Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures.

AIM: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves' orbitopathy (GO) receiving surgery for disfiguring proptosis. METHOD: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. RESULTS: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. CONCLUSIONS: In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.

Cosmetic orbital surgery.

PURPOSE: Current indications for orbital surgery primarily aimed at improving cosmesis are considered in the context of subspecialist orbital practice by an ophthalmologist. SCOPE: Thyroid eye disease, orbital vascular anomalies, and dermolipomas are common orbital diseases in which the symptoms can be purely cosmetic. Accurate anatomical awareness, preoperative scanning, control of medical factors including smoking and thyroid status, and endoscopic techniques have all contributed to the aesthetic outcome of orbital surgery. The threshold for performing reconstructive orbital surgery has also been lowered by public demand. CONCLUSIONS: Orbital surgeons can therefore offer the familiar techniques, such as orbital decompression, for pure cosmesis. Sensitive history taking and awareness of the psychological element are of paramount importance for the orbital surgeon who develops a cosmetic practice.

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Two brothers with trichiasis, entropion and corneal scarring, sensorineural hearing loss, progressive thinning of scalp hair, mild learning difficulties and distinct facial features. A new syndrome?

Two brothers with very similar phenotypes involving trichiasis (misdirected lashes), entropion with corneal abrasions, strabismus, progressive thinning of the scalp hair, sensorineural hearing impairment, mild learning difficulties, and inguinal hernias are described. They have similar, distinctive facial features with deep-set eyes, a high nasal bridge and a short philtrum. Both brothers are carriers of a maternally inherited apparently balanced translocation of chromosomes 11 and 18: 46,XY, t(11;18)(p13;q21)mat. However, this is thought to be coincidental, since their younger brother also carries this translocation and is phenotypically normal. Although they have many features that are found in the ectodermal dysplasia syndromes, their combination of features is distinct and has to our knowledge not been previously reported.

Orbital cellulitis caused by Fusobacterium necrophorum.

PURPOSE: To report the case of a previously healthy young female who developed orbital cellulitis caused by Fusobacterium necrophorum. We are unaware of previous reports of this condition caused by the same anaerobic, gram-negative, nonsporeforming bacterium and could find no reference to it in a computer search using MEDLINE. METHODS: Case report. RESULTS: In the case of orbital cellulitis presented here, the patient required 3 sinus debridement operations and 30 days of intravenous antibiotics. Despite this, her vision did not fully recover. CONCLUSION: F. necrophorum is capable of causing severe orbital disease that requires aggressive and prompt treatment to preserve sight.

Selective disruption of nuclear import by a functional mutant nuclear transport carrier.

p10/NTF2 is a nuclear transport carrier that mediates the uptake of cytoplasmic RanGDP into the nucleus. We constructed a point mutant of p10, D23A, that exhibited unexpected behavior both in digitonin-permeabilized and microinjected mammalian cells. D23A p10 was markedly more efficient than wild-type (wt) p10 at supporting Ran import, but simultaneously acted as a dominant-negative inhibitor of classical nuclear localization sequence (cNLS)-mediated nuclear import supported by karyopherins (Kaps) alpha and beta1. Binding studies indicated that these two nuclear transport carriers of different classes, p10 and Kap-beta1, compete for identical and/or overlapping binding sites at the nuclear pore complex (NPC) and that D23A p10 has an increased affinity relative to wt p10 and Kap-beta1 for these shared binding sites. Because of this increased affinity, D23A p10 is able to import its own cargo (RanGDP) more efficiently than wt p10, but Kap-beta1 can no longer compete efficiently for shared NPC docking sites, thus the import of cNLS cargo is inhibited. The competition of different nuclear carriers for shared NPC docking sites observed here predicts a dynamic equilibrium between multiple nuclear transport pathways inside the cell that could be easily shifted by a transient modification of one of the carriers.

Presence of P210bcrabl is associated with decreased expression of a beta chemokine C10 gene in a P210bcrabl-positive myeloid leukemia cell line.

