A pilot study of a web-based physical activity motivational program for adults with physical disabilities

Purpose. Develop, deliver, and assess the efficacy of a 4-week web-based leisure-time physical activity (LTPA) motivational program based on the Transtheoretical Model and tailored to inactive adults with physical disabilities.

Method. This was a pilot-based study incorporating a true experimental design with one treatment and one control group. The intervention program was delivered on the web and was based on the constructs of the Transtheoretical Model. From the 151 individuals who completed the LTPA standardized questionnaire at baseline, 75 people participated in the 1-month post-test assessment.

Results. The results of the analysis confirmed the pretest LTPA scores as the study covariate for the post-test assessment (F (1,72) = 16.06, p = 0.001, η² = 0.18). Based on the one-way ANCOVA, there were no statistically significant differences in LTPA scores between the treatment and control groups at post-test. However, the corresponding effect size and variance explained by the treatment approached a moderate level of significance (d = 0.34 and η² = 0.04).

Conclusions. Although conclusive statements about program effectiveness cannot be secured, several 'lessons learned' from this project may be 'key factors' for program improvement. Given the pilot nature of the study and the limited resources for program development and monitoring, continued examination of such motivational materials and delivery mechanisms for people with physical disabilities appear warranted.     

Expression of inducible nitric oxide synthase in colorectal cancer and its association with prognosis

BACKGROUND: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. METHODS: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. RESULTS: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. CONCLUSIONS: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer.     

The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P<0.0001), the volume-corrected mitotic index (P<0.0001), histological grade (P<0.0001), the apoptotic index (P<0.0001), oestrogen and progesterose receptor content (P<0.0001 for both) and p53 accumulation (P=0.001). No correlation was found between Ki-67 expression and lymph node status (P=0.25), metastasis at operation (n=0.81) or tumour size (n=0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P=0.001) and in axillary-lymph-node-negative (ANN) patients (P=0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P=0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P=0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.Abbreviations M/V index the volume-corrected mitotic index - ANN axillary lymph node negative - ANP axillary lymph node positive     

Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs

OBJECTIVE: To monitor the concentration of markers of cartilage and synovium metabolism in the knee (stifle) joint synovial fluid of young beagles subjected to immobilisation and subsequent remobilisation. METHODS: The right hind limb of 17 dogs was immobilised in flexion for 11 weeks. Simultaneously, the contralateral left knee was exposed to increased weight bearing. The remobilisation period lasted 50 weeks. Litter mates served as controls. The concentration in joint lavage fluid of interleukin 1alpha (IL1alpha) was measured by immunoassay, the activity of phospholipase A(2) (PLA(2)) was determined by an extraction method, chondroitin sulphate (CS) concentration by precipitation with Alcian blue, hyaluronan (HA) by an ELISA-like assay using biotinylated HA-binding complexes, matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinases 1 (TIMP-1) by sandwich ELISA, and synovitis was scored by light microscopy. RESULTS: Synovitis or effusion was absent in all experimental and control groups. Immobilisation decreased the joint lavage fluid levels of IL1alpha (p<0.05), TIMP (p< 0.05), and the concentration of CS down to 38% (p<0.05) in comparison with untreated litter mates with normal weight bearing. Immobilisation did not affect the activity of PLA(2), or the concentration of MMP-3 or HA in synovial fluid. Joint remobilisation restored the decreased concentrations of markers to control levels. Increased weight bearing did not change the concentrations of markers in comparison with the control joints with normal weight bearing. CONCLUSIONS: 11 weeks' joint immobilisation decreased the concentration of markers of cartilage and synovium metabolism in the synovial fluid, and remobilisation restored the concentrations to control levels. The changes in joint metabolism induced by immobilisation, as reflected by the markers, are thus different from those found in osteoarthritis, where increased levels of these markers are associated with enhanced degradation and synthesis. These findings suggest that the change induced in joint metabolism by immobilisation is reversible in its early stages.     

PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2

Background:

Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version (Predict+), and to compare its performance with the original Predict and Adjuvant!.

Methods:

The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict+, Predict and Adjuvant! were compared with observed outcomes.

