Tumor clearance of technetium 99m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer

PURPOSE: Since we have previously shown that the efflux rate of technetium 99m (99mTc) sestamibi, a transport substrate of P-glycoprotein (Pgp), is directly correlated with Pgp levels in untreated breast carcinoma, we tested whether tumor clearance of 9mTc-sestamibi may be predictive of therapeutic response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Thirty-nine patients with stage III disease, median tumor diameter 5.8 cm (range, 3 to 10) were enrolled onto this prospective clinical trial and underwent 99mTc-sestamibi scan before neoadjuvant chemotherapy. Patients were injected intravenously (i.v.) with 740 MBq of 99mTc-sestamibi; a 15-minute dynamic study was performed, and static planar images were obtained at 0.5, 1, 2, and 4 hours. The time to half clearance of 99mTc-sestamibi was calculated in each patient from decay corrected time-activity curves using a monoexponential fitting. Patients were treated with epirubicin 150 mg/m2 i.v. every 2 weeks for three courses and then underwent surgery within 3 weeks from the completion of chemotherapy. Residual tumor was assessed by pathologic examination of mastectomy specimens. RESULTS: Seventeen of 39 patients showed a rapid tumor clearance of 9mTc-sestamibi (time to half clearance [t1/2] < or = 204 minutes) and 15 of these 17 (88%) showed a highly cellular macroscopic residual tumor at histology that indicated lack of tumor response to neoadjuvant chemotherapy. In contrast, only eight of 22 (36%) with prolonged retention of 99mTc-sestamibi (t1/2 > 204 minutes) showed residual macroscopic tumor at histology (Fisher's exact test, P < .01). CONCLUSION: A rapid tumor clearance of 99mTc-sestamibi may predict lack of tumor response to neoadjuvant chemotherapy with drugs affected by the multidrug-resistant phenotype in patients with locally advanced breast carcinoma.     

The use of different fixatives and hydrophilic embedding media (Historesin and Unicryl) for the study of embryonic tissues

As part of a research project exploring ways through which we can understand the crying infant and its family, this study focuses on the experiences of fathers during labour and delivery of their infant. In a previous part of the project it was shown that fathers' negative experiences during the childbirth were correlated with the amount of crying in the infant during the first months after birth. The aim of the present study was to explore and interpret the experiences that fathers reported in an interview when the infant was between six months and one year of age. A hundred and nine fathers were interviewed. The interviews, which took place in the families' homes and with both parents present, were carried out in dialogue form with open-ended questions. The results reveal that complications during the delivery were significantly correlated with the amount of crying in the infant. Feelings of helplessness, of guilt and that staff behaviour had been negative were more common in the group of fathers who experienced the delivery as a negative event. 'Locus of control' seems to be the most relevant concept.     

Induction of long-term depression (with anxiety and fear components) by immunization of rats against pargyline

The active immunization of albino rats against pargyline (a MAO B inhibitor) induced the formation of antibody to pargyline and results in deep depressive changes and fear. These changes were observed within 6 weeks after the first immunization. Therefore, it opens the possibility to model depression long by exerting the minimum influences. There was also a long-term modulation of craving for alcohol.     

Unsuspected pulmonary embolism: prospective detection on routine helical CT scans

PURPOSE: To determine the prevalence of unsuspected pulmonary embolism (PE) on routine thoracic helical computed tomographic (CT) scans and to quantify the improvement in PE detection by using a cine-paging mode on a workstation instead of hard-copy review. MATERIALS AND METHODS: Seven hundred eighty-five patients referred for routine contrast medium-enhanced thoracic CT within 9 months were prospectively recruited. Helical CT was performed. Studies were prospectively interpreted by four radiologists. Two radiologists performed routine, undirected, hard-copy consensus review for official interpretation; two of three thoracic radiologists independently performed a dedicated workstation-based search for PE. The presence of PE involving the main, lobar, or segmental pulmonary arteries was assigned a score of 1-5 (1 = definitely negative, 5 = definitely positive) by each independent reviewer. Patients with a score of 4 or 5 underwent lower-extremity ultrasound, ventilation-perfusion scintigraphy, or both, followed by pulmonary CT angiography if the findings were still equivocal. RESULTS: Twelve (1.5%) of the 785 patients had unsuspected PE, with an inpatient prevalence of 5% (eight of 160) and an outpatient prevalence of 0.6% (four of 625). Of the 12 patients with unsuspected PE, 10 (83%) had cancer. Of the 81 inpatients with cancer, seven (9%) had unsuspected PE. A dedicated workstation-based search resulted in detection of PE in three more patients (25%) than did hard-copy interpretation. CONCLUSION: The prevalence of unsuspected PE was highest among inpatients with cancer. A directed, workstation-based search can improve the PE detection rate over that with hard-copy review.     

