Inhibition of aspartate release from the retina of the anaesthetised rabbit by stimulation with light flashes. Rabbits were anaesthetised and the cornea, iris, lens and vitreous were removed from eyes to form an eye-cup which was filled with Krebs-bicarbonate Ringer. The medium in the eye-cup was replaced at 10-min intervals and the amino acids in each resulting sample were assayed. Exposure of the dark-adapted retina to flashes of light (3 Hz) did not alter the efflux of glutamate glutamine, alanine, glycine or GABA. The efflux of taurine and ACh was greatly increased by light flashes, but in contrast, the release of aspartate was reduced by more than 50%, a result consistent with the suggestion that aspartate may be a photoreceptor transmitter substance.


Immunoreactive somatostatin release from rat spinal cord in vitro. A calcium-dependent release of immunoreactive somatostatin from rat spinal cord in vitro in response to two depolarising stimuli (60 mM KCl and 75 micrometer veratrine) has been demonstrated. Released somatostatin immunoreactivity comprised 0.53% of total tissue content, showed parallelism when serial dilutions were compared to the immunoassay dose-response curve and eluted similarly to synthetic somatostatin on Sephadex G-25 (f) chromatography. These results provide further evidence for a neurotransmitter or neuromodulator role for somatostatin in mammalian spinal cord.


A statistical model supports the subunit hypothesis of quantal relsease. Successive frequency amplitude histograms of miniature endplate potentials (MEPPs) from mouse neuromuscular junctions show peaks at integral multiples of the smallest peak (s-MEPPs). The s-MEPPs are assumed to have normally distributed amplitudes and to represent the subunit size. A model has been derived from assumptions based on the hypothesis of MEPPs are generated by the synchronous release of transmitter subunits. The model was statistically tested on amplitude histograms and in the majority of cases the model produced extremely good fits to observed distributions.


Mesolimbic dopaminergic neurones and somatodendritic mechanisms. The concept that a neurone may release transmitter from both dendritic and axonal sites was investigated by studying mesolimbic dopaminergic neurones. The rat ventral tegmentum (containing dendrites and somata of mesolimbic dopaminergic neurones) possessed high levels of dopamine and tyrosine hydroxylase. Slices of ventral tegmentum accumulated [3H]dopamine (15 or 60 nM) and stimulus-induced release of [3H]dopamine was observed after elevated potassium (44 mM). The potassium-induced release was calcium-dependent. These dopaminergic parameters were compared to those found for nucleus accumbens (containing terminals of mesolimbic dopaminergics neurones). Thioridazine and clozapine elevated 3,4-dihydroxyphenylacetic acid (DOPAC) concentration in ventral tegmentum.


Projections of intestinal neurons showing immunoreactivity for vasoactive intestinal polypeptide are consistent with these neurons being the enteric inhibitory neurons. Experiments were performed to determine if the distribution of vasoactive intestinal peptide(VIP)-like immunoreactivity in nerve cell bodies and axons of the myenteric plexus and circular muscle of the small intestine is consistent with VIP being the transmitter of enteric inhibitory neurons. Immunoreactivity for VIP was found in nerve cell bodies of the myenteric plexus and in axons within the myenteric plexus and circular muscle. When the axons in the myenteric plexus were interrupted, there was accumulation of material showing reactivity for VIP on the oral side, indicating that the neurons project in an anal direction. The VIP-like immunoreactivity in axons which supply the circular muscle disappeared after a myectomy in which the overlying myenteric plexus was removed, but remained intact when extrinsic nerves were served. The projections of VIP neurons from the myenteric plexus to the circular muscle correspond to the expected projections of enteric inhibitory neurons determined by functional studies.


Effect of runway training on rat brain tyrosine hydroxylase: differential effect of continuous and partial reinforcement schedules. Previous experiments have implicated ascending noradrenergic systems in the development of the behavioural responses to different patterns of reward. In this report food deprived male Sprague--Dawley rats were trained to run a straight alley for good reward on a continuous reinforcement (CRF) or a partial reinforcement (PRF) schedule. Tyrosine hydroxylase measured in a partially solubilized preparation from hippocampus and hypothalamus at the end of acquisition was not different from controls, indicating that enzyme induction does not occur during either training schedules. However, hippocampal synaptosomal tyrosine hydroxylation rates from the CRF group was significantly higher than from either the PRF group or the handled controls. This indicates that at the end of the acquisition schedule the noradrenergic projection to hippocampus was more active in the CRF group than with the PRF group or the handled control.


The role of bacterial enzymes in inducing inflammation in the middle ear cavity. Current knowledge of the pathophysiology of bacterial infections is elementary. Thie initial events leading to the invasion of host tissues are a matter of conjecture for many bacterial organisms. This is particularly true for pneumococci, the most frequent causative organisms of acute otitis media. Bacterial enzymes may account for the initial disruption of host tissues, and this study explored their role in the infectious process. As first step, pneumococcal cultures were analyzed, and significant levels of the enzymes lipase and hyaluronidase were demonstrated. Secondly, the presence of these enzymes in middle ear effusions was explored in an animal model of acute otitis media. The enzymes reached peak levels at seven days. The third and most important portion of the study examined the significance of these enzymes in producing inflammation and alterations in the middle ear cavity of normal experimental animals. This portion was a histologic comparison of temporal bone specimens and demonstrated that marked acute and chronic changes can be induced by placing solutions of these enzymes in the middle ear cavity. This study concludes that bacterial enzymes play an important role in the induction of acute otitis media.


The neuroendocrine system of the gastrointestinal tract. The use of increasingly refined techniques in endocrinologic research resulted in a challenge to the classical concept of hormones. The regulatory activity of the highly complicated neuroendocrine system is mediated not only by hormones but by neurotransmitters, paracrine substances, and possibly by substances secreted into the gastrointestinal lumen as well. The system is divided into the central and peripheral nervous system and the endocrine system. The latter consists of the endocrine glands and the disseminated endocrine system. Research into the activities of the system will result in important advances in the fields of physiology, pathophysiology and pathology.


[X-ray diffraction analysis of disintegration of polyglycolic acid suture material both in vivo and in model media]. Examined were the structural variations of polyglycolic acid surgical suture material by X-ray diffraction methods subsequent to sejour in vivo and in several model mediums. After a long stay in vivo, water and buffer at pH 2 the following structural variations in the polymer were observed: diminution of macroperiod, and certain increase of crystallinity. Rather profound, ten times faster destruction of suture material in alkaline medium at pH 12 did not cause the variation of macroperiod and crystallinity. Even in the case of extensive destruction with mass losses approaching 90% and variation of crystalline structure of the polymer was not observed. These data confirm the theory described previously by the authors on the existence of two possible methods of polymer destruction in aggressive mediums passing through total volume and on the plastic surface only.


"Classical" and "atypical" antipsychotic drugs: differential antagonism of amphetamine- and apomorphine-induced alterations of spontaneous neuronal activity in the neostriatum and nucleus accumbens. The ability of clozapine and haloperidol to antagonize the depression of firing rate produced by d-amphetamine and apomorphine in the neostriatum and nucleus accumbens was tested in immobilized, locally anesthetized rats. In the neostriatum, an intraperitoneal injection of 2.5 mg/kg d-amphetamine or 1.0 mg/kg apomorphine produced a prolonged inhibition of neuronal activity that was reversed by a subjsequent injection of either 20 mg/kg clozapine or 2.0 mg/kg haloperidol. An analysis of the onset and magnitude of the blockade revealed that clozapine was more effective than haloperidol in reversing the amphetamine response but that both antipsychotic drugs produced a comparable blockade of the apomorphine-induced depression. Similar results were obtained in the nucleus accumbens. The data indicate that although clozapine acts equieffectively in the neostriatum and nucleus accumbens, this atypical antipsychotic drug, aside from blocking postsynaptic dopamine receptors, may exert at least some of its effects by preventing dopamine release.


Comparison of the long-term cumulative effects of reserpine and syrosingopine on general activity. Reserpine, but not syrosingopine, produced a cumulative decrease in general motor activity when administered once every 10 days for a total of 8 drug treatments. The maximum depression of activity was evident following the second reserpine administration. Following a 30 day drug-free period animals previously treated with reserpine still exhibited decreased motor activity. The data suggest that chronic reserpine treatment may result in long term, and perhaps permanent behavioral effects.


Displacements of Simulium damnosum and strategy of control against onchocerciasis. Regular aerial treatment of 14 000 km of watercourses has achieved and maintained, over an area of 700 000 km2 of West African savannah, a very high degree of control of the larvae of Simulium damnosum sensu stricto and S. sirbanum, the vectors of onchocerciasis in this area. However, particular and relatively restricted parts of this area, mainly in northern Ivory Coast and neighbouring parts of Upper Volta, experience regular and prolonged reinvasions by parous female vectors, which have already taken bloodmeals (and many of them carrying the parasites) and arrive from unknown sources probably hundreds of kilometres away, from directions probably between southwest and north. This reinvasion, now experienced in three successive years, represents the outstanding scientific, epidemiological and logistic problem still facing the WHO Onchocerciasis Control Programme. An outline is presented of the multidisciplinary investigations being undertaken to find a solution.


