Organ Donation in Switzerland - An Analysis of Factors Associated with Consent Rate

Background and Aim

Switzerland has a low post mortem organ donation rate. Here we examine variables that are associated with the consent of the deceased’s next of kin (NOK) for organ donation, which is a prerequisite for donation in Switzerland.

Methods and Analysis

During one year, we registered information from NOK of all deceased patients in Swiss intensive care units, who were approached for consent to organ donation. We collected data on patient demographics, characteristics of NOK, factors related to the request process and to the clinical setting. We analyzed the association of collected predictors with consent rate using univariable logistic regression models; predictors with p-values <0.2 were selected for a multivariable logistic regression.

Results

Of 266 NOK approached for consent, consent was given in 137 (51.5%) cases. In multivariable analysis, we found associations of consent rates with Swiss nationality (OR 3.09, 95% CI: 1.46–6.54) and German language area (OR 0.31, 95% CI: 0.14–0.73). Consent rates tended to be higher if a parent was present during the request (OR 1.76, 95% CI: 0.93–3.33) and if the request was done before brain death was formally declared (OR 1.87, 95% CI: 0.90–3.87).

Conclusion

Establishing an atmosphere of trust between the medical staff putting forward a request and the NOK, allowing sufficient time for the NOK to consider donation, and respecting personal values and cultural differences, could be of importance for increasing donation rates. Additional measures are needed to address the pronounced differences in consent rates between language regions.     

Influence of hypoxemia and respiratory acidosis on the plasma kinetics and tissue distribution of digoxin in the conscious dog

The aim of the present study was to investigate the influence of hypoxemia combined with respiratory acidosis on the kinetics of digoxin in conscious dogs. One group of three beagles was exposed to air and 7 days later to 10% O2, 10% CO2, and 80% N2. In a second group of three dogs, the order of exposure to the two atmospheric conditions was reversed. The dogs received 25 micrograms/kg digoxin and blood and urine samples were collected over the next 29 h. At the conclusion of the second treatment, the dogs were sacrificed to determine digoxin concentrations in the left ventricle, liver, renal cortex, and skeletal muscle. Digoxin total body clearance increased from 6.2 +/- 0.9 in control to 9.0 +/- 1.0 mL X min-1 X kg-1 in hypoxemic and hypercapnic dogs (p less than 0.05). The digoxin apparent volume of distribution at steady state (Vss) was increased in the dogs with hypoxemia and hypercapnia (11.63 +/- 1.11 vs. 8.62 +/- 0.41 L/kg in the controls, p less than 0.05). As a consequence the digoxin plasma half-life remained unchanged (18.6 +/- 1.5 h in hypoxemic and hypercapnic dogs versus 20.1 +/- 2.8 h in the controls). In dogs with hypoxemia and hypercapnia, the ratio of tissue to plasma digoxin concentrations tended to increase in the liver, in the renal cortex, and in the left ventricle and remained unchanged in the left hind leg muscle. In vitro studies showed that the digoxin total binding to erythrocyte membranes was slightly increased in the dogs with hypoxemia and hypercapnia, resulting from an increase in the apparent intrinsic association constant for digoxin (p less than 0.003). It is concluded that hypoxemia combined with respiratory acidosis changes digoxin disposition in the conscious dog and is the cause of a digoxin redistribution into the tissues.     

Altered Dopamine Receptor and Dopamine Transporter Binding and Tyrosine Hydroxylase mRNA Expression Following Perinatal NMDA Receptor Blockade

This study examined how perinatal phencyclidine (PCP) treatment would affect dopamine D2 receptor and dopamine transporter (DAT) binding at different stages after treatment cessation. Female rat pups received injections of PCP (10 mg/kg, s.c.) or saline on postnatal day (PN)7, 9 and 11. D2 receptor and transporter binding was examined at four time-points (PN12, 18, 32 and 96) following injections. PCP treatment altered D2 receptor binding throughout development, with a final end-point of 22-33% decreased binding at adulthood in the nucleus accumbens and caudate putamen (P < 0.01), accompanied by a small but significant increase in DAT binding in the caudate putamen. Tyrosine hydroxylase mRNA expression was also significantly increased by 25% (P < 0.05) in the ventral tegmental area of adult rats, suggesting that this model may produce a long-term increase in dopamine output. This study demonstrates that early insult to the brain from NMDA receptor hypofunction alters the dopaminergic system at different stages of development.     

