Food-chain selenium and human health: spotlight on speciation

There is a growing appreciation that it is not just the total intake of dietary Se that is important to health but that the species of Se ingested may also be important. The present review attempts to catalogue what is known about Se species in foods and supplements and the health effects in which they are implicated. The biosynthetic pathways involved in Se assimilation by plants and the way in which Se species are metabolised in animals are presented in order to give an insight into the species likely to be present in plant and animal foods. Known data on the species of Se in the food chain and in food supplements are tabulated along with their concentrations and the analytical methodology used. The latter is important, since identification that is only based on retention-time matching with authentic standards must be considered as tentative: for evidence of structural confirmation, fragmentation of the molecular ion in addition to MS data is required. Bioavailability, as normally defined, is higher for organic Se species. Health effects, both beneficial and toxic, thought to be associated with specific Se species are described. Potent anti-tumour effects have been attributed to the low-molecular-weight species, Se-methyl-selenocysteine and its gamma-glutamyl-derivative, found in a number of edible plants of the Allium and Brassica families. There remain considerable gaps in our knowledge of the forms of Se that naturally occur in foods. Without adequate knowledge of Se speciation, false conclusions may be drawn when assessing Se requirements for optimal health.     

MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy

Sunitinib is a receptor tyrosine kinase inhibitor (TKI) that is front-line therapy for metastatic renal cell carcinoma (mRCC). Its antitumor activity is related to its ability to block tumor cell and tumor vasculature cell signaling via several TKI receptors (i.e. vascular endothelial growth factor receptors VEGFRs, platelet-derived growth factors (PDGFs), and stem cell factors). Sunitinib also targets myeloid derived suppressor cells (MDSCs) significantly reducing their accumulation in the peripheral blood and reversing T cell (IFNγ) suppression in both mRCC patients and in murine tumor models. This reduction in immune suppression provides a rationale for combining sunitinib with immunotherapy for the treatment of certain tumor types. Despite these encouraging findings, however, we have observed that sunitinib has variable impact at reducing MDSCs and restoring T cell function within the tumor microenvironment. Given the immunosuppressive and proangiogenic activities of MDSC, it seems plausible that their persistence may contribute to the resistance that develops in sunitinib-treated patients. While sunitinib reduced tumor infiltrating MDSCs in Renca and CT26-bearing mice, coinciding with strong to modest decreases in tumor size respectively, it was ineffective at reducing MDSCs (<35% reduction in Gr1+CD11b+) or tumor burden in 4T1-bearing mice. Persistence of intratumor MDSCs was paralleled by depressed intratumor T cell IFNγ response and increased GM-CSF expression. Additionally, in vitro and in vivo experiments showed that GM-CSF prolongs survival of MDSCs, thus protecting them from the effects of sunitinib via a pSTAT5-dependent pathway. Although preliminary, there is evidence of intratumor MDSC resistance in some mRCC patients following sunitinib treatment. Intratumor MDSC persistence and T cell IFNγ response post nephrectomy in patients receiving sunitinib in a neoadjuvant setting are being compared to RCC patients undergoing nephrectomy without prior sunitinib treatment. Tumors from untreated patients showed suppressed T cell IFNγ response along with substantial expression of MDSCs (5% of total digested cells). Thus far, tumors from 5/8 neoadjuvant patients showed persistence of intratumor MDSCs and low T cell IFNγ production post sunitinib treatment, findings that parallel results from untreated tumors. In the remaining 3 neoadjuvant patients, intratumor MDSCs were detected at low levels which coincided with a T cell IFNγ response similar to that observed with normal donor peripheral T cells. GM-CSF's role in promoting MDSC survival in patient tumors is supported by the observation that GM-CSF is produced in short-term RCC cultures at levels capable of protecting MDSCs from sunitinib-induced cell death. Additionally, persistence of MDSC also may be associated with increased expression of proangiogenic proteins, such as MMP9, MMP8, and IL-8 produced by tumor stromal cells or infiltrating MDSCs. Indeed our findings suggest that the most dominate MDSC subset in RCC patients is the neutrophilic population that produces proangiogenic proteins. We propose that the development of sunitinib resistance is partly mediated by the survival of MDSCs intratumorally, thereby providing sustained immune suppression and angiogenesis.     

Bivalirudin as an anticoagulant for simultaneous integrated coronary artery revascularization – a novel approach to an inherent concern

BACKGROUND:

Simultaneous integrated coronary artery revascularization combines coronary artery bypass surgery and percutaneous coronary intervention into a single procedure. This approach provides immediate, complete and optimal myocardial revascularization in a less invasive manner. Because simultaneous integrated coronary revascularization necessitates two distinct anticoagulation protocols for the surgical and percutaneous aspects of the procedure, combining these anticoagulation protocols carries a bleeding risk. Using a single anticoagulant to facilitate the necessities of both aspects of the integrated approach may alleviate this risk.

