The impact of stress and discomfort on experimental outcome.

Stress refers to a physiological and emotional state of man and higher animals in which the autonomic regulation is overstrained and temporarily disturbed under the impact of conflicting stimuli. Stress activates, invigorates, acts life-sustaining, and initiates and drives adaptive changes towards improved fitness. While the positive action is commonly underestimated, much attention is given to the discomfort and the strain of efforts required during coping. The label of stress as being bad and the core of suffering has been applied with particular empathy to laboratory animals, for they are kept in captivity and are exposed to experimental procedures. The husbandry conditions to which the animals are adapted are commonly standardized. This applies to procedures for subacute and chronic toxicity testing. Acute toxicity tests are the classical example of stress research in which the demands on the organism exceed the limits of its regulative capacity. Stressors are: the test compound, the procedure proper and preceding treatment of the animal. The experimental stress contributes to model the real situation. The weighting between the stressors may modify the outcome of the test.

[Human adaptation to climatic changes]. / Adaptation des Menschen im Klimawechsel.

The causes for the currently predicted change in climate result from behaviours of the rapidly growing human population consuming more natural resources for fulfillment of more natural resources for fulfillment of basic needs and high demands on health and comfort and interfering with homeostasis mechanisms of nature beyond adaptive capacities. Human adaptive potential is considered and strategies for adaptation are outlined aiming at an equilibrium between human and natural systems by behavioural modification, without loss of basic needs for health.

[Multiple sclerosis: atrophy of the corpus callosum and psychosyndrome]. / Multiple Sklerose: Balkenatrophie und Psychosyndrom.

Examination with magnetic resonance imaging of 176 patients with multiple sclerosis showed that corpus callosum (CC) atrophy is common. The thinning of the CC depends on the extension of the coalescent periventricular white matter changes. A highly significant association was found between CC-atrophy and, the severity of organic mental disorder.

[Allergies to laboratory animals. An epidemiological, allergological study in persons exposed to laboratory animals]. / Labortier-Allergien. Eine epidemiologische, allergologische Studie bei Labortier-exponierten Personen.

The nature, frequency and symptoms of laboratory animal allergies (LAA) were explored in 110 persons having contacts with laboratory animals and working in research laboratories at Zürich University Hospital and institutes. 20.9% of these persons were actually suffering from a laboratory animal allergy, a percentage corresponding to international reports in the literature (12-27%). 82.6% of persons with LAA were atopic subjects. In a group without LAA we found an atopic disposition only in 25.3%. The commonest signs of LAA were a combination of rhinoconjunctivitis with bronchial asthma and with contact urticaria in 43.5% over-all. Rats and mice were the laboratory animals most contacted and they represented the largest number of sensitizations. The interval between the beginning of exposure and onset of the symptoms of LAA ranged between a few months and many years. In general, the time space is much shorter in atopic subjects than in non-atopic persons. Skin tests gave better and more precise results in the detection of a LAA than in vitro examinations. This means that investigations with RAST (PHARMACIA) were less sensitive than the prick multitest (STALLERGENES). The last-mentioned can be recommended as very good for serial allergological examinations. The new Phadiatop-test (PHARMACIA)--in the study we obtained positive results in 38.5%--is a sound and most specific examination for discrimination between atopic and non-atopic disposition. Determination of total IgE was of less value.

The influence of climatic factors on the nasal mucosa of rats.

The influence of indoor climate on goblet cells and intraepithelial glands of nasal mucosa was analysed. A cold and heat adapted group of twenty rats were compared with a neutral adapted group after eight weeks of climatic exposure. There was a decrease of density of the goblet cells and the intrapeithelial glands in cold adapted rats. It is suggested that the adaptive changes of the mucous membranes of the rats may be correlated with the increased ventilation rate in the cold.

[Prognostic significance of lacunar lesions in magnetic resonance tomography in multiple sclerosis]. / Die prognostische Bedeutung von lakunären Herden im Magnetischen Resonanztomogramm bei Multipler Sklerose.

175 patients with definite multiple sclerosis underwent nuclear magnetic resonance imaging. T1-weighted images showed in 59 patients (34%) periventricular lesions with a central area of decreased signal intensity. They appear as lacunar defects in the walls of the lateral ventricle system. In accordance with neuropathological findings we suggest that in these plaques a cystic degeneration has replaced gliosis. Patients with cystic defects are characterized by a high activity of the disease (e.d. increased annual production of plaques) and a poor prognosis. Lacunae are found in the early stages of the disease and provide a prognostic sign in multiple sclerosis.

[Diagnostic value of magnetic resonance tomography in disseminated encephalomyelitis]. / Zur diagnostischen Wertigkeit der magnetischen Resonanztomographie bei Encephalomyelitis disseminata.

