Dynamics of lymphatic regeneration and flow patterns after lymph node dissection.

Knowledge about the mechanisms of regeneration of the lymphatic vasculature after surgical trauma is essential for the development of strategies for the prevention and therapy of lymphedema. However, little is known about the alterations of lymphatic flow directly after surgical trauma. We investigated lymphatic function in mice using near-infrared imaging for a period of 4 weeks after surgeries that mimic sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), by removal of the popliteal lymph node (LN) alone or together with the popliteal fat pad, respectively. SLNB-like surgery did not cause changes in lymphatic drainage in the majority of cases. In contrast, lymphatic drainage impairment shown by collecting vessel rupture, dermal backflow and rerouting of lymph flow via collateral vessels were observed after ALND-like surgery. All collateral vessels drained to the inguinal LN. These results indicate that less invasive surgery prevents lymphatic decompensation. They also reveal the development and maturation of collateral lymphatic vessels after extensive surgical trauma, which reroute the flow of lymph towards a different LN. These findings might be helpful for the development of strategies to prevent and/or treat post-surgical lymphedema

Feasibility of quality of life assessment in patients with upper gastrointestinal tract cancer

Quality of life (QOL) is an important outcome after treatment for upper gastrointestinal tract cancer but few studies report good accrual and subsequent attrition is usually high. This study investigated the feasibility of a nurse-led service to obtain longitudinal QOL assessments and explored how clinical and sociodemographic factors influence patients' need for help to complete questionnaires. Fully informed patients were invited into the study. Baseline hospital assessments were scheduled by telephone and thereafter by post unless patients' health indicated the need for a home visit. In all, 128 out of 140 (91%) baseline QOL assessments were performed. Follow-up questionnaire completion was good, with 114 patients (89%) completing all but one of the expected assessments. At baseline, 41 (32%) patients required a lot of help to complete questionnaires. Patients requiring help were more likely to be undergoing palliative treatment than treatment aimed at cure (68 vs 33%; odds ratio 3.48, P < 0.01). Patients' with advanced stage cancer of the upper gastrointestinal tract receiving palliative treatment require dedicated staff to ensure good compliance with longitudinal QOL data collection. It is essential to budget for this in clinical trails. © 2003 Cancer Research UK

Assessing community perspectives of the community based education and service model at Makerere University, Uganda: a qualitative evaluation

<p>Abstract</p> <p>Background</p> <p>Community partnerships are defined as groups working together with shared goals, responsibilities, and power to improve the community. There is growing evidence that these partnerships contribute to the success and sustainability of community-based education and service programs (COBES), facilitating change in community actions and attitudes. Makerere University College of Health Sciences (MakCHS) is forging itself as a transformational institution in Uganda and the region. The College is motivated to improve the health of Ugandans through innovative responsive teaching, provision of service, and community partnerships. Evaluating the COBES program from the community perspective can assist the College in refining an innovative and useful model that has potential to improve the health of Ugandans.</p> <p>Methods</p> <p>A stratified random sample of 11 COBES sites was selected to examine the community’s perception of the program. Key Informant Interviews of 11 site tutors and 33 community members were completed. The data was manually analyzed and themes developed.</p> <p>Results</p> <p>Communities stated the students consistently engaged with them with culturally appropriate behaviour. They rated the student’s communication as very good even though translators were frequently needed. Half the community stated they received some feedback from the students, but some communities interpreted any contact after the initial visit as feedback. Communities confirmed and appreciated that the students provided a number of interventions and saw positive changes in health and health seeking behaviours. The community reflected that some programs were more sustainable than others; the projects that needed money to implement were least sustainable. The major challenges from the community included community fatigue, and poor motivation of community leaders to continue to take students without compensation.</p> <p>Conclusions</p> <p>Communities hosting Makerere students valued the students’ interventions and the COBES model. They reported witnessing health benefits of fewer cases of disease, increased health seeking behavior and sustainable healthcare programs. The evidence suggests that efforts to standardize objectives, implement structural adjustments, and invest in development of the program would yield even more productive community interactions and a healthcare workforce with public health skills needed to work in rural communities.</p

Vascular endothelial growth factor signaling requires glycine to promote angiogenesis

Peripheral vascular occlusive disease (PVOD) is a common manifestation of atherosclerosis, and it has a high rate of morbidity. Therapeutic angiogenesis would re-establish blood perfusion and rescue ischemic tissue. Vascular endothelial growth factor (VEGF) induces angiogenesis and can potentially be used to treat ischemic diseases, yet in clinical trials VEGF has not fulfilled its full potential with side effects. Whether amino acids promote angiogenesis and the molecular mechanisms are largely unknown. Here we showed that (1) Glycine significantly promoted angiogenesis both in vitro and in vivo and effectively protected mitochondrial function. (2) Activation of glycine transporter 1(GlyT1) induced by VEGF led to an increase in intracellular glycine. (3) Glycine directly bounded to voltage dependent anion channel 1 (VDAC1) on the mitochondrial outer membrane and inhibited its opening. These original results highlight glycine as a necessary mediator in VEGF signalling via the GlyT1-glycine-mTOR-VDAC1 axis pathway. Therefore, the findings in this study are of significance providing new mechanistic insights into angiogenesis and providing better understanding of glycine function in angiogenesis, which may provide valuable information for development of novel therapeutic targets for the treatment of angiogenic vascular disorders

