion size of 56 cm and 102 cm, respectively, and color ranging from pink to purple were treated. They underwent a mean of 7.3 and 8.5 sessions (range: 4-10 session), respectively. A mean lightening of 54% in flat and 40% in hypertrophic PWS was observed. After 10 treatments, 46.6% of flat PWS cases showed >75% lightening and an equal number had 25% to 75% improvement. A >75% improvement was observed in 12.5% of hypertrophic PWS with 75% of cases showing between 25% to 75% improvement. No significant side effects were noted. The 595-nm tunable PDL produced moderate response with no significant side effects.

Gait pattern in two rare genetic conditions characterized by muscular hypotonia: Ehlers-Danlos and Prader-Willi syndrome.

PubMed

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Camerota, Filippo; Celletti, Claudia; Albertini, Giorgio; Rigoldi, Chiara; Capodaglio, Paolo

2011-01-01

This study aimed to quantify and compare the gait pattern in Ehlers-Danlos (EDS) and Prader-Willi syndrome (PWS) patients to provide data for developing evidence-based rehabilitation strategies. Twenty EDS and 19 PWS adult patients were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of 20 normal-weight controls (CG). The results showed that PWS patients walked with longer stance duration and reduced velocity than EDS, close to CG. Both EDS and PWS showed reduced anterior step length than CG. EDS kinematics evidenced a physiological position at proximal joints (pelvis and hip joint) while some deficits were displayed at knee (reduced flexion in swing phase) and ankle level (plantar flexed position in stance and reduced dorsal flexion in swing). PWS showed a forward tilted pelvis in the sagittal plane, excessive hip flexion during the whole gait cycle and an increased hip movement in the frontal plane. Their knees were flexed at initial contact with reduced range of motion while ankle joints showed a plantar flexed position during stance. No differences were found in terms of ankle kinetics and joint stiffness. Our data showed that EDS and PWS patients were characterized by a different gait strategy: PWS showed functional limitations at every level of the lower limb joints, whereas in EDS limitations, greater than PWS, were reported mainly at the distal joints. PWS patients should be encouraged to walk for its positive impact on muscle mass and strength and energy balance. For EDS patients the rehabilitation program should be focused on ankle strategy improvement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Anthropometric study with emphasis on hand and foot measurements in the Prader-Willi syndrome: sex, age and chromosome effects.

PubMed

Butler, M G; Haynes, J L; Meaney, F J

1991-01-01

Age, sex and chromosome effects on weight, height, sitting height, three head dimensions, and five hand and three foot measurements were analyzed from 57 patients (35 males and 22 females) with the Prader-Willi syndrome (PWS). No significant differences were observed in anthropometric data between PWS patients with the 15q chromosome deletion and those with normal chromosomes. Preschool children were found to have dolichocephaly, while hand and foot measurements, stature and sitting height were within normal range, although foot size was smaller than hand size in females when compared with PWS males. However, anthropometric measurements, excluding weight, head length and ankle breadth, were less than -2 SD in adult patients. Abnormal growth patterns apparently exist with significant negative correlations with age, particularly in PWS males, for height, sitting height, head circumference, and hand and foot measurements, but a significant positive correlation for weight was found in patients below 10 years of age.

The BigCAT: A Normative and Comparative Investigation of the Communication Attitude of Nonstuttering and Stuttering Adults

ERIC Educational Resources Information Center

Vanryckeghem, Martine; Brutten, Gene J.

2011-01-01

The purpose of this investigation was to provide normative and comparative data for the BigCAT, the adult form of the Communication Attitude Test, a sub-test of the Behavior Assessment Battery. The BigCAT, a 35-item self-report test of speech-associated attitude was administered to 96 adults who stutter (PWS) and 216 adults who do not (PWNS). The…

Time-domain near-field/near-field transform with PWS operations

NASA Astrophysics Data System (ADS)

Ravelo, B.; Liu, Y.; Slama, J. Ben Hadj

2011-03-01

This article deals with the development of computation method dedicated to the extraction of the transient EM-near-field at certain distance from the given 2D data for the baseband application up to GHz. As described in the methodological analysis, it is based on the use of fft combined with the plane wave spectrum (PWS) operation. In order to verify the efficiency of the introduced method, a radiating source formed by the combination of electric dipoles excited by a short duration transient pulse current with a spectrum bandwidth of about 5 GHz is considered. It was shown that compared to the direct calculation, one gets the same behaviors of magnetic near-field components Hx, Hy and Hz with the presented extraction method, in the planes placed at {3 mm, 8 mm, 13 mm} of the initial reference plane. To confirm the relevance of the proposed transform, validation with a standard commercial tool was performed. In future, we envisage to exploit the proposed computation method to predict the transient electromagnetic (EM) field emissions notably in the microwave electronic devices for the EMC applications.

MeCP2 deficiency in Rett syndrome causes epigenetic aberrations at the PWS/AS imprinting center that affects UBE3A expression.

PubMed

Makedonski, Kirill; Abuhatzira, Liron; Kaufman, Yotam; Razin, Aharon; Shemer, Ruth

2005-04-15

Rett syndrome (RS) is a severe and progressive neurodevelopmental disorder caused by heterozygous mutations in the X-linked methyl CpG binding protein 2 (MeCP2) gene. MeCP2 is a nuclear protein that binds specifically to methylated DNA and functions as a general transcription repressor in the context of chromatin remodeling complexes. RS shares clinical features with those of Angelman syndrome (AS), an imprinting neurodevelopmental disorder. In AS patients, the maternally expressed copy of UBE3A that codes for the ubiquitin protein ligase 3A (E6-AP) is repressed. The similar phenotype of these two syndromes led us to hypothesize that part of the RS phenotype is due to MeCP2-associated silencing of UBE3A. Indeed, UBE3A mRNA and protein are shown here to be significantly reduced in human and mouse MECP2 deficient brains. This reduced UBE3A level was associated with biallelic production of the UBE3A antisense RNA. In addition, MeCP2 deficiency resulted in elevated histone H3 acetylation and H3(K4) methylation and reduced H3(K9) methylation at the PWS/AS imprinting center, with no effect on DNA methylation or SNRPN expression. We conclude, therefore, that MeCP2 deficiency causes epigenetic aberrations at the PWS imprinting center. These changes in histone modifications result in loss of imprinting of the UBE3A antisense gene in the brain, increase in UBE3A antisense RNA level and, consequently reduction in UBE3A production.

Combined 595-nm and 1,064-nm laser irradiation of recalcitrant and hypertrophic port-wine stains in children and adults.

PubMed

Alster, Tina S; Tanzi, Elizabeth L

2009-06-01

Although pulsed dye laser (PDL) treatment of port-wine stain (PWS) has long been proven safe and effective, incomplete clearance of these vascular malformations can be problematic. In addition, advanced PWS with deeper coloration and tissue hypertrophy can be particularly difficult to treat because of the superficial dermal penetration of 585- to 595-nm light. The purpose of this study was to evaluate the safety and efficacy of a novel device that delivers sequential pulses of 595- and 1,064-nm wavelengths in the treatment of recalcitrant and hypertrophic PWS. Twenty-five children and adults (skin phototypes I-III) with recalcitrant or hypertrophic PWS showing incomplete clearance after 10 prior PDL treatments were included in the study. Successive treatments using a 595-nm PDL and a 1,064-nm neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser were delivered at 6- to 8-week intervals. Two masked assessors determined clinical improvement of treatment areas using independent evaluation of comparative photographs at baseline and 3 months after treatment using a standard quartile grading scale. The use of dual 595-/1,064-nm wavelengths provided continued improvement of PWS that were previously recalcitrant to ongoing PDL therapy. Side effects were limited to transient erythema, edema, and mild purpura. Rare vesicle formation was observed, with no subsequent scarring or undesirable pigmentary changes. The novel dual 595-nm PDL and 1,064-nm Nd:YAG laser is an effective treatment for PWS that are recalcitrant to PDL therapy alone.

25OH vitamin D levels in pediatric patients affected by Prader-Willi syndrome.

PubMed

Fintini, D; Pedicelli, S; Bocchini, S; Bizzarri, C; Grugni, G; Cappa, M; Crinò, A

2018-06-01

Obesity, insulin resistance, and puberty seem to influence and been inversely associated with 25-hydroxy vitamin D (25OHD) levels. To our knowledge, a study on 25OHD in children and adolescents with Prader-Willi syndrome (PWS), a genetic form of obesity, is not yet available. To analyze the 25OHD values in pediatric PWS subjects in comparison with a control group (CNT), highlighting the possible correlations with IR, BMD, body composition, pubertal stage, and GH therapy (GHT). Auxological and laboratory parameters, HOMA-IR, Vitamin D status, and bone density and body composition by DEXA scan were analyzed in 52 PWS and 110 controls (CNT), gender-, age-, and BMI-SD matched. None of them was on calcium or vitamin D. 20 PWS were on growth hormone (GH) therapy and 32 were previously treated. Altogether, PWS had similar values of 25OHD compared to CNT.16 PWS (30.7%) and 27 CNT (24.5%) had low 25OHD levels (< 20 ng/ml) (p = NS). 25OHD of PWS on GHT were comparable to those previously treated. In both groups, univariate analysis showed a negative correlation between 25OHD and fat mass% (FM%). GH therapy and pubertal stage were positively correlated with bone parameters analyzed by DXA. Multivariate regression confirmed only FM% as negative predictor of 25HOD in PWS patients, as previously described. GHT does not seem to influence 25OHD in PWS. Our data showed that PWS had similar values of 25OHD compared to CNT. As already described, FM seems to be the only parameter influencing 25OHD levels. Finally, GHT does not seem to influence 25OHD metabolism in PWS.

Impact of molecular mechanisms, including deletion size, on Prader-Willi syndrome phenotype: study of 75 patients.

PubMed

Varela, M C; Kok, F; Setian, N; Kim, C A; Koiffmann, C P

2005-01-01

Prader-Willi syndrome (PWS) can result from a 15q11-q13 paternal deletion, maternal uniparental disomy (UPD), or imprinting mutations. We describe here the phenotypic variability detected in 51 patients with different types of deletions and 24 patients with UPD. Although no statistically significant differences could be demonstrated between the two main types of PWS deletion patients, it was observed that type I (BP1-BP3) patients acquired speech later than type II (BP2-BP3) patients. Comparing the clinical pictures of our patients with UPD with those with deletions, we found that UPD children presented with lower birth length and started walking earlier and deletion patients presented with a much higher incidence of seizures than UPD patients. In addition, the mean maternal age in the UPD group was higher than in the deletion group. No statistically significant differences could be demonstrated between the deletion and the UPD group with respect to any of the major features of PWS. In conclusion, our study did not detect significant phenotypic differences among type I and type II PWS deletion patients, but it did demonstrate that seizures were six times more common in patients with a deletion than in those with UPD.

Impact of transitional care on endocrine and anthropometric parameters in Prader-Willi syndrome.

PubMed

Paepegaey, A C; Coupaye, M; Jaziri, A; Ménesguen, F; Dubern, B; Polak, M; Oppert, J M; Tauber, M; Pinto, G; Poitou, C

2018-05-01

The transition of patients with Prader-Willi syndrome (PWS) to adult life for medical care is challenging because of multiple comorbidities, including hormone deficiencies, obesity and cognitive and behavioral disabilities. To assess endocrine management, and metabolic and anthropometric parameters of PWS adults who received ( n  = 31) or not ( n  = 64) transitional care, defined as specialized pediatric care followed by a structured care pathway to a multidisciplinary adult team. Hormonal and metabolic parameters were retrospectively recorded in 95 adults with PWS (mean ± s.d. age 24.7 ± 8.2 years, BMI: 39.8 ± 12.1 kg/m²) referred to our Reference Center and compared according to transition. Among the entire cohort, 35.8% received growth hormone (GH) during childhood and 16.8% had a GH stimulation test after completion of growth. In adulthood, 14.7% were treated with GH, 56.8% received sex-hormone therapy, whereas 91.1% were hypogonadic and 37.9% had undergone valid screening of the corticotropic axis. The main reason for suboptimal endocrine management was marked behavioral disorders. Patients receiving transitional care were more likely to have had a GH stimulation test and hormonal substitutions in childhood. They also had a lower BMI, percentage of fat mass, improved metabolic parameters and fewer antidepressant treatments. Transitional care remained significantly associated with these parameters in multivariate analysis when adjusted on GH treatment. A coordinated care pathway with specialized pediatric care and transition to a multidisciplinary adult team accustomed to managing complex disability including psychiatric troubles are associated with a better health status in adults with PWS. © 2018 The authors.

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

PubMed

Oto, Yuji; Matsubara, Keiko; Ayabe, Tadayuki; Shiraishi, Masahisa; Murakami, Nobuyuki; Ihara, Hiroshi; Matsubara, Tomoyo; Nagai, Toshiro

2018-06-01

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. © 2018 Wiley Periodicals, Inc.

A new case of interstitial 6q16.2 deletion in a patient with Prader-Willi-like phenotype and investigation of SIM1 gene deletion in 87 patients with syndromic obesity.

PubMed

Varela, Monica C; Simões-Sato, Alex Y; Kim, Chong A; Bertola, Débora R; De Castro, Claudia I E; Koiffmann, Celia P

2006-01-01

The association of obesity, phenotypic abnormalities and mental retardation characterizes syndromic obesity. Its most common form is the Prader-Willi syndrome (PWS-- neonatal hypotonia, poor sucking, delayed psychomotor development, hyperphagia, severe obesity, short stature, small hands and feet, hypogonadism, mild to moderate mental retardation and behavioral disorders). A PWS-like phenotype has been described in patients with chromosome abnormalities involving the chromosome region 6q16.2 that includes the SIM1 gene. Herein we report cytogenetic and gene studies including a screening for the SIM1 gene deletion, performed on 87 patients with PWS-like phenotype, and describe the fifth case of syndromic obesity with an interstitial deletion of the chromosome segment 6q16-q21 and suggest that mutational analysis and further studies of the parental origin of chromosome alterations of 6q16.2 in patients with and without PWS-like phenotype are needed to evaluate possible imprinting effects of SIM1 gene and establish the contribution that alterations in this gene makes to the etiology of syndromic and non-syndromic obesity.

Periodic oscillation of intracranial pressure in ventricular dilation: a preliminary report.

PubMed

Kuchiwaki, H; Misu, N; Kageyama, N; Ishiguri, H; Takada, S

1987-12-01

Artificial pressure waves (PWs) were generated by manual inflation of a balloon in the trigonum of the lateral ventricle in seven adult mongrel dogs with normal cerebrospinal fluid (CSF) circulation. In 14 of 16 series of continuous appearances of artificial PWs, local shifts of the brain were successfully monitored using small strain-gauge sensors at the periventricular structures in these animals. Of the 14 series, 13 showed displacements of the periventricular structures, suggesting ventricular dilation. These results did not always correlate with macroscopic findings. They are thought to be due largely to periventricular oedemas and, in part, non-uniform dilations of the ventricles during PWs. We conclude that a water hammer formed by reflection of an increased pulse pressure of PWs at the site of CSF absorption causes a shift of CSF from the ventricle to the periventricular structures through the wall of the ventricle. This phenomenon appears amplified in patients with impaired CSF absorption. Thus, PWs have a pathological role in the progress of ventricular dilation in patients with normal pressure hydrocephalus.

MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings.

PubMed

Miller, L; Angulo, M; Price, D; Taneja, S

1996-01-01

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.

A comprehensive team approach to the management of patients with Prader-Willi syndrome.

PubMed

Eiholzer, Urs; Whitman, Barbara Y

2004-09-01

Prader-Willi syndrome (PWS) is a genetic disorder characterized by extreme obesity accompanied by other, multisystem clinical manifestations encompassing both physical and behavioral/cognitive abnormalities. The multi-dimensional problems of patients with PWS cannot be treated with a single intervention and benefit from a team approach to management to optimize outcomes. Childhood stature below target height and reduced final height are some defining characteristics of PWS, and compelling evidence from growth hormone (GH) treatment trials suggests that hypothalamic GH deficiency exists. Treatment with GH has been shown to increase height velocity in children with PWS, decrease weight-for-height index values and body fat mass, and have a positive effect on lean body mass during at least the first year of therapy. In addition to medical concerns, the behavioral manifestations, including an uncorrectable deficit in appetite control, and cognitive limitations associated with PWS, require long-term multidisciplinary management.

Treatment with growth hormone in the prader-willi syndrome.

PubMed

Moix Gil, Eugènia; Giménez-Palop, Olga; Caixàs, Assumpta

2018-04-01

The Prader-Willi syndrome (PWS) is a rare genetic disorder caused by absence of expression of the paternal alleles in región 15q11.2-q13. Obesity and hormonal deficiencies, especially of growth hormone (GH), are the most important signs from the therapeutic viewpoint. Recombinant GH (rGH) is effective in children and represents the mainstay in treatment; by contrast, little evidence in available in adult patients. To review the reported evidence on the beneficial and adverse effects of treatment with rGH in children and adults. A review was made of 62 original articles published between 2000 and 2017 using the PubMed database. In pediatric and adult PWS, rGH improves body morphology and composition, physical performance, cognition, psychomotor development, respiratory function, and quality of life with few adverse effects. Treatment with rGH is effective and safe and improves quality of life in both children and adults with PWS. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Growth hormone therapy for Prader-willi syndrome: challenges and solutions.

PubMed

Grugni, Graziano; Sartorio, Alessandro; Crinò, Antonino

2016-01-01

Prader-Willi syndrome (PWS) is characterized by a dysregulation of growth hormone (GH)/insulin-like growth factor I axis, as the consequence of a complex hypothalamic involvement. PWS' clinical picture seems to resemble the classic non-PWS GH deficiency (GHD), including short stature, excessive body fat, decreased muscle mass, and impaired quality of life. GH therapy is able to ameliorate the phenotypic appearance of the syndrome, as well as to improve body composition, physical strength, and cognitive level. In this regard, however, some pathophysiologic and clinical questions still remain, representing a challenge to give the most appropriate care to PWS patients. Data about the prevalence of GHD in PWS children are not unequivocal, ranging from 40% to 100%. In this context, to establish whether the presence (or not) of GHD may have a different effect on clinical course during GH therapy may be helpful. In addition, the comparison of GH effects in PWS children diagnosed as small for gestational age with those obtained in subjects born appropriate for gestational age is of potential interest for future trials. Emerging information seems to demonstrate the maintenance of beneficial effects of GH therapy in PWS subjects after adolescent years. Thus, GH retesting after achievement of final height should be taken into consideration for all PWS patients. However, it is noteworthy that GH administration exerts positive effects both in PWS adults with and without GHD. Another critical issue is to clarify whether the genotype-phenotype correlations may be relevant to specific outcome measures related to GH therapy. Moreover, progress of our understanding of the role of GH replacement and concomitant therapies on bone characteristics of PWS is required. Finally, a long-term surveillance of benefits and risks of GH therapy is strongly recommended for PWS population, since most of the current studies are uncontrolled and of short duration.

The Effect of Vision on Postural Strategies in Prader-Willi Patients

ERIC Educational Resources Information Center

Cimolin, Veronica; Galli, Manuela; Vismara, Luca; Grugni, Graziano; Priano, Lorenzo; Capodaglio, Paolo

2011-01-01

The aim of this study was to quantify the role of visual contribution in patients with Prader-Willi syndrome (PWS) on balance maintenance using a force platform. We enrolled 14 individuals with PWS free from conditions associated with impaired balance, 44 obese (OG) and 20 healthy controls (CG). Postural sway was measured for 60 s while standing…

The oro-dental phenotype in Prader-Willi syndrome: a survey of 15 patients.

PubMed

Bailleul-Forestier, Isabelle; Verhaeghe, Veroniek; Fryns, Jean-Pierre; Vinckier, Frans; Declerck, Dominique; Vogels, Annick

2008-01-01

Prader-Willi syndrome (PWS) is a rare disorder caused by genetic defects in certain regions of chromosome 15q11-13. It is characterized by severe neonatal hypotonia and feeding problems, childhood-onset hyperphagia and obesity, short stature, facial dysmorphy, hypogonadism, learning and behavioural difficulties, and dental abnormalities. To describe the oro-dental phenotypic spectrum of patients with PWS. Fifteen PWS patients (3-35 years of age) being followed at the Centre for Human Genetics of the University Hospital of Leuven were examined at the dental clinic of the same institution. Medical information collected included age at diagnosis, body mass index (BMI) and level of cognitive functioning. Oral, clinical and radiological evaluations were performed. Caries experience (cavitation level), dental erosion and salivary flow rates were assessed. The 15 patients had dmft/DMFT scores ranging from 0 to 28, while nine were cavity-free. Those with severe caries experience also presented advanced dental erosion. BMI ranged from 16 to 42.6. There was no association between BMI and caries experience or erosive tooth wear. The PWS patients in our survey presented with a more favourable oral health status than those in previous studies. This might be due to early diet management or better oral hygiene during childhood or both.

A novel deletion of SNURF/SNRPN exon 1 in a patient with Prader-Willi-like phenotype.

PubMed

Cao, Yang; AlHumaidi, Susan S; Faqeih, Eissa A; Pitel, Beth A; Lundquist, Patrick; Aypar, Umut

2017-08-01

Here we report the smallest deletion involving SNURF/SNRPN that causes major symptoms of Prader-Willi syndrome (PWS), including hypotonia, dysmorphic features, intellectual disability, and obesity. A female patient with the aforementioned and additional features was referred to the Mayo Clinic Cytogenetics laboratory for genetic testing. Chromosomal microarray analysis and subsequent Sanger sequencing identified a de novo 6.4 kb deletion at 15q11.2, containing exon 1 of the SNURF gene and exon 1 of the shortest isoform of the SNRPN gene. SNURF/SNRPN exon 1, which is methylated on the silent maternal allele, is associated with acetylated histones on the expressed paternal allele. This region also overlaps with the PWS-imprinting center (IC). Subsequent molecular methylation analysis was performed using methylation-specific MLPA (MS-MLPA), which characterized that the deletion of SNURF/SNRPN exon 1 was paternal in origin, consistent with the PWS-like phenotype. Since SNURF/SNRPN gene and the PWS-IC are known to regulate snoRNAs, it is likely that the PWS-like phenotype observed in patients with paternal SNURF/SNRPN deletion is due to the disrupted expression of SNORD116 snoRNAs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cognitive Strengths and Weaknesses Associated with Prader-Willi Syndrome.

ERIC Educational Resources Information Center

Conners, Frances A.; Rosenquist, Celia J.; Atwell, Julie A.; Klinger, Laura Grofer

2000-01-01

Nine adults with Prader-Willi syndrome (PWS) and nine age- and IQ-matched adults with PWS completed standardized tests of long-term and short-term memory, visual and auditory processing, and reading and mathematics achievement. Contrary to previous findings, long-term memory in PWS subjects was strong relative to IQ and there was no evidence that…

Behavioral Phenotype in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Sinnema, Margje; Einfeld, Stewart L.; Schrander-Stumpel, Constance T. R. M.; Maaskant, Marian A.; Boer, Harm; Curfs, Leopold M. G.

2011-01-01

Prader-Willi syndrome (PWS) is characterized by temper tantrums, impulsivity, mood fluctuations, difficulty with change in routine, skinpicking, stubbornness and aggression. Many studies on behavior in PWS are limited by sample size, age range, a lack of genetically confirmed diagnosis of PWS and inconsistent assessment of behavior. The aim of…

Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vgontzas, A.N.; Kales, A.; Bixler, E.O.

To assess whether sleep abnormalities are related to the genetic abnormalities in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) and determined the chromosome 15 genotypes in eight patients with PWS. Four patients demonstrated sleep onset REM periods (SOREM), and five met the objective polysomnographic criteria for severe or moderate excessive daytime sleepiness (EDS). Three of the four patients with SOREM displayed a paternally derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal uniparental heterodisomy in this chromosomal region (UPD). Two of the four patients that did not display SOREM carried paternally derived deletions; the remaining twomore » demonstrated UPD. Four of the five patients with EDS displayed paternal deletions, and the fifth exhibited UPD. One of three patients without evidence of EDS demonstrated paternal deletion; the remaining two showed UPD. Although neither EDS nor SOREM was not consistently associated with a specific genetic abnormality, these phenotypes may be more common in patients with paternal deletions than in those with UPD. Sleep abnormalities in PWS cannot be explained by a single genetic model. 32 refs., 1 tab.« less

Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

PubMed

Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Takahashi, Shoki; Mori, Etsuro

2011-07-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age- and gender-matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole-brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel-based morphometry. The PWS subjects showed small gray-matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray-matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas. Copyright © 2010 Wiley-Liss, Inc.

Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan.

PubMed

Shida, Dai; Ahiko, Yuka; Tanabe, Taro; Yoshida, Takefumi; Tsukamoto, Shunsuke; Ochiai, Hiroki; Takashima, Atsuo; Boku, Narikazu; Kanemitsu, Yukihide

2018-03-27

The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear. This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance. Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033). Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.

Hormonal and metabolic defects in a prader-willi syndrome mouse model with neonatal failure to thrive.

PubMed

Stefan, M; Ji, H; Simmons, R A; Cummings, D E; Ahima, R S; Friedman, M I; Nicholls, R D

2005-10-01

Prader-Willi syndrome (PWS) has a biphasic clinical phenotype with failure to thrive in the neonatal period followed by hyperphagia and severe obesity commencing in childhood among other endocrinological and neurobehavioral abnormalities. The syndrome results from loss of function of several clustered, paternally expressed genes in chromosome 15q11-q13. PWS is assumed to result from a hypothalamic defect, but the pathophysiological basis of the disorder is unknown. We hypothesize that a fetal developmental abnormality in PWS leads to the neonatal phenotype, whereas the adult phenotype results from a failure in compensatory mechanisms. To address this hypothesis and better characterize the neonatal failure to thrive phenotype during postnatal life, we studied a transgenic deletion PWS (TgPWS) mouse model that shares similarities with the first stage of the human syndrome. TgPWS mice have fetal and neonatal growth retardation associated with profoundly reduced insulin and glucagon levels. Consistent with growth retardation, TgPWS mice have deregulated liver expression of IGF system components, as revealed by quantitative gene expression studies. Lethality in TgPWS mice appears to result from severe hypoglycemia after postnatal d 2 after depletion of liver glycogen stores. Consistent with hypoglycemia, TgPWS mice appear to have increased fat oxidation. Ghrelin levels increase in TgPWS reciprocally with the falling glucose levels, suggesting that the rise in ghrelin reported in PWS patients may be secondary to a perceived energy deficiency. Together, the data reveal defects in endocrine pancreatic function as well as glucose and hepatic energy metabolism that may underlie the neonatal phenotype of PWS.

Growth hormone therapy for Prader–willi syndrome: challenges and solutions

PubMed Central

Grugni, Graziano; Sartorio, Alessandro; Crinò, Antonino

2016-01-01

Prader–Willi syndrome (PWS) is characterized by a dysregulation of growth hormone (GH)/insulin-like growth factor I axis, as the consequence of a complex hypothalamic involvement. PWS’ clinical picture seems to resemble the classic non-PWS GH deficiency (GHD), including short stature, excessive body fat, decreased muscle mass, and impaired quality of life. GH therapy is able to ameliorate the phenotypic appearance of the syndrome, as well as to improve body composition, physical strength, and cognitive level. In this regard, however, some pathophysiologic and clinical questions still remain, representing a challenge to give the most appropriate care to PWS patients. Data about the prevalence of GHD in PWS children are not unequivocal, ranging from 40% to 100%. In this context, to establish whether the presence (or not) of GHD may have a different effect on clinical course during GH therapy may be helpful. In addition, the comparison of GH effects in PWS children diagnosed as small for gestational age with those obtained in subjects born appropriate for gestational age is of potential interest for future trials. Emerging information seems to demonstrate the maintenance of beneficial effects of GH therapy in PWS subjects after adolescent years. Thus, GH retesting after achievement of final height should be taken into consideration for all PWS patients. However, it is noteworthy that GH administration exerts positive effects both in PWS adults with and without GHD. Another critical issue is to clarify whether the genotype–phenotype correlations may be relevant to specific outcome measures related to GH therapy. Moreover, progress of our understanding of the role of GH replacement and concomitant therapies on bone characteristics of PWS is required. Finally, a long-term surveillance of benefits and risks of GH therapy is strongly recommended for PWS population, since most of the current studies are uncontrolled and of short duration. PMID:27330297

A further case of a Prader-Willi syndrome phenotype in a patient with Angelman syndrome molecular defect.

PubMed

De Molfetta, Greice Andreotti; Felix, Temis Maria; Riegel, Mariluce; Ferraz, Victor Evangelista de Faria; de Pina Neto, João Monteiro

2002-12-01

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct human neurogenetic disorders; however, a clinical overlap between AS and PWS has been identified. We report on a further case of a patient showing the PWS phenotype with the AS molecular defect. Despite the PWS phenotype, the DNA methylation analysis of SNRPN revealed an AS pattern. Cytogenetic and FISH analysis showed normal chromosomes 15 and microsatellite analysis showed heterozygous loci inside and outside the 15q11-13 region. The presence of these atypical cases could be more frequent than previously expected and we reinforce that the DNA methylation analysis is important for the correct diagnosis of severe mental deficiency, congenital hypotonia and obesity.

Strength characterization of knee flexor and extensor muscles in Prader-Willi and obese patients.

PubMed

Capodaglio, Paolo; Vismara, Luca; Menegoni, Francesco; Baccalaro, Gabriele; Galli, Manuela; Grugni, Graziano

2009-05-06

despite evidence of an obesity-related disability, there is a lack of objective muscle functional data in overweight subjects. Only few studies provide instrumental strength measurements in non-syndromal obesity, whereas no data about Prader-Willi syndrome (PWS) are reported. The aim of our study was to characterize the lower limb muscle function of patients affected by PWS as compared to non-syndromal obesity and normal-weight subjects. We enrolled 20 obese (O) females (age: 29.1 +/- 6.5 years; BMI: 38.1 +/- 3.1), 6 PWS females (age: 27.2 +/- 4.9 years; BMI: 45.8 +/- 4.4) and 14 healthy normal-weight (H) females (age: 30.1 +/- 4.7 years; BMI: 21 +/- 1.6). Isokinetic strength during knee flexion and extension in both lower limbs at the fixed angular velocities of 60 degrees /s, 180 degrees /s, 240 degrees /s was measured with a Cybex Norm dynamometer. the H, O and PWS populations appear to be clearly stratified with regard to muscle strength.: PWS showed the lowest absolute peak torque (PT) for knee flexor and extensor muscles as compared to O (-55%) and H (-47%) (P = 0.00001). O showed significantly higher strength values than H as regard to knee extension only (P = 0.0014). When strength data were normalised by body weight, PWS showed a 50% and a 70% reduction in PT as compared to O and H, respectively. Knee flexors strength values were on average half of those reported for extension in all of the three populations. the novel aspect of our study is the determination of objective measures of muscle strength in PWS and the comparison with O and H patients. The objective characterization of muscle function performed in this study provides baseline and outcome measures that may quantify specific strength deficits amendable with tailored rehabilitation programs and monitor effectiveness of treatments.

Speech sequence skill learning in adults who stutter.

PubMed

Bauerly, Kim R; De Nil, Luc F

2011-12-01

The present study compared the ability of 12 people who stutter (PWS) and 12 people who do not stutter (PNS) to consolidate a novel sequential speech task. Participants practiced 100 repetitions of a single, monosyllabic, nonsense word sequence during an initial practice session and returned 24-h later to perform an additional 50 repetitions. Results showed significantly slower sequence durations in the PWS compared to PNS following extensive practice and consolidation. However, the hypothesis that poor performance gains in PWS compared to PNS during practice would be maintained following a 24-h consolidation period was not supported. Further descriptive analysis revealed large within group differences in PWS which to some extent were attributed to a subgroup of PWS who failed to show any improvements in performance following practice or consolidation. The results and the possible presence of subgroups of PWS are discussed with regard to their limitations in motor learning abilities. The reader will be able to (1) explain the difference between practice and learning, (2) define consolidation and explain the importance of measuring performance following a consolidation period, (3) understand past research on PWS' performance during both speech and nonspeech motor tasks, and (4) explain why individual differences in practice effects and learning may have important implications for client variability in treatment outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

Disorders of glucose metabolism in Prader-Willi syndrome: Results of a multicenter Italian cohort study.

PubMed

Fintini, D; Grugni, G; Bocchini, S; Brufani, C; Di Candia, S; Corrias, A; Delvecchio, M; Salvatoni, A; Ragusa, L; Greggio, N; Franzese, A; Scarano, E; Trifirò, G; Mazzanti, L; Chiumello, G; Cappa, M; Crinò, A

2016-09-01

Prader-Willi syndrome (PWS) is characterized by a high incidence of altered glucose metabolism (AGM). However, epidemiological data on impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) are still discordant. We performed a multicenter study based on 274 PWS patients [144 females, aged 20.3 ± 10.4 yrs (range: 8.1-50.1 years)] evaluating the prevalence for AGM in the entire group, and according to age (children <10 yrs; adolescents 10-18 yrs, and adults >18 yrs), Body Mass Index (BMI = kg/m(2)), gender, genotypes (deletion or uniparental disomy for chromosome 15), and GH therapy (GHT) (untreated, previously or currently treated). Altogether, AGM was detected in 67 (24.4%) of patients (0.7% IFG, 10.2% IGT, 13.5% T2DM). The prevalence of AGM was correlated to age (p = 0.001), BMI (p = 0.001) and HOMA-IR (p = 0.001). However, gender, genotype, and GHT did not influence AGM development in univariate analysis. These data were confirmed as positive predictors when inserted in a multivariate analysis model. This study is the first report on the prevalence of AGM in a large population of PWS. Overall, PWS subjects show a high prevalence of AGM that appears more common in obese and adult subjects. Our data confirm the main role of obesity on the individual metabolic risk clustering in PWS, and thus reinforce the concept that improvement in weight control remains the most important goal of any PWS treatment program. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Long-term health outcomes in patients with Prader-Willi Syndrome: a nationwide cohort study in Denmark.

PubMed

Hedgeman, E; Ulrichsen, S P; Carter, S; Kreher, N C; Malobisky, K P; Braun, M M; Fryzek, J; Olsen, M S

2017-10-01

Prader-Willi syndrome (PWS) is a rare congenital disease that affects growth, sexual development, cognitive function and behavior. Individuals exhibit food preoccupation and hyperphagia, which may lead to obesity with premature morbidity and mortality. The aim of this work was to evaluate the risk of venous thromboembolisms (VTEs), myocardial infarction, pulmonary hypertension, sleep apnea, depression, anxiety and all-cause mortality among persons with PWS as compared with an age- and sex-matched general-population cohort. All persons diagnosed with PWS (n=155) were identified in the Danish Health Registries; an age- and sex-matched comparison group was selected from the general population of Denmark (n=15 500); diseases of interest were identified through the health registry and cause of death register. Follow-up began on date of birth or first medical record availability through to first occurrence of an outcome of interest; follow-up ceased at emigration from Denmark or end of study. Incidence rates (IRs) were calculated and Cox's proportional hazards models were used to understand the relative risk (RR) of disease. The IRs for VTE among patients with PWS was 144 (60-347) per 100 000 person-years. Risks for VTE events and all-cause mortality were 9.4 times (95% confidence interval (CI): 3.7-23.5) and 11.0 times (95% CI: 5.7-21.1) higher, respectively, for patients with PWS versus the general population. Increased risks were also found individually for deep venous thromboses (DVTs) (RR: 9.1; 95% CI: 3.2-25.2), pulmonary embolisms (RR: 11.0; 95% CI: 1.4-86.9), myocardial infarction (RR: 7.2; 95% CI: 1.7-30.2) and anxiety (RR: 2.8; 95% CI: 1.0-7.5). No cases of pulmonary hypertension, sleep apnea or depressive disorders were identified within this PWS cohort. Multiple cardiovascular and behavioral illnesses are more likely to occur among patients with PWS than within the general population. These increased risks may provide an impetus for enhanced disease

Molecular and clinical characterization of two patients with Prader-Willi syndrome and atypical deletions of proximal chromosome 15q.

