Professor Robert-Henri Regamey, 1907-1978.
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Biomedical subjects
Publications and source records attributed to F T Perkins.
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In the developing countries there is a need for greater activity in the quality control of vaccines used in immunization programmes. The establishment of a quality control facility can give assistance not only in the checking of vaccines at the time of release, but also in monitoring the efficacy of the cold chain. Furthermore, the antibody responses of the local child population to the vaccines can be measured. Quality control should be established before vaccine manufacturer, therefore, and the economics of importing vaccine in the bulk concentrated form with dilution, blending and filling locally is worthy of consideration.
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Serum neutralizing antibodies to polioviruses were titrated in serum samples from 182 police cadets aged 16-18 years before and, in 168 of the cadets, 6 weeks after vaccination with a single dose of oral polio vaccine (OPV). Faecal excretion of poliovirus was also followed. Vaccination histories were obtained and confirmed whenever possible. Pre-vaccination antibody could not be detected against type 1 in 9-3% cadets, against type 2 in 2-7% and against type 3 in 7-7%. Absence of antibody to at least one virus type was found in 14-3% of the cadets. In 93 cadets in whom vaccination histories could be confirmed 40 had received only inactivated polio vaccine (IPV) previously; of these 23% lacked antibody to at least one virus type, and they had less intestinal immunity to a challenge dose of OPV than those previously given OPV. Only two of the cadets known to have had OPV were non-immune - both had received a single dose following full courses of IPV. However, cadets who had received OPV had their last dose of vaccine more recently (average 4-6 years) than those who had received only IPV (all 12 years or more). The serum antibody response to a single booster dose of OPV, and the faecal excretion of each type of virus after vaccination, showed an inverse relation to the corresponding pre-vaccination antibody concentration. A single dose of OPV did not reliably boost the immunity of those who possessed adequate immunity, and a failure to respond was also observed in a proportion of the cadets with no detectable antibody, mostly in the case of type 3 antibody and particularly if antibody to types 1 or 2 virus was also absent. No evidence was obtained that intestinal immunity could be expected in the absence of detectable circulating antibody. The reasons for the absence of a serological response to OPV in some subjects are discussed and consideration is given to the practical significance of the findings. It is suggested that reinforcement of polio immunity at school-leaving is important, particularly at the present time when many of those aged 16-18 years will have been vaccinated only with IPV. A single dose of OPV is not ideal for this purpose, not only because a small proportion of persons are liable to be left unprotected, but also because failure to produce a reliable boost in persons with adequate immunity at the time of vaccination gives rise to the possibility that they may become susceptible later in adult life.
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The effect of exogenous sex hormones on the cell mediated response in male and female mice has been studied by measuring the subcutaneous growth of HeLa tumour nodules and the variation in the total lymphocyte count. It was found that oestrogen treated male and female mice experienced a profound lymphopenia which was vary rapid in onset. Concurrent with the lymphopenia there was prolongation of HeLa tumour nodule growth in female mice, but not in males. A lymphopenia occurred in androgen treated male mice with subsequent prolongation of HeLa tumour nodule growth, and a lymphocytosis in female mice, with reduction of HeLa tumour nodule growth.
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Immunosuppressed mice have been used to support the growth of xenogeneic human and animal malignant cell populations. The optimal conditions for tumor growth are neonatal thymectomy coupled with antithymocyte serum or thymectomy, followed by whole-body irradiation and bone marrow reconstitution. When mice are inoculated with a mixture of normal and malignant cells, the malignant cells have a selective advantage. No such selectivity is found when the mixed populations are grown in vitro. Human tumors may also be grown in immunosuppressed mice. These tumors retain the organization of the original tumor in the human host. The advantages of this system to cancer researchers are discussed.
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Three commercial preparations of cocksfoot pollen (Dactylis glomerata) from different manufacturers were compared by skin prick tests in man, allergen activity as measured by the RAST test and protein nitrogen unit (PNU) and total nitrogen (N) content. The skin prick tests were made on the forearm with the undiluted preparations and also with solutions of 1/5 and 1/25 dilutions. Three groups each of 9 subjects were tested and the sites for the 9 tests were determined by 3 different latin squares. Taking one of the preparations as having a potency of unity, the estimated potencies for the other two were 0.28 and 0.18 when the areas of the weals were measured by a graph paper method and they were 0.27 and 0.19 when the areas were calculated by taking the product of the longest diameter of the weal and that at right angles to it. No notable differences were observed when the solutions were inoculated at different test sites. The three preparations were ranked in the same order of potency by the skin prick test, by measurement of allergen activity as measured by a RAST-based allergen assay method using the sera of the test subjects, and by measurement of their PNU but not their total N content. Comparisons such as these could possibly lead to the production of allergen extract preparations of similar or with consistent potency.
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The use of standards in the control of biological substances is of particular importance because the potency of such substances cannot be adequately determined by physical or chemical means. For these substances, therefore, it is necessary to compare the activity or potency of a given quantity with that of a similar quantity of a standard or reference preparation to which a unitage has been assigned. In order to eliminate as far as possible the inherent variables in biological tests, especially in tests involving animals, the comparison between the standard and the unknown must be made in a single test. Furthermore it is essential that the biological activity of the standard has the same properties as those products for which the standard is used as a control. The master standards are the International Standards held by the World Health Organization and it is necessary to establish European or National Standards calibrated in International Units in order to conserve the stocks of the master standards. Criteria for the quality of preparations suitable as standards will be considered and some examples of their use will be presented.
Optimal conditions for the detection of malignant cells substrates were investigated. Three approaches were used: (1) neonatally thymectomized, antithymocyte serum (ATS) treated mice, (2) thymectomized, lethally irriadiated, bone marrow reconstituted (T-B+mice, and (3) congenitally athymic nu/nu (nude) mice. All three systems successfully distinguished between normal and malignant cell lines. However, differences were observed between different colonies of nude mice as to their capacity to support progressive growth of certain tumours. Advantages and disadvantages of the immunosuppressed mouse model system will be discussed. They will include: (a) detection of malignant cells in mixed populations, (b) need for different routes of inoculation for different cell types, (c) comparison with other malignancy testing systems, (d) long term versus short term immunosuppression.