bluuebunny/crossref_metadata_2025_split huggingface dataset:
A surgical tendonitis model in horses: Technique, clinical, ultra-sonographic and histological characterisation
Authors: Hunter S. , Campbell N. , Blikslager A. , Smith R. , Schramme M. 
Published: June 2010

Summary
Objective: Tendon injuries are common in all athletic activities in both humans and horses. Research of treatment modalities for this disease has typically been performed on a model of collagenase-induced tendonitis. This model has several disadvantages. Our hypothesis was that a reproducible core lesion could be created surgically in superficial digital flexor tendons (SDFT), which could then be evaluated consistently using ultrasonography. Materials and methods: Four horses free of forelimb lameness were used in this study. Each horse underwent general anaesthesia and a synovial resector was used to create a core lesion in the SDFT of each forelimb. Sono-graphic examination was conducted weekly using 2 cm intervals between a section 7 and 25 cm distal to the accessory carpal bone. At two, four, eight, and 12 weeks after injury, a horse was euthanatized. Histopathological evaluation of the SDFT was performed at the same levels as the sonographic examination. Results: Only mild clinical signs of tendonitis were observed. Ultrasonographic core lesions were 10–16 cm long and had a mean maximum cross-sectional area (CSA) of 18.25 ± 5.91% occurring at 17–23 cm distal to the accessory carpal bone, and a mean volume of 1.86 ± 0.26 cm3. Mean duration taken to achieve maximum lesion CSA and lesion volume was 35 ± 7 days. Histologically, the lesions were characterised by mild inflammation followed by fibroplasia. Conclusion: The reported surgical technique resulted in core lesions that were consistent in size and location, were readily evaluated with ultrasonography, and showed similarities with the ultrasonographic and histological progression of naturally occurring tendonitis lesions.
Treatment of lumbosacral discospondylitis by surgical stabilisation and application of a gentamicin-impregnated collagen sponge
Authors: Dennis R. , Gemmill T. J. , Renwick A. I. C. 
Published: June 2010

SummaryThis report describes a case of lumbosacral discospondylitis in a two-year-old boxer dog. The dog had been presented with chronic hindlimb lameness and signs of lumbar spinal pain. The diagnosis was confirmed with a magnetic resonance imaging scan and positive blood culture. Following unsuccessful conservative management, the dog was treated with surgical stabilisation using screws and polymethylmethacrylate, and implantation of a gentamicin-impregnated collagen sponge into the L7-S1 disc space. This technique has not previously been described. The dog had a successful long-term outcome with complete resolution of clinical signs
IL-12p35 Promotes Antibody-Induced Joint Inflammation by Activating NKT Cells and Suppressing TGF-β
Authors: Park Yuna , Kim Hye Sung , Ahn Ji Ye , Yun Daesun , Cho Mi La , Hong Seokmann , Kim Ho Youn , Chung Doo Hyun 
Published: June 2010

AbstractThe functional role of IL-12 in rheumatoid arthritis is controversial. Moreover, whether IL-12 contributes to regulation of Ab-induced joint inflammation remains unclear. To address these issues, we explored the functional roles of IL-12 in Ab-induced arthritis using the K/BxN serum transfer model. IL-12p35−/− and IL-12Rβ2−/− mice were resistant to the development of arthritis. Injection of K/BxN serum into IL-12p40–yellow fluorescence protein reporter (yet40) mice induced CD11b+ cells, CD11c+ cells, and Gr-1+ granulocytes to produce IL-12p40 in the joints. The levels of IFN-γ, IL-4, and IL-6 production were lower in joint tissues of IL-12p35−/− and IL-12Rβ2−/− mice than in B6 mice, whereas levels of TGF-β expression were higher. Administering IL-12p35−/− mice rIL-12 or IFN-γ restored joint inflammation and suppressed TGF-β production in joint tissues. Moreover, administering neutralizing anti–TGF-β mAb enhanced joint inflammation. Among the immune cells that infiltrated joint tissues during Ab-induced arthritis, NKT cells expressed IL-12β2 receptors. Furthermore, the adoptive transfer of splenocytes from B6 or Gr-1+ granulocyte-depleted mice restored joint inflammation in IL-12Rβ2−/− mice as much as in B6 mice, whereas splenocytes from Jα18−/− mice did not. These findings indicate that signals via IL-12β2 receptors on NKT cells play a critical role in the development of Ab-induced arthritis. The IL-12p35/IFN-γ axis promotes Ab-induced joint inflammation by activating NKT cells and suppressing TGF-β, which may provide novel information for the development of new therapeutic strategies for the inhibition of rheumatoid arthritis.
Improving Clinical Trial Participant Tracking Tools Using Knowledge-anchored Design Methodologies
Authors: Embi P.J. , Johnson S.B. , Mendonca E. , Starren J. , Payne P.R.O. 
Published: June 2010