PubMed

Calounova, Gabriela; Hedvicakova, Petra; Silhanova, Eva; Kreckova, Gabriela; Sedlacek, Zdenek

2008-08-01

Prader-Willi syndrome (PWS) is caused by the disturbed expression of genes from the imprinted region of 15q11-q13, but the specific contributions of individual genes remain unknown. Most paternal PWS deletions are bracketed by recurrent breakpoints BP1 or BP2 and BP3. Atypical deletions are very rare. In the present work, we describe the molecular analysis of two patients with atypical deletions using microsatellite analysis, methylation-specific MLPA, and microarray CGH. A deletion of about 2 Mb in Patient 1 started at BP2 and ended in the middle of the typically deleted region within the UBE3A gene. The deletion in Patient 2 started 1.3 Mb distal from BP2 within the C15ORF2 gene, extended over 9.5 Mb, and ended within the AVEN gene in proximal 15q14. In Patient 1 both deletion breakpoints involved repetitive regions, which precluded cloning of the junction and pointed to non-allelic homologous recombination as a possible mechanism of this rearrangement. The breakpoints in Patient 2 were sequenced, and their structure suggested non-homologous end joining as the most likely cause of this deletion. The phenotype of both patients did not depart significantly from the typical clinical picture of PWS, although some symptoms in Patient 2 were also reminiscent of the phenotype of individuals with the recently described 15q13.3 microdeletion syndrome. Our findings support previous observations of relatively mild phenotypic effects resulting from deletions that extend distally from the PWS region and observations of the modest effects of different types of genetic defects on the spectrum and severity of symptoms in PWS. Copyright 2008 Wiley-Liss, Inc.

Genetic studies of Prader-Willi patients provide evidence for conservation of genomic architecture in proximal chromosome 15q.

PubMed

Hou, Aihua; Lin, Shuan-Pei; Ho, Shi Yun; Chen, Chi-Fung Jennifer; Lin, Hsiang-Yu; Chen, Yen-Juin; Huang, Chi-Yu; Chiu, Huei-Ching; Chuang, Chih-Kuang; Chen, Ken-Shiung

2011-03-01

Prader-Willi syndrome (PWS) is a neurogenetic disorder associated with recurrent genomic recombination involving low copy repeats (LCRs) located in the human chromosome 15q11-q13. Previous studies of PWS patients from Asia suggested that there is a higher incidence of deletion and lower incidence of maternal uniparental disomy (mUPD) compared to that of Western populations. In this report, we present genetic etiology of 28 PWS patients from Taiwan. Consistent with the genetic etiology findings from Western populations, the type II deletion appears to be the most common deletion subtype. Furthermore, the ratio of the two most common deletion subtypes and the ratio of the maternal heterodisomy to isodisomy cases observed from this study are in agreement with previous findings from Western populations. In addition, we identified and further mapped the deletion breakpoints in two patients with atypical deletions using array CGH (comparative genomic hybridization). Despite the relatively small numbers of patients in each subgroup, our findings suggest that the genomic architecture responsible for the recurrent recombination in PWS is conserved in Taiwanese of the Han Chinese heritage and Western populations, thereby predisposing chromosome 15q11-q13 to a similar risk of rearrangements. © 2010 The Authors Annals of Human Genetics © 2010 Blackwell Publishing Ltd/University College London.

Long-term psychological impact and perceived efficacy of pulsed-dye laser therapy for patients with port-wine stains.

PubMed

Hansen, Kristen; Kreiter, Clarence D; Rosenbaum, Marcy; Whitaker, Duane C; Arpey, Christopher J

2003-01-01

The rationale for treatment of patients with port-wine stain (PWS) birthmarks has focused on the belief that eventual soft-tissue hypertrophy and negative psychological effects might be diminished or avoided. Pulsed-dye laser (PDL) therapy has become widely accepted as the treatment of choice for PWS, and a variety of studies have been conducted that evaluate its short-term efficacy. Long-term data regarding outcome and patient satisfaction are lacking. Our objective was to evaluate the long-term efficacy of pulsed-dye laser therapy from the patient's perspective. A survey was mailed to all patients or parents of minor patients whose last known laser treatment was performed between January 1, 1989, and January 1, 1996. Patients were asked to quantify changes in their PWS as well as their psychological well-being. A formal qualitative analysis was performed on their written comments as well. A total of 164 surveys were mailed to the most recent address available by the patient record. Fifty-two surveys were returned as undeliverable, and 55 evaluable surveys were returned, yielding a 49% overall return rate for patients who could be located. The mean age of respondents was 28.8 years, 96% of whom were white and 62% female. The mean number of years since last treatment was 7.04. The vast majority of patients noted little or no change in texture, height, or dimension of their PWS, whereas 62% noted color improvement. A majority or patients (60%) worried less about their appearance after treatment, whereas a similar number (61%) believed their ability to make friends or meet others was unaffected by treatment. Only 19% thought others looked at or treated them differently because of their PWS. Overall, 48% of patients indicated satisfaction with treatment, 24% dissatisfaction, and 28% neutral. On a 10-point scale indicating their likelihood of recommending treatment to someone similarly affected, the mean score was 7.42. Men were significantly and consistently less

Weight control and behavior rehabilitation in a patient suffering from Prader Willi syndrome.

PubMed

Di Lorenzo, Rosaria; Sberveglieri, Sara; Marrama, Donatella; Landi, Giulia; Ferri, Paola

2016-04-01

This study reports a case of Prader Willi syndrome (PWS), a genomic imprinting disease related to chromosome regions 15q11.2-q13 15, which includes hypothalamic dysfunction leading to hyperphagia, obesity, shortness, sleep abnormalities. Our case is extremely severe, in comparison to other PWS cases described in literature, due to the association with severe emotional and psychiatric symptoms: oppositional behaviour, rigidity of thought, skin picking and pathological hoarding. We described the case of a Caucasian male patient suffering from PWS, treated in outpatient care by local Mental Health Centre and supported by Social Service, who was admitted to a residential rehabilitative facility. After a 2-year follow-up, the patient showed a global improvement in symptoms and functioning, as registered by the rating scales administered. At the end of observation period, we also reported an important improvement in weight control, reducing the risk of obesity and related diseases, therefore improving the prognosis of life. This case highlights the need for long-term, individualized and multi-professional treatment in patients suffering from a complex genetic syndrome with both organic and psychological alterations, for which medical care setting and pharmacological treatments are not sufficient. Clinical observation of this case leads us to compare PWS to drug addiction and indirectly endorse the neurophysiological hypothesis that food and drugs stimulate the same brain circuits in the limbic system.

Motor Practice Effects and Sensorimotor Integration in Adults who Stutter: Evidence from Visuomotor Tracking Performance

PubMed Central

Tumanova, Victoria; Zebrowski, Patricia M.; Goodman, Shawn S.; Arenas, Richard M.

2015-01-01

Purpose The purpose of this study was to utilize a visuomotor tracking task, with both the jaw and hand, to add to the literature regarding non-speech motor practice and sensorimotor integration (outside of auditory-motor integration domain) in adults who do (PWS) and do not (PWNS) stutter. Method Participants were 15 PWS (14 males, mean age = 27.0) and 15 PWNS (14 males, mean age = 27.2). Participants tracked both predictable and unpredictable moving targets separately with their jaw and their dominant hand, and accuracy was assessed by calculating phase and amplitude difference between the participant and the target. Motor practice effect was examined by comparing group performance over consecutive tracking trials of predictable conditions as well as within the first trial of same conditions. Results Results showed that compared to PWNS, PWS were not significantly different in matching either the phase (timing) or the amplitude of the target in both jaw and hand tracking of predictable and unpredictable targets. Further, there were no significant between-group differences in motor practice effects for either jaw or hand tracking. Both groups showed improved tracking accuracy within and between the trials. Conclusion Our findings revealed no statistically significant differences in non-speech motor practice effects and integration of sensorimotor feedback between PWS and PWNS, at least in the context of the visuomotor tracking tasks employed in the study. In general, both talker groups exhibited practice effects (i.e., increased accuracy over time) within and between tracking trials during both jaw and hand tracking. Implications for these results are discussed. PMID:25990027

Strength characterization of knee flexor and extensor muscles in Prader-Willi and obese patients

PubMed Central

Capodaglio, Paolo; Vismara, Luca; Menegoni, Francesco; Baccalaro, Gabriele; Galli, Manuela; Grugni, Graziano

2009-01-01

Background despite evidence of an obesity-related disability, there is a lack of objective muscle functional data in overweight subjects. Only few studies provide instrumental strength measurements in non-syndromal obesity, whereas no data about Prader-Willi syndrome (PWS) are reported. The aim of our study was to characterize the lower limb muscle function of patients affected by PWS as compared to non-syndromal obesity and normal-weight subjects. Methods We enrolled 20 obese (O) females (age: 29.1 ± 6.5 years; BMI: 38.1 ± 3.1), 6 PWS females (age: 27.2 ± 4.9 years; BMI: 45.8 ± 4.4) and 14 healthy normal-weight (H) females (age: 30.1 ± 4.7 years; BMI: 21 ± 1.6). Isokinetic strength during knee flexion and extension in both lower limbs at the fixed angular velocities of 60°/s, 180°/s, 240°/s was measured with a Cybex Norm dynamometer. Results the H, O and PWS populations appear to be clearly stratified with regard to muscle strength.: PWS showed the lowest absolute peak torque (PT) for knee flexor and extensor muscles as compared to O (-55%) and H (-47%) (P = 0.00001). O showed significantly higher strength values than H as regard to knee extension only (P = 0.0014). When strength data were normalised by body weight, PWS showed a 50% and a 70% reduction in PT as compared to O and H, respectively. Knee flexors strength values were on average half of those reported for extension in all of the three populations. Conclusion the novel aspect of our study is the determination of objective measures of muscle strength in PWS and the comparison with O and H patients. The objective characterization of muscle function performed in this study provides baseline and outcome measures that may quantify specific strength deficits amendable with tailored rehabilitation programs and monitor effectiveness of treatments. PMID:19419559

Gait initiation and termination strategies in patients with Prader-Willi syndrome.

PubMed

Cimolin, Veronica; Cau, Nicola; Galli, Manuela; Santovito, Cristina; Grugni, Graziano; Capodaglio, Paolo

2017-05-23

Gait Initiation (GI) is a functional task representing one of the first voluntary destabilizing behaviours observed in the development of a locomotor pattern as the whole body centre of mass transitions from a large to a small base of support. Conversely, Gait Termination (GT) consists in the transition from walking to standing which, in everyday life, is a very common movement. Compared to normal walking, it requires higher control of postural stability. For a safe GT, the forward movement of the body has to be slowed down to achieve a stable upright position. Stability requirements have to be fulfilled for safe GT. In individuals with Prader-Willi syndrome (PWS), excessive body weight negatively affects the movement, such as walking and posture, but there are no experimental studies about GI and GT in these individuals. The aim of this study was to quantitatively characterise the strategy of patients with PWS during GI and GT using parameters obtained by the Center of Pressure (CoP) track. Twelve patients with PWS, 20 obese (OG) and 19 healthy individuals (HG) were tested using a force platform during the GI and GT tasks. CoP plots were divided into different phases, and duration, length and velocity of the CoP trace in these phases were calculated and compared for each task. As for GI, the results showed a significant reduction of the task duration and lower velocity and CoP length parameters in PWS, compared to OG and HG. In PWS, those parameters were reduced to a higher degree with respect to the OG. During GT, longer durations, similar to OG, were observed in PWS than HG. Velocity is reduced when compared to OG and HG, especially in medio-lateral direction and in the terminal part of GT. From these data, GI appears to be a demanding task in most of its sub-phases for PWS individuals, while GT seems to require caution only towards the end of the task. Breaking the cycle of gait into the phases of GI and GT and implementing specific exercises focusing on weight

Clinical comparison of 59 Prader-Willi patients with and without the 15(q12) deletion.

PubMed

Wenger, S L; Hanchett, J M; Steele, M W; Maier, B V; Golden, W L

1987-12-01

Fifty-nine patients with Prader-Willi syndrome (PWS) (including three blacks) were enrolled in a behavior modification program including dietary restriction, nutritional education for self-management of food intake, and exercise. Caloric intake for most patients was 700-800 calories per day. The average stay per patient was 5 weeks with a mean weight loss of 6.6 kg. Thirty-one patients (53%) had apparently normal chromosomes compared to 25 patients (42%) with apparent 15(q12) deletion. Three patients had other chromosome abnormalities including two with mosaicism for idic(15)(q11) and one with a de novo apparently balanced translocation t(8q;18q). There were no differences in manifestations or the effects of the behavior modification program between chromosomally normal and abnormal patients. However, the mean weight loss in the 59 PWS patients was less than would have been expected based on their calculated daily caloric requirements suggesting that PWS patients have reduced caloric needs per unit of body weight compared to normal individuals. Supporting this also was that weight maintenance could be accomplished with only 1000 calories per day on the average. In general, behavioral response to the modification program was successful in that tantrum responses, while not eliminated, were reduced in frequency and severity.

Anthropometric adjustments are helpful in the interpretation of BMD and BMC Z-scores of pediatric patients with Prader-Willi syndrome.

PubMed

Hangartner, T N; Short, D F; Eldar-Geva, T; Hirsch, H J; Tiomkin, M; Zimran, A; Gross-Tsur, V

2016-12-01

Anthropometric adjustments of bone measurements are necessary in Prader-Willi syndrome patients to correctly assess the bone status of these patients. This enables physicians to get a more accurate diagnosis of normal versus abnormal bone, allow for early and effective intervention, and achieve better therapeutic results. Bone mineral density (BMD) is decreased in patients with Prader-Willi syndrome (PWS). Because of largely abnormal body height and weight, traditional BMD Z-scores may not provide accurate information in this patient group. The goal of the study was to assess a cohort of individuals with PWS and characterize the development of low bone density based on two adjustment models applied to a dataset of BMD and bone mineral content (BMC) from dual-energy X-ray absorptiometry (DXA) measurements. Fifty-four individuals, aged 5-20 years with genetically confirmed PWS, underwent DXA scans of spine and hip. Thirty-one of them also underwent total body scans. Standard Z-scores were calculated for BMD and BMC of spine and total hip based on race, sex, and age for all patients, as well as of whole body and whole-body less head for those patients with total-body scans. Additional Z-scores were generated based on anthropometric adjustments using weight, height, and percentage body fat and a second model using only weight and height in addition to race, sex, and age. As many PWS patients have abnormal anthropometrics, addition of explanatory variables weight, height, and fat resulted in different bone classifications for many patients. Thus, 25-70 % of overweight patients, previously diagnosed as normal, were subsequently diagnosed as below normal, and 40-60 % of patients with below-normal body height changed from below normal to normal depending on bone parameter. This is the first study to include anthropometric adjustments into the interpretation of BMD and BMC in children and adolescents with PWS. This enables physicians to get a more accurate diagnosis of

What is the value of growth hormone therapy in Prader Willi syndrome?

PubMed

Bridges, Nicola

2014-02-01

Prader Willi syndrome (PWS) is a genetic condition caused by loss of the paternal copy of a region of imprinted genes on chromosome 15. There is severe muscular hypotonia in the neonatal period, with the onset of hyperphagia and food-seeking behaviour in childhood. All individuals with PWS have developmental delay. Without careful control of food intake and the food environment, individuals with PWS become morbidly obese and are likely to die as young adults from the complications of obesity. The aims of growth hormone (GH) treatment in PWS are distinct from the use of GH in other conditions-although GH does increase final height in PWS, the main benefits of treatment are improved body composition and better exercise capacity, which can help with the aim of preventing obesity. GH trials in PWS have demonstrated improved muscle bulk, reduced fat mass and increased levels of physical activity. GH has also been demonstrated to improve attainment of developmental and cognitive milestones in children with PWS. GH treatment appears to change respiratory status in PWS, possibly because of growth of lymphoid tissue at the start of treatment. Respiratory assessment is recommended prior to, and just after starting GH treatment. Ideal age for starting GH is not clear, although there has been a trend towards starting at younger ages. It may be that GH treatment in childhood confers benefits into adult life. There are less data to support continuing GH treatment into adult life.

Changes in body composition, blood lipid profile, and growth factor hormone in a patient with Prader-willi syndrome during 24 weeks of complex exercise: a single case study.

PubMed

Joung, Hee Joung; Lim, In Soo

2018-03-30

Prader-Willi syndrome (PWS) is a genetic disorder characterized by excessive appetite with progressive obesity and growth hormone (GH) deficiency. Excessive eating causes progressive obesity with increased risk of morbidities and mortality. Although GH treatment has beneficial effects on patients with PWS, adverse events have occurred during GH treatment. Exercise potentially has a positive effect on obesity management. The purpose of this research was to examine the effects of 24-week complex exercise program on changes in body composition, blood lipid profiles, and growth factor hormone levels in a patient with PWS. The case study participant was a 23-year-old man with PWS who also had type II diabetes mellitus because of extreme obesity. Complex exercises, including strength and aerobic exercises, were conducted 5 times one week for 60 minutes per session, over 24 weeks. Blood sampling was conducted five times: before and at 8, 16, 20, and 24 weeks after commencement of the exercise program. Weight, fat mass, triglycerides/high-density lipoprotein (TG/HDL) ratio, mean blood glucose, and GH decreased after training. Blood insulin and insulin-like growth factor (IGF-1) levels increased after training. At 15 and 20 weeks, insulin injection was discontinued. Insulin levels increased and average blood glucose decreased to normal levels; IGF-1 increased continuously during the 24-week exercise program. Conclusion] Twenty-four weeks of complex exercises had a positive effect on obesity and diabetes in the patient with PWS. Therefore, long-period complex exercises might be an effective intervention for improvement of metabolic factors in PWS patients. ©2018 The Korean Society for Exercise Nutrition.

Imprinted expression of UBE3A in non-neuronal cells from a Prader–Willi syndrome patient with an atypical deletion

PubMed Central

Martins-Taylor, Kristen; Hsiao, Jack S.; Chen, Pin-Fang; Glatt-Deeley, Heather; De Smith, Adam J.; Blakemore, Alexandra I.F.; Lalande, Marc; Chamberlain, Stormy J.

2014-01-01

Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are two neurodevelopmental disorders most often caused by deletions of the same region of paternally inherited and maternally inherited human chromosome 15q, respectively. AS is a single gene disorder, caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, while PWS is still considered a contiguous gene disorder. Rare individuals with PWS who carry atypical microdeletions on chromosome 15q have narrowed the critical region for this disorder to a 108 kb region that includes the SNORD116 snoRNA cluster and the Imprinted in Prader–Willi (IPW) non-coding RNA. Here we report the derivation of induced pluripotent stem cells (iPSCs) from a PWS patient with an atypical microdeletion that spans the PWS critical region. We show that these iPSCs express brain-specific portions of the transcripts driven by the PWS imprinting center, including the UBE3A antisense transcript (UBE3A-ATS). Furthermore, UBE3A expression is imprinted in most of these iPSCs. These data suggest that UBE3A imprinting in neurons only requires UBE3A-ATS expression, and no other neuron-specific factors. These data also suggest that a boundary element lying within the PWS critical region prevents UBE3A-ATS expression in non-neural tissues. PMID:24363065

"Hungry Eyes": Visual Processing of Food Images in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Key, A. P. F.; Dykens, E. M.

2008-01-01

Background: Prader-Willi syndrome (PWS) is a genetic disorder associated with intellectual disabilities, compulsivity, hyperphagia and increased risks of life-threatening obesity. Food preferences in people with PWS are well documented, but research has yet to focus on other properties of food in PWS, including composition and suitability for…

Effects of exenatide on weight and appetite in overweight adolescents and young adults with Prader-Willi syndrome.

PubMed

Salehi, P; Hsu, I; Azen, C G; Mittelman, S D; Geffner, M E; Jeandron, D

2017-06-01

Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS. The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS. Ten overweight and obese subjects with PWS (13-25 years) were recruited for a 6-month open-label, non-randomized, longitudinal study conducted at Children's Hospital Los Angeles. Exenatide was given using standard diabetes dosing without dietary modifications. Weight, body mass index (BMI), truncal fat, appetite and plasma acylated ghrelin were measured over 6 months. Mixed meal tolerance tests were performed at 0 and 6 months. Appetite scores significantly decreased from baseline (32.2 ± 8.7) after 1, 3 and 6 moths of treatment (27.5 ± 8.8, 25.4 ± 9.3, and 25.4 ± 7.2 respectively; p = 0.004). Hemoglobin A1c decreased significantly after treatment, but weight, BMI z-score and adiposity did not. There was no significant change in ghrelin. This is the first longitudinal investigation of the effects of exenatide in subjects with PWS. It was effective in decreasing appetite, without change in weight or BMI in the short term. Larger, controlled, longer-term trials in patients with PWS are needed to confirm the efficacy and safety of exenatide and to evaluate whether its use might induce weight loss when given in conjunction with behavioural modification. © 2016 World Obesity Federation.

The Need for Control/Comparison Studies in Establishing Diagnostic Indicators: Prader-Willi Syndrome as a Case in Point.

ERIC Educational Resources Information Center

Taylor, Ronald L.; Caldwell, Mary Lou

1990-01-01

The psychometric characteristics of 12 adults with Prader-Willi syndrome (PWS) and a group without PWS but with other similar traits were compared. Results found cognitive, behavioral and educational traits often associated with PWS to be present in both groups, illustrating the importance of control/comparison groups in research establishing…

Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome.

PubMed

Lassi, Glenda; Priano, Lorenzo; Maggi, Silvia; Garcia-Garcia, Celina; Balzani, Edoardo; El-Assawy, Nadia; Pagani, Marco; Tinarelli, Federico; Giardino, Daniela; Mauro, Alessandro; Peters, Jo; Gozzi, Alessandro; Grugni, Graziano; Tucci, Valter

2016-03-01

Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome. We studied sleep in mutant mice that carry a deletion of Snord116 at the orthologous locus (mouse chromosome 7) of the human PWS critical region (PWScr). In particular, we assessed EEG and temperature profiles, across 24-h, in PWScr (m+/p-) heterozygous mutants compared to wild-type littermates. High-resolution magnetic resonance imaging (MRI) was performed to explore morphoanatomical differences according to the genotype. Moreover, we complemented the mouse work by presenting two patients with a diagnosis of PWS and characterized by atypical small deletions of SNORD116. We compared the individual EEG parameters of patients with healthy subjects and with a cohort of obese subjects. By studying the mouse mutant line PWScr(m+/p-), we observed specific rapid eye movement (REM) sleep alterations including abnormal electroencephalograph (EEG) theta waves. Remarkably, we observed identical sleep/EEG defects in the two PWS cases. We report brain morphological abnormalities that are associated with the EEG alterations. In particular, mouse mutants have a bilateral reduction of the gray matter volume in the ventral hippocampus and in the septum areas, which are pivotal structures for maintaining theta rhythms throughout the brain. In PWScr(m+/p-) mice we also observed increased body temperature that is coherent with REM sleep alterations in mice and human patients. Our study indicates that paternally expressed Snord116 is involved in the 24-h regulation of

Sleep Disorders in Adult Sickle Cell Patients

PubMed Central

Sharma, Sunil; Efird, Jimmy T.; Knupp, Charles; Kadali, Renuka; Liles, Darla; Shiue, Kristin; Boettger, Peter; Quan, Stuart F.

2015-01-01

Study Objectives: While sleep apnea has been studied in children with sickle cell disease (SCD), little is known about sleep disorders in adult sickle cell patients. The objective of this study was to evaluate sleep disordered breathing and its polysomnographic characteristics in adult patients with sickle cell disease. Methods: The analysis cohort included 32 consecutive adult SCD patients who underwent a comprehensive sleep evaluation and overnight polysomnography in an accredited sleep center after reporting symptoms suggesting disordered sleep or an Epworth Sleepiness Scale score ≥ 10. Epworth score, sleep parameters, comorbid conditions, and narcotic use were reviewed and compared in patients with and without sleep disordered breathing. SCD complication rates in the two groups also were compared. Results: In adult SCD patients who underwent overnight polysomnography, we report a high prevalence (44%) of sleep disordered breathing. Disease severity was mild to moderate (mean apnea-hypopnea index = 17/h (95% CI: 10–24/h). Concomitant sleep disorders, including insomnia complaints (57%) and delayed sleep-phase syndrome (57%), also were common in this population. In this limited cohort, we did not find increased SCD complications associated with sleep disordered breathing in adult patients with sickle cell disease. Conclusions: A high burden of sleep disordered breathing and other sleep-related complaints were identified in the adult sickle cell population. Our results provide important information on this unique population. Citation: Sharma S, Efird JT, Knupp C, Kadali R, Liles D, Shiue K, Boettger P, Quan SF. Sleep disorders in adult sickle cell patients. J Clin Sleep Med 2015;11(3):219–223. PMID:25515282

Update on flashlamp pumped pulsed dye laser treatment for port wine stains (capillary malformation) patients

PubMed Central

Hsiao, Yen-Chang; Chang, Cheng-Jen

2011-01-01

Background and Aims: Currently, the method of choice for the treatment of port-wine stains is laser photocoagulation. Because of evolving treatment options, it is no longer enough for port-wine stains merely to be lightened through laser treatment. The best course of management consists of the most appropriate laser that will produce the most complete clearing of a lesion in the fewest treatment sessions with the least morbidity. The goal is generally accomplished with the use of yellow-light lasers. Materials (Subjects) and Methods: Absorption of laser energy by melanin causes localized heating in the epidermis, which may, if not controlled, produce permanent complications such as hypertrophic scarring or dyspigmentation. Refinements of the results can be achieved by using the flashlamp-pumped pulsed dye laser (FLPDL) in conjunction with the cryogen spray cooling (CSC) system. In our related studies, the infrared thermal image instrument is used for doctors in determining the optimum laser light dosage and preventing the side effects caused by FLPDL. Topic application of angiogenesis inhibitor (Imiquimod) in conjunction with pulsed dye laser treatment for the PWS patients has been assessed for improvement of FLPDL treatment. Results: We present the clinical effect of FLPDL, and the efficacy and safety of cooled laser treatment of PWS birthmarks. Our clinical outcome in the laser treatment of patients with PWS has been achieved to maximize thermal impact on targeted vessels, while minimizing adverse complications. Conclusions: CSC in conjunction with FLPDL can improve the treatment of PWS. The infrared image instrument is helpful for doctors in determining the optimum laser light dosage. Topic application of angiogenesis inhibitor (Imiquimod) in conjunction with laser treatment for the PWS patients is promising in the near future. PMID:24155536

Mathematical skills in Prader-Willi Syndrome.

PubMed

Bertella, L; Girelli, L; Grugni, G; Marchi, S; Molinari, E; Semenza, C

2005-02-01

This paper investigates mathematical skills in Prader-Willi Syndrome (PWS), a pathological condition because of congenital alterations of chromosome pair 15. The following questions were addressed: (1) Are mathematical skills in PWS relatively more impaired with respect to other cognitive functions (as has been repeatedly but anecdotally reported)?; and (2) What is the nature of the mathematical impairment? The first study employed the Wechsler Adult Intelligence Scale (WAIS) and an extensive battery of cognitive tasks for which norms are known. Both batteries include a mathematical section. The second study used a theoretically motivated series of mathematical tasks specifically designed to individually assess the different cognitive components underlying mathematical skills. Mathematical skills were found to be the most impaired cognitive abilities together with short-term memory capacity. No specific mathematical domain was seen to be unaffected in PWS participants. The clearest deficits observed concern 'syntactic' processes in number transcoding, multiplication, number facts retrieval and calculation procedures. Failure of mathematical skills is the most distinctive feature in the cognitive profile of PWS. However, to determine whether this is indeed a specific pattern of performance related to PWS, results must be compared with those obtained with patients manifesting other genetic disorders.

Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia.

PubMed

Bassett, J K; Chandler, K E; Douzgou, S

2016-08-01

Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

High unacylated ghrelin levels support the concept of anorexia in infants with prader-willi syndrome.

PubMed

Beauloye, Veronique; Diene, Gwenaelle; Kuppens, Renske; Zech, Francis; Winandy, Coralie; Molinas, Catherine; Faye, Sandy; Kieffer, Isabelle; Beckers, Dominique; Nergårdh, Ricard; Hauffa, Berthold; Derycke, Christine; Delhanty, Patrick; Hokken-Koelega, Anita; Tauber, Maithé

2016-05-04

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with different nutritional phases from suckling deficit with failure to thrive to early onset of obesity. Hyperghrelinemia has been described in PWS long before the development of obesity. Ghrelin is found in both acylated (AG) and unacylated (UAG) forms in the circulation. In contrast to AG, UAG has been shown to inhibit food intake and to be elevated in anorexia nervosa. The present project is aiming to determine the underlying mechanisms driving the different nutritional phases in PWS. Measurement of at least 4 h-fasting plasma acylated and unacylated ghrelin in 37 infants with a genetic diagnosis of PWS aged from 1 month to 4 years and in 100 age-matched controls without endocrine disorder recruited prior to minor surgery. One blood sampling was analysed for each patient/control and clinical data were recorded. Eleven PWS infants underwent repetitive blood samples at 3 or 6-month intervals during routine visits. In infants with PWS, AG is not elevated (p = 0.45), UAG is significantly higher (p = 0.0044; confidence interval 1.06;1.33) resulting in a low AG/UAG ratio (p = 0.0056; confidence interval 0.76;0.95) compared to controls. Unlike children and adults with PWS that have high AG and AG/UAG ratio, infants with PWS have elevated UAG that supports the concept of anorexia in the early phases of the disease. The change in AG/UAG ratio possibly drives the switch from failure to thrive to obesity. NCT02529085 .

Sexual dichotomy of gonadal function in Prader-Willi syndrome from early infancy through the fourth decade.

PubMed

Hirsch, H J; Eldar-Geva, T; Bennaroch, F; Pollak, Y; Gross-Tsur, V

2015-11-01

At what age does the type of hypogonadism, namely hypothalamic or primary gonadal defect, become established in men and women with Prader-Willi syndrome (PWS)? The type of hypogonadism becomes established only in late adolescence and early adulthood. The etiology of hypogonadism in PWS is heterogeneous and the clinical expression is variable. Primary testicular failure is common in PWS men, while combinations of ovarian dysfunction and gonadotrophin deficiency are seen in women. This is a prospective study of a cohort of 106 PWS patients followed for a mean duration of 4.5 years. Serial blood samples were obtained and assayed for gonadotrophins, inhibin B, anti-Mullerian hormone (AMH), dehydroepiandrosterone sulfate (DHEAS), testosterone (males), and estradiol (females). Results were compared with normal reference values obtained from the literature. For the purpose of this study, we defined the following age groups: infants <1 year; children 1-10 years; adolescents 11-20 years and adults >20 years. Study participants were 49 males (aged 2 months to 36 years) and 57 females (aged 1 month to 37 years) with genetically confirmed diagnoses of PWS (deletions 60, uniparental disomy 54, imprinting center defect 2) followed in the Israel national multidisciplinary PWS clinic. Serum LH levels were in the normal range (1.0-6.0 mIU/ml) for 7/10 adult men, and high in 3, while FSH (normal range 1.0-6.1 mIU/ml) was elevated (34.4 ± 11.5 mIU/ml) in 6 and normal (3.5 ± 1.6 mIU/ml) in 4 men. Testosterone was low (5.7 ± 3.4 nmol/l) compared with the normal range of 12.0-34.5 nmol/l in the reference population in all men >20 years. AMH showed a normal decrease with age, despite low testosterone levels. Inhibin B was normal (241 ± 105 pg/ml) in infant boys, but low or undetectable in most adult men. Hormonal profiles were more heterogeneous in women than in men. Estradiol was consistently detectable in only 7/13 adult women. Inhibin B was low or undetectable in all PWS females

Genotype and phenotype in patients with Prader-Willi syndrome in Taiwan.

PubMed

Lin, Hsiang-Yu; Lin, Shuan-Pei; Chuang, Chih-Kuang; Chen, Ming-Ren; Yen, Jui-Lung; Lee, Yann-Jinn; Huang, Chi-Yu; Tsai, Li-Ping; Niu, Dau-Ming; Chao, Mei-Chyn; Kuo, Pao-Lin

2007-06-01

Several different genetic defects have been found to result in the characteristic phenotypic expression of Prader-Willi syndrome (PWS). We performed a retrospective analysis of 67 cases of molecularly confirmed PWS diagnosed from January 1980 through July 2006 in five medical centres in Taiwan. Clinical manifestations were compared between patients with deletion and those with maternal uniparental disomy (UPD). Deletion was present in 56 (84%), UPD in 10 (15%), and a probable imprinting centre deletion or imprinting defect in 1 (1%). PWS with deletion was more likely than that with UPD to be characterized by hypogonadism (p < 0.001), small hands and feet (p < 0.001), and hypopigmentation (p < 0.002). Both maternal (p = 0.015) and paternal age (p = 0.021) were higher in the UPD group. No other clinical features differed significantly different between the two groups. In contrast to most Western populations with a higher incidence of UPD, this study of PWS in Taiwan shows a higher incidence of deletion. There may be subtle phenotypic differences between the UPD and deletion genotypes, but its not clear that these are important clinically.

Relations between causal attributions for stuttering and psychological well-being in adults who stutter.

PubMed

Boyle, Michael

2016-02-01

This study attempted to understand the relationship between causal attributions for stuttering and psychological well-being in adults who stutter. The study employed a cross-sectional design using a web survey distribution mode to gain information related to causal attributions and psychological well-being of 348 adults who stutter. Correlation analyses were conducted to determine relationships between participants' causal attributions (i.e. locus of causality, external control, personal control, stability, biological attributions, non-biological attributions) for stuttering and various measures of psychological well-being including self-stigma, self-esteem/self-efficacy, hope, anxiety and depression. Results indicated that higher perceptions of external control of stuttering were related to significantly lower ratings of hope and self-esteem/self-efficacy and higher ratings of anxiety and depression. Higher perceptions of personal control of stuttering were related to significantly lower ratings of self-stigma and higher ratings of hope and self-esteem/self-efficacy. Increased biological attributions were significantly related to higher ratings of permanency and unchangeableness of stuttering and lower ratings of personal control of stuttering. The findings demonstrate the importance of instilling a sense of control in PWS regarding their ability to manage their stuttering. Findings also raise questions regarding the benefits of educating PWS about the biological underpinnings of stuttering.

Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems.