Strategies, systems, value judgements and dieldrin in control of locust hoppers. The physiology and field biology of locusts have been extensively studied, and ecological control of Red Locusts has been investigated by field experiment. No fruitful or even promising non-insecticidal method of control has emerged. An effective and economical system requires an insecticide that is: (i) effective at very small area dosages, as a stomach poison placed on the natural vegetation can be, if it is also cumulative; (ii) persistent enough in sunshine and rain to retain effectiveness over the locust's non-feeding periods; (iii) capable of being well distributed by well-tried methods; and (iv) not dangerous to users or consumers and posing a minimal overall risk. Only one insecticide, dieldrin, satisfies all these requirements. Dieldrin is not in the small class of insecticides that are dangerous to man by skin absorption (such as parathion, arsenicals, DNC) and, at the area dosages needed for locust control, is not dangerous to stock. The Sayer exhaust sprayer in a Land Rover, with work rates of the order of square kilometres per hour is excellent for many situations; aircraft spraying at he rate of square kilometres per minute is quicker and less subject to difficulties of terrain, but requires trained and appropriately directed aircrew. Apart from checking, aircraft methods require no party on the ground to find, assess and control locust hoppers. Several ideas about dieldrin are found to be based on insufficient evidence and are probably not true: for example that dieldrin in the atmosphere at a few parts in a million million (10(12)) becomes concentrated in a food web and harmful to man, or that dieldrin is carcinogenic in man. It is noteworthy, however, that one species of antelope in South Africa is exceptionally susceptible to dieldrin poisoning, though harm occurs at area dosages considerably greater than are required in the method of aircraft spraying of Courshee & McDonald (1963). To attack tsetse flies, emissions two orders of magnitude greater have been used. Care must be taken with any insecticide, but the risks of using dieldrin as properly used in locust hopper control have been exaggerated by propaganda. If harm is to be expected, then a quantitative comparison of that with the undoubted benefits of locust control is required to enable one to make a value judgement.


Pesticides for locust control.

Pesticides for locust control. The factors influencing the choice of insecticides for locust control are effectiveness, safety in use, relative cost, and the formulations available. The relative importance of these factors varies with the scale of control. In small scale control by farmers safety and simplicity are paramount and a BHC dust is commonly used, but in large scale control operations by specialized organizations more toxic formulations ultra-low-volume (u.l.v.) concentrates and methods of application requiring considerable skills can be used. The remarkable effectiveness of dieldrin as a stomach poison appears to be due to its conversion to photodieldrin after application. Cases of poisoning following large scale control operations are rare, and fatalities in man unknown. Alternatives to organochlorine insecticides include fenitrothion, already recommended and used on a large scale against adults. Against nymphs the correct dosage of fenitrothion would cost nearly 11 times as much as that of dieldren. Recent experimental work with new insecticides has included safety tests with domestic animals and measurements of persistence. 1 microgram deposits of cyanofenphos, decamethrin and mecarphon, as well as of dieldrin and photodieldrin, on wheat seedlings left in the open under tropical conditions for two days, killed 80% or more first instar nymphs of the Desert Locust which fed on them.


Geochemical surveys in the United States in relation to health. Geochemical surveys in relation to health may be classified as having one, two or three dimensions. One-dimensional surveys examine relations between concentrations of elements such as Pb in soils and other media and burdens of the same elements in humans, at a given time. The spatial distributions of element concentrations are not investigated. The primary objective of two-dimensional surveys is to map the distributions of element concentrations, commonly according to stratified random sampling designs based on either conceptual landscape units or artificial sampling strata, but systematic sampling intervals have also been used. Political units have defined sample areas that coincide with the units used to accumulate epidemiological data. Element concentrations affected by point sources have also been mapped. Background values, location of natural or technological anomalies and the geographic scale of variation for several elements often are determined. Three-dimensional surveys result when two-dimensional surveys are repeated to detect environmental changes.


Epidemiology for geochemists.

Epidemiology for geochemists. Epidemiologists study the distribution and the determinants of disease in human populations. Geochemists may be more concerned to find diseases to fit the observed patterns of geochemistry. This paper is concerned with the application of epidemiological techniques to the interrelations between health, disease and geochemistry, with particular reference to the hazards of man-made chemicals in the environment. Descriptive studies of disease in terms of person, place and time allow for crude comparison with the results of geochemical mapping and for the development of hypotheses. Analytical studies allow for the exploration of these hypotheses but demand careful sampling techniques and vigorous quality control. The epidemiological approach should be directed towards the identification of national/regional problems and of high-risk groups, the definition of priorities and the opportunities for preventative measures. The problems and possibilities for epidemiological research are illustrated from recent and current studies.


A review of recent activity in the United States. Either an overabundance or a deficiency of trace metals in the food chain can ultimately affect adversely the health of livestock and man. Increasing interest in the United States in the distribution of metals in the environment and in metal pollutants has led to widespread interdisciplinary research sponsored by governmental, private and academic groups concerning the availability of trace elements for absorption by plants and animals, and the effects of trace elements throughout the food chain. The state of the art and the needs for research are reviewed by interdisciplinary committees in the National Academy of Sciences and in many government agencies. Research is encouraged through contracts and grants awarded by federal and state agencies and the National Science Foundation to universities for studies of specific metals, specific diseases and correlations between metals and health in specific geographic areas. Effects on the environment of coal-fired power plants, the mining and processing of metals, asbestos, and phosphate, and the disposal of industrial and nuclear wastes have also received much attention in the past few years.


Trace elements in soils and crops.

Trace elements in soils and crops. To demonstrate the total amounts to be expected in soils, the ranges of contents of some 60 trace elements in ten representative Scottish arable surface soils are compared with ranges in soil-forming rocks and with crustal averages. It is, however, the amounts potentially available to plants rather than the total contents that are biologically significant. In temperate climates, trace element mobilization is greatest when weathering takes place under conditions of impeded pedological drainage, leading to the formation of gleyed soils. Mobilized trace elements occur in arable surface soils largely in adsorbed and chelated forms, which are available to plants to a greater or smaller extent depending on the prevailing soil parameters and on the element in question. Different species take up different amounts of trace elements: the proportions in the various plant parts vary with the element and the stage of growth. Information is required about the mobilization and uptake of many elements about which little is at present known but which may affect the functions of essential elements through inter-element interactions. Systematic soil surveys in which soils are mapped by associations related to parent material, with their series related to genetic soil types, provide a useful countrywide guide to trace element status.


Geochemistry and health in the United Kingdom. Before the 1960s, comparisons between the distribution of trace elements in the environment and health in the United Kingdom were primarily confined to ad hoc studies in areas associated with particular agricultural disorders or with unusual human mortality or morbidity records. More recently, increasing interest in the importance of trace elements in crop and animal production and in the hazards of environmental pollution have created a need for more systematic geochemical data. Geochemical reconnaissance maps for England, Wales, Northern Ireland and parts of Scotland have demonstrated the extent of many known clinical trace element problems in agriculture and have also been valuable in delineating areas within which subclinical disorders may occur. Their application to studies on the composition of soils, food crops and surface waters in relation to public health has proved encouraging. Current knowledge and present investigations into environmental geochemistry and human health in the U.K. are reviewed, together with future research requirements.


Geochemistry and ecology.

Geochemistry and ecology. This paper discusses the importance of geochemistry as a determining factor in the evolutionary development of plant assemblages. Three contrasting examples of geochemical systems are described and considered in relation to their effects on plant growth and development. Soils derived from serpentines may contain elevated and sometimes toxic concentrations of Cr and Ni depending on mineral composition and weathering processes. These conditions have so modified plant growth during the past few million years that specialized floras have evolved on particular sites. Extensive areas throughout the world contain high concentrations of Se but these have not always been accompanied by the development of specific floras. Geochemistry can help explain how Se-specific floras have developed in several Western States of America but are absent on Se-rich sites in the Republic of Ireland. Pronounced effects of As toxicity in plants have been recognized in recent years especially from areas polluted by smelter waste and fallout. As-tolerant genotypes have developed during the past 100 years and may still be evolving at the present time.


Geochemistry and pollution.

Geochemistry and pollution. During the past 7 years, the National Science Foundation-Research Applied to National Needs (R.A.N.N.) programme has supported extensive interdisciplinary research concerned with Pb, Cd and other hazardous trace metals. Various aspects of geochemistry and pollution research at the universities of Missouri, Illinois, Colorado State and Purdue are presented and summarized. The transport, pathways and distribution of Pb, Cd and other trace metals are discussed and the utilization of research findings by government and state agencies for the development of standards and by industries for pollution control are presented.


