Percutaneous tumor ablation: microencapsulated echo-guided interstitial chemotherapy combined with cryosurgery increases necrosis in prostate cancer.

This study aimed at confirming the increased growth inhibition (GI) of human prostate tumors produced by a intentionally palliative combination treatment of cryochemotherapy, i.e., partial cryoablation (CA) followed by intratumor partial chemotherapy with injection of microencapsulated 5-fluorouracil (MCC/5FU) at the ice ball (IB) periphery. We report the local effectiveness of cryochemotherapy compared to chemotherapy only with using multiple injections of MCC/5FU spaced out to maximize cumulative effect of sustained release of 5-fluorouracil (5FU) during a 21-day period. Prostate bioluminescent tumor cells - DU145 Luc+ - were implanted sub-cutaneously and bilaterally in each flank of nude mice. Tumors were treated with: (i) cryoablation alone (CA), causing necrosis in approximately 45% of the tumor volume; (ii) cryo-chemotherapy (CA+MCC/5FU), a combined regimen consisting of partial CA followed immediately and on day 14 by ultrasound assisted, intra-tumor injections (40 mul) of MCC/5FU( 0.81 ng/mm3 of tumor) containing Ethiodol (IPO) an imaging contrast agent, on two opposite sides of the unfrozen part of tumor; (iii) intratumor chemotherapy (MCC/5FU), consisting of three successive intra-tumor injections of microencapsulated 5FU on two opposite sides on Day 0, 4, and 11, and (iv) control series (MM), consisting of a single injection of echogenic microcapsules (mucaps) containing IPO but no 5FU. Tumor growth and viability were followed during a 21-day period with using biometric measurements, bioluminescent imaging (BLI) and ultrasonography (US), and then animals were sacrificed. CA, spared 54.4% of the tumor volume and the IB kill ratio was 0.4 +/-0.9. The maximum tumor volume reduction observed by Day 3 was short-lived as re-growth became significant by Day 6. CA+ MCC/5FU spared 55.6% of the tumor volume and the IB kill ratio was 0.54 +/- 0.12. The viable tumor cells, as measured by BLI remained at preoperative levels. After 11 days CA+ MCC/5FU limited the growth of the partially ablated tumors to only 10.6% of the growth of CA treated tumors (p=0.04). By Day 18 the CA+MCC/5FU had inhibited tumor growth by 78% compared to the CA treated tumors (p=0.05) and after 21 days the growth was inhibited by 71% (p=0.04) compared to more than 650% growth in the MM group and 600% growth in the CA treated group. The two injections of MCC/5FU produced a visible focal necrosis in 55% of the tumors. MCC/5FU proved effective by themselves and reduced the growth of prostate tumor volumes by 51% (p=0.025) compared to MM controls during the 21 days. Focal necrosis was macroscopically visible at the site of 66% of the tumors injected only with MCC/5FU. The BLI clearly showed zones of reduced tumor cell viability at the injection sites. The mean number of bioluminescent (viable) tumor cells, remained below preoperative levels for the first 6 days and then increased at a rate approximately 20% that of the growth of control tumor cells. The chemoablative effects of intentionally limited doses of MCC/5FU injected within the IB margin augment the effects of incomplete cryoablation in this prostate tumor model, with dramatic tumor GI and directionally increased necrosis dimensions compared to CA alone, confirming the results of a previous study. Our results indicate the potential advantages of our combination cryochemotherapy that utilizes different mechanisms to kill tumor cells and retard tumor growth in the region surrounding the IB where tumor cells escape the lethal effects of cryosurgery. The study suggests that cryochemotherapy may become a more predictable technique that could be indicated as an adjuvant or an alternative to palliative therapy of hormone refractory prostate cancer (HRPC).

Anterior ischaemic optic neuropathy after coronary artery bypass graft: the role of anaemia in diabetics.

PURPOSE: To ascertain factors associated with anterior ischaemic optic neuropathy (AION) following coronary artery bypass graft (CABG) in a Lebanese population. METHODS: A retrospective chart review of consecutive CABG performed over a 5-year period (1995-1999) in one medical centre. A comparison of clinical characteristics was carried out between AION cases and subjects free from AION. The variables analysed included history of diabetes as well as preoperative, intraoperative, or postoperative values of haematocrit, blood sugar, oxygen saturation, and arterial blood pressure. RESULTS: A total of 1,594 persons were included. Three subjects experienced acute visual loss from AION following CABG, all had diabetes mellitus, and two suffered from severe postoperative anaemia. Among diabetics (n=484), the risk of AION was significantly higher in subjects with postoperative haematocrit falling below 22 (28.6%) than the rest (0.21%) (P=0.001). Blood transfusion was given in two subjects with prompt visual recovery. CONCLUSIONS: Severe anaemia in patients undergoing CABG appears to be a risk factor for AION, especially in diabetics, and needs prompt correction to prevent or reverse the ischaemic ocular events.

