Clusters of drug involvement in Panama: results from Panama's 1996 National Youth Survey

This report is based on the first epidemiological investigation of clustering of tobacco, alcohol, inhalant, and other drug involvement within individual schools using data from Panama's 1996 National Youth Survey on Alcohol and Drug Use. Clustering was estimated with the Alternating Logistic Regression method. Adjusted estimates of pair-wise cross-product ratios (PWCPR), a measure of clustering, show modest clustering (i.e. PWCPR>1.0) at the school level for tobacco smoking (PWCPR=1.41; 95% confidence interval, CI=1.22–1.64), alcohol consumption (PWCPR=1.33; 95% CI=1.22–1.45), use of inhalants, (PWCPR=1.35; 95%CI=1.07–1.69), and other drug use (PWCPR=1.38; 95%CI=1.14–1.68). These findings provide preliminary evidence that the odds of drug use among school-attending youths increase when another youth in the same school uses drugs, and suggest a new line of research on within-school diffusion that should include the identification of school-level factors that contribute to student drug use.     

Genotoxic stress leads to centrosome amplification in breast cancer cell lines that have an inactive G1/S cell cycle checkpoint

Centrosome amplification plays a key role in the origin of chromosomal instability during cancer development and progression. In this study, breast cancer cell lines with different p53 backgrounds were used to investigate the relationship between genotoxic stress, G(1)/S cell cycle checkpoint integrity, and the development of centrosome amplification. Introduction of DNA damage in the MCF-7 cell line by treatment with hydroxyurea (HU) or daunorubicin (DR) resulted in the arrest of both G(1)/S cell cycle progression and centriole duplication. In these cells, which carry functional p53, HU treatment also led to nuclear accumulation of p53 and p21(WAF1), retinoblastoma hypophosphorylation, and downregulation of cyclin A. MCF-7 cells carrying a recombinant dominant-negative p53 mutant (vMCF-7(DNp53)) exhibited a shortened G(1) phase of the cell cycle and retained a normal centrosome phenotype. However, these cells developed amplified centrosomes following HU treatment. The MDA-MB 231 cell line, which carries mutant p53 at both alleles, showed amplified centrosomes at the outset, and developed a hyperamplified centrosome phenotype following HU treatment. In cells carrying defective p53, the development of centrosome amplification also occurred following treatment with another DNA damaging agent, DR. Taken together, these findings demonstrate that loss of p53 function alone is not sufficient to drive centrosome amplification, but plays a critical role in this process following DNA damage through abrogation of the G(1)/S cell cycle checkpoint. Furthermore, these studies have important clinical implications because they suggest that breast cancers with compromised p53 function may develop centrosome amplification and consequent chromosomal instability following treatment with genotoxic anticancer drugs.     

Delayed versus immediate exercises following surgery for breast cancer: a systematic review

SummaryBackground Seroma formation, wound healing and fluid drainage are a concern for both surgeons and patients. Excessive fluid production can result in seroma formation, and inadequate drainage of seromas is known to cause infection, pain, discomfort and longer periods of hospitalisation. Postoperative exercises given to maintain movement of the arm are believed to increase the amount of fluid production following surgery. This review aimed to determine whether a program of delayed exercises reduces the risk of seroma formation, fluid loss and hospital stay, without loss of arm movement.Method A systematic review. RCTs of early versus delayed shoulder mobilisation after surgery in females with breast cancer were included in the review. Outcomes. One or more measurements of shoulder range of motion, wound complications, fluid drainage volumes and incidence of seroma formation. Design. Randomised controlled trials, control group of delayed exercise/mobilisation. Validity assessment was carried out using a data extraction form based on the CONSORT statement. Study characteristics recorded include sample size, intervention, control, period of exercise delay, surgical procedure and conclusions drawn. Data synthesis was carried out using random effects and weighted mean differences to test for heterogeneity and combined effects.Results 12 RCTs were included in the review of which 6 were included for meta-analysis. Delaying exercises significantly decreases seroma formation (OR=0.4; 95%CI 0.2–0.5; p=0.00001). No significant differences were found for drainage volume or hospital stay.Conclusion Current evidence from RCTs supports the use of a delayed program of arm exercises to reduce seroma formation. Clinical and statistical inconsistencies between studies did not allow any conclusions to be drawn regarding the effects of delayed exercises on fluid drainage, hospital stay and immediate or long term ability to move the arm.     