CD4+ T cells from IRF-1-deficient mice exhibit altered patterns of cytokine expression and cell subset homeostasis

The cyclic hexapeptide CWLDVC (TBC 772) is an antagonist of alpha4 integrins and a potent inhibitor of lymphocyte interactions with fibronectin, vascular cell adhesion molecule-1, and muscosal vascular addressin cell adhesion molecule-1 (MAdCAM-1). As such, peptide TBC 772 effectively inhibits the activation of freshly isolated human T lymphocytes stimulated with purified vascular cell adhesion molecule-1 coimmobilized with anti-CD3 mAb. The influence of peptide binding on distinct sites of the alpha4beta1 complex was determined by flow cytometry and cellular adhesion assays employing a panel of mAbs. Binding of the alpha4-specific mAb L25 and the beta1-specific mAb 33B6 was not altered by the peptide; however, binding of mAb 19H8, which is specific for a combinatorial epitope of alpha4beta1, was dramatically inhibited. Treatment of lymphocytes with the peptide caused an increase in a ligand-induced epitope on beta1 integrin defined by mAb 15/7. In T cell activation studies using coimmobilized anti-CD3 mAb and the anti-integrin mAbs, the peptide had broader inhibitory activity, suppressing costimulation induced by all the integrin mAbs. The peptide was not generally toxic and was integrin selective in its suppressive activity, as coactivation by ligation of CD3 in conjunction with CD28 or CD26 was not affected. These results suggest that the antagonist peptide CWLDVC can effectively neutralize integrin coactivation systems by a mechanism independent of competitive binding.     

First-cycle blood counts and subsequent neutropenia, dose reduction, or delay in early-stage breast cancer therapy

PURPOSE: If patients could be ranked according to their projected need for supportive care therapy, then more efficient and less costly treatment algorithms might be developed. This work reports on the construction of a model of neutropenia, dose reduction, or delay that rank-orders patients according to their need for costly supportive care such as granulocyte growth factors. PATIENTS AND METHODS: A case series and consecutive sample of patients treated for breast cancer were studied. Patients had received standard-dose adjuvant chemotherapy for early-stage nonmetastatic breast cancer and were treated by four medical oncologists. Using 95 patients and validated with 80 additional patients, development models were constructed to predict one or more of the following events: neutropenia (absolute neutrophil count [ANC] < or = 250/microL), dose reduction > or = 15% of that scheduled, or treatment delay > or = 7 days. Two approaches to modeling were attempted. The pretreatment approach used only pretreatment predictors such as chemotherapy regimen and radiation history; the conditional approach included, in addition, blood count information obtained in the first cycle of treatment. RESULTS: The pretreatment model was unsuccessful at predicting neutropenia, dose reduction, or delay (c-statistic = 0.63). Conditional models were good predictors of subsequent events after cycle 1 (c-statistic = 0.87 and 0.78 for development and validation samples, respectively). The depth of the first-cycle ANC was an excellent predictor of events in subsequent cycles (P = .0001 to .004). Chemotherapy plus radiation also increased the risk of subsequent events (P = .0011 to .0901). Decline in hemoglobin (HGB) level during the first cycle of therapy was a significant predictor of events in the development study (P = .0074 and .0015), and although the trend was similar in the validation study, HGB decline failed to reach statistical significance. CONCLUSION: It is possible to rank patients according to their need of supportive care based on blood counts observed in the first cycle of therapy. Such rankings may aid in the choice of appropriate supportive care for patients with early-stage breast cancer.     

Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B

Interleukin-12, a cytokine with an important role against intracellular pathogens, promotes Th1 cell development, cellmediated cytotoxicity, and interferon-gamma production. We investigated the immunoregulatory role of IL-12 in 72 chronic hepatitis B virus (HBV) carriers, 33 of whom were monitored longitudinally during interferon-alpha treatment. Serum levels of IL-12 heterodimer, IL-12 p40 subunit, IL-4, and Th1 cytokines were determined by specific ELISAs, and hepatitis B core antigen-specific T cell response by a proliferation assay. Chronic HBV carriers had higher serum levels of IL-12 and IL-12 p40 in comparison with controls (P < 0.01), suggesting that IL-12 production is not impaired. The longitudinal analysis revealed a further substantial increase (> 2.5x baseline level) of bioactive IL-12 and Th1 cytokines in patients who cleared HBV and seroconverted to anti- hepatitis B e, unlike the 23 nonresponders with persistent HBV replication (P < 0.01). The IL-12 peak followed the peak of hepatocytolysis by 9.8+/-2.8 wk and occurred either before or simultaneously with hepatitis B e seroconversion. Hepatitis B core antigen-specific T cell proliferation closely correlated with hepatocytolysis and increased significantly in all patients (8 responders and 15 nonresponders) who developed hepatitis flare, irrespective of the virological outcome. These results provide in vivo evidence that IL-12 may have an important role for viral clearance in chronic HBV infection.     

Pharmacy economic repercussions and other expenses in changing vascular equipment with no change in the rate of infection

OBJECTIVE: Comparison of infections when modifying the protocol of change of vascular equipment, from 48 to 72 hours, and its repercussion on pharmacy expenses and fungibles. DESIGN: Prospective study of operation. CONTEXT: Medical and surgical ICU of a University Hospital. PATIENTS: Bacteriological data of the catheters and hemocultures of two groups of patients are studied. The Control Group is formed by 105 patients admitted for three months, and the Study Group are 106 patients admitted in the other months of the following year, after the change in the protocol of vascular catheters. OPERATIONS: In the first group of patients, the vascular equipment (Monitoring kit of pressure, drop equipment, stopcock valves, accuracy valves and medication) were changed according to the established protocol, every 48 hours. In the second group of patients, the same changes were done every 72 hours. MAIN RESULTS: The diagnosis, age, average stay and survival were recorded in both groups. The infection rate by catheters and bacteremias did not show significant differences between both groups. However, the load of nursing work was reduced when changing the equipment every 72 hours and, in the same way, there was a noticeable saving in the pharmacy and fungible material consumption. CONCLUSIONS: The changes of equipment of vascular catheters may be done every 72 hours without having a higher rate of infections and with an optimum use of resources.