Summary
Objective: Rigorous human-computer interaction (HCI) design methodologies have not traditionally been applied to the development of clinical trial participant tracking (CTPT) tools. Given the frequent use of iconic HCI models in CTPTs, and prior evidence of usability problems associated with the use of ambiguous icons in complex interfaces, such approaches may be problematic. Presentation Discovery (PD), a knowledge-anchored HCI design method, has been previously demonstrated to improve the design of iconic HCI models. In this study, we compare the usability of a CTPT HCI model designed using PD and an intuitively designed CTPT HCI model.
Methods: An iconic CPTP HCI model was created using PD. The PD-generated and an existing iconic CTPT HCI model were subjected to usability testing, with an emphasis on task accuracy and completion times. Study participants also completed a qualitative survey instrument to evaluate subjective satisfaction with the two models.
Results: CTPT end-users reliably and reproducibly agreed on the visual manifestation and semantics of prototype graphics generated using PD. The performance of the PD-generated iconic HCI model was equivalent to an existing HCI model for tasks at multiple levels of complexity, and in some cases superior. This difference was particularly notable when tasks required an understanding of the semantic meanings of multiple icons.
Conclusion: The use of PD to design an iconic CTPT HCI model generated beneficial results and improved end-user subjective satisfaction, while reducing task completion time. Such results are desirable in information and time intensive domains, such as clinical trials management.
Citation: Payne PRO, Embi PJ, Johnson SB, Mendonca E, Starren J. Improving clinical trial participant tracking tools using knowledge-anchored design methodologies. Appl Clin Inf 2010; 1: 177–196 http://dx.doi.org/10.4338/ACI-2010-02-RA-0012
Pheochromocytoma in a 2.75‐year‐old‐girl with a germline von Hippel–Lindau mutation Q164R
Authors: Sovinz Petra , Urban Christian , Uhrig Sabine , Stepan Vinzenz , Lackner Herwig , Schwinger Wolfgang , Benesch Martin , Moser Andrea , Spuller Ekkehard , Speicher Michael R. 
Published: June 2010

AbstractPheochromocytomas are rare tumors of the adrenal gland occurring sporadically or as part of familial cancer syndromes. Here we report on the case of a pheochromocytoma due to the germline missense mutation c.491A>G (Q164R) in exon 3 of the von Hippel–Lindau gene in a girl as young as 2.75 years. Extended analyses of her relatives showed that the mutation occurred de novo in the patient's father who was subsequently diagnosed with bilateral pheochromocytomas and a retinal angioma. To the best of our knowledge, this is the youngest patient presenting with pheochromocytoma so far described in the literature. The same VHL mutation has been reported in a patient who developed a pheochromocytoma at the age of 10 years; therefore, for known VHL Q164R mutation carriers, we suggest screening for pheochromocytoma beginning at 2 years of age. © 2010 Wiley‐Liss, Inc.
Hemifacial myohyperplasia sequence
Authors: Pereira‐Perdomo Diego F. , Vélez‐Forero Juanita , Prada‐Madrid Rolando 
Published: June 2010

AbstractThis is a report of an additional patient affected by hemifacial myohyperplasia (HMH). We postulate that this condition originates around the fourth gestational week at any step of cranial muscle development from somitomeres to branchial arches, most probably due to prolonged period of proliferation during cranial muscle development, subsequent abnormal contact between cranial neural crest (CNC) cells and cranial myoblasts, and an impaired interaction among CNC cells and cranial myoblasts derivatives. HMH may represent another example of somatic mosaicism and its features can be explained by a combination of morphostatic and morphodynamic mechanisms of pattern formation during development. Here we suggest that HMH is a sequence in which the primary defect is hyperplasia of the facial muscles and the other findings are secondary to this. © 2010 Wiley‐Liss, Inc.
The right to ignore genetic status of late onset genetic disease in the genomic era; Prenatal testing for Huntington disease as a paradigm
Authors: Erez A. , Plunkett K. , Sutton V.R. , McGuire A.L. 
Published: June 2010

