Biomedical subjects
R Hess
Publications and source records attributed to R Hess.
Evaluation of skin carcinogenicity of technical 2,2-bis-(p-glycidyloxyphenyl)-propane in CF1 mice.
The carcinogenic potential of a technical-grade epoxy resin, Araldite GY 250, of which the diglycidyl ether of bisphenol A (DGEBPA) is the main component, was investigated in CF1 mice. Groups of 50 male and 50 female mice were treated for 2 yr by repeated epidermal application of a 1 or 10% (v/v) solution in acetone. The controls, 50 mice of each sex, were treated with acetone alone. The treatment had no effect on survival and no excess incidence of skin tumours occurred. A positive control group of 50 male and 50 female CF1 mice was treated by epidermal application of 2% (v/v) beta-propiolactone in acetone. In this group there was a high incidence of malignant skin tumours at the site of application and, consequently, increased mortality. Treatment with neither DGEBPA technical nor beta-propiolactone induced systemic neoplasia.
The role of the Prevention Advisory Committee in Michigan.
The role of a prevention advisory committee in maintaining Michigan's prevention effort is examined. Accomplishments in the areas of program development, communication, policy formulation, and advocacy are described and structural aspects contributing to the success of the committee are discussed.
[Gamete intra-fallopian transfer (GIFT). Report of the 1st pregnancy].
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[Predictive experimental animal test of contact allergenicity. Relevance of the methods of the OECD and EEC guidelines. The organization for Economic Co-operation and Development].
In the first part of this article a historical note is given on the development of predictive contact allergenicity tests in guinea pigs starting with the Draize test, including epidermal methods and at least induction procedures using Freund complete adjuvant as a nonspecific enhancer of immunoreactivity. The tests of the OECD and EEC guidelines are listed and classified according to their predictive sensitivity. It is recommended to test reference allergens by different test methods in one's own laboratory to obtain personal experience with the various methods. Comparisons of the different methods based only on the literature are difficult, because there are so many influences on the performance of sensitization tests and because one is often not sure how the animals were termed positive, i.e. the threshold of a positive erythema score is often not clearly defined. Correlations between test results obtained in guinea pigs and man are presented for the Draize test, the maximization and the optimization test. It is emphasized that guinea pig tests are performed to assess the contact allergenic potential of a compound or formulation, but that the risk assessment is dependent on many other factors and should, therefore, be evaluated separately.
[Classification of epilepsy].
The epilepsies may, according to the particular purpose, be classified in different ways. Etiology is often unknown, but the age of onset may give a lead as to the most probable causes. In planning treatment it is important to know the seizure form, as defined by clinical observation and the EEG. The international classifications of the epileptic seizures (symptoms) and the epilepsies (diseases) are too particularized for use in daily practice. For this it suffices to distinguish the age-dependent minor attacks (flexion spasms, myoclonic-astatic petit mal, absences, myoclonic petit mal), from the partial seizures, which are divided into simple (neocortical focal) and complex (limbic) seizures. All can combine with generalized seizures (grand mal) or lead on to such.
What can specific behavioural testing procedures contribute to the assessment of neurotoxicity in laboratory animals?
Subchronic testing of laboratory animals in accordance with present regulatory guidelines involves maximum exposure with the chemical under investigation and serves for the evaluation of systemic toxicity as well as of lesions in organs and organ systems, including neurotoxicity. The primary assessment of neurotoxicity is essentially based on the overall observation of animal behaviour in the course of the customary toxicity studies and on the subsequent neuropathological evaluation with contemporary techniques. Under this maximum exposure the absence of symptoms and signs of neural abnormalities indicates that the material tested would be devoid of neurotoxicity. Any overt or suspicious symptoms for neurotoxicity appearing in the course of subchronic testing may be further characterized with additional functional tests such as neurological examination, electrodiagnostics and possibly with specific behavioural tests. The subsequent neuropathological investigation would have to be expanded to include a detailed evaluation of all neural structures possibly related with the above functional derangements. In case of relevant neurotoxicity subsequent specific behavioural tests might include the evaluation of complex neural functions such as integrated psycho-neuro-motor activity and memory. These behavioural tests might help to explain neurotoxicity and to assess behaviour at low levels of exposure. The implementation of such specific behavioural testing procedures beyond the scope of routine toxicity studies would require a group of investigators capable to carry out appropriate tests.(ABSTRACT TRUNCATED AT 250 WORDS)
Predictive contact allergenicity influence of the animal strain used.
In order to determine the validity of reported alleged differences in the susceptibility of various strains of guinea pigs to the sensitizing action of known allergens, three unrelated strains of guinea pigs, namely Pirbright White, Hartley and Himalayan spotted strain, were selected. In our investigation, 3 haptens differing in their sensitization potential were used. The results showed that the sensitivity of the 3 given guinea pig strains was comparable. Furthermore, the sensitivity of a given guinea pig strain can only be determined by comparison of the sensitization reaction of several known contact allergens of various sensitizing potential.
[Effect of the daily concentration of estradiol on the morphological characteristics of the cumulus-corona-oocyte complex obtained in in vitro fertilization programs].