Geochemical ecology and problems of health. The state of health or disease is determined by the nature of the organism, the properties of the biosphere, the heterogeneity of its natural geochemical composition and changes brought about by technology (technogenic changes). For a systematic study of the conditions of health and endemic diseases we have suggested a system of biogeochemical regionalizing of the biosphere with the aid of biospheric taxa: regions of the biosphere, subregions of the biosphere, biogeochemical provinces. The main criteria of the regionalizing are biogenous cycles of chemical elements (links of the biogeochemical food chain from soil-forming rocks to man). An important criterion of the biogeochemical regionalizing is threshold concentrations of chemical elements. The organism regulates its metabolism within the ranges of chemical element concentration between the upper and lower thresholds (necessity range). When chemical elements are present in concentrations above the upper threshold and below the lower threshold, dysfunctions and endemic diseases are observed. Hence, the biogeochemical food chain allows us to establish critical links responsible for the state of health or endemic disease. Principles of optimizing the conditions of the environment and life have been worked out. The creation by us in the U.S.S.R. of biogeochemical maps relating conditions of the environment to biological reactions of organisms has proved a useful method of studying the ecological structure of the biosphere.


Geochemistry and cardiovascular diseases. Deficiencies or excesses in the content or availability of trace elements in rocks and soils, or in water flowing through them, is hypothesized as a possible cause of certain chronic diseases, including cardiovascular diseases. Geographic distribution of cardiovascular diseases is often associated with geochemical differences. This trend is particularly evident in the United States and in Europe, with higher rates for cardiovascular mortalities being present in areas uunderlain by soils that are poor in most essential trace elements. Confirmation of this trend is found in connection with the degree of mineralization of local water supplies. Areas that are served by soft waters usually show higher rates of cardiovascular mortality and other forms of cardiovascular pathology, compared with the areas that are served by hard waters. Such a negative association between water hardness and cardiovascular pathology is evident in many countries, both industrialized and developing.


Geochemical and man-made sources of lead and human health. Multiple sources of Pb have been identified for human populations, but there is little agreement as to their relative significance. Marked regional geochemical anomalies in the distribution of Pb have been identified and, in one district, their impact on rural communities has been determined. The absorption of ingested Pb is modified by its chemical and physical form, by interaction with dietary minerals and lipids and by the nutritional status of the individual. Studies on children of various ethnic groups have demonstrated differences in soft tissue Pb burdens which may in part have a nutritional basis. Erythrocyte protoporphyrin determinations suggest that metabolic disturbances attributable to Pb may occur at soft tissue burdens previously regarded as acceptable. The problem of defining an adverse health effect in relation to environmental sources of Pb is discussed.


Trace metals in waters.

Trace metals in waters. The topic of this paper is extremely broad, and to allow more useful discussion, emphasis is placed on trace (less than 1 mg/l) metals in fresh surface waters and in drinking waters. An attempt is made to give a broad overview of current knowledge, problems and research with particular reference to the following: (1) metals of interest, current standards of water quality relevant to health, and concentrations of metals in waters; (2) sources of, and other factors affecting, the concentrations of metals; (3) general problems in the measurement of metal concentrations; (4) important research topics.


Trace elements in the atmosphere.

Trace elements in the atmosphere. The distribution and behaviour of particulate trace elements in the atmosphere have been studied by continuous measurements for 5 years at seven non-urban sites in the United Kingdom. Samples have been taken regularly of airborne dust, rainwater and dry deposition: these have been analysed for up to 36 elements. Concentrations of trace elements vary considerably between sites but the relative concentrations are among uniform: this suggests similarity of origin or good atmospheric mixing. By comparing the relative concentrations with those in soil it is possible to differentiate between trace elements that are derived from soil and those that may be attributed to industrial activity. This classification is supported by estimates of the particle sizes in air. The deposition of trace elements can be related to the concentrations presnet in soil and to the annual removal by crops. Retrospective analyses of stored samples from one site describe the history of trace element concentrations in air since 1957. The sea surface is considered as a possible source of atmospheric trace elements.


Trace elements and health: an overview.

Trace elements and health: an overview. Trace element deficiencies, toxicities and imbalances in man are more difficult to relate to geochemical factors than they are in farm animals. The reasons for this are discussed and examples of such differences between man and grazing animals presented. The most convincing evidence of a geochemical causal link with human disease comes from the incidence and distribution of endemic goitre. The influence of technological developments upon this relation is discussed. Other associations between the physical environment, including the air and drinking water, and to health are given and critically examined in relation to the criteria necessary to distinguish between association and causation. The nature and extent of man-made modifications of the natural geochemical environment through technological change are discussed in relation to intakes of Fe, I, Zn, Pb and Se and their relation, in turn, to human health and disease. The currently proposed permissible limits or maximum tolerances of potentially toxic elements are presented, and the importance to these tolerances of the chemical and physical forms of the element and their metabolic interactions with other elements is emphasized.


Trace elements in animals.

Trace elements in animals. Trace element deficiency and toxicity in animals induces a wide variety of clinical effects although few are sufficiently specific to permit diagnosis without supporting investigation of changes in tissue trace element content or of the activity of metabolic processes influenced by trace element supply. Study of such trace element dependent processes has shown that extensive changes often arise before overt signs of disease appear. Some of these subclinical effects have pathological consequences and thus cannot be ignored when seeking correlations between geochemical anomalies and disease incidence. Many past estimates of the quantitative requirements of animals for the essential trace elements are imprecise. Although recent work is providing clearer definition of requirements, many common dietary components have a marked influence upon the efficiency with which such elements can be utilized from the diet. Recent evidence indicates that such antagonists influence both the absorption and the subsequent fate of essential and toxic elements in body tissues and these processes have to be taken into account when investigating the aetiology of disorders believed to be attributable to anomalies in trace element supply. Their existence is not always detectable if attention is confined to the trace element analysis of body tissues or to the nature of clinical lesions. Provided the complexity of soil-plant-animal relations with respect to trace element supply is fully recognized in the interpretation of data, the geochemical approach to the initial recognition of areas associated with a high risk of anomalies in trace element supply to animals and man has considerable potential value. This is already apparent from investigations upon the incidence of trace element problems in animals. As yet, its validity for similar purposes in man is less fully established.


Trace elements in man.

Trace elements in man. It is likely that most, if not all, of the elements found to be essential in animals will be shown to be so for man, and the clinical picture produced by deficiency of the elements in the human patient will differ little from that seen in the animal, although this has been established for only five elements (I, Fe, Cu, Co and Zn). However, the link between lack of a given element in the soil and a human patient is far less direct and much more complex than that met with in the animal grazing on deficient pastures, except in isolated primitive communitis. Zn is the most protean of the trace elements and has been chosen to illustrate this in human practice. Excesses of essential elements (both trace and major) give rise to toxic effects and the importance of a proper balance especially of the transitional elements in the human diet is discussed with special reference to Cu, Zn and Fe. Certain non-essential trace elements are individual and community hazards: Cd, Pb and Hg are the principal offenders for humans. Mankind is now largely dependent on grassland products, cereals and livestock with increasing dominance of the former in human nutrition. This has reduced the bioavailability of trace elements so that study of trace metals, especially Zn and Cu, in skeletal and dental remains at human burial and occupation sites should prove useful in assessing the consequences of this striking change in dietary habits.


Regional geochemical mapping.

Regional geochemical mapping. One of the prime requirements for effective study of environmental geochemistry in relation to health is the production of multi-element atlases showing the distribution of the elements on the regional scale. The choice of method for compiling such atlases can vary according to a number of geological, environmental and other factors. The overriding consideration, however, is to assist (in conjunction with other relevant sources of information) in defining, quickly and cheaply, potential problem areas wherein to concentrate more detailed studies to ensure maximum return from the funds and scientific manpower available. Numerous sampling and analytical techniques have been employed. Each technique and approach has its own scope, limitation and problems of interpretation. Whatever method is chosen, the use of computer-based statistical data reduction, analysis and map compilation is mandatory. Although it was apparent more than 20 years ago that geochemical atlases would eventually become a national cartographic requirement, regional geochemical mapping is still in the experimental stage. This trend is now evident in activity in a number of countries. The methods being employed, however, are so diverse that there is an urgent need for international collaboration aimed at securing data that are as mutually compatible as possible, having regard to the conditions, needs and resources of the individual countries involved.


Regional geochemical mapping and interpretation in Britain. Regional geochemical atlases of Britain and the British North Sea prepared by the Institute of Geological Sciences are discussed with special reference to their environmental significance. Factors affecting the selection of sample types are considered, and sample preparation, analytical procedure and monitoring error discussed. Stream sediment is shown to be the optimum sample type for regional geochemistry in areas of upland Britain underlain by crystalline bedrock, although soils may provide the optimum sample medium in areas of intensive agriculture. Geochemical mapping of the continental shelf is based on superficial seabed material obtained by grab or cone dredge. Examples of geochemical maps of northern Scotland for several elements of environmental significance including Cu, Mo, Pb, and U are considered in relation to geology, topography, vegetation, land use and the chemistry of surface waters. Geochemical maps are shown to provide the best available source of information on chemical variations in bedrock, although there are many difficulties in relating geochemical or biological activity to the total trace element values. In any attempt to correlate trace element levels with disease, careful consideration must be given to factors affecting the availability and flux of the trace elements if meaningful associations are to be obtained. Geochemical maps of the North Sea indicate that the contents of Cu, Pb, Zn, Cd and Hg are uniformly low over most of the offshore area although higher concentrations occur in coastal samples. The highest concentrations of Cu, Pb and Zn occur off the Tyne estuary while the highest values for Cd and Hg occur further south.


