Book Review: Adolescents, Alcohol and Substance Abuse: Reaching Teens Through Brief Interventions. Edited by Peter M. Monti, Suzanne M. Colby, and Tracy A. O'Leary, New York, The Guilford Press, 2001, 350 pp., ISBN 1-57230-658-0 (Hardback)

The book reviewed in this article discusses the use of brief interventions in the treatment of adolescent substance abuse. Topics covered include the developmental context within which adolescent substance use occurs, the use of the harm reduction approach to reduce substance use, current assessment instruments, and the role of cognitive and genetic factors in the etiology of substance abuse. Examples of specific brief interventions with adolescents are described and possible avenues for future transdisciplinary research are explored. This expansive sourcebook will be of value to clinicians and academicians alike.     

Higher-dose and less frequent dendritic cell infusions with PSMA peptides in hormone-refractory metastatic prostate cancer patients

BACKGROUND: Infusion of dendritic cells (DCs) pulsed with PSMA peptides was considered possible in hormone-refractory metastatic prostate cancer patients both with or without prior treatment with a greater number of DCs and for lesser infusions than previously administered. METHODS: DCs + PSMA peptides in patients undergoing leukapheresis were administered monthly 1-4 times, at rates greater than 20 million DCs in 17 patients not previously treated, and in 11 patients previously treated. RESULTS: Three partial responders and one complete responder were noted in the 17 previously untreated persons. DCs + PSMA peptides averaged 28.5 million cells (range in millions, 21.0-42.3). All responders received 3 or 4 infusions of greater than 22 million cells (3-4 times). In the previously treated group of 11 patients, DCs infused averaged 29.3 million cells (range in millions, 20-40.5). One new responder (bone scan) was noted. Two prior responders continued. Observation times were similar. Toxicity was minimal. CONCLUSIONS: These results suggest that DCs + PSMA peptide infusions can be given with greater numbers of DCs with a lesser number of infusions (1-4 monthly) with no loss of response rates compared to those noted previously, and without increased side effects. In previously treated patients (both relapsing and nonrelapsing), adverse effects were not noted, and new responses can be anticipated to be without harmful side effects. However, the follow-up time, and number of patients in this group, were small.     

Diphenylhydantoin-induced pure red cell aplasia after neurological surgery: report of two cases

Pure red cell aplasia (PRCA) is characterized by severe anemia, reticulocytopenia, marked selective hypoplasia of the erythroid precursor cells in the bone marrow and normal peripheral leukocyte and platelet counts. We reported two cases of diphenylhydantoin (DPH)-induced PRCA after neurological surgery. They recovered completely with discontinuance of DPH therapy. Neurosurgeons should be aware of this side effect because most reported cases of PRCA have occurred about a few months after neurological surgery under general anaesthesia and DPH therapy.     

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy.

PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.     

42nd Annual Meeting of the American Society for Cell Biology,San Francisco,California, USA, 14–18 December 2002

The Annual Meeting of the American Society for Cell Biology (ASCB) is a diverse conference covering all topics in cell biology. While all of the basic biology presented at this meeting may potentially contribute to breast cancer research, there were a significant number of presentations and posters directly pertinent to this field. Here we have summarized the research that is of greatest immediate relevance to breast cancer, with particular emphasis on mammary gland development and tumorigenesis in vivo, three-dimensional in vitro models of mammary morphogenesis, alterations of signal transduction pathways in breast cancer, and global studies in expression profiling and drug screening.     

Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.

Increasing reports of time-dependent inhibition of cytochrome P450 (P450) suggest further emphasis on interpreting the consequences, either from a pharmacokinetic or toxicological perspective. Two automated, time-dependent inhibition assays with a liquid chromatography-tandem mass spectrometric endpoint are presented. The initial assay utilizes human liver microsomes, a single concentration of inhibitor, and a single preincubation time of 30 min. Phenacetin, diclofenac, S-mephenytoin, bufuralol, and midazolam are used as substrates for CYP1A2, 2C9, 2C19, 2D6, and 3A4, and the assay differentiates between reversible and irreversible inhibition. The second assay uses individual recombinant human P450s, six inhibitor concentrations, and three time points to accurately define kinact and KI. A good correlation is demonstrated between kinact/KI and partition ratio, indicating that both terms are related in describing the efficiency of enzyme inactivation. Despite the single preincubation time point of 30 min used in the initial assay, a good relationship has been found to exist between the unbound IC50 estimated from this initial screen and the kinact/KI ratio derived from the more extensive subsequent single P450 assay. The higher throughput human liver microsomal assay can therefore generate IC50 values that can be used to predict the pharmacokinetic impact on cotherapies from the estimated kinact/KI ratio, predicted human dose, and pharmacokinetics.     

Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.