A Comparison of Current Practice in School-Based Substance Use Prevention Programs with Meta-Analysis Findings

The series of seminal meta-analytic studies of school-based substance use prevention program studies conducted by the late Nancy S. Tobler and colleagues concluded that programs with content focused on social influences' knowledge, drug refusal skills, and generic competency skills and that use participatory or interactive teaching strategies were more effective than programs focused on knowledge and attitudes and favoring traditional didactic instruction. The present study compared current school practice against evidence-based standards for effective content and effective delivery, derived from the Tobler findings. Respondents were the lead staff who taught substance use prevention in the 1998–1999 school year in a national sample of public and private schools that included middle school grades (N = 1,795). Results indicate that most providers (62.25%) taught effective content, but few used effective delivery (17.44%), and fewer still used both effective content and delivery (14.23%). Those who taught an evidence-based program (e.g., Life Skills Training, Project ALERT), however, were more likely to implement both effective content and delivery, as were those teachers who were recently trained in substance use prevention and were comfortable using interactive teaching methods. The findings indicate that the transfer to practice of research knowledge about school-based substance use prevention programming has been limited.     

Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells

Following observations that curcumin inhibited proliferation (IC(50)=1-5 microM), invasiveness and progression through S/G2/M phases of the cell cycle in the non-tumourigenic HBL100 and tumourigenic MDA-MB-468 human breast cell lines, it was noted that apoptosis was much more pronounced in the tumour line. Therefore, the ability of curcumin to modulate signalling pathways which might contribute to cell survival was investigated. After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines. At a lower dose (10 microM), it also inhibited the ability of anisomycin to activate JNK, resulting in decreased c-jun phosphorylation, although it did not inhibit JNK activity directly. In contrast, the activation of p38 mitogen activated protein kinase (MAPK) by anisomycin was not inhibited. Curcumin inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells. The MAPK kinase (MKK) inhibitor U0126 (10 microM), while preventing ERK phosphorylation in MDA-MB-468 cells, did not induce apoptosis. The PI3K inhibitor LY294002 (50 microM) inhibited PKB phosphorylation in both cells lines, but only induced apoptosis in the MDA-MB-468 line. These results suggest that while curcumin has several different molecular targets within the MAPK and PI3K/PKB signalling pathways that could contribute to inhibition of proliferation and induction of apoptosis, inhibition of basal activity of Akt/PKB, but not ERK, may facilitate apoptosis in the tumour cell line.     

Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat

Rationale. A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. However, the neurochemical rationale behind this strategy needs to be further clarified. Objectives. We examined the effect of chronic citalopram and subchronic lithium, alone or in combination, on (a) serum levels of citalopram and lithium, (b) animal behaviour and (c) hippocampal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. Furthermore, we examined the serum level of citalopram and hippocampal 5-HT following one acute citalopram injection. Methods. Microdialysis in the freely moving animals was used to determine hippocampal 5-HT and 5-HIAA. The animal behaviour was examined in the open field and forced swim test. Results. We found that chronic administration of citalopram (20 mg/kg/24 h s.c.) significantly increased the 5-HT baseline relative to vehicle-treated rats. Addition of subchronic lithium (60 mmol/kg chow pellet p.o.) to chronic citalopram therapy further elevated the 5-HT levels. Moreover, we found acute citalopram (5 mg/kg s.c.) to increase the 5-HT level. The immobility time in the FST and the locomotion in the OF were unaffected by any treatments. Conclusions. The present results support the assumption that increases in hippocampal 5-HT neurotransmission may be important in the augmentatory effect of lithium. Electronic Publication     

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

Background

We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints.

Methods

From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125).

Results

The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9–12.8 months).

Conclusion

The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centres.     

Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

Background

Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines.

Methods

Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO₂ from¹⁴C-labelled substrate, and polyamine levels were measured by HPLC.

Results

I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G₂/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration.

Conclusion

While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation of spermine may cause cytotoxicity and contribute to cell death. The precise mechanism by which putrescine enhances the growth inhibitory effect of the agent remains to be elucidated, but does result in cells undergoing necrosis, possibly following accumulation in the G₂/M phase of the cell cycle.     