Effects of clonidine in schizophrenic patients with primary polydipsia: three single case studies

A pilot study was conducted in schizophrenic patients with primary polydipsia to determine the tolerability of adding clonidine to an existing antipsychotic drug regimen and to seek evidence of an antidipsic effect. Three patients with chronic schizophrenia and primary polydipsia underwent open controlled prospective trials of treatment with clonidine in doses of up to 800 microg/day. The trials lasted from 2 to 5 months each, and analysis of variance was used to test for changes in dependent variables on a case-by-case basis. Blood pressure and pulse declined significantly in a dose-dependent manner, but fluid intake, as assessed by measurements of weight and 24-h urine volume, was not affected. Hypotension and bradycardia limited the extent to which the dose of clonidine could be increased. The lack of evident effect of clonidine on polydipsia in this small sample and the inconsistent results of two other recent studies of clonidine in patients with schizophrenia and primary polydipsia provide little overall support for the effectiveness of clonidine treatment in primary polydipsia associated with schizophrenia.     

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome.     

Does PBL Matter? Relations Between Instructional Context,Learning Strategies,and Learning Outcomes

Purpose:To compare learning strategies used in Problem based learning (PBL) and lectures, and the relations between learning strategies and learning outcomes to determine how different learning strategies associated with PBL and lectures contribute to aspects of clinical competence. Design:The 52-item learning strategies questionnaire was given to preclinical medical students during lecture and PBL sessions in first and third year from 1994 to1998. Response patterns were compared across the two contexts and factor structures investigated. Regression analyses examined relations between learning strategies and outcomes.Main Outcome Measures/Results:Comparison of responses on the 326 complete pairs of lecture and PBL questionnaires indicated differences at the 0.05 level on 44 of the 52 items. The mean differences were greater than 0.5 (on a 5 point scale)at the 0.001 level for 20 items. Of these, five strategies were used more often in PBL and 15 in lectures. Comparisons of learning strategy use across years showed significant changes with time in both instructional contexts. Principal component analysis revealed a stable factor structure with 4 factors distinctly associated with PBL and 4 factors with the lecture learning context. The remaining 6 factors were mixed and independent of context. Exploratory regression analysis revealed that learning outcomes in examinations were influenced by learning strategies. Multiple choice performance was positively predicted by learning associated with lecture class notes and negatively by group work, whereas the OSCE (objective structured clinical exam) performance was positively predicted by class participation in PBL, self-directed note making and lecture class notes.Conclusion:We have developed a learning strategies questionnaire that shows that students' learning strategies are influenced by instructional context, and patterns of learning strategy use change over time. There is tentative evidence that the students' learning strategies influence learning outcomes. This revised version was published online in June 2006 with corrections to the Cover Date.     

A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients.

PURPOSE: A multicentric, phase II study to evaluate the efficacy and safety of the combination paclitaxel and oxaliplatin in patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS: Patients received 175 mg/m(2) paclitaxel (over 3 h) followed by 130 mg/m(2) oxaliplatin (over 2 h) every 21 days for up to nine cycles without hydration or primary granulocyte colony-stimulating factor prophylaxis. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2 and to have received no more than one prior cisplatin- and/or carboplatin-containing chemotherapy regimen with a platinum-progression-free interval > or =6 months. RESULTS: Of the 105 patients enrolled and treated, 98 were eligible. An overall response rate of 81% (79 of 98 patients) (95% confidence interval 71% to 88%) was observed according to RECIST criteria (third party reviewed), and 88% (86 of 98) when this was complemented with CA-125 response. With a median follow up of 43.6 months (range 30.2-64.2) the median progression-free survival was 10.2 months (range 0.3-21.4) and the overall survival 32.4 months. Seven hundred and eight cycles were administered (median seven per patient; range one to nine). A total of 67% of patients experienced National Cancer Institute Common Toxicity Criteria grade 3-4 neutropenia, including 8% with concomitant febrile episode, without treatment-related deaths. Ninety-three per cent of patients experienced neuropathy of grade 1 or more, including 25% with cumulative reversible peripheral neuropathy of grade 3-4. Oxaliplatin doses were reduced in 30 patients due to neurotoxicity. CONCLUSIONS: The oxaliplatin/paclitaxel combination can be administered in an outpatient setting every 3 weeks without specific measures. The high level of activity and its duration observed warrants further evaluation of this combination in pretreated platinum-sensitive advanced ovarian cancer patients.     

