Transverse glabellar flap for obliteration/isolation of the nasofrontal duct from the anterior cranial base

Management of fractures involving the nasofrontal duct region of the frontal sinus has focused on preserving function when possible or obliterating the sinus and duct when fracture patterns potentiate ductal obstruction and possible transcranial seeding of bacteria. When frontal sinus preservation is in doubt, controversy surrounds the use of cranialization versus obliteration, and the method of obliteration. Perioperative and late postoperative infections are uncommon, but their occurrence jeopardizes an often complex reconstruction and can be life threatening. This paper describes the design and indications for a pedicled transverse glabellar muscle flap for obliteration of the nasofrontal duct, thereby isolating the anterior cranial base from the aerodigestive system. This vascularized muscle flap utilizes the corrugator supercilii and procerus muscles, which are introduced into the sinus via a small, surgically created window in the superomedial orbital wall without disturbing the central facial aesthetic contours. Six patients with comminuted fractures at the nasofrontal duct level associated with displaced posterior frontal sinus fractures have been treated with the transverse glabellar flap. Follow-up ranges from 8 to 30 months. There have been no early or late postoperative complications. The transverse glabellar flap is a reliable and versatile method of partitioning the upper aerodigestive tract from the anterior cranial base with vascularized tissue, thus minimizing the risk of infectious complications. The resulting donor site deformity is more acceptable than that seen with the traditional pedicled galeal frontalis flap.     

Improved oxygenation utilizing a prone positioner in patients with acute respiratory distress syndrome

OBJECTIVES: (a) To determine whether placing patients with acute respiratory distress syndrome in the prone position by a light-weight portable support frame improves oxygenation, (b) whether one can determine which patients benefit from prone positioning, and (c) to determine an effective technique for prone positioning of patients. DESIGN: Prospective, controlled trial without blinding. SETTING: Medical intensive care units in two urban university-affiliated hospitals. PATIENTS: Fifteen patients meeting a standard definition for acute respiratory distress syndrome were studied prospectively. Each patient acted as his own control for purposes of comparison. INTERVENTION: Patients were assigned randomly to begin in either supine or prone positions. The positioning frame was used to turn patients from one position to the other, and oxygenation, ventilation, respiratory mechanics, and hemodynamics were measured. RESULTS: Significantly better oxygenation was seen in the prone positions than in the supine (P < 0.05). In the overall population there was a decrease in AaDO2 of 21 mmHg when the patients were placed prone. The groups were then divided into responders (n = 9) and nonresponders (n = 6). There were significant differences between the groups (but not between positions) regarding PaO2, baseline, PaCO2, pulmonary artery pressures, and peak inspiratory pressures on the ventilator and in ICU length of stay and time on mechanical ventilatory support. CONCLUSION: Prone positioning improves oxygenation in the majority of patients studied and can be achieved relatively easily.     

Identification of a Gialpha binding site on type V adenylyl cyclase

The stimulatory G protein alpha subunit Gsalpha binds within a cleft in adenylyl cyclase formed by the alpha1-alpha2 and alpha3-beta4 loops of the C2 domain. The pseudosymmetry of the C1 and C2 domains of adenylyl cyclase suggests that the homologous inhibitory alpha subunit Gialpha could bind to the analogous cleft within C1. We demonstrate that myristoylated guanosine 5'-3-O-(thio)triphosphate-Gialpha1 forms a stable complex with the C1 (but not the C2) domain of type V adenylyl cyclase. Mutagenesis of the membrane-bound enzyme identified residues whose alteration either increased or substantially decreased the IC50 for inhibition by Gialpha1. These mutations suggest binding of Gialpha within the cleft formed by the alpha2 and alpha3 helices of C1, analogous to the Gsalpha binding site in C2. Adenylyl cyclase activity reconstituted by mixture of the C1 and C2 domains of type V adenylyl cyclase was also inhibited by Gialpha. The C1b domain of the type V enzyme contributed to affinity for Gialpha, but the source of C2 had little effect. Mutations in this soluble system faithfully reflected the phenotypes observed with the membrane-bound enzyme. The pseudosymmetrical structure of adenylyl cyclase permits bidirectional regulation of activity by homologous G protein alpha subunits.     

Kaposi's sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi's sarcoma and malignant lymphoma

A new human herpesvirus was recently identified in all forms of Kaposi's sarcoma (Kaposi's sarcoma-associated herpesvirus [KSHV] or human herpesvirus 8), as well as in primary effusion (body cavity-based) lymphomas (PELs). A 12.3-kb-long KSHV clone was obtained from a PEL genomic library. Sequencing of this clone revealed extensive homology and colinearity with the right end of the herpesvirus saimiri (HVS) genome and more limited homology to the left end of the Epstein-Barr virus genome. Four open reading frames (ORFs) were sequenced and characterized; these are homologous to the following viral and/or cellular genes: (i) Epstein-Barr virus membrane antigen p140 and HVS p160, (ii) HVS and cellular type D cyclins, (iii) HVS and cellular G protein-coupled receptors, and (iv) HVS. Since there is considerable evidence that cyclin D1 and some G protein-coupled receptors contribute to the development of specific cancers, the presence of KSHV homologs of these genes provides support for a role for KSHV in malignant transformation. All ORFs identified are transcribed in PELs and Kaposi's sarcoma tissues, further suggesting an active role for KSHV in these diseases.     

Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: a genetic model of meningioma progression

To investigate chromosomal events that underlie formation and progression of meningiomas, we have examined a set of 18 benign (WHO grade I), 15 atypical (grade II), and 13 anaplastic/malignant (grade III) meningiomas for loss of heterozygosity (LOH) on chromosomes 1p, 6p, 9q, 10q, and 14q. Frequent loss of loci on these chromosomes was seen in grade II and grade III tumors, specifically, 14q (II and III, 47 and 55%), 1p (40 and 70%), and 10q (27 and 40%). In contrast, LOH for these loci was infrequent in benign meningiomas, specifically, 14q (0%), 1p (11%), and 10q (12%). The smallest common regions of deletion that could be defined were 14q24-q32, 1p32-pter, and 10q24-qter. These observations indicate the likely presence of tumor suppressor genes in these regions that are involved in the development of WHO grade II and grade III meningiomas. Because LOH for loci on chromosomes 1p and 10q was found in tumors of all grades and because the frequency of LOH in all three regions increased with tumor grade, these results would support a model for the formation of aggressive meningiomas through tumor progression.