PubMed

D'Angelo, Carla S; Da Paz, José A; Kim, Chong A; Bertola, Débora R; Castro, Claudia I E; Varela, Monica C; Koiffmann, Célia P

2006-01-01

Monosomy 1p36 is one of the most commonly observed mental retardation (MR) syndromes that results in a clinically recognizable phenotype including delayed psychomotor development and/or MR, hypotonia, epilepsy, hearing loss, growth delay, microcephaly, deep-set eyes, flat nasal bridge and pointed chin. Besides, a Prader-Willi syndrome (PWS)-like phenotype has been described in patients with 1p36 monosomy. Forty-one patients presenting hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who tested negative for PWS were investigated by FISH and/or microsatellite markers. Twenty-six were analyzed with a 1p-specific subtelomeric probe, and one terminal deletion was identified. Thirty patients (15 of which also studied by FISH) were investigated by microsatellite markers, and no interstitial 1p36 deletion was found. Our patient presenting the 1p36 deletion did not have the striking features of this monosomy, but her clinical and behavioral features were quite similar to those observed in patients with PWS, except for the presence of normal sucking at birth. The extent of the deletion could be limited to the most terminal 2.5 Mb of 1p36, within the chromosomal region 1p36.33-1p36.32, that is smaller than usually seen in monosomy 1p36 patients. Therefore, chromosome 1p36.33 deletion should be investigated in patients with hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who test negative for PWS.

Dysphonia in adults with developmental stuttering: A descriptive study.

PubMed

Botha, Anél; Ras, Elizbé; Abdoola, Shabnam; Van der Linde, Jeannie

2017-06-26

Persons with stuttering (PWS) often present with other co-occurring conditions. The World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) proposes that it is important to understand the full burden of a health condition. A few studies have explored voice problems among PWS, and the characteristics of voices of PWS are relatively unknown. The importance of conducting future research has been emphasised. This study aimed to describe the vocal characteristics of PWS. Acoustic and perceptual data were collected during a comprehensive voice assessment. The severity of stuttering was also determined. Correlations between the stuttering severity instrument (SSI) and the acoustic measurements were evaluated to determine the significance. Twenty participants were tested for this study. Only two participants (10%) obtained a positive Dysphonia Severity Index (DSI) score of 1.6 or higher, indicating that no dysphonia was present, while 90% of participants (n = 18) scored lower than 1.6, indicating that those participants presented with dysphonia. Some participants presented with weakness (asthenia) of voice (35%), while 65% presented with a slightly strained voice quality. Moderately positive correlations between breathiness and SSI (r = 0.40, p = 0.08) have been reported. In addition, participants with high SSI scores also scored a poor DSI of below 1.6, as observed by a moderate positive correlation between SSI and DSI (r = 0.41). The majority of PWS presented with dysphonia, evident in the perceptual or acoustic parameters of their voices. These results can be used for further investigation to create awareness and to establish intervention strategies for voice disorders among PWS.

Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome.

PubMed

Burnett, Lisa C; LeDuc, Charles A; Sulsona, Carlos R; Paull, Daniel; Rausch, Richard; Eddiry, Sanaa; Carli, Jayne F Martin; Morabito, Michael V; Skowronski, Alicja A; Hubner, Gabriela; Zimmer, Matthew; Wang, Liheng; Day, Robert; Levy, Brynn; Fennoy, Ilene; Dubern, Beatrice; Poitou, Christine; Clement, Karine; Butler, Merlin G; Rosenbaum, Michael; Salles, Jean Pierre; Tauber, Maithe; Driscoll, Daniel J; Egli, Dieter; Leibel, Rudolph L

2017-01-03

Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell-derived (iPSC-derived) neurons. Moreover, Nhlh2 and Pcsk1 expression were reduced in hypothalami of fasted Snord116 paternal knockout (Snord116p-/m+) mice. Hypothalamic Agrp and Npy remained elevated following refeeding in association with relative hyperphagia in Snord116p-/m+ mice. Nhlh2-deficient mice display growth deficiencies as adolescents and hypogonadism, hyperphagia, and obesity as adults. Nhlh2 has also been shown to promote Pcsk1 expression. Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Here, we found that Snord116p-/m+ mice displayed in vivo functional defects in prohormone processing of proinsulin, pro-GH-releasing hormone, and proghrelin in association with reductions in islet, hypothalamic, and stomach PC1 content. Our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency.

Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome

PubMed Central

Burnett, Lisa C.; LeDuc, Charles A.; Sulsona, Carlos R.; Paull, Daniel; Rausch, Richard; Eddiry, Sanaa; Carli, Jayne F. Martin; Morabito, Michael V.; Skowronski, Alicja A.; Hubner, Gabriela; Zimmer, Matthew; Wang, Liheng; Day, Robert; Levy, Brynn; Dubern, Beatrice; Poitou, Christine; Clement, Karine; Rosenbaum, Michael; Salles, Jean Pierre; Tauber, Maithe; Egli, Dieter

2016-01-01

Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell–derived (iPSC-derived) neurons. Moreover, Nhlh2 and Pcsk1 expression were reduced in hypothalami of fasted Snord116 paternal knockout (Snord116p–/m+) mice. Hypothalamic Agrp and Npy remained elevated following refeeding in association with relative hyperphagia in Snord116p–/m+ mice. Nhlh2-deficient mice display growth deficiencies as adolescents and hypogonadism, hyperphagia, and obesity as adults. Nhlh2 has also been shown to promote Pcsk1 expression. Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Here, we found that Snord116p–/m+ mice displayed in vivo functional defects in prohormone processing of proinsulin, pro-GH–releasing hormone, and proghrelin in association with reductions in islet, hypothalamic, and stomach PC1 content. Our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency. PMID:27941249

Heredity of port-wine stains: investigation of families without a RASA1 mutation.

PubMed

Troilius Rubin, Agneta; Lauritzen, Edgar; Ljunggren, Bo; Revencu, Nicole; Vikkula, Mikka; Svensson, Åke

2015-01-01

The prevalence of capillary malformations, also known as port-wine stains (PWS), is 0.3%. Familial segregation can occur. The capillary malformation-arteriovenous malformation (CM-AVM) phenotype is caused by mutations in the RASA1 gene. In PWS familial cases, the inheritance is considered to be autosomal dominant with variable penetrance. Investigation of the heredity of PWS among patients who attended the vascular anomaly section at the Department of Dermatology in Malmoe, Southern Sweden, between 1993 and 2004 and to study the involvement of the RASA1 gene in patients with a positive family history of PWS. A total of 254 patients were examined and given a questionnaire regarding family history of PWS. The first group of 175 patients (109 females and 66 males) reported a negative family history. The other group of 65 patients (46 females and 19 males) reported a positive family history (50% parents or brothers and sisters). The heredity of PWS was 27% (65/240). Twenty-one patients with a positive family history and relatives had no CM-AVM phenotype for mutations in the RASA1 gene. PWS may have a stronger heredity component than it was reported earlier and inheritance should be considered when counseling a patient. RASA1 mutations do not explain the PWS in our patients.

Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.

PubMed

Bravo, Gabriela L; Poje, Albert B; Perissinotti, Iago; Marcondes, Bianca F; Villamar, Mauricio F; Manzardo, Ann M; Luque, Laura; LePage, Jean F; Stafford, Diane; Fregni, Felipe; Butler, Merlin G

2016-03-01

Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P < 0.05, 30 days) and Total Scores (Ƶ = 2.3, P < 0.02, 30 days), and participant ratings of the DHQ Severity (Ƶ = 1.8, P < 0.06, 5 days) and Total Scores (Ƶ = 1.9, P < 0.05, 15 days). These findings support sustained neuromodulatory effects and efficacy of tDCS to reduce food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS. © 2015 Wiley Periodicals, Inc.

Normal aging increases postural preparation errors: Evidence from a two-choice response task with balance constraints.

PubMed

Verrel, Julius; Lisofsky, Nina; Kühn, Simone; Lindenberger, Ulman

2016-02-01

Correlational studies indicate an association between age-related decline in balance and cognitive control, but these functions are rarely addressed within a single task. In this study, we investigate adult age differences in a two-choice response task with balance constraints under three levels of response conflict. Sixteen healthy young (20-30 years) and 16 healthy older adult participants (59-74 years) were cued symbolically (letter L vs. R) to lift either the left or the right foot from the floor in a standing position. Response conflict was manipulated by task-irrelevant visual stimuli showing congruent, incongruent, or no foot lift movement. Preparatory weight shifts (PWS) and foot lift movements were recorded using force plates and optical motion capture. Older adults showed longer response times (foot lift) and more PWS errors than younger adults. Incongruent distractors interfered with performance (greater response time and PWS errors), but this compatibility effect did not reliably differ between age groups. Response time effects of age and compatibility were strongly reduced or absent in trials without PWS errors, and for the onset of the first (erroneous) PWS in trials with preparation error. In addition, in older adults only, compatibility effects in the foot lift task correlated significantly with compatibility effects in the Flanker task. The present results strongly suggest that adult age differences in response latencies in a task with balance constraints are related to age-associated increases in postural preparation errors rather than being an epiphenomenon of general slowing. Copyright © 2015 Elsevier B.V. All rights reserved.

Dermatoglyphic features in Prader-Willi syndrome with respect to chromosomal findings

PubMed Central

Reed, Terry; Butler, Merlin G.

2017-01-01

Dermatoglyphic findings were compared in 38 Prader-Willi syndrome (PWS) patients and 270 normal controls. Twenty-one of the PWS patients had an interstitial deletion of the proximal long arm of chromosome 15 and seventeen PWS cases had normal chromosomes. Findings in PWS are not diagnostic but do show some consistent deviations that can be used in the clinical evaluation of PWS patients. These include a displacement of the axial triradius away from the normal proximal position, an excess of whorls primarily on the thumbs, radial termination of the palmar A mainline, and lack of arches on the big toe. Deletion PWS patients were much more homogeneous than non-deletion cases with respect to plantar patterns. The previously reported deficit of plantar pattern intensity was restricted only to deletion PWS and was characterized by a lack of plantar interdigital II–IV patterns with almost exclusively hallucal distal loops. PMID:6713710

Dietary intake and nutritional status in cancer patients; comparing adults and older adults.

PubMed

Gómez Valiente da Silva, Henyse; Fonseca de Andrade, Camila; Bello Moreira, Annie Seixas

2014-04-01

Evaluate the nutrient intake and nutritional status of food in cancer patients admitted to a university hospital, with comparison of adult and older adult age category. Cross-sectional study. This study involved cancer patients admitted to a hospital in 2010. Dietary habits were collected using a Brazilian food frequency questionnaire. Participants were divided in two groups: adults or older adults and in 4-cancer category: hematologic, lung, gastrointestinal and others. Body Mass Index evaluated nutritional status. A total of 86 patients with a mean age of 56.5 years, with 55% males and 42% older adults were evaluated. The older adult category had a higher frequency of being underweight (24.4% vs 16.3%, p < 0.01) and a lower frequency of being overweight (7% vs. 15.1%, p < 0.01) than adults. Both, adult and older adults had a high frequency of smoking, alcohol consumption and physical inactivity. The older adults had lower consumption of calories, intake of iron and folic acid. Inadequacy of vitamin intake was observed in both groups; respectively, 52%, 43%, 95%, 76% and 88% for Vitamin A, C, D, E and folic acid. The older adults had a higher folic acid and calcium inadequacy than the adults (97% vs 82%, p <0.01; 88% vs 72%, p < 0.01). There was no association of micronutrient intake with cancer, nor with nutritional status. The food intake, macro and micronutrients ingestion is insufficient among cancer individuals. Food intake of older adults was inferior, when compared to the adult category. There was a high prevalence of BMI excess in the adult group and a worst nutritional status in the older adult category. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

A modified MS-PCR approach to diagnose patients with Prader-Willi and Angelman syndrome.

PubMed

Dos Santos, Jéssica Fernandes; Mota, Laís R; Rocha, Pedro Henrique Silva Andrade; Ferreira de Lima, Renata Lúcia L

2016-11-01

Prader-Willi (PWS) and Angelman (AS) syndromes are clinically distinct neurodevelopmental genetic diseases with multiple phenotypic manifestations. They are one of the most common genetic syndromes caused by non-Mendelian inheritance in the form of genomic imprinting, and can be attributable to the loss of gene expression due to imprinting within the chromosomal region 15q11-q13. Clinical diagnosis of PWS and AS is challenging, and the use of molecular and cytomolecular studies is recommended to help in determining the diagnosis of these conditions. The methylation analysis is a sensible approach; however there are several techniques for this purpose, such as the methylation-sensitive polymerase chain reaction (MS-PCR). This study aims to optimize the MS-PCR assay for the diagnosis of potential PWS and AS patients using DNA modified by sodium bisulfite. We used the MS-PCR technique of PCR described by Kosaki et al. (1997) adapted with betaine. All different concentrations of betaine used to amplify the methylated and unmethylated chromosomal region 15q11-q13 on the gene SNRPN showed amplification results, which increased proportionally to the concentration of betaine. The methylation analysis is a technically robust and reproducible screening method for PWS and AS. The MS-PCR assures a faster, cheaper and more efficient method for the primary diagnosis of the SNRPN gene in cases with PWS and AS, and may detect all of the three associated genetic abnormalities: deletion, uniparental disomy or imprinting errors.

A case of acquired port wine stain: an association with repeated sunburn?

PubMed

Seremet, Sila; Benar, Elif B; Afsar, Fatma Sule; Calli, Aylin; Ulusarac, Ozlem

2016-10-01

Unlike congenital port wine stain (PWS), an acquired PWS is a rare vascular lesion that develops later in life. Although solar damage is associated with acquired PWS, there is no reported case of acquired PWS after sunburn in the literature. We report a case of a 54-year-old man diagnosed with acquired PWS possibly caused by repeated sunburn. We recommended laser treatment to our patient; however, the patient did not chose to receive any treatment. Our case demonstrates a possible rare occurrence of an acquired PWS after sunburn with larger lesions and more diffuse distribution. For this reason, our case differs from other acquired PWS cases. © 2016 The International Society of Dermatology.

Study of inhaler technique in asthma patients: differences between pediatric and adult patients

PubMed Central

Manríquez, Pablo; Acuña, Ana María; Muñoz, Luis; Reyes, Alvaro

2015-01-01

Objective: Inhaler technique comprises a set of procedures for drug delivery to the respiratory system. The oral inhalation of medications is the first-line treatment for lung diseases. Using the proper inhaler technique ensures sufficient drug deposition in the distal airways, optimizing therapeutic effects and reducing side effects. The purposes of this study were to assess inhaler technique in pediatric and adult patients with asthma; to determine the most common errors in each group of patients; and to compare the results between the two groups. Methods: This was a descriptive cross-sectional study. Using a ten-step protocol, we assessed inhaler technique in 135 pediatric asthma patients and 128 adult asthma patients. Results: The most common error among the pediatric patients was failing to execute a 10-s breath-hold after inhalation, whereas the most common error among the adult patients was failing to exhale fully before using the inhaler. Conclusions: Pediatric asthma patients appear to perform most of the inhaler technique steps correctly. However, the same does not seem to be true for adult patients. PMID:26578130

Clinical Features of Adult Patients Admitted to Pediatric Wards in Japan.

PubMed

Michihata, Nobuaki; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo

2015-10-01

Pediatricians generally need to treat adult patients who require long-term care for pediatric diseases. However, little is known about the characteristics of adult patients in pediatric wards. Using a national inpatient database, the aim of this study was to determine the clinical details of adult patients admitted to pediatric wards in Japanese acute-care hospitals. We extracted all inpatients aged ≥19 years who were admitted to pediatric departments in Japan from April 2012 to March 2013. We examined the patients' main diagnoses and the use of life-supporting home medical devices. Of 417,352 patients admitted to pediatric wards during the study period, we identified 4,729 (1.1%) adult patients. The major diagnoses of the adult patients were malignancy, congenital heart disease, epilepsy, and cerebral palsy. More than 35% of the patients with cerebral palsy had a tracheostomy tube, gastrostomy tube, home central venous alimentation, or home respirator. More than 20% of patients aged ≥40 years in pediatric wards had adult diseases, including ischemic heart diseases, cerebrovascular diseases, and adult malignancy. Many adult patients in pediatric wards had adult diseases. It is essential to establish a disease-oriented support system for adults with chronic conditions that originated in their childhood. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

High levels of caregiver burden in Prader-Willi syndrome

PubMed Central

Farrar, Evan; Comtois, Katherine Anne; Strong, Theresa V.

2018-01-01

Objectives Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder that is characterized by hyperphagia, developmental delay, incomplete sexual development, mild-to-moderate intellectual disability, and a variety of challenging behavioral and psychiatric symptoms. The characteristics of PWS can be difficult for caregivers to cope with and are likely to cause significant and long- term caregiver burden. The current study examined burden in 142 caregivers of children and adults with PWS living in the US using the Zarit Burden Interview (ZBI). The study aimed to measure the level of burden in caregivers of individuals with PWS, to explore the impact of PWS on caregiver quality of life, and to assess ZBI as an indicator of that impact. Results Caregivers participating in this study were predominantly mothers, 30–59 years old, non-Hispanic Whites, married or in a relationship, with an annual household income slightly distributed towards higher income. Nearly 90% of the caregiver`s children with PWS lived at home. Caregivers experienced high caregiver burden with an average ZBI score of 44.4 ± 15.4. ZBI scores were highest for caregivers of teenage and young adult individuals with PWS (49.2 ± 14.6 and 49.2 ± 14.1, respectively), while those caring for older adults (>30) and the youngest age group had lower scores (38.6 ±10.5 and 34.8 ±12.5, respectively). Caregivers reported that caring for a person with PWS negatively impacted their romantic relationship, ability to work, sleep, and mood. Whereas we did not find strong correlations between family income or level of help the caregiver receives and ZBI scores, the results showed significant correlations and a linear relationship between ZBI scores and caregiver depressed mood, feelings of anxiety, negative romantic relationship impact, as well as sleep and work disruption. Conclusions Our study reveals that PWS incurs high caregiver burden and impacts many aspects of the lives of caregiver. We

High levels of caregiver burden in Prader-Willi syndrome.

PubMed

Kayadjanian, Nathalie; Schwartz, Lauren; Farrar, Evan; Comtois, Katherine Anne; Strong, Theresa V

2018-01-01

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder that is characterized by hyperphagia, developmental delay, incomplete sexual development, mild-to-moderate intellectual disability, and a variety of challenging behavioral and psychiatric symptoms. The characteristics of PWS can be difficult for caregivers to cope with and are likely to cause significant and long- term caregiver burden. The current study examined burden in 142 caregivers of children and adults with PWS living in the US using the Zarit Burden Interview (ZBI). The study aimed to measure the level of burden in caregivers of individuals with PWS, to explore the impact of PWS on caregiver quality of life, and to assess ZBI as an indicator of that impact. Caregivers participating in this study were predominantly mothers, 30-59 years old, non-Hispanic Whites, married or in a relationship, with an annual household income slightly distributed towards higher income. Nearly 90% of the caregiver`s children with PWS lived at home. Caregivers experienced high caregiver burden with an average ZBI score of 44.4 ± 15.4. ZBI scores were highest for caregivers of teenage and young adult individuals with PWS (49.2 ± 14.6 and 49.2 ± 14.1, respectively), while those caring for older adults (>30) and the youngest age group had lower scores (38.6 ±10.5 and 34.8 ±12.5, respectively). Caregivers reported that caring for a person with PWS negatively impacted their romantic relationship, ability to work, sleep, and mood. Whereas we did not find strong correlations between family income or level of help the caregiver receives and ZBI scores, the results showed significant correlations and a linear relationship between ZBI scores and caregiver depressed mood, feelings of anxiety, negative romantic relationship impact, as well as sleep and work disruption. Our study reveals that PWS incurs high caregiver burden and impacts many aspects of the lives of caregiver. We identified the ZBI as a good

The usefulness of biliopancreatic diversion/Scopinaro operation in treatment of patients with Prader-Willi syndrome

PubMed Central

Michalik, Maciej; Frask, Agata; Zdrojewski, Michal; Doboszynska, Anna

2015-01-01

Prader-Willi syndrome (PWS) is the most common form of obesity with a genetic basis. The short expected survival time due to numerous accompanying diseases and their complications is the reason for research on the maximally efficient method of treatment of obesity in this syndrome. Undertaken attempts of conservative treatment, for example with somatostatin, are ineffective. It seems that the only effective treatment of obesity in this syndrome may be surgical. In this article we present 2 cases of patients with PWS who underwent surgery consisting of biliopancreatic diversion (BPD)/Scopinaro procedure. The BPD/Scopinaro operation in selected cases of disciplined patients with a co-operative family, which we find of key importance, can be considered as one option of treatment of this syndrome in patients with prior neglect of conservative treatment. PMID:26240637

Fractal dimension approach in postural control of subjects with Prader-Willi Syndrome

PubMed Central

2011-01-01

Background Static posturography is user-friendly technique suitable for the study of the centre of pressure (CoP) trajectory. However, the utility of static posturography in clinical practice is somehow limited and there is a need for reliable approaches to extract physiologically meaningful information from stabilograms. The aim of this study was to quantify the postural strategy of Prader-Willi patients with the fractal dimension technique in addition to the CoP trajectory analysis in time and frequency domain. Methods 11 adult patients affected by Prader-Willi Syndrome (PWS) and 20 age-matched individuals (Control group: CG) were included in this study. Postural acquisitions were conducted by means of a force platform and the participants were required to stand barefoot on the platform with eyes open and heels at standardized distance and position for 30 seconds. Platform data were analysed in time and frequency domain. Fractal Dimension (FD) was also computed. Results The analysis of CoP vs. time showed that in PWS participants all the parameters were statistically different from CG, with greater displacements along both the antero-posterior and medio-lateral direction and longer CoP tracks. As for frequency analysis, our data showed no significant differences between PWS and CG. FD evidenced that PWS individuals were characterized by greater value in comparison with CG. Conclusions Our data showed that while the analysis in the frequency domain did not seem to explain the postural deficit in PWS, the FD method appears to provide a more informative description of it and to complement and integrate the time domain analysis. PMID:21854639

Laser Doppler line scanner for monitoring skin perfusion changes of port wine stains during vascular-targeted photodynamic therapy

NASA Astrophysics Data System (ADS)

Chen, Defu; Ren, Jie; Wang, Ying; Gu, Ying

2014-11-01

Vascular-targeted photodynamic therapy (V-PDT) is known to be an effective therapeutic modality for the treatment of port wine stains (PWS). Monitoring the PWS microvascular response to the V-PDT is crucial for improving the effectiveness of PWS treatment. The objective of this study was to use laser Doppler technique to directly assess the skin perfusion in PWS before and during V-PDT. In this study, 30 patients with PWS were treated with V-PDT. A commercially laser Doppler line scanner (LDLS) was used to record the skin perfusion of PWS immediately before; and at 1, 3, 5, 7, 10, 15 and 20 minutes during V-PDT treatment. Our results showed that there was substantial inter- and intra-patient perfusion heterogeneity in PWS lesion. Before V-PDT, the comparison of skin perfusion in PWS and contralateral healthy control normal skin indicated that PWS skin perfusion could be larger than, or occasionally equivalent to, that of control normal skin. During V-PDT, the skin perfusion in PWS significantly increased after the initiation of V-PDT treatment, then reached a peak within 10 minutes, followed by a slowly decrease to a relatively lower level. Furthermore, the time for reaching peak and the subsequent magnitude of decrease in skin perfusion varied with different patients, as well as different PWS lesion locations. In conclusion, the LDLS system is capable of assessing skin perfusion changes in PWS during V-PDT, and has potential for elucidating the mechanisms of PWS microvascular response to V-PDT.

Risk assessment of medically assisted reproduction and advanced maternal ages in the development of Prader-Willi syndrome due to UPD(15)mat.

PubMed

Matsubara, K; Murakami, N; Fukami, M; Kagami, M; Nagai, T; Ogata, T

2016-05-01

Recent studies have suggested that disomic oocyte-mediated uniparental disomy 15 (UPD(15)mat) is increased in patients with Prader-Willi syndrome (PWS) born after medically assisted reproduction (MAR). However, it remains unknown whether the increase is primarily due to MAR procedure itself or advanced maternal childbearing ages as a predisposing factor for the disomic oocyte production. To examine this matter, we studied 122 naturally conceived PWS patients (PWS-NC group) and 13 MAR-conceived patients (PWS-MAR group). The relative frequency of disomic oocyte-mediated UPD(15)mat was significantly higher in PWS-MAR group than in PWS-NC group (7/13 vs 20/122, p = 0.0045), and the maternal childbearing ages were significantly higher in PWS-MAR group than in PWS-NC group [median (range), 38 (26-45) vs 30 (19-42), p = 0.0015]. However, the logistic regression analysis revealed no significant association between the occurrence of disomic oocyte-mediated UPD(15)mat and MAR, after adjusting for childbearing age (p = 0.25). Consistent with this, while the frequency of assisted reproductive technology (ART)-conceived livebirths was higher in the PWS patients than in the Japanese general population (6.4% vs 1.1%, p = 0.00018), the distribution of childbearing ages was significantly skewed to the increased ages in the PWS patients (p < 2.2 × 10(-16) ). These results argue against a positive association of MAR procedure itself with the development of UPD(15)mat. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Speech and Nonspeech Sequence Skill Learning in Adults Who Stutter

ERIC Educational Resources Information Center

Smits-Bandstra, Sarah; De Nil, Luc; Saint-Cyr, Jean A.

2006-01-01

Two studies compared the speech and nonspeech sequence skill learning of nine persons who stutter (PWS) and nine matched fluent speakers (PNS). Sequence skill learning was defined as a continuing process of stable improvement in speed and/or accuracy of sequencing performance over practice and was measured by comparing PWS's and PNS's performance…

Hedonic eating in Prader–Willi syndrome is associated with blunted PYY secretion

PubMed Central

Rigamonti, A. E.; Bini, S.; Piscitelli, F.; Lauritano, A.; Di Marzo, V.; Vanetti, C.; Agosti, F.; De Col, A.; Lucchetti, E.; Grugni, G.; Sartorio, A.

2017-01-01

ABSTRACT Hedonic and homeostatic hunger represent two different forms of eating: just for pleasure or following energy deprivation, respectively. Consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and some specific endocannabinoids in normal-weight subjects and patients with morbid obesity. To date, the effects of palatable food on these mediators in Prader–Willi syndrome (PWS) are still unknown. To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, cholecystokinin (CCK), peptide YY (PYY), anandamide (AEA), 2-arachidonoyl-glycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) in eight satiated adult PWS patients after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same macronutrient composition. Evaluation of hunger and satiety was also performed by visual analogic scale. The anticipatory phase and the consumption of food for pleasure were associated with decreased circulating levels of PYY. An increase in PEA levels was also observed. By contrast, circulating levels of ghrelin, CCK, AEA, 2-AG and OEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were similar in the hedonic and non-palatable sessions. In conclusion, when motivation to eat is promoted by highly palatable foods, a depressed post-prandial PYY secretion is observed in PWS. Although preliminary, these findings seem to hypothesize a possible role of PYY agonists in the management of PWS patients. Abbreviations: AEA, Anandamide; 2-AG, 2-arachidonoyl-glycerol; CB1, cannabinoid receptor type 1; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; PWS: Prader-Willi syndrome; VAS, visual analog scales PMID:28659728

Diagnosis of Adult Patients with Cystic Fibrosis.

PubMed

Nick, Jerry A; Nichols, David P

2016-03-01

The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia.

PubMed

Bista, Rajan K; Brentnall, Teresa A; Bronner, Mary P; Langmead, Christopher J; Brand, Randall E; Liu, Yang

2011-12-01

Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting, and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study was to evaluate whether optical markers of rectal mucosa derived from a novel optical technique, partial-wave spectroscopic microscopy (PWS), could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. Banked frozen nondysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross-validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

PubMed Central

Tony, Michèle; Höybye, Charlotte; Allen, David B.; Tauber, Maïthé; Christiansen, Jens Sandahl; Ambler, Geoffrey R.; Battista, Renaldo; Beauloye, Véronique; Berall, Glenn; Biller, Beverly M. K.; Butler, Merlin G.; Cassidy, Suzanne B.; Chihara, Kazuo; Cohen, Pinchas; Craig, Maria; Farholt, Stense; Goetghebeur, Mireille; Goldstone, Anthony P.; Greggi, Tiziana; Grugni, Graziano; Hokken-Koelega, Anita C.; Johannsson, Gudmundur; Johnson, Keegan; Kemper, Alex; Kopchick, John J.; Malozowski, Saul; Miller, Jennifer; Mogul, Harriette R.; Muscatelli, Françoise; Nergårdh, Ricard; Nicholls, Robert D.; Radovick, Sally; Rosenthal, M. Sara; Sipilä, Ilkka; Tarride, Jean-Eric; Vogels, Annick; Waters, Michael J.

2013-01-01

Context: Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events. Objective: The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS. Evidence: We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries. Methodology: Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). Conclusions: Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as

GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome.

PubMed

Deal, Cheri L; Tony, Michèle; Höybye, Charlotte; Allen, David B; Tauber, Maïthé; Christiansen, Jens Sandahl

2013-06-01

Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events. The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS. We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries. Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN). Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.

Third Prader-Willi syndrome phenotype due to maternal uniparental disomy 15 with mosaic trisomy 15.

PubMed

Olander, E; Stamberg, J; Steinberg, L; Wulfsberg, E A

2000-07-31

We report on a boy with mosaicism for trisomy 15 and Prader-Willi syndrome (PWS) due to maternal isodisomy for chromosome 15. His phenotype is consistent with PWS and trisomy 15 mosaicism. Although our patient is unusual in having maternal isodisomy rather than the more common maternal heterodisomy, we think that his more severe PWS phenotype is due to his trisomy 15 mosaicism rather than to homozygosity for deleterious chromosome 15 genes. We propose that individuals with PWS have one of three similar but distinctive phenotypes depending on the cause of their condition. Patients with paternal deletions have the typical PWS phenotype, patients with maternal UPD have a slightly milder phenotype with better cognitive function, and those with maternal UPD and mosaic trisomy 15 have the most severe phenotype with a high incidence of congenital heart disease. These phenotype-genotype differences are useful to guide the work-up of patients with suspected PWS and to provide prognostic counseling for families.

Participation of family members and quality of patient care - the perspective of adult surgical patients.

PubMed

Leino-Kilpi, Helena; Gröndahl, Weronica; Katajisto, Jouko; Nurminen, Matti; Suhonen, Riitta

2016-08-01

The aim of this study is to describe the participation of family members in the care of Finnish adult surgical patients and the connection of the participation with the quality of patient care as perceived by surgical patients. The family members of adult surgical patients are important. Earlier studies vary concerning the nature of participation, its meaning and the connection of participation with patient-centred quality of care. In this study, we aim to produce new knowledge about adult surgical patients whose family members have participated in their care. This was a cross-sectional descriptive survey study. The data were collected among adult surgical patients (N = 481) before being discharged home from hospital with two instruments: the Good Nursing Care scale and the Received Knowledge of Hospital Patients. Based on the results, most adult surgical patients report that family members participate in their care. Participation was connected with received knowledge and preconditions of care, which are components of the quality of patient care. In future, testing of different solutions for improving the participation of surgical patients' family members in patient care should be implemented. Furthermore, the preconditions of family members' participation in care and the concept of participation should be analysed to emphasise the active role of family members. The results emphasised the importance of family members for the patients in surgical care. Family members' participation is connected with the quality of patient care. © 2016 John Wiley & Sons Ltd.

Laparoscopic sleeve gastrectomy in children and adolescents with Prader-Willi syndrome: a matched-control study.

PubMed

Alqahtani, Aayed R; Elahmedi, Mohamed O; Al Qahtani, Awadh R; Lee, Jaehoon; Butler, Merlin G

2016-01-01

Obesity is a leading cause of mortality and morbidity in Prader-Willi syndrome (PWS). To study weight loss and growth after laparoscopic sleeve gastrectomy (LSG) in pediatric patients with PWS compared with those without the syndrome. Academic center with a standardized care pathway for pediatric bariatric surgery as a part of a prospective clinical outcome study on children and adolescents undergoing weight loss surgery. Clinical data of all PWS patients who underwent LSG were abstracted from our prospective database, which included all pediatric patients who underwent bariatric surgery. These data were then compared with a 1:3 non-PWS group matched for age, gender, and body mass index (BMI). Data for up to 5 years follow-up were analyzed. The 24 PWS patients (mean age 10.7; 6<8 yr old, range 4.9-18) had a preoperative BMI of 46.2 ± 12.2 kg/m(2). All PWS patients had obstructive sleep apnea (OSA), 62% had dyslipidemia, 43% had hypertension, and 29% had diabetes mellitus. BMI change at the first, second, third, fourth, and fifth annual visits was -14.7 (n = 22 patients), -15.0 (n = 18), 12.2 (n = 13), -12.7 (n = 11), and -10.7 (n = 7), respectively, in the PWS group, whereas the non-PWS group had a BMI change of -15.9 (n = 67), -18.0 (n = 50), -18.4 (n = 47), -18.9 (n = 26), and -19.0 (n = 20), respectively. No significant difference was observed in postoperative BMI change (P = .2-.7) or growth (postoperative height z-score P value at each annual visit = .2-.8); 95% of co-morbidities in both groups were in remission or improved, with no significant difference in the rate of co-morbidity resolution after surgery (P = .73). One PWS patient was readmitted 5 years after surgery with recurrence of OSA and heart failure. No other readmissions occurred, and there were no reoperations, postoperative leaks, or other complications. No mortality or major morbidity was observed during the 5 years of follow-up. Among the PWS patients who reached their follow-up visit time

Executive functions and Prader-Willi syndrome: global deficit linked with intellectual level and syndrome-specific associations.

PubMed

Chevalère, Johann; Postal, Virginie; Jauregui, Joseba; Copet, Pierre; Laurier, Virginie; Thuilleaux, Denise

2015-05-01

The aim of this study was to support the growing evidence suggesting that Prader-Willi Syndrome (PWS) might present with an impairment of executive functions (EFs) and to investigate whether this impairment is specific to patients with PWS or due to their intellectual disability (ID). Six tasks were administered to assess EFs (inhibition, switching, updating, cognitive estimation, and planning) to 17 patients with PWS and 17 age-matched healthy individuals. Performance was significantly impaired in the PWS group on all EFs and after controlling for IQ level, intergroup differences remained only for switching and cognitive estimation. In conclusion, PWS seems to be associated with a global impairment of EFs that appears to be closely linked with intellectual impairment but also with the PWS itself.

The High Direct Medical Costs of Prader-Willi Syndrome.