BACKGROUND: Chronic myelogenous leukemia (CML) is thought to start with the acquisition of the t(9;22) chromosomal translocation that codes for the P210bcrabl tyrosine-specific protein kinase. The CML cells exhibit anchorage-independent cell growth and genetic instability. After the initial phase, the cells acquire the phenotype of growth factor-independent growth. After the chronic phase, the disease evolves into the accelerated and blastic phases through the process of sequential random mutation. MATERIALS AND METHODS: To identify some of the genetic changes that contribute to the phenotype of blastic and accelerated phase cells, we used differential display PCR to compare levels of cDNA reverse transcripts of mRNA in 32Dc13 cells and 32Dc13 cells that were stably transfected with a bcrabl cDNA plasmid in a constitutively expressed transcription unit. These cells were designated 32Dc13P210bcrabl. For these studies, we used the 32D myeloid leukemia cell line, which depends on IL-3 for growth. RESULTS: Following introduction of the bcr-abl cDNA through transfection, the cell line became growth factor independent, mimicking the change in phenotype that occurs during the later phases of CML. These differential display screening assays detected altered levels of transcripts for 28 genes. Of interest to the biology of growth factor-independent growth in the bcrabl-positive 32D cells was the fact that the C10 beta chemokine gene was expressed at higher levels in the 32Dc13 cells than in the 32Dc13P210bcrabl cells. CONCLUSIONS: These studies show that a C10 beta chemokine gene was expressed at different levels with or without P210bcrabl.

Viral protein R regulates nuclear import of the HIV-1 pre-integration complex.

Replication of human immunodeficiency virus type 1 (HIV-1) in non-dividing cells critically depends on import of the viral pre-integration complex into the nucleus. Genetic evidence suggests that viral protein R (Vpr) and matrix antigen (MA) are directly involved in the import process. An in vitro assay that reconstitutes nuclear import of HIV-1 pre-integration complexes in digitonin-permeabilized cells was used to demonstrate that Vpr is the key regulator of the viral nuclear import process. Mutant HIV-1 pre-integration complexes that lack Vpr failed to be imported in vitro, whereas mutants that lack a functional MA nuclear localization sequence (NLS) were only partially defective. Strikingly, the import defect of the Vpr- mutant was rescued when recombinant Vpr was re-added. In addition, import of Vpr- virus was rescued by adding the cytosol of HeLa cells, where HIV-1 replication had been shown to be Vpr-independent. In a solution binding assay, Vpr associated with karyopherin alpha, a cellular receptor for NLSs. This association increased the affinity of karyopherin alpha for basic-type NLSs, including that of MA, thus explaining the positive effect of Vpr on nuclear import of the HIV-1 pre-integration complex and BSA-NLS conjugates. These results identify the biochemical mechanism of Vpr function in transport of the viral pre-integration complex to, and across, the nuclear membrane.

Rescue from apoptosis in early (CD34-selected) versus late (non-CD34-selected) human hematopoietic cells by very late antigen 4- and vascular cell adhesion molecule (VCAM) 1-dependent adhesion to bone marrow stromal cells.

Monoclonal antibodies to very late antigen 4 (VLA-4) recognize the alpha4beta1 integrin receptor. This monoclonal antibody blocks the adhesion between early hematopoietic progenitor cells (CD34-selected cells) and stromal cells when added to cultures of these cells. Addition of the VLA-4 monoclonal antibody to cultures of stromal cells and CD34-selected cells was shown to induce apoptosis of CD34-selected cells in these CD34-selected cell/stromal cell cocultures, as measured by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method. In contrast to these experiments with early hematopoietic progenitor cells (CD34+), the level of adhesion between more differentiated cells (unfractionated hematopoietic cells) and stromal cells was not significantly altered by addition of the anti-VLA-4 monoclonal antibody. Similarly, the level of apoptosis of unfractionated hematopoietic cells was not significantly increased by the addition of anti-VLA-4 monoclonal antibody to cultures of the latter cells with stromal cells. The binding of the unfractionated cells is less than that of the CD34-selected cells. Given that there is no difference between the alpha4beta1 integrin expression level of the early and late myeloid cells, there may be a difference in the functional state of the integrin between the early and late myeloid cells. We also show that CD34+-selected precursor cells proliferate at a higher rate when these cells are plated on recombinant vascular cell adhesion molecule 1 molecules. These data indicate that the alpha4beta1 integrin receptor (VLA-4) plays a central role in the apoptosis rescue function that results from the anchorage-dependent growth of the CD34-selected early hematopoietic cells on stromal cells. The data suggest that these apoptosis rescue pathways have less significance as the cells mature and become anchorage independent in their growth. These data should assist in the design of systems for the ex vivo proliferation and transduction of early hematopoietic cells for genetic therapy.

