Optimization of radiation controlled gene expression by adenoviral vectors in vitro

The radiation-inducible EGR-1-promoter has been used in different gene therapy approaches in order to enhance and locally restrict therapeutic efficacy. The aim of this study was to reduce nonspecific gene expression in the absence of irradiation (IR) in an adenoviral vector. Rat rhabdomyosarcoma R1H tumor cells were infected with adenoviral vectors expressing either EGFP or HSV-TK under control of the murine EGR-1 promoter/enhancer. Cells were irradiated at 0-6 Gy. Gene expression was determined by FACS-analysis (EGFP), or crystal violet staining (HSV-TK). The bovine growth hormone polyadenylation signal (BGH pA) was used as insulating sequence and was introduced upstream or upstream and downstream of the expression cassette. Infected R1H cells displayed IR dose-dependent EGFP expression. Cells treated with IR, AdEGR.TK and ganciclovir displayed a survival of 17.3% (6 Gy). However, significant gene expression was observed in the absence of IR with EGR.TK and EGR.EGFP constructs. Introduction of BGHpA upstream or upstream and downstream of expression cassette resulted in decreased nonspecific cytotoxicity by a factor of 1.6-2.3 with minor influence on the induced level of cytotoxicity. Introduction of insulating sequences in adenoviral vectors might allow tighter temporospatial control of gene expression by the radiation-inducible EGR-1 promoter.     

Understanding locally advanced breast cancer: what influences a woman's decision to delay treatment?

BACKGROUND: Despite early detection having been identified as a key factor in long-term survival of patients with breast cancer, women with locally advanced breast cancer continued to present at many medical centers. METHODS: Women with locally advanced breast cancer (LABC) (N = 11) and matched controls (N = 11) with Stage I or II breast cancer completed semi-structured interviews and the Hospital Anxiety and Depression Scale, Life Orientation Test, Multidimensional Health Locus of Control Scale, Body Investment Scale, Monitor-Blunter Style Scale, and Religious Coping Scale. Five spouses of the LABC group and eight control partners were similarly assessed. RESULTS: On psychological tests, no significant differences were found between patient groups; however, LABC spouses reported significantly greater active religious surrender (t = 2.37, P = 0.037) and depression (t = 3.54, P = 0.047) than control spouses. The women's semi-structured interviews identified that LABC was associated with inattention to routine breast cancer screening, denial, fatalism and reliance on alternative therapies. Spouses of the LABC group tended to be more passive in their wives' medical care, and also utilized fatalistic thinking and denial. CONCLUSIONS: It is important for health care providers to identify patients who will require extra encouragement to seek timely medical care and to follow through with treatment recommendations.     

Diet and biomarkers of oxidative damage in women previously treated for breast cancer

This study sought to evaluate the relationship between dietary intake of fat, polyunsaturated fat, saturated fat, arachidonic acid, and selected dietary antioxidants and levels of oxidative damage as measured by urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epi-prostaglandin F2alpha (8-iso-PGF2alpha) in women previously treated for breast cancer. Two hundred two study subjects participating in the Women's Healthy Eating and Living (WHEL) study were included in this ancillary study. Dietary intakes and concentrations of urinary 8-OHdG and 8-iso-PGF2alpha were measured at baseline and 12 mo in the 179 women included in the analytical cohort. Study subjects demonstrated a significant reduction in dietary total, polyunsaturated, and saturated fat intake and a significant increase in vitamins E and C and beta-carotene intake from baseline to 12 mo. Linear mixed-models analysis using baseline and Year 1 data indicated that vitamin E intake was inversely associated with both 8-OHdG and 8-iso-PGF2alpha. 8-Iso-PGF2alpha is increased with increased body mass index (BMI) and polyunsaturated fatty acid (PUFA) intake, indicating an increase in lipid peroxidation with greater BMI and higher PUFA intake. 8-OHdG was inversely related to age but positively related to arachidonic acid, indicating an increase in DNA damage with higher intake of arachidonic acid (meat). The results of this nested case-controlled study provide potential mechanisms by which a high fruit and vegetable, low-fat diet might reduce the recurrence rate of or early-stage breast cancer.     

Association of adult celiac disease with surgical abdominal pain: a case-control study in patients referred to secondary care

BACKGROUND: Acute abdominal pain is the most common indication for surgical admission. Nonspecific abdominal pain (NSAP) may account for up to 40% of cases. There has been no published prospective study in which adult patients presenting with acute abdominal pain are investigated for celiac disease. AIMS: We aimed to assess the association of celiac disease with surgical abdominal pain. PATIENTS AND METHODS: A case-control study was undertaken involving 300 consecutive new unselected patients presenting with acute abdominal pain (in a university hospital) and healthy controls (age and sex matched) without abdominal pain (n = 300). Initial investigations for celiac disease were immunoglobulins, IgA/IgG anti-gliadin (AGA), and endomysial antibodies (EMA). Any patient with a positive IgA AGA, EMA, or only IgG AGA in the presence of IgA deficiency was offered a small bowel biopsy to confirm the diagnosis. RESULTS:: There were 33 patients with abdominal pain who had positive antibodies, of whom 9 had histologically confirmed celiac disease (6 EMA positive; 3 EMA negative). One antibody positive patient (EMA in isolation) declined duodenal biopsy and the remaining 23 had normal duodenal mucosa. Within the control group, there were 2 cases of celiac disease. Compared with matched controls the association of acute abdominal pain with celiac disease gave an odds ratio 4.6. (P = 0.068, 95% confidence interval, 1.11-19.05). When only considering NSAP the prevalence of celiac disease was highly significant at 10.5% (9 of 86, P = 0.006). Patients' symptoms improved on a gluten-free diet at 12- to 18-month follow-up. CONCLUSION: Celiac disease was diagnosed in 3% of patients who presented with unselected acute abdominal pain to secondary care. Targeting patients who have NSAP or celiac associated symptoms/diseases may improve the diagnostic yield.     

Musculoskeletal disorders among full-time homemakers in poor communities

OBJECTIVE: To examine factors associated with self-reported musculoskeletal disorders (MSD) among full-time female homemakers. METHODS: Data on socio-demographic characteristics, lifestyle and health were collected on 1266 married women aged 15-59 years living in poor suburbs in the outskirts of Beirut, Lebanon. Independent associations with MSD of factors and characteristics were examined using odds ratios (ORs) derived from multiple logistic regression. RESULTS: Women's age, weight, and number of children were significantly, positively, independently associated with self-reported MSD, while women's conduct of specific household tasks were not. Women with MSD were more likely to be stressed than women without MSD (OR = 1.5). CONCLUSION: A major finding of this study was the positive association between distress and musculoskeletal disorders. The measures used to assess women's involvement in housework did not account for the duration of time spent performing each household task. Better measures of domestic labor, including housework and childcare, are required to understand better their impact on the health of full-time homemakers and on MSD in particular. Intervention programs to alleviate MSD in full-time homemakers should address psychosocial factors.     

Relapsing polychondritis studied by computed tomography

Computed tomographic findings in a patient with relapsing polychondritis are described. Collapse of the cartilage of the nose and calcification in cartilages of the ears were clearly demonstrated. CT scanning was also helpful in evaluating the tracheobronchial tree for airway compromise, which could prove fatal in this condition.