Benoît Boland

Critical evaluation of cytosolic calcium determination in resting muscle fibres from normal and dystrophic (mdx) mice.

The fluorescent probe Fura-2/AM was used to determine cytosolic free calcium concentration in soleus muscle and in isolated flexor digitorum brevis fibres. This required a precise calibration; therefore, each calibration parameter was studied in situ. The influence of the dye concentration on calcium measurements was also examined. This precise calibration technique was used to compare absolute free calcium concentration in resting preparations from dystrophic (mdx) and control (C57) mice. We showed that the behavior of the dye was not similar in C57 and in mdx muscles. For this reason, we did not confirm the previous results that cytosolic free calcium concentration is increased in mdx muscles.

Health care workers: vectors of influenza virus? Low vaccination rate among hospital health care workers.

The influenza vaccination rate among health care workers is not very high and needs to be improved. The authorities of our university hospital decided to encourage vaccination among health care workers and to include it in the hospital quality of care program. A survey about knowledge of influenza disease and its vaccination was undertaken, and 37.2% of the workers participated in the survey. Among them, 31.8% were vaccinated. The vaccination rate was higher when workers were older, men, physicians, technicians, or laboratory workers, vaccinated in the previous flu season and had fewer contacts with patients. The variables with the highest impact on the vaccination rate were vaccination the previous year, belief that vaccination is highly effective, and affirmation that prevention is important. Our study shows that an active vaccination campaign is also necessary for health workers to put them in the stream of usually vaccinated people.

Predicting functional adverse outcomes in hospitalized older patients: a systematic review of screening tools.

BACKGROUND Functional decline frequently occurs following hospitalisation in older people and may be prevented or minimized by specific management. Such care processes needs appropriate early screening of older hospitalized patients. OBJECTIVE To identify instruments able to detect on admission older hospitalized patients at risk of functional decline at and after discharge. METHODS Functional decline is defined as loss of independence in activities of daily living (functional decline) or admission in nursing home. The systematic search used Medline 1970-2007, Web of Science 1981-2007 and references list of relevant papers. An independent epidemiologist assessed methodological quality of the retained articles. RESULTS We found 12 studies developing predictive tools, including 7145 patients. Functional outcomes were assessed at or after discharge. Preadmission functional status, cognition, and social support were major components for prediction of functional evolution. Few instruments are fully validated and data concerning reliability are often lacking. Operational characteristics are moderate (sensitivity 29-87%, negative likelihood ratio 0.2-0.8). CONCLUSIONS Instruments predicting functional adverse outcomes are difficult to compare due to heterogeneity of functional outcomes and hospital settings. The reason why so many tools have been developed is probably because none gives full satisfaction: their general predictive validity and performances are insufficient. Further research is needed to improve the screening of frail older patients admitted to hospital with standardized and validated tools.

Drug therapy optimization at the end of life

Older people reaching end-of-life status are particularly at risk of adverse effects of drug therapy. Polypharmacy, declining organ function, comorbidity, malnutrition, cachexia and changes in body composition all sum up to increase the risk of many drug-related problems in individuals who receive end-of-life care.End of life is defined by a limited lifespan or advanced disability. Optimal prescribing for end-of-life patients with multimorbidity, especially in those dying from non-cancer conditions, remains mostly unexplored, despite the increasing recognition that the management goals for patients with chronic diseases should be redefined in the setting of reduced life expectancy. Most drugs used for symptom palliation in end-of-life care of older patients are used without solid evidence of their benefits and risks in this particularly frail population. Appropriate dosing or optimal administration routes are in most cases unknown.Avoiding or discontinuing drugs that aim to prolong life or prevent disability is usually common sense in end-of-life care, particularly when the time needed to obtain the expected benefits from the drug is longer than the life expectancy of a particular individual. However, discontinuation of drugs is not standard practice, and prescriptions are usually not adapted to changes in the course of advanced diseases. Careful consideration of remaining life expectancy, time until benefit, goals of care and treatment targets for each drug seems to be a sensible framework for decision making.In this article, some key issues on drug therapy at the end of life are discussed, including principles of decision making about drug treatments, specific aspects of drug therapy in some common geriatric conditions (heart failure and dementia), treatment of acute concurrent problems such as infections, evidence to guide the choice and use of drugs to treat symptoms in palliative care, and avoidance of some long-term therapies in end-of-life care.Solid evidence is lacking to guide optimal pharmacotherapy in most end-of-life settings, especially in non-cancer diseases and very old patients. Some open questions for research are suggested.

ATP activates P2x-contracting and P2y-relaxing purinoceptors in the smooth muscle of mouse vas deferens

1 The mechanism for the low potency of exogenous ATP in producing contraction at the P2x‐purinoceptors in the smooth muscle of the mouse vas deferens (VD) was examined. 2 The measure of the breakdown of ATP in contact with the VD showed that its degradation was limited and did not account for its weak contractile effect. 3 Externally applied, ATP induced a small and transient contraction but a marked and prolonged increase of the cytosolic Ca2+ concentration ([Ca2+]i), which suggests an efficient binding to the P 2x‐purinoceptors. Such a calcium‐force dissociation was not observed with β,γ‐methylene ATP (β,γ‐Me‐ATP), a structural ATP analogue. 4 The force response of precontracted VD to ATP was biphasic, consisting of a small initial contraction followed by a sustained marked relaxation. In contrast, β,γ‐Me‐ATP elicited a pronounced contraction without ensuing relaxation. 5 ATP was more potent than adenosine in producing relaxation, and the relaxation was not antagonized by 8‐phenyltheophylline, suggesting the activation of P2‐purinoceptors. 6 For this relaxation, the rank order of potency was 2‐methyl‐thio‐ATP (2‐MeSATP) > ATP>β,γ‐Me‐ATP, which is characteristic for the P2y‐purinoceptors. 7 Reactive Blue 2, a P2y‐purinoceptor antagonist, was found to reduce the relaxation mediated by ATP. 8 These results indicate that ATP acts in VD not only on contracting but also on relaxing P2‐purinoceptors, eliciting thereby overlapping opposite effects. In VD, the classical low potency of ATP for contraction is thus not explained by its low bioavailability or its low binding, but rather by its low specificity for the contracting P2x‐purinoceptors, leading to the activation of the relaxing P2y‐purinoceptors.

ATP induced‐relaxation in the mouse bladder smooth muscle

1 The effect of adenosine 5′‐triphosphate (ATP) on the free cytosolic Ca2+ concentration ([Ca2+]i) as measured with the fluorescent Ca2+‐indicator fura‐2, and on force was investigated in the intact smooth muscle strips of the mouse urinary bladder. 2 ATP elicited, when exogenously applied, a large increase of [Ca2+]i with limited force development resulting in a marked Ca2+‐force dissociation. 3 Release of endogenous neurotransmitters by transmural electrical stimulation (TES) for 30 s induced a steady increase of [Ca2+]i and a peak contraction, followed within 15 s by a relaxation. 4 In carbachol‐prestimulated preparations, ATP elicited an initial rise of [Ca2+]i followed by a return to the initial precontraction Ca2+‐level. Force in contrast presented a biphasic pattern, i.e. an initial contraction was followed by a sustained relaxation. 5 In the K+‐depolarized precontracted preparation, ATP elicited a slight initial rise of [Ca2+]i. The partial relaxation of the force during depolarization was not preceded by a transient contraction. 6 The ATP‐induced relaxation of the K+‐prestimulated preparations was not inhibited by 8‐phenyltheophylline, a potent P1‐purinoceptor antagonist. 7 The order of potency for relaxation of the ATP analogues was 2‐MeSATP>ATP>βγMe‐ATP, which is characteristic for P2y‐purinoceptors. 8 These results indicate that, besides its activating effect, ATP also relaxes the mouse urinary bladder. It is suggested that the relaxant effect, mediated through P2y‐purinoceptors, is mainly responsible for the low contractile potency of ATP in the bladder.

Type 2 Diabetes in Primary Care in Belgium: Need for Structured Shared Care

OBJECTIVE To picture the profile of type 2 diabetic patients in Belgium and to study the quality of care in the primary care setting, with regard, to multi-factorial approach of the disease. METHODS Observational study of all known DM2-patients registered by 120 volunteer general practitioners. Quality of care was evaluated by the achievement of three major treatment targets: HbA1c<7%; Systolic Blood Pressure </=130 mmHg; LDL-Cholesterol<100 mg/dl (ADA 2003). Multivariate analysis was performed. RESULTS 2495 DM2-patients were included with a mean age of 68+/-12 years and 51% being women. One fifth of the patients had microvascular complications and 27% had macrovascular complications. Sixty-eight percent received oral anti-diabetic drugs and 19% were on insulin. Satisfactory glycaemic control (HbA1c<7%) was achieved in 54% of the patients, with however glucose control deteriorating with disease progression despite more intensive hypoglycaemic treatment. Systolic blood pressure targets were reached in 50%. Statin use was present in 39% and LDL levels<100 mg/dl were reached in 42%. 59% of insulin treated patients were followed up in shared care with specialised diabetes centres. These patients obtained lower values for HbA1c (7.5+/-1.2% vs. 7.8+/-1.5%, p=0.038) and LDL-C (90+/-34 vs. 111+/-37, p<0.001) compared to insulin-treated patients only followed up in primary care. CONCLUSION Overall metabolic control in type 2 diabetic patients in primary care in Belgium was acceptable for glucose control, but major room for improvement exists especially for statin use and blood pressure control. Clinical inertia is present and the presence of more structured care in specialised diabetes centres, focusing on therapeutic guidelines, may explain the better overall metabolic control in patients followed up in shared care with these centres.

Start improving the quality of care for people with type 2 diabetes through a general practice support program: A cluster randomized trial

AIMS To evaluate the effectiveness of a two-arm quality improvement program (QIP) to support general practice with limited tradition in chronic care on type 2 diabetes patient outcomes. METHODS During 18 months, we performed a cluster randomized trial with randomization of General Practices. The usual QIP (UQIP: 53 GPs, 918 patients) merged standard interventions including evidence-based treatment protocol, annual benchmarking, postgraduate education, case-coaching for GPs and patient education. The advanced QIP (AQIP: 67 GPs, 1577 patients) introduced additional interventions focussing on intensified follow-up, shared care and patient behavioural changes. Main outcomes were HbA1c, systolic blood pressure (SBP), and low density lipoprotein cholesterol (LDL-C), analyzed by generalized estimating equations and linear mixed models. RESULTS In UQIP, endpoints improved significantly after intervention: HbA1c -0.4%, 95% CI [-0.4; -0. 3]; SBP -3mmHg, 95% CI [-4; -1]; LDL-C -13mg/dl, 95% CI [-15; -11]. In AQIP, there were no significant additional improvements in outcomes: HbA1c -0.4%, 95% CI [-0.4; -0.3]; SBP -4mmHg, 95% CI [-5; -2]; LDL-C -14mg/dl, 95% CI [-15; -11]. CONCLUSIONS A multifaceted program merging standard interventions in support of general practice induced significant improvements in the quality of diabetes care. Intensified follow-up in AQIP with focus on shared care and patient behaviour changes did not yield additional benefit.

Lung function study and diffusion capacity in anorexia nervosa

Abstract.  Pieters T, Boland B, Beguin C, Veriter C, Stanescu D, Frans A, Lambert M (Cliniques, Universitaires Saint‐Luc, Brussels, Belgium). Lung function study and diffusion capacity in anorexia nervosa. J Intern Med 2000; 248: 137–142.

Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage.

Abstract. Aggressive mastocytosis is a form of systemic mast cell disease (SMCD) characterized by organ infiltration, bone lesions, eosinophilia and lymphadenopathies. Here we report a patient with unusual clinical features, namely osteolysis without other bone lesions commonly found in SMCD, major eosinophilia and cerebral infarction. The mast cells exhibited a classical immunophenotype (CD2+, CD9+, CD13+, CD25+, CD35+, CD45c+ and CD117+). Cytogenetic investigation showed novel complex aberrations, and clonal evolution was correlated with clinical progression. The screening for recurrent point mutations affecting the c-kit gene was negative. Mainly, the ASP816VAL substitution was not detected in our patient. Treatment with steroids and interferon was only temporarily effective.