The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells.

The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.

Influences on decision for mastectomy in patients eligible for breast conserving surgery.

Increasing emphasis is being placed on low mastectomy rates. Our objective was to investigate factors influencing rates of mastectomy and breast conserving surgery. A group of 171 patients (27%) who could have had breast conserving surgery (BCS) but chose mastectomy was identified as well as all patients who underwent BCS over a 6 year period. A questionnaire asking patient's attitudes to factors which could influence their choice of operation was compiled and sent to this study group. Results showed surgical advice to be the most important factor, with significantly more influence in BCS patients. No significant difference was found in distance to treatment between the groups. Shorter duration radiotherapy would have made 47% of mastectomy patients more likely to accept BCS. BCS rates are a poor measure of quality of patient care. More emphasis should be put on choices offered to patients rather than overall uptake of a specific choice.

"Covering our backs": ambulance crews' attitudes towards clinical documentation when emergency (999) patients are not conveyed to hospital.

BACKGROUND: Up to 30% of people who call for an emergency ambulance are, for various reasons, not conveyed to hospital. Across the UK, the majority of ambulance services have policies and procedures requiring ambulance crews to complete clinical documentation for these patients, as they do for patients who travel to hospital. However, studies have suggested that documentation does not get completed for a large proportion of non-conveyed patients. METHODS: A qualitative study in one large ambulance service trust used focus groups to explore crew members' attitudes towards clinical documentation and non-conveyed patients. RESULTS: Considerable ambiguity was found: crews were aware of the need to "cover their backs" by completing clinical records, but at the same time expressed doubts about the value of this documentation. There appeared to be two main circumstances in which records were not completed. Firstly, there were the cases where crews may have been unable to obtain necessary information from patients who were intoxicated or otherwise uncooperative. Secondly, there were cases where the crews may not have recognised their encounter with a patient as having a clinical dimension, such as older people who had fallen but were apparently uninjured. These circumstances were combined with a lack of monitoring by managers of whether forms were being completed, and a disinclination on the part of some crew members to do what they regarded as unnecessary work. CONCLUSION: The low rates of completion of clinical records for non-conveyed patients appeared to result from crew members not believing they were important in every circumstance, combined with a lack of management focus. Low rates of completion may lead in turn to clinical risk and a risk of litigation if things go wrong.

Tuberculosis screening in migrants in selected European countries shows wide disparities.

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35 yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

HIV seroprevalence by anonymous testing in patients with Mycobacterium tuberculosis and in tuberculosis contacts.

Having witnessed a large increase in Mycobacterium tuberculosis notifications in south London, we wanted to ascertain the prevalence of HIV and tuberculosis co-infection in our patients. All patients with tuberculosis and their contacts were anonymously tested for HIV in blood and saliva, respectively. 11.4% of patients (from various demographic groups) with tuberculosis who attend chest clinics in south London are HIV positive. In addition, 5% of individuals seen in the tuberculosis contact screening clinics and 4% new entrants are HIV positive. All patients with Mycobacterium tuberculosis, irrespective of background, should be urged to have an HIV test.

The impact of ethanol and Marinol/marijuana usage on HIV+/AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytidine, or dideoxyinosine therapy.

Therapeutic observations suggest that azidothymidine (AZT)-resistant HIV+/AIDS patients are frequently offered AZT/dideoxycytidine (DDC) or dideoxyinosine (DDI) therapy. The latter therapies have been associated with the development of acute pancreatitis. During the initial portion of this study, when patients reported limiting ethanol consumption, an increase in CD4+, a decrease in amylase, and a decrease in lipase was observed in patients on DDI monotherapy. Marinol/marijuana usage was associated with depressed CD4+ counts and elevated amylase levels within the DDI subgroup. The purpose of this study was to follow these patients over 1 year and compare clinical indicators of pancreatitis and HIV progression. After 1 year, the remaining 56 patients were reexamined in the follow-up portion for clinical indicators of HIV disease progression and pancreatoxic/hepatotoxic effects. Those in the AZT group, who remained on this therapy throughout the year, had significantly increased amylase values from 55.3 to 69.3 IU/liter (p < 0.05). In the AZT/DDC group, those who remained on combination therapy throughout the year, 4 of the 5 clinical indicators of disease progression changed. Amylase, ALT, and AST all increased significantly from 55.2 to 77.8 IU/liter (p < 0.01), from 38.0 to 92.3 IU/liter (p < 0.05), and from 55.2 to 97.0 IU/liter (p < 0.05), respectively. Lipase levels decreased significantly (106.0 to 74.6 IU/liter, p < 0.05). The most remarkable changes occurred in the AZT/DDC group (who reduced ethanol consumption), wherein clinical indicators of pancreatitis and liver dysfunction declined, including amylase (65.0 to 20.0 IU/liter, p < 0.05), ALT (350.0 to 100.0 IU/liter, p < 0.01), and AST (240.0 to 95.0 IU/liter, p < 0.01). No significant changes were noted in the DDI or AZT groups. Marinol/marijuana use was associated with declining health status in both the AZT and AZT/DDC groups. In contrast, all clinical indicators of pancreatitis improved in the DDI patients who utilized Marinol/marijuana, including amylase (-34%), lipase (-30.8%), ALT (-21.4%), and AST (-20.1%). This paired follow-up study suggests that HIV+/AIDS patients on antiretroviral therapies should restrict their ethanol consumption. In HIV+/AIDS patients with the lowest CD4+ counts (those on DDI monotherapy), utilization of Marinol/marijuana does not seem to have a deleterious impact.

Cataract and corneal opacity are the main causes of blindness in the Samburu tribe of Kenya.

An ocular status survey of the Samburu tribe of Kenya was carried out. There were 844 survey members in an age and sex stratified cluster sample. The prevalence of those who were found to have moderate visual loss or worse (less than 20/60 [6/18] in the better eye) was 3.8%. Those blind by USA criteria represented 1.7% of the total population. The two principal causes of blindness, cataract and corneal opacity, are both surgically amenable. A description of the Samburu people, the survey methods, and a summary of the survey findings are included.

Appropriate ophthalmic surgical technology in developing nations.

Ophthalmologists working in developing nations are faced with shortages in surgical equipment and expendable supplies. Invention and improvisation can extend financial resources and reduce the unit cost per operation. Examples of appropriate ophthalmic technological invention are described and illustrated.