Arterial to end-tidal carbon dioxide difference in children undergoing mechanical ventilation of the lungs during general anaesthesia.

Capnography (ETCO2 ) is routinely used as a non-invasive estimate of arterial carbon dioxide (PaCO2 ) levels in order to modify ventilatory settings, whereby it is assumed that there is a positive gap between PaCO2 and ETCO2 of approximately 0.5 kPa. However, negative values (ETCO2 > PaCO2 ) can be observed. We retrospectively analysed arterial to end-tidal carbon dioxide differences in 799 children undergoing general anaesthesia with mechanical ventilation of the lungs in order to elucidate predictors for a negative gap. A total of 2452 blood gas analysis readings with complete vital sign monitoring, anaesthesia gas analysis and spirometry data were analysed. Mean arterial to end-tidal carbon dioxide difference was -0.18 kPa (limits of 95% agreement -1.10 to 0.74) and 71.2% of samples demonstrated negative values. The intercept model revealed PaCO2 to be the strongest predictor for a negative PaCO2 -ETCO2 difference. A decrease in PaCO2 by 1 kPa resulted in a decrease in the PaCO2 -ETCO2 difference by 0.23 kPa. This study demonstrates that ETCO2 monitoring in children whose lungs are mechanically ventilated may paradoxically lead to overestimation of ETCO2 (ETCO2 > PaCO2 ) with a subsequent risk of unrecognised hypocarbia.

Cerebral oxygenation in patients undergoing shoulder surgery in beach chair position: comparing general to regional anesthesia and the impact on neurobehavioral outcome.

BACKGROUND: Ischemic brain damage has been reported in healthy patients after beach chair position for surgery due to cerebral hypoperfusion. Near-infrared spectroscopy has been described as a non-invasive, continuous method to monitor cerebral oxygen saturation. However, its impact on neurobehavioral outcome comparing different anesthesia regimens has been poorly described. METHODS: In this prospective, assessor-blinded study, 90 patients undergoing shoulder surgery in beach chair position following general (G-group, n=45) or regional anesthesia (R-group; n=45) were enrolled to assess the prevalence of cerebral desaturation events comparing anesthesia regimens and their impact on neurobehavioral and neurological outcome. Anesthesiologists were blinded to regional cerebral oxygen saturation values. Baseline data assessed the day before surgery included neurological and neurobehavioral tests, which were repeated the day after surgery. The baseline data for regional cerebral oxygen saturation/bispectral index and invasive blood pressure both at heart and auditory meatus levels were taken prior to anesthesia, 5 min after induction of anesthesia, 5 min after beach chair positioning, after skin incision and thereafter all 20 min until discharge. RESULTS: Patients in the R-group showed significantly less cerebral desaturation events (p<0.001), drops in regional cerebral oxygen saturation values (p<0.001), significantly better neurobehavioral test results the day after surgery (p<0.001) and showed a greater hemodynamic stability in the beach chair position compared to patients in the G-group. CONCLUSIONS: The incidence of regional cerebral oxygen desaturations seems to influence the neurobehavioral outcome. Regional anesthesia offers more stable cardiovascular conditions for shoulder surgery in beach chair position influencing neurobehavioral test results at 24h.

Precision determination of the dpi<-->NN transition strength at threshold.

An unusual but effective way to determine at threshold the dpi<-->NN transition strength alpha is to exploit the hadronic ground-state broadening Gamma(1s) in pionic deuterium, accessible by x-ray spectroscopy. The broadening is dominated by the true absorption channel dpi(-)-->nn, which is related to s-wave pion production pp-->dpi(+) by charge symmetry and detailed balance. Using the exotic atom circumvents the problem of Coulomb corrections to the cross section as necessary in the production experiments. Our dedicated measurement finds Gamma(1s)=(1171(-49)(+23)) meV yielding alpha=(252(-11)(+5)) microb.

Targeted therapies for prostate cancer against the prostate specific membrane antigen.

Prostate cancer is the most common cancer in men from Western industrialized countries and a significant proportion of patients progress to advanced metastatic disease, for which currently no curative treatment exists. Therefore, new therapeutic approaches need to be considered. Prostate specific membrane antigen (PSMA) is an integral, non-shed type 2 membrane protein that is highly and specifically expressed on prostate epithelial cells and strongly upregulated in prostate cancer. PSMA is also present in the neovasculature of other solid tumors. These findings have spurred the development of PSMA-targeted therapies and first-generation products have entered clinical testing. The proposed strategies range from targeted toxins and radionuclides to immunotherapeutic agents. The present review provides an overview of these approaches.

A bispecific diabody directed against prostate-specific membrane antigen and CD3 induces T-cell mediated lysis of prostate cancer cells.

