Assessment of quality of life and oral function of patients participating in a phase II study of radioprotection of oral and pharyngeal mucosa by the prostaglandin E(1) analog misoprostol (RTOG 96-07)

: The oral complications associated with radiotherapy to the head and neck are a significant dose-limiting factor. The goals of this study were to determine whether oropharyngeal rinsing and ingestion of misoprostol protect mucous membranes from the acute effects of irradiation, and to evaluate the quality-of-life (QOL) outcomes of patients receiving misoprostol. We report the results of the QOL outcomes of patients in this study.

: A total of 33 patients with resected or intact cancer of the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were registered to receive postoperative radiotherapy plus misoprostol or primary radiotherapy plus misoprostol. All patients were scheduled to receive 60–70 Gy at 2 Gy/d within 6–7 weeks. QOL and function were evaluated.

: A decrease in the QOL and function occurred in all areas covered by the questionnaire at the 6-week interval. This decrease was significant for eating, saliva, taste, and mucous. Of these significant factors, taste, saliva, and mucous consistency had not resolved by 12 weeks.

: Increased understanding of the impact of treatment on QOL and symptoms will formulate the rational design of toxicity interventions and enhance the multidisciplinary care of head-and-neck patients.     

Characterisation of an acapsular mutant of Burkholderia pseudomallei identified by signature tagged mutagenesis

A Burkholderia pseudomallei mutant which was attenuated in a mouse model of melioidosis was identified by a signature tagged mutagenesis approach. The transposon was shown to be inserted into a gene within the capsular biosynthetic operon. Compared with the wild-type bacteria this mutant demonstrated a 10(5)-fold increase in the median lethal dose in a mouse model and it did not react with a monoclonal antibody against high mol. wt polysaccharide of B. pseudomallei. To determine the kinetics of infection, mice were dosed intraperitoneally (i.p.) and intravenously (i.v.) with mutant and wild-type bacteria. After i.p challenge, the number of mutant bacteria in the peritoneal cavity declined, whereas wild-type bacteria proliferated. When administered by the i.v. route, the mutant was able to cause disease but the time to death was increased compared with the wild type. Mice were dosed with the mutant and subsequently challenged with wild-type B. pseudomallei, but the mutant failed to induce a protective immune response.     

Experience-dependent visual cue integration based on consistencies between visual and haptic percepts

We study the hypothesis that observers can use haptic percepts as a standard against which the relative reliabilities of visual cues can be judged, and that these reliabilities determine how observers combine depth information provided by these cues. Using a novel visuo-haptic virtual reality environment, subjects viewed and grasped virtual objects. In Experiment 1, subjects were trained under motion relevant conditions, during which haptic and visual motion cues were consistent whereas haptic and visual texture cues were uncorrelated, and texture relevant conditions, during which haptic and texture cues were consistent whereas haptic and motion cues were uncorrelated. Subjects relied more on the motion cue after motion relevant training than after texture relevant training, and more on the texture cue after texture relevant training than after motion relevant training. Experiment 2 studied whether or not subjects could adapt their visual cue combination strategies in a context-dependent manner based on context-dependent consistencies between haptic and visual cues. Subjects successfully learned two cue combination strategies in parallel, and correctly applied each strategy in its appropriate context. Experiment 3, which was similar to Experiment 1 except that it used a more naturalistic experimental task, yielded the same pattern of results as Experiment 1 indicating that the findings do not depend on the precise nature of the experimental task. Overall, the results suggest that observers can involuntarily compare visual and haptic percepts in order to evaluate the relative reliabilities of visual cues, and that these reliabilities determine how cues are combined during three-dimensional visual perception.     

Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems

This study has examined the persistence, distribution and pathological changes following intramuscular administration of Semliki Forest virus (SFV) vaccine vectors in mice and chickens. Administration of recombinant SFV RNA particles showed persistence at the injection site of mice up to 7 days, transient detection in secondary lymphoid organs and no dissemination to distal sites. In contrast, administration of a layered SFV DNA/RNA vector and a conventional standard naked DNA vector resulted in long-term persistence at the injection site, plasmid DNA being detected at 8 months post-inoculation in mice. Plasmid DNA was found distributed throughout the body, and tissues distal from the site of injection were positive up to 3 months. A similar pattern was observed in chickens. Mild pathological changes were observed at the injection site only, and plasmid DNA or recombinant RNA was not detected in mouse foetuses. These findings indicate that SFV-based vectors have the potential to be developed as safe vaccines.     

Case report. Successful treatment of cutaneous Paecilomyces lilacinus infection with oral itraconazole in an immune competent host

A 59-year-old woman presented to us with an eight-month history of Paecilomyces lilacinus soft tissue infection. She was treated with a six-month course of oral itraconazole. The lesion resolved fully without the need for adjunctive surgery. Susceptibility testing confirmed susceptibility to itraconazole. This is the second case of confirmed P. lilacinus soft tissue infection in an immunocompetent host treated with oral itraconazole alone.     

Kidney cancer: The cytokine working group experience (1986–2001)

The Cytokine Working Group (CWG) was initially established in 1986 as the Extramural IL-2/LAK Working Group. With funding from the National Cancer Institute (NCI), the CWG was mandated to confirming data regarding the efficacy of the high-dose interleukin-2 (IL2)/lymphokine-activated killer cell (LAK cell) regimen piloted at the NCI in the treatment of renal cell cancer. Since those initial studies, the CWG has conducted a series of clinical trials, often with correlative immunologic investigations, to evaluate combination immunotherapy in attempts to enhance the efficacy of IL-2 or to reduce toxicity. Subsequently, the CWG conducted trials to demonstrate the activity of lower-dose outpatient combination cytokine regimens to help determine their role in the armamentarium of treatment for metastatic renal cell cancer. This has culminated in a phase III randomized trial comparing the activity of high-dose IL-2 with the activity of outpatient IL-2 plus interferon-alpha. The CWG also has honed the management of both high-dose IL-2 and outpatient IL-2 regimens to make these safer in the hands of experienced clinicians. In addition, the CWG has produced a series of carefully conducted clinical trials of new cytokines, again attempting to define their clinical efficacy as anticancer agents. These include studies of IL-4, IL-6, and IL-12. Currently, the CWG is conducting studies with new approaches to IL-2 therapy, as well as planning trials with new agents for treatment of renal cell cancer. This review describes these efforts conducted over the past 15 yr.