Results:

All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvant!. In the subset of patients with HER2-positive tumours, Predict+ performed substantially better than the other two models for both OS and BCSS.

Conclusion:

Predict+ is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients.     

Combined respiratory effects of cold air with SO(2) or NO(2) in single 1-hour exposures of hyperventilating guinea pigs

The present study is a continuation of our previous experiments on repeated 10-min exposures of anesthetized, mechanically ventilated guinea pigs to clean cold dry air (H?linen et al., 2000a), and to cold air plus gaseous air pollutants (H?linen et al., 2000b). This time we made continuous 60-min exposures to clean cold dry air, cold air + SO(2) at 1 ppm, cold air + NO(2) at 1 ppm, and warm humid air + NO(2) at 1 ppm, and focused on responses at 10-60 min. Clean cold dry air and cold air + pollutants (n = 8-9 in each group) produced similar cooling in the guinea pig lower respiratory tract. The decreases in intratracheal temperature (T(tr)) reached a plateau at 20 min with mean maximal decreases of 9.7-11.3 degrees C from the pre-exposure control values of 36.0-37.3 degrees C. In contrast, there were progressive decreases in esophageal temperature (T(oe)) during the exposures, indicating constant conductive and evaporative heat losses from the tracheobronchial tissues. The mean maximal decreases in T(oe) were 1.2-1.4 degrees C from the preexposure control values of 37.8-38.0 degrees C. Clean cold dry air induced 4. 5-10.8% mean decreases in peak expiratory flow (PEF) at 10-60 min of exposure, which were statistically nonsignificant due to a relatively large variation between animals. Cold air + SO(2) at 1 ppm induced a mean decrease of 11.4% in PEF at 10 min (p <.05), which was spontaneously abolished during the next 10 min of exposure. Cold air + NO(2) at 1 ppm caused no decrease, but in fact small, nonsignificant increases in PEF at 30-60 min of exposure. Cold air + NO(2) at 1 ppm, and to some extent also cold air + SO(2) at 1 ppm, attenuated significantly the mechanical ventilation induced gradual decrease in tidal volume (V(T)), when compared to clean cold dry air exposure. Cold air + NO(2) at 1 ppm, but not warm humid air + NO(2) at 1 ppm, increased significantly the proportion of macrophages in the differential count of bronchoalveolar lavage fluid (BALF) white cells when compared to both clean warm humid air and cold dry air. None of the exposure conditions caused morphological or inflammatory changes in the respiratory tissues. In conclusion, continuous 60-min exposures to clean cold dry air, cold air + SO(2), and cold air + NO(2) produced weaker functional effects on the lower respiratory tract of guinea pigs than our previous consecutive 10-min exposures to these air conditions. After the first 10 min, there was a strong attenuation of the bronchoconstrictor responses, especially to cold air + NO(2) at 1 ppm. The small airway effects of prolonged mechanical ventilation were significantly modified by NO(2) at 1 ppm in both cold dry and warm humid breathing air. Finally, cold air + NO(2) at 1 ppm increased the proportion of macrophages in BALF white cells.     

Mouse Subrenal Capsule Assay Chemosensitivity and DNA Flow Cytometry Parameters of Human Melanoma Metastases

Chemosensitivity was analyzed by mouse subrenal capsule assay (SRCA) in 103 human melanoma metastases 79 of which were also analyzed by DNA flow cytometry. The most effective combination was dacarbazine, vincristine, and carmustine (DOB), followed by cisplatin plus etoposide (Plat-VP16). By the original criteria of the assay, 35% of tumors were sensitive to DOB treatment while 15% responded to Plat-VP16. Chemosensitivity of DNA diploid and aneuploid tumors showed no significant difference; 35% of the aneuploid tumors were sensitive to DOB and 19% to Plat-VP16, whereas 41% and 13% respectively of the diploid tumors were sensitive. An association between DNA index and chemosensitivity was observed. Growth of the implant was observed in 44% of tumors with a DNA index above 1.5 receiving DOB treatment, whereas only 12% of tumors with an aneuploid DNA index ≤1.5 grew. No significant difference was observed in the SPF of chemotherapy sensitive and insensitive tumors, though a tendency to lower SPF was observed in sensitive tumors.