Evaluation of an end-tidal portable ETCO2 colorimetric breath indicator (COLIBRI)

Evaluation of tube position is important after in-hospital and prehospital emergency intubation. Colorimetric breath indicators are devices for immediate control of tube positioning by showing a color change according to end-tidal CO2 (ETCO2) concentrations. We hypothesized that colorimetric breath indicators can yield reliable results for confirmation of tube position. The aim of this study was to evaluate the effectiveness and safety of a new colorimetric breath indicator (Colibri, ICOR AB, Bromma, Sweden) in 147 patients during general anesthesia, in critically ill patients, during transport to in-hospital interventions, and in a study design after insertion of a second tube into the esophagus in long-term ventilated patients. The Colibri was attached between the respective airway and ventilatory tubing. Seventy-three patients were investigated during general anesthesia, 39 patients were observed during long-term ventilation with an average duration of 33 hours, in 15 patients during transport to an intervention for up to 4 hours, and in 20 long-term ventilated patients at the medical intensive-care unit after insertion of a second tube intentionally into the esophagus with the help of a laryngoscope. The Colibri worked well in all groups investigated and showed no false results in the group with tubes inserted into the trachea and esophagus. Data suggest that the Colibri might serve as a valuable tool for evaluating and controlling tube position. This device is independent of power supply or electronic equipment, portable, small, and immediately ready for use.     

Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia

Five patients with sickle cell anemia were treated with hydroxyurea (HU), in hopes of augmenting their production of fetal hemoglobin. Laboratory responses in two patients treated for more than 2 years were encouraging and there were suggestions of clinical improvement. Long- term HU therapy should be considered for severely affected adults with sickle cell anemia who are willing to accept what is probably a small risk of carcinogenesis. Preliminary chromosomal analysis and knowledge of the clastogenic properties of HU suggest that conception and pregnancy should be avoided. Pharmacokinetic studies will probably be necessary to adjust individual dosage schedules so that cytotoxicity is avoided. F cell responses can be seen in 2 to 3 weeks if the HU dose is optimal, but establishment of a large number of F cells in the circulation may take a month or longer.     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

Prognostic value of hemodynamic vs big endothelin measurements during long-term IV therapy in advanced heart failure patients

STUDY OBJECTIVE: To compare hemodynamics and plasma big endothelin levels in patients awaiting heart transplantation who are receiving continuous IV therapy, and to establish their respective potency for predicting future cardiac events. DESIGN: A randomized, prospective trial of ambulatory continuous treatment with IV prostaglandin E(1) (PGE(1)) vs dobutamine. A subanalysis was conducted of all patients who completed 4 weeks of follow-up in regard to treatment effects on hemodynamics and big endothelin plasma levels. PATIENTS: Thirty-two listed heart transplant candidates who were refractory to oral treatment, 21 patients who were receiving PGE(1), and 11 patients receiving dobutamine. MEASUREMENTS AND RESULTS: Hemodynamics and plasma big endothelin levels were measured at baseline and after 4 weeks. The cardiac index increased significantly (PGE(1) group, 1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m(2); dobutamine group, 1.8 +/- 0.3 vs 2.3 +/- 0.6 L/min/m(2); p < 0.05), whereas the systemic vascular resistance index (SVRI) decreased significantly only in the PGE(1) group (3,352 +/- 954 vs 2,178 +/- 519 dyne. s. cm(-5)/m(2); p < 0. 05). The plasma big endothelin level decreased significantly (PGE(1) group, 7.6 +/- 3.1 vs 4.7 +/- 2.6 fmol/mL; dobutamine group, 6.5 +/- 3.7 vs 5.0 +/- 2.6 fmol/mL; p < 0.01 for the time effect). Plasma big endothelin (beta = 0.393; chi(2) = 10.8; p = 0.001) and SVRI (beta = 0.003; chi(2) = 6.9; p < 0.01), both measured after 4 weeks of continuous treatment, were the only independent predictors of future outcome. CONCLUSION: Continuous treatment over 4 weeks with either PGE(1) or dobutamine in patients awaiting heart transplantation yields an improved hemodynamic state accompanied by a reduction of increased big endothelin levels. Plasma big endothelin measured after 4 weeks of continuous therapy provides prognostic information about future outcome.     

Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity

We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies.     

Detection of human papillomavirus DNA in cervical lesions by in situ hybridization using biotinylated DNA probes

In situ hybridization (ISH) for human papillomavirus (HPV)-6, -11, -16, -18, and -31 DNA was performed on 615 formalin-fixed paraffin-embedded cervical biopsies using biotinylated DNA probes. Results were obtained from 584 samples with 266 (45.5%) containing HPV-DNA sequences. Ninety percent of condyloma acuminatum specimens were positive for HPV-DNA with 18 of 19 positive cases containing HPV-6 or -11 DNA. The detection rate of HPV in cervical intraepithelial neoplasia (CIN) lesions was 50.6% (239 of 472), while only 8 of 91 (8.9%) cervical biopsies considered to be histologically normal or with minimal dysplasia contained HPV-DNA as demonstrated by ISH. The prevalence of HPV-16, -18, and/or -31 DNA increased with the severity of the lesions, with 20 of 20 (100%) positive CIN-III lesions containing these viral types compared with 102 of 157 (65.0%) positive CIN-I lesions. ISH with biotinylated DNA probes appears helpful in identifying lesions containing higher risk viral strains.     

Psychosocial consequences of dental fear and anxiety

OBJECTIVES: The aim of this study was to examine the negative psychosocial impacts of dental anxiety in a sample of dentally fearful and anxious individuals recruited from the general population. The associations between psychosocial impacts, dental anxiety scale (DAS) scores and other severe fears were explored. METHODS: One hundred and thirty-five subjects who were anxious or fearful about dental treatment were divided into low and high general fear groups based on the number of other severe fears they reported. Negative psychosocial impacts were assessed using a modified form of the scale developed by Kent et al. (1996). This consisted of three dimensions: psychological reactions, social relationships and avoidance/inhibition. Other measures included self-ratings of oral, general and emotional health and scales to assess self-esteem and morale. RESULTS: Overall, 93.1% of subjects reported one or more impacts. Those in the high-fear group had higher psychosocial impact scores than those in the low-fear group (means of 4.19 vs. 2.85; P < 0.05). Differences were most marked with respect to psychological consequences and avoidance/inhibition. The high-fear group had scores indicative of lower self-esteem and lower morale. Forward stepwise linear and logistic regression analyses indicated that both dental anxiety and general fearfulness contributed to these negative outcomes. However, the latter was a more consistent predictor in that it entered six of seven models generated while the former entered only four. CONCLUSION: The study indicated that dental fear and anxiety have pervasive psychosocial consequences, and that these are more marked among subjects with high levels of general fearfulness. It also provided evidence of the validity of a modified form of the psychosocial impact scale developed by Kent et al. (1996).