Behavioral problems and tobacco use among adolescents in Central America and the Dominican Republic.

OBJECTIVES: The purpose of this study was to examine the association between behavioral problems and tobacco use among adolescent students in six countries of Central America and in the Dominican Republic. METHODS: Data were drawn from a multinational collaborative study that included questionnaire surveys of between 451 and 1,170 school-attending adolescents in each of the seven countries studied. Assessments were based on an adapted, Spanish-language version of the Drug Use Screening Inventory (DUSI). The conditional form of logistic regression was employed for analysis, matching students on type of school and area, with further statistical adjustments for sex, age, and selected risk factors. RESULTS: Occurrence of tobacco use was observed to vary dramatically from country to country. Nonetheless, for the combined group of countries, the estimated odds of tobacco use in youths at the highest levels of behavioral problems was more than five times that for youths at the lowest levels, after controlling for sex, age, lack of participation in recreational activities, level of irritability, and levels of problems with school, family, and mental health. Country-specific analyses show that youths at the highest levels of behavioral problems have a consistently greater occurrence of tobacco use as compared to youths at the lowest levels of behavioral problems. CONCLUSIONS: These findings are concordant with prior studies on tobacco use among adolescents with behavioral problems. Although the magnitude of observed associations varied according to the country of residence, the strength of these associations and their significance by conventional standards were observed in nearly all the countries sampled. This is the first study in these seven countries on potentially causal relationships such as these. More research is needed to augment our knowledge regarding the observed cross-country differences and ultimately to develop, implement, and evaluate effective tobacco preventive intervention programs.     

Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura

Several reports have defined nonfamilial thrombotic thrombocytopenic purpura (TTP) as an autoimmune disorder caused by antibodies to von Willebrands factor-cleaving protease (vWF-CP). This raises the possibility that rituximab, a monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in the treatment of TTP. We report five consecutively treated patients with relapsed TTP who responded rapidly to immune suppression by rituximab at our institution. These two male and three female patients had a median age of 37 years (27–70). The median time from diagnosis to therapy was 24 months (8–60). Prior therapies included plasma exchange and corticosteroids in all cases, splenectomy (4), vincristine and aspirin (3), and azathioprine (2). The median number of plasma exchanges received prior to therapy was 59 (21–158). The cohort had a median platelet count of 48×10⁹/l (23–110), median hemoglobin of 9 g/dl (8–11), and median lactate dehydrogenase of 632 IU/l (311–945) prior to administration of rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity with detectable inhibitors in four patients. All patients attained a complete response. The median time to response after the first dose of rituximab was 5 weeks. Responses are maintained in all patients from 10 to 21 months after treatment. This report adds to the evidence that rituximab has efficacy in nonfamilial TTP and warrants further study.     

Cigarette smoking among low-income African Americans: a serious public health problem

BACKGROUND: This study examines the current prevalence of cigarette smoking and the number of cigarettes smoked in a community-based sample of 1021 low-income African-American men and women. METHODS: Participants were selected using a two-stage, area probability sample design. Data were collected in 2002-2003 in face-to-face interviews and analyzed in 2005. All data and analyses were weighted to account for the complex sampling design. RESULTS: Fifty-nine percent of men and 41% of women were current smokers, with younger individuals apparently initiating smoking at an earlier age than older individuals. CONCLUSIONS: The high prevalence of cigarette use provides further evidence that the excess burden of tobacco-related disease among low-income African-American families may be on the rise. This is of great concern, and if confirmed by further research, indicates an urgent need for preventive intervention.