Against the family veto in organ procurement: Why the wishes of the dead should prevail when the living and the deceased disagree on organ donation

The wishes of registered organ donors are regularly set aside when family members object to donation. This genuine overruling of the wishes of the deceased raises difficult ethical questions. A successful argument for providing the family with a veto must (a) provide reason to disregard the wishes of the dead, and (b) establish why the family should be allowed to decide. One branch of justification seeks to reconcile the family veto with important ideas about respecting property rights, preserving autonomy, and preventing harm. These arguments are ultimately unsuccessful. Another branch of arguments is consequentialist, pointing out the negative consequences of removing the veto. Whether construed as concerning family distress or as a potential drop in the organs available, these arguments are unsuccessful; the first fails to recognize the tremendous distress associated with waiting for an organ, while the second has little supporting evidence. A final section considers and rejects whether combining some of the arguments just examined could justify the family veto. We should thus remove the family veto in organ donation.     

Chromosome analysis of the lymphocytes of wild rats living close to waterways contaminated with effluents from nuclear plants

Chromosomes of peripheral lymphocytes of wild rats living in the vicinity of a water stream contaminated by radioactive liquid releases from nuclear stations were studied. Our observations show that the quantities of radionuclides accumulated in different organs of the exposed rats were in some animals slightly but not significantly higher than in the control ones. Such low internal radioactivity does not result in an enhancement of the yield of structural chromosome aberrations. Since the radiosensitivity of rat chromosomes is roughly comparable to that of human chromosomes one has to conclude that our results can be extrapolated to human beings.     

Subset Selection for Exponential Populations: Determination of the Selection Constant

Given are k(≧2) exponential populations differing only in their location parameter. One wishes to choose the best one, that is the population with the largest value of the location parameter. A possible method for solving this problem is to select a subset of the k populations of size at least one which includes the best population with a required confidence P*(k^?1 ≤ P* ≤1). In this paper the required selection constant is determined for different values of k and P*. Also an approximation for the selection constant is derived. A comparison with the exact results is made.     

A Mathematical Model For Analysing Cellular Age-Response Functions In Terms of Physiological Age

A mathematical model is presented which facilitates the analysis of cellular age-response functions in terms of the physiological ages of the cells. Age-response functions are generally determined by obtaining synchronous cohorts of cells and measuring the sensitivity of the cohorts to the treatment agent at different times after selection (i.e., at several different chronological ages). the model described here uses data on the [³H]TdR labelling patterns of the cell population to determine the distribution of physiological ages for the cohorts at the times of treatment. the age-response function data are then analysed in terms of the physiological ages of the cells. the compartments used in the analysis may be chosen according to the biology of the system and the wishes of the experimenters and not imposed by the variability of the phase durations. the application of the model is illustrated using the age-response functions for EMT6 cells exposed to radiation and HeLa cells exposed to hydroxyurea.     

The cytogenetic effect in a group of settlers from a 30-kilometer area of right of way

One of the critical human group of potential risk is the group of population from 30-km zone around the Chernobyl nuclear power plant. The cytogenetical examination of 12 persons (8 man, 4 woman, 30-60 years old) from 5 villages situated in north-west and south-east directions from the ChNPP in the frame of this zone was conducted. The data of the conventional analysis showed relatively low cytogenetic effects comparable with the effects in exposed people out of the zone (the mean level of unstable cytogenetic markers in different villages was 0.21-0.35 per 100 cells). The level of stable translocations in one case (woman, 59 years old) determined using FISH (16.62 per 100 cells for the whole genome) exceeded their spontaneous aged frequency and confirmed the high sensitivity of this method for the evaluation of real radiation exposure.     

Use of moving optical gradient fields for analysis of apoptotic cellular responses in a chronic myeloid leukemia cell model

To facilitate quantitation of cellular apoptotic responses to various antineoplastic agents, a laser-based technology, Optophoresis, has been developed to provide analysis of cells without any need for labeling or cell processing. Optophoresis is defined as the analysis of the motion of cells, where the motion is either induced or modified by a moving optical gradient field, which produces radiation pressure forces on the cells in an aqueous suspension. Quantitation of the induced motion provides a basis for distinguishing one population of cells from another. One Optophoretic technique, Fast Scan, measures the distribution of distances traversed by a population of cells when exposed to a fast-moving optical gradient. Fast Scan was validated using a cell-based model of chronic myeloid leukemia treated with Gleevec, a specific inhibitor of aberrant Bcr-Abl protein kinase. The Optophoretic measurements were quantitatively comparable to reference assays with regard to drug selectivity and potency and to target specificity, demonstrating the suitability of this technology for pharmaceutical and clinical applications.     

