Childhood cancer in relation to infections in the community during pregnancy and around the time of birth

In a retrospective cohort study of 404,106 live births in the northern region of England, 1975-1986, we investigated whether higher levels of community infections during the mother's pregnancy and in early life were risk factors for cancer, by diagnostic group (leukaemia and non-Hodgkin's lymphoma, Hodgkin's disease, brain/spinal tumours, neuroblastoma, other tumours), diagnosed 1975-2001 under age 15 years. Logistic regression was used to relate risk to measures of community infections (measles, respiratory and other infections) in 3 prenatal and 2 postnatal quarters. There was an increased risk of Hodgkin's disease among children exposed around birth to higher levels of measles (odds ratio for trend = 2.3, 95% confidence interval 1.3-4.2, p = 0.01). For other diagnostic groups, there was no consistent evidence of an association between risk and exposure to infections. Although the significant association observed for Hodgkin's disease may be a chance finding, consequent to multiple hypothesis testing or the ecologic nature of the study, it is consistent with other recent epidemiologic results suggesting that the risk of Hodgkin's disease may be associated with exposure to infections.     

Breast cancers among very young premenopausal women (United States)

Objective: To assess risk factors for breast cancer among very young compared to older premenopausal women. Methods: Between 1990 and 1992 a population-based case–control study conducted in Atlanta, GA, Seattle/Puget Sound, WA, and central NJ interviewed 3307 premenopausal women aged 20–54 years. Logistic regression models estimated adjusted relative risks (RR) and 95% confidence intervals (CI) for each of three 10-year age groups. Results: Among the youngest age group (<35 years, n = 545), significant predictors of risk included African-American race (RR = 2.66; 95% CI 1.4–4.9) and recent use of oral contraceptives (RR = 2.26; 95% CI 1.4–3.6). Although these relationships were strongest for estrogen receptor-negative (ER–) tumors (RRs of 3.30 for race and 3.56 for recent oral contraceptive use), these associations were also apparent for young women with ER+ tumors. Delayed childbearing was a risk factor for ER+ tumors among the older premenopausal women (p _trend < 0.01), but not for women <35 years in whom early childbearing was associated with an increased risk, reflecting a short-term increase in risk immediately following a birth. Family history of early-onset breast cancer was more strongly associated with risk among women <35 years (RR = 3.22) than those 45–54 years (RR = 1.51). Risk factors for premenopausal breast cancer not significantly modified by age at diagnosis included early age at menarche, low body mass index, and heavy alcohol consumption. Conclusion: These findings suggest the possibility that women who develop breast cancers at very young ages may be etiologically as well as clinically distinct.     

A longitudinal study of the impact of childhood and adolescent physical activity experiences on adult physical activity perceptions and behaviors

The authors describe the influence of childhood and adolescent physical activity on adult physical activity attitudes and behaviors. They conducted one-on-one, semistructured, indepth interviews with 16 men and 15 women from a longitudinal growth and development study and a follow-up investigation 25 years later. They used thematic analyses to analyze the data. Three themes emerged from the men's interviews: significant others, size and maturation, and physical ability, with clear distinctions among the active, average, and inactive men. The themes transitions, body image concerns, and significant others influenced the active, average, and inactive women. Specific relationships, circumstances, and attitudes formed in childhood and adolescence influenced adult physical activity predilection and behaviors.     

An empirical comparison of EQ-5D and SF-6D in liver transplant patients

There remains disagreement about the preferred utility-based measure of health-related quality of life for use in constructing quality-adjusted life years (QALYs). The recent development of a new measure, the SF-6D, has highlighted this issue. The SF-6D and EuroQol EQ-5D measure health-related utilities on a scale where 0 represents death and 1 represents full health, and both have utility scores generated from random samples of the general UK population. This study explored whether, in a large sample of liver transplant patients, the two instruments provide similar results. The empirical data highlight important variation in the results generated from the use of the two instruments. The data are consistent with a view that the SF-6D does not describe health states at the lower end of the utility scale but is more sensitive than EQ-5D in detecting small changes towards the top of the scale.     

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.