Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21.

PURPOSE: To determine the clinical toxicities and antibody response against sTn and tumor cells expressing sTn following immunization of high-risk breast cancer patients with clustered sTn-KLH [sTn(c)-KLH] conjugate plus QS-21. EXPERIMENTAL DESIGN: Twenty-seven patients with no evidence of disease and with a history of either stage IV no evidence of disease, rising tumor markers, stage II (>or=4 positive axillary nodes), or stage III disease received a total of five injections each during weeks 1, 2, 3, 7, and 19. Immunizations consisted of sTn(c)-KLH conjugate containing 30, 10, 3, or 1 microg sTn(c) plus 100 microg QS-21. Induction of IgM and IgG antibodies against synthetic sTn(c) and natural sTn on ovine submaxillary mucin were measured before and after therapy. Fluorescence-activated cell sorting analyses assessed reactivity of antibodies to LSC and MCF-7 tumor cells. RESULTS: The most common toxicities were transient local skin reactions at the injection site and mild flu-like symptoms. All patients developed significant IgM and IgG antibody titers against sTn(c). Antibody titers against ovine submaxillary mucin were usually of lower titers. IgM reactivity with LSC tumor cells was observed in 21 patients and with MCF-7 cells in 13 patients. There was minimal IgG reactivity with LSC cells. CONCLUSION: Immunization with sTn(c)-KLH conjugate plus QS-21 is well tolerated and immunogenic in high-risk breast cancer patients. Future trials will incorporate sTn(c) as a component of a multiple antigen vaccine.     

Utilization of an abbreviated diabetes impact management scale to assess change in subjective disability during a trial of pulsatile insulin delivery demonstrates benefit

A prospective interventional study of pulsatile intravenous insulin infusion therapy has demonstrated reduction of left ventricular mass and blunting of progression of diabetic nephropathy. We anticipated that improvements in objective parameters would be associated with similar improvement measurable by the self-administered Diabetes Impact Management Scale (DIMS). The DIMS was administered at baseline and 12 months for 19 participants randomized to receive either standard insulin treatment of 3 to 4 injections of insulin daily or insulin treatment plus an additional day per week of 3 intravenous pulses over an 8-hour period. For standard vs pulsed intravenous insulin therapy, mean baseline scores were similar for the 12 total questions as well as the groups of 7 questions with emotional content and 5 with physical (neurologic) content. Mean study group scores at 1 year and changes over 1 year were not significantly different for the 7 questions with emotional content (P = .3143, .7574). Score results for the 5 questions related to neurologic status at 1 year and changes over 1 year were significantly different between patients with standard and with pulsed insulin therapy (P = .0144, 0.0004). Pulsatile intravenous insulin, when added to standard multiple-dose insulin therapy, was demonstrated to improve subjective perception of neurologic disability on repeated use of an abbreviated form of the DIMS.     

Population Responses of Peromyscus Resident in Iowa Cornfields Treated with the Organophosphorus Pesticide COUNTER®

We examined the effects of a field application of 1.41 kg/ha active ingredient COUNTER® insecticide on resident small mammal populations in a corn agroecosystem in Iowa. The majority of individuals captured were Peromyscus maniculatus and Peromyscus leucopus; preliminary results showed no differential effects by species and further analyses were done at the generic level. The study design was a treatment-reference and before-after application comparison. Demographic parameters examined were: minimum number known alive, total number of captures as an index of activity, captures by habitat type, number of first captures (recruitment) and last captures (mortality plus emigration), sex ratio, age class structure, and several measures of reproductive activity. Brain ChE levels were also examined for treatment and reference animals. COUNTER® residues were detected only in treatment site mice. There were no significant differences in most demographic parameters. There was a significant interaction between reproductive activity and time (three factor loglinear analysis); however the effect was consistent on the treatment and reference sites. There was a significant increase in activity measured as number of captures on the reference site relative to the treatment site post-application as well as a lower than expected number of captures in the cornfield habitat on the treatment site post-application; this did not appear to be related to mortality on the treatment site. The only possible treatment effect appeared to be some depression of activity, especially in the corn field; this is consistent with other published research on the effect of organophosphorus pesticides on small mammals in agroecosystems.     

The role of laparoscopic-assisted myomectomy (LAM).

Laparoscopic myomectomy has recently gained wide acceptance. However, this procedure remains technically highly demanding and concerns have been raised regarding the prolonged time of anesthesia, increased blood loss, and possibly a higher risk of postoperative adhesion formation. Laparoscopic-assisted myomectomy (LAM) is advocated as a technique that may lessen these concerns regarding laparoscopic myomectomy while retaining the benefits of laparoscopic surgery, namely, short hospital stay, lower costs, and rapid recovery. By decreasing the technical demands, and thereby the operative time, LAM may be more widely offered to patients. In carefully selected cases, LAM is a safe and efficient alternative to both laparoscopic myomectomy and myomectomy by laparotomy. These cases include patients with numerous large or deep intramural myomas. LAM allows easier repair of the uterus and rapid morcellation of the myomas. In women who desire a future pregnancy, LAM may be a better approach because it allows meticulous suturing of the uterine defect in layers and thereby eliminates excessive electrocoagulation.     

Addressing the specificity of affective startle modulation: fear versus disgust.

Previous research is equivocal regarding whether startle reflex eyeblink is specifically sensitive to the emotion of fear, or is more generally influenced by the valence dimension of emotion. Thirty-five undergraduate participants (17 male) viewed 60 pictures from five affective categories (pleasant, neutral, fear, disgust-blood, and disgust-other). Bilateral eyeblink EMG responses to acoustic startle probes were assessed during 2/3 of picture presentations, and 1/3 of intertrial intervals. Left corrugator and levator EMG responses to no-startle pictures were also examined. Supporting an emotional valence model of affective startle modulation, the startle potentiation effect was not specific to fear materials. In fact, women, but not men, had larger startles during disgust compared with fear pictures. Both corrugator and levator EMG responses were greater to disgust than fear stimuli. These findings limit the generalizability of corrugator as an index of all negative emotions and extend evidence for the specificity of levator to disgust.