CASE PRESENTATION:

A 45-year-old man with an occluded left anterior descending artery and a moderately stenotic circumflex artery underwent simultaneous integrated coronary revascularization. Bivalirudin was used to achieve anticoagulation for the duration of the procedure. The patient was asymptomatic with excellent patency of both the bypass graft and the stented circumflex artery via angiography at 10 months.

CONCLUSION:

Bivalirudin can be used to effectively achieve a unified anticoagulation protocol for simultaneous integrated revascularization.     

Are we underestimating diabetes-related lower-extremity amputation rates? Results and benefits of the first prospective study

OBJECTIVE: The objective of this study was to accurately determine the incidence of lower-extremity amputation using prospective data collection and to compare the results with those obtained by retrospective methods. RESEARCH DESIGN AND METHODS: The study was carried out over a 3-year period in a large district general hospital covering a clearly defined and relatively static population. All diabetic inpatients with foot problems were identified and followed-up until discharge or death. The demographic and admission details, medical history, investigations, procedures, and history and etiology of the foot lesion were collected twice weekly by a specialist nurse and podiatrist from all relevant wards. Thus, all subjects who underwent amputation could be identified. For comparison, retrospective data were collected from the hospital coding activities database, operating theater log books, anesthetic database, and limb-fitting records. RESULTS: The total population of the region in 2000 was 337,859, of which 9,183 were known to have diabetes. The total number of amputations during the 3-year survey period was 79, of which 45 were major and 34 minor. In our local population, the mean incidence during the survey period (1997-2000) equates to 7.8/100,000 general population and 2.85/1,000 diabetic population for all amputations, 4.5/100,000 general population and 1.62/1,000 diabetic population for major amputations, and 3.3/100,000 general population and 1.23/1,000 diabetic population for minor amputations. The prospective survey detected all lower-extremity amputations identified by the various retrospective methods; however, for the reverse, this was not the case. All of the retrospective methods, including the most commonly used (ICD-9 and OPCS-4 coding), failed to detect all of the cases revealed by the prospective survey (error rate ranging from 4.2 to 90.6%), and between 4.5 and 17.4% of amputations were misclassified. CONCLUSIONS: This study demonstrates the advantages of prospective data collection as a means of determining the incidence of lower-extremity amputations and highlights the limitations of retrospective data collection methods, which underestimate the incidence. In particular, the operating theater records, which have been the gold standard for many surveys, were found to be unreliable. Moreover, we have shown a 47% reduction in the major amputations during the survey period. Thus, we recommend that a prospective audit be incorporated into the activities of the specialist foot care team as a means of assessing and improving clinical care.     

Resources for inflight medical care

With the anticipated growth of air travel, inflight illness and injury are expected to increase as well. This is because more elderly people and people with preexisting disease are taking to the air. Although inflight medical events and deaths are uncommon, physician passengers are occasionally called upon to render care. Resources for the physician may include emergency medical kits, automatic external defibrillators (AEDs), ECG monitors, portable oxygen bottles, and first-aid kits. Most airlines provide around-the-clock air-to-ground radio consultation either with their own medical department personnel or contracted medical consultants. Furthermore, some flight attendants are trained in cardiopulmonary resuscitation, first-aid, and operation of AEDs. This paper describes those inflight resources available to a physician who is called upon to treat an ill or injured passenger. In a broader sense, it is also providing advice to physicians who administer inflight medical care. The Aviation Medical Assistance Act of 1998 ("Good Samaritan act") is also discussed.     

Exploring the use of an alginate dressing for diabetic foot ulcers

Few studies have investigated the use of dressings on patients with diabetic foot ulceration. This paper reports the results of a non-comparative, two-centre study investigating the performance characteristics of SeaSorb dressing in patients with this condition. This was an exploratory study to determine the potential use of this dressing, and not a large randomised control trial. All patients had diabetic foot ulceration of 1 cm or more in diameter, classified as Wagner grade I or II, with an ankle brachial pressure index of > 0.4. The investigators carried out objective assessments including photography and ulcer tracing as well as subjective assessments of exudate levels, wound bed condition, peri-ulcer skin condition, ease of application and removal of the dressing, dressing conformability, discomfort during dressing application and removal, and clinical signs of infection. Investigators recruited 41 patients in two sites (31 in site one and 10 in site two). Of these, the findings relating to 39 patients could be evaluated. The patients were treated for a maximum of six weeks or until the ulcer healed. The study found that 28.2% (11/39) of the ulcers healed within the six-week period. Overall, there was a significant reduction in mean ulcer area from 2.8 cm 2 to 1.02 cm 2 from week 0 to week six. The relative ulcer area showed a significant decrease from 100% to 33%. For patients who experienced ulcer pain (11 patients), its intensity decreased over the six weeks. Severe maceration was not reported for any patient throughout the study. Six patients required treatment for infection. A total of 12 adverse events were reported: seven mild to moderate and five severe. None were directly attributed to the study dressing.