A metabolomics approach exploring the function of the ESX-3 type VII secretion system of M. smegmatis

The genome of Mycobacterium, including Mycobacterium tuberculosis, contains five copies of a cluster of genes encoding a novel type VII secretion system, named the ESX gene cluster region. This ESX-3 gene cluster is essential for in vitro growth and is thought to play a role in iron and zinc homeostasis, however, its exact functionality remains an enigma. A metabolomics research approach was subsequently used to compare the metabolite profiles of a M. smegmatis ESX-3 knockout strain to that a wild type parental strain, in order to elucidate its functionality from a metabolic perspective. Statistical analysis of the GC–MS generated data showed a clear separation between the wild type and knockout sample groups, based on the analysed metabolite profiles of these organisms. Of all the metabolite markers identified, various amino acids and metabolite pathways related to these, appeared to be most affected by the ESX-3 knockout, especially those with enzymes regulated by iron and zinc, supporting previous genomics and proteomics generated hypotheses and findings. This study is the first to demonstrate the capacity of using metabolomics, in conjunction with previous genomics and proteomic findings, to identify underlying metabolic changes and confirm previous hypotheses related to the functionality of ESX-3 in Mycobacterium growth and survival.     

Distinction between cultivated and wild chicory gene pools using AFLP markers

The cultivation area of industrial chicory, Cichorium intybus L. cv Sativum, coincides with the natural distribution area of its wild relative, C. intybus L., which could lead to gene flow between wild and cultivated types. The genetic diversity within and between the two types has therefore been studied using AFLP genotyping of samples from 12 wild populations collected in Belgium and ten commercial varieties. The genotyping of 233 individuals allowed the identification of 254 AFLP markers. Similar levels of genetic diversity were observed within wild populations and cultivated varieties, suggesting the absence of any strong bottleneck in the history of the cultivated types. The phylogenetic analysis pointed to a monophyletic origin of cultivated varieties as compared to the local wild populations studied, hence the two types of chicory form two separate gene pools. The genotyping of some individuals sampled in ruderal sites clearly showed that they belong to the cultivated gene pool, which suggests the existence of feral or weedy types. The low differentiation observed among wild populations indicates that gene flow might be important in this species.     

Kinetics of growth and leukotoxin production by <Emphasis Type="Italic">Mannheimia haemolytica</Emphasis> in continuous culture

The growth and product formation kinetics of the bovine pathogen Mannheimia (Pasteurella) haemolytica strain OVI-1 in continuous culture were investigated. The leukotoxin (LKT) concentration and yield on biomass could substantially be enhanced by supplementation of a carbon-limited medium with an amino acid mixture or a mixture of cysteine and glutamine. Acetic acid was a major product, increasing to 1.66 g l(-1) in carbon-limited chemostat culture at intermediate dilution rates and accounting for more than 80% of the glucose carbon, whereas in amino acid-limited cultures high acetic acid concentrations were produced at low dilution rates, suggesting a carbon-overflow metabolism. The maintenance coefficients of carbon-limited and carbon-sufficient cultures were 0.07 and 0.88 mmol glucose g(-1) h(-1), respectively. LKT production was partially growth-associated and the LKT concentration was maximised to 0.15 g l(-1) and acetic acid production minimised by using a carbon-limited medium and a low dilution rate.     

The plasminogen polymorphism in South African Negro populations: genetics and anthropogenetics

Summary Genetic polymorphism of human plasminogen (PLG) was investigated in 1252 unrelated individuals from eight South African Bantu-speaking Negro tribes. PLG phenotypes were determined by isoelectric focusing (pH 3.5–9.5 and 5–8 gradients) of neuraminidase-treated samples and subsequent detection by caseinolytic overlay or immunoblotting with specific antibody. No significant difference in the distribution of PLG alleles among the eight ethnic groups was observed. The combined allele frequencies of the common alleles in South African Negroes were 0.6977 for PLG*A, 0.2736 for PLG*B. In addition, six rare alleles were seen: PLG*A3, *A1, *M2, *B1, *B2, *B3. The rare variant PLG*B2 was proven to segregate by autosomal Mendelian inheritance in a family. The combined frequency for the rare alleles was 0.0287. The distribution of phenotypes in the total population sample was found to be in Hardy-Weinberg equilibrium. A striking difference in PLG allele distribution between Negroes from South Africa and published Negroid frequencies from North America could be observed. This difference was also seen in comparison with Mongoloid populations; in contrast, PLG frequencies for South African Negroes were similar or almost identical to known Caucasoid distributions.     

