Osseous free tissue transfer in head and neck reconstruction

Large palatomaxillary and oromandibular defects have a dramatic impact on speech, deglutition, mastication, and cosmesis. Traditional methods of reconstruction, such as locoregional flaps, free bone grafts, alloplastic materials, and prosthetic devices, have difficulty providing meaningful aesthetic and functional reconstruction of these defects. This article discusses current concepts in the reconstruction of large composite palatomaxillary and oromandibular defects with an emphasis on the role of free tissue transfer, including the factors to be evaluated when choosing a method of reconstruction, indications for specific donor sites, and recent technical refinements.     

Balancing the equation: The significance of professional and lay perceptions in the promotion of cervical screening amongst minority ethnic women

Studies of minority ethnic women and cancer screening have, in the past, suffered from many theoretical and methodological weaknesses. In addition, no attempts have been made to study the complexity of the issue involved in the intercultural context, or the possible contribution of women's experiences to low uptake rates. In order to further our understanding of the issues, an alternative approach, participatory action research (PAR), was adopted to identify factors that might have contributed to the persistently low participation of minority ethnic women in the cervical screening programme, and address them collaboratively. This paper presents the key findings of the ‘problem identification' phase of the project. Using mainly the focus-group method, it explores both smear takers' and minority ethnic women's perceptions and experiences of cervical screening. Data suggest that there was a divergence in perceptions held by these groups regarding cervical screening, which contributed to negative experiences for both groups. There is also clear evidence of dysfunctional clinical communication arising from these differing perceptions. Opportunistic screening at post-natal examination adopted by many general practices appeared to have perpetuated the perceptions that the majority of minority ethnic women held about the purpose of the smear test. Compounded by language differences, the majority of women who had undergone smear testing understood neither the purpose of screening programme nor the procedure of the test. This has clear implications for promoting regular uptake, and more importantly for informed consent and choice.     

Chiari osteotomy and shelf augmentation in the treatment of hip dysplasia

The clinical and radiographic results of Chiari osteotomy and shelf augmentation for acetabular dysplasia in 30 hips were reported. The average age at operation was 17 years for Chiari osteotomy and 13.8 years for shelf augmentation. The mean follow-up was 7.1 years for Chiari osteotomy and 4.1 years for shelf augmentation. Of the 14 Chiari osteotomies, 12 had good results by Tonnis clinical grading and 2 had poor results. There were significant improvements in the radiographic parameters measured (p < 0.01). They included center-edge angle of Wiberg, the acetabular angle of Sharp, the percentage of femoral head coverage, and the "c/b" ratio. For the 16 shelf augmentations, there were 8 good, 2 fair, and 6 poor results. The radiographic parameters measured were also all significantly improved (p < 0.01). The final Severin grading of the hips were improved by both Chiari osteotomy and shelf augmentation.     

Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: a potential target to increase anticancer activity.

PURPOSE: The antitumor efficacy of a herpes simplex virus (HSV)-1 oncolytic virus depends on the cytotoxic effect of the virus, but also on viral replication and spread within the tumor. Apoptosis is considered a defense mechanism of infected cells that minimizes the spread of viral progeny by limiting cellular production of virus. We sought to determine whether oncolytic HSV-1 infection induces apoptosis in neighboring, uninfected cells and whether manipulation of apoptosis can increase viral replication and cytotoxicity. EXPERIMENTAL DESIGN: NV1066 is an oncolytic HSV-1 mutant that contains the marker gene for enhanced green fluorescent protein. OCUM human gastric cancer cells were infected with NV1066 in vitro and inspected for apoptosis by Hoechst and terminal deoxynucleotidyltransferase-mediated nick end labeling staining and for infection by expression of green fluorescence. RESULTS: A significant increase in apoptosis was seen in cells infected by NV1066. More interestingly, a significant percentage (10%) of uninfected cells also proceeded to apoptosis. After NV1066 infection, cells were also treated with N-acetylcysteine (NAC), an inhibitor of apoptosis. By day 4 after infection, 2.7x more NV1066 was produced in cells exposed to NAC than in those not exposed to NV1066 (P = 0.04). NAC also increased tumor kill when administered with virus. CONCLUSIONS: These data suggest that NV1066 induces apoptosis in uninfected cocultured cells, potentially hindering propagation of viral progeny and concomitant tumor kill. Inhibition of apoptosis may improve the efficacy of oncolytic HSV-1 therapy.     

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.     

Regional muramyl tripeptide phosphatidylethanolamine administration enhances hepatic immune function and tumor surveillance

BACKGROUND: Immune status of the liver may affect growth of liver metastases. We analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and protect against tumor growth, with or without an immunosuppressive partial hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was assessed. METHODS: Buffalo rats (n = 7 to 12/group) were treated with saline, 40 microg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5 x 10(5) hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact on KC stimulation in animals undergoing PH, a known stimulant of tumor cell growth, groups were treated with saline or MTP-PE and challenged with tumor and underwent 30% PH. KCs were harvested and analyzed for superoxide production. Statistical analysis was performed with Mann-Whitney U test or chi-square test. RESULTS: MTP-PE-treated animals had fewer tumor nodules than control animals (19 vs 184, P <.005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs 36, P <.05). MTP-PE treatment before PH resulted in fewer tumor nodules compared with control animals (192 vs 276, P <. 05). MTP-PE administration increased macrophage superoxide production (20.6 +/- 2 vs 11.9 +/- 1.1 nmol/10(6) cells, P <.005). CONCLUSIONS: MTP-PE improved KC function and decreased growth of microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive hepatectomy. Portal administration was the most effective. MTP-PE administration may be useful as a neoadjuvant therapy for patients undergoing resection of liver malignancies.     

Effect of adult microsurgical varicocelectomy on testicular volume

OBJECTIVES: To re-examine the potential influence of varicocelectomy on testicular volume using scrotal ultrasonography, because it has been reported that total testicular volume (assessed by physical examination) increases after adult varicocele ligation. METHODS: A retrospective review of the testicular volume and semen parameters of 61 men who underwent microsurgical varicocelectomy between 1996 and 1998 was performed. Ultrasound-derived testicular volumes and total motile sperm counts were compared before varicocelectomy and at a mean of 7.2 months postoperatively. RESULTS: Bilateral varicocelectomy was performed in 22 men; 39 men underwent a left-sided procedure only. Overall, no significant change was found in the mean total testicular volume after varicocelectomy compared with preoperatively (24.0 versus 23.9 mL, respectively; P = 0.74). Similarly, the testicular volumes did not change significantly after left or bilateral varicocelectomy (P >0.05). Overall, the mean total motile sperm count increased significantly after varicocelectomy (17. 9 to 25.4, P = 0.05). CONCLUSIONS: This was the first study to examine the effect of adult varicocelectomy on testicular volume using ultrasound-derived measurements of volume. Unlike previous findings, our data suggest that although adult varicocelectomy improves semen quality in most infertile men, it does not result in a significant increase in testicular volume.     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.