Asthma in children: Management practices among paediatricians and family physicians

OBJECTIVE:

To ascertain the variation in asthma management practices among paediatricians and family physicians to determine how to improve care.

DESIGN:

Questionnaire study of paediatricians and family physicians that focused on the use of beta₂-agonists, inhaled corticosteroids, patient asthma education, quantitative measurements of airflow and diagnostic investigations for asthma. Case scenarios were used in the questionnaire.

RESULTS:

The response rate was 66% (415 of 632) among paediatricians and 42% (1156 of 2750) among family physicians. In general, both groups followed consensus guidelines. There were some differences in management practices among paediatricians and family physicians. Paediatricians were more likely to develop an action plan and less likely to use xanthines or inhaled anticholinergic agents. However, family physicians were more likely to use spirometry or home peak expiratory flow rates to make a diagnosis of asthma.

CONCLUSION:

Family physicians and paediatricians require a different focus on educational interventions to improve the care of children with asthma.     

Nitric oxide metabolites are not reduced in exhaled breath condensate of patients with primary ciliary dyskinesia

STUDY OBJECTIVES: To investigate whether nitric oxide (NO) metabolites would be reduced in children affected by primary ciliary dyskinesia (PCD). DESIGN: Single-center observational study. PATIENTS: Fifteen children with PCD (seven boys; mean [+/- SEM] age, 10.3 +/- 0.7 years; mean FEV(1), 73 +/- 2.1% predicted) were recruited along with 14 healthy age-matched subjects (seven boys; mean age, 11.5 +/- 0.4 years; mean FEV(1), 103 +/- 5% predicted). INTERVENTIONS: We assessed the levels of nitrite (NO(2)(-)), NO(2)(-)/NO(3)(-) (NO(2)(-)/NO(3)(-)), and S-nitrosothiol in exhaled breath condensate, exhaled NO, and nasal NO from children with PCD compared to those in healthy children. MEASUREMENTS AND RESULTS: The mean exhaled and nasal NO levels were markedly decreased in children with PCD compared to those without PCD (3.2 +/- 0.2 vs 8.5 +/- 0.9 parts per billion [ppb], respectively [p < 0.0001]; 59.6 +/- 12.2 vs 505.5 +/- 66.8 ppb, respectively [p < 0.001]). Despite the lower levels of exhaled NO in children with PCD, no differences were found in the mean levels of NO(2)(-) (2.9 +/- 0.4 vs 3.5 +/- 0.3 microM, respectively), NO(2)(-)/NO(3)(-) (35.2 +/- 5.0 vs 34.3 +/- 4.5 microM, respectively), or S-nitrosothiol (1.0 +/- 0.2 vs 0.6 +/- 0.1 microM, respectively) between children with PCD and healthy subjects. CONCLUSION: These findings suggest that NO synthase activity may not be decreased as much as might be expected on the basis of low exhaled and nasal NO levels.     

Molecular cytogenetic aberrations in autosomal dominant polycystic kidney disease tissue

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder characterized by focal cyst formation from any part of the nephron. The molecular bases include germinal mutation of either PKD1 or PKD2 genes, enhanced expression of several protooncogenes, alteration of the TGF-alpha/EGF/EGF receptor (EGFR) axis, and disturbed regulation of proliferative/apoptosis pathways. To identify new locations of ADPKD related oncogenes and/or tumor suppressor genes (TSG), comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analyses were performed for a series of individual cysts (n = 24) from eight polycystic kidneys. By CGH, imbalances were detected predominantly on chromosomes 1p, 9q, 16p, 19, and 22q in all tissues. DNA copy number gain was seen on chromosomes 3q and 4q in five samples. The CGH data were supplemented by LOH analysis using 83 polymorphic microsatellite markers distributed along chromosomes 1, 9, 16, 19, and 22. The highest frequency of LOH was found on the 1p35-36 and 16p13.3 segments in cysts from seven samples. Allelic losses on 9q were detected in six, whereas deletions at 19p13 and 22q11 bands were observed in three polycystic kidneys. These results indicate that the deleted chromosomal regions may contain genes important in ADPKD initiation and progression.     