The effects of gender and obesity on myocardial tolerance to ischemia

Obesity is increasing at an alarming rate globally. Several studies have shown that premenopausal women have a reduced risk of CV disease and a reduced myocardial susceptibility to ischemia/reperfusion injury. The effect of obesity on myocardial tolerance to ischemia in women has not been established. To determine how obesity affects myocardial susceptibility to ischemia/reperfusion injury in both males and females, we fed male and female Wistar rats a high caloric diet (HCD) or a control rat chow diet (CD) for 18 weeks. Rats were subsequently fasted overnight, anesthetized and blood was collected. In separate experiments, 18-week-fed (HCD and CD) rats underwent 45 min in vivo coronary artery ligation (CAL) followed by 2 hours reperfusion. Hearts were stained with TTC and infarct size determined. Both male and female HCD fed rats had increased body and visceral fat weights. Homeostasis model assessment (HOMA) index values were 13.95+/-3.04 for CD and 33.58+/-9.39 for HCD male rats (p<0.01) and 2.98+/-0.64 for CD and 2.99+/-0.72 for HCD fed female rats. Male HCD fed rats had larger infarct sizes than CD fed littermates (43.2+/-9.3 % vs. 24.4+/-7.6 %, p<0.05). Female HCD and CD diet fed rats had comparable infarct sizes (31.8+/-4.3 % vs. 23.9+/-3.3 %). We conclude that male rats on the HCD became viscerally obese, dyslipidemic and insulin-resistant, while female HCD fed rats became viscerally obese without developing dyslipidemia or insulin resistance. Obesity increased myocardial infarct size in males but not the females.     

Effect of acetic acid on astaxanthin production by Phaffia rhodozyma

Summary Low concentrations of acetic acid decreased the growth rate of and astaxanthin production by Phaffia rhodozyma on glucose, with growth completely inhibited by 2 g acetic acid/l. Using H₂SO₄ for pH control after sugar depletion caused a decline in the biomass concentration, whereas using acetic acid as titrant resulted in an increase in the biomass with a high astaxanthin content of 1430 g/g cells. An extended culture with a continuous glucose feed failed to maintain a high astaxanthin content.     

Effect of pH, temperature and nutrient limitations on growth and leukotoxin production by Mannheimia haemolytica in batch and continuous culture

AIMS: Quantification of the effects of pH, temperature and nutrient limitations on the growth and leukotoxin (LKT) production parameters of Mannheimia haemolytica in batch and chemostat culture. METHODS AND RESULTS: Mannheimia haemolytica strains OVI-1 and PH12296 were grown aerobically in two semi-defined media. In amino acid-limited cultures, the LKT concentration and yield in terms of biomass (Y(LKT/x)) were up to eightfold greater than in carbon-limited cultures. Supplementing amino acid-limited chemostat cultures with cysteine, glutamine, ferric iron and manganese further enhanced the Y(LKT/x) values up to threefold. Supplementation of an amino acid-limited batch culture of M. haemolytica strain OVI-1 with these nutrients resulted in an LKT concentration of 1.77 g l(-1) that was 45-fold greater than that obtained in RPMI 1640 medium. Aerobiosis enhanced LKT production. High acetic acid concentrations were produced under carbon-sufficient conditions. The highest maximum specific growth rates were recorded in the range of pH 6.8 to 7.8 and 37 to 40 degrees C. CONCLUSIONS: An amino acid-limited culture medium greatly improved LKT production in aerobic batch culture, which could be further enhanced by supplementation with cysteine, glutamine, ferric iron and manganese. SIGNIFICANCE AND IMPACT OF THE STUDY: It was demonstrated that LKT production by M. haemolytica could be dramatically increased through manipulation of the culture medium composition, which could benefit the production of LKT-based vaccines against bovine shipping fever pneumonia.