Reversible and irreversible changes in hydrogen ion titration curves of melanins. Hydrogen ion titration curves obtained on melanins prepared and modified differently show recognizable differences. Melanin prepared with NaOH exhibits irreversible loss of functional groups in the base range once titrated acidic. Melanin prepared with NH4OH shows two main branches selected by incubation at an extreme pH for 24 h. Longer exposure reveals other curves but they disappear once a 24-h schedule of titration is resumed. The existence of two major pH branches appears consistent with the oxidation-reduction properties of melanins. These results demonstrate the ability to obtain a reproducible feature in the hydrogen ion titration curves. Thus it is finally possible to quantitate CO2 adsorbed to melanin in solution at basic pH.


Verdohemoglobin as a substrate for proteases is applicable to assays over a wide pH range. Verdohemoglobin, a heme-modified derivative readily obtained by ascorbic acid-coupled oxidation of oxyhemoglobin, was found to be a suitable substrate for protease with which assay can be carried out at all pH values. The advantage of verdohemoglobin over such popular substrates as alkali-and-urea-denatured hemoglobin and casein was demonstrated by a pH-profile study with Pronase E.


Cat liver cystathionase.

Cat liver cystathionase. Cat liver cystathionase was about 300-fold purified in comparison with the supernatant of the homogenate, and the characteristics were compared with those of rat. Optimum pHs for several substrates were found to be somewhat lower, and isoelectric point remarkably lower, in cat than in rat. Molecular weight of the cat liver cystathionase was about 158,000.


d-Amphetamine and punished responding: the role of catecholamines and anorexia. Rats were trained to press a lever for food on a schedule in which components of variable interval reinforcement (V12') alternated with conflict components in which every response resulted in food delivery and footshock. Low doses of d-amphetamine selectively suppressed responding in the conflict component in a dose-dependent manner, whereas prefeeding suppressed responding in both components. Pretreatment with noradrenergic blocking agents (propranolol, phentolamine and phenoxybenzamine) did not diminish the suppressant effect of d-amphetamine, but this effect was reduced by pretreatment with alpha-methyl-para-tyrosine methylester and dopamine blockers (spiroperidol, haloperidol and clozapine) indicating that d-amphetamine was exerting its selective suppressant effect via the release of dopamine. It is suggested that the effects of low doses d-amphetamine on behaviour in conflict situations may provide a useful model for investigating the mode of action of neuroleptic drugs.


Normal prolactin responses in tardive dyskinesia. Tardive dyskinesia has been hypothesized to be caused by a neuroleptic-induced dopamine hypersensitivity in the nigrostriatal system. This study evaluated with dopamine antagonists the possibility that such dopamine hypersensitivity extends to the tuberoinfundibular dopamine (TIDA) system, which regulates, by inhibition, pituitary prolactin secretion. Plasma prolactin concentrations in six patients with tardive dyskinesia were assessed in four conditions: During chronic haloperidol therapy; serially after abrupt haloperidol withdrawal; while unmediated; and in response to an acute dose of 0.5 mg IM haloperidol. In all four conditions, prolactin responses did not differ from those observed in normal subjects and schizophrenic patients without tardive dyskinesia. It is concluded that there is no evidence for post-synaptic dopamine hypersensitivity in the TIDA-pituitary pathway in patients with tardive dyskinesia, consistent with other reports assessing hormonal responses to dopamine agonists in such cases. It is further suggested that neuroleptic-induced dopamine hypersensitivity does not occur in the TIDA-pituitary system in humans, since it was not manifest in these tardive dyskinesia patients who would be thought particularly prone to develop it.


Effects of a histamine synthesis inhibitor and antihistamines on the sexual behavior of female rats. Intraventricular administration of alpha-hydrazinohistidine, a histamine synthesis inhibitor, at different doses and times before testing produced a significant decrease of lordotic responses and sexual receptivity in ovariectomized estrogen plus progesterone-primed female rats. The H1-antihistamines pyrilamine and chlorfeniramine and the H2-antihistamine metiamide, injected in the lateral ventricle, significantly decreased the lordosis quotient but did not modify receptivity; antihistamine-injected rats showed no soliciting behavior. Exploratory activity was decreased by both alpha-hydrazinohistidine and metiamide but not by the H1-antihistamines. It is concluded that treatments which either deplete histamine or block their receptors can alter female copulatory responsiveness. The mechanism of this antihistamine effect appears to be unrelated to that of other side effects, such as motor impairment, sedation, or local anesthesia.


Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine. The pharmacokinetic properties of estazolam, a triazolo benzodiazepine hypnotic agent, were assessed in a series of healthy volunteers following single and multiple doses. After single oral doses of 2--16 mg, peak plasma concentrations were reached within 6 h. Values of elimination half-life ranged from 8.3--31.2 h (mean 17.0 h) and did not vary significantly with dose. During 3 weeks of therapy, steady-state plasma concentrations increased approximately in proportion to increasing doses. and accumulation was essentially complete within 3 days of each dose change. The mean observed accumulation ratio was 1.84, which was slightly larger than the predicted ratio of 1.53. Exposure to multiple-dose estazolam therapy had no significant influence on the kinetics of a single dose of antipyrine, suggesting that estazolam neither stimulates nor inhibits enzyme activity in humans. Thus the accumulation and elimination kinetics of estazolam can be classified as intermediate to those of the short-acting (such as oxazepam) and the long-acting (such as diazepam) benzodiazepine derivatives.


Self-rated sedation and plasma concentrations of desmethyldiazepam following single doses of clorazepate. Plasma concentrations of desmethyldiazepam (DMDZ) and intensity of self-rated sedation (SRS) were measured at multiple points in time during 6 h after a single 15 mg oral dose of clorazepate dipotassium. Mean plasma DMDZ levels and mean SRS scores both became maximal at 1.0--2.5 h after drug dosage. By 6 h, however, mean SRS had returned to the predrug baseline score while mean DMDZ concentration fell only slighty from the maximum value. Disappearance of SRS despite persistence of high DMDZ levels might be due to adaptation or tolerance. If this is the case, subjective effects of benzodiazepines may depend upon duration of drug exposure as well as dose and concentration.


Impaired performance and sedation after a single dose of lorazepam. In a double-blind cross-over study using normal student volunteers, the effects of 1 and 2.5 mg lorazepam on self-rated mood and bodily symptoms, as well as performance in a number of tests were assessed. Both doses significantly increased self ratings of physical and mental sedation, the effects being more marked 4 h after drug administration than after 1 h. Lorazepam impaired simple reaction time, verbal learning, number cancellation, symbol copying and performance in the digit-symbol substitution test. The impairments were greater with the 2.5 mg dose and were more marked 4 h after drug administration than after 1 h.


Arachidonic acid activation of guinea pig lung guanylate cyclase by two independent mechanisms. The purpose of this study was to elucidate the mechanisms by which arachidonic acid activates guanylate cyclase from guinea pig lung. Guanylate cyclase activities in both homogenate and soluble fractions of lung were examined. Guanylate cyclase activity was determined by measuring formtion of [32-P] cyclic GMP from alpha-[32-P] GTP in the presence of Mn2+, a phosphodiesterase inhibitor and a suitable GTP regenerating system. Arachidonic acid, and to a slight extent dihomo-gamma-linolenic acid, activated guanylate cyclase in homogenate but not soluble fractions. Similarly, phospholipase A2 activated homogenate but not soluble guanylate cyclase. Methyl arachidonate, linolenic, linoleic and oleic acids did not activate guanylate cyclase in either fraction. High concentrations of indomethacin, meclofenamate and aspirin inhibited activation of homogenate guanylate cyclase by arachidonic acid and phospholipase A2, without altering basal enzyme activity. These data suggested that a product of cyclooxygenase activity, present in the microsomal fraction, may have accounted for the capacity of arachidonic acid to activate homogenate guanylate cyclase. This view was supported by the findings that addition of the microsomal fraction to be soluble fraction enabled arachidonic acid to activate soluble guanylate cyclase, an effect which was reduced with cycloooxygenase inhibitors. Lipoxygenase activated guanylate cyclase in homogenate and soluble fractions. Arachidonic acid potentiated the activation of soluble guanylate cyclase by lipoxygenase, and this effect was inhibited with nordihydroguairetic acid, 1-phenyl-3-pyrazolidone and hydroquinone, but not with high concentrations of indomethacin, meclofenamate or aspirin. These data suggest that arachidonic acid activates guinea pig lung guanylate cyclase indirectly, via two independent mechanisms, one involving the microsomal fraction and the other involving lipoxygenase.


