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Biomedical subjects

T Fong

Publications and source records attributed to T Fong.

15 recordsLinked to original sources

A non-contact mouse for surgeon-computer interaction.

We have developed a system that uses computer vision to replace standard computer mouse functions with hand gestures. The system is designed to enable non-contact human-computer interaction (HCI), so that surgeons will be able to make more effective use of computers during surgery. In this paper, we begin by discussing the need for non-contact computer interfaces in the operating room. We then describe the design of our non-contact mouse system, focusing on the techniques used for hand detection, tracking, and gesture recognition. Finally, we present preliminary results from testing and planned future work.

Computer Peripherals↗

Comparison of serum interleukin-10 (IL-10) levels between normal volunteers and patients with advanced melanoma.

Melanoma is an immunoresponsive malignancy. Interleukin-10 (IL-10) is a potent regulator of immunosuppression. The purpose of this research was to define the relationship of serum IL-10 to survival in patients with metastatic melanoma. Forty-one melanoma patients and 50 normal volunteers were analyzed. The median IL-10 level as determined by enzyme-linked immunosorbent assay (ELISA) in melanoma patients was 8.75 pg/ml compared to < 3.0 pg/ml in normal volunteers (p = 0.0001). Survival of melanoma patients with an IL-10 level above 10.0 pg/ml was 365 days compared to 557 days in patients with IL-10 levels less than 10.0 pg/ml (p = 0.0259, Wilcoxon). Elevated IL-10 levels were correlated with poor survival.

Adult↗

Phase I trial of interferon gamma retroviral vector administered intratumorally with multiple courses in patients with metastatic melanoma.

The purpose of this study was to determine the safety and antitumor activity of IFN-gamma retroviral vector in patients with advanced melanoma. Seventeen patients (9 single courses, 8 multiple courses) received a total of 363 intratumor injections of IFN-gamma retroviral vector (1 x 10(7) PFU/ml administered at 0.3, 0.5, and 1.0 ml per cohort). No grade III/IV adverse events were attributed to study medication. Replication-competent retrovirus was not detected in any of the 17 patients by polymerase chain reaction studies. Eight patients showed elevated anti-tumor antibody responses in comparison with baseline by ELISA. One of nine patients treated with a single course had an optimal response of stable disease, compared with eight of eight multiple-injected patients. Median survival of single-injected patients was 150 days, and patients who received multiple injections have still not achieved median survival duration, with four of eight still living (p = 0.0462, Wilcoxon; p = 0.0273, log rank). We conclude that intratumor injection of IFN-gamma is safe and well tolerated. Evidence of antitumor activity is suggested in patients with advanced malignancy that received multiple injections.

Adult↗

MCA106 fibrosarcoma cells transduced with granulocyte/macrophage colony-stimulating factor are not superior to the wild-type cells in suppressing the growth of hepatic metastases.

BACKGROUND AND OBJECTIVES: Vaccination with cytokine gene-modified tumor cells augments the immune response against established tumors and protects against tumor challenges. In this study, we investigated the vaccine potential of GM-CSF-transduced MCA106 fibrosarcoma (MCA-GMCSF) cells in the C57BL/6 (B6) murine hepatic metastasis model. METHODS: Experimental mice received one to three weekly vaccines (subcutaneous/intramuscular, s.c./i.m.) of irradiated, parental, or GM-CSF-transduced MCA106 tumor cells. One week after the last immunization, hepatic metastases were established through the intrasplenic injection of live MCA106 parental (MCA106P) tumor cells. The animals were then sacrificed 3-4 weeks after surgery for evaluation of hepatic tumor burden. RESULTS: Based on in vivo experiments, both GM-CSF-modified and parental MCA106 tumor cell vaccines induced strong protection against hepatic tumor growth with grossly visible tumors rarely identified. This protection was evident even at a single vaccine dose of as low as 1x10(5) irradiated cells. Unimmunized control mice, on the other hand, consistently developed substantial hepatic tumors. Cytotoxicity assays on splenocytes (cultured in vitro for 4-5 days) showed that both groups of vaccinated mice developed strong tumor-specific cytotoxic T-lymphocyte (CTL) responses. Immunohistochemical analysis of injection sites showed infiltration of dendritic cells (DCs) and macrophages into subcutaneously injected MCA-GMCSF cells. Mostly macrophages, however, were seen at the injection site of MCA106P cells. Furthermore, the MCA106P cells expressed high levels of MHC class I antigens and the level of expression was not significantly altered by transduction with the GM-CSF gene. The high expression of MHC class I antigens probably contributed to the strong immunogenicity of the MCA106P cell vaccine. CONCLUSIONS: This study demonstrates that MCA106 parental cells are as effective as the GM-CSF-transduced cells in suppressing the growth of hepatic metastases. The cellular immune responses induced by these two vaccines, however, are probably mediated by different subsets of host effector cells. These results have important implications for the use of GM-CSF-transduced cell vaccines in the immunotherapy of tumors that have the propensity to metastasize through the lymphatic channels and the circulatory system.