Monoclonal antibodies to beet soil-borne virus

Four monoclonal antibodies (MCA) were obtained to the ‘Ahlum’ serotype of beet soil-borne virus (BSBV). On ELISA plates which had been precoated with polyclonal antibodies (PCA) all four MCA detected this serotype with a higher sensitivity than alkaline phosphatase-labelled PCA. Three of the MCA were specific for the ‘Ahlum’ serotype, but a fourth one also detected the distantly related ‘Wierthe’ serotype. Cross-reactions with wheat soil-borne or oat golden stripe furoviruses were not observed. One of the MCA reacted with an epitope which is exposed along the entire length of the BSBV particles, whereas two others were specific for epitopes which are exposed on one particle extremity only. Although these latter two epitopes occur apparently on the same extremity of the particles, they seem to be different, because one is found only on the particles of the ‘Ahlum’ serotype, whereas the other one is present also on the particles of the ‘Wierthe’ serotype. The fourth MCA is specific for a cryptotope which is not exposed on the intact virus particles, but presumably on some degradation product or precursor of the viral coat protein present in crude sap preparations. All four epitopes are SDS-labile; they are not detected on denatured viral coat protein on Western blots.     

Functional structure of protein: exposed vs hidden function

The dev analysis was used to construct the functional structure of protein (3). Based on this principle, the intramolecular interaction of dev peak was investigated. Two types of peak were observed: one is the hidden peak which interacts strongly with another region of the molecule and the other is the exposed peak whose interaction was weak. Analysis was made with trypsin and its inhibitor and on the intermolecular interaction between their exposed peaks. One interaction between their exposed peaks was found to coincide with one which had been already known to be authentic between their active sites.     

Microtubule-synaptic vesicle associations in cultured rat spinal cord neurons

Summary This paper describes new ultrastructural features of neural processes and of synapses in cultured CNS tissue treated with albumin before fixation using a modification of the technique recently introduced by Gray (1975). Nerve fibre bundles in explants of foetal spinal cord grown in vitro for 15–18 days were transected microsurgically. After transection the cultures were exposed to 20% albumin in distilled water and then fixed in unbuffered osmium tetroxide followed by unbuffered glutaraldehyde.In this material, but not in controls (injured but not exposed to albumin; exposed to albumin without injury) microtubules were found within many axonal varicosities, often situated close to presynaptic membrane specializations. These microtubules were closely associated with vesicles resembling synaptic vesicles, which were occasionally aligned in rows along the microtubules. Similar vesicle-microtubule associations were also found in non-terminal axons. Microtubules were also observed very close to some postsynaptic densities.The possibility that the microtubule-vesicle associations are involved in vesicle movements (along axons and/or within axon terminals) is discussed. A more direct involvement of microtubules in terminals in the mechanism of transmitter release is also considered.The author wishes to thank Dr. A.R. Lieberman for his help and advice, Mr. Derek Fraser and Mr. Peter Felton for their technical assistance, Mr. Stuart Waterman for the photographic prints, and Professor D.W. James for laboratory facilities     

Transfer of entomopathogenic fungi among formosan subterranean termites and subsequent mortality

Strains of the entomopathogens Beauveria bassiana (Balsamo) Vuillemin and Metarhizium anisopliae (Metschnikoff) Sorokin were screened for effectiveness against the Formosan subterranean termite, Coptotermes formosanus (Shiraki). Biological control methods are being considered to augment current integrated pest management schemes that involve chemical baits and nonrepellent termiticides. In this study Formosan subterranean termites selected from four colonies in the field were exposed in the laboratory to three strains of Beauveria bassiana and two strains of Metarhizium anisopliae . The exposed termites were then allowed to mingle with an equal number of unexposed termites from the same nest and mortality of the combined group was determined. One week after exposure, B. bassiana strains, ATCC 26037 and ATCC 90519, had caused significantly higher mortality than the two M. anisopliae strains, ESC 1 and II B and the remaining strain of B. bassiana , ATCC 90518. The LT₅₀ measurement for strains 26037 and 90519 was comparable at 1.8 and 2.0 days, respectively. Strains ESC 1 and 90518 caused 50% mortality at 6.5 and 11.0 days, respectively. Termites exposed to strain II B and the control group of termites did not reach 50% mortality during the 21 day experimental period. Exposure of termites to all fungal strains resulted in mortality in excess of that seen in the control groups of unexposed termites.     