Prostaglandins have limited actions on abnormalities of beating induced in cultured heart cells. Prostaglandins are antiarrhythmic in a variety of situations including ischaemic arrhythmias, but the mechanisms  involved are not known. In view of this, the protective actions of prostaglandins A2, E2, F1 alpha, F2 beta, and I2 against abnormalities of beating induced in cultured heart cells were investigated. Abnormalities of beating were induced in single cells by variety of agents including ouabain Ca++, K+, dinitrophenol (DNP), and toxic material from the jellyfish Cyanea. Abnormalities were assessed in terms of rate, rate range, subjective arrhythmic behaviour and percent cells beating. The prostaglandins (at 10(-7)-10(-5) M) were added with the arrhythmogenic agent to test for their ability to modify agent-induced beating abnormalities and were compared with lidocaine and quinidine. Prostaglandins alone had minimal direct effects on the cells and only minimally reduced responses to arrhythmogenic agents. The most protective prostaglandins, PGE2 and PGF1 alpha, tended to normalise beating behaviour most noticeably in DNP-treated cells, unlike lidocaine and quinidine which were effective against Ca++-induced changes while worsening those of K+. Thus, a general ability to protect disturbed cardiac cells is not seen with high concentrations of prostaglandins.


[Radiation decomposition of humic substances in landfill disposal leachate. TOC reduction and CO2 formation (author's transl)]. The leachate generated from landfill contains humic substances such as humic acid and fluvic acid. It shows, in general, high chemical oxygen demand (COD) and biological oxygen demand (BOD), and colors in dark brown. When the leachate collected on the No. 15 landfill in Tokyo Bay was irradiated by gamma-rays from a 60Co source in bubbling air, the total organic carbon (TOC) decreased with increasing dose and the brown color was bleached. The effects of pH, flow rate, and dose rate on the decrease of TOC, the variations of UV spectrum, and the formation of carbon dioxide by the irradiation were examined. The decreasing rate of TOC increased with an increase of the flow rate up to approximately 1l/min and showed a maximum value in the region of pH 4 approximately 6. It was also dependent on the dose rate and increased with a decrease of the dose rate. The radiation chemical yield, G(--TOC), reached 162 at low dose rate of 1.3 X10(4) rad/h. This result suggests that a radiation-induced chain reaction occurred. The amount of TOC decreased was almost equal to that of carbon dioxide formed. This result shows that the organic substances were decomposed by irradiation to carbon dioxide as a final product and it was ejected from the solution.


Candida lipolytica isolated from Guanabara Bay and its ability to grow in marine and estuarine conditions. Although the petroleum degrading ability of Candida lipolytica is well known, its ability to grow in seawater is questionable. Sixteen strains of C. lipolytica were isolated from marine sites in Rio de Janeiro. Some variations from the standard description were noted including strains intermediate between the varieties lipolytica and deformans. A representative strain which grew well on petroleum was found to grow well in marine and estuary conditions which reinforces its potential as a seed organism for marine oil spills.


[Hypertrophic sialosis: general review and report on 13 cases (author's transl)]. The authors describe 13 cases of hypertrophic sialosis and discuss possible mechanisms which could explain their appearance. In spite of different etiologies there is uniformity in the reactions produced. The authors therefore compared the clinical findings with those reported from animal experiments in which such lesions were artificially produced. Whether the processes of cellular hyperplasia and hypertrophy observed are related to an autonomic nervous system disorder, is open to question.


Removal of endogenous ligands from a high-affinity antiserum for radioimmunoassay. A method for removal of endogenous ligands from high-affinity antisera (stripping) is described. A thyroxine antiserum of very high affinity was used to develop the method. The antiserum was incubated at 50 degrees C in a glutamate buffer at pH 4.4 together with some ethanol and methyl cellulose and a large amount of activated charcoal. After incubation for up to 2 days, the stripped antibodies were separated from the ligand adsorbed to the charcoal by centrifugation. The estimated titre increased several fold by the stripping, although the stripping method caused a loss of about 13% of the total number of binding sites over a period of 2 days. When stripped antiserum was used instead of unstripped antiserum in an assay system, the sensitivity was up to 3 times better, and the concentration, which could be measured with the best relative precision, was 3 times lower. The stripped antiserum showed a poorer specificity than the unstripped antiserum when a short incubation period was used. However, when a long incubation period was used, the specificity was nearly the same.


Resynthesis of creatine phosphate in human muscle after exercise in relation to intramuscular pH and availability of oxygen. After exhaustive exercise the muscular store of creatine phosphate (CP) is almost completely depleted. The resynthesis of CP during recovery normally occurs rapidly, but is totally inhibited if the local circulation to the muscle is occluded. The limiting factor for CP resynthesis which could be a low intramuscular pH or availability of oxygen has been investigated in the present study. Biopsies from musculis quadriceps femoris of man were analyzed for pH, ATP, ADP, CP, creatine, lactate and pyruvate. It was shown that resynthesis of CP only occurs when the blood supply to the muscle is intact. From this it was concluded that the creatine kinase reaction is at a steady state or at equilibrium during the period of recovery. The influence of oxygen on the resynthesis of CP was investigated by incubating muscle samples taken after a fatiguing isometric contraction in atmospheres of oxygen and nitrogen, respectively. During 15 min incubation in oxygen CP was resynthesized from a starting value of 4% to 68% of the normal value at rest. No resynthesis was observed when parallel muscle samples were incubated for the same time in nitrogen. It is suggested that the initial fast phase of CP resynthesis is limited by the availability of oxygen whereas the subsequent slow phase is limited by the hydrogen ion transport out from the muscle.


Plasma acetate concentrations during canine haemorrhagic shock. Acetate, pyruvate, lactate and NEFA concentrations, as well as acid-base-parameters were followed during bleeding, stable hypotension and re-infusion in five dogs. Mean arterial blood pressures were kept at 30 mmHg during the shock phase. An increase in acetate concentrations (P less than 0.01) was found in arterial as well as in venous plasma samples. The maximal mean acetate concentration was 0.19 mmol/l (during reinfusion) as compared to 0.06 mmol/l prior to bleeding. There was no difference between arterial and inferior caval venous concentrations. A definite correlation (r = 0.81, P less than 0.02) was found between blood pyruvate and plasma acetate concentrations. There was no correlation between plasma glucose or NEFA and acetate concentrations or between blood excess lactate and plasma acetate. The plasma acetate accumulation was negligible compared to the concomitant lactate accumulation (1:60), and did not contribute to the metabolic acidosis of shock. The correlation between acetate and pyruvate concentrations may indicate that pyruvate is the main substrate of acetate production in hypovolemic shock.


Utilization of exogenous acetate during canine haemorrhagic shock. Plasma acetate and lactate, as well as acid-base-parameters were followed during acetate (dogs I-V) or lactate (dogs VI-X) loading during stable hypotension (mean arterial blood pressure 30 mmHg). Acetate or lactate were infused at a constant rate of 4 mmol/kg/h as 0.5 mol/l solutions (50% as the sodium salt, 50% as the free acid) without simultaneous treatment of the volume deficit. The acetate metabolizing capacity was well preserved even in profound haemorrhagic shock. The actual loads were rapidly removed, while the equivalent lactate loads caused progressive accumulation of the lactate ion. Acetate loading did not aggravate the lactic acidosis, and the acid-base-parameters showed a more favourable development during acetate loading than during lactate loading. Acetate may thus be given during haemorrhagic shock without the same risk of accumulation that is carried by the equivalent amounts of lactate.


Characterization of somatostatin release from the pancreas: the role of potassium. The effect of potassium on somatostatin secretion from the isolated perfused canine pancreas was studied. Potassium stimulated dose-dependent somatostatin release in a monophasic response pattern. The effect of potassium was abolished in the absence of calcium. Perfusion of 1 micronmol/l atropine and 1 micronmol/l propranolol was without effect on the potassium induced somatostatin release. The results suggest that the stimulatory effect of potassium on somatostatin release is secondary to increases in calcium influx into the D cell. The sympathetic and parasympathetic nerve endings in the pancreas are apparently not involved in the potassium mediated secretory processes.


Reference values for six enzymes in plasma from newborns and women at delivery. We have determined the distribution in cord blood from healthy newborns of six enzymes: creatine kinase, lactate dehydrogenase, aspartate and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltransferase. The concentration of enzymes were determined according to the methods recommended by the Scandinavian Committee on Enzymes. The distribution of isoenzymes and of enzymes in blood from women at delivery was investigated also. All distributions were positively skewed. The upper reference limits of cord blood exceeded those found in mother blood by a factor of eight for gamma-glutamyltransferase, and for lactate dehydrogenase and creatine kinase by a factor of two.