Animals↗

Inhibition of angiogenesis by interleukin 4.

Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose-response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (TH0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.

Adenocarcinoma↗

High dose intravitreal ganciclovir for CMV retinitis: a shelf life and cost comparison study.

BACKGROUND: It was previously found that high dose intravitreal ganciclovir provided superior treatment of cytomegalovirus retinitis compared with intravenous treatment. This study examined the stability and solubility of the ganciclovir solution to determine the shelf life of prepared solution, and compared the cost of intravitreal with intravenous therapy. METHODS: For the solubility studies high performance liquid chromatography was used to determine the ganciclovir concentration in various solutions. Measurements were taken of freshly made 20 mg/ml solution, the same solution stored at room temperature or frozen for 10, 17, and 24 days, after the solution was filtered, and after it was heated at 56 degrees C. For the cost comparison analysis the cost of 22 patients treated exclusively with intravitreal high dose ganciclovir was compared with cost estimates for the same patients treated with a standard intravenous therapy regimen over the same time. RESULTS: There was little variation in the concentration of ganciclovir regardless of the storage conditions, suggesting that the 20 mg/ml solution was very stable. The heating and filtering experiments suggest that maximum solubility was achieved both in the freshly prepared and thawed frozen stored solution. The total cost of the intravitreal treatment was Aus $172,435 and the estimate of intravenous treatment was Aus $490,521. This represents a total saving of $318,086 (65%), or $14,458 per patient. The average number of weeks of treatment for each patient was 27.9 (613 weeks/22 patients), so the saving per patient per year was $29,946. CONCLUSION: High dose intravitreal ganciclovir therapy may be administered in a very cost effective way, which along with its acceptability, safety, and clinical efficacy make it an attractive method of treatment of CMV retinitis.

Cytomegalovirus Retinitis↗

Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases.

The tachykinin neuropeptides substance P and neurokinin (NK) A have been postulated to participate in the inflammatory reaction in airways of smokers and asthmatics. We have examined the hypothesis that the expression of one or more of the three cloned tachykinin receptors (NK1, NK2, and NK3) is increased in inflammatory airway disorders, which could result in augmentation of the effect of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3-receptor mRNA were detected by ribonuclease protection assay in RNA from both cartilaginous and membranous bronchi and subpleural lung. In lung samples containing membranous airways, NK2-receptor mRNA expression was increased fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression was increased twofold in smokers without airflow obstruction compared with nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in patients with chronic obstructive pulmonary disease compared with smoking controls. In situ hybridization indicated NK1-receptor mRNA was expressed in submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3-receptor mRNA were not detected. These observations have implications for the pathophysiology and treatment of both asthma and tobacco smoke-induced airway inflammation.

Adult↗

Failure of intravenous infusions in neonates.

The median life expectancy (survival) of 286 peripheral intravenous infusion sites in 105 babies in a children's intensive care unit was 36 h. Unadjusted univariate survival analysis revealed that dextrose infusions and the initial infusions received by a baby had longer survival than total parenteral nutrition (TPN) infusions and later infusions respectively. Also infusions with cloxacillin and penicillin survived for longer than average while infusions with phenytoin had reduced survival. Gestational age, weight, infusion site, other drugs, co-infusion of Intralipid with TPN solutions and neutralization of TPN did not influence survival of infusions. Multivariate survival analysis confirmed the findings for TPN and penicillin but not for cloxacillin, phenytoin or later infusions. Multivariate analysis also suggested that survival was improved with ampicillin and aminophylline and worse for leg sites, for older babies and for infusions in which the fluids were given at greater rates. It also indicated that neutralization of TPN improved survival.

