Development of an avian model for restenosis.

Recurrence of atherosclerotic plaque growth after interventional therapy, restenosis, is a significant clinical problem occurring in 20%-50% of cases. We have developed a new avian model for the investigation of restenosis after arterial injury in cholesterol fed White Leghorn roosters. Atherosclerotic plaque growth 1-30 weeks after angioplasty balloon mediated endothelial injury in the abdominal aorta was studied in 37 roosters. Roosters were maintained on either normal poultry diet or high cholesterol diet. Twelve cholesterol fed roosters were also fed a hormone supplemented diet in order to modify plaque morphology. The procedural success rate was high. Angiographic stenoses (mean 36% with maximum of 74%) were detectable in cholesterol fed roosters after balloon angioplasty with associated histological evidence of plaque growth (P < 0.017). Cholesterol feeding enhanced fatty plaque growth; hormone manipulation increased calcific and ulcerated plaque but with high associated morbidity. Three interventional devices were subsequently examined in 32 roosters (16 laser angioplasty, 7 atherectomy, and 9 stent implant). Plaque development was again assessed by contrast angiography and histological analysis. We conclude that balloon mediated arterial injury in cholesterol fed roosters produces early proliferative and late, complex atherosclerotic lesions providing an inexpensive model for plaque development after intimal injury.

A qualitative examination of borderline personality disordered (BPD) patients: interpersonal dynamics and underlying paradoxes.

Theoretical conceptualizations of symptomatology in patients with borderline personality disorder (BPD) have noted an inability to integrate contradictory perceptions (splitting, or dichotomous thinking) as a hallmark of the disorder. This study investigated contradictions manifest in the thinking and behavior of BPD patients, using the concept of paradox. A paradox occurs when an apparent contradiction contains an underlying logic which makes the contradiction comprehensible. Using qualitative methods of analysis, this study explored paradoxes evident in 10 BPD patient narratives about relationship events. Specific paradoxes relating to interpersonal conflicts and self-destructiveness are presented, along with the underlying logic of each paradox as described by patients. Implications for treatment are discussed.

Secretion of rubella virions and virus-like particles in cultured epithelial cells.

Rubella virus (RV) is an enveloped RNA virus that causes systemic infections in humans. More importantly, first trimester in utero infection leads to a collection of devastating birth defects known as congenital rubella syndrome. Epithelial cells are the first line of defense against viruses and consequently, the polarity of virus secretion is an important factor affecting viral spread. As a first step toward understanding how RV interacts with epithelial cells, we have examined the release of RV-like particles and virions from polarized cells in culture. RV structural proteins were targeted to the Golgi complex and virus particle formation occurred on intracellular membranes in three different polarized epithelial cells. Polarized cells could be infected from the apical and basal membranes, indicating that receptors are not confined to one surface. The secretion of virus-like particles and infectious virions varied according to cell type. In two of the three polarized cell lines examined, virus was released primarily from the apical surface, but significant quantities were also secreted from the basolateral membrane. Release of virus from the apical surface may facilitate virus spread from person to person, whereas basolateral secretion could be important for establishing a systemic infection and/or crossing the placenta prior to fetal infection.

Oculoplastic uses of cranial bone grafts.

Cranial bone grafting for craniofacial reconstruction has gained wide acceptance in recent years and is being used with increasing frequency by ophthalmic plastic surgeons. Alloplastic materials (particularly newer materials such as porous polyethylene, hydroxyapatite, and rigidly fixated metal alloys) have a clear role in orbital reconstruction, and in many oculoplastic applications are the material of choice. However, in certain applications cranial bone grafts may be superior, eg, in managing large posttraumatic or postsurgical orbital defects or orbito-sinus defects in the milieu of chronic sinusitis. We describe our current techniques for harvesting full-thickness outer-table grafts and split-thickness periosteally-bound "fish-scale" grafts. Harvesting cranial bone grafts is not without risk and donor site morbidity, and we do not advocate the use of cranial bone grafts in those cases that might be managed as well (or better) with alloplastic material. At the same time, ophthalmic surgeons involved in orbital reconstruction should be familiar with the indications for bone grafts and comfortable with harvesting techniques so that they are not limited when circumstances warrant the use of autogenous material.

Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in European rabbits.

Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that induces a rapidly lethal infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of proteins to circumvent or inhibit a variety of host antiviral immune mechanisms. M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was originally identified as an interferon-gamma receptor homolog (Upton, Mossman, and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is dispensable for virus replication in cultured cells but is a critical virulence factor for virus pathogenesis in European rabbits. Disruption of both copies of the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7 coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac-T7gpt expressed no detectable M-T7 protein and infected cells supernatants were devoid of any detectable interferon-gamma binding activities. Immunohistochemical staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic reduction in disease symptoms and viral dissemination to secondary sites, but also dramatically influenced host leukocyte behavior. Notably, primary lesions in wild-type virus infections were generally underlayed by large masses of inflammatory cells that did not effectively migrate into the dermal sites of viral replication, whereas in vMyxlac-T7gpt infections this apparent block to leukocyte influx was relieved. A second major phenotypic distinction noted for the M-T7 knockout virus was the extensive activation of lymphocytes in secondary immune organs, particularly the spleen and lymph nodes, by Day 4 of the infection. This is in stark contrast to infection by wild-type myxoma virus, which results in relatively little, if any, cellular activation of germinal centers of spleen and lymph node by Day 4. We conclude that M-T7 functions early in infection to (1) retard inflammatory cell migration into infected tissues and (2) disrupt the communication between sentinel immune cells at the site of primary virus infection in the subdermis and lymphocytes in the secondary lymphoid organs, thereby disabling the host from mounting an effective cellular immune response. To summarize, in addition to neutralizing host interferon-gamma at infected sites, we propose that M-T7 protein also modifies leukocyte traffic in the vicinity of virus lesions, thus effectively severing the link between antigen presenting cells of the infected tissue and the effector lymphocytes of the peripheral immune organs.

Role of rubella virus glycoprotein domains in assembly of virus-like particles.

Rubella virus is a small enveloped positive-strand RNA virus that assembles on intracellular membranes in a variety of cell types. The virus structural proteins contain all of the information necessary to mediate the assembly of virus-like particles in the Golgi complex. We have recently identified intracellular retention signals within the two viral envelope glycoproteins. E2 contains a Golgi retention signal in its transmembrane domain, whereas a signal for retention in the endoplasmic reticulum has been localized to the transmembrane and cytoplasmic domains of E1 (T. C. Hobman, L. Woodward, and M. G. Farquhar, Mol. Biol. Cell 6:7-20, 1995; T. C. Hobman, H. F. Lemon, and K. Jewell, J. Virol. 71:7670-7680, 1997). In the present study, we have analyzed the role of these retention signals in the assembly of rubella virus-like particles. Deletion or replacement of these domains with analogous regions from other type I membrane glycoproteins resulted in failure of rubella virus-like particles to be secreted from transfected cells. The E1 transmembrane and cytoplasmic domains were not required for targeting of the structural proteins to the Golgi complex and, surprisingly, assembly and budding of virus particles into the lumen of this organelle; however, the resultant particles were not secreted. In contrast, replacement or alteration of the E2 transmembrane or cytoplasmic domain, respectively, abrogated the targeting of the structural proteins to the budding site, and consequently, no virion formation was observed. These results indicate that the transmembrane and cytoplasmic domains of E2 and E1 are required for early and late steps respectively in the viral assembly pathway and that rubella virus morphogenesis is very different from that of the structurally similar alphaviruses.

Orbital decompression for non-Graves' orbitopathy: a consideration of extended indications for decompression.

Orbital decompression is typically indicated for Graves' orbitopathy. Other causes of proptosis can also be safely and effectively addressed surgically with orbital decompression. Patients with prominent globes can have significant discomfort related to exposure keratopathy, lagophthalmos, and inefficient function of the globe-eyelid interface. We present six cases of non-Graves' proptosis that were addressed with orbital decompression. Indications for surgery included hypoplastic malar eminence with scleral show, enlarged globes, and congenital shallow orbits. Successful reduction of proptosis was achieved by orbital decompression with subsequent relief of presenting symptoms. Graded balanced orbital decompression was used to minimize shifts of the muscle cone. In some cases osteotomies and advancement of the lateral wall and malar region were also employed. Complications included transient esotropia, esotropia requiring surgery, and microplate granuloma. Orbital decompression should be considered for patients with relative proptosis and related eyelid malpositions regardless of the underlying etiology.

Surgical morbidity in the North Coast Health Region.

A comparison of morbidity following 20 selected surgical procedures was conducted in the North Coast Health Region of NSW in 1988. Morbidity rates between procedures, hospitals and hospital levels were compared and the effects of age, gender and the American Society of Anesthesiologists rating on morbidity were examined. The respective perceptions of doctors and patients regarding complications were also compared. The study gives conditional support to the continuation of a surgical programme in Level 3 hospitals in the North Coast Health Region.