PubMed

Shoffstall, Andrew J; Gaebler, Julia A; Kreher, Nerissa C; Niecko, Timothy; Douglas, Diah; Strong, Theresa V; Miller, Jennifer L; Stafford, Diane E; Butler, Merlin G

2016-08-01

To assess medical resource utilization associated with Prader-Willi syndrome (PWS) in the US, hypothesized to be greater relative to a matched control group without PWS. We used a retrospective case-matched control design and longitudinal US administrative claims data (MarketScan) during a 5-year enrollment period (2009-2014). Patients with PWS were identified by Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 759.81. Controls were matched on age, sex, and payer type. Outcomes included total, outpatient, inpatient and prescription costs. After matching and application of inclusion/exclusion criteria, we identified 2030 patients with PWS (1161 commercial, 38 Medicare supplemental, and 831 Medicaid). Commercially insured patients with PWS (median age 10 years) had 8.8-times greater total annual direct medical costs than their counterparts without PWS (median age 10 years: median costs $14 907 vs $819; P < .0001; mean costs: $28 712 vs $3246). Outpatient care comprised the largest portion of medical resource utilization for enrollees with and without PWS (median $5605 vs $675; P < .0001; mean $11 032 vs $1804), followed by mean annual inpatient and medication costs, which were $10 879 vs $1015 (P < .001) and $6801 vs $428 (P < .001), respectively. Total annual direct medical costs were ∼42% greater for Medicaid-insured patients with PWS than their commercially insured counterparts, an increase partly explained by claims for Medicaid Waiver day and residential habilitation. Direct medical resource utilization was considerably greater among patients with PWS than members without the condition. This study provides a first step toward quantifying the financial burden of PWS posed to individuals, families, and society. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Using Optical Markers of Non-dysplastic Rectal Epithelial Cells to Identify Patients With Ulcerative Colitis (UC) - Associated Neoplasia

PubMed Central

Bista, Rajan K.; Brentnall, Teresa A.; Bronner, Mary P.; Langmead, Christopher J.; Brand, Randall E.; Liu, Yang

2011-01-01

BACKGROUND Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study is to evaluate whether optical markers of rectal mucosa derived from a novel optical technique – partial-wave spectroscopic microscopy (PWS) could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. METHODS Banked frozen non-dysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. RESULTS We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. CONCLUSIONS Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for a high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. PMID:21351200

Asperger Syndrome: a frequent comorbidity in first diagnosed adult ADHD patients?

PubMed

Roy, Mandy; Ohlmeier, Martin D; Osterhagen, Lasse; Prox-Vagedes, Vanessa; Dillo, Wolfgang

2013-06-01

Because adult ADHD is often accompanied by psychiatric comorbidities, the diagnostic process should include a thorough investigation for comorbid disorders. Asperger-Syndrome is rarely reported in adult ADHD and commonly little attention is paid to this possible comorbidity. We investigated 53 adult ADHD-patients which visited our out patient clinic for first ADHD-diagnosis (17 females, 36 males; range of age: 18-56 years) for the frequency of a comorbid Asperger-Syndrome. Diagnosis of this autism-spectrum disorder was confirmed by applying the appropriate DSM-IV-criteria. Additionally we tested the power of the two screening-instruments "Autism-spectrum quotient" (AQ) and "Empathy quotient" (EQ) by Baron-Cohen for screening Asperger-Syndrome in adult ADHD. Eight ADHD-patients were diagnosed with a comorbid Asperger-Syndrome (15.1%). The difference in AQ- and EQ-scores between pure ADHD-patients and comorbid patients was analysed, showing significantly higher scores in AQ and significant lower scores in EQ in comorbid patients. Results show that the frequency of Asperger-Syndrome seems to be substantially increased in adult ADHD (versus the prevalence of 0.06% in the general population), indicating that investigators of adult ADHD should also be attentive to autism-spectrum disorders. Especially the AQ seems to be a potential screening instrument for Asperger-Syndrome in adult ADHD-patients.

Wellness during Midlife and Older Adulthood: A Different Perception

ERIC Educational Resources Information Center

Foster, Thomas W.; Levitov, Justin E.

2012-01-01

The authors explored how midlifers and older adults perceive wellness by factor analyzing the Perceived Wellness Survey (PWS; Adams, Bezner, & Steinhardt, 1997). Results indicated a 4-factor solution different from the 6 originally proposed wellness dimensions of the PWS, suggesting that wellness perceptions change as people age. Suggestions…

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial.

PubMed

Allas, Soraya; Caixàs, Assumpta; Poitou, Christine; Coupaye, Muriel; Thuilleaux, Denise; Lorenzini, Françoise; Diene, Gwenaëlle; Crinò, Antonino; Illouz, Frédéric; Grugni, Graziano; Potvin, Diane; Bocchini, Sarah; Delale, Thomas; Abribat, Thierry; Tauber, Maithé

2018-01-01

Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial

PubMed Central

Caixàs, Assumpta; Poitou, Christine; Coupaye, Muriel; Thuilleaux, Denise; Lorenzini, Françoise; Diene, Gwenaëlle; Crinò, Antonino; Illouz, Frédéric; Grugni, Graziano; Potvin, Diane; Bocchini, Sarah; Delale, Thomas; Abribat, Thierry; Tauber, Maithé

2018-01-01

Context and objective Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials. PMID:29320575

Behavioral and psychiatric disorders in Prader-Willi syndrome: a population study in Japan.

PubMed

Hiraiwa, Rika; Maegaki, Yoshihiro; Oka, Akira; Ohno, Kousaku

2007-10-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder characterized by mental retardation and distinct physical, behavioral, and psychiatric features. Based on parents' questionnaires, we examined the prevalence of behavioral and psychiatric disorders of 165 persons with PWS aged 2-31 years in Japan. The data were analyzed comparing four different age groups with PWS: group 1, 2-5 years (n=34); group 2, 6-11 years (n=57); group 3, 12-17 years (n=45); and group 4, 18-31 years (n=29). Further, we compared the results of our PWS group 4 with those of 42 age-, gender-, and intelligence level-matched intellectual disability (ID) individuals without PWS. Our results showed that repetitive speech and stubbornness were prominent from early childhood and other behavioral problems such as hyperphagia, stealing food, temper tantrums, lying, and emotional lability tended to be more frequent with age among persons with PWS. Moreover, young adults with PWS have significantly higher rates of behavioral and psychiatric disorders than IDs without PWS, such as stubbornness, hyperphagia, temper tantrums, self-injurious behavior (skin picking), hypersomnia, inactivity, and delusion. Degree of obesity was not necessarily related to behavioral and psychiatric features associated with PWS. Our findings revealed that persons with PWS are more vulnerable to behavioral and psychiatric disorders particularly in young adulthood compared to those with ID from other etiologies in Japan.

Early maladaptive schemas in adult patients with attention deficit hyperactivity disorder.

PubMed

Philipsen, Alexandra; Lam, Alexandra P; Breit, Sigrid; Lücke, Caroline; Müller, Helge H; Matthies, Swantje

2017-06-01

The main purpose of this study was to examine whether adult patients with attention deficit hyperactivity disorder (ADHD) demonstrate sets of dysfunctional cognitive beliefs and behavioural tendencies according to Jeffrey Young's schema-focused therapy model. Sets of dysfunctional beliefs (maladaptive schemas) were assessed with the Young Schema Questionnaire (YSQ-S2) in 78 adult ADHD patients and 80 control subjects. Patients with ADHD scored significantly higher than the control group on almost all maladaptive schemas. The 'Failure', 'Defectiveness/Shame', 'Subjugation' and 'Emotional Deprivation' schemas were most pronounced in adult ADHD patients, while only 'Vulnerability to Harm or Illness' did not differ between the two groups. The schemas which were most pronounced in adult patients with ADHD correspond well with their learning histories and core symptoms. By demonstrating the existence of early maladaptive schemas in adults suffering from ADHD, this study suggests that schema theory may usefully be applied to adult ADHD therapy.

Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome.

PubMed

Miller, Jennifer L; James, G Andrew; Goldstone, Anthony P; Couch, Jessica A; He, Guojun; Driscoll, Daniel J; Liu, Yijun

2007-06-01

Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine Stains Compared with Single Pass: A Randomized Comparison with Histological Examination.

PubMed

Yu, Wenxin; Zhu, Jiafang; Wang, Lizhen; Qiu, Yajing; Chen, Yijie; Yang, Xi; Chang, Lei; Ma, Gang; Lin, Xiaoxi

2018-03-27

To compare the efficacy and safety of double-pass pulsed dye laser (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS). The increase in the extent of vascular damage attributed to the use of double-pass techniques for PWS remains inconclusive. A prospective, side-by-side comparison with a histological study for virgin PWS is still lacking. Twenty-one patients (11 flat PWS, 10 hypertrophic PWS) with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was divided into three treatment sites: SWL, DWL, and untreated control. Chromametric and visual evaluation of the efficacy and evaluation of side effects were conducted 3 months after final treatment. Biopsies were taken at the treated sites immediately posttreatment. Chromametric and visual evaluation suggested that DWL sites showed no significant improvement compared with SWL (p > 0.05) in treating PWS. The mean depth of photothermal damage to the vessels was limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side effects were not observed in any patients. Double-pass PDL does not enhance PWS clearance. To improve the clearance of PWS lesions, either the depth of laser penetration should be increased or greater photothermal damage to vessels should be generated.

Patient engagement in research with older adults with cancer.

PubMed

Puts, Martine T E; Sattar, Schroder; Ghodraty-Jabloo, Vida; Hsu, Tina; Fitch, Marg; Szumacher, Ewa; Ayala, Ana Patricia; Alibhai, Shabbir M H

2017-11-01

Cancer is a disease that mostly affects older adults. Older adults have been under-represented in clinical cancer research. Around the world there is a push for patient engagement on study teams as it is anticipated to improve study design, recruitment and dissemination of findings. In the current overview we examined the evidence with regard to: 1) the history of patient engagement in research and frameworks developed; 2) impact of patient engagement on patient and research outcomes; 3) use of patient engagement in geriatrics and oncology, 4) recommendations for successful engagement; and 5) gaps in the literature that should be studied further. A narrative review was conducted. Articles published in English were searched in Medline with the help of a librarian. Patient engagement has been shown to improve the conduct of studies by making the study design more relevant and feasible, and improving recruitment rates and uptake of research findings by patients. However, the best way to engage patients is not clear yet. Several resources have been developed to support researchers engaging older adults with cancer in research. While patient engagement in research seems promising to improve study outcomes, little evidence is available thus far in geriatric oncology settings. Several gaps in the literature are identified that should be further studied to determine the value of, and best approaches to, patient engagement with older adults with cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

EEG Mu (µ) rhythm spectra and oscillatory activity differentiate stuttering from non-stuttering adults.

PubMed

Saltuklaroglu, Tim; Harkrider, Ashley W; Thornton, David; Jenson, David; Kittilstved, Tiffani

2017-06-01

Stuttering is linked to sensorimotor deficits related to internal modeling mechanisms. This study compared spectral power and oscillatory activity of EEG mu (μ) rhythms between persons who stutter (PWS) and controls in listening and auditory discrimination tasks. EEG data were analyzed from passive listening in noise and accurate (same/different) discrimination of tones or syllables in quiet and noisy backgrounds. Independent component analysis identified left and/or right μ rhythms with characteristic alpha (α) and beta (β) peaks localized to premotor/motor regions in 23 of 27 people who stutter (PWS) and 24 of 27 controls. PWS produced μ spectra with reduced β amplitudes across conditions, suggesting reduced forward modeling capacity. Group time-frequency differences were associated with noisy conditions only. PWS showed increased μ-β desynchronization when listening to noise and early in discrimination events, suggesting evidence of heightened motor activity that might be related to forward modeling deficits. PWS also showed reduced μ-α synchronization in discrimination conditions, indicating reduced sensory gating. Together these findings indicate spectral and oscillatory analyses of μ rhythms are sensitive to stuttering. More specifically, they can reveal stuttering-related sensorimotor processing differences in listening and auditory discrimination that also may be influenced by basal ganglia deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraoperative monitoring of blood perfusion in port wine stains by laser Doppler imaging during vascular targeted photodynamic therapy: A preliminary study.

PubMed

Chen, Defu; Ren, Jie; Wang, Ying; Li, Buhong; Gu, Ying

2016-06-01

The objective of this study was to monitor blood perfusion dynamics of port wine stains (PWS) during vascular targeted photodynamic therapy (V-PDT) with laser Doppler imaging (LDI). The PWS lesions of 30 facial PWS patients received V-PDT, while the normal skins on the forearm of 5 healthy subjects were treated as light-only controls for comparison. Furthermore, two different PWS lesions in the same individual from each of 3 PWS patients successively received laser irradiation only and V-PDT, respectively. LDI was used to monitor intraoperative blood perfusion dynamics. During V-PDT, the blood perfusion (278±96 PU) in PWS lesions for 31 of 33 PWS patients significantly increased after the initiation of V-PDT treatment, then reached a peak (638±105 PU) within 10min, followed by a slow decrease to a relatively lower level (515±100 PU). Furthermore, the time for reaching peak and the subsequent magnitude of decrease in blood perfusion varied with different patients. For light-only controls, an initial perfusion peak at 3min followed by a nadir and a secondary increase were found not only in normal skin, but also in PWS lesions. The preliminary results showed that the LDI permits non-invasive monitoring blood perfusion changes of PWS lesions during V-PDT. There was a clear trend in blood perfusion responses during V-PDT and laser irradiation. The blood perfusion changes during treatment were due to V-PDT effects as well as local temperature increase induced by laser irradiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Phoneme Monitoring in Silent Naming and Perception in Adults Who Stutter

ERIC Educational Resources Information Center

Sasisekaran, Jayanthi; De Nil, Luc F.

2006-01-01

The present study investigated phonological encoding skills in persons who stutter (PWS). Participants were 10 PWS (M=31.8 years, S.D.=5.9) matched for age, gender, and handedness with 12 persons who do not stutter (PNS) (M=24.3 years, S.D.=4.3). The groups were compared in a phoneme monitoring task performed during silent picture naming. The…

Mechanical external work and recovery at preferred walking speed in obese subjects.

PubMed

Malatesta, Davide; Vismara, Luca; Menegoni, Francesco; Galli, Manuela; Romei, Marianna; Capodaglio, Paolo

2009-02-01

The aim of this study was to compare the mechanical external work (per kg) and pendular energy transduction at preferred walking speed (PWS) in obese versus normal body mass subjects to investigate whether obese adults adopt energy conserving gait mechanics. The mechanical external work (Wext) and the fraction of mechanical energy recovered by the pendular mechanism (Rstep) were computed using kinematic data acquired by an optoelectronic system and were compared in 30 obese (OG; body mass index [BMI] = 39.6 +/- 0.6 kg m(-2); 29.5 +/- 1.3 yr) and 19 normal body mass adults (NG; BMI = 21.4 +/- 0.5 kg m(-2); 31.2 +/- 1.2 yr) walking at PWS. PWS was significantly lower in OG (1.18 +/- 0.02 m s(-1)) than in NG (1.33 +/- 0.02 m s(-1); P PWS (r = 0.57; P < 0.001). Obese adults do not appear to alter their gait to improve pendular energy transduction and may select slower PWS to reduce mechanical and metabolic work.

Hyperghrelinemia in Prader-Willi Syndrome Begins in Early Infancy Long Before the Onset of Hyperphagia

PubMed Central

Kweh, Frederick A.; Miller, Jennifer L.; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J.; Goldstone, Anthony P.; Driscoll, Daniel J.

2015-01-01

Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P<0.001) higher in earlier nutritional phases: phase 1a (7,906 ± 5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P=0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. PMID:25355237

Evaluating the pictorial warnings on tobacco products in Arabian Gulf countries against other international pictorial warnings.

PubMed

BinDhim, Nasser F; McGeechan, Kevin; Alanazi, Anwar K T; Alanazi, Hossam M S; Alanazi, Sasoun A J; Al-Hadlaq, Solaiman M; Aljadhey, Hisham; Alhawassi, Tariq M; Alghamdi, Nadia A; Shaman, Ahmed M; Alquwayzani, Meshari S; Basyouni, Mada H

2017-05-12

Few assessments of pictorial warnings (PWs) on cigarette packs implemented in Gulf Cooperation Council (GCC) countries have been done. This article includes two cross-sectional studies. In Study 1, convenience samples of adults from the Kingdom of Saudi Arabia (n=111) and USA (n=115) participated in a consumer survey to rate a total of nine PWs from the GCC, Australia and the UK. Outcome measures were affective responses to PWs and concerns about smoking. In Study 2, tobacco control experts (n=14) from multiple countries rated the same PWs on a potential efficacy scale and completed one open-ended question about each. The PWs were altered to mask their country of origin. Analyses compared ranking on multiple outcomes and examined ratings by country of origin and by smoking status. In the consumer survey, participants from both countries rated the PWs from GCC lower than PWs from other countries on the two measures. The mixed-model analysis showed significant differences between the PWs from Australia and those from the GCC and between the PWs from the UK and those from the GCC (p<0.001) in the consumer and expert samples. The experts' comments about the PWs implemented in the GCC were negative overall and confirmed previously identified themes about effective PWs. This study shows PWs originating from the GCC had significantly lower ratings than those implemented in Australia and the UK. The GCC countries may need to re-evaluate the currently implemented PWs and update them periodically. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Speeded Verbal Responding in Adults Who Stutter: Are There Deficits in Linguistic Encoding?

ERIC Educational Resources Information Center

Hennessey, Neville W.; Nang, Charn Y.; Beilby, Janet M.

2008-01-01

Linguistic encoding deficits in people who stutter (PWS, n = 18) were investigated using auditory priming during picture naming and word vs. non-word comparisons during choice and simple verbal reaction time (RT) tasks. During picture naming, PWS did not differ significantly from normally fluent speakers (n = 18) in the magnitude of inhibition of…

Assessment of motivation and psychological characteristics of adult orthodontic patients.

PubMed

Pabari, Sona; Moles, David R; Cunningham, Susan J

2011-12-01

In recent years, the demand for adult orthodontic treatment has grown rapidly; yet there is a paucity of information on this subgroup of patients. It is well known that understanding the psychological characteristics and motives of any patient is fundamental and that these factors might affect patient satisfaction and adherence with treatment. There is therefore a need for clinicians to improve their understanding of this subgroup to enhance the patient's experience of treatment delivery and to increase the potential for a successful treatment outcome. The aim of this study was to develop a measure for the assessment of motivating factors and psychological characteristics of adults seeking orthodontic treatment. This study involved the qualitative development of a valid patient-centered questionnaire to assess motivating factors for adults seeking orthodontic treatment. This was achieved through semi-structured in-depth interviews; key themes were identified and used to construct a questionnaire assessing motivation for treatment. This was then combined with 3 previously validated questionnaires to measure self-esteem, anxiety or depression, and body image and facial body image. The questionnaire was distributed to 172 adult orthodontic patients at different stages of treatment in a large teaching hospital in the United Kingdom. In addition, the self-esteem, body image, and facial body image scores were compared with data on orthognathic patients from the same hospital and with data from members of the general public. Desire to straighten the teeth and improve the smile were the key motivating factors for the adult group studied. Other motives included to improve the bite, improve facial appearance, and close (dental) spacing. With respect to the psychological characteristics of self-esteem, body image, and facial body image, the adult orthodontic group was comparable with the general public. However, differences were noted when comparing data from the adult

[Qualitative research on pain experiences of adult burn patients].

PubMed

Li, L; Pan, Q; Xu, L; Lin, R Q; Dai, J X; Chen, Z H

2018-03-20

Objective: To explore the pain experiences of adult burn patients so as to lay foundation for practical analgesic measures. Methods: Using phenomenological method in qualitative research, semi-structured interviews were conducted on 12 adult burn patients hospitalized in our burn units from May to November 2015, aiming at pain experiences from immediately after burns to 3 to 7 months after being discharged from hospital. Then the Colaizzi's analysis method was applied to analyze, induce, and refine themes of interview data. Results: After analysis, pain experiences of adult burn patients were generalized into 6 themes: deep pain experiences, heavy psychological burden, limited daily life, poor assessment and treatment of pain, different attributions of pain, and different ways of coping of pain. Conclusions: Burn pain brings harm to the patients' physiology, mentality, and daily life. Nevertheless, pain processing modes of medical staff and patients themselves are the key factors affecting patients' pain experiences. Therefore, according to the deficiency of current situation of pain management, the targeted analgesic intervention measures should be carried out from the perspectives of medical staff and patients.

Developmental deficits in adult patients with arteriovenous malformations.

PubMed

Lazar, R M; Connaire, K; Marshall, R S; Pile-Spellman, J; Hacein-Bey, L; Solomon, R A; Sisti, M B; Young, W L; Mohr, J P

1999-01-01

Cerebral arteriovenous malformations (AVMs) are congenital masses of arteries and veins that appear to undergo an unclear "maturation" for many years. Using structured interviews, we compared developmental history of adult patients with AVM with a comparison group of patients with cerebral tumor or aneurysm. To determine whether a remote history of developmental abnormality in adult patients with AVM might be an early marker of cerebral status. Adult patients with AVM and a comparison group of patients with cerebral aneurysm or low-grade tumor participated in a survey. Urban medical school-based tertiary care center. Forty-four randomly selected patients with AVM from the Columbia-Presbyterian AVM Database. There were 32 comparison patients:15 randomly chosen patients from the institution's Cerebral Aneurysm Database and all 17 patients who underwent a biopsy from 1990 to 1995 with a diagnosis of low-grade tumor and who could be contacted. A brief, structured interview adapted from the Centers for Disease Control and Prevention for its 1994 study of the prevalence of learning disabilities in American children. We defined the positive occurrence of a condition as an affirmative answer to the question, " Did have (condition) during his/her school-age years?" Each patient was also asked if there had been any problems in the following skill areas: reading, writing, listening, speaking, attention, impulsivity, organization, mathematics, or drawing. The AVM size was calculated on the angiographic film by measuring its longest diameter in any dimension. Patients with AVM were significantly more likely to report a positive occurrence to any survey question (P<.05). Two thirds of all patients with AVM (66%) reported at least 1 skill difficulty during their school years, significantly more than the comparison group (P<.001). Neither the maximum AVM diameter nor the occurrence of hemorrhage as an adult differed between patients with AVM with and without early skill difficulty

Systematic review of surgical treatment techniques for adult and pediatric patients with pectus excavatum

PubMed Central

2014-01-01

This compares outcome measures of current pectus excavatum (PEx) treatments, namely the Nuss and Ravitch procedures, in pediatric and adult patients. Original investigations that stratified PEx patients based on current treatment and age (pediatric = 0–21; adult 17–99) were considered for inclusion. Outcome measures were: operation duration, analgesia duration, blood loss, length of stay (LOS), outcome ratings, complications, and percentage requiring reoperations. Adult implant patients (18.8%) had higher reoperation rates than adult Nuss or Ravitch patients (5.3% and 3.3% respectively). Adult Nuss patients had longer LOS (7.3 days), more strut/bar displacement (6.1%), and more epidural analgesia (3 days) than adult Ravitch patients (2.9 days, 0%, 0 days). Excluding pectus bar and strut displacements, pediatric and adult Nuss patients tended to have higher complication rates (pediatric - 38%; adult - 21%) compared to pediatric and adult Ravitch patients (12.5%; 8%). Pediatric Ravitch patients clearly had more strut displacements than adult Ravitch patients (0% and 6.4% respectively). These results suggest significantly better results in common PEx surgical repair techniques (i.e. Nuss and Ravitch) than uncommon techniques (i.e. Implants and Robicsek). The results suggest slightly better outcomes in pediatric Nuss procedure patients as compared with all other groups. We recommend that symptomatic pediatric patients with uncomplicated PEx receive the Nuss procedure. We suggest that adult patients receive the Nuss or Ravitch procedure, even though the long-term complication rates of the adult Nuss procedure require more investigation. PMID:24506826

Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy.

PubMed

Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

2016-12-27

Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD.

Elimination disorders in persons with Prader-Willi and Fragile-X syndromes.

PubMed

Equit, Monika; Piro-Hussong, Aline; Niemczyk, Justine; Curfs, Leopold; von Gontard, Alexander

2013-09-01

Elimination disorders are common in typically developing children. Only few studies have addressed elimination disorders in persons with intellectual disability (ID)-and even fewer studies in those with specific syndromes. The aim of the study was to investigate the rates of elimination disorders and behavioral symptoms in persons with Prader-Willi (PWS) and Fragile-X syndromes (FXS) in a large sample. Three hundred fifty-seven persons with PWS or FXS were recruited through parent self-help groups. A questionnaire regarding elimination symptoms, as well as the child behavior checklist (CBCL)/young adult behavior checklist (YABCL) were filled out by parents or caregivers. The sample included 191 persons with PWS (54.5% male) with a mean age of 20.0 years and 166 persons with FXS (92.2% male) with a mean age of 15.4 years. Persons with FXS were significantly more often affected by elimination disorders. 29.3% of persons with PWS and 48.8% of persons with FXS had at least one elimination disorder. Persons with FXS also had more often DUI (29.5% vs. 12.0%) and FI (28.9% vs. 12.6%). Rates of NE were similar in both groups (22.0% in PWS vs. 28.9% in FXS). Young adults with PWS had more behavioral symptoms in the clinical range (70.8% vs. 48.3%). Incontinence and behavioral symptoms were significantly associated in persons with FXS. NE, DUI, and FI are very common in persons with FXS and PWS and are associated with other behavioral symptoms in persons with FXS. They persist into adulthood. Early assessment and treatment are recommended. Copyright © 2012 Wiley Periodicals, Inc.

Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay.

PubMed

Lukoshe, Akvile; Hokken-Koelega, Anita C; van der Lugt, Aad; White, Tonya

2014-01-01

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in

Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia.

PubMed

Kweh, Frederick A; Miller, Jennifer L; Sulsona, Carlos R; Wasserfall, Clive; Atkinson, Mark; Shuster, Jonathan J; Goldstone, Anthony P; Driscoll, Daniel J

2015-01-01

Circulating total ghrelin levels are elevated in older children and adults with Prader-Willi syndrome (PWS). However, the presence or absence of hyperghrelinemia in young children with PWS remains controversial. We hypothesized that a more robust way to analyze appetite-regulating hormones in PWS would be by nutritional phases rather than age alone. Our objectives were to compare total serum ghrelin levels in children with PWS by nutritional phase as well as to compare total ghrelin levels in PWS (5 weeks to 21 years of age) to normal weight controls and individuals with early-onset morbid obesity (EMO) without PWS. Fasting serum total ghrelin levels were measured in 60 subjects with PWS, 39 subjects with EMO of unknown etiology, and in 95 normal non-obese sibling controls of PWS or EMO subjects (SibC) in this 12 year longitudinal study. Within PWS, total ghrelin levels were significantly (P < 0.001) higher in earlier nutritional phases: phase 1a (7,906  ±  5,887); 1b (5,057 ± 2,624); 2a (2,905 ± 1,521); 2b (2,615 ± 1,370) and 3 (2,423 ± 1,350). Young infants with PWS also had significantly (P = 0.009) higher total ghrelin levels than did the sibling controls. Nutritional phase is an important independent prognostic factor of total ghrelin levels in individuals with PWS. Circulating ghrelin levels are elevated in young children with PWS long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding. Therefore, it seems unlikely that high ghrelin levels are directly responsible for the switch to the hyperphagic nutritional phases in PWS. © 2014 Wiley Periodicals, Inc.

Personal Perceptions and Perceived Public Opinion About Stuttering in the United States: Implications for Anti-Stigma Campaigns.

PubMed

Boyle, Michael P

2017-08-15

This exploratory study was the first to obtain quantitative and qualitative data on both personal perceptions and perceived public opinion about stuttering in order to identify topics to include in anti-stigma programs for stuttering. Three-hundred ten adults in the United States completed a web survey that assessed knowledge about stuttering and attitudes toward people who stutter (PWS) with questions addressing personal perceptions (direct questions) and perceived public opinion (indirect questions). Many participants reported favorable personal perceptions of PWS regarding their intelligence, competence, and potential for success. However, most participants did not personally believe PWS were confident, and most believed they were shy. Perceived public opinion was more unfavorable as a majority agreed that the public is uncomfortable talking with PWS and that the public would recommend PWS avoid jobs requiring high speech demands and avoid talking to large audiences. A minority of participants agreed PWS are perceived publicly as capable or mentally healthy. The survey demonstrated misunderstandings and negative perceptions of PWS, especially when measured with perceived public opinion. Results can increase our understanding of content areas that should be included in anti-stigma programs for stuttering and highlight different methods for analyzing public perceptions of stuttering.

Adult Patients' Experiences of Nursing Care Dependence.

PubMed

Piredda, Michela; Matarese, Maria; Mastroianni, Chiara; D'Angelo, Daniela; Hammer, Marilyn J; De Marinis, Maria Grazia

2015-09-01

Care dependence can be associated with suffering and humiliation. Nurses' awareness of patients' perception of care dependence is crucial to enable them in helping the dependent persons. This study aimed to describe adult patients' experience of nursing care dependence. A metasynthesis was conducted to integrate qualitative findings from 18 studies published through December 2014 on adult patients' experiences of care dependency. Procedures included the Johanna Briggs Institute approach for data extraction, quality appraisal, and integration of findings. The experience of dependence revealed the concept of the embodied person, particularly in relation to care of the physical body. The relationship between the individual and nurses within the context of care had a major impact for dependent patients. When the care relation was perceived as positive, the experience led to the development of the person in finding new balances in life, but when it was perceived as negative, it increased patient' suffering. Care dependence is manifested mostly as bodily dependence and is consistent with its relational nature. The nurse-patient relationship is important to the dependent patients' experience. A greater understanding of patients' experiences of dependence is crucial to enable nurses in improving care and decreasing patient suffering. © 2015 Sigma Theta Tau International.

Comparing catheter-related bloodstream infections in pediatric and adult cancer patients.

PubMed

Zakhour, Ramia; Hachem, Ray; Alawami, Hussain M; Jiang, Ying; Michael, Majd; Chaftari, Anne-Marie; Raad, Issam

2017-10-01

Central venous catheters (CVCs) are essential to treatment of children with cancer. There are no studies comparing catheter-related bloodstream infections (CRBSIs) in pediatric cancer patients to those in adults, although current guidelines for management of CRBSI do not give separate guidelines for the pediatric population. In this study, we compared CRBSIs in both the pediatric and adult cancer population. We retrospectively reviewed the electronic medical records of 92 pediatric and 156 adult patients with CRBSI cared for at MD Anderson Cancer Center between September 2005 and March 2014. We evaluated 248 patients with CRBSI. There was a significant difference in etiology of CRBSI between pediatric and adult patients (P = 0.002), with the former having less Gram-negative organisms (27 vs. 46%) and more polymicrobial infections (10 vs. 1%, P = 0.003). Pediatric patients had less hematologic malignancies (58 vs. 74%) and less neutropenia at presentation (40 vs. 54%) when compared with adult patients. Peripheral blood cultures were available in only 43% of pediatric cases. CVC was removed in 64% of pediatric cases versus 88% of adult cases (P < 0.0001). We found higher rates of Gram-negative organisms in adults and higher rates of polymicrobial in children. Because of the low rates of peripheral blood cultures and the low rates of CVC removal, CRBSI diagnosis could be challenging in pediatrics. A modified CRBSI definition relying more on clinical criteria may be warranted. © 2017 Wiley Periodicals, Inc.

Cognitive Profile in a Large French Cohort of Adults with Prader-Willi Syndrome: Differences between Genotypes

ERIC Educational Resources Information Center

Copet, P.; Jauregi, J.; Laurier, V.; Ehlinger, V.; Arnaud, C.; Cobo, A. -M.; Molinas, C.; Tauber, M.; Thuilleaux, D.

2010-01-01

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of…

1p36 deletion syndrome associated with Prader-Willi-like phenotype.

PubMed

Tsuyusaki, Yu; Yoshihashi, Hiroshi; Furuya, Noritaka; Adachi, Masanori; Osaka, Hitoshi; Yamamoto, Kayono; Kurosawa, Kenji

2010-08-01

1p36 deletion syndrome is one of the most common subtelomeric deletion syndromes, characterized by moderate to severe mental retardation, characteristic facial appearance, hypotonia, obesity, and seizures. The clinical features often overlap with those of Prader-Willi syndrome (PWS). To elucidate the phenotype-genotype correlation in 1p36 deletion syndrome, two cases involving a PWS-like phenotype were analyzed on molecular cytogenetics. Two patients presenting with the PWS-like phenotype but having negative results for PWS underwent fluorescence in situ hybridization (FISH). The size of the chromosome 1p36 deletions was characterized using probes of BAC clones based on the University of California, Santa Cruz (UCSC) Genome Browser. PWS was excluded on FISH and methylation-specific polymerase chain reaction. Subsequent FISH using the probe D1Z2 showed deletion of the 1p36.3 region, confirming the diagnosis of 1p36 deletion syndrome. Further analysis characterized the 1p36 deletions as being located between 4.17 and 4.36 Mb in patient 1 and between 4.89 and 6.09 Mb in patient 2. Patients with 1p36 deletion syndrome exhibit a PWS-like phenotype and are therefore probably underdiagnosed. The possible involvement of the terminal 4 Mb region of chromosome 1p36 in the PWS-like phenotype is hypothesized. © 2010 Japan Pediatric Society.

Neuropsychological Assessment of Adult Patients with Shunted Hydrocephalus

PubMed Central

Bakar, Emel Erdogan

2010-01-01

Objective This study is planned to determine the neurocognitive difficulties of hydrocephalic adults. Methods The research group contained healthy adults (control group, n : 15), and hydrocephalic adults (n : 15). Hydrocephalic group consisted of patients with idiopathic aquaduct stenosis and post-meningitis hydrocephalus. All patients were followed with shunted hydrocephalus and not gone to shunt revision during last two years. They were chosen from either asymptomatic or had only minor symptoms without motor and sensorineural deficit. A neuropsychological test battery (Raven Standart Progressive Matrices, Bender-Gestalt Test, Cancellation Test, Clock Drawing Test, Facial Recognition Test, Line Orientation Test, Serial Digit Learning Test, Stroop Color Word Interference Test-TBAG Form, Verbal Fluency Test, Verbal Fluency Test, Visual-Aural Digit Span Test-B) was applied to all groups. Results Neuropsychological assessment of hydrocephalic patients demonstrated that they had poor performance on visual, semantic and working memory, visuoconstructive and frontal functions, reading, attention, motor coordination and executive function of parietal lobe which related with complex and perseverative behaviour. Eventually, these patients had significant impairment on the neurocognitive functions of their frontal, parietal and temporal lobes. On the other hand, the statistical analyses performed on demographic data showed that the aetiology of the hydrocephalus, age, sex and localization of the shunt (frontal or posterior parietal) did not affect the test results. Conclusion This prospective study showed that adult patients with hydrocephalus have serious neuropsychological problems which might be directly caused by the hydrocephalus; and these problems may cause serious adaptive difficulties in their social, cultural, behavioral and academic life. PMID:20379471

Effects of underwater treadmill training on leg strength, balance, and walking performance in adults with incomplete spinal cord injury.