Canadian Society of Plastic Surgeons Société Canadienne des Chirurgiens Plasticiens: Abstracts presented at the 57th Annual Meeting/57e Réunion annuelle June 25–28 juin,Whistler, British Columbia

INTRODUCTION:

Perforator flaps are increasingly indicated for the often problematic coverage of soft tissue defects in the leg. Knowledge of the vascular supply of the skin is helpful in selecting free or pedicled flaps based on perforator vessels. The objective of this study was to document the vascular supply to the skin of the leg with reference to diameter, pedicle length, location and area supplied by perforator vessels.

METHODS:

A series of 15 fresh human cadavers were injected with the modified lead oxide and gelatin technique. The skin was meticulously dissected preserving all perforators ≥ 0.5 mm in diameter) and their source vessels carefully noting its course through the septa or muscle. Angiograms of the skin were studied and the vascular territory of the source vessels was calculated.

RESULTS:

Seven vascular territories supplied the leg skin. The average number of perforators, percentage of total skin area of the leg supplied, ratio of musculocutaneous to septocutaneous perforators, average diameter (mm), and area supplied (cm²) by each vessel was: Inferior medial genicular [2.4, 6.8%, 3:7, 0.62, 83.2]; Inferior lateral genicular [2.0, 5.3%, 0:1, 0.58, 104]; Descending genicular [6.4, 19.8%, 1:1, 0.84, 254]; Popliteal [4.8, 12.3%, 1:9, 0.87, 280.6]; Posterior Tibial [17.8, 20.8%, 4:1, 0.69, 331]; Anterior Tibial [8.8, 10.0%;4:1;0.60;190.4]; Peroneal [9.8, 11.5%, 7:3, 0.84, 209]. Total number of perforators in the leg was 48 ± 13. The average diameter of the perforators was 0.71 mm.

CONCLUSION:

The cutaneous blood supply was studied and perforating vessels from each source artery described. Large perforator vessels supplying the skin were found in each territory that could be used as potential perforator flaps. This study provides a blueprint of the vascular anatomy of the leg that may be useful for preoperative planning of pedicled and/or free skin flaps.

• Can J Plast Surg. 2003 Summer; 11(2): 95–115.
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• 02: The Effect of Tension on End-To-End Nerve Repair

Can J Plast Surg. 2003 Summer; 11(2): 95.

02: The Effect of Tension on End-To-End Nerve Repair

IRP Sunderland, J Singham, M Brenner, and SE Mackinnon Copyright and License information DisclaimerCopyright © 2003, Pulsus Group Inc. All rights reserved     

Microglia density decreases with age in a mouse model of Huntington's disease

Huntington's disease (HD) is characterized by selective neuronal loss and reactive gliosis. In the R6/2 transgenic HD mouse model, there is no selective cell loss, although astrocytosis has been reported. Since there have been no previous studies on microglia in this model, we have undertaken a detailed investigation of microglia in six different forebrain regions in the R6/2 mouse and their wild-type littermates at two time points. Microglia were identified using the histochemical marker isolectin B4 and interactions of genotype, region, and age were analyzed. Results showed that there was a significant decrease in the number of microglia with age in both wild-type and R6/2 brains, which was more pronounced in the transgenic mouse. There were also morphological changes with age observed in both genotypes. As early as 7 weeks of age, structural microglial abnormalities could be seen in R6/2 brains, including bulbous swellings and long stringy processes; comparable changes were seen at 16 weeks in wild-type brains. At 14.5 weeks, microglia in R6/2 mouse brains were smaller in size with condensed nuclei and fragmentation of their processes. We suggest that the density and morphology of microglia change with normal aging and that this process is accelerated in R6/2 brains. Such changes in the dynamic status of microglia may lead to an impairment of their neurosupportive functions. Further studies are needed to understand better the role of microglia in aging and neurodegeneration.