A Rasch and factor analysis of the Functional Assessment of Cancer Therapy-General (FACT-G)

BACKGROUND: Although the Functional Assessment of Cancer Therapy – General questionnaire (FACT-G) has been validated few studies have explored the factor structure of the instrument, in particular using non-sample dependent measurement techniques, such as Rasch Models. Furthermore, few studies have explored the relationship between item fit to the Rasch Model and clinical utility. The aim of this study was to investigate the dimensionality and measurement properties of the FACT-G with Rasch Models and Factor analysis. METHODS: A factor analysis and Rasch analysis (Partial Credit Model) was carried out on the FACT-G completed by a heterogeneous sample of cancer patients (n = 465). For the Rasch analysis item fit (infit mean squares ≥ 1.30), dimensionality and item invariance were assessed. The impact of removing misfitting items on the clinical utility of the subscales and FACT-G total scale was also assessed. RESULTS: The factor analysis demonstrated a four factor structure of the FACT-G which broadly corresponded to the four subscales of the instrument. Internal consistency for these four scales was very good (Cronbach's alpha 0.72 – 0.85). The Rasch analysis demonstrated that each of the subscales and the FACT-G total scale had misfitting items (infit means square ≥ 1.30). All these scales with the exception of the Social & Family Well-being Scale (SFWB) were unidimensional. When misfitting items were removed, the effect sizes and the clinical utility of the instrument were maintained for the subscales and the total FACT-G scores. CONCLUSION: The results of the traditional factor analysis and Rasch analysis of the FACT-G broadly agreed. Caution should be exercised when utilising the Social & Family Well-being scale and further work is required to determine whether this scale is best represented by two factors. Additionally, removing misfitting items from scales should be performed alongside an assessment of the impact on clinical utility

No hypoperfusion is produced in the epicardium during application of myocardial topical negative pressure in a porcine model

ABSTRACT: BACKGROUND: Topical negative pressure (TNP), commonly used in wound therapy, has been shown to increase blood flow and stimulate angiogenesis in skeletal muscle. We have previously shown that a myocardial TNP of -50 mmHg significantly increases microvascular blood flow in the myocardium. When TPN is used in wound therapy (on skeletal and subcutaneous tissue) a zone of relative hypoperfusion is seen close to the wound edge. Hypoperfusion induced by TNP is thought to depend on tissue density, distance from the negative pressure source, and the amount negative pressure applied. When applying TNP to the myocardium, a significant, long-standing zone of hypoperfusion could theoretically cause ischemia, and negative effects on the myocardium. The current study was designed to elucidate whether hypoperfusion was produced during myocardial TNP. METHODS: Six pigs underwent median sternotomy. Laser Doppler probes were inserted horizontally into the heart muscle in the LAD area, at depths of approximately, 1-2 mm. The microvascular blood flow was measured before and after the application of a TNP. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium) and after 20 minutes of LAD occlusion (ischemic myocardium). RESULTS: A TNP of -50 mmHg induced a significant increase in microvascular blood flow in normal myocardium (**p = 0.01), while -125 mmHg did not significantly alter the microvascular blood flow. In ischemic myocardium a TNP of -50 mmHg induced a significant increase in microvascular blood flow (*p = 0.04), while -125 mmHg did not significantly alter the microvascular blood flow. CONCLUSION: No hypoperfusion could be observed in the epicardium in neither normal nor ischemic myocardium during myocardial TNP

Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers

BACKGROUND: Many breast, pancreatic, colonic and non-small-cell lung carcinoma lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we compare both antigens as a function of histological phenotype in breast, pancreatic, lung, ovarian, and prostatic cancers, including patient-matched normal, primary tumor, and metastatic breast and colonic cancer specimens. METHODS: Antigen expression was determined by immunohistochemistry (IHC) using tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N-domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3 domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining. The average score ± SD (0 = negative/8 = highest) for each histotype was recorded. RESULTS: For all tumors, the amount of CEACAM6 expressed was greater than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6 was highest in papillary > infiltrating ductal > lobular > phyllodes; in pancreatic tumors, moderately-differentiated > well-differentiated > poorly-differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes metastases > normal intestine. However, CEACAM6 expression was similar in prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon tumors found in liver was higher than in many primary colon tumors. In contrast, CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung tumors was similar to the primary tumor. CONCLUSION: CEACAM6 expression is elevated in many solid tumors, but variable as a function of histotype. Based on previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res 65: 8809–8817, 2005), it may be a promising target for antibody-based therapy