The therapeutic effect of methyl-salazosulphapyridine versus salazosulphapyridine in active ulcerative colitis. A double-blind controlled trial. In an attempt to improve the ratio between therapeutic effect and side effects of salazosulphapyridine (SASP), methyl-salazosulphapyridine (methyl-SASP) was compared with SASP in a randomized controlled double-blind trial, without cross-over, in patients with active ulcerative colitis. The patient group comprised 53 patients. The daily doses were 1 g SASP x 3 and 125 mg methyl-SASP x 3. The methyl-SASP group comprised 26 patients, the SASP group 27 patients. The treatment period was 4 weeks. Applying clinical symptoms (bowel movements, registered by the patients on special charts), clinical condition (assessed by the patient), proctoscopic signs, and registration of side effects, it is concluded that methyl-SASP had an effect on ulcerative colitis indistinguishable from that of SASP. The rate of side effects was significantly less in the methyl-SASP group. The blood concentrations of SASP, methyl-SASP, sulphapyridine, and methyl-sulphapyridine were estimated at start during, and at the end of the trial. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-sulphapyridine on an average 1/13 of sulphapyridine, the differences being significant. It is concluded that methyl-SASP presents an improvement in the effect/side effect ratio when dealing with symptomatic ulcerative colitis. The discrepancy between the outcome of the present trial and the lack of effect in a controlled trial on the relapse-preventing effect of methyl-SASP is at present unexplained. A type II error in the present trial (or a type I error in the prophylactic one) is a possibility, or the patient-group selected for the present trial had a spontaneously benign course, cases demanding prednisone or colectomy having been excluded.


Serum group I pepsinogens during prolonged infusion of pentagastrin and secretin in man. Six 20- to 25-year-old healthy men were studied with an intravenous pentagastrin infusion in a dose of 6 micrograms/kg-h for 4.5 h. Four of these were also studied on separate days with an intravenous secretin infusion in a dose of 2 CU/kg-h for 4.5 h. Gastric juice was collected continuously for one 30-min period before and in 30-min periods throughout the infusion periods, and the gastric H+ and pepsin outputs were determined during the pentagastrin infusion only. Blood was drawn before, every 30 min throughout the infusion, and the next morning for determination of serum group I pepsinogens (PG I), serum gastrin, and plasma secretin. Pentagastrin evoked a sustained rise in gastric H+ and pepsin secretions, a more delayed and sustained increase in serum PG I in the four subjects with a normal pentagastrin-stimulated maximal gastric secretion, and a fall in serum PG I in the remaining two subjects with a low gastric secretion. Secretin also elicited a sustained elevation in serum PG I in all four examined, including one who showed a fall in serum PG I during pentagastrin infusion. It is proposed that pentagastrin may exert its stimulatory effect of pepsinogen synthesis subsequent to degranulation of the chief cells, whereas secretin may stimulate the pepsinogen synthesis more directly. Thus, the fall in serum PG I during pentagastrin infusion in the two subjects with low gastric secretion may possibly be due to a defective cellular storage of PG I in atrophic gastritis. Plasma secretin was not affected by gastric suction or by prolonged infusion of pentagastrin, whereas serum gastrin fell during secretion infusion accompanied by gastric suction.


Folate deficiency in chronic inflammatory bowel diseases. In a consecutive study of 216 outpatients with chronic inflammatory bowel diseases (CIBD) low serum and erythrocyte folate levels were found in 59% and 26%, respectively. In patients with low folate levels in both serum and erythrocytes, megaloblastic changes in the bone marrow ere found in 67% (29 out of 44). Their folate intakes were borderline. Absorption studies with tritiated folate showed low absorption values on repeated examinations in 23% of the patients with low folate values (9 out of 40), with no relationship to the intake of salazosulphapyridine. In patients with low folate values the reticulocyte count was elevated (related to the dose of salazosulphapyridine), and the 51Cr erythrocyte survival was decreased. It is suggested that folate deficiency in CIBD is of multiple origin: inadequate diet, malabsorption, and chronic drug-induced low-grade haemolysis. The clinical consequence of the findings remains to be evaluated.


Gastro-oesophageal sphincter pressure and reflux in controls and patients with abnormal duodenal loop. Twenty-two patients with chronic upper dyspepsia but without ulcer disease were examined for gastro-oesophageal reflux and gastro-oesophageal sphincter pressure. Thirteen had an abnormal duodenal loop and nine a normal duodenum. An increased incidence of gastro-oesophageal reflux was found in patients with abnormal duodenal loop, whereas no differences were seen in the gastro-oesophageal sphincter pressure.


Immunoreactive secretin release in patients after duodenectomy and partial or total pancreatectomy. Seven patients were investigated 8--22 months after duodenectomy and pancreatectomy for chronic pancreatitis or cancer. Seven other patients, admitted for minor surgery, served as controls. 40 ml 100 mmol/l HCl was infused over 5 min into the jejunum 10 cm beyond the gastrojejunal stoma in the duodenectomized patients and 10 cm beyond the pylorus in the controls. Plasma immunoreactive secretin (IRS) increased from 3.0 +/- 0.8 pmol/l (mean +/- S.E.M.) to 9.8 +/- 0.5 pmol/l (p less than 0.01) in the duodenectomized patients. In the controls the increase was significantly higher than in the patients (p less than 0.01)--from 1.5 +/- 0.3 pmol/l to 19.5 +/- 3.3 pmol/l (p less than 0.01). The study shows that the jejunum is able to release IRS after acid infusion in duodenectomized patients.


[A case of acute left myocardial insufficiency after tocolysis by means of beta stimulation]. A case is presented to demonstrate that tocolysis by beta adrenergic stimulation can be complicated by metabolic myocardial infarction. The possible role of pathophysiologic and pharmacologic facts is discussed, but additional clinical features involved in this particular case may be partly responsible for the above-mentioned complication. Finally, some recommendations are made with a view to assessing risk factors and improving cardioprotective effects.


[Value of the meiosis test in male infertility]. The histological evaluation of testicular biopsy in the investigation of infertility was supplemented by cytogenetic analysis of spermatogenesis in 72 patients from 1976--1978. The results show meiosis analysis to be a practical aid in the assessment of male infertility. It enables the point of interruption in the meiotic process to be accurately identified. A review of relative populations of meiotic and of interphase nuclei (the meiotic index) permits evaluation of a quantitative disturbance of spermatogenesis, a finding that is of particular value when establishing a patient's prognosis. Moreover, meiotic analysis makes it possible to recognize cytogenetic anomalies which could be responsible for the infertility state and which were chiefly seen in patients whose so-called primary infertility was hitherto classified as being of unknown origin. In two patients we thus identified a small additional chromosome in a fraction of the germinal cells, and also an abnormal pairing of all chromosomes, or the sex chromosomes alone, during the first meiotic division.


[Progress in bone marrow transplantation in acute leukemia and aplastic anemia]. Experience with 17 allogeneic bone marrow transplantation (BMT) patients with refractory acute leukemia is reported. The authors show that it is extremely difficult to cure patients with end stage disease by this procedure. Based on experience that, if performed early, BMT can bring about over 50% potential cures, it is postulated that marrow grafts should be performed much earlier than is done at present. From the results in 45 patients with severe aplastic anemia it is concluded that the majority do not have a defect at the pluripotent stem cell itself. There is disturbed maturation to functional end cells which can be corrected in most instances by ALG, infusion of allogeneic marrow and low dose androgens. BMT between HLA-identical siblings need not cause major problems, but it involves a considerable risk of fatal complications such as irreversible marrow rejection and GvH.


Effects of deferoxamine methanesulfonate on Trichophyton mentagrophytes. Deferoxamine methanesulfonate (Desferal), an iron chelator, inhibited germ tube formation and growth of Trichophyton mentagrophytes in a microculture assay. A 50% reduction of germ tube formation required Desferal at 5 mg/ml and a 50% reduction of growth required 1.5 mg/ml. Growth was almost completely inhibited with 50 and 100 mg/ml. Also, Desferal at 100 mg/ml inhibited further elongation when added to short hyphae (II and 21 micrometer), but showed less inhibitory effects when added to long hyphae (64 micrometer). Iron (133 microgram/ml) reversed the inhibition of growth produced by incubating spores with Desferal at 5 mg/ml, providing iron was added before 72 h incubation. Desferal at 100 mg/ml decreased viability of activated spores incubated for 3 days at 30 degrees C, but did not decrease viability of spores incubated for 3 days at 4 degrees C. The growth inhibitory effect of Desferal and transferrin were compared. Transferrin was inhibitory at low molarities (0.001 to 1.0 mM), while Desferal was inhibitory only at higher molarities (greater than 1 mM). Desferal (0.05 mM) also reversed the inhibition expected with 0.05 mM transferrin. These findings indicate that Desferal and transferrin deprive T. mentagrophytes of nutritional iron and thus inhibit growth of the fungus. Low concentrations of Desferal can also promote growth in the presence of transferrin.


