Requests for euthanasia or physician-assisted suicide from older persons who do not have a severe disease: an interview study

OBJECTIVE: To determine how often requests are made for euthanasia and physician-assisted suicide (EAS) in the absence of severe disease and how such requests are dealt with in medical practice in The Netherlands. METHOD: Retrospective interview study. Participants: 125 general practitioners (GPs), 77 nursing home physicians (NHPs), and 208 clinical specialists. RESULTS: In The Netherlands, each year approximately 400 people request EAS, because they are 'weary of life'. Thirty per cent of all physicians have at some time received an explicit request for EAS in the absence of severe disease; 3% of all physicians had granted a request for EAS in such a case. Most requests for EAS to GPs in the absence of severe disease (n = 29) were made by single people aged 80 years and over. While their problems were most frequently of a social nature, 79% had one or more non-severe illnesses. Most GPs refused the request; half of them proposed an alternative treatment, which the patient often refused. Nineteen people who did not receive any treatment persisted in their wish to die; the request for EAS from 5 out of 10 patients who received one or more types of treatment was withdrawn or became less explicit. CONCLUSIONS: Most physicians in The Netherlands refuse requests for EAS in the absence of severe disease. Most patients persist in their request. In an ageing population more research is needed to provide physicians with practical interventions to prevent suicide and to make life bearable and satisfactory for elderly people who wish to die.     

Determination of equine serum inhibitors for poliovirus by the gel-adsorption technique

Summary Inhibitors found in certain equine sera active against poliovirus type 1 have been determined by the gel-adsorption method using aluminiumhydroxide-gel in the absence of cells. The inhibitor belongs to the 19S-class of macroglobulins (IgM), as revealed by gel-filtration with Sephadex G 200, by DEAE-cellulose-chromatography, and by sucrose density centrifugation. It is bound to the viral surface in-vitro in the absence of tissue cells. The specific complex may be precipitated with anti-equine globulin from rabbits. The inhibitor is destroyed by papain and by 2-mercapto-ethanol. The residual infectivity (10–25%) has been found bound to the inhibitor in-vitro. Its behavior in the gel-adsorption system is not altered if the virus-inhibitor complexes have previously been diluted. — Nonsensitive mutants and double mutants have been selected. There must exist at least three different combining sites for equine inhibitors on the surface of poliovirus type 1, strain Mahoney. Equine sera may be grouped according to the specificity of their inhibitory activity. The specific binding capacity is lost if the virus is heated at 50° C for 30 min.Supported by the Deutsche Forschungsgemeinschaft, Unit Medizinische Virologie; partly presented at the 5th Viruscolloquium of the Deutsche Forschungsgemeinschaft, Marburg Sept. 1965.The authors wish to acknowledge the excellent technical assistance of MissSigrid Bonk.     

Similarities and differences of human and experimental mouse lymphangiomas.

Lymphangioma is a disfiguring malformation of early childhood. A mouse lymphangioma model has been established by injecting Freund's incomplete adjuvant (FIA) intraperitoneally, but has not been compared with the human disease. We show that, in accordance with studies from the 1960s, the mouse model represents an oil-granuloma, made up of CD45-positive leukocytes and invaded by blood and lymph vessels. Several markers of lymphatic endothelial cells are expressed in both mouse and human, like CD31, Prox1, podoplanin, and Lyve-1. However, the human disease affects all parts of the lymphovascular tree. We observed convolutes of lymphatic capillaries, irregularly formed collectors with signs of disintegration, and large lymph cysts. We observed VEGFR-2 and -3 expression in both blood vessels and lymphatics of the patients, whereas in mouse VEGFR-2 was confined to activated blood vessels. The experimental mouse FIA model represents a vascularized oil-granuloma rather than a lymphangioma and reflects the complexity of human lymphangioma only partially.     

Significant differences between plasma HIV-1 RNA assays in HIV-1 subtype E infected patients treated with antiretroviral therapy

A total of 72 HIV-1 infected Thai patients treated with didanosine (ddI) or stavudine (d4T) plus ddI at the time of interim analysis were analyzed. Sixty patients (83%) carried subtype E documented by HIV-1 V3 serotyping. HIV-1 RNA levels were measured using three commercial viral load assays. At baseline (n = 57), Quantiplex 2.0 and NucliSens 2.0 showed mean log10 HIV-1 RNA of 0.7 log10 or 5 fold lower than Amplicor 1.5 (mean 4.29 versus 5.0 log10, respectively, p < 0.001). At week 20 of treatment (n = 29), HIV-1 RNA levels were detected in 55.2%, 31%, and 33.5% of subjects tested by Amplicor 1.5, Quantiplex 2.0, and NucliSens 2.0, respectively. In conclusion: plasma HIV-1 RNA analyses showed comparable values with Quantiplex 2.0 and NucliSens 2.0 assays. In contrast, Amplicor 1.5 resulted in approximately 5 folds higher HIV-1 RNA levels and a 25% higher rate of detection of plasma HIV-1 RNA as compared to the other two assays. As the current goal of therapy is to suppress plasma viral load below the detection limit of the assays, the significant differences between the assays may influence antiretroviral efficacy evaluation and management.     

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium- 111-OV-TL-3 F(ab)₂]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for ¹¹¹ In-OV TL-3 and between 0.13 and 0.68 mGy/MBq for ¹³¹I-16-88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation. Correspondence to: M.A.B.D. Plaizier     

Controlled Release of Theophylline Monohydrate from Amylodextrin Tablets: In Vitro Observations

Amylodextrin is a linear dextrin and can be produced by enzymatic hydrolysis of the -1,6 glycosidic bonds of amylopectin. Tablets compacted from pure amylodextrin showed good binding properties and did not disintegrate in aqueous media. Extended and decreasing drug release rates were found for tablets of 300 mg with a diameter of 9 mm containing 70% amylodextrin and 30% theophylline monohydrate, when compacted at 5 kN. Almost-constant drug release rates were obtained for these tablets when compacted at 10 or 15 kN. Nearly constant drug release rates were also shown for amylodextrin tablets with a drug load up to 75% compacted at 10 kN. Both release rate and release profile could be adjusted by selecting tablet thickness and incorporation of either lactose as a highly soluble excipient or talc as a hydrophobic excipient.     

Alcohol consumption and gender in the 20th century: the case of Switzerland

Given the changes of gender roles in this century it is hardly justified to assume constant proportions of alcohol consumption for males and females. The purpose of the study was to reconstruct the consumption trends of males and females in Switzerland since the beginning of the 20th century. Cirrhosis mortality and survey data were used to disaggregate by sex the per capita alcohol consumption based on liver cirrhosis mortality suggests that the evolution of alcohol consumption in Switzerland followed a parallel course for both sexes only until the 1930 s. The low consumption during World War II and the evident increase until the beginning of the '60s seem to have resulted above all from the variations in consumption of beer by men. The decrease in total alcohol consumption observed since the '70s is also most probably due only to men; there is no indication of a decreasing consumption by women. The tendency of male and female consumption patterns to become more similar should be taken into account in the prevention of alcohol misuse.