Bilateral consecutive central corneal perforations associated with hypogammaglobulinemia.

OBJECTIVE: To describe the presentation and the clinical course of a patient with consecutive central sterile corneal perforations associated with common variable immunodeficiency. DESIGN: Case report. METHODS: Multiple corneal cultures and scrapings were performed in an effort to identify an infectious cause and all were negative. Corneal biopsy did not demonstrate any evidence of micro-organisms. An extended investigation failed to uncover a collagen vascular cause or atopy. RESULTS: Progressive sterile stromal thinning with intact epithelium in the left eye proceeded to perforation despite topical treatment, and cyanoacrylate gluing was performed. However, a secondary Haemophilus influenza endophthalmitis developed, and the eye was eventually lost. The fellow eye proceeded along the same clinical course with sterile stromal thinning. A lamellar patch graft was performed when the central ulceration progressed to a descemetocele. The eye remained quiet with 20/25 vision for 2 years, until the patient died from complications of a liver transplant. CONCLUSIONS: Devastating central sterile corneal thinning leading to perforation may occur in patients with hypogammaglobulinemia.

A general population survey on patterns of benzodiazepine use and dependence in Lebanon.

OBJECTIVE: In Lebanon, benzodiazepines are often available without medical prescription. We aimed to carry out the first community-based pharmaco-epidemiological study on benzodiazepine consumption in the Middle East Area. METHOD: The prevalence of past-month benzodiazepine use was assessed in a 1000-subject randomized sample from the Lebanese community, and risk factors were studied in a group of 496 current users. RESULTS: Benzodiazepine use during the past month was found in 9.6% of subjects. Four variables were significantly associated with use: age higher than 45 years, female sex, cigarette smoking and the existence of a recent life event. Benzodiazepine dependence was found in 50.2% of users. CONCLUSION: Benzodiazepine use in Lebanon is particularly high, and can be related to well-known factors such as female sex and age, but other potent specific variables, such as war stress or the lack of control on drug access, can be hypothesized.

Characterization and expression of a glycoprotein encoded by the Epstein-Barr virus BamHI I fragment.

Computer-assisted analysis of the Epstein-Barr virus (EBV) open reading frame BILF2 (B95-8 nucleotides 150,525 to 149,782) predicts that it codes for a membrane-bound glycoprotein. [3H]glucosamine labeling of cells infected with vaccinia virus recombinants that expressed the BILF2 open reading frame revealed several diffuse species of glycoproteins of around 80,000 and 55,000 daltons. A monoclonal antibody derived from spleens of mice immunized with EBV immunoprecipitated the EBV-derived protein made by the vaccinia virus recombinants and also precipitated a late envelope glycoprotein with a mobility of 78,000 to 55,000 from EBV-producing cells. N-Glycanase treatment of the immunoprecipitated BILF2 product from EBV-producing cells resulted in a polypeptide of 28 kilodaltons, closely agreeing with the predicted molecular mass for the unmodified BILF2 gene product. Western (immuno-) blots using recombinant infected cells as a source of antigen showed that the majority of EBV-seropositive individuals have a serum antibody response to the BILF2-encoded gp78/55.

Depletion of glycoprotein gp85 from virosomes made with Epstein-Barr virus proteins abolishes their ability to fuse with virus receptor-bearing cells.

Entry of an enveloped virus such as Epstein-Barr virus (EBV) into host cells involves fusion of the virion envelope with host cell membranes either at the surface of the cell or within endocytic vesicles. Previous work has indirectly implicated the EBV glycoprotein gp85 in this fusion process. A neutralizing monoclonal antibody to gp85, F-2-1, failed to inhibit binding of EBV to its receptor but interfered with virus fusion as measured with the self-quenching fluorophore octadecyl rhodamine B chloride (R18) (N. Miller and L. M. Hutt-Fletcher, J. Virol. 62:2366-2372, 1988). To test further the hypothesis that gp85 functions as a fusion protein, EBV virion proteins including or depleted of gp85 were incorporated into lipid vesicles to form virosomes. Virosomes were labeled with R18, and those that were made with undepleted protein were shown to behave in a manner similar to that of R18-labeled virus. They bound to receptor-positive but not to receptor-negative cells and fused with Raji cells but not with receptor-positive, fusion-incompetent Molt 4 cells; monoclonal antibodies that inhibited binding or fusion of virus inhibited binding and fusion of virosomes, and virus competed with virosomes for attachment to cells. In contrast, virosomes made from virus proteins depleted of gp85 by immunoaffinity chromatography remained capable of binding to receptor-positive cells but failed to fuse. These results are compatible with the hypothesis that gp85 is actively involved in the fusion of EBV with lymphoblatoid cell lines and suggest that the ability of antibody F-2-1 to neutralize infectivity of EBV represents a direct effect on the function of gp85 as a fusion protein.