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Ranking carcinogens for regulation.
In the issue of 9 August 1968 (p. 541), Science printed the Nobel lecture of Hans A. Bethe on "Energy production in stars." Eddington had at one time hypothesized that stellar energy arises from complete annihilation of matter. The energy to be set free by such a process, if it could occur, would be enough to supply the sun's radiation for 15,000 billion years. In the lecture, this number was erroneously given as 1500 billion years.
Advances in the design and reporting of conventional carcinogenicity tests.
It is generally acknowledged that animal experiments provide the most important and best reliable service of information for assessing the possible carcinogenic activity of chemicals. In the past, experimental procedure has mainly concentrated on the choice of species, improved animal husbandry, the modes of exposure, test conditions and pathological examination. Although experience gained thereby indicated the necessity for further scientific exploitation of bioassay models, the rather rigid stereotyped procedures--proposed for convenience--were generally accepted and adopted. Nevertheless, continuous improvements have been made in the design of carcinogenicity tests in rodents. Current developments in test design tend to be primarily concerned with the predictive significance of carcinogenicity studies. Modern protocols call for optimum facility operation as much as for computerized support of study monitoring and data evaluation. Of particular significance are the automated handling of autopsy and histopathological data and their proper statistical evaluation. By the economical use of modern technology, cost-saving protocols can be designed for the production of the data which are essential for the reliable assessment of risk.
[Neurophysiological mechanisms of pain perception].
Information on noxious stimuli is perceived in the periphery by free nerve endings and conveyed to the spinal cord by A delta and C-fibres. They mostly terminate within the substantia gelatinosa (SG) of the dorsal horn. Within this structure, transmission of pain information is modified by serotoninergic and enkephalinergic mechanisms. Neurones from the deeper layers of the dorsal horn relay pain information via the ventrolateral tract to the brain stem reticular formation and thalamic nuclei. From there, pathways to the somatosensory cortex, basal ganglia, and limbic structures were described, which probably mediate conscious perception, subconscious motor reactions and emotional colouring of pain perception, respectively. For the efferent control of pain transmission, the periaqueductal gray matter (PGM) is the central structure. Electrical stimulation of PGM can relieve patients at least temporarily from states of chronic pain. PGM is connected to the midbrain raphe nuclei, from where serotoninergic fibres descend to the spinal cord to modify pain transmission in neurones within SG. Enkephalin is present in the terminals of SG interneurones and reduces pain transmission by acting on opiate receptors on the terminals of nociceptive primary afferents and probably also postsynaptic sites. Analgesia produced by natural or electrical stimulation of other cutaneous afferents and by acupuncture is believed to be mediated by these enkephalin-containing interneurones within SG of the dorsal horn.
[Elevation of the threshold in the rabbit dental pulp test with coumarin: unspecified (local) effect rather than analgesic activity?].
The antinociceptive efficacy of Coumarin was tested in mice, rats, and rabbits. No increase in threshold for the antinociceptive reaction was observed in the hot plate test and tail flick response in mice and rats. Using the tooth pulp test in rabbits, the threshold for the licking reaction was increased. This effect was dose dependent and could, at least partially, be antagonized by Naloxone. Because there is no direct opiate-like activity of Coumarin, these results suggest that the effect may be mediated by the release of endogeneous opiate-like peptides. It remains totally unclear why this effect could only be demonstrated in one particular test in one species.
The value of the fluorescence histochemistry of biogenic amines in neurotoxicology.
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Radicular myelinopathy in aging rats.
Naturally occurring degenerative lesions of nerve fibers in the spinal cord, spinal roots and peripheral nerves in nine male rats 877 days old were swollen myelin sheaths, forming "myelin bubbles." The myelin swellings were distributed throughout the spinal tracts and the peripheral nerves, but most frequently in the lumbar ventral spinal roots. Although most axons surrounded by swollen myelin were intact, some were constricted and degenerated, while others showed signs of remyelination.
Pyridoxine megavitaminosis produces degeneration of peripheral sensory neurons (sensory neuronopathy) in the dog.
Pyridoxine, a water-soluble vitamin, produces a sensory neuronopathy when administered in high doses to dogs. Beagles who received a daily oral dose of 300 mg/kg of pyridoxol hydrochloride developed a swaying gait within 9 days. They eventually became unable to walk, but were not weak. Animals were sacrificed at intervals up to 78 days. Morphological examination revealed widespread neuronal degeneration in the dorsal root ganglia and the Gasserian ganglia. Cytoplasmic changes were first observed after 8 days and consisted of small, electronlucent vacuoles that subsequently coalesced leading to death of the cells. Degeneration of sensory nerve fibers in peripheral nerves, dorsal columns of the spinal cord and the descending spinal tract of the trigeminal nerve was apparent. The pathogenesis of these changes is unclear, but may, in part, reflect the selective permeability of blood vessels in the peripheral ganglia. It is apparent that the peripheral neuropathy previously attributed to pyridoxine actually represents a toxic, peripheral sensory neuronopathy.
[Diagnostic study of 114 infertile couples].
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