In 83 of 86 patients with multiple sclerosis (MS) cranial magnetic resonance imaging (MRT) demonstrated lesions consistent with the clinical diagnosis. All the patients had either clinically typical MS oralaboratory-confirmed diagnosis of MS. The sensitivity of MRI is compared to those of computed tomographic (CT) scanning, evoked potential testing and cerebrospinal fluid analysis. The features of MS revealed by MRI are interpreted in terms of the macroscopic pathology and correlated with the clinical findings. The importance of particular findings (cystic appearance of lesions, spread of periventricular patches into the centrum semiovale) for the patients prognosis in stressed.

[Bone replacement using beta-tricalcium phosphate--results of experimental studies and initial clinical case examples]. / Knochenersatzplastiken mit Beta-Tricalciumphosphat--Resultate experimenteller Studien und erste klinische Fallbeispiele.

Beta-Tricalcium phosphate granulates (Ceros 82) implanted in femurs of the rat led to osteoconduction already one week after implantation. Compared to the problems of autologous implants, TCP presents many advantages: No operation on the donor site, no limitation of quantity, clinically negligible resorption, immediate osteoconduction. The results on femoral defects of 26 rats filled up by beta-TCP and our first clinical experiences on juvenile bone cysts are presented.

Regulation of animal experimentation. The international experience: Switzerland.

The reviewer is head of a Central Animal Laboratory of a Medical Center, where about 140 researchers, chiefly M.D.'s work on 11 species: monkeys, dogs, cats, calves, pigs, sheep, rabbits, guinea pigs, rats, mice and gerbils. In 1984 there were 120 licence projects with 32.000 experiments, 74% were carried out on mice, 24.6% on rats and the rest on the other species. Approximately two third of all animals were used for in vitro studies. Each researcher has to apply for a licence for a limited project by giving the title, a brief description of the method, his reasons for wanting to do the experiment and the value of the expected results, and the exact number of animals required. Details of the planned experiments are discussed with the staff of the Central Animal Laboratory. All information is filled in by the responsible researcher on a nation-wide standardized form. The completed form is signed by the head and forwarded by the secretariat to the Cantonal Veterinary Department. Four copies are submitted of which one goes to the Federal Veterinary Department. All applications for a licence are handled by the cantonal veterinary officer. The decisions are controlled by a Cantonal Commission for animal experiments, consisting of 8 members out of which 4 are animal protectionists. In addition the Department of Education has set up a bioethical commission consisting of 4 members of the university, one from the veterinary faculty, two from the medical faculty and one from the life sciences. This commission can also be called on by a researcher if he needs to clarify points before the application is submitted. The animal protection law requests the cantonal veterinary officer to make a thorough check of the project which often demands one or more letters asking for further information. He has to check whether an animal experiment is necessary at all, whether the experiment is properly designed, whether animals of lower order could be used and whether the demanded number of animals is needed. After a project has been completed or every year for a larger project, the number of animals used in the project has to be reported to the cantonal veterinarian who will prepare statistics on total number of animals used. A division of the experiments into in vivo and in vitro experiments will be prepared and categorization according to the estimated degree of stress and pain is being considered.

Use and misuse of an imprecise concept: alternative methods in animal experiments.

The concept of inhumanity of Russell & Burch in 1959 with proposals for human procedures in experiments on animals by way of replacement, reduction and refinement (the 3 R's) and the revival of these by Smyth (1978) as alternatives to animal experiments are presented. Since then under the name 'alternative methods', replacement of in vivo by in vitro methods has found great public attention and promotion. It is argued that alternative methods are a fallacy, because in the progress of research a continual control and reinvestigation of findings on each system level is required until knowledge is complete, which makes in vivo experiments irreplaceable. True alternatives exist only for refinement within a system level. On the level of the organism, refinement would be in the care of animals and experimental procedure through alleviation of stress. The possibilities which refinement offers for animal welfare have been nearly forgotten and need promotion among researchers, animal technicians and attendants.

The haematological and cardiac patterns of adaptation of rabbits to 4,500 m simulated altitude and of readaptation to 400 m.

The haemoglobin (Hb), red blood cell count (RBC) and haematocrit (Hct) of 11 male rabbits were measured at weekly intervals during a 5-week exposure period to hypobaric hypoxia (simulated altitude, 4,500 m) and the following 4 weeks after restoring normoxic conditions in a climatic chamber at constant temperature. RBC showed the slowest response, Hct the fastest during adaptation to hypoxia and readaptation to normoxia. The body weight decreased during the 1st week at hypoxia and remained at a reduced level for 2 weeks after the return to normoxia. In female rabbits exposed up to 43 days to hypoxia the heart ventricle quotient (HVQ) (weights of left ventricle + septum/right ventricle) was determined. There was a gradual decrease of HVQ expressing the development of right heart hypertrophy which was not stabilised within the observation period.