BACKGROUND: Although cancer of the prostate is one of the most commonly diagnosed cancers in men, no curative treatment currently exists after its progression beyond resectable boundaries. Therefore, new agents for targeted treatment strategies are needed. Cross-linking of tumor antigens with T-cell associated antigens by bispecific monoclonal antibodies have been shown to increase antigen-specific cytotoxicity in T-cells. Since the prostate-specific membrane antigen (PSMA) represents an excellent tumor target, immunotherapy with bispecific diabodies could be a promising novel treatment option for prostate cancer. METHODS: A heterodimeric diabody specific for human PSMA and the T-cell antigen CD3 was constructed from the DNA of anti-CD3 and anti-PSMA single chain Fv fragments (scFv). It was expressed in E. coli using a vector containing a bicistronic operon for co-secretion of the hybrid scFv V(H)CD3-V(L)PSMA and V(H)PSMA-V(L)CD3. The resulting PSMAxCD3 diabody was purified from the periplasmic extract by immobilized metal affinity chromatography (IMAC). The binding properties were tested on PSMA-expressing prostate cancer cells and PSMA-negative cell lines as well as on Jurkat cells by flow cytometry. For in vitro functional analysis, a cell viability test (WST) was used. For in vivo evaluation the diabody was applied together with human peripheral blood lymphocytes (PBL) in a C4-2 xenograft-SCID mouse model. RESULTS: By Blue Native gel electrophoresis, it could be shown that the PSMAxCD3 diabody is mainly a tetramer. Specific binding both to CD3-expressing Jurkat cells and PSMA-expressing C4-2 cells was shown by flow cytometry. In vitro, the diabody proved to be a potent agent for retargeting PBL to lyze C4-2 prostate cancer cells. Treatment of SCID mice inoculated with C4-2 tumor xenografts with the diabody and PBL efficiently inhibited tumor growth. CONCLUSIONS: The PSMAxCD3 diabody bears the potential for facilitating immunotherapy of prostate cancer and for the elimination of minimal residual disease.

A recombinant PSMA-specific single-chain immunotoxin has potent and selective toxicity against prostate cancer cells.

Prostate cancer is the most commonly diagnosed form of cancer and the second leading cancer-related death among men in the Western civilization. Since no effective therapy exists for this tumor after progression beyond resectable boundaries, there is an urgent need for new treatment strategies. Prostate specific membrane antigen (PSMA) represents an excellent target on prostate cancer cells, and therefore specific immunotherapy may be a novel therapeutic option for the management of this tumor. We constructed a fully recombinant immunotoxin (A5-PE40) from a single-chain antibody fragment (scFv) against cell-adherent PSMA and a truncated form of Pseudomonas exotoxin A (PE40) lacking its natural binding domain Ia. The scFv A5 was obtained from a mAb elicited with native PSMA by phage display technology and direct selection on cells carrying the antigen. The bacterially expressed and purified immunotoxin A5-PE40 specifically binds to PSMA-positive prostate cancer cells and induces a 50% reduction of viability (IC50) at a concentration of 20 pM, while PSMA-negative cells remain unaffected. Due to its high and specific toxicity this recombinant immunotoxin is a promising candidate for therapeutic applications in patients with prostate cancer.

The high-energy proton fluxes in the SAA observed with REM aboard the MIR orbital station.

During two years, from November 1994 to 1996, the particle detector REM measured the highly energetic electron and proton environment at the outside of the MIR orbital station. Using mission averaged data we investigate various aspects of the proton fluxes in the SAA. Comparison with the radiation belt model AP8 reveal important differences.

REM measurements aboard MIR during 1995.

Measurements of the South Atlantic Anomaly (SAA) made with the Radiation Environment Monitor (REM) aboard Mir from November 1994 to February 1996 are presented. During this period an increase of the SAA radiation by approximately 25% is observed, which coincides with a lowering of the radio solar flux. Radio solar flux is one of the parameters controlling the earth's atmospheric distribution and with it the absorption of inner radiation belt protons forming the SAA. Due to the altitude gradient of the atmospheric density, the proton fluxes in the SAA are anisotropic (loss cone, east-west effect). The measured distribution can be accounted for by basic models.

Observations of the low Earth orbit radiation environment from Mir.

Recent measurements of the high-energy charged particle environment with the Radiation Environment Monitor (REM) aboard the Russian Mir space station are presented. Ionizing dose rates in a silicon detector have been measured with two shieldings. The dose is mainly accumulated in two distinct areas, the South Atlantic Anomaly (SAA) and the region of closest approach to the magnetic poles. Whereas the radiation in the South Atlantic Anomaly varied little during 1995, large changes of the daily absorbed doses in the polar regions are observed. A comparison of REM doses with the NASA AP-8 and AE-8 radiation models revealed major differences. AP-8 tends to underestimate the average REM doses, whereas AE-8 overestimates REM doses, and rather describes the worst case.

Effectiveness of a pregnancy smoking cessation program.

OBJECTIVE: To evaluate two nursing approaches to promoting smoking cessation during initial antenatal visits. DESIGN: Experimental, with assignment to interventions using a random, alternate-day strategy and blind assessment of smoking at baseline, 1 month postintervention, 36 weeks' gestation, and 6 weeks postpartum. SETTING/PARTICIPANTS: 224 daily smokers, fewer than 31 weeks gestation, during first prenatal visit, at a teaching hospital antenatal clinic. INTERVENTIONS: An evening class providing guidance on a self-help program for 2 hours on a group basis or 20 minutes on an individual basis during the prenatal appointment. MAIN OUTCOME MEASURE: Smoking cessation, confirmed by urinary cotinine levels. RESULTS: All women assigned to the referral intervention received a referral, but none attended the classes. In contrast, 93% assigned to the immediate intervention received the intervention. The group receiving immediate intervention had two to three times higher rates of cessation at all follow-up periods, with significant differences at the 1-month follow-up. There were certain similarities between the groups. CONCLUSION: Cessation interventions should be administered during the first prenatal visit.