Distribution and development of Brugia malayi in reinfected cats.

At various time periods after an initial exposure to 50 Brugia malayi larvae on one hind foot cats were reexposed to an additional 50 larvae in one of 3 ways: on the previously infected limb only, on the contralateral, uninfected limb only, or on both hind limbs simultaneously. At the time of reexposure uninfected controls were exposed to 50 larvae on one hind foot in a similar manner. From 2 to 4 weeks after reexposure to larvae, the cats were necropsied and the appropriate lymph nodes and vessels examined for adult or developing worms. An existing infection in one limb did not influence early migration or development of larvae introduced into the contralateral leg. Previous infection in the same limb did not consistently result in decreases in the number of developing larvae from the second exposure but did alter the distrubution of larvae. In repeat infections, larvae were consistently located in a moe distal area of the limb than were larvae from an initial infection at a comparable time.     

Stimulation of rat liver cyclic 3':5'-nucleotide phosphodiesterase by cyclic GMP is dependent on enzyme concentration

A high-speed supernatant of rat liver extract displayed multiple forms of cyclic nucleotide phosphodiesterase (EC 3.1.4.17). One of the forms catalyzed the hydrolysis of cyclic AMP and cyclic GMP, with approximately comparable facility. One salient feature of the enzyme is that at micromolar concentrations, cyclic GMP stimulated the hydrolysis of cyclic AMP, but not vice versa. Another is that the activity of phosphodiesterase varied as a function of enzyme concentration in the assayed system: the enzyme activity was higher at low than at high enzyme concentrations. A concentrated enzyme was not stimulated by cyclic GMP but was stimulated by cyclic GMP upon dilution of the enzyme. Conversely, stimulation of the enzyme by cyclic GMP could be reversed by increasing the enzyme concentration. The cyclic GMP-stimulated cyclic AMP phosphodiesterase was partially purified by a continuous sucrose density gradient. The apparent change of phosphodiesterase activity as a function of enzyme concentration was also observed after partial purification by the sucrose density gradient. High enzyme concentrations favored the aggregated form of phosphodiesterase, whereas low concentrations favored the dissociated form. Dilution of the enzyme shifted the equilibrium toward the dissociated form, which presumably exposed the cyclic GMP regulatory site on the enzyme molecule.     

AIDS vaccination studies using an ex vivo feline immunodeficiency virus model: failure to protect and possible enhancement of challenge infection by four cell-based vaccines prepared with autologous lymphoblasts

Immunogenicity and protective activity of four cell-based feline immunodeficiency virus (FIV) vaccines prepared with autologous lymphoblasts were investigated. One vaccine was composed of FIV-infected cells that were paraformaldehyde fixed at the peak of viral expression. The other vaccines were attempts to maximize the expression of protective epitopes that might become exposed as a result of virion binding to cells and essentially consisted of cells mildly fixed after saturation of their surface with adsorbed, internally inactivated FIV particles. The levels of FIV-specific lymphoproliferation exhibited by the vaccinees were comparable to the ones previously observed in vaccine-protected cats, but antibodies were largely directed to cell-derived constituents rather than to truly viral epitopes and had very poor FIV-neutralizing activity. Moreover, under one condition of testing, some vaccine sera enhanced FIV replication in vitro. As a further limit, the vaccines proved inefficient at priming animals for anamnestic immune responses. Two months after completion of primary immunization, the animals were challenged with a low dose of homologous ex vivo FIV. Collectively, 8 of 20 vaccinees developed infection versus one of nine animals mock immunized with fixed uninfected autologous lymphoblasts. After a boosting and rechallenge with a higher virus dose, all remaining animals became infected, thus confirming their lack of protection.     

Mouse models of human genetic disease: Which mouse is more like a man?