Alteration of OBCAM conformation as a result of opioid receptor expression and opioid ligand treatment.

Several lines of evidence link the opioid binding cell adhesion molecule (OBCAM) to opioid function. When delta-opioid receptor cDNA (DOR-1) was expressed in CHO cells, OBCAM immunoreactivity (OBCAM-ir) was detected. Transfected cell lines which displayed high opioid binding also expressed high cell surface OBCAM-ir, while untransfected CHO and vector control cells did not. The positive control, neural cell adhesion molecule (NCAM), a protein with structural homology to OBCAM, displayed the same levels of immunofluorescence in transfected and nontransfected cell lines. Membranes from CHO cells transfected with and expressing a variety of muscarinic and dopamine receptors were tested for immunoreactivity. No significant OBCAM-ir was detected in any of these cell membranes. When anti-OBCAM peptide antibodies were used for immunoblots of CHO cells, untransfected, non-binding transfected, and high binding transfected cells revealed the same banding patterns with approximately equal intensity. These observations suggest that in untransfected cells OBCAM is either not present on the extracellular side of the CHO cell membrane or that it exists in an altered conformation which changes upon transfection with opioid receptors to allow recognition of the non-denatured protein by anti-OBCAM antibodies.

MRI of idiopathic orbital inflammatory syndrome using fat saturation and Gd-DTPA.

Idiopathic orbital inflammatory syndrome encompasses a group of inflammatory conditions for which no systemic or local cause can be found, and is commonly referred to as orbital pseudotumour. On conventional MRI sequences subtle areas of inflammation or enhancing tissue can easily be masked by the high signal intensity of orbital fat and involvement of the fat itself may not be appreciated. We describe the MRI features of three patients with idiopathic orbital inflammation using frequency-selective fat saturation and Gd-DTPA.

Reviews.

THE MANAGEMENT OF WOUNDS AND BURNS CHRONIC VENOUS DISEASES OF THE LEG FRAUD AND MISCONDUCT IN MEDICAL RESEARCH PSYCHOLOGY, PSYCHIATRY AND CHRONIC PAIN.

Regulation of an opioid-binding protein in NG108-15 cells parallels regulation of delta-opioid receptors.

An opioid-binding protein has recently been purified from bovine brain and cloned, and its cDNA sequence has been obtained. Indirect evidence suggests that this protein has a role in opioid-receptor function. However, because direct testing of its function by expression of its cDNA has not yet been possible and because its structure bears no resemblance to G protein-coupled receptors, the role of this protein in opioid-receptor activity is still in question. An antibody raised to a portion of the predicted amino acid sequence of opioid-binding cell-adhesion molecule (OBCAM) specifically labeled the surface of NG108-15 cells, as visualized by immunofluorescence with confocal microscopy. Furthermore, chronic treatment of these cells with opioid agonist, which down-regulates opioid receptors, reduced OBCAM immunoreactivity (ir). Down-regulation of both opioid receptors and OBCAM-ir was greatest after chronic treatment of NG108-15 cells with delta-opioid agonists, as well as with nonselective agonists such as etorphine, whereas other agonists including [D-Ala2-N-MePhe4-Gly-ol]enkephalin, morphine, levorphanol, dynorphin A-(1-13), and U-50,488H were less effective or ineffective. Chronic treatment of NG108-15 cells with muscarinic agonists had no effect on OBCAM-ir. Furthermore, NG108-15 cells transfected with an antisense construct to OBCAM have a reduced density of opioid-binding sites as well as reduced OBCAM-ir. Taken together, these results strongly suggest that OBCAM has a role in opioid-receptor function in NG108-15 cells.

Ocular fundus lesions in sports divers using safe diving practices.

Ocular fundus fluorescein angiography was performed on 26 divers, who had used safe diving practices for at least 10 years, and on seven controls. There was no significant difference in the incidence of macular abnormalities between these groups and those of a previous study. Adherence to safe diving practice confers some protection against the macular abnormalities known to occur in divers with a history of decompression sickness.