AbstractDuring the last decade, the field of human genome research has gone through a phase of rapid discovery that has provided scientists and physicians with a wide variety of research tools that are applicable to important medical issues. We describe a true case of familial Huntington disease (HD) in which we modified personal details to protect patient's privacy, where the proband at risk preferred not to know his disease status but wanted to know the status in his unborn child. Once we found the father to be negative, the case raised an important ethical question regarding the management of this as well as future pregnancies. This article discusses the arguments for and against the right not to know of one's carrier status, as well as professional obligations in the context of withholding unwanted information that may have direct implications not only for the patient himself but also for other family members. HD has served as a model for many other adult onset genetic diseases in terms of carrier testing guidelines. Hence, we feel it is time to revisit the issue of prenatal testing for HD and consider updating the current recommendations regarding the patient's right to “genetic ignorance”, or the right not to know genetic information. © 2010 Wiley‐Liss, Inc.
Molecular characterization of a de novo 6q24.2q25.3 duplication interrupting UTRN in a patient with arthrogryposis
Authors: Tabet Anne‐Claude , Aboura Azzedine , Gérard Marion , Pilorge Marion , Dupont Céline , Gadisseux Jean‐François , Hervy Nadège , Pipiras Eva , Delahaye Andrée , Kanafani Samia , Verloes Alain , Benzacken Brigitte , Betancur Catalina 
Published: June 2010

AbstractChromosome 6q duplications have been documented repeatedly, allowing the delineation of a “6q duplication syndrome,” characterized by hypertelorism, downslanting palpebral fissures, tented upper lip, short neck, severe mental and growth retardation, and joint contractures. Most reported cases result from malsegregation of a reciprocal translocation leading to a terminal 6q duplication and partial monosomy of another chromosome. Only 11 cases of de novo pure duplication have been reported so far. The breakpoints do not appear to be recurrent, but in most cases they have not been characterized molecularly, precluding genotype–phenotype correlation. We report on an 8‐year‐old girl with a phenotype consistent with mild 6q duplication syndrome, including characteristic physical findings, mild mental retardation, and joint contractures. She carries a 13 Mb de novo 6q24.2q25.3 duplication, diagnosed by high‐resolution karyotype and confirmed by array‐CGH. Molecular characterization of the duplicated segment with quantitative PCR showed that the proximal breakpoint is localized within the UTRN gene, encoding utrophin, the autosomal homologue of dystrophin. We discuss the possible implication of UTRN in arthrogryposis associated with duplications spanning the 6q23q26 region. © 2010 Wiley‐Liss, Inc.
Cohesin biology and the cohesinopathies: Abstracts from the Second Biennial Conference, Pontignano, Italy, 2009
Authors: Musio Antonio , Krantz Ian D. 
Published: June 2010

AbstractThe cohesin proteins compose an evolutionarily conserved complex whose fundamental role in chromosomal cohesion and coordinated segregation of sister chromatids has been well characterized across species. Recently regulators and structural components of cohesin have been found to surprisingly cause specific human developmental disorders (collectively termed “cohesinopathies”) and some cancers when mutated. Since the first report of cohesin's role in regulating gene expression 10 years ago, there has been an explosion of literature implicating cohesin in multiple diverse cellular and gene regulatory processes. While downregulating cohesin sufficiently to cause significant sister chromatid cohesion defects is universally lethal to multicellular organisms, the mechanism of action by which cohesin effects developmental processes appears to be through a non‐canonical role as a regulator of gene expression. It became evident that there was a need to bring cohesin basic scientists together with clinical investigators interested in the medical disorders associated with cohesin dysfunction to cross pollinate their fields and advance both the basic biology as well as the understanding of, and improved treatments for, this newly classified group of clinical disorders. Towards this end an international meeting hosted by the CNR in Italy and jointly supported by funds from the CdLS USA Foundation and the National Institute of Child Health and Development (NIH) was established in 2007. Based upon the success of that meeting a standing biennial meeting was established and the proceedings from the Second International Cohesin Biology and the Cohesinopathies Biennial Meeting held in Pontignano, Italy in 2009 are presented here. © 2010 Wiley‐Liss, Inc.
Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey
Authors: Rohatgi Sarika , Clark Dinah , Kline Antonie D. , Jackson Laird G. , Pie Juan , Siu Victoria , Ramos Feliciano J. , Krantz Ian D. , Deardorff Matthew A. 
Published: June 2010

AbstractCornelia de Lange syndrome (CdLS) is a dominant disorder with classic severe forms and milder atypical variants. Central to making the diagnosis is identification of diagnostic facial features. With the recognition that patients with SMC1A and SMC3 mutations have milder, atypical features, we surveyed 65 dysmorphologists using facial photographs from 32 CdLS patients with the goals of (1) Illustrating examples of milder patients with SMC1A mutations and (2) Obtaining objective data to determine which facial features were useful and misleading in making a diagnosis of CdLS. Clinicians were surveyed whether the patient had CdLS or another diagnosis, the certainty of response and the clinical features used to support each response. Using only facial photographs, an average of 24 cases (75%) were accurately diagnosed per clinician. Correct diagnoses were made in 90% of classic CdLS and 87% of non‐CdLS cases, however, only 54% of mild or variant CdLS were correctly diagnosed by respondents. We confirmed that CdLS is most accurately diagnosed in childhood and the diagnosis becomes increasingly difficult with age. This survey demonstrated that emphasis is placed on the eyebrows, nasal features, prominent upper lip and micrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathism with age dissuaded survey takers from arriving at a diagnosis of CdLS in individuals with mild NIPBL and SMC1A mutations. This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS. © 2010 Wiley‐Liss, Inc.
Wormian bones in osteogenesis imperfecta: Correlation to clinical findings and genotype
Authors: Semler Oliver , Cheung Moira S , Glorieux Francis H , Rauch Frank 
Published: June 2010

AbstractThe presence of a larger than usual number of Wormian bones (accessory skull bones completely surrounded by a suture line) is a well‐known radiographic sign of osteogenesis imperfecta (OI), but the phenotypic and genotypic correlates are not well characterized. In the present study we retrospectively analyzed skull radiographs of 195 OI patients (median age 11.8 years, range 0.4–48 years; 100 female). A significant number of Wormian bones (SNWB, defined as the presence of 10 or more Wormian bones) were found in at least one patient in all of the OI types studied (I, III to VII). SNWB were observed in 35% of patients with OI type I, in 96% of patients with OI type III and 78% of patients with OI type IV. SNWB were present in 28% of patients with haploinsufficiency (nonsense and frameshift) mutations in COL1A1, in 96% of patients with helical glycine substitutions in the alpha 1 chain of collagen type I and in 72% of patients with helical glycine substitutions in the alpha 2 chain of collagen type I. Stepwise multivariate logistic regression analysis showed that height z‐score, an indicator of disease severity, was inversely related with the prevalence of SNWB. SNWB were visible in 19 of the 26 patients who had skull radiographs in the first year of life, including a 2‐week‐old newborn. Thus, it appears that SNWB occur more frequently in more severely affected OI patients and seem to develop mostly in utero. © 2010 Wiley‐Liss, Inc.
Paternal isodisomy of chromosome 2 as a cause of long chain 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD) deficiency
Authors: Baskin Berivan , Geraghty Michael , Ray Peter N. 
Published: June 2010

AbstractLong‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency is an autosomal recessive disorder affecting mitochondrial fatty acid oxidation due to mutations in the HADHA gene. We report on a 22‐month‐old child who was identified on expanded newborn screening with an abnormal acylcarnitine pattern and increased C14OH. Molecular analysis showed that the child was homozygous for the common mutation, c.1526G > C (p.Glu510Gln) in the HADHA gene. Carrier testing on the parental samples revealed that the father was heterozygous for the mutation whereas the mother did not carry the mutation. Short tandem repeat testing with markers covering both short and long arms of chromosome 2 showed that the child has paternal uniparental isodisomy. We highlight the importance of parental testing in cases of homozygosity in autosomal recessive disorders and its impact on genetic counseling of the family. © 2010 Wiley‐Liss, Inc.
Recurrence of achondrogenesis type 2 in sibs: Additional evidence for germline mosaicism
Authors: Comstock Jessica M. , Putnam Angelica R. , Sangle Nikhil , Lowichik Amy , Rose Nancy C. , Opitz John M. 
Published: June 2010

AbstractAchondrogenesis Type II (ACG2) is a lethal skeletal disorder caused by a dominant mutation in the type II collagen gene (COL2A1). Familial cases have been reported, suggesting both germline and somatic mosaicism. We report on two pregnancies from the same couple with gross, radiologic, and microscopic findings of ACG2. Molecular analysis of the second infant demonstrated heterozygosity for a c.2303G > A transition (p.Gly768Asp) in exon 33 of the COL2A1 gene. Although this mutation could not be proven by molecular studies in the first infant, identical findings in two affected pregnancies support germline mosaicism as the cause of ACG2 in this family. © 2010 Wiley‐Liss, Inc.
Autosomal dominant prelingual hearing loss with Palmoplantar Keratoderma syndrome: Variability in clinical expression from mutations of R75W and R75Q in the GJB2 gene
Authors: Birkenhäger Ralf , Lüblinghoff Nicola , Prera Erick , Schild Christian , Aschendorff Antje , Arndt Susan 
Published: June 2010

AbstractAbout one to three of a 1,000 neonates are afflicted at birth with a serious hearing impairment, with about half of the cases due to genetic causes. Genetic causes of hearing impairment are very heterogeneous. About half of all cases of genetically caused nonsyndromic hearing loss can be ascribed to mutations in the GJB2 gene (connexin 26) and to deletions in the GJB6 gene(connexin 30). Thus far, about 90 different mutations have been identified in the GJB2 gene, of which the majority are autosomal recessive. Ten mutations are autosomal dominant and are in most cases associated with various skin diseases: the keratitis‐ichthyosis‐deafness (KID) syndrome, Vohwinkel syndrome and palmoplantar keratoderma with deafness. To date, the following mutations have been identified which lead to the Palmoplantar Keratoderma syndrome with deafness; Gly59Ala, Gly59Arg, His73Arg, Arg75Trp, and Arg75Gln. We are reporting on four patients with severe hearing impairment. They are members of three unrelated families, who are carriers of mutations Arg75Trp or Arg75Gln, but unlike patients of other publications, do not all present with Palmoplantar Keratoderma syndrome. Our investigations document additional evidence for the correlation between the cited mutations in the GJB2 gene and a syndromic hearing impairment with palmoplantar keratoderma. © 2010 Wiley‐Liss, Inc.
Holoprosencephaly and holoprosencephaly‐like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients
Authors: Ribeiro Lucilene Arilho , Quiezi Rodrigo Gonçalves , Nascimento Adriana , Bertolacini Claudia Pereira , Richieri‐Costa Antonio 
Published: June 2010

AbstractHoloprosencephaly (HPE) is genetically heterogeneous. Variable phenotypic manifestations within families with normal and affected patients have been attributed to the number and type of HPE gene mutations. Environmental agents may also contribute to the severity as well as the requirement of multiple hits. Clinical expression is extremely variable ranging from minor facial signs to complex craniofacial anomalies such as cyclopia. Main genes involved include SHH, GLI2, PTCH1, TGIF, ZIC2, TDGF1, SIX3; however, several other candidates have been proposed. Recently it was established that the human growth arrest specific gene 1 (GAS1) is a potential locus for several human craniofacial malformations. Here, we report on four Brazilian patients with GAS1 DNA sequence change who presented variable phenotypical manifestations ranging from classic HPE to HPE‐like signs. Two patients had single DNA sequence change in the GAS1 gene, while in other two, an additional mutation in the SHH gene was observed. Clinical manifestations presented by these patients suggest that GAS1 could be considered a candidate locus for one of the types of human HPE. © 2010 Wiley‐Liss, Inc.
Petty syndrome and Fontaine–Farriaux syndrome: Delineation of a single syndrome
Authors: Braddock Stephen R. , Ardinger Holly H. , Yang Chun‐Song , Paschal Bryce M. , Hall Bryan D. 
Published: June 2010

AbstractIn 1990, Petty et al. described two patients representing a novel syndrome with “congenital progeriod” features and neither had classical progeria nor Wiedemann–Rautenstrauch syndrome, though many findings were overlapping. One of the cases had previously been described by Dr. Wiedemann in 1948. The key features of Petty syndrome include pre and postnatal growth restriction, decreased subcutaneous fat with loose skin, enlarged fontanelle with underdeveloped calvarium, coronal synostosis, unruly hair pattern with non‐uniform distribution, prominent eyebrows, umbilical hernia, distal digital hypoplasia, and normal or near normal development. Significant overlap to other syndromes, particularly the Fontaine–Farriaux syndrome, is apparent. In 2004, Ardinger postulated that Petty syndrome, like classical progeria, might be secondary to a defect in the lamin A/C (LMNA) gene. The purpose of this paper is to describe two new unrelated cases of this unique syndrome that further delineate the phenotype, compare to phenotypically similar syndromes, and postulate that Petty syndrome could represent a new laminopathy. In addition, evidence suggesting that the Petty syndrome and Fontaine–Farriaux syndromes are variable expressions of the same condition is discussed. © 2010 Wiley‐Liss, Inc.