Anti-Bacterial Agents↗

Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma.

BACKGROUND: Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral injection of IFN-gamma retroviral vector in advanced melanoma patients. METHODS: This was a phase I study, in which 13 patients received a single daily injection of a retroviral vector with the IFN-gamma gene for 5 consecutive days (1.5 x 10(8) colony-forming units total dose); patients subsequently underwent resection of the injected lesion to confirm DNA transduction in situ. RESULTS: No toxicity related to the injected vector was observed. Replication competent retrovirus was not observed in any prepared samples (n = 65). IFN-gamma expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-linked immunospot assay in six samples. CONCLUSIONS: An injection of IFN-gamma gene/retroviral vector is well tolerated. DNA transduction was demonstrated in human subjects, confirming the feasibility of the direct injection approach for the gene therapy of solid tumors. Further trials to determine optimal schedule and potential efficacy are indicated.

Adult↗

Eradication of melanoma pulmonary metastases by immunotherapy with tumor cells engineered to secrete interleukin-2 or gamma interferon.

This study was undertaken to investigate the effectiveness of interleukin-2 (IL-2) and gamma interferon (gammaIFN)-modified B16 melanoma cells in the immunotherapy of established melanoma pulmonary metastases. The genes for IL-2 and gammaIFN were introduced retrovirally into B16 melanoma cells. Transduction with the gammaIFN, but not the IL-2, gene caused significant increases in the expression of major histocompatibility complex (MHC) antigens on B16-gammaIFN cells. The in vivo tumor-forming capacity of both IL-2- and gammaIFN-transduced B16 cells was drastically reduced when the cells were inoculated subcutaneously (SC) in syngeneic C57BL/6 mice. After intravenous (IV) inoculation, most of the B16-gammaIFN cells were rejected, but B16-IL-2 cells were relatively tumorigenic and formed pulmonary metastases. C57BL/6 mice bearing 4-day established parental B16 lung metastases were treated with B16 parental (B16P) unmodified cells, IL-2- or gammaIFN-modified B16 cells, or a combination of both transduced cells. Treatment consisted of a weekly intraperitoneal (IP) injection of one million irradiated (10,000 rad) tumor cells alone or in combination with exogenous IL-2 for a total of three to four injections. Immunotherapy with B16 parental or B16-IL-2 secreting cells caused a moderate reduction in the number of lung metastases. However, mice treated with gammaIFN-secreting B16 cells showed a significant reduction or complete elimination of lung metastases. There was no additive effect for combining both IL-2- and gammaIFN-modified tumor cells in the immunotherapy. Exogenous IL-2 (50,000-100,000 U/day for 3 days) caused a significant enhancement of the immunotherapeutic benefit of the vaccines. Moreover, mice treated with gammaIFN-modified B16 cells survived longer than the other groups. Twenty-five percent of these mice were tumor free and remained alive for an observation period of 4 months. The in vitro cytolytic activity of splenocytes in chromium release assays did not correlate in every case with the in vivo antitumor effect of the treatment. Our findings have implications for the use of cytokine-modified cells for immunotherapy and for evaluating the therapeutic benefit of this novel treatment.

Animals↗

Phase I trial of retroviral vector-mediated interferon (IFN)-gamma gene transfer into autologous tumor cells in patients with metastatic melanoma.

The purpose of this study was to determine the safety of treating melanoma patients with retroviral vector-mediated interferon (IFN)-gamma gene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing the IFN-gamma gene were injected subcutaneously every 2 weeks with escalating cell doses for six injections. Tumor tissue was harvested from 58 patients with metastatic melanoma. Twelve patients had sufficient expansion of autologous tumor (0.56-160 x 10(7) cells) and adequate IFN-gamma expression after gene transduction (2-79,000 U/10(6) cells/24 hours) for injections. Five patients received injections. No toxicity was attributed to the IFN-gamma retroviral vector in the patients injected. One of the injected patients remains disease-free after 13 injections, following the surgical removal of brain, adrenal, and lung metastases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop primary autologous melanoma cell lines was limited, and only a minority of patients were injected.

Adolescent↗