Enhanced activity of mouse peritoneal cells after aclacinomycin administration

We have investigated the activation of mouse peritoneal macrophages by injection of aclacinomycin (ACM). Macrophages from ACM-treated mice have an increased phagocytic activity as measured by Candida ingestion. The microbicidal activity indirectly evaluated by chemiluminescence and superoxide determination in response to stimulation with zymosan and 4 beta-phorbol-12-myristate-13 alpha-acetate is also greater in the cells from treated mice. Direct measurement of the cytostatic function, and of in vitro and in vivo cytotoxicity shows comparable significant increases against L1210 or P815 target cells. The enhanced antitumoral activity could not be attributed to the residual presence of ACM in the peritoneal cells since no drug was detected by high-performance liquid chromatography and since their freeze-thaw lysates incubated with P815 cells did not modify the growth of tumor cells as measured by [3H]-thymidine incorporation. We also checked that the presence of ACM did not influence the intensity of the chemiluminescence. In all tests performed, only i.p. ACM administration could stimulate the peritoneal cells. Since the doses of ACM inducing an increase in macrophage activity are effective on the survival of tumor-bearing mice, the participation of this mechanism in tumor control might be suggested.     

Feasibility of near real-time image-guided sinus surgery using intraoperative fluoroscopic computed axial tomography.

OBJECTIVE: One of the main limitations of image-guided surgery is that navigation relies on the use of a CT scan obtained before surgery and is unable to be updated during the procedure. A software addition has been developed to allow reconstruction of CT-like images from a series of fluoroscopic scans and integrate these into an image-guided system (GE Healthcare Surgical Navigation, Lawrence, MA). We report our initial experience with a series of patients undergoing intraoperative fluoroscopic navigation in sinus surgery. STUDY DESIGN AND SETTINGS: After institutional review board clearance, we prospectively studied 14 consecutive patients undergoing image-guided sinus surgery with the use of intraoperative fluoroscopy. RESULTS: All patients had preoperative and postoperative fluoroscopic images reconstructed into CT-like images. By the conclusion of the study, images were adequate in quality and accurate navigation was achieved. CONCLUSION: Real-time image-guided sinus surgery using fluoroscopy is feasible. Future studies will need to focus on defining the procedures that could benefit, such as tumor resection, to enhance patient safety during these operations.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Upper gastrointestinal tract dysfunction in bulimia

Bulimia nervosa is a health problem of increasing magnitude that is estimated to affect 2–5% of the American adolescent and young adult female population. Because of the magnitude of this clinical problem and because of the importance of the upper gastrointestinal tract in its expression, a intradepartmental program of health care for patients affected with the disease was initiated. Eleven consecutive symptomatic bulimic individuals have been evaluated jointly by the gastroenterology and the psychiatry departments of the University of Pittsburgh. Five of these 11 individuals were found to have clinically important upper gastrointestinal pathology including ulcerative esophagitis, erosive gastritis, duodenal ulcer, and delayed gastric emptying. These gastrointestinal conditions could have been either a result of or have contributed to the symptomatology of these five patients. These data suggest that bulimic subjects have clinically important gastroenterological disease processes that require specific diagnosis and treatment independent of the psychiatric treatment provided for the bulimic condition.This work was supported in part by grants from NIDDK AM 32556.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.     

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.     

Endotracheal suctioning causes right upper lobe collapse in intubated children

Objective: Right upper lobe collapse is a common radiographic finding in intubated children. We hypothesized that deep suctioning and uncontrolled negative pressures during endotracheal tube suctioning were significant contributory factors. Methods : The incidence of right upper lobe (RUL) collapse in intubated, ventilated children on a paediatric cardiac intensive care unit was determined over a 3-month period ( n = 102). Graduated suction catheters and suction vacuums of < 165 cm H₂O were then introduced. Another prospective audit was carried out 3 months later ( n = 60). Results : We found that 24% developed RUL collapse and 4 developed an apical pneumothorax. Following the introduction of graduated catheters and controlled vacuums pressures, a significant reduction in the incidence of RUL collapse, to 7%, was observed ( p < 0.05). Conclusions : We conclude that high negative pressure and deep-suctioning causes RUL collapse in children. Any lobar collapse not only prolongs the child's stay in intensive care, but can be associated with further morbidity which may have a serious implication. By improving suctioning technique this morbidity can be significantly reduced.