PubMed

Stevens, Sandra L; Caputo, Jennifer L; Fuller, Dana K; Morgan, Don W

2015-01-01

To document the effects of underwater treadmill training (UTT) on leg strength, balance, and walking performance in adults with incomplete spinal cord injury (iSCI). Pre-test and post-test design. Exercise physiology laboratory. Adult volunteers with iSCI (n = 11). Participants completed 8 weeks (3 × /week) of UTT. Each training session consisted of three walks performed at a personalized speed, with adequate rest between walks. Body weight support remained constant for each participant and ranged from 29 to 47% of land body weight. Increases in walking speed and duration were staggered and imposed in a gradual and systematic fashion. Lower-extremity strength (LS), balance (BL), preferred and rapid walking speeds (PWS and RWS), 6-minute walk distance (6MWD), and daily step activity (DSA). Significant (P < 0.05) increases were observed in LS (13.1 ± 3.1 to 20.6 ± 5.1 N·kg(-1)), BL (23 ± 11 to 32 ± 13), PWS (0.41 ± 0.27 to 0.55 ± 0.28 m·s(-1)), RWS (0.44 ± 0.31 to 0.71 ± 0.40 m·s(-1)), 6MWD (97 ± 80 to 177 ± 122 m), and DSA (593 ± 782 to 1310 ± 1258 steps) following UTT. Physical function and walking ability were improved in adults with iSCI following a structured program of UTT featuring individualized levels of body weight support and carefully staged increases in speed and duration. From a clinical perspective, these findings highlight the potential of UTT in persons with physical disabilities and diseases that would benefit from weight-supported exercise.

The Adult Diabetic Patient: An Education Challenge

DTIC Science & Technology

1993-05-01

finding that he/she, too, must care for sicker patients. To better prepare these patients for life after discharge, patient education must be initiated as...admitted, patient education often begins at the physicians’ office. This paper explores diabetes mellitus in relation to concepts of self-care and adult...betting foj.L eduuation and iio.w, wore ofteni, patient education and follow-up sercvices- a:leL beiny p~rovided on ani outpatient bcdtsis" (p. 36) . Thet

Does the Genetic Cause of Prader-Willi Syndrome Explain the Highly Variable Phenotype?

PubMed

Dobrescu, Andreea-Iulia; Chirita-Emandi, Adela; Andreescu, Nicoleta; Farcas, Simona; Puiu, Maria

2016-09-01

Prader-Willi syndrome (PWS) is characterized by extensive clinical and genetic variability caused by lack of expression of imprinted genes of the chromosomal region 15q11.2-q13. The genotye-phenotype correlation has not been yet fully elucidated. To analyze these correlations in order to determine the role of specifi c geneic alterations in the development of clinical symptoms in PWS. We retrospectively analyzed data routinely collected as part of the clinical care of 52 patients with clinical suspicion of PWS. FISH test was performed in all patients; in case of negative results, methylation test was performed. PWS was confi rmed in 35 patients that were divided in two groups according to the genetic cause of PWS: group A-21 patients with 15q11-q13 region deletion, mean age at evaluation 8.1 years (SD= 5.6) and mean of clinical score 9.4 ± 1.8; group B-14 patients with positive methylation test, with mean age at evaluation 6.7 years (SD= 4.6) and mean of clinical score 10.1 ± 1.9. Facial dysmorphism and neonatal hypotonia were present in all evaluated patients; while, higher frequency of major and minor PWS criteria were noted in the group A. Onset of hyperphagia, was around the age of 2 years in most patients, however one patient from group B had normal eating behavior and normal weight beyond age 5 years. In our study, the various genotypes did not seem to explain the diff erence in phenotype in PWS patients. We found a delayed time until diagnosis in these patients, although all had neonatal hypotonia and other suggestive phenotypic features, underlining once more the need for increased awareness of this syndrome, as well as easier accessibility to genetic counseling.

Behavioural and Emotional Disturbances in People with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Steinhausen, H.-C.; Eiholzer, U.; Hauffa, B. P.; Malin, Z.

2004-01-01

The study of the behaviour profile in subjects with Prader-Willi Syndrome (PWS). A total of fifty-eight 3- to 29-year-old subjects with PWS were studied using a standardized parent report of behavioural and emotional disturbances. There was an increase of behavioural and emotional disturbances for the adolescent and young adult age range, whereas…

Phonation Interval Modification and Speech Performance Quality during Fluency-Inducing Conditions by Adults Who Stutter

ERIC Educational Resources Information Center

Ingham, Roger J.; Bothe, Anne K.; Wang, Yuedong; Purkhiser, Krystal; New, Anneliese

2012-01-01

Purpose: To relate changes in four variables previously defined as characteristic of normally fluent speech to changes in phonatory behavior during oral reading by persons who stutter (PWS) and normally fluent controls under multiple fluency-inducing (FI) conditions. Method: Twelve PWS and 12 controls each completed 4 ABA experiments. During A…

Individuals with Smith-Magenis syndrome display profound neurodevelopmental behavioral deficiencies and exhibit food-related behaviors equivalent to Prader-Willi syndrome.

PubMed

Alaimo, Joseph T; Barton, Laura V; Mullegama, Sureni V; Wills, Rachel D; Foster, Rebecca H; Elsea, Sarah H

2015-12-01

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder associated with intellectual disability, sleep disturbances, early onset obesity and vast behavioral deficits. We used the Behavior Problems Inventory-01 to categorize the frequency and severity of behavioral abnormalities in a SMS cohort relative to individuals with intellectual disability of heterogeneous etiology. Self-injurious, stereotyped, and aggressive/destructive behavioral scores indicated that both frequency and severity were significantly higher among individuals with SMS relative to those with intellectual disability. Next, we categorized food behaviors in our SMS cohort across age using the Food Related Problems Questionnaire (FRPQ) and found that problems began to occur in SMS children as early as 5-11 years old, but children 12-18 years old and adults manifested the most severe problems. Furthermore, we evaluated the similarities of SMS adult food-related behaviors to those with intellectual disability and found that SMS adults had more severe behavioral problems. Many neurodevelopmental disorders exhibit syndromic obesity including SMS. Prader-Willi syndrome (PWS) is the most frequent neurodevelopmental disorder with syndromic obesity and has a well-established management and treatment plan. Using the FRPQ we found that SMS adults had similar scores relative to PWS adults. Both syndromes manifest weight gain early in development, and the FRPQ scores highlight specific areas in which behavioral similarities exist, including preoccupation with food, impaired satiety, and negative behavioral responses. SMS food-related behavior treatment paradigms are not as refined as PWS, suggesting that current PWS treatments for prevention of obesity may be beneficial for individuals with SMS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spine Surgery Outcomes in Elderly Patients Versus General Adult Patients in the United States: A MarketScan Analysis.

PubMed

Lagman, Carlito; Ugiliweneza, Beatrice; Boakye, Maxwell; Drazin, Doniel

2017-07-01

To compare spine surgery outcomes in elderly patients (80-103 years old) versus general adult patients (18-79 years-old) in the United States. Truven Health Analytics MarketScan Research Databases (2000-2012) were queried. Patients with a diagnosis of degenerative disease of the spine without concurrent spinal stenosis, spinal stenosis without concurrent degenerative disease, or degenerative disease with concurrent spinal stenosis and who had undergone decompression without fusion, fusion without decompression, or decompression with fusion procedures were included. Indirect outcome measures included length of stay, in-hospital mortality, in-hospital and 30-day complications, and discharge disposition. Patients (N = 155,720) were divided into elderly (n = 10,232; 6.57%) and general adult (n = 145,488; 93.4%) populations. Mean length of stay was longer in elderly patients versus general adult patients (3.62 days vs. 3.11 days; P < 0.0001). In-hospital mortality was more common in elderly patients versus general adult patients (0.31% vs. 0.06%; P < 0.0001). In-hospital and 30-day complications were more common in elderly patients versus general adult patients (11.3% vs. 7.15% and 17.8% vs. 12.6%; P < 0.0001). Nonroutine discharge was more common in elderly patients versus general adult patients (33.7% vs. 16.2%; P < 0.0001). Our results revealed significantly longer hospital stays, more in-hospital mortalities, and more in-hospital and 30-day complications after decompression without fusion, fusion without decompression, or decompression with fusion procedures in elderly patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Pre-adult versus adult onset major depressive disorder in a naturalistic patient sample: the Leiden Routine Outcome Monitoring Study.

PubMed

van Noorden, M S; Minkenberg, S E; Giltay, E J; den Hollander-Gijsman, M E; van Rood, Y R; van der Wee, N J; Zitman, F G

2011-07-01

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients. Altogether, 1552 out-patients, mean age 39.2 ± 11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender. Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26-2.60) in patients with pre-adult versus adult onset MDD. Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Ab interno trabeculectomy in the adult patient.

PubMed

SooHoo, Jeffrey R; Seibold, Leonard K; Kahook, Malik Y

2015-01-01

Glaucoma is a potentially blinding disease that affects millions of people worldwide. The mainstay of treatment is lowering of intraocular pressure (IOP) through the use of medications, laser and/or incisional surgery. The trabecular meshwork (TM) is thought to be the site of significant resistance to aqueous outflow in open angle glaucoma. Theoretically, an incision through TM or TM removal should decrease this resistance and lead to a significant reduction in IOP. This approach, commonly referred to as goniotomy or trabeculotomy, has been validated in the pediatric population and has been associated with long-term IOP control. In adults, however, removal of TM tissue has been historically associated with more limited and short-lived success. More recent evidence, reveals that even adult patients may benefit significantly from removal of diseased TM tissue and can lead to a significant reduction in IOP that is long-lasting and safe. In this review, we discuss current evidence and techniques for ab interno trabeculectomy using various devices in the adult patient.

Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome

PubMed Central

Gillett, Emily S.; Perez, Iris A.

2016-01-01

Prader-Willi syndrome (PWS) is an imprinted genetic disorder conferred by loss of paternal gene expression from chromosome 15q11.2-q13. Individuals with PWS have impairments in ventilatory control and are predisposed toward sleep disordered breathing due to a combination of characteristic craniofacial features, obesity, hypotonia, and hypothalamic dysfunction. Children with PWS progress from failure to thrive during infancy to hyperphagia and morbid obesity during later childhood and onward. Similarly, the phenotype of sleep disordered breathing in PWS patients also evolves over time from predominantly central sleep apnea in infants to obstructive sleep apnea (OSA) in older children. Behavioral difficulties are common and may make establishing effective therapy with continuous positive airway pressure (CPAP) more challenging when OSA persists after adenotonsillectomy. Excessive daytime sleepiness (EDS) is also common in patients with PWS and may continue after OSA is effectively treated. We describe here the characteristic ventilatory control deficits, sleep disordered breathing, and excessive daytime sleepiness seen in individuals with PWS. We review respiratory issues that may contribute to sudden death events in PWS patients during sleep and wakefulness. We also discuss therapeutic options for treating sleep disordered breathing including adenotonsillectomy, weight loss, and CPAP. Lastly, we discuss the benefits and safety considerations related to growth hormone therapy. PMID:28933403

Disorders of Sleep and Ventilatory Control in Prader-Willi Syndrome.

PubMed

Gillett, Emily S; Perez, Iris A

2016-07-08

Prader-Willi syndrome (PWS) is an imprinted genetic disorder conferred by loss of paternal gene expression from chromosome 15q11.2-q13. Individuals with PWS have impairments in ventilatory control and are predisposed toward sleep disordered breathing due to a combination of characteristic craniofacial features, obesity, hypotonia, and hypothalamic dysfunction. Children with PWS progress from failure to thrive during infancy to hyperphagia and morbid obesity during later childhood and onward. Similarly, the phenotype of sleep disordered breathing in PWS patients also evolves over time from predominantly central sleep apnea in infants to obstructive sleep apnea (OSA) in older children. Behavioral difficulties are common and may make establishing effective therapy with continuous positive airway pressure (CPAP) more challenging when OSA persists after adenotonsillectomy. Excessive daytime sleepiness (EDS) is also common in patients with PWS and may continue after OSA is effectively treated. We describe here the characteristic ventilatory control deficits, sleep disordered breathing, and excessive daytime sleepiness seen in individuals with PWS. We review respiratory issues that may contribute to sudden death events in PWS patients during sleep and wakefulness. We also discuss therapeutic options for treating sleep disordered breathing including adenotonsillectomy, weight loss, and CPAP. Lastly, we discuss the benefits and safety considerations related to growth hormone therapy.

[Bacterial parotitis in an immunocompromised patient in adult ICU].

PubMed

Vassal, O; Bernet, C; Wallet, F; Friggeri, A; Piriou, V

2013-09-01

Bacterial parotitis is a common childhood disease with a favorable outcome. Staphylococcus aureus is the most frequently involved pathogen. Clinical presentation in adult patients can be misleading, Onset occurs in patients with multiple comorbidities, making diagnosis difficult--particularly in ICU. Different pathogens are found in adults with worse outcomes observed. We report here the case of a critically ill patient and discuss diagnosis and management of bacterial parotitis. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

[The reproductive system in Prader-Willi syndrome].

PubMed

Eldar-Geva, Talia; Hirsch, Harry J; Gross-Tsur, Varda

2015-03-01

Prader-Willi syndrome (PWS) is a genetic syndrome caused by the lack of expression of imprinted genes located on paternal chromosome 15q11-q13, characterized by endocrine defects, an insatiable appetite, short stature, cognitive and behavioral difficulties and dysmorphic features. Nearly all PWS males and most PWS women show clinical and/or laboratory evidence of hypogonadism, affecting their habitus, health and quality of life. Until recently, hypogonadism in PWS was generally considered to be of centrall, hypothalamic origin. However, recent studies have shown that primary gonadal dysfunction is the major contributor to hypogonadism in this condition, while severe gonadotropin deficiency is rare. Despite clinical and laboratory evidence of hypogonadism, young adult PWS men and women have sexual and romantic interests and aspirations. Pregnancies have been reported in a few women with genetically documented PWS. Fertility has not been reported in PWS men. Recognition of these interests is essential for physicians and caregivers in order to offer proper anticipatory guidance, psychological and sex education and counseling. Individual variations in pubertal development, reproductive hormone profiles, bone-mineral density and individual appeal need to be considered when recommending sex hormone replacement in this population. Testosterone should be considered in most hypogonadal PWS males, considering possible side effects. Hormone replacement may be indicated in PWS women with decreasing bone mineral density or in PWS women who wish to have regular menses. Contraception should be considered in women with normal inhibin B levels. Hormone replacement is likely to improve bone density, quality of life and body image.

Regional cerebral blood flow and abnormal eating behavior in Prader-Willi syndrome.

PubMed

Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Fukuda, Hiroshi; Mori, Etsuro

2013-05-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Comparative characteristics of primary hyperparathyroidism in pediatric and young adult patients.

PubMed

Nicholson, Kristina J; McCoy, Kelly L; Witchel, Selma F; Stang, Michael T; Carty, Sally E; Yip, Linwah

2016-10-01

Primary hyperparathyroidism is rare in pediatric patients. Our study aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young adult (19-29 years) patients. A prospectively collected database from a single, high-volume institution was queried for all patients age <30 years who had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546 (2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87 young adult patients. Presenting symptoms, operative data, and postoperative course were compared for patients age 0-19 years and 20-29 years. Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among patients with hereditary primary hyperparathyroidism, multiple endocrine neoplasia type 1 was the most common type. Multiglandular disease was common in both pediatric (30.7%) and young adult (21.8%) patients. Following parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P = .44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple endocrine neoplasia 1-related primary hyperparathyroidism in all cases. Although primary hyperparathyroidism is sporadic in most patients <19 years, they are more likely to have multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (23%). Parathyroidectomy for primary hyperparathyroidism can be performed safely in pediatric patients with a high rate of cure. Follow-up for patients with hereditary disease is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Personality Traits and Common Psychiatric Conditions in Adult Patients with Acne Vulgaris

PubMed Central

Çölgeçen, Emine

2015-01-01

Background We believe that instances of neuroticism and common psychiatric disorders are higher in adults with acne vulgaris than the normal population. Objective Instances of acne in adults have been increasing in frequency in recent years. The aim of this study was to investigate personality traits and common psychiatric conditions in patients with adult acne vulgaris. Methods Patients who visited the dermatology outpatient clinic at Bozok University Medical School with a complaint of acne and who volunteered for this study were included. The Symptom Checklist 90-Revised (SCL 90-R) Global Symptom Index (GSI), somatization, depression, and anxiety subscales and the Eysenck Personality Questionnaire-Revised Short Form (EPQ-RSF) were administered to 40 patients who fulfilled the inclusion criteria before treatment. The results were compared with those of a control group. Results Of the 40 patients included in this study, 34 were female and 6 were male. The GSI and the somatization, depression, and anxiety subscales of the SCL 90-R were evaluated. Patients with adult acne had statistically significant higher scores than the control group on all of these subscales. In addition, patients with adult acne had statistically significantly higher scores on the neuroticism subscale of the EPQ-RSF. Conclusion Our results show that common psychiatric conditions are frequent in adult patients with acne. More importantly, neurotic personality characteristics are observed more frequently in these patients. These findings suggest that acne in adults is a disorder that has both medical and psychosomatic characteristics and requires a multi-disciplinary approach. PMID:25673931

Determinants of gait stability while walking on a treadmill: A machine learning approach.

PubMed

Reynard, Fabienne; Terrier, Philippe

2017-12-08

Dynamic balance in human locomotion can be assessed through the local dynamic stability (LDS) method. Whereas gait LDS has been used successfully in many settings and applications, little is known about its sensitivity to individual characteristics of healthy adults. Therefore, we reanalyzed a large dataset of accelerometric data measured for 100 healthy adults from 20 to 70 years of age performing 10 min treadmill walking. We sought to assess the extent to which the variations of age, body mass and height, sex, and preferred walking speed (PWS) could influence gait LDS. The random forest (RF) and multiple adaptive regression splines (MARS) algorithms were selected for their good bias-variance tradeoff and their capabilities to handle nonlinear associations. First, through variable importance measure (VIM), we used RF to evaluate which individual characteristics had the highest influence on gait LDS. Second, we used MARS to detect potential interactions among individual characteristics that may influence LDS. The VIM and MARS results indicated that PWS and age correlated with LDS, whereas no associations were found for sex, body height, and body mass. Further, the MARS model detected an age by PWS interaction: on one hand, at high PWS, gait stability is constant across age while, on the other hand, at low PWS, gait instability increases substantially with age. We conclude that it is advisable to consider the participants' age as well as their PWS to avoid potential biases in evaluating dynamic balance through LDS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of a 6-Month Home-Based Training Program in Prader-Willi Patients

ERIC Educational Resources Information Center

Vismara, Luca; Cimolin, Veronica; Grugni, Graziano; Galli, Manuela; Parisio, Cinzia; Sibilia, Olivia; Capodaglio, Paolo

2010-01-01

In addition to hypotonia and relative sarcopenia, patients with Prader-Willi syndrome (PWS) show reduced spontaneous physical activity and gait disorders. Scant evidence exists that daily muscle training increases their lean mass and physical activity levels. Whether adequate long-term physical training is feasible and effective in improving…

Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients with Rheumatoid Arthritis: Large-Scale, Prospective, Single-Cohort ANOUVEAU Study.

PubMed

Takeuchi, Tsutomu; Nakajima, Ryo; Komatsu, Shuichi; Yamazaki, Kiyotaka; Nakamura, Tomohiro; Agata, Naoki; Igarashi, Ataru; Tango, Toshiro; Tanaka, Yoshiya

2017-03-01

The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan. Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness. Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%. Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA. AbbVie GK and Eisai Co., Ltd. ClinicalTrials.gov identifier, NCT01346488.

Molecular and clinical overlap of Angelman and Prader-Willi syndrome phenotypes.

PubMed

Kirkilionis, A J; Chudley, A E; Gregory, C A; Hamerton, J L

1991-09-15

The Prader-Willi (PWS) and Angelman syndromes (AS) share the same apparent cytogenetic and molecular lesions of 15q11-13 and yet exhibit distinct clinical phenotypes. The etiology of PWS or AS appears to depend on the parental origin of the aberrant chromosome 15. Substantial clinical overlap has not been reported between deletion-positive PWS and AS patients. In the present study, we report the clinical, cytogenetic, and molecular findings in three AS patients. The first patient is a mentally retarded woman with a visible deletion of 15q11-13 with typical craniofacial, behavioral, and neurologic changes of AS. This patient is hyperphagic, and she is moderately obese for her height. Her hands and feet are small. These manifestations are more characteristic of PWS and not of AS. The molecular studies showed deletions of maternal origin for five distal PWCR loci. The most proximal locus, D15S18, was not deleted. These findings are identical to those found in our third AS patient who does not have any PWS features. To the best of our knowledge, this is the first report of concurrence of hyperphagia with consequent obesity and the AS phenotype in a patient with a del 15(q11-13) of maternal origin. These clinical findings suggest that overlap in the symptoms of PWS and AS can occur. Our second AS patient presents with atypical molecular findings in that he cannot be classed into any of the three proposed sub-groups of AS patients and may be representative of a fourth sub-group of AS patients.

QOL in caregivers of Japanese patients with Prader-Willi syndrome with reference to age and genotype.

PubMed

Ihara, Hiroshi; Ogata, Hiroyuki; Sayama, Masayuki; Kato, Aya; Gito, Masao; Murakami, Nobuyuki; Kido, Yasuhiro; Nagai, Toshiro

2014-09-01

This study aimed to measure quality of life (QOL) of the primary family caregivers for patients with Prader-Willi syndrome (PWS). Comparisons were made between caregivers' QOL in regard to their dependents' genotype and age group. The participants with PWS consisted of 22 children (aged from 6 to 12 years) and 23 adolescents (aged from 13 to 19 years), including 6 children and 7 adolescents with maternal uniparental disomy (mUPD) and 16 children and 16 adolescents with deletion (DEL). The QOL of the primary family caregiver for each patient was assessed using the Japanese version of the WHOQOL-BREF. To examine the effect that age (children vs. adolescents) and genotype (DEL vs. mUPD) have on the QOL of caregivers, a two-way ANOVA was conducted, followed by the Bonferroni procedure to test the simple main effects. The two age groups and the two genotypes of PWS were used as independent variables and the total QOL of caregivers as a dependent variable. The two-way ANOVA (F(1, 41) = 6.98, P < 0.05), followed by the Bonferroni procedure, showed the following: the total QOL of caregivers of DEL adolescents showed little difference from that with DEL children, but the QOL of caregivers for mUPD adolescents was shown to be lower than that with mUPD children along with that of caregivers with DEL adolescents. There is hence a growing tendency for the deterioration in the QOL of caregivers to manifest itself later in the patients' adolescence, found mainly with mUPD patients. © 2014 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Safety and efficacy of dual-wavelength laser (1064 + 595 nm) for treatment of non-treated port-wine stains.

PubMed

Wang, T; Chen, D; Yang, J; Ma, G; Yu, W; Lin, X

2018-02-01

Patients with port-wine stain (PWS) suffer physically and psychologically because of the high incidence (0.3%-0.5%) of the disease. Pulsed-dye laser (PDL) at 595 nm is the gold standard of the treatment for PWS. Nevertheless, clinicians intend to determine whether the dual-wavelength laser (DWL; 595-nm PDL + 1064-nm Nd:YAG) is an adequate choice in the treatment of non-treated PWS. This study is the first prospective within-patient controlled research seeking to investigate the safety and efficacy of DWL for the treatment of non-treated PWS. A total of 61 patients with non-treated flat facial PWS, who were treated using the Cynergy laser system in our clinic, were included in this study. Each PWS lesion was divided into two adjacent test treatment sites of similar size and colour. The two sites were randomly assigned to PDL or DWL treatment in a blinded manner of participants. In each case, two sets of treatment parameters were used: (i) 595-nm PDL and (ii) 595-nm PDL + 1064-nm Nd:YAG. Both had a 10 mm spot size, an epidermal cooling system and 1-s interpulse interval between two pulses. Clinical efficacy and safety outcomes were evaluated by visual assessment 2 months after treatment. Comparison by visual evaluation suggests that the responses of non-treated PWS to treatment by PDL and DWL were not significantly different. Moreover, three patients developed scarring after DWL treatment. Compared with PDL, DWL exhibits a higher risk of potential scarring and has no advantage in efficacy of treating non-treated PWS. © 2017 European Academy of Dermatology and Venereology.

[Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

PubMed

Jaramillo González, Luis Eduardo; Gómez Restrepo, Carlos; García Valencia, Jenny; de la Hoz Bradford, Ana María; Ávila-Guerra, Mauricio; Bohórquez Peñaranda, Adriana

2014-01-01

To determine the indications of long-acting antipsychotic injection and what its effectiveness and safety in adult patients with schizophrenia during the treatment maintenance phase. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The literature review shows that the evidence has moderate to low quality. 8 articles were used. The risk of relapse was lower with depot risperidone and paliperidone palmitate when compared with placebo. For the risk of hospitalizations comparing depot antipsychotics (APD) versus oral AP, the result is inconclusive. Globally the second-generation APD had a lower risk of discontinuation when compared with placebo. The second generation AP had higher risk of extrapyramidal syndromes than placebo, as in the use of antiparkinsonian. The comparison of second-generation AP injections versus placebo showed an increased risk of early weight gain. The use of depot antipsychotics in the maintenance phase of adult patients diagnosed with schizophrenia is recommended if there is no adherence to oral antipsychotics as the patient's preference. It is not recommended depot antipsychotics in the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Posterior nasal septal abscess in a healthy adult patient.

PubMed

George, A; Smith, W K; Kumar, S; Pfleiderer, A G

2008-12-01

We report an extremely rare case of bilateral posterior nasal septal abscess in an otherwise healthy adult patient. Case report and a review of the world literature concerning atraumatic nasal septal abscess and its management. The development of an atraumatic nasal septal abscess is rare, but it has been reported in association with acute sinusitis, in patients with poor immunity and in children. The presentation, clinical course and treatment are discussed in the presented patient. To our knowledge, this is the first report in the world literature of a bilateral posterior septal abscess associated with acute sinusitis in an otherwise healthy adult.

Pyridoxine deficiency in adult patients with status epilepticus.

PubMed

Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan

2015-11-01

An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Three siblings with Prader-Willi syndrome caused by imprinting center microdeletions and review.

PubMed

Hartin, Samantha N; Hossain, Waheeda A; Weisensel, Nicolette; Butler, Merlin G

2018-04-01

Prader-Willi syndrome (PWS) is a complex genetic imprinting disorder characterized by childhood obesity, short stature, hypogonadism/hypogenitalism, hypotonia, cognitive impairment, and behavioral problems. Usually PWS occurs sporadically due to the loss of paternally expressed genes on chromosome 15 with the majority of individuals having the 15q11-q13 region deleted. Examples of familial PWS have been reported but rarely. To date 13 families have been reported with more than one child with PWS and without a 15q11-q13 deletion secondary to a chromosome 15 translocation, inversion, or uniparental maternal disomy 15. Ten of those 13 families were shown to carry microdeletions in the PWS imprinting center. The microdeletions were found to be of paternal origin in nine of the ten cases in which family studies were carried out. Using a variety of techniques, the microdeletions were identified in regions within the complex SNRPN gene locus encompassing the PWS imprinting center. Here, we report the clinical and genetic findings in three adult siblings with PWS caused by a microdeletion in the chromosome 15 imprinting center inherited from an unaffected father that controls the activity of genes in the 15q11-q13 region and summarize the 13 reported cases in the literature. © 2018 Wiley Periodicals, Inc.

Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome.

PubMed

Gumus Balikcioglu, Pinar; Balikcioglu, Metin; Muehlbauer, Michael J; Purnell, Jonathan Q; Broadhurst, David; Freemark, Michael; Haqq, Andrea M

2015-10-01

The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) -matched obese controls (OCs). In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive.

Ab Interno Trabeculectomy in the Adult Patient

PubMed Central

SooHoo, Jeffrey R.; Seibold, Leonard K.; Kahook, Malik Y.

2015-01-01

Glaucoma is a potentially blinding disease that affects millions of people worldwide. The mainstay of treatment is lowering of intraocular pressure (IOP) through the use of medications, laser and/or incisional surgery. The trabecular meshwork (TM) is thought to be the site of significant resistance to aqueous outflow in open angle glaucoma. Theoretically, an incision through TM or TM removal should decrease this resistance and lead to a significant reduction in IOP. This approach, commonly referred to as goniotomy or trabeculotomy, has been validated in the pediatric population and has been associated with long-term IOP control. In adults, however, removal of TM tissue has been historically associated with more limited and short-lived success. More recent evidence, reveals that even adult patients may benefit significantly from removal of diseased TM tissue and can lead to a significant reduction in IOP that is long-lasting and safe. In this review, we discuss current evidence and techniques for ab interno trabeculectomy using various devices in the adult patient. PMID:25624670

Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

PubMed Central

Lukoshe, Akvile; Hokken-Koelega, Anita C.; van der Lugt, Aad; White, Tonya

2014-01-01

Background Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. Methods High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Results Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. Conclusions These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene

High-flow nasal cannula therapy for adult patients

PubMed Central

Zhang, Jian; Lin, Ling; Pan, Konghan; Zhou, Jiancang

2016-01-01

High-flow nasal cannula (HFNC) oxygen therapy has several physiological advantages over traditional oxygen therapy devices, including decreased nasopharyngeal resistance, washing out of the nasopharyngeal dead space, generation of positive pressure in the pharynx, increasing alveolar recruitment in the lungs, humidification of the airways, increased fraction of inspired oxygen and improved mucociliary clearance. Recently, the use of HFNC in treating adult critical illness patients has significantly increased, and it is now being used in many patients with a range of different disease conditions. However, there are no established guidelines to direct the safe and effective use of HFNC for these patients. This review article summarizes the available published literature on the positive physiological effects, mechanisms of action, and the clinical applications of HFNC, compared with traditional oxygen therapy devices. The available literature suggests that HFNC oxygen therapy is an effective modality for the early treatment of critically adult patients. PMID:27698207

Prader-Willi-like syndrome in a patient with an Xq23q25 duplication.

PubMed

Monaghan, K G; Van Dyke, D L; Feldman, G L

1998-11-16

We report on a 24-year old woman with an Xq duplication and findings suggestive of Prader-Willi syndrome (PWS). Her birth weight was at the 3rd centile and her birth length was less than the 3rd centile. She was hypotonic and had a weak cry as an infant. There were no feeding difficulties, although her mother reports that as an infant, she was "small for her age." Excessive weight gain began between 3 and 4 years. The patient's development was delayed and she received special education. She has a history of hiding food. She has a sleep disturbance disorder and inappropriate social behavior. At the age of 24 years her height was below the 5th centile and weight >95th centile. She has physical findings typical of PWS, skin picking, and speech articulation defects. Cytogenetic analysis showed a 46,X,dup(X)(q23q25) karyotype. Fluorescent in situ hybridization (FISH) studies using a chromosome X painting probe demonstrated that the rearrangement was intrachromosomal. The X-chromosome fold scoring technique was used to determine the X inactivation pattern and indicated that some cells expressed the abnormal X chromosome. Results of FISH studies using the SNRPN probe localized to 15q11q13 and DNA studies using the PW71B and SNRPN probes were normal. The duplicated X chromosome, random X inactivation pattern, and the negative molecular studies for PWS indicate that the abnormal X chromosome is the basis of this patient's phenotype. This patient emphasizes the importance of obtaining a karyotype even when a syndrome diagnosable by molecular methods is strongly suspected.

The effect of growth hormone treatment or physical training on motor performance in Prader-Willi syndrome: a systematic review.

PubMed

Reus, Linda; van Vlimmeren, Leo A; Staal, J Bart; Otten, Barto J; Nijhuis-van der Sanden, Maria W G

2012-09-01

Although motor problems in Prader-Willi syndrome (PWS) are prominent in infants, and continue into childhood and adulthood, there is little insight into the factors important for clinical management. The literature was reviewed to: (1) provide an overview of the characteristics and prevalence of motor problems and (2) evaluate the effects of growth hormone (GH) treatment and physical training on motor performance. A systematic search revealed 34 papers: 13 on motor performance; 12 on GH treatment; and nine on physical training. In infants, motor development is 30-57% of the normal reference values, and children and adults also have significant problems in skill acquisition, muscle force, cardiovascular fitness, and activity level. GH treatment positively influenced motor performance in infants, children, and adults, although not all studies demonstrated an effect. All studies on physical training demonstrated beneficial effects in PWS patients. We suggest a combination of GH treatment and physical training to be started as soon as possible, especially in infants, to improve motor development as this will positively influence general development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lifestyle Habits among Adult Congenital Heart Disease Patients in Malta.

PubMed

Caruana, Maryanne; Grech, Victor

2016-07-01

Adult congenital heart disease patients are prone to health risk behaviors like their peers. Such behaviors can have serious implications, particularly in patients with complex congenital lesions. We investigated patterns in tobacco smoking, alcohol consumption, substance misuse, dental reviews, and physical activity in Maltese patients. A questionnaire modeled on the 2008 European Health Interview Survey was offered to consecutive adult congenital heart disease outpatients, aged 16 years and over, between May 2013 and May 2014. Foreigners and patients with learning difficulties or cognitive impairment were excluded. Data on these habits was compared with that from 372 age-matched and sex-matched 2008 survey responders (general population cohort). There were 125 patient responders (65 males; mean age 30.64, SD 12.80 years). Adult congenital heart disease patients smoked less (patients 18.4%, general 32.0% P = .004) and had more regular dental reviews (patients 60.9%, general 45.2% P = .003) but were less physically active than the general population cohort (patients 30.6%, general 62.9% P < .001). The difference in smoking was only significant in patients born after the mid-1970s (younger) and females, while dental reviews were only better in younger and male patients. Male patients consumed alcohol more frequently (38.1%) than general population males (23.3%, P = .02). In the patient cohort, smoking was more likely with milder congenital lesions (OR 4.689, P = .007), substance misuse more likely in males (OR 5.703, P = .036) and with milder lesions (OR 5.405, P = .030) and alcohol consumption more likely in males (OR 11.697, P < .001). Although there is an overall lower uptake of some unhealthy habits by Maltese adult congenital heart disease patients, this is not consistent between sexes or age groups. Male and older patients and those with milder lesions might need more reinforcement of the advice given regarding lifestyle habits

A neuropsychological assessment of frontal cognitive functions in Prader-Willi syndrome.

PubMed

Jauregi, J; Arias, C; Vegas, O; Alén, F; Martinez, S; Copet, P; Thuilleaux, D

2007-05-01

Prader-Willi syndrome (PWS) is associated with a characteristic behavioural phenotype whose main features are, alongside compulsive hyperphagia, deficits in social behaviour: social withdrawal, temper tantrums, perseverative speech and behaviour, mental rigidity, stereotyped behaviour, impulsiveness, etc. Similar symptoms may also be found in autistic spectrum disorders and lesional pathologies of the frontal lobe. In both cases, such symptoms have been related to dysfunctions in frontal cognitive processes such as attention, working memory and executive functions. This study uses standardized neuropsychological instruments to analyse the degree to which these processes are affected in PWS. The sample comprised 16 individuals with a genetically confirmed PWS diagnosis. Subjects' IQ (Wechsler Adult Intelligence Scale), academic level, laterality and body mass index (BMI) were calculated. Attention, memory and executive functions were analysed using standard, widely employed neuropsychological tests. We compared the results of the sample group with the general population. Correlation analyses were carried out with IQ, academic level and BMI. In all the neuropsychological measures focusing on attention, executive functions and visuoperceptual organization, the study sample scored significantly lower than the normative reference population. The scores of the tests used for measuring immediate memory were also significantly lower when trials required sequential processing, although not when they required simultaneous processing. In the memorization of a list of words, subjects showed an initial deficit which disappeared with repetition, enabling them to obtain scores similar to the reference population. No significant correlations were found with BMI, and a higher IQ or academic level did not improve scores in the majority of tests. The study shows a deficit in elementary frontal cognitive processes in PWS patients. This deficit may be involved in the social behaviour

General practitioners' use of caries-preventive agents in adult patients versus pediatric patients: findings from the dental practice-based research network.

PubMed

Riley, Joseph L; Gordan, Valeria V; Rindal, D Brad; Fellows, Jeffrey L; Williams, O Dale; Ritchie, Lloyd K; Gilbert, Gregg H

2010-06-01

In this study, the authors tested the frequency of dentists' recommendations for and use of caries-preventive agents for children as compared with adults. The authors surveyed 467 general dentists in the Dental Practice-Based Research Network who practice within the United States and treat both pediatric and adult patients. They asked dentists to identify the percentage of their patients for whom they had administered or recommended dental sealants, in-office and at-home fluoride, chlorhexidine rinse and xylitol gum. Dentists were less likely to provide adult patients than pediatric patients with in-office caries-preventive agents. However, the rate at which they recommended at-home preventive regimens for the two groups of patients was similar. Dentists with a conservative approach to caries treatment were the most likely to use and recommend the use of caries-preventive agents at similar rates in adults as in children. In addition, dentists in practices with a greater number of patients who had dental insurance were significantly more likely to provide in-office fluoride or sealants to adult patients than to pediatric patients. General dentists use in-office caries-preventive agents more commonly with their pediatric patients than with their adult patients. General dentists should consider providing additional in-office caries-preventive agents for their adult patients who are at increased risk of experiencing dental caries.

Comparative clinical outcomes between pediatric and young adult dialysis patients.

PubMed

Atkinson, Meredith A; Lestz, Rachel M; Fivush, Barbara A; Silverstein, Douglas M

2011-12-01

Published data on the comparative achievement of The Kidney Disease Dialysis Outcome Quality Initiative (KDOQI) recommended clinical performance targets between children and young adults on dialysis are scarce. To characterize the achievement of KDOQI targets among children (<18 years) and young adults (18-24 years) with prevalent end stage renal disease (ESRD), we performed a cross-sectional analysis of data collected by the Mid-Atlantic Renal Coalition, in conjunction with the 2007 and 2008 ESRD Clinical Performance Measures Projects. Data on all enrolled pediatric dialysis patients, categorized into three age groups (0-8, 9-12, 13-17 years), and on a random sample of 5% of patients ≥ 18 years in ESRD Network 5 were examined for two study periods: hemodialysis (HD) data were collected from October to December 2006 and from October to December 2007 and peritoneal dialysis (PD) data were collected from October 2006 to March 2007 and from October 2007 to March 2008. In total, 114 unique patients were enrolled the study, of whom 41.2% (47/114) were on HD and 58.8% (67/114) on PD. Compared to the pediatric patients, young adults were less likely to achieve the KDOQI recommended serum phosphorus levels and serum calcium × phosphorus product values, with less than one-quarter demonstrating values at or below each goal. Multivariate analysis revealed that both young adults and 13- to 17-year-olds were less likely to achieve target values for phosphorus [young adults: odds ratio (OR) 0.04, 95% confidence interval (95% CI) 0.01-0.19, p < 0.001; 13- to 17-year-olds: OR 0.17, 95% CI 0.04-0.77, p = 0.02] and calcium × phosphorus product (young adults: OR 0.01, 95% CI 0.002-0.09, p < 0.001; 13- to 17-year-olds: OR 0.09, 95% CI 0.02-0.56, p = 0.01) than younger children. In summary, there are significant differences in clinical indices between pediatric and young adult ESRD patients.

Relationship between the blood perfusion values determined by laser speckle imaging and laser Doppler imaging in normal skin and port wine stains.

PubMed

Chen, Defu; Ren, Jie; Wang, Ying; Zhao, Hongyou; Li, Buhong; Gu, Ying

2016-03-01

Laser Doppler imaging (LDI) and laser speckle imaging (LSI) are two major optical techniques aiming at non-invasively imaging the skin blood perfusion. However, the relationship between perfusion values determined by LDI and LSI has not been fully explored. 8 healthy volunteers and 13 PWS patients were recruited. The perfusions in normal skin on the forearm of 8 healthy volunteers were simultaneously measured by both LDI and LSI during post-occlusive reactive hyperemia (PORH). Furthermore, the perfusions of port wine stains (PWS) lesions and contralateral normal skin of 10 PWS patients were also determined. In addition, the perfusions for PWS lesions from 3 PWS patients were successively monitored at 0, 10 and 20min during vascular-targeted photodynamic therapy (V-PDT). The average perfusion values determined by LSI were compared with those of LDI for each subject. In the normal skin during PORH, power function provided better fits of perfusion values than linear function: powers for individual subjects go from 1.312 to 1.942 (R(2)=0.8967-0.9951). There was a linear relationship between perfusion values determined by LDI and LSI in PWS and contralateral normal skin (R(2)=0.7308-0.9623), and in PWS during V-PDT (R(2)=0.8037-0.9968). The perfusion values determined by LDI and LSI correlate closely in normal skin and PWS over a broad range of skin perfusion. However, it still suggests that perfusion range and characteristics of the measured skin should be carefully considered if LDI and LSI measures are compared. Copyright © 2015 Elsevier B.V. All rights reserved.

Patient Portal Use and Experience Among Older Adults: Systematic Review

PubMed Central

2017-01-01

Background The older adult population (65 years or older) in the United States is growing, and it is important for communities to consider ways to support the aging population. Patient portals and electronic personal health records (ePHRs) are technologies that could better serve populations with the highest health care needs, such as older adults. Objective The aim of this study was to assess the existing research landscape related to patient portal and ePHR use and experience among older adults and to understand the benefits and barriers to older adults’ use and adoption of patient portals and ePHRs. Methods We searched six pertinent bibliographic databases for papers, published from 2006 to 2016 and written in English, that focused on adults 60 years or older and their use of or experience with patient portals or ePHRs. We adapted preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to review papers based on exclusion and inclusion criteria. We then applied thematic analysis to identify key themes around use, experience, and adoption. Results We retrieved 199 papers after an initial screening and removal of duplicate papers. Then we applied an inclusion and exclusion criteria, resulting in a final set of 17 papers that focused on 15 separate projects. The majority of papers described studies involving qualitative research, including interviews and focus groups. They looked at the experience and use of ePHRs and patient portals. Overall, we found 2 main barriers to use: (1) privacy and security and (2) access to and ability to use technology and the Internet. We found 2 facilitators: (1) technical assistance and (2) family and provider advice. We also reported on older adults’ experience, including satisfaction with the system and improvement of the quality of their health care. Several studies captured features that older adults wanted from these systems such as further assistance managing health-related tasks and contextual

Alpha-1-antitrypsin phenotypes in adult liver disease patients

PubMed Central

Alempijevic, Tamara; Milutinovic, Aleksandra Sokic; Kovacevic, Nada

2009-01-01

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers. PMID:19961268

Minimal and moderate oral sedation in the adult special needs patient.

PubMed

Coke, John M; Edwards, Michael D

2009-04-01

Oral minimal/moderate sedation can be an effective tool to aid in the dental management of adult special needs patients. Specific sedative drugs must be chosen by the dentist that can be used safely and effectively on these patients. This article focuses on a select number of these drugs, specific medical and pharmacologic challenges presented by adult special needs patients, and techniques to safely administer oral minimal and moderate sedation.

Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome

PubMed Central

Balikcioglu, Metin; Muehlbauer, Michael J.; Purnell, Jonathan Q.; Broadhurst, David; Freemark, Michael; Haqq, Andrea M.

2015-01-01

Background: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. Objective: We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) –matched obese controls (OCs). Methods: In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. Results: Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. Conclusion: Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive. PMID:26259133

Maternal uniparental disomy 14 syndrome demonstrates prader-willi syndrome-like phenotype.

PubMed

Hosoki, Kana; Kagami, Masayo; Tanaka, Touju; Kubota, Masaya; Kurosawa, Kenji; Kato, Mitsuhiro; Uetake, Kimiaki; Tohyama, Jun; Ogata, Tsutomu; Saitoh, Shinji

2009-12-01

To delineate the significance of maternal uniparental disomy 14 (upd(14)mat) and related disorders in patients with a Prader-Willi syndrome (PWS)-like phenotype. We examined 78 patients with PWS-like phenotype who lacked molecular defects for PWS. The MEG3 methylation test followed by microsatellite polymorphism analysis of chromosome 14 was performed to detect upd(14)mat or other related abnormalities affecting the 14q32.2-imprinted region. We identified 4 patients with upd(14)mat and 1 patient with an epimutation in the 14q32.2 imprinted region. Of the 4 patients with upd(14)mat, 3 had full upd(14)mat and 1 was mosaic. Upd(14)mat and epimutation of 14q32.2 represent clinically discernible phenotypes and should be designated "upd(14)mat syndrome." This syndrome demonstrates a PWS-like phenotype particularly during infancy. The MEG3 methylation test can detect upd(14)mat syndrome defects and should therefore be performed for all undiagnosed infants with hypotonia.

The utility of presacral drainage in penetrating rectal injuries in adult and pediatric patients.

PubMed

Savoie, Kate B; Beazley, Thomas M; Cleveland, Brent; Khaneki, Sina; Markel, Troy A; Hammer, Peter M; Savage, Stephanie; Williams, Regan F

2017-11-01

With changing weaponry associated with injuries in civilian trauma, there is no clinical census on the utility of presacral drainage (PSD) in penetrating rectal injuries (PRIs), particularly in pediatric patients. Patients with PRI from July 2004-June 2014 treated at two free-standing children's hospitals and two adult level 1 trauma centers were compared by age (pediatric patients ≤16 years) and PSD. A stratified analysis was performed based on age. The primary outcome was pelvic/presacral abscess. We identified 81 patients with PRI; 19 pediatric, 62 adult. Forty patients had PSD; only three pediatric patients had a drain. Adult patients were more likely to have sustained gunshot wounds (84%), whereas pediatric patients were more likely to sustain impalement injuries (59%). Pediatric patients were more likely to have distal extraperitoneal injuries (56% versus 27% in adults, P = 0.03). PSD was more common in adult patients (59% versus 14%, P = 0.0004), African-Americans (71% versus 11% Caucasian, P < 0.01), and those sustaining gun shot wounds (63% versus 18% impalement, P < 0.01); only race remained significant in stratified analysis for both adult and pediatric patients. There were three cases of pelvic/presacral abscess, all in the adult patients (P = 0.31); one patient with PSD and two without PSD (P = 0.58). In stratified analysis, there were no differences in any infectious complication between those with and without PSD. Pelvic/presacral abscess is a rare complication of PRI, especially in pediatric patients. PSD is not associated with decreased rates of infectious complications and may not be necessary in the treatment of PRI. Copyright © 2017 Elsevier Inc. All rights reserved.

Klinefelter's syndrome and Prader-Willi syndrome: a rare combination.

PubMed

Verhoeven, W M A; de Vries, B B A; Duffels, S J H; Egger, J I M; Noordam, C; Tuinier, S

2007-01-01

In this paper a review is presented of the rare combination of Klinefelter's syndrome and Prader-Willi syndrome (PWS) and a second case of this combination with a uniparental disomy (UPD) etiology of PWS is described. Patients outlined in all other 8 reports and the present case have a PWS phenotype. Virtually no information is available on the behavioral and psychopathological phenotype in this combination. The latter may be explained by the observation that psychiatric syndromes are especially prevalent in PWS patients with a UPD. It is concluded that instability in mood and behavior in this and other syndromes should be preferentially treated with mood stabilizing agents. Copyright (c) 2007 S. Karger AG, Basel.

Psychotherapy Termination Practices with Older Adults: Impact of Patient and Therapist Characteristics.

PubMed

Sullivan, Daniel J; Zeff, Patricia; Zweig, Richard A

2018-02-06

The aims of this study were to survey clinicians' opinions regarding psychotherapy practices in mutual termination with a specified population (depressed older adult outpatients) and to examine the patient and therapist characteristics that may influence such practices. We surveyed psychologists' (N = 96) psychotherapy termination practices, using a hypothetical depressed older adult as a referent, to assess consensus on the appropriateness of various guidelines to termination and to examine whether these differ as a function of patient and therapist characteristics. Several practices were generally agreed to be "extremely appropriate" when terminating psychotherapy with older adults, including collaborating to determine the end date of treatment and discussing patient growth. Data also indicate that patient factors, such as personality pathology, and therapist factors, such as having an Integrative theoretical orientation were associated with differential endorsement of termination practices. Identification as a geropsychologist or working regularly with older adults were associated with a more cautious approach to termination. There is substantial consensus regarding many approaches to termination, but modifications might be appropriate depending on patient characteristics. Clinicians agree on a set of fundamental termination practices when working with older adults, but modify these based on orientation and diagnosis.

Wellness perception in persons with traumatic brain injury and its relation to functional independence.

PubMed

Bezner, J R; Hunter, D L

2001-06-01

To test the reliability and validity of a perceptual wellness measure in persons after traumatic brain injury (TBI) and to determine whether a relation exists between functional independence and wellness perceptions in the same population. Survey research. A private, residential brain injury program. A convenience sample of 49 patients (43 men, 6 women) with TBI whose mean age was 32.1 years (range, 18-61yr) and mean time since injury was 10.47 years (range, 1-21yr). The Perceived Wellness Survey (PWS) assessed wellness. The PWS has 6 subscales measuring physical, psychologic, emotional, intellectual, spiritual, and social wellness. The FIM instrument was used to measure functional status. The mean PWS score (15.99) for the sample was comparable to published samples of adults (mean, 15.31-16.51); however, the reliability of the composite score (alpha = .58) and the subscales (alpha = .32-.64) was less than that obtained in previous samples (composite alpha = 0.91; subscale alpha = .64-.81). The correlations between the PWS and the FIM scores were not significant. The PWS in its composite form is a reliable measure for use with persons with TBI. The finding that perceived wellness and functional independence were not related suggests that these constructs are unique and thus should both be measured. The measurement of perceptions will enable the provider to consider a client holistically and to develop programs that address quality of life issues. Further, because perceptions influence behaviors, understanding a person's perceptions in multiple dimensions may provide a useful and necessary framework for developing intervention programs that address behavioral and cognitive issues that are important to that person.

[Psychological aspects in adult congenital heart disease patients].

PubMed

Lahlou-Laforêt, Khadija

2013-03-01

Patients with congenital heart disease mostly owe their survival to a saving chirurgical intervention which confers them a survivor's identity. The relationships between parents and children are strongly influenced by these early events. The effort made by parents to allow a good quality of life to their child is often successful. However, difficulties to anticipate late complications are frequently observed in adolescents and young adult patients. In adulthood, these patients seem to discover suddenly their disease, its consequences and the necessity of long term follow-up. The coexistence of several changes, i.e adolescence, change of medical team, transfer of parental decision to the young adult own decision make this period a vulnerable way. An adapted multidisciplinary support aimed to a real transition may limit the risks of breaking off and better organize long term follow-up.

[Orofacial clinical manifestations in adult patients with variable common immunodeficiency].

PubMed

Chávez-García, Aurora Alejandra; Moreno-Alba, Miguel Ángel; Elizalde-Monroy, Martín; Segura-Méndez, Nora Hilda; Romero-Flores, Jovita; Cambray-Gutiérrez, Julio César; López-Pérez, Patricia; Del Rivero-Hernández, Leonel Gerardo

2015-01-01

Common variable immunodeficiency is the primary immunodeficiency (CVID) frequently found in adults. Its prevalence is estimated from 1:25,000 to 75,000 alive newborns; there are variations by ethnic groups, it is estimated about 50-70% in Caucasian patients. Oral cavity lesions are rarely found in adult patients with CVID, there are reports about lesions on pediatric patients mostly caused by infections. To describe the orofacial lesions (oral, maxillofacial and neck area) affecting adults with CVID. A transversal, prospective study was done in patients with CVID attended at Specialties Hospital, CMN SXXI, Mexico City. Patients where examined by the oral and maxillofacial surgeon and clinical findings were reported, then the descriptive analysis of the lesions was done. We evaluated 26 patients, 16 female and 10 males, average age of 38.6 years. In 18/26 patients we found oral lesions on 7 different types. The most frequent was minor salivary glands hiperplasia (19/26),petechiae (12/26) and herpetic ulcers (7/26). In head and neck, we found 4 different lesions, the most common was lymphadenopathy <2cm (4/26). The immunologic alterations associated to CVID favors the development of lesions mainly of infectious and probably autoinmune origin that affects the oral cavity and head and neck area.

Prevalence of vitamin D deficiency and insufficiency among adult asthmatic patients in Karachi.

PubMed

Kamran, Afshan; Alam, Syed Mahboob; Qadir, Farida

2014-11-01

Vitamin D deficiency has assumed pandemic proportions all over the world. It has been documented as a frequent problem in studies of young adults, elderly person and children in other countries, but there is no reliable data on vitamin D status of adult asthmatic patients in Pakistan. To determine the prevalence of vitamin D deficiency and insufficiency in adult asthmatic patients with moderate to severe asthma using a cross-sectional study design in Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi.311 adult asthmatic patients with moderate to severe asthma were recruited from JPMC, tertiary care hospital in Karachi. Questionnaires were administered together demographics, height, weight, nutritional and physical activity assessment. Blood samples for vitamin D measurement were also taken. Results show high prevalence of vitamin D deficiency and insufficiency (88.10%) in adult patients with moderate to severe persistent asthma. Vitamin D deficiency and insufficiency was more frequently observed in female than in male patients.67.66% of the female patients had serum vitamin D level less than 20 ng/ml as compare to 56.1% of the male patients (p=0.01).

Topical rapamycin combined with pulsed dye laser in the treatment of capillary vascular malformations in Sturge-Weber syndrome: phase II, randomized, double-blind, intraindividual placebo-controlled clinical trial.

PubMed

Marqués, Laura; Núñez-Córdoba, Jorge M; Aguado, Leyre; Pretel, Maider; Boixeda, Pablo; Nagore, Eduardo; Baselga, Eulalia; Redondo, Pedro

2015-01-01

Sturge-Weber syndrome (SWS) is characterized by port-wine stains (PWS) affecting the face, eyes, and central nervous system. Pulsed dye laser (PDL) is the standard treatment for PWS. Unfortunately, recurrence is frequent because of reformation and reperfusion of blood vessels. We sought to assess the clinical efficacy of topical rapamycin combined with PDL in PWS of patients with SWS. We conducted a phase II, randomized, double-blind, intraindividual placebo-controlled, clinical trial. We recruited 23 patients with SWS and facial PWS (12 women; median age 33 years, age range 17-65 years) from the University Clinic of Navarra, Spain. Four interventions were evaluated: placebo, PDL + placebo, rapamycin, and PDL + rapamycin. Clinical and histologic responses were evaluated using a chromatographic computerized system, spectrometry, and histologic analyses at 6, 12, and 18 weeks after the intervention. PDL + rapamycin yielded the lowest digital photographic image score and the lowest percentage of vessels in histologic analysis, and showed a statistically significant improvement compared with the other interventions. The treatment was generally well tolerated. PDL was only applied to the lateral parts of the PWS area. Topical rapamycin associated with PDL seems to be an effective treatment for PWS in patients with SWS. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Systematic review of the clinical and genetic aspects of Prader-Willi syndrome

PubMed Central

2011-01-01

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. This syndrome has a characteristic phenotype including severe neonatal hypotonia, early-onset hyperphagia, development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioral problems, and psychiatric problems. PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect. Over 99% of PWS cases can be diagnosed using DNA methylation analysis. Early diagnosis of PWS is important for effective long-term management. Growth hormone (GH) treatment improves the growth, physical phenotype, and body composition of patients with PWS. In recent years, GH treatment in infants has been shown to have beneficial effects on the growth and neurological development of patients diagnosed during infancy. There is a clear need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy in patients with PWS. PMID:21503198

Systematic review of the clinical and genetic aspects of Prader-Willi syndrome.

PubMed

Jin, Dong Kyu

2011-02-01

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder that is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. This syndrome has a characteristic phenotype including severe neonatal hypotonia, early-onset hyperphagia, development of morbid obesity, short stature, hypogonadism, learning disabilities, behavioral problems, and psychiatric problems. PWS is an example of a genetic condition caused by genomic imprinting. It can occur via 3 main mechanisms that lead to the absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and an imprinting defect. Over 99% of PWS cases can be diagnosed using DNA methylation analysis. Early diagnosis of PWS is important for effective long-term management. Growth hormone (GH) treatment improves the growth, physical phenotype, and body composition of patients with PWS. In recent years, GH treatment in infants has been shown to have beneficial effects on the growth and neurological development of patients diagnosed during infancy. There is a clear need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy in patients with PWS.

Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.

PubMed

Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F

2016-12-01

Current threshold recommendations for elective abdominal aortic aneurysm (AAA) repair are based solely on maximal AAA diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than AAA diameter of AAA rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict AAA rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured AAA (rAAA) were retrospectively identified and grouped into patients with small rAAA (maximum diameter <6 cm) or large rAAA (>6 cm). Patients with large (>6 cm) non-rAAA were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with rAAA, of which 15 ruptured with AAA diameter <60 mm (small rAAA group). Patients with small rAAAs were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-rAAA group. Patients with small rAAAs were also more likely to have AOO compared with non-rAAAs >60 mm (27% vs 8%; P = .047). Among all patients with rAAAs, those with AOO ruptured at smaller mean AAA diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small rAAA and a large non-rAAA showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in AAA are associated with rAAAs at

Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management.

PubMed

Lane, Laura C; Flowers, Josephine; Johnstone, Helen; Cheetham, Tim

2018-04-25

There is little adult height data in patients with familial male-limited precocious puberty (FMPP) and no management consensus. We assessed the treatment and adult height in local patients with FMPP and those reported in the literature. Growth data were obtained on four local patients with FMPP and a search performed to obtain management details and adult height data on cases in the literature. UK (90) population standards were used to calculate standard deviation scores (SDS). Adult height data were available on 25 men with FMPP of whom 21 were treated. Median adult height SDS of patients was -1.5 SD with a mid-parental target of -0.6 SD (p=0.1). Eight patients (32%) had an adult height above the mid-parental target and seven patients (28%) had a height >2 SD below the mean. The median height SD was -0.03 in untreated patients and +0.5 SD in those receiving an aromatase inhibitor. There was no relationship between height and age at presentation. Aromatase inhibitor therapy is associated with a positive height outcome in FMPP but the outcome with and without intervention is unpredictable. Clinicians need to be cautious when counselling families about the potential height outcome in FMPP.

Urinary incontinence in persons with Prader-Willi Syndrome.

PubMed

Von Gontard, Alexander; Didden, Robert; Sinnema, Margje; Curfs, Leopold

2010-12-01

To assess and identify the frequency and type of urinary incontinence (UI), as well as associated symptoms in persons with Prader-Willi syndrome (PWS). PWS is characterized by mental retardation, short stature, obesity and hypogonadism. The behavioural phenotype includes eating problems, temper outbursts, affective disorders, stereotypies and speech abnormalities. UI is common in children with mental retardation in general, but has not been reported systematically in children with PWS so far. The Dutch version of the 'Parental Questionnaire: Enuresis/Urinary Incontinence' was completed by 118 parents of children with PWS. This questionnaire includes items referring to day- and night-time wetting, toilet habits, observable voiding behaviours and reactions, urinary tract infections, stool habits and behavioural symptoms. The rate of nocturnal enuresis in persons with PWS was 13.6% (16) at a mean age of 15.1 years. 3.8% (5) had additional daytime urinary incontinence, and 3.3% (4) had faecal incontinence. Lower urinary tract symptoms were commonly indicative of overactive bladder, dysfunctional voiding and postponement. Also, the rate of internalizing and externalizing behavioural problems was high. Urinary incontinence is more common in persons with PWS than in typically developing children, adolescents and adults. As lower urinary tract symptoms are common, detailed assessment and specific treatment of UI should be part of the care of all persons with PWS. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

PET scan perfusion imaging in the Prader–Willi syndrome: new insights into the psychiatric and social disturbances

PubMed Central

Mantoulan, Carine; Payoux, Pierre; Diene, Gwenaëlle; Glattard, Mélanie; Rogé, Bernadette; Molinas, Catherine; Sevely, Annick; Zilbovicius, Monica; Celsis, Pierre; Tauber, Maïthé

2011-01-01

The Prader–Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H215O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals. PMID:20588317

PET scan perfusion imaging in the Prader-Willi syndrome: new insights into the psychiatric and social disturbances.

PubMed

Mantoulan, Carine; Payoux, Pierre; Diene, Gwenaëlle; Glattard, Mélanie; Rogé, Bernadette; Molinas, Catherine; Sevely, Annick; Zilbovicius, Monica; Celsis, Pierre; Tauber, Maïthé

2011-01-01

The Prader-Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H(2)(15)O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals.

Phonation interval modification and speech performance quality during fluency-inducing conditions by adults who stutter

PubMed Central

Ingham, Roger J.; Bothe, Anne K.; Wang, Yuedong; Purkhiser, Krystal; New, Anneliese

2012-01-01

Purpose To relate changes in four variables previously defined as characteristic of normally fluent speech to changes in phonatory behavior during oral reading by persons who stutter (PWS) and normally fluent controls under multiple fluency-inducing (FI) conditions. Method Twelve PWS and 12 controls each completed 4 ABA experiments. During A phases, participants read normally. B phases were 4 different FI conditions: auditory masking, chorus reading, whispering, and rhythmic stimulation. Dependent variables were the durations of accelerometer-recorded phonated intervals; self-judged speech effort; and observer-judged stuttering frequency, speech rate, and speech naturalness. The method enabled a systematic replication of Ingham et al. (2009). Results All FI conditions resulted in decreased stuttering and decreases in the number of short phonated intervals, as compared with baseline conditions, but the only FI condition that satisfied all four characteristics of normally fluent speech was chorus reading. Increases in longer phonated intervals were associated with decreased stuttering but also with poorer naturalness and/or increased speech effort. Previous findings concerning the effects of FI conditions on speech naturalness and effort were replicated. Conclusions Measuring all relevant characteristics of normally fluent speech, in the context of treatments that aim to reduce the occurrence of short-duration PIs, may aid the search for an explanation of the nature of stuttering and may also maximize treatment outcomes for adults who stutter. PMID:22365886

Unique medical issues in adult patients with mucopolysaccharidoses.

PubMed

Mitchell, John; Berger, Kenneth I; Borgo, Andrea; Braunlin, Elizabeth A; Burton, Barbara K; Ghotme, Kemel A; Kircher, Susanne G; Molter, David; Orchard, Paul J; Palmer, James; Pastores, Gregory M; Rapoport, David M; Wang, Raymond Y; White, Klane

2016-10-01

The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2-4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Genomic Imprinting Is Implicated in the Psychology of Music.

PubMed

Mehr, Samuel A; Kotler, Jennifer; Howard, Rhea M; Haig, David; Krasnow, Max M

2017-10-01

Why do people sing to babies? Human infants are relatively altricial and need their parents' attention to survive. Infant-directed song may constitute a signal of that attention. In Prader-Willi syndrome (PWS), a rare disorder of genomic imprinting, genes from chromosome 15q11-q13 that are typically paternally expressed are unexpressed, which results in exaggeration of traits that reduce offspring's investment demands on the mother. PWS may thus be associated with a distinctive musical phenotype. We report unusual responses to music in people with PWS. Subjects with PWS ( N = 39) moved more during music listening, exhibited greater reductions in heart rate in response to music listening, and displayed a specific deficit in pitch-discrimination ability relative to typically developing adults and children ( N = 589). Paternally expressed genes from 15q11-q13, which are unexpressed in PWS, may thus increase demands for music and enhance perceptual sensitivity to music. These results implicate genomic imprinting in the psychology of music, informing theories of music's evolutionary history.

[Eye contact in adult patients with Asperger syndrome].

PubMed

Roy, M; Wolfgang, D

2015-05-01

It is unclear if individuals with autism spectrum disorders rarely hold direct eye contact because eyes are unimportant for them, or if it is actively avoided. The aim of the current investigation was to gain a better understanding for their views on direct eye contact by exploring adult patients with Asperger syndrome. 63 adult patients with Asperger syndrome (28 females, 35 males, 21 - 62 years old) were explored about using and sensing direct eye contact by means of a standardised questionnaire. 87 % of investigated patients depict direct eye contact as being disagreeable. They describe it as arduous and distracting. Therefore they mostly actively avoid direct eye contact. The here gained knowledge about aversion towards direct eye contact in individuals with autism should lead to a stronger understanding and acceptance of this problem in the non-autistic population. © Georg Thieme Verlag KG Stuttgart · New York.

Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

PubMed

Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

2016-09-01

OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

Endoscopic Third Ventriculostomy before Posterior Fossa Tumor Surgery in Adult Patients.

PubMed

Marx, Sascha; El Damaty, Ahmed; Manwaring, Jotham; El Refaee, Ehab; Fleck, Steffen; Fritsch, Michael; Gaab, Michael R; Schroeder, H W S; Baldauf, Jörg

2018-03-01

 Obstructive hydrocephalus in patients with posterior fossa tumors is frequently seen. Treatment options include immediate tumor removal or prior cerebrospinal fluid (CSF) diversion procedures. The necessity and feasibility of an ETV in these situations has not yet been proven in adult patients.  We retrospectively reviewed our prospectively maintained database for ETVs before surgery of posterior fossa tumors in adults. The primary focus of data analyses was the question of whether the ETV was suitable to treat the acute situation of hydrocephalus without an increased rate of complications due to the special anatomical situation with a posterior fossa tumor. We also analyzed whether any further CSF diverting procedures were necessary.  A total of 40 adult patients who underwent an ETV before posterior fossa tumor surgery were analyzed. Overall, 33 patients (82.5%) had clinical signs of hydrocephalus, and all of them improved in their clinical course after ETV. Seven patients (17.5%) did not demonstrate clinical signs of hydrocephalus, but ETV was performed with prophylactic or palliative intent in six patients and one patient, respectively. No complications were observed due to ETV itself. No permanent shunting procedure was necessary in a mean follow-up of 76.5 months. Early additional CSF diverting procedures (redo ETV, external ventricular drain) were performed in five patients (12.5%).  The present series confirms the feasibility and safety of ETV before posterior fossa tumor surgery in adult patients. If patients had symptomatic hydrocephalus before tumor surgery, an ETV can be performed, followed by early elective tumor surgery. A prophylactic ETV in asymptomatic patients is not advised. Early elective tumor surgery should be performed in these patients. Georg Thieme Verlag KG Stuttgart · New York.

Change in prevalence of congenital defects in children with Prader-Willi syndrome.

PubMed

Torrado, M; Foncuberta, M E; Perez, M F de Castro; Gravina, L P; Araoz, H V; Baialardo, E; Chertkoff, L P

2013-02-01

The aim of this study was to assess the prevalence of congenital defects observed in patients with Prader-Willi syndrome (PWS) and to compare this prevalence with that described in the general population. In addition, these findings were correlated with the different etiologic subtypes. A total of 180 children with PWS followed for 13 years were included in this study. Diagnosis was confirmed by the methylation test, and genetic subtypes were established by using fluorescence in situ hybridization or multiplex ligation-dependent probe amplification and microsatellite analyses. The prevalence of congenital defects was compared with national and international registries of congenital defects in the general population (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas, European Surveillance of Congenital Anomalies, and the New York Registry). Twenty-two percent of the patients presented congenital defects with a risk of 5.4 to 18.7 times higher than that of the general population. The most frequent congenital defects were heart defects, renoureteral malformations, vertebral anomalies, hip dysplasia, clubfoot, and agenesis/hypoplasia of the corpus callosum. Each of these congenital defects was significantly more frequent in the children with PWS than in the general population. The congenital heart defects were more frequent in girls than in boys with PWS. No significant differences were found when the defects were correlated with the different etiologic subtypes. An increased prevalence of congenital defects was found in our PWS patients. This finding suggests the need for further studies in PWS children that allow physicians to detect the congenital defects found in this series and, thus, to anticipate complications, with the ultimate aim of enhancing the management of PWS patients.

A prospective study of risk for Sturge-Weber syndrome in children with upper facial port-wine stain.

PubMed

Dutkiewicz, Anne-Sophie; Ezzedine, Khaled; Mazereeuw-Hautier, Juliette; Lacour, Jean-Philippe; Barbarot, Sébastien; Vabres, Pierre; Miquel, Juliette; Balguerie, Xavier; Martin, Ludovic; Boralevi, Franck; Bessou, Pierre; Chateil, Jean-François; Léauté-Labrèze, Christine

2015-03-01

Upper facial port-wine stain (PWS) is a feature of Sturge-Weber syndrome (SWS). Recent studies suggest that the distribution of the PWS corresponds to genetic mosaicism rather than to trigeminal nerve impairment. We sought to refine the cutaneous distribution of upper facial PWS at risk for SWS. This was a prospective multicenter study of consecutive cases of upper facial PWS larger than 1 cm² located in the ophthalmic division of trigeminal nerve distribution in infants aged less than 1 year, seen in 8 French pediatric dermatology departments between 2006 and 2012. Clinical data, magnetic resonance imaging, and photographs were systematically collected and studied. PWS were classified into 6 distinct patterns. In all, 66 patients were included. Eleven presented with SWS (magnetic resonance imaging signs and seizure). Four additional infants had suspected SWS without neurologic manifestations. Hemifacial (odds ratio 7.7, P = .003) and median (odds ratio 17.08, P = .008) PWS patterns were found to be at high risk for SWS. A nonmedian linear pattern was not associated with SWS. Small number of patients translated to limited power of the study. Specific PWS distribution patterns are associated with an increased risk of SWS. These PWS patterns conform to areas of somatic mosaicism. Terminology stipulating ophthalmic division of trigeminal nerve territory involvement in SWS should be abandoned. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cluster Analysis on Longitudinal Data of Patients with Adult-Onset Asthma.

PubMed

Ilmarinen, Pinja; Tuomisto, Leena E; Niemelä, Onni; Tommola, Minna; Haanpää, Jussi; Kankaanranta, Hannu

Previous cluster analyses on asthma are based on cross-sectional data. To identify phenotypes of adult-onset asthma by using data from baseline (diagnostic) and 12-year follow-up visits. The Seinäjoki Adult Asthma Study is a 12-year follow-up study of patients with new-onset adult asthma. K-means cluster analysis was performed by using variables from baseline and follow-up visits on 171 patients to identify phenotypes. Five clusters were identified. Patients in cluster 1 (n = 38) were predominantly nonatopic males with moderate smoking history at baseline. At follow-up, 40% of these patients had developed persistent obstruction but the number of patients with uncontrolled asthma (5%) and rhinitis (10%) was the lowest. Cluster 2 (n = 19) was characterized by older men with heavy smoking history, poor lung function, and persistent obstruction at baseline. At follow-up, these patients were mostly uncontrolled (84%) despite daily use of inhaled corticosteroid (ICS) with add-on therapy. Cluster 3 (n = 50) consisted mostly of nonsmoking females with good lung function at diagnosis/follow-up and well-controlled/partially controlled asthma at follow-up. Cluster 4 (n = 25) had obese and symptomatic patients at baseline/follow-up. At follow-up, these patients had several comorbidities (40% psychiatric disease) and were treated daily with ICS and add-on therapy. Patients in cluster 5 (n = 39) were mostly atopic and had the earliest onset of asthma, the highest blood eosinophils, and FEV 1 reversibility at diagnosis. At follow-up, these patients used the lowest ICS dose but 56% were well controlled. Results can be used to predict outcomes of patients with adult-onset asthma and to aid in development of personalized therapy (NCT02733016 at ClinicalTrials.gov). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Gastro-oesophageal reflux - an important causative factor of severe tooth wear in Prader-Willi syndrome?

PubMed

Saeves, Ronnaug; Strøm, Finn; Sandvik, Leiv; Nordgarden, Hilde

2018-04-23

Prader-Willi syndrome (PWS) is the most common genetic human obesity syndrome and is characterized by hypotonia, endocrine disturbances, hyperphagia, obesity and mild mental retardation. Oral abnormalities, such as decreased salivary flow rates and extreme tooth wear, have also been described. Studies have shown a significant increase in reflux symptoms in individuals with obstuctive sleep apnoea syndrome and increased BMI, both of which are typical findings in PWS. Gastro-oesophageal reflux disease (GORD) has been identified in some individuals with PWS and is a significant intrinsic factor in dental tooth wear. The aim of this study was therefore to estimate the prevalence of GORD in adults and children and to evaluate a possible correlation between GORD and tooth wear in adults with PWS. They were all registered at the TAKO-centre. Twenty-nine individuals, 17 adults with a mean age of 32.6 years (range 18-48) and 12 children with a mean age of 8.8 years (range 3-17), agreed to undergo 24-hour oesophageal pH monitoring, and 90% of those enrolled managed to complete the examination. Four children and eleven adults were diagnosed with pathological gastro-oesophageal reflux, which is defined as acid exposure (pH less than 4) more than 3.6 or 4.3 percent of the time, respectively. Manometry performed in the adult group showed a pathologically high lower oesophageal sphincter pressure in four of the five individuals who had normal oesophageal pH values (pH under 4 less than 4.3% of the time). The two groups (reflux and non-reflux) were well balanced according to BMI, genotype, tooth grinding and hyposalivation. However, twice as many individuals in the reflux group as in the non-reflux group reported high consumption of acidic foods and drinks. Increased tooth wear was significantly correlated with GORD in the two groups (reflux n=6 and non-reflux n=6). The prevalence of gastro-oesophageal reflux is high in individuals with PWS. Tooth wear was strongly associated with

Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

ERIC Educational Resources Information Center

de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

2007-01-01

This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

Taiwanese adult cancer patients' reports of using complementary therapies.

PubMed

Lu, Jui-Hua; Tsay, Shiow-Luan; Sung, Su-Ching

2010-01-01

More information is needed by cancer clinicians regarding cancer patients' use of complementary and alternative medicine (CAM). In this qualitative study, in-depth interviews were used to obtain the reports of adult cancer patients regarding their use of CAM. Seven cancer patients (4 women, 3 men) who reported using CAM were recruited by snowball sampling. Content analysis was used to examine the interview transcriptions. Five themes and multiple categories were identified related to CAM use: (1) facing the challenges of cancer (I can't be defeated, need to cooperate with conventional medical treatment, rebuilding my confidence), (2) handling the physical and psychological distress of CAM use (extra loading due to the therapy, uncertainty and fear about the efficacy of CAM, being understood and supported, feeling guilty about being sick, (3) lifestyle disruption (altering social life, changing family living style), (4) having reasons for seeking other therapies (finding a way to cure the disease, boosting my immunity, improving my overall health status, and prolonging life and searching for peace of mind), and (5) unresolved practical concerns about CAM (finding an easy and effective way to practice CAM, needing CAM to be integrated into mainstream health care, and where to get the related information). Adult Taiwanese cancer patients who use CAM do experience burdens secondary to CAM use and prefer that oncology specialists be more informed about CAM. Oncology specialists who know where adult cancer patients could obtain helpful information about CAM would help to decrease the burdens that patients who use CAM experience.

Review of Prader-Willi syndrome: the endocrine approach

PubMed Central

Heksch, Ryan; Kamboj, Manmohan; Anglin, Kathryn

2017-01-01

Prader-Willi syndrome (PWS) is a complex genetic disorder with implications on the endocrine and neurologic systems, metabolism, and behavior. Early in life, PWS is characterized by hypotonia and failure to thrive, followed by obesity and hyperphagia. Patients with PWS develop hypothalamic dysfunction which may lead growth hormone deficiency (GHD), hypogonadism, hypothyroidism, adrenal insufficiency, and poor bone mineral density (BMD). In addition to hypothalamic dysfunction, individuals with PWS have increased risk for obesity which may be complicated by metabolic syndrome and type 2 diabetes mellitus (T2DM). In this paper, we will review the current literature pertaining to the endocrine concerns of PWS and current recommendations for screening and management of these conditions. PMID:29184809

Prader-Willi syndrome: a case report with atypical developmental features.

PubMed

Sewaybricker, Letícia E; Guaragna-Filho, Guilherme; Paula, Georgette B; Andrade, Juliana G R; Tincani, Bruna J; D'Souza-Li, Lília; Lemos-Marini, Sofia H V; Maciel-Guerra, Andréa T; Guerra-Júnior, Gil

2014-09-01

To describe the case of a male Prader-Willi syndrome (PWS) patient with atypical development features. We report the case of a male adolescent with confirmed diagnosis of PWS which presents atypical phenotype. The patient progressed with spontaneous and complete pubertal development, stature in the normal range, and weight control without any pharmacological treatment, except metformin. PWS is an imprinting paternally inherited disorder of 15q11-13 characterized by hypotonia in infant age, hyperphagia, varied degrees of mental retardation, behavior problems, hypogonadism, short stature, and other less common findings.

Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

PubMed Central

Finnerty, Celeste C; Jeschke, Marc G; Herndon, David N; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Silver, Geoff; Arnoldo, Brett; Remick, Daniel; Tompkins, Ronald G

2008-01-01

A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structural changes of essential organs. The release of cytokines has been implicated in this hypermetabolic response. The severity of the hypermetabolic response following burn injury increases with age, as does the mortality rate. Due to the relationship between the hypermetabolic and inflammatory responses, we sought to compare the plasma cytokine profiles following a severe burn in adults and in children. We enrolled 25 adults and 24 children who survived a flame burn covering more than 20% of total body surface area (TBSA). The concentrations of 22 cytokines were measured using the Linco multiplex array system (St. Charles, MO, USA). Large perturbations in the expression of pro- and anti-inflammatory cytokines were seen following thermal injury. During the first week following burn injury, IFN-γ, IL-10, IL-17, IL-4, IL-6, and IL-8 were detected at significantly higher levels in adults compared with children, P < 0.05. Significant differences were measured during the second week post-burn for IL-1β (higher in children) and IL-5 (higher in adults), P < 0.05. IL-18 was more abundant in children compared with adults during the third week post-burn, P < 0.05. Between post-burn d 21 and d 66, IL-1α was detected at higher concentrations in pediatric compared with adult patients, P < 0.05. Only GM-CSF expression was significantly different at all time points; it was detected at lower levels in pediatric patients, P < 0.05. Eotaxin, G-CSF, IL-13, IL-15, IP-10, MCP-1, and MIP-1α were detected at significantly different concentrations in adult compared with pediatric patients at multiple time points, P < 0.05. There were no differences in IL-12, IL-2, IL-7, or TNF levels in adult compared with pediatric burn patients at any of these time points. Following severe flame burns, the cytokine profiles in pediatric patients differ compared with those in adult patients, which may

Trauma injury in adult underweight patients

PubMed Central

Hsieh, Ching-Hua; Lai, Wei-Hung; Wu, Shao-Chun; Chen, Yi-Chun; Kuo, Pao-Jen; Hsu, Shiun-Yuan; Hsieh, Hsiao-Yun

2017-01-01

Abstract The aim of this study was to investigate and compare the injury characteristics, severity, and outcome between underweight and normal-weight patients hospitalized for the treatment of all kinds of trauma injury. This study was based on a level I trauma center Taiwan. The detailed data of 640 underweight adult trauma patients with a body mass index (BMI) of <18.5 kg/m2 and 6497 normal-weight adult patients (25 > BMI ≥ 18.5 kg/m2) were retrieved from the Trauma Registry System between January 1, 2009, and December 31, 2014. Pearson's chi-square test, Fisher's exact test, and independent Student's t-test were performed to compare the differences. Propensity score matching with logistic regression was used to evaluate the effect of underweight on mortality. Underweight patients presented a different bodily injury pattern and a significantly higher rate of admittance to the intensive care unit (ICU) than did normal-weight patients; however, no significant differences in the Glasgow Coma Scale (GCS) score, injury severity score (ISS), in-hospital mortality, and hospital length of stay were found between the two groups. However, further analysis of the patients stratified by two major injury mechanisms (motorcycle accident and fall injury) revealed that underweight patients had significantly lower GCS scores (13.8 ± 3.0 vs 14.5 ± 2.0, P = 0.020), but higher ISS (10.1 ± 6.9 vs 8.4 ± 5.9, P = 0.005), in-hospital mortality (odds ratio, 4.4; 95% confidence interval, 1.69–11.35; P = 0.006), and ICU admittance rate (24.1% vs 14.3%, P = 0.007) than normal-weight patients in the fall accident group, but not in the motorcycle accident group. However, after propensity score matching, logistic regression analysis of well-matched pairs of patients with either all trauma, motorcycle accident, or fall injury did not show a significant influence of underweight on mortality. Exploratory data analysis revealed that underweight patients

Response to growth hormone treatment in Prader-Willi syndrome: auxological criteria versus genetic diagnosis.

PubMed

Scheermeyer, Elly; Hughes, Ian; Harris, Mark; Ambler, Geoff; Crock, Patricia; Verge, Charles F; Craig, Maria E; Bergman, Phil; Werther, George; van Driel, Mieke; Davies, Peter Sw; Choong, Catherine S Y

2013-12-01

The Australian Prader-Willi Syndrome (PWS) database was established to monitor the efficacy and safety of growth hormone (GH) treatment in PWS. This study aims to compare response to GH based on eligibility criteria. Comparative study: 72 children received GH on the basis of short stature or evidence of GH deficiency (pre-2009: PWS-SS) and 94 on a genetic diagnosis (post-2009: PWS-Dx). We report on mandatory patient data for GH prescription: median and standard deviation score (SDS) for height and body mass index (BMI), waist/height ratio, bone age/chronological age ratio and adverse events. Comparisons were made using non-parametric tests. At baseline, the PWS-SS cohort was shorter (height SDS: -2.6 vs. -1.1, P < 0.001), had a lower BMI (0.6 vs. 1.5 SDS, P < 0.05) and greater bone age delay (bone age/chronological age: 0.7 vs. 0.9, P < 0.05) than the PWS-Dx cohort. PWS-SS parents were shorter (mid-parental height SDS: -0.13 vs. 0.28, P < 0.005). Mean change in height over 2 years was 0.9 SDS and in BMI using PWS reference standards -0.3 SDSPWS (n = 106) (year 2, height SDS: PWS-SS = -1.7, PWS-Dx = 0.1; BMI SDSPWS : PWS-SS = -1.0, PWS-Dx = -0.6). The waist/height ratio reduced (PWS-Dx: 0.60 vs. 0.56, P < 0.05) and bone age delay was unchanged over this period. No serious adverse events were reported. The PWS-SS cohort represents a subgroup of the wider PWS-Dx population; however both cohorts improved height SDS with normalisation of height in the PWS-Dx cohort and lowering of BMI relative to PWS standards supporting the efficacy of treatment under the current Australian GH programme. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Evaluation of agreement among dermatologists in the assessment of the color of port wine stains and their clearance after treatment with the flashlamp-pumped dye laser.

PubMed

Pérez, B; Abraira, V; Núñez, M; Boixeda, P; Perez Corral, F; Ledo, A

1997-01-01

Color classification and its subjective clearance evaluation in response to treatment are essential in the management of patients with port wine stains (PWS). But color perception by physicians is not an objective measurement so that it can change among observers. Agreement among physicians is essential for the reliability of the color classification and the clinical assessment of the response to laser treatment. The purpose of our study was to determine the reliability of the clinical color classification of port wine stains and of their color change or clearance in response to laser treatment. The study was not designed to evaluate the outcome of laser treatment in PWS or the factors that could predict the final response. We used the kappa index to evaluate the proportion of agreement in color and clearance perception among dermatologists. Six dermatologists classified the initial color of PWS in 80 patients. Three of them also assessed the amount of clearance achieved after treatment with the flashlamp-pumped dye laser. These three dermatologists were usually dedicated to treat patients with PWS, while the other three were not. The kappa index showed a substantial agreement in both cases. No difference in the initial color perception was observed between the group of dermatologists specialized in PWS and the other three dermatologists. These results favor the reliability of the clinical method in the assessment of PWS before and after laser treatment. So, although subjective, color perception by physicians can be used in the study of laser treatment outcome in PWS and its related factors, and the results of different authors can be compared.

Carbamazepine and oxcarbazepine in adult patients with Dravet syndrome: Friend or foe?

PubMed

Snoeijen-Schouwenaars, F M; Veendrick, M J B M; van Mierlo, P; van Erp, G; de Louw, A J A; Kleine, B U; Schelhaas, H J; Tan, I Y

2015-07-01

In newly diagnosed patients with Dravet syndrome sodium channel blockers are usually avoided. However, in many adult patients the diagnosis was made long after the initiation of therapy. The purpose of our study was to acquire information concerning the potential risks and benefits of (ox)carba(ma)zepine withdrawal in adult patients with genetically confirmed Dravet syndrome. We identified 16 adults with Dravet syndrome, living in a tertiary care facility for people with epilepsy and an intellectual disability. We reviewed clinical history, genetic findings, the type and duration of sodium channels blockers that were used, seizure types and frequency, and the effect of a change in these medications. The study population consisted of 9 men and 7 women. Median age was 35 years (range 20-61 years). An attempt to withdraw carbamazepine (CBZ) was made in 9 patients. In 3 of these patients an increase in tonic-clonic seizures was observed. An attempt to withdraw oxcarbazepine (OXC) was made in 3 patients, leading to a complete stop in 2 patients. 3 of the 4 deaths in the withdrawal-group were related to epilepsy. In adult patients with Dravet syndrome withdrawal of CBZ or OXC is not without risks. We suggest that (ox)carba(ma)zepine withdrawal should be considered in these patients but only if there is a good reason to do so and only if they are closely monitored. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Outcomes in adult pectus excavatum patients undergoing Nuss repair

PubMed Central

Ewais, MennatAllah M; Chaparala, Shivani; Uhl, Rebecca

2018-01-01

Pectus excavatum (PEx) is one of the most common congenital chest wall deformities. Depending on the severity, presentation of PEx may range from minor cosmetic issues to disabling cardiopulmonary symptoms. The effect of PEx on adult patients has not been extensively studied. Symptoms may not occur until the patient ages, and they may worsen over the years. More recent publications have implied that PEx may have significant cardiopulmonary implications and repair is of medical benefit. Adults presenting for PEx repair can undergo a successful repair with a minimally invasive “Nuss” approach. Resolution of symptoms, improved quality of life, and satisfying results are reported. PMID:29430201

Genetics of Prader-Willi syndrome and Prader-Will-Like syndrome

PubMed Central

2016-01-01

The Prader-Willi syndrome (PWS) is a human imprinting disorder resulting from genomic alterations that inactivate imprinted, paternally expressed genes in human chromosome region 15q11-q13. This genetic condition appears to be a contiguous gene syndrome caused by the loss of at least 2 of a number of genes expressed exclusively from the paternal allele, including SNRPN, MKRN3, MAGEL2, NDN and several snoRNAs, but it is not yet well known which specific genes in this region are associated with this syndrome. Prader-Will-Like syndrome (PWLS) share features of the PWS phenotype and the gene functions disrupted in PWLS are likely to lie in genetic pathways that are important for the development of PWS phenotype. However, the genetic basis of these rare disorders differs and the absence of a correct diagnosis may worsen the prognosis of these individuals due to the endocrine-metabolic malfunctioning associated with the PWS. Therefore, clinicians face a challenge in determining when to request the specific molecular test used to identify patients with classical PWS because the signs and symptoms of PWS are common to other syndromes such as PWLS. This review aims to provide an overview of current knowledge relating to the genetics of PWS and PWLS, with an emphasis on identification of patients that may benefit from further investigation and genetic screening. PMID:27777904

Genetics of Prader-Willi syndrome and Prader-Will-Like syndrome.

PubMed

Cheon, Chong Kun

2016-09-01

The Prader-Willi syndrome (PWS) is a human imprinting disorder resulting from genomic alterations that inactivate imprinted, paternally expressed genes in human chromosome region 15q11-q13. This genetic condition appears to be a contiguous gene syndrome caused by the loss of at least 2 of a number of genes expressed exclusively from the paternal allele, including SNRPN , MKRN3 , MAGEL2 , NDN and several snoRNAs , but it is not yet well known which specific genes in this region are associated with this syndrome. Prader-Will-Like syndrome (PWLS) share features of the PWS phenotype and the gene functions disrupted in PWLS are likely to lie in genetic pathways that are important for the development of PWS phenotype. However, the genetic basis of these rare disorders differs and the absence of a correct diagnosis may worsen the prognosis of these individuals due to the endocrine-metabolic malfunctioning associated with the PWS. Therefore, clinicians face a challenge in determining when to request the specific molecular test used to identify patients with classical PWS because the signs and symptoms of PWS are common to other syndromes such as PWLS. This review aims to provide an overview of current knowledge relating to the genetics of PWS and PWLS, with an emphasis on identification of patients that may benefit from further investigation and genetic screening.

Prescribing errors in adult congenital heart disease patients admitted to a pediatric cardiovascular intensive care unit.

PubMed

Echeta, Genevieve; Moffett, Brady S; Checchia, Paul; Benton, Mary Kay; Klouda, Leda; Rodriguez, Fred H; Franklin, Wayne

2014-01-01

Adults with congenital heart disease (CHD) are often cared for at pediatric hospitals. There are no data describing the incidence or type of medication prescribing errors in adult patients admitted to a pediatric cardiovascular intensive care unit (CVICU). A review of patients >18 years of age admitted to the pediatric CVICU at our institution from 2009 to 2011 occurred. A comparator group <18 years of age but >70 kg (a typical adult weight) was identified. Medication prescribing errors were determined according to a commonly used adult drug reference. An independent panel consisting of a physician specializing in the care of adult CHD patients, a nurse, and a pharmacist evaluated all errors. Medication prescribing orders were classified as appropriate, underdose, overdose, or nonstandard (dosing per weight instead of standard adult dosing), and severity of error was classified. Eighty-five adult (74 patients) and 33 pediatric admissions (32 patients) met study criteria (mean age 27.5 ± 9.4 years, 53% male vs. 14.9 ± 1.8 years, 63% male). A cardiothoracic surgical procedure occurred in 81.4% of admissions. Adult admissions weighed less than pediatric admissions (72.8 ± 22.4 kg vs. 85.6 ± 14.9 kg, P < .01) but hospital length of stay was similar. (Adult 6 days [range 1-216 days]; pediatric 5 days [Range 2-123 days], P = .52.) A total of 112 prescribing errors were identified and they occurred less often in adults (42.4% of admissions vs. 66.7% of admissions, P = .02). Adults had a lower mean number of errors (0.7 errors per adult admission vs. 1.7 errors per pediatric admission, P < .01). Prescribing errors occurred most commonly with antimicrobials (n = 27). Underdosing was the most common category of prescribing error. Most prescribing errors were determined to have not caused harm to the patient. Prescribing errors occur frequently in adult patients admitted to a pediatric CVICU but occur more often in pediatric patients of adult weight. © 2013 Wiley

Scatter Plot Analysis of Excessive Daytime Sleepiness and Severe Disruptive Behavior in Adults with Prader-Willi Syndrome: A Pilot Study

ERIC Educational Resources Information Center

Maas, Anneke P. H. M.; Didden, Robert; Bouts, Lex; Smits, Marcel G.; Curfs, Leopold M. G.

2009-01-01

Individuals with Prader-Willi syndrome (PWS) are at risk for excessive daytime sleepiness (EDS) and disruptive behavior. This pilot study explores temporal characteristics of EDS and severe disruptive behavior across time of day and day of week in seven individuals with PWS (aged between 33 and 49 years) of whom five were matched to controls.…

Multicentre study of maternal and neonatal outcomes in individuals with Prader-Willi syndrome.

PubMed

Singh, Preeti; Mahmoud, Ranim; Gold, June-Anne; Miller, Jennifer L; Roof, Elizabeth; Tamura, Roy; Dykens, Elisabeth; Butler, Merlin G; Driscoll, Dan J; Kimonis, Virginia

2018-05-18

Prader-Willi syndrome (PWS) is a complex genetic disorder associated with three different genetic subtypes: deletion of the paternal copy of 15q11-q13, maternal UPD for chromosome 15 and imprinting defect. Patients are typically diagnosed because of neonatal hypotonia, dysmorphism and feeding difficulties; however, data on the prenatal features of PWS are limited. The aim of the study was to identify and compare frequencies of prenatal and neonatal clinical features of PWS among the three genetic subtypes. Data from 355 patients with PWS from the Rare Diseases Clinical Research Network PWS registry were used to analyse multiple maternal and neonatal factors collected during an 8-year multisite study. Among our cohort of 355 patients with PWS (61% deletion, 36% UPD and 3% imprinting defect) 54% were born by caesarean section, 26% were born prematurely and 34% with a low birth weight (frequencies 32%, 9.6% and 8.1%, respectively, in the general population). Fetal movements were reported as decreased in 72%. All babies were hypotonic, and 99% had feeding difficulties. Low Apgar scores (<7) were noted in 17.7% and 5.6% of patients, respectively, compared with 1% and 1.4%, respectively, in the general population. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (p=0.01 and <0.001, respectively). We found a higher rate of perinatal complications in PWS syndrome compared with the general population. No significant differences in the genetic subtypes were noted except for a higher maternal age and pre-pregnancy weight in the UPD subgroup. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mandibular fractures: a comparative analysis between young and adult patients in the southeast region of Turkey

PubMed Central

ATILGAN, Serhat; EROL, Behçet; YAMAN, Ferhan; YILMAZ, Nezih; UCAN, Musa Can

2010-01-01

Objective The purpose of this study was to review and compare the differences between mandibular fractures in young and adult patients. Material and Methods Patients treated at the Oral and Maxillofacial Department of Dicle University during a five-year period between 2000 and 2005 were retrospectively evaluated with respect to age groups, gender, etiology, localization and type of fractures, treatment methods and complications. Result 532 patients were included in the study, 370 (70%) males and 162 (30%) females, with a total of 744 mandibular fractures. The mean age of young patients was 10, with a male-female ratio of 2:1. The mean age of adult patients was 28, with a male-female ratio of 3:1. The most common causes of injury were falls (65%) in young patients and traffic accidents (38%) in adults. The most common fracture sites were the symphysis (35%) and condyle (36%) in young patients, and the symphysis in adults (36%). Mandibular fractures were generally treated by arch bar and maxillomandibular fixation in both young (67%) and adult (39%) patients, and 43% of the adult patients were treated by open reduction and internal fixation. Conclusion There was a similar gender, monthly and type of treatment distribution in both young and adult patients in the southeast region of Turkey. However, there were differences regarding age, etiology and fracture site. These findings between young and adult patients are broadly similar to those from other studies. Analysis of small differences may be an important factor in assessing educational and socioeconomic environments. PMID:20379677

Enhanced appetitive learning and reversal learning in a mouse model for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Humby, Trevor; Hagan, Jim J; Wilkinson, Lawrence S; Isles, Anthony R

2012-06-01

Prader-Willi syndrome (PWS) is caused by lack of paternally derived gene expression from the imprinted gene cluster on human chromosome 15q11-q13. PWS is characterized by severe hypotonia, a failure to thrive in infancy and, on emerging from infancy, evidence of learning disabilities and overeating behavior due to an abnormal satiety response and increased motivation by food. We have previously shown that an imprinting center deletion mouse model (PWS-IC) is quicker to acquire a preference for, and consume more of a palatable food. Here we examined how the use of this palatable food as a reinforcer influences learning in PWS-IC mice performing a simple appetitive learning task. On a nonspatial maze-based task, PWS-IC mice acquired criteria much quicker, making fewer errors during initial acquisition and also reversal learning. A manipulation where the reinforcer was devalued impaired wild-type performance but had no effect on PWS-IC mice. This suggests that increased motivation for the reinforcer in PWS-IC mice may underlie their enhanced learning. This supports previous findings in PWS patients and is the first behavioral study of an animal model of PWS in which the motivation of behavior by food rewards has been examined. © 2012 American Psychological Association

Self-help conferences for people who stutter: a qualitative investigation.

PubMed

Trichon, Mitchell; Tetnowski, John

2011-12-01

stuttering has on their lives. The reader will be able to: (1) describe recurring themes associated with the lived experience having attended a self-help conference(s) for people who stutter (PWS) from the perspective of a group of adults who stutter, and (2) describe the potential benefits of attending self-help conferences for PWS in order to make appropriate evidence-based referrals to self-help conferences for PWS. Copyright © 2011 Elsevier Inc. All rights reserved.

Transition of adolescent and young adult patients with childhood-onset chronic kidney disease from pediatric to adult renal services: a nationwide survey in Japan.

PubMed

Hattori, Motoshi; Iwano, Masayuki; Sako, Mayumi; Honda, Masataka; Okada, Hirokazu; Akioka, Yuko; Ashida, Akira; Kawasaki, Yukihiko; Kiyomoto, Hideyasu; Terada, Yoshio; Hirano, Daishi; Fujieda, Mikiya; Fujimoto, Shouichi; Masaki, Takao; Maruyama, Shoichi; Mastuo, Seiich

2016-12-01

Transition of adolescent and young adult (AYA) patients with childhood-onset chronic kidney diseases (C-CKD) from pediatric to adult renal services has received increasing attention. However, information on transition of Japanese patients with C-CKD is limited. The Transition Medicine Working Group, in collaboration with the Japanese Society for Nephrology, the Japanese Society for Pediatric Nephrology and the Japanese Society of Pediatric Urology, conducted a retrospective cross-sectional study in 2014 on issues concerning the transition of Japanese patients with C-CKD. Few institutions in Japan had transition programs and/or transition coordinators for patients with C-CKD. Refusal to transfer by patients or their families, lack of concern about transition and inability to decide on transfer were common reasons for non-transfer of patients still followed by pediatric renal services. Around 25 % of patients who had ended or interrupted follow-up by pediatric renal services presented to adult renal services because of symptoms associated with C-CKD. Patients with various types of childhood-onset nephrourological diseases were transferred from pediatric to adult renal services. IgA nephropathy, minimal change nephrotic syndrome and congenital anomalies of the kidney and urinary tract were the most frequent primary kidney diseases in adult patients with C-CKD. These survey results indicate the need for introduction of transitional care for Japanese AYA patients with C-CKD. Consensus guidelines for the optimal clinical management of AYA patients with C-CKD are required to ensure the continuity of care from child to adult renal services.

Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD.

PubMed

Kato, Harumi; Yamamoto, Kazuhito; Kodaira, Takeshi; Higuchi, Yusuke; Yamamoto, Hideyuki; Saito, Toko; Taji, Hirofumi; Yatabe, Yasushi; Nakamura, Shigeo; Kinoshita, Tomohiro

2018-03-01

Immunophenotype is an important prognostic factor for childhood and adult T-cell acute lymphoblastic leukemia. However, immunophenotypic data from adult patients with T-cell lymphoblastic lymphoma (T-LBL) are scarcely available. Subjects were unselected adult patients with T-LBL who were treated with intensive chemotherapy. Immunophenotyping of tumor cells was performed according to standard techniques. A total of eight patients with a median age of 31 years were analyzed who received hyper-CVAD treatment for LBL. Immunophenotypic analysis showed that the most common tumor type was cortical T-cell type [early T (n = 2), cortical T (n = 4), and medullary T (n = 2)]. Two patients diagnosed with early T-cell type had early disease progression. Assessment of T-cell differentiation stages in malignant T lymphoblasts would be important in choosing treatment strategies for adult patients with T-LBL.

Evaluation of port-wine stain treatment outcomes using multispectral imaging

NASA Astrophysics Data System (ADS)

Samatham, Ravikant; Choudhury, Niloy; Krol, Alfons L.; Jacques, Steven L.

2012-02-01

Port-wine Stain (PWS) is a vascular malformation characterized by ectasia of superficial dermal capillaries. The flash-lamp pumped pulsed dye laser (PDL) treatment has been the mainstay of PWS for the last decade. Despite the success of the PDL in significantly fading the PWS, the overall cure rate is less than 10%. The precise efficacy of an individual PDL treatment is hard to evaluate and the treatment outcome is measured by visual observation of clinical fading. A hand-held multi-spectral imaging system was developed to image PWS before and after PDL treatment. In an NIH-funded pilot study multi-spectral camera was used to image PWS in children (2- 17 years). Oxygen saturation (S) and blood content (B) of PWS before and after the treatment was determined by analysis of the reflectance spectra. The outcome of the treatment was evaluated during follow up visits of the patients. One of the major causes of failure of laser therapy of port-wine stains (PWS) is reperfusion of the lesion after laser treatment. Oxygen saturation and blood content maps of PWS before and after treatment can predict regions of reperfusion and subsequent failure of the treatment. The ability to measure reperfusion and to predict lesions or areas susceptible to reperfusion, will help in selection of patients/lesions for laser treatment and help to optimize laser dosimetry for maximum effect. The current studies also should provide a basis for monitoring of future alternative therapies or enhancers of laser treatment in resistant cases.

Use of Patient Portals for Personal Health Information Management: The Older Adult Perspective

PubMed Central

Turner, Anne M.; Osterhage, Katie; Hartzler, Andrea; Joe, Jonathan; Lin, Lorelei; Kanagat, Natasha; Demiris, George

2015-01-01

The personal health information management (PHIM) practices and needs of older adults are poorly understood. We describe initial results from the UW SOARING project (Studying Older Adults & Researching Information Needs and Goals), a participatory design investigation of PHIM in older adults (60 years and older). We conducted in-depth interviews with older adults (n=74) living in a variety of residential settings about their management of personal health information. A surprising 20% of participants report using patient portals and another 16% reported prior use or anticipated use of portals in the future. Participants cite ease of access to health information and direct communication with providers as valuable portal features. Barriers to the use of patient portals include a general lack of computer proficiency, high internet costs and security concerns. Design features based on consideration of needs and practices of older adults will facilitate appeal and maximize usability; both are elements critical to adoption of tools such as patient portals that can support older adults and PHIM. PMID:26958263

Extracorporeal respiratory support in adult patients

PubMed Central

Romano, Thiago Gomes; Mendes, Pedro Vitale; Park, Marcelo; Costa, Eduardo Leite Vieira

2017-01-01

ABSTRACT In patients with severe respiratory failure, either hypoxemic or hypercapnic, life support with mechanical ventilation alone can be insufficient to meet their needs, especially if one tries to avoid ventilator settings that can cause injury to the lungs. In those patients, extracorporeal membrane oxygenation (ECMO), which is also very effective in removing carbon dioxide from the blood, can provide life support, allowing the application of protective lung ventilation. In this review article, we aim to explore some of the most relevant aspects of using ECMO for respiratory support. We discuss the history of respiratory support using ECMO in adults, as well as the clinical evidence; costs; indications; installation of the equipment; ventilator settings; daily care of the patient and the system; common troubleshooting; weaning; and discontinuation. PMID:28380189

Outcomes of interfacility critical care adult patient transport: a systematic review

PubMed Central

Fan, Eddy; MacDonald, Russell D; Adhikari, Neill KJ; Scales, Damon C; Wax, Randy S; Stewart, Thomas E; Ferguson, Niall D

2006-01-01

Introduction We aimed to determine the adverse events and important prognostic factors associated with interfacility transport of intubated and mechanically ventilated adult patients. Methods We performed a systematic review of MEDLINE, CENTRAL, EMBASE, CINAHL, HEALTHSTAR, and Web of Science (from inception until 10 January 2005) for all clinical studies describing the incidence and predictors of adverse events in intubated and mechanically ventilated adult patients undergoing interfacility transport. The bibliographies of selected articles were also examined. Results Five studies (245 patients) met the inclusion criteria. All were case-series and two were prospective in design. Due to the paucity of studies and significant heterogeneity in study population, outcome events, and results, we synthesized data in a qualitative manner. Pre-transport severity of illness was reported in only one study. The most common indication for transport was a need for investigations and/or specialist care (three studies, 220 patients). Transport modalities included air (fixed or rotor wing; 66% of patients) and ground (31%) ambulance, and commercial aircraft (3%). Transport teams included a physician in three studies (220 patients). Death during transfer was rare (n = 1). No other adverse events or significant therapeutic interventions during transport were reported. One study reported a 19% (28/145) incidence of respiratory alkalosis on arrival and another study documented a 30% overall intensive care unit mortality, while no adverse events or outcomes were reported after arrival in the three other studies. Conclusion Insufficient data exist to draw firm conclusions regarding the mortality, morbidity, or risk factors associated with the interfacility transport of intubated and mechanically ventilated adult patients. Further study is required to define the risks and benefits of interfacility transfer in this patient population. Such information is important for the planning and

A polymorphism in the growth hormone receptor is associated with height in children with Prader-Willi syndrome.

PubMed

Park, Sung Won; Lee, Seung-Tae; Sohn, Young Bae; Kim, Se Hwa; Cho, Sung-Yoon; Ko, Ah-Ra; Ji, Sun-Tae; Kwon, Jeong-Yi; Yeau, Sunghee; Paik, Kyung-Hoon; Kim, Jong-Won; Jin, Dong-Kyu

2011-12-01

The exon-3 deletion polymorphism (d3, Database of Genomic Variants ID: Variation_64191) in the growth hormone receptor (GHR) gene is associated with increased growth response to growth hormone (GH) therapy in GH-deficient patients. However, an association of the GHR genotype with height has not yet been reported in Prader-Willi syndrome (PWS). The aim of this study was to assess the association of GHR alleles with height before starting GH therapy in patients with PWS. Seventy-four patients with PWS were genotyped and their medical records were retrospectively reviewed (45 males and 29 females, median age 8.7 years). One hundred normal controls, with known final height, were also genotyped. The GH-exon 3 locus was genotyped using a PCR multiplex assay. The distribution of alleles in the patients with PWS was not different from controls [(fl/fl n = 53 (72%), fl/d3 n = 21 (28%)) in PWS vs. (fl/fl n = 72(72%), fl/d3 n = 26(26%), and d3/d3 n = 2(2%)]. However, patients with PWS carrying a d3 allele had significantly greater height standard deviation scores (SDS) (P = 0.025) and higher insulin-like growth factor I (IGF-I) level (P = 0.041), although the age at the start of GH therapy, weight, BMI, and body fat were not different. The d3 allele was associated with height and IGF-I levels before GH therapy and suggests that even before GH therapy, d3 allele may influence height through GH secretion. Copyright © 2011 Wiley Periodicals, Inc.

Mosaicism for maternal uniparental disomy 15 in a boy with some clinical features of Prader-Willi syndrome.

PubMed

Zilina, Olga; Kahre, Tiina; Talvik, Inga; Oiglane-Shlik, Eve; Tillmann, Vallo; Ounap, Katrin

2014-01-01

Prader-Willi syndrome (PWS) is caused by the lack of paternal expression of imprinted genes in the human chromosomal region 15q11.2-q13.2, which can be due to an interstitial deletion at 15q11.2-q13 of paternal origin (65-75%), maternal uniparental disomy (matUPD) of chromosome 15 (20-30%), or an imprinting defect (1-3%). The majority of PWS-associated matUPD15 cases represent a complete heterodisomy of chromosome 15 or a mixture of hetero- and isodisomic regions across the chromosome 15. Pure maternal isodisomy is observed in only a few matUPD15 patients. Here we report a case of an 18-year-old boy with some clinical features of Prader-Willi syndrome, such as overweight, muscular hypotonia, facial dysmorphism and psychiatric problems, but there was no reason to suspect PWS in the patient based solely on the phenotype estimation. However, chromosomal microarray analysis (CMA) revealed mosaic loss of heterozygosity of the entire chromosome 15. Methylation-specific multiplex ligation-dependant probe amplification (MS-MLPA) analysis showed hypermethylation of the SNRPN and NDN genes in the PWS/AS critical region of chromosome 15 in this patient. Taking into consideration the MS-MLPA results and the presence of PWS features in the patient, we concluded that it was matUPD15, although the patient's parents were not enrolled in the study. According to CMA and karyotyping, no trisomic or monosomic cells were present. To the best of our knowledge, only two PWS cases with mosaic maternal isodisomy 15 and without trisomic/monosomic cell lines have been reported so far. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Delineation of behavioral phenotypes in genetic syndromes: characteristics of autism spectrum disorder, affect and hyperactivity.

PubMed

Oliver, Chris; Berg, Katy; Moss, Jo; Arron, Kate; Burbidge, Cheryl

2011-08-01

We investigated autism spectrum disorder (ASD) symptomatology, hyperactivity and affect in seven genetic syndromes; Angelman (AS; n = 104), Cri du Chat (CdCS; 58), Cornelia de Lange (CdLS; 101), Fragile X (FXS; 191), Prader-Willi (PWS; 189), Smith-Magenis (SMS; 42) and Lowe (LS; 56) syndromes (age range 4-51). ASD symptomatology was heightened in CdLS and FXS. High levels of impulsivity were seen in SMS, AS, CdCS, FXS and adults with CdLS. Negative affect was prominent in adults with CdLS, while positive affect was prominent in adults with AS and FXS. Heightened levels of overactivity and impulsivity were identified in FXS, AS and SMS while low levels were identified in PWS. These findings confirm and extend previously reported behavioral phenotypes.

Clinical characteristics of adult patients with tics and/or Tourette's syndrome.

PubMed

Ohta, Masataka; Kano, Yukiko

2003-12-01

This study was conducted to describe the natural course of tic disorders over a long period of time in Japanese adults patients with Tourette's syndrome (TS) in terms of symptomatology. An extensive literature on TS cases was reviewed selectively and 31 TS patients (mean age: 31.4 years; sex: 28 males and 3 females) at our outpatient clinic were examined. The mean follow-up period of the patients was 7.6 years (SD: 8.1; 0 to 26). All the data available for this study, including medical charts, were examined systematically by two experienced child psychiatrists. The adult patients with tic disorders could be classified into the four groups: group A - tics only, group B - tics + comorbidities, group C - comorbidities only and group D - sub-clinical (remission) cases. Our 31 subjects consisted of 10 patients (32.3%) for group A, 14 (45.2%) for group B, 7 (22.6%) for group C, and 0 for group D. Further investigation into the natural course and clinical characteristics of adult TS needs to be done in order to acquire a better understanding of the broad spectrum of TS and to make improvements to the treatment for this illness.

Characterizing Pelvic Organ Prolapse in Adult Spina Bifida Patients.

PubMed

Liu, Joceline S; Vo, Amanda X; Doolittle, Johnathan; Hamoui, Nabeel; Lewicky-Gaupp, Christina; Kielb, Stephanie J

2016-11-01

To report the distribution of pelvic organ prolapse (POP) stages in adult spina bifida (SB) patients. The severity of POP in the SB population has not been previously reported. Retrospective review of SB patients ≥18 years with a documented POP quantification examination between 2006 and 2014 were included. Patient demographics, gestation, parity, POP quantification examinations and prolapse symptoms were obtained. Thirty-three SB patients were identified with a mean age of 33.2 years. Five patients (15.2%) had stage 0 prolapse, 12 (36.4%) had stage 1, 12 (36.4%) had stage 2, 3 (9.1%) had stage 3, and 1 (3.0%) had stage 4. Of the 16 patients with advanced POP (stage 2 prolapse or greater), only 6 patients (37.5%) reported symptoms related to POP. All 6 symptomatic patients endorsed sensation of a vaginal bulge. Two of the 6 patients also reported dyspareunia. Additionally, 1 patient with advanced POP presented with vaginal bulge, noted by a caregiver, and cervical bleeding, but was otherwise asymptomatic. Twenty-four patients (72.7%) were nulliparous, and 12 of the 24 nulliparous patients (50%) demonstrated prolapse. Despite young age and frequent nulliparity, patients with SB are more likely to have POP than the general population. Additionally, the majority of SB patients with prolapse are asymptomatic. Assessment of pelvic organ prolapse should be included in the evaluation of adult SB females due to the low rate of symptoms even in the setting of advanced stage prolapse and potential impact on both urinary and bowel function. Copyright © 2016 Elsevier Inc. All rights reserved.

[Phenotype-genotype correlation analysis of 12 cases with Angelman/Prader-Willi syndrome].

PubMed

Chen, Chen; Peng, Ying; Xia, Yan; Li, Haoxian; Zhu, Huimin; Pan, Qian; Yin, Fei; Wu, Lingqian

2014-12-01

To investigate the genotype-phenotype correlation in patients with Angelman syndrome/Prader-Willi syndrome (AS/PWS) and assess the application value of high-resolution single nucleotide polymorphism microarrays (SNP array) for such diseases. Twelve AS/PWS patients were diagnosed through SNP array, fluorescence in situ hybridization (FISH) and karyotype analysis. Clinical characteristics were analyzed. Deletions ranging from 4.8 Mb to 7.0 Mb on chromosome 15q11.2-13 were detected in 11 patients. Uniparental disomy (UPD) was detected in only 1 patient. Patients with deletions could be divided into 2 groups, including 7 cases with class I and 4 with class II. The two groups however had no significant phenotypic difference. The UPD patient had relatively better development and language ability. Deletions of 6 patients were confirmed by FISH to be of de novo in origin. The risk to their sibs was determined to be less than 1%. The phenotypic differences between AS/PWS patients with class I and class II deletion need to be further studied. SNP array is useful in detecting and distinguishing of patients with deletion or UPD. This method may be applied for studying the genotype-phenotype association and the mechanism underlying AS/PWS.

Assessing Quality of Life in Older Adult Patients with Skin Disorders

PubMed Central

Farage, Miranda A.; Miller, Kenneth W.; Sherman, Susan N.; Tsevat, Joel

2012-01-01

Significance for Public Health The global population is aging. In the industrial world, adults over 65 outnumber children and comprise almost 20% of the population in some countries. Older adults experience a number of skin diseases and disorders that substantially affect their quality of life. Opportunity exists for developing and validating health-related quality of life (HRQoL) measures specifically for dermatological conditions most pertinent to older patients. Older adults experience a number of skin diseases and disorders that substantially affect quality of life. In the last two decades, a number of instruments have been developed for use among general dermatology patients to assess the effects of treatment and disease progression, perceptions of well-being, and the value that patients place on their dermatologic state of health. This chapter reviews some health-related quality of life (HRQoL) (HRQoL) measures developed and validated specifically for dermatological conditions. However, opportunity exists for developing and validating HRQoL measures specifically for dermatological conditions most pertinent to older patients. PMID:22980159

Spatial Frequency Domain Imaging of Port Wine Stain Biochemical Composition in Response to Laser Therapy: A Pilot Study

PubMed Central

Mazhar, Amaan; Sharif, Seyed A.; Cuccia, J. David; Nelson, J. Stuart; Kelly, Kristen M.; Durkin, Anthony J.

2012-01-01

Background and Objective Objective methods to assess port wine stain (PWS) response to laser treatment have been the subject of various research efforts for several years. Herein, we present a pilot study using a newly developed, light emitting diode (LED) based spatial frequency domain imaging (SFDI) device to record quantitatively biochemical compositional changes in PWS after laser therapy. Study Design/Patients and Methods A SFDI system was used to image before, and after, five PWS treatment sessions [n = 4 subjects (one subject was imaged before and after two consecutive laser treatments)]. SFDI derived wide-field optical properties (absorption and scattering) and tissue chromophore concentrations including oxy-hemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb), total hemoglobin (ctTHb), and tissue oxygen saturation (stO2) are presented for skin imaged prior to and immediately after laser treatment. The SFDI derived images were analyzed by comparing the above measurements in PWS to those of normal skin and tracking changes immediately after laser exposure. Results Elevated oxy-hemoglobin (>20%) and tissue oxygen saturation (>5%) were measured in all PWS lesions and compared to values for normal skin prior to treatment. Laser treatment resulted in an increase in deoxy-hemoglobin (>100%), decrease in tissue oxygen saturation (>10%), and reduced scattering (>15%) in all PWS lesions. One subject was followed before and after two consecutive laser treatments and the overall improvement in PWS lesion blanching was quantitatively assessed by measuring a 45% decrease in dermal blood volume. Conclusion SFDI is a rapid non-contact wide-field optical technique that shows potential as an imaging device that can be used to quantify biochemical compositional changes in PWS after laser therapy. Future work will investigate the potential of SFDI to provide intra-operative guidance for laser therapy of PWS lesions on an individual patient basis. PMID:22911574

The optimal blood glucose level for critically ill adult patients.

PubMed

Lv, Shaoning; Ross, Paul; Tori, Kathleen

2017-09-01

Glycaemic control is recognized as one of the important aspects in managing critically ill patients. Both hyperglycaemia and hypoglycaemia independently increase the risk of patient mortality. Hence, the identification of optimal glycaemic control is of paramount importance in the management of critically ill patients. The aim of this literature review is to examine the current status of glycaemic control in critically ill adult patients. This literature review will focus on randomized controlled trials comparing intensive insulin therapy to conventional insulin therapy, with an objective to identify optimal blood glucose level targets for critically ill adult patients. A literature review was conducted to identify large randomized controlled trials for the optimal targeted blood glucose level for critically ill adult patients published since 2000. A total of eight studies fulfilled the selection criteria of this review. With current human and technology resources, the results of the studies support commencing glycaemic control once the blood glucose level of critically ill patients reaches 10 mmol/L and maintaining this level between 8 mmol/L and 10 mmol/L. This literature review provides a recommendation for targeting the optimal blood glucose level for critically ill patients within moderate blood glucose level target range (8-10 mmol/L). The need for uniformed glucometrics for unbiased reporting and further research for optimal blood glucose target is required, especially in light of new technological advancements in closed-loop insulin delivery and monitoring devices. This literature review has revealed a need to call for consensus in the measurement and reporting of glycaemic control using standardized glucometrics. © 2017 British Association of Critical Care Nurses.

Effects of underwater treadmill training on leg strength, balance, and walking performance in adults with incomplete spinal cord injury

PubMed Central

Stevens, Sandra L.; Caputo, Jennifer L.; Fuller, Dana K.; Morgan, Don W.

2015-01-01

Objective To document the effects of underwater treadmill training (UTT) on leg strength, balance, and walking performance in adults with incomplete spinal cord injury (iSCI). Design Pre-test and post-test design. Setting Exercise physiology laboratory. Participants Adult volunteers with iSCI (n = 11). Intervention Participants completed 8 weeks (3 × /week) of UTT. Each training session consisted of three walks performed at a personalized speed, with adequate rest between walks. Body weight support remained constant for each participant and ranged from 29 to 47% of land body weight. Increases in walking speed and duration were staggered and imposed in a gradual and systematic fashion. Outcome measures Lower-extremity strength (LS), balance (BL), preferred and rapid walking speeds (PWS and RWS), 6-minute walk distance (6MWD), and daily step activity (DSA). Results Significant (P < 0.05) increases were observed in LS (13.1 ± 3.1 to 20.6 ± 5.1 N·kg−1), BL (23 ± 11 to 32 ± 13), PWS (0.41 ± 0.27 to 0.55 ± 0.28 m·s−1), RWS (0.44 ± 0.31 to 0.71 ± 0.40 m·s−1), 6MWD (97 ± 80 to 177 ± 122 m), and DSA (593 ± 782 to 1310 ± 1258 steps) following UTT. Conclusion Physical function and walking ability were improved in adults with iSCI following a structured program of UTT featuring individualized levels of body weight support and carefully staged increases in speed and duration. From a clinical perspective, these findings highlight the potential of UTT in persons with physical disabilities and diseases that would benefit from weight-supported exercise. PMID:24969269

Comparison of pigeon guillemot, Cepphus columba, blood parameters from oiled and unoiled areas of Alaska eight years after the Exxon Valdez oil spill

USGS Publications Warehouse

Seiser, P.E.; Duffy, L.K.; McGuire, David A.; Roby, D.D.; Golet, Gregory H.; Litzow, Michael A.

2000-01-01

In 1997, we compared the haematological and plasma biochemical profiles among populations of pigeon guillemots, Cepphus columba, in areas oiled and not oiled by the 1989 Exxon Valdez oil spill (EVOS) that occurred in Prince William Sound (PWS), Alaska. Pigeon guillemot populations in PWS were injured by EVOS and have not returned to pre-spill levels. If oil contamination is limiting recovery of pigeon guillemots in PWS, then we expected that blood parameters of pigeon guillemots would differ between oiled and unoiled areas and that these differences would be consistent with either toxic responses or lower fitness. We collected blood samples from chicks at approximately 20 and 30 days after hatching. Physiological changes associated with chick growth were noted in several blood parameters. We found that only calcium and mean cell volume were significantly different between the chicks in oiled and unoiled areas. Despite these differences, blood biomarkers provided little evidence of continuing oil injury to pigeon guillemot chicks, eight years after the EVOS. Preliminary data from adults indicated elevated aspartate aminotransferase activity in the adults from the oiled area, which is consistent with hepatocellular injury. Because adults have greater opportunities for exposure to residual oil than nestlings, we recommend studies that fully evaluate the health of adults residing in oiled areas. (C) 2000 Elsevier Science Ltd.

Approximate Quantification in Young, Healthy Older Adults', and Alzheimer Patients

ERIC Educational Resources Information Center

Gandini, Delphine; Lemaire, Patrick; Michel, Bernard Francois

2009-01-01

Forty young adults, 40 healthy older adults, and 39 probable AD patients were asked to estimate small (e.g., 25) and large (e.g., 60) collections of dots in a choice condition and in two no-choice conditions. Participants could choose between benchmark and anchoring strategies on each collection of dots in the choice condition and were required to…

Fungal infections in adult patients on extracorporeal life support.

PubMed

Cavayas, Yiorgos Alexandros; Yusuff, Hakeem; Porter, Richard

2018-04-17

Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit. They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction. These factors are thought to predispose them to fungal infections. We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO. We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers. We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture. Our study comprised 2129 adult patients (10.8%) with fungal colonization or infection. Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge. There were 245 patients (1.2%) with Candida invasive bloodstream infection, with 35.9% survival. Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p < 0.001), and influenza infection (OR 2.48; p < 0.001). Risk factors for candidemia included sepsis (OR 1.60; p = 0.005) and renal replacement therapy (OR 1.55; p = 0.007). In multivariable analysis, Aspergillus involvement (OR 0.40; p < 0.001) and candidemia (OR 0.47; p < 0.001) were both independently associated with decreased survival. The prevalence of Aspergillus involvement and Candida invasive bloodstream infection were not higher in patients on ECMO than what has been reported in the general intensive care population. Both were independently associated with a reduced survival. Aspergillus involvement was strongly associated with ECMO for respiratory support and influenza.

Molecular Diagnostic Experience of Whole-Exome Sequencing in Adult Patients

PubMed Central

Posey, Jennifer E.; Rosenfeld, Jill A.; James, Regis A.; Bainbridge, Matthew; Niu, Zhiyv; Wang, Xia; Dhar, Shweta; Wiszniewski, Wojciech; Akdemir, Zeynep H.C.; Gambin, Tomasz; Xia, Fan; Person, Richard E.; Walkiewicz, Magdalena; Shaw, Chad A.; Sutton, V. Reid; Beaudet, Arthur L.; Muzny, Donna; Eng, Christine M.; Yang, Yaping; Gibbs, Richard A.; Lupski, James R.; Boerwinkle, Eric; Plon, Sharon E.

2015-01-01

Purpose Whole exome sequencing (WES) is increasingly used as a diagnostic tool in medicine, but prior reports focus on predominantly pediatric cohorts with neurologic or developmental disorders. We describe the diagnostic yield and characteristics of whole exome sequencing in adults. Methods We performed a retrospective analysis of consecutive WES reports for adults from a diagnostic laboratory. Phenotype composition was determined using Human Phenotype Ontology terms. Results Molecular diagnoses were reported for 17.5% (85/486) of adults, lower than a primarily pediatric population (25.2%; p=0.0003); the diagnostic rate was higher (23.9%) in those 18–30 years of age compared to patients over 30 years (10.4%; p=0.0001). Dual Mendelian diagnoses contributed to 7% of diagnoses, revealing blended phenotypes. Diagnoses were more frequent among individuals with abnormalities of the nervous system, skeletal system, head/neck, and growth. Diagnostic rate was independent of family history information, and de novo mutations contributed to 61.4% of autosomal dominant diagnoses. Conclusion Early WES experience in adults demonstrates molecular diagnoses in a substantial proportion of patients, informing clinical management, recurrence risk and recommendations for relatives. A positive family history was not predictive, consistent with molecular diagnoses often revealed by de novo events, informing the Mendelian basis of genetic disease in adults. PMID:26633545

Effects of neurofeedback on adult patients with psychiatric disorders in a naturalistic setting.

PubMed

Cheon, Eun-Jin; Koo, Bon-Hoon; Seo, Wan-Seok; Lee, Jun-Yeob; Choi, Joong-Hyeon; Song, Shin-Ho

2015-03-01

Few well-controlled studies have considered neurofeedback treatment in adult psychiatric patients. In this regard, the present study investigates the characteristics and effects of neurofeedback on adult psychiatric patients in a naturalistic setting. A total of 77 adult patients with psychiatric disorders participated in this study. Demographic data and neurofeedback states were retrospectively analyzed, and the effects of neurofeedback were evaluated using clinical global impression (CGI) and subjective self-rating scales. Depressive disorders were the most common psychiatric disorders (19; 24.7 %), followed by anxiety disorders (18; 23.4 %). A total of 69 patients (89.6 %) took medicine, and the average frequency of neurofeedback was 17.39 ± 16.64. Neurofeedback was applied to a total of 39 patients (50.6 %) more than 10 times, and 48 patients (62.3 %) received both β/SMR and α/θ training. The discontinuation rate was 33.8 % (26 patients). There was significant difference between pretreatment and posttreatment CGI scores (<.001), and the self-rating scale also showed significant differences in depressive symptoms, anxiety, and inattention (<.001). This is a naturalistic study in a clinical setting, and has several limitations, including the absence of a control group and a heterogenous sample. Despite these limitations, the study demonstrates the potential of neurofeedback as an effective complimentary treatment for adult patients with psychiatric disorders.

Upper and Lower Urinary Tract Outcomes in Adult Myelomeningocele Patients: A Systematic Review

PubMed Central

Veenboer, Paul W.; Bosch, J. L. H. Ruud; van Asbeck, Floris W. A.; de Kort, Laetitia M. O.

2012-01-01

Background The introduction of sophisticated treatment of bladder dysfunction and hydrocephalus allows the majority of SB patients to survive into adulthood. However, no systematic review on urological outcome in adult SB patients is available and no follow-up schemes exist. Objectives To systematically summarize the evidence on outcome of urinary tract functioning in adult SB patients. Methods A literature search in PubMed and Embase databases was done. Only papers published in the last 25 years describing patients with open SB with a mean age >18 years were included. We focused on finding differences in the treatment strategies, e.g., clean intermittent catheterization and antimuscarinic drugs versus early urinary diversion, with regard to long-term renal and bladder outcomes. Results A total of 13 articles and 5 meeting abstracts on urinary tract status of adult SB patients were found describing a total of 1564 patients with a mean age of 26.1 years (range 3–74 years, with a few patients <18 years). All were retrospective cohort studies with relatively small and heterogeneous samples with inconsistent reporting of outcome; this precluded the pooling of data and meta-analysis. Total continence was achieved in 449/1192 (37.7%; range 8–85%) patients. Neurological level of the lesion and hydrocephalus were associated with incontinence. Renal function was studied in 1128 adult patients. In 290/1128 (25.7%; range 3–81.8%) patients some degree of renal damage was found and end-stage renal disease was seen in 12/958 (1.3%) patients. Detrusor-sphincter dyssynergy and detrusor-overactivity acted as adverse prognostic factors for the development of renal damage. Conclusions These findings should outline follow-up schedules for SB patients, which do not yet exist. Since renal and bladder deterioration continues beyond adolescence, follow-up of these individuals is needed. We recommend standardization in reporting the outcome of urinary tract function in adult SB

[Prader-Willi and Angelman syndromes: 21 years of experience].

PubMed

Royo Pérez, D; Monge Galindo, L; López Pisón, J; Pérez Delgado, R; Lafuente Hidalgo, M; Peña Segura, J L; Miramar Gallart, M D; Rodriguez Valle, A; Calvo Martín, M T

2012-09-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) were the first syndromes in humans that were known to originate from the phenomenon of the genomic imprinting. We review our experience of 21 years with PWS and AS that were confirmed with the genetically. Of the 13,875 patients recorded during the study period, 11 were diagnosed with PWS (18%), 7 males (63.6%) and 4 females (36.4%), with a mean age of 9.06 years (+/- 6.92, range: 0.68-21.6). The time of the follow up of this group was 3.83 years (+/- 4.03, range: 0.49-15.3), and the age at diagnosis was 4.4 years (+/- 6.84, range: 0.03-19.38). Almost three quarters (72.7% of the PWS patients had a uniparental dysomy and 27.3% a paternal deletion. Six patients (8%) were diagnosed with AS, 4 females (66.6%) and 2 males (33.4%), with a mean age of 14.65 years (+/- 11.89, range: 1.3-30.7). The time of follow up was 6.76 years (+/- 5.89,range: 0.16-15), and the age at diagnosis was 8.84 years (+/- 9.11, range: 1.10-23). A maternal deletion was present in 83.3% of the AS patients and 16.7% had a maternal dysomy. As genetic advances are made these pathologies are confirmed before. Unlike the data in the literature, in our series most patients diagnosed with PWS (72'3%) had uniparental disomy. Recent studies correlation genotype with phenotype, in PWS is more serious if it occurs a deletion and in SA is milder in the case of uniparental disomy. Genetic studies must be performed in view of the established clinical symptoms: neonatal hypotonia of unknown cause in PWS and psychomotor deficits with autism features, particularly associated with epilepsy, must be evaluated in AS to prevent diagnostic uncertainties, unnecessary complementary examinations and to provide early genetic counselling. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth

PubMed Central

Castner, Diobel M.; Clark, Susan J.; Judelson, Daniel A.; Rubin, Daniela A.

2016-01-01

Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR) in both children and adults. Young people with Prader-Willi Syndrome (PWS), a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8–18 years) and lean and obese controls (8–11 years) completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest), standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30) and 60 (HRRV60) s post-exercise). PWS and obese had a smaller HRRV30 than lean (p < 0.01 for both). Additionally, PWS had a smaller HRRV60 than lean and obese (p = 0.01 for both). Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness. PMID:28933384

Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth.

PubMed

Castner, Diobel M; Clark, Susan J; Judelson, Daniel A; Rubin, Daniela A

2016-01-15

Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR) in both children and adults. Young people with Prader-Willi Syndrome (PWS), a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8-18 years) and lean and obese controls (8-11 years) completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest), standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30) and 60 (HRRV60) s post-exercise). PWS and obese had a smaller HRRV30 than lean ( p < 0.01 for both). Additionally, PWS had a smaller HRRV60 than lean and obese ( p = 0.01 for both). Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness.

Late diagnosis of influenza in adult patients during a seasonal outbreak.

PubMed

Choi, Seong-Ho; Chung, Jin-Won; Kim, Tark; Park, Ki-Ho; Lee, Mi Suk; Kwak, Yee Gyung

2018-03-01

Due to advances in diagnostic techniques, clinicians are more frequently performing influenza diagnostic tests and referring to their test results ahead of the administration of neuraminidase inhibitors (NAIs). To investigate the clinical significance of the time from symptom onset to laboratory diagnosis, we reviewed the clinical characteristics of adult patients with influenza who had an early laboratory diagnosis (ED) or a late laboratory diagnosis (LD) at one of four tertiary care centers during a seasonal outbreak of influenza. Clinical data were collected from 1,405 adults during the 2013 to 2014 influenza season. A patient was regarded as receiving an ED or LD if he/she received an influenza diagnostic test at 0 to 1 or 4 to 7 days after symptom onset, respectively. Early NAI therapy and late NAI therapy were defined as the administration of NAI ≤ 2 or > 2 days after symptom onset, respectively. Nearly half of the patients (47.0%) received an ED (n = 661), whereas 13.5% (n = 190) received a LD. Patients with a LD had initial symptoms of cough, sputum production, and dyspnea and experienced pneumonia, antibiotic therapy, hospitalization, and admission to the intensive care unit more often than those with an ED. NAI therapy and early NAI therapy were less frequent in patients with a LD than those with an ED. Of the analyzed baseline characteristics, age ≥ 50 years, influenza B infection, and diagnosis using a polymerase chain reaction test were significantly associated with a LD. LD was associated with inappropriate antiviral therapy and complicated presenting features in adult patients with seasonal influenza. ED of influenza should be emphasized, especially for older adults.

Clinical and histopathological results of the adult patients with unilateral cryptorchidism

PubMed Central

Ateş, Ferhat; Soydan, Hasan; Okçelik, Sezgin; Çırakoğlu, Abdullah; Yılmaz, İsmail; Malkoç, Ercan; Karademir, Kenan

2016-01-01

Objective To evaluate the clinical and histopathological results of adult unilateral cryptorchidism patients. Material and methods Data from adult unilateral cryptorchidism patients that underwent orchiectomy in our clinic between between January 2004 and March 2013 were retrospectively evaluated. Patients were divided into three groups as intra-abdominal, inguinal canal and superficial inguinal region according to the location of the undescended testes. Patients were also grouped according to their testicular volume (<4 cc, 4.1–12 cc, and >12 cc). Histopathology results of orchiectomy specimens were classified as follows: 1. Sertoli cells only, testicular atrophy and vanished testis (anorchia) 2. Hypospermatogenesis, and 3. Maturation arrest. Patients were grouped as normospermia, azoospermia and oligo/astheno/teratospermia groups according to semen analysis results. Correlations between testicular localization, testicular size, semen analysis and pathology results were evaluated. Incidental tumor detection rates were also calculated. Results Two hundred and forty-four adult unilateral cryptorchidism patients underwent orchiectomy in our clinic. There was no a significant relationship between location of the testis and testicular pathology results (p=0.707). Most common semen analysis results was normospermia in patients with high testicular volume group however azoospermia and oligoasthenospermia observed commonly in patients with low testicular volume group. There was a significant relationship between testicular volume and semen analysis results (p=0.023). No significant relationship was observed between semen analysis and pathological results (p=0.929). After an evaluation of all factors with possible effects on the semen analysis results, only testicular volume (p=0.036) was found to have a significant impact. Only one case (0.4%) was incidentally diagnosed seminoma after a review of 233 patients with available histopathological results on record

Uniparental Disomy of Chromosome 15 in Two Cases by Chromosome Microarray: A Lesson Worth Thinking.

PubMed

Liu, Shu; Zhang, Kaihui; Song, Fengling; Yang, Yali; Lv, Yuqiang; Gao, Min; Liu, Yi; Gai, Zhongtao

2017-01-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders caused by loss of function of the imprinted genes at 15q11q13. A 5-7 Mb paternal/maternal deletion of chromosomal region 15q11.2q13 is the major genetic cause of PWS/AS, but in a small group of patients, the PWS/AS phenotype can result from maternal/paternal uniparental disomy (UPD) of chromosome 15. Various mechanisms leading to UPD include gametic complementation, trisomy rescue, and compensatory UPD, which can be inferred from the pattern of uniparental heterodisomy (heteroUPD) or uniparental isodisomy (isoUPD). However, heteroUPD and isoUPD, especially mixed heteroUPD and isoUPD, are very rare in patients with PWS/AS. Here, we report 2 children with PWS/AS caused by mixed segmental heteroUPD 15 and isoUPD 15 which failed to be identified by chromosome microarray (CMA) but could be detected by other molecular genetic methods. The present report unravels the mechanism of mixed iso/heteroUPD 15 in PWS/AS and phenotype-genotype correlations. Moreover, our study suggests that CMA is prone to misdiagnosis for imprinting disorders such as PWS/AS, though it is considered a highly useful tool for copy number variations. As a result, other molecular detection methods, such as methylation analysis and STR marker analysis for UPD, should be supplementary used in this situation. © 2017 S. Karger AG, Basel.

A Correlational Study of Spiritual Well-being and Depression in the Adult Cancer Patient.

PubMed

Stutzman, Hannah; Abraham, Sam

Depression in adult cancer patients has been widely studied, along with spiritual effects of traumatic events and even spiritual growth after a diagnosis of cancer. There has been limited research determining a direct correlation between spiritual well-being and depression in adult cancer patients. The purpose of this research study was to examine the relationship between spiritual well-being and depression in adult cancer patients. This was a descriptive correlational study using 59 patients older than 18 years from an outpatient cancer center. The researchers hypothesized that patients with a low spiritual well-being score would be more likely to have a high depressive symptom score, thus providing support for a correlation between cancer patient's spiritual well-being and risk of depression. Implications of this study lead to evidence for better screening processes for cancer patients regarding spiritual well-being.

Infective Dermatitis in an Adult Patient With HTLV-1

PubMed Central

Riveros, Rosalba; Medina, Raquel; Morel, Maida

2015-01-01

Abstract: Infective dermatitis is a chronic exudative eczematous eruption presenting in human T-lymphotropic virus type 1 (HTLV-1)–infected people. It presents with relapsing erythematous, scaly, and crusted lesions affecting simultaneously the scalp, external ear, retroauricular area, eyelid, paranasal skin, neck axilla, and groin. Superimposed Staphylococcus and Streptococcus infection are common. It mainly affects children and exceptionally adults, and there are only a few published cases. The authors present the first reported case in Paraguay of an adult patient who had symptoms of human T-lymphotropic virus type 1–associated progressive tropical spastic paraparesis, and 6 years after the onset of the neurological symptoms, the patient developed infective dermatitis lesions on the skin, with frequent exacerbations since then. PMID:26588341

Impact of Milrinone Administration in Adult Cardiac Surgery Patients: Updated Meta-Analysis.

PubMed

Ushio, Masahiro; Egi, Moritoki; Wakabayashi, Junji; Nishimura, Taichi; Miyatake, Yuji; Obata, Norihiko; Mizobuchi, Satoshi

2016-12-01

To determine the effects of milrinone on short-term mortality in cardiac surgery patients with focus on the presence or absence of heterogeneity of the effect. A systematic review and meta-analysis. Five hundred thirty-seven adult cardiac surgery patients from 12 RCTs. Milrinone administration. The authors conducted a systematic Medline and Pubmed search to assess the effect of milrinone on short-term mortality in adult cardiac surgery patients. Subanalysis was performed according to the timing for commencement of milrinone administration and the type of comparators. The primary outcome was any short-term mortality. Overall analysis showed no difference in mortality rates in patients who received milrinone and patients who received comparators (odds ratio = 1.25, 95% CI 0.45-3.51, p = 0.67). In subanalysis for the timing to commence milrinone administration and the type of comparators, odds ratio for mortality varied from 0.19 (placebo as control drug, start of administration after cardiopulmonary bypass) to 2.58 (levosimendan as control drug, start of administration after cardiopulmonary bypass). Among RCTs to assess the effect of milrinone administration in adult cardiac surgery patients, there are wide variations of the odds ratios of administration of milrinone for short-term mortality according to the comparators and the timing of administration. This fact may suggest that a simple pooling meta-analysis is not applicable for assessing the risk and benefit of milrinone administration in an adult cardiac surgery cohort. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic Characteristics and Risks Associated with Stone Recurrence in Korean Young Adult Stone Patients.

PubMed

Kang, Ho Won; Seo, Sung Pil; Kim, Won Tae; Kim, Yong-June; Yun, Seok-Joong; Kim, Wun-Jae; Lee, Sang-Cheol

2017-08-01

The aim of this study was to assess the metabolic characteristics and risks of stone recurrence in young adult stone patients in Korea. The medical records of 1532 patients presenting with renal or ureteric stones at our stone clinic between 1994 and 2015 were retrospectively reviewed. Patients were grouped according to age (young adult, 18-29 years; intermediate onset, 30-59 years; old age, ≥60 years) at first presentation, and measurements of clinicometabolic characteristics and risks of stone recurrence were compared. Overall, excretion of urinary stone-forming substances was highest in the intermediate onset group, followed by the young adult and old age groups. Importantly, excretion of urinary citrate was lowest in the young adult group. Kaplan-Meier analyses identified a significant difference between the three age groups in terms of stone recurrence (log rank test, p < 0.001). Multivariate Cox regression analyses revealed that age at first stone presentation was an independent risk factor for stone recurrence. Urinary citrate excretion was an independent risk factor for stone recurrence in young adult stone patients. Younger age (18-29 years) at first stone presentation was a significant risk factor for stone recurrence, and urinary citrate excretion was an independent risk factor affecting recurrence in this group. Metabolic evaluation and potassium citrate therapy should be considered for young adult stone patients to prevent recurrence.

Brain morphological changes in adolescent and adult patients with anorexia nervosa.

PubMed

Seitz, J; Herpertz-Dahlmann, B; Konrad, K

2016-08-01

Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM -0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains.

Patient-accident-fracture (PAF) classification of acute distal radius fractures in adults.

PubMed

Herzberg, G; Galissard, T; Burnier, M

2018-05-19

There is not enough evidence in the literature to support the use of any classification system for distal radius fractures (DRF) in adults. However, there is a need for identification of more homogeneous groups of patients with DRF so that the extent of preoperative workup and sophistication of treatment would best match the needs of the patient. The authors propose an innovative method to analyse and stratify acute DRF in adults. A one-page chart includes criteria related to the patient (P), the energy of the accident (A) and the pathology of the fracture (F). Analysis of the pathology includes not only the distal radius itself but also the associated ulnar and carpal lesions. Radiological suspicion of associated carpal of distal radio-ulnar joint ligamentous injuries is included in the analysis. The preliminary results of the use of this chart in 1610 consecutive adult patients (16-102 years) with unilateral acute DRF are presented. A total of six homogeneous groups of patients are described, and the relevance of this classification regarding the therapeutic options is discussed.