Isolation and characterization of CHO cell mutants with altered asparagine synthetase. Two asparagine auxotrophic mutants (N3, N4) were isolated from the Gat- strain of Chinese hamster ovary cells, using a selection procedure modified from that of Goldfarb et al. (1). The defect in these mutants is due to a deficiency in asparagine synthetase activity. N3, in particular, had no measurable enzyme activity. Complementation analysis by PEG-mediated cell fusion showed that the auxotrophic phenotype behaved as a recessive trait; complementation was obtained between N3 or N4 and the pseudoauxotroph, Asn3, which has a temperature-sensitive asparagyl-tRNA synthetase activity. Revertants obtained by plating N3 or N4 in asparagine-free medium had about normal levels of asparagine synthetase activity and were produced with a probability of about 10(-6) per cell per generation. Three particular revertants of N3 and one revertant of N4 were shown to have asparagine synthetase activities that were different in thermolability from that of the wild type. This observation is consistent with the suggestion that N3 and N4 have defective structural genes rather than defective regulatory genes for asparagine synthetase.


Biogenic amines in neuroendocrine systems: multiple sources, messages, targets and controls. Biogenic amines are small chemical mediator molecules synthesized from amino acids by the body. Our research has centered on functions and controls of three categories of biogenic amines in neuroendocrine and neural systems of laboratory species of mammals as models of similar processes in the human body. Experimental analyses have been made of possible contributions of particular of these compounds, or their sources, to regulation of reproductive and 24-hour rhythms, and to responses and adaptations to stress. Results from this and related work, by many other investigators as well, have general implications for biomedical research, including: (A) Biogenic amines have multiple sources, messages, targets and possible controls, depending on species (genetics), developmental stage and age, and in relation to tissue regions and responses during both adaptations and disease states. (B) Functions or actions of biogenic amines in either the nervous or the neuroendocrine system go beyond what can be accommodated by the classical paradigms or terms of neurophysiology. Labeling these compounds in their various tissue sites as "neurotransmitters", or "neuromodulators", or "neurohormones" adds little to our understanding of their actions and roles. (C) Future understanding of how these chemical mediators function and are controlled in health and in disease should be enhanced by investigation of the spectrum of adaptive tissue changes in which these compounds and their control mechanisms participate. This suggested approach contrasts with the usual and classic paradigm in which primary, if not unitary, sources, actions and controls are emphasized to the exclusion and ignoring of others that may have vital significance at particular times or in particular circumstances.


[Acute overdosage with benzodiazepine derivatives (author's transl)]. The study of 210 cases of voluntary intoxications by benzodiazepines alone, out of a total of 2080 intoxicated patients admitted at the Hospital of Tours, shows that when no other drugs is associated the prognosis is good, both for children and for adults. The association with ethanol does not change the prognosis. The clinical symptoms alone cannot prove the nature of the gravity of the intoxications. After having analysed the drugs present in the gastric juice, and after having checked that only benzodiazepines are implied, the patient can usually be taken care of on a non specialized ward.


Influence of stroma-free hemoglobin solution on renal function in dogs. In the presented series of experiments, stroma-free hemoglobin solution (SFHS) was used as a perfusate for extracorporeal perfusion of kidneys and for exchange transfusion. It was shown that SFHS was adequatly oxygenated both as perfusate during the extracorporal perfusion and in the lungs after the blood exchange. Furthermore, there was provided evidence that oxygen was being transported and released in the tissues. Histologic examination of the kidneys demonstrated hemoglobin casts in the glomerules. Most of them were seen after extracorporal perfusion of isolated kidneys, less frequently after perfusion in situ and few casts were present after exchange transfusion. The cause of these depositions may be small remnants of stroma in the preparation. Furthermore it is possible, that at the beginning of the extracorporal perfusion of the kidneys the urine pH was below 6 and then a hemoglobin casts formation could occur. There were essential no changes in urine pH in the course of blood exchange. In this group were only few casts present in the kidneys.


[Ethanol in parenteral feeding and its effect on liver metabolism]. Investigations of the leucine aminopeptidase (LAP) and the gamma-glutamyl transpeptidase (gamma-GT) as a dimension for a damage of the liver cells under ethanol infusion did not show any damage of the liver parenchyma with a slow infusion velocity and a limited ethanol quantity (25 g daily). Since especially in the postoperative phase a sufficient caloric nutrition improves the therapeutic results, one could make use of the possibility of ethanol supply. This is mainly recommendable for patients who should demand only a small infusion volume or such a one which should not carry a high quantity of sugar (for instance diabetics). The parenteral ethanol application in the postoperative phase is frequently indicated for the immobilisation of alcoholics.


[The behavior of sensory and ganglia cells of the vestibular apparatus of the guinea pig in response to inadequate stimulations]. The behaviour of the sensory- and the ganglia cells in response to inadequate stimuli was studied at 12 adult guinea pigs. The sensory cells of the three Cristae ampullares dont respond remarkably to acoustic stimulation. At the range of 1000 Hz a recognizable increase in the size of the sensory cells at the upper ampulle was noticed. Of no account was the rest of the volume variations. At the range of 5000 Hz the sensory cells of the Maculae staticae responded with a considerable increase in the size of their sensory nuclei up to 38%. The cells of the Ganglion vestibulare react upon acoustic stimulation throughout with an increase in their nuclei up to between 16% and 54%. It was noticed that the volume enlargement increases from the lower to the higher frequencys. The cells of the Ganglion geniculi nervi facialis react upon acoustic impulses too with an increase in their nuclear volume. In low tone acoustic range and in high tone acoustic range the growth rates are more than 50% beyond the standard. Thos cells respond to frequency of 1000 Hz remarkably intensive. It was noticed that the maximum volume increase of their nuclei was in the average up to 103%. All the sensory and ganglia cells react upon rinsing the external auditory canal with 12 degrees C water, with a shrinkage of their nuclei. Besides that the sensory cells of the Cristae and the Maculae show a volume decrease between 8% and 19%. The cells of the Ganglion vestibulare et geniculi respond with a considerable volume decrease of their nuclei from 32 to 41% under the average.


[Storage behavior of Collins' solution under various conditions]. It is reported on examinations of the precipitation reactions in the Collins solution. The solution which is produced in three and two compartments, respectively, has been given together and stored under three different conditions. During a period of 48 hours the electrolytes sodium and potassium and the pH-value were controlled. Hereby significant differences of these values are shown in the various kinds of compilation as well as between the three- and the two-compartment solution. No or only slight precipitations in the closed system are observed at 20 and 40 degrees C in contrast to the open system.


[Conditioned reflex, electrographic and mediator-humoral changes during intermittent hypokinesia of different duration in rats]. Intermittent hypokinetic stress in rats, lasting from 1 to 6 weeks was attended by a complex of shifts of behavioural, conditioned, bio-electrical and mediator-humoral parameters. They considered as an evidence of the changes occuring in the tonic level of emotional state. Different phases of emotional state follow one another with the progress of hypokinesia. Acute emotional stress is observed, as well as the development of a compensatory systemic reaction and initial symptoms of the exhaustion of adaptational systems.


[Effects of beta-sympathicomimetics on ionogram, transaminases, and ECG in pregnancy (author's transl)]. Beta-adrenergics have recently come in the focus of clinical, physiological, and pharmacological research. The side-effects of tocolytically active substances are under thorough study at present. The authors checked the laboratory values recorded from 45 patients in pregnancy. Electrocardiographic follow-up checks were also conducted, with the view to establishing the effects of Dilatol and Partusisten on both the electrolyte balance and myocardium.--The results are described and discussed, and conclusions are suggested.


[Clinical importance of antiprolactinaemic treatment of functional infertility (author's transl)]. Reported in this paper is the effectiveness of antiprolactinaemic treatment of 40 infertile women. All case histories revealed previous unsuccessful attempts to induce ovulation. Antiprolactinaemic treatment was in all cases preced by RIA determination of prolactin and gonadotrophin. Prolactin levels were found to be somewhat increase in 19 cases, while 21 women were normal. The gonadotrophin plasma levels usually were closer to the lower limits of normal values. The presence of hypophyseal adenoma had been ruled out beforehand. Long-time treatment was based on the administration of 5 mg Parlodel/die. The effect was excellent in all cases of hyperprolactinaemia, but response was recorded, as well, from a group of patients with normal prolactin levels. Galactorrhoea ceased to exist in all cases. Clomiphen was applied again to induce ovulation in those patients who had not responded at all or developed only bleeding without ovulation. That treatment proved to be effective in several cases.


Sympathectomy and prostaglandin deficiency do not prevent gastrogenic hyperglycaemia and hyperinsulinaemia. To examine the mechanism of the recently reported effect of an acidified intragastric test meal on insulin release and glucose homeostasis, a liver extract test meal at either pH 2 or pH 7 was instilled into the stomach of normal dogs and dogs with a chemical sympathectomy or indomethacin-induced prostaglandin deficiency, all of which had a bisected pylorus and gastric fistula. In the normal dogs the instillation of the liver meal at pH 2 elicited a significant rise in plasma glucose, glucagon and insulin levels, while in response to the meal at pH 7 only glucagon rose significantly. This was not altered in chemically sympathectomized dogs, nor during the infusion of indomethacin. In all experiments gastrin or gastric glucagon release in response to the meal at pH 2 was either lower than or similar to the response to the meal at pH 7. These data suggest that the influence of the stomach upon islet cell function and glucose homeostasis does not depend on either adrenergic innervation or the presence of prostaglandings, but rather is mediated by a yet undetermined mechanism.


