Hemoglobin loss from erythrocytes in vivo results from spleen-facilitated vesiculation

Previous studies have shown that approximately 20% of hemoglobin is lost from circulating red blood cells (RBCs), mainly during the second half of the cells' life span. Because hemoglobin-containing vesicles are known to circulate in plasma, these vesicles were isolated. Flow cytometry studies showed that most RBC-derived vesicles contain hemoglobin with all hemoglobin components present. The hemoglobin composition of the vesicles resembled that of old RBCs. RBC cohort studies using isotope-labeled glycine have been described, which showed a continuous presence of this label in hemoglobin degradation products. The label concentration of these products increased during the second half of the RBC life span, accompanied by a decrease within the RBC. It is concluded that the hemoglobin loss from circulating RBCs of all ages can be explained by shedding hemoglobin-containing vesicles. This loss occurs predominantly in older RBCs. Apparently the spleen facilitates this process since asplenia vesicle retention within RBCs of all ages has been described, accompanied by an increase in the percentage of total HbA(1). The present study shows that in old RBCs of asplenic individuals, the decrease of hemoglobin content per cell such as seen in old RBCs of control individuals is absent due to an increase in the absolute amount of HbA(1c) and HbA(1e2). It is concluded that hemoglobin-containing vesicles within old RBCs are "pitted" by the spleen.     

Centenary of the Health Council of the Netherlands. VI. Coordination mechanisms and the authority of the Health Council of the Netherlands

What do scientific advisory boards such as the Health Council of the Netherlands get their authority from? How does the Council ensure that its advice is incorporated into policy and into the practices at which the advice is directed? A frequently heard answer to this question is: by describing 'the state of knowledge' as optimally as possible. However, case studies on advisory work by the Health Council have shown that this explanation is too simplistic. It is more likely that the explanation lies in the use of 'co-ordination tools'--such as problem definition, the committee process and a specific use of language--that enable the Council to both separate and bridge science and policy. The authority of the Council is based on the hybrid nature of its work.     

Memory Complaints in Medically Refractory Epilepsy: Relationship to Epilepsy-Related Factors

This study reports the results of a multicenter study on memory complaints in 252 patients with epilepsy who presented with subjective complaints about memory problems in daily life. Memory complaints were measured with a standardized memory questionnaire (GKLE). The main purpose was to analyze the type of memory complaints and to examine the relationship between subjective complaints and several epilepsy-related factors. These include seizure type, lateralization and location of the focus, etiology, duration, age at onset, and antiepileptic medication. As expected patients experienced significantly more memory complaints. In particular, patients of older age and higher intelligence level complained more about their memory functioning. Although the clinical significance is marginal, neuroticism showed a significant relationship to the total complaint score. The total amount of subjective complaints is not related to the localization or lateralization of the epileptic disturbances. Patients with a longer duration of epilepsy complained significantly more about memory problems, especially about retrieving information from memory. All other epilepsy-related factors showed no relationship to memory complaints.     

The matrix metalloproteinase inhibitor BB-94 improves the strength of intestinal anastomoses in the rat

BACKGROUND AND AIMS: The strength of intestinal anastomoses is relatively low in the first days after operation, possibly as a result of localized degradation of the supporting matrix by enzymes from the matrix metalloproteinase (MMP) family. This study examined whether BB-94, a broad spectrum inhibitor of MMP activity, could enhance anastomotic strength. MATERIALS AND METHODS: Male Wistar rats received anastomoses in both ileum and colon. From the day before operation onwards, animals were treated daily with BB-94 intraperitoneally at a dose of 30 mg/kg or with saline only. Rats were killed 1, 3, or 7 days after operation, and anastomotic bursting pressure and breaking strength were measured. On day 3 anastomotic hydroxyproline levels were measured, and MMP (gelatinase) activity was analyzed by gelatin zymography. RESULTS: BB-94 strongly enhanced wound strength, but only on day 3, when it was at its lowest. Daily administration increased median colonic and ileal breaking strength by 27% and 108%, respectively; colonic and ileal bursting pressure were increased by 54% and 58%, respectively. MMP activities were significantly lowered in anastomotic extracts from the rats treated with BB-94.CONCLUSION: Administration of BB-94 enhances anastomotic strength. Specific inhibition of MMP activity should be investigated further as a means to preserve anastomotic integrity.     

Moderate alcohol consumption is associated with lower risk for incident diabetes and mortality: the Hoorn Study

In the present study we examined the association between baseline alcohol consumption and 10-year mortality in subjects with normal and abnormal glucose levels (diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)). Furthermore, we assessed the 6-year cumulative incidence of diabetes in categories of alcohol consumption. In the Hoorn Study, which started in 1989, alcohol intake was assessed by questionnaire in 2393 subjects who were subsequently categorised into four groups of alcohol consumption (non-drinkers, up to 10 g per day, 10-30 and >or=30 g per day). Glucose tolerance status by oral glucose tolerance test was classified according to the WHO-1999 diagnostic criteria. Subjects who drank up to 10 g per day of alcohol had the lowest mortality risk. The age- and sex-adjusted mortality risks for non-drinkers were 1.55 (1.04-2.32) for subjects with normal glucose levels and 1.72 (1.05-2.82) for subjects with abnormal glucose levels. The risk of diabetes was also lowest for subjects who consumed up to 10 g per day: 8.0 versus 12.9% for non-drinkers (P<0.05). Higher alcohol intakes were associated with increasing risks for mortality and diabetes. Adjustment for classical cardiovascular risk factors and other lifestyle variables did not materially affect the estimates. In conclusion, moderate alcohol consumption was associated with a lower risk for mortality and diabetes.     

Considered judgement in evidence-based guideline development.

BACKGROUND: Clinical practice guidelines should be based on the best available evidence. However, this evidence is often incomplete, controversial, or lacking. Other considerations beyond the evidence are therefore needed to be able to formulate specific and applicable recommendations for clinical practice. OBJECTIVE: The aim of this study is to obtain consensus among experts about a set of domains and items covering the most relevant 'other considerations' to formulate recommendations in evidence-based guideline development. METHODS: An initial list of 10 domains and 49 items for a systematic and considered judgement of scientific evidence was generated from the literature. A panel of Dutch experts in guideline development tested this list using a two-round Delphi consensus technique. Each expert was asked to independently score the relevance of the items on a 4-point Likert scale, ranging from 'very important' to 'not important'. The final list consisted of items that were included by at least 60% consensus. RESULTS: Twenty-eight experts participated in the first Delphi round and 21 of them in the second round. High scoring domains were 'clinical relevance', 'safety', and 'availability of resources'. There was consensus about the relevance of 37 items. The domain 'conflicts of interest by industry' was excluded because of lack of consensus. CONCLUSION: This is the first formal consensus approach towards structuring the considered judgement process in formulating recommendations in clinical guidelines. The final list of items can be used to facilitate the process of guideline development. The next step is to test the practical usefulness and applicability of this list in guideline development.     

The cost-effectiveness of a new disease management model for frail elderly living in homes for the elderly,design of a cluster randomized controlled clinical trial

Background  

The objective of this article is to describe the design of a study to evaluate the clinical and economic effects of a Disease Management model on functional health, quality of care and quality of life of persons living in homes for the elderly.