Imminent brain death: point of departure for potential heart-beating organ donor recognition

Contains fulltext : 88186.pdf (publisher's version ) (Closed access)PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.1 september 201

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

HbA1c measurements from dried blood spots:validation and patient satisfaction

Background: This study evaluates HbA1c measurements from dried blood spots collected on filter paper and compares HbA1c from filter paper (capillary blood) with HbA1c measured in venous blood. Methods: Patient satisfaction was evaluated using a questionnaire. The performance with the filter paper method was assessed by comparing HbA1c results from EDTA-blood samples obtained via dried blood spots with HbA1c results obtained with freshly hemolyzed blood (routine HbA1c). Adult patients visiting the outpatient clinic for HbA1c analyses were recruited for the evaluation of dried blood spot sampling at home. Laboratory personnel collected a capillary blood sample on filter paper as well as a venous EDTA-blood sample. The participants collected another capillary blood sample at home and sent the dried filter paper back to the laboratory. Samples were analyzed with an immunoturbidimetric assay. Results: Between-filter coefficient of variation was 1.8%. Filter paper HbA1c increased slightly during storage, particularly during the first 5 days. Filter paper HbA1c highly correlated with routine HbA1c (r=0.987). The evaluation of samples collected at home showed comparable HbA1c values by filter paper and routine sampling methods (n=93). Eighty-three percent of participants said they would like the filter method to be brought into practice. Conclusions: Home HbA1c sampling on filter paper is an acceptable sampling alternative for analysis of HbA1c. Clin Chem Lab Med 2009;47:1259–64.Peer Reviewe

Screening for M-proteinemia: serum protein electrophoresis and free light chains compared

Peer Reviewe

An observational study on the effects of nadroparin-based and citrate-based continuous venovenous hemofiltration on calcium metabolism

Backgrounds: To study calcium homeostasis during citrate-based compared to nadroparin-based CVVH in critically-ill patients with acute renal failure. Methods: 11 patients were observed during citrate anticoagulation, 9 with nadroparin and 10 controls. Citrate was chosen for patients with active or at risk for bleeding. Results: The controls had, at 24 h, a median serum iCa of 1.1 mmol/l, the citrate group 0.87 mmol/ l and the nadroparin group 1.1 mmol/l (citrate vs. control p = 0.001, citrate vs. nadroparin p = 0.002). At 48 h, iCa was not significantly different anymore. Ca balance was negative for the citrate group in contrast to the nadroparin group ( p = 0.012). Median serum PTH was higher (30.0 pmol/l vs. 6.5 pmol/l, p = 0.003) in the citrate group. Conclusion: With a relative low target-serum-iCa (0.8-0.9 mmol/l) citrate CVVH- treated patients had a negative daily calcium balance and a temporarily lower iCa level resulting in an enhanced PTH response in comparison to nadroparin. Copyright (c) 2007 S. Karger AG, Basel

Functionalized calixspherands: synthesis and peptide coupling

Calixspherands, like 1, form kinetically stable complexes with alkali metal cations. For practical in vivo applications coupling of these complexes with carrier molecules is mandatory. Therefore, a general method for the synthesis of functionalized.calixspherand 17 was developed starting from functionalized m-terphenyl 10 and p-tert-butylcalix[ 4]arene (14). The functionalized m-terphenyl was synthesized by a Suzuki-,cross-coupling reaction. Functionalized calixspherand 17 has been coupled to a low molecular weight protein

Exclusion of Acute Myocardial Infarction. The Value of Measuring Creatine Kinase Slope

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Clinical and prognostic value of advanced glycation end-products in chronic heart failure

Aims Advanced glycation end-products (AGEs) have been proposed as a novel factor involved in the development and progression of chronic heart failure (CHF). We aimed to determine whether plasma levels of N-epsilon-(carboxymethyl)lysine (CML) and N-epsilon-(carboxyethyl)lysine (CEL), two well-known AGEs, are related to the severity and prognosis of CHF. Methods and results A total of 102 CHF patients, aged 58 +/- 12 years, with an average left ventricular ejection fraction of 28 +/- 9% were followed for 1.7 (1.2-1.9) years. NYHA functional class and NT-pro-BNP were used as estimates of the severity of CHF. CML and CEL were determined by LC-MS/MS. CML levels were associated with NYHA functional class (P <0.001) and NT-pro-BNP levels (P <0.001). Survival analysis for the combined end-point of death, heart transplantation, ischaemic cardiovascular event, and hospitalization for heart failure revealed that CML levels predicted outcome, even after adjustment for age, gender, aetiology of CHF, identified risk modifiers, and several known predictors of outcome in CHF. The predictive value of CML subsided after correction for renal function. CEL was not associated with the severity or prognosis of CHF. Conclusion Plasma AGEs, in particular CML levels, are related to the severity and prognosis of CHF. The fact that the relation between CML and prognosis subsided after correction for renal function may suggest that AGE accumulation in renal failure explains part of the prognostic value of renal function in CHF. However, further investigation is warranted to exclude the possibility that CML is just an innocent marker of renal function