The mechanism of the acid activation of rabbit uterine renin. Besides active renin an inactive form of renin could be demonstrated in uterine tissue. On gel filtration it was eluted as a molecule of slightly higher molecular weight than active renin, and it could be irreversibly activated by acidification at 37 degrees C. The activation had a pH optimum between pH 3.8 and pH 5.3. Acid activated uterine renin was found identical to active uterine renin by 1) the formation of angiotensin I with time after addition of rat substrate, 2) the pressor response in the rat, 3) neutralization by antirenin and 4) similar Michaelian constants. Repeated freezing and thawing, acidification at 4 degrees C and dialysis against 4 mol/l NaCl did not give any activation. A lower rate of activation of diluted samples and activation by trypsin at pH 7.4 suggest that proteolytic enzymes are involved in the activation.


Inactivation of renin in a mixed mitochondrial-lysosomal fraction of post-partum uterus. The marked renin inactivation seen during in vitro incubation of post-partum uterine slices which mimics the in vivo condition, is not accompanied by a similar general proteolysis. The inactivating mechanism is so far non-specific with respect to organ or species as added hog renal renin is inactivated at a similar rate as endogenous renin. Endogenous alkaline phosphatase is not significantly inactivated and added alkaline phosphatase is completely stable. A marked inactivation of endogenous renin also takes place during incubation of a mixed mitochondrial-lysosomal suspension prepared from post-partum uterus. The process is more pronounced at pH 7.4 than at 6.8. Freezing and thawing and addition of Triton X-100 prior to incubation inhibits the inactivation. ATP and alpha-ketoglutarate slightly stimulates the process while CoA and chloroquine have no effect. Both iodoacetate and phenylmethylsulphonylfluoride inhibit the inactivation, suggesting that more than one enzyme is involved in the inactivation.


Induction of tyrosine aminotransferase in galactosamine hepatitis. We have induced acute hepatitis in rats with the amino sugar Galactosamine by i.p. injection. The development of the disease was controlled by measurements of several metabolites and enzymes in serum, and light and electronic microscopy. Tyrosine transaminase was induced by i.p. injection of Cortisol, that increases ten times enzyme activity in liver parenchyma of normal rats. This inductive phenomenon cannot be observed in animals with galactosamine hepatitis. We discuss the probable mechanism and their relationship with some forms of viral hepatitis in human beings.


Serum glutamic oxalacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase and glutamic dehydrogenase levels in favism. Serum GOT, GPT, gamma-GT and GLDH were determined in 15 G-6-PD-deficient subjects during a hemolytic crisis and hemoglobinuria due to ingestion of fresh fava beans. The same G-6-PD-deficient subjects were studied again 2 months after the crisis, when they were asymptomatic. 15 normal healthy children served as controls. A statistically significant increase, above normal, in serum GOT, GLDH and gamma-GT was observed in the favic subjects during the crisis. All the values reverted to normal in the asymptomatic period.


Effects of thoracic epidural block and the beta-1-adrenoreceptor agonist prenalterol on the cardiovascular response to infrarenal aortic cross-clamping in man. Sixteen patients scheduled for abdominal aortic resection and grafting were randomly assigned to two groups to study the cardiovascular effects of infrarenal aortic cross-clamping. The patients in the first group had received a thoracic epidural block followed by intravenous administration of the selective beta-1-adrenoreceptor agonist prenalterol prior to induction of general anaesthesia. The patients in the second group served as controls and received no specific treatment prior to general anaesthesia. In both groups, aortic cross-clamping was followed by an equal rise in pulmonary artery diastolic pressure and mean systemic arterial pressure. There was a significant difference in systemic vascular resistance, as the control group had a 46% increase 30 s after cross-clamping, while the pretreated patients had only a 7% increase at the same time. Moreover, the patients given the thoracic epidural block followed by prenalterol increased their stroke volume and cardiac indices, as compared to the patients in the control group who showed a significant decrease in these parameters. Possible mechanisms for the mode of action of the combined thoracic epidural block and beta-1-adrenoreceptor agonist pretreatment are discussed.


Continuous positive airway pressure during mechanical and spontaneous ventilation. Effects on central haemodynamics and oxygen transport. The effect of continuous positive airway pressure during continuous mechanical (CMV + PEEP) and spontaneous (CPAP) ventilation on central haemodynamics and systemic oxygen transport was studied in 10 male patients who had undergone aortocoronary bypass graft operation 18 h earlier. With the change from CMV + PEEP 5 cmH2O to CPAP 5 cmH2O, cardiac index was found to increase from 2.58 +/- 0.44 (s.e. mean) to 2.88 +/- 0.19 l/min/m2 (P less than 0.005), and systemic oxygen transport improved from 8.5 +/- 0.6 to 9.5 +/- 1.0 ml/min/kg (P less than 0.05). Arterial oxygen tension and content did not change, but mixed venous blood oxygen tension increased from 3.5 +/- 0.2 to 4.2 +/- 0.2 kPa (P less than 0.005), reflecting the increase in cardiac output. Arteriovenous oxygen content difference decreased from 4.6 +/- 0.5 (CMV + PEEP) to 3.6 +/- 0.2 (CPAP) ml/100 ml (P less than 0.05), while total oxygen consumption remained unchanged. Mean systemic arterial pressure was found to increase from 10.8 +/- 0.4 to 11.6 +/- 0.4 kPa (P less than 0.05) and mean pulmonary arterial pressure changed from 2.2 +/- 0.1 to 2.4 +/- 0.1 kPa (P less than 0.05). Right atrial and pulmonary capillary wedge pressures did not change. Our observations suggest that, in terms of central haemodynamics and tissue oxygen supply, CPAP offers a noteworthy alternative weaning method and an alternative to CMV + PEEP in cases where therapy is prolonged and the patient is able to breathe spontaneously.


Cardiovascular effects of neurolept anaesthesia in patients with coronary artery disease. An anaesthetic technique comprising a combination of phenoperidine (0.1 mg . kg-1), diazepam (0.06 mg . kg-1) and pancuronium bromide (0.1 mg . kg-1) with controlled ventilation was evaluated in 12 patients with severe coronary artery disease. The heart rate, cardiac output and mean arterial blood pressure did not change significantly between the preinduction and postinduction measurements. The right atrial pressure and pulmonary capillary wedge pressure decreased significantly by 33% and 36%, respectively, probably due to the influence of positive-pressure ventilation. There was no depression of the left ventricular performance.


Fluoride kinetics and renal function during enflurane anaesthesia. Renal function, fluoride formation and excretion were studied during and after enflurane anaesthesia in seven patients. During anaesthesia, urine flow rate, inulin clearance, PAH clearance and fractional sodium excretion were 13, 78, 65 and 49% of control values, respectively. Renal function was promptly restored postoperatively. Enflurane was metabolized to inorganic fluoride with a mean maximal serum level of 17.4 +/- 3.3 microM. Fractional fluoride excretion decreased during anaesthesia to 35% of the control value. Postoperatively, there was a highly significant correlation between the increase in fractional fluoride excretion and the rise in urinary pH during two consecutive 3-hour periods. It is suggested that tubular reabsorption of fluoride is inversely related to tubular fluid pH and that fluoride is reabsorbed by non-ionic diffusion.


Influence of enflurane on cerebral blood flow in man. Cerebral blood flow was measured by means of a 10-channel cerebrograph in anesthetised patients before and during 2% enflurane. This investigation was carried out after carotid angiography; 2-3 mCi Xe133 was injected into the internal carotid artery. The clearance curves of Xe133 were captured by 10 scintillation counters. In addition to regional cerebral blood flow (rCBF), arterial blood pressure, heart rate, stroke volume, cardiac output and arterial blood gases were measured in seven adult patients. During 2% enflurane, a small, and in two regions a significant decrease in rCBF was observed. Mean arterial pressure and heart rate decreased significantly, but cardiac output did not. The decrease in PaCO2 was not significant.


Circulatory and metabolic effects of acute beta 1-blockade in severe pre-eclampsia. Five mg of a beta 1-adrenoceptor antagonist (atenolol) was given i.v. to 5 women with severe pre-eclampsia in the 3rd trimester of pregnancy. There was a significant decrease of both mean systolic blood pressure, from 171 to 155 mm Hg, and mean diastolic blood pressure, from 116 to 107 mm Hg. The mean maternal heart rate decreased significantly from 90 to 74 and mean fetal heart rate significantly from 145 to 138 beats per min. There were no significant changes in the plasma levels of cyclic AMP, insulin, glucose, free fatty acids, 3-hydroxy-butyrate or glycerol.


Observations on long bone medullary pressures in relation to arterial PO2, PCO2 and pH in the anaesthetized dog. To investigate the influence of variations in arterial oxygen tensions (PaO2), arterial carbon dioxide tensions (PaCO2), and arterial pH on long bone medullary pressures, seven anaesthetized dogs were investigated. Comparing the control medