Cranial defects in the Goldenhar syndrome

Four patients are presented with the Goldenhar syndrome (GS) and cranial defects consisting of plagiocephaly, microcephaly, skull defects, or intracranial dermoid cysts. Twelve cases from the literature add hydrocephalus, encephalocele, and arhinencephaly to a growing list of brain anomalies in GS. As a group, these patients emphasize the variability of GS and the increased risk for developmental retardation with multiple, severe, or unusual manifestations. The temporal relation of proposed teratogenic events in GS provides an opportunity to reconstruct biological relationships within the 3–5-week human embryo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38235/1/1320140306_ftp.pd

Genetic engineering: Principles and methods, Vol. 2. J.K. Setlow and A. Hollaender, eds. Plenum Press, New York, 1980, 289 pp., $32.50

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38145/1/1420230117_ftp.pd

Counseling in medical genetics, third edition, Sheldon Reed, Alan R. Liss, Inc., New York, 1980, 246 pp., $26.00

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38152/1/1420240312_ftp.pd

Further delineation of the dup(3q) syndrome

Three patients with duplication of 3q regions ranging from 3q25→qter to the entire long arm provide additional documentation of the dup(3q) malformation syndrome. Data on 40 cases now reported define a characteristic face with hirsutism, synophrys, broad nasal root, anteverted nares, downturned corners of the mouth, micrognathia, and malformed ears recognizable even in the 30-week fetus and distinct from that of the Brachmann-de Lange syndrome. Other characteristic anomalies include congenital heart anomalies involving primarily septal defects, hand malformations including simian creases, abnormal dermatoglyphics, clinodactyly or camptodactyly, omphalocele, skeletal anomalies, and genitourinary malformations. Severe mental and growth retardation are common in those patients (64%) who survive the first year. Chromosome study of relatives is extremely important for counseling because only 10 of 40 cases represented de novo duplications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38239/1/1320220113_ftp.pd

Oral ether lipid therapy in patients with peroxisomal disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42493/1/10545_2005_Article_BF01811415.pd

Structure and variation of human ribosomal DNA: molecular analysis of cloned fragments

Eco-RI-A fragments of the human ribosomal RNA gene family from two types of tissue and three individuals were cloned in [lambda] vectors and compared by restriction enzyme digestion and electron microscopy. The EcoRI fragment A contains (i) 0.2 kb of the 3' end of the 18S rDNA, (ii) 2.5 kb of internal transcribed spacer and the 5.8S rDNA, and (iii) 4.6 kb of the 28S rDNA gene. All of the six cloned rDNA fragments isolated are identical by these analyses. Moreover, all contain a HincII site that is absent in about 50% of the rDNA identified by genomic blotting. Polymorphism in the nontranscribed spacer rDNA was studied on genomic blots of BamHI-digested DNA, using the 3' end of the 28S rDNA as a probe. The boundaries between the 18S rDNA, internal transcribed spacer, 28S rDNA, and external nontranscribed spacer were determined by R-loop analysis, further defining the organization of the ribosomal RNA precursor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24168/1/0000426.pd

Zellweger syndrome: Diagnostic assays, syndrome delineation, and potential therapy

Patients with the cerebrohepatorenal syndrome of Zellweger lack peroxisomes and certain peroxisomal enzymes such as dihydroxyacetone phosphate acyltransferase in their tissues. Deficiency of this enzyme, which is necessary for glycerol ether lipid synthesis, provides a biochemical method for recognizing patients with subtle manifestations of Zellweger syndrome and suggests the utility of exogenous ether lipid precursors as a therapeutic strategy for these children. We describe the results of glycerol ether lipid supplementation to two children, one with classic Zellweger syndrome and 9% of control fibroblast dihydroxyacetone phosphate acyltransferase activity, and one with mild facial manifestations, wide sutures, hypotonia, developmental delay, hepatomegaly, peripheral retinal pigmentation, and 50% of control fibroblast dihydroxyacetone phosphate acyltransferase activity. An increase in erythrocyte plasmalogen levels following therapy was clearly demonstrated in the milder patient, and neither patient showed evidence of toxicity. Evaluation of therapy by comparison to the usual clinical course of Zellweger syndrome was not helpful because of the variability and incomplete documentation of 90 previously reported cases. The literature survey did provide criteria for classic Zellweger syndrome, which include hypotonia with or without deformation of limbs, large fontanels and split sutures, prominent forehead, flattened facial profile with hypoplastic supraorbital ridges, anteverted nares, highly arched palate, cryptorchidism or labial hypoplasia, hepatomegaly or elevated liver enzymes, peripheral pigmentation of the retina, renal cortical cysts, and characteristic neuropathology involving decreased myelinization, abnormal neuronal migration, and sudanophilic macrophages. Less severe patients, as exemplified by our case 2 and others from the literature, will not have all the classic features and can be recognized only by a growing panel of biochemical indicators. Our patient studies illustrate the complexity of designing comprehensive therapy for Zellweger-like conditions, suggest other diseases that may involve peroxisomal alterations, and emphasize the need for multicenter, collaborative studies to evaluate biochemical heterogeneity and therapy of peroxisomal disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38241/1/1320240109_ftp.pd

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

Outcomes of obstructed abdominal wall hernia: results from the UK national small bowel obstruction audit

Background: Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO). Methods: NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co-morbidity, imaging, operative treatment, and in-hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling. Results: NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non-operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in-hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001). Conclusion: NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group