There has always been great interest in animal models of human genetic disease, and mice provide the largest number of examples. A mutation in the homologous gene in mice does not always lead to the same phenotype as is found in man, however. Recent studies made it apparent that one mutation can have markedly different phenotypes when placed on different genetic backgrounds. This variation is due to different alleles at modifying loci in various inbred strains. Thus, if one wishes to obtain the optimal mouse model for a human disease, one needs to choose the correct genetic background as well as the correct mutation.     

Management of 41 persons exposed to a rabid dog: unplanned experience with human diploid vaccine.

Thirty-six persons -- veterinarians, technicians and students at a veterinary clinic -- were unwittingly exposed to a rabid dog over a period of 21/2 days. One veterinarian received a penetrating bite, two other individuals were grabbed by the dog but the skin was not penetrated, and many were exposed to saliva or urine or both. In addition, the owner of the dog and his wife and three children, while not bitten, were exposed to saliva. The diagnosis was made post mortem when specimens of the dog''s brain were examined by indirect fluorescent antibody testing. All but one of the students had been vaccinated against rabies with hamster kidney vaccine, but eight members of the veterinary college''s staff had not been so vaccinated. Treatment started with duck embryo vaccine; if necessary, rabies (human) immune globulin was also given. When one student reacted severely to the first dose of duck embryo vaccine permission was sought to bring a human diploid vaccine into Canada. In five patients the human diploid vaccine was substituted for the duck embryo vaccine because of severe reactions to the latter. Twenty-five staff members and the family of five received both vaccines. Reactions to the human diploid vaccine were minor and transient. Recommendations include the early licensing of the human diploid vaccine in Canada.     

Online tool for the discrimination of equi-distributions

Background  

For many applications one wishes to decide whether a certain set of numbers originates from an equiprobability distribution or whether they are unequally distributed. Distributions of relative frequencies may deviate significantly from the corresponding probability distributions due to finite sample effects. Hence, it is not trivial to discriminate between an equiprobability distribution and non-equally distributed probabilities when knowing only frequencies.     

Time dependent cadmium uptake by fathead minnows (Pimephales promelas) during field and laboratory exposure

Fathead minnows (Pimephales promelas) exposed to 2.5 ppb cadmium in an industrially contaminated lake accumulated whole body burdens of 3.19 ppm Cd in 12 hours, while minnows exposed to 48 ppb Cd in a continuous flow laboratory system did not reach comparable levels until the eighth day of exposure. Significant whole body accumulation of Cd (approximately 9 ppm) peaked within 17–20 days of exposure in the laboratory.     

Adversaries at the Bedside: Advance Care Plans and Future Welfare

Advance care planning refers to the process of determining how one wants to be cared for in the event that one is no longer competent to make one's own medical decisions. Some have argued that advance care plans often fail to be normatively binding on caretakers because those plans do not reflect the interests of patients once they enter an incompetent state. In this article, we argue that when the core medical ethical principles of respect for patient autonomy, honest and adequate disclosure of information, institutional transparency, and concern for patient welfare are upheld, a policy that would allow for the disregard of advance care plans is self‐defeating. This is because when the four principles are upheld, a patient's willingness to undergo treatment depends critically on the willingness of her caretakers to honor the wishes she has outlined in her advance care plan. A patient who fears that her caretakers will not honor her wishes may choose to avoid medical care so as to limit the influence of her caretakers in the future, which may lead to worse medical outcomes than if she had undergone care. In order to avoid worse medical outcomes and uphold the four core principles, caregivers who are concerned about the future welfare of their patients should focus on improving advance care planning and commit to honoring their patients’ advance care plans.     

An effect of fibronectin in epidermal growth factor (EGF)-stimulated membrane protein phosphorylation in human carcinoma cells

Membrane components of about 20 kd (kilodalton) which appear weakly phosphorylated in protein kinase assays of A431 human carcinoma plasma membranes to which epidermal growth factor (EGF) is added, increase their relative phosphorylation when human serum fibronectin is also included in the assay. Membranes prepared from ³²PO₄-labelled cells exposed to EGF and fibronectin prior to organelle isolation revealed the presence of an anodic 20 kd component not detected in cells which were not exposed to fibronectin. No comparable effects were apparent with bovine heart protein kinase and with membrane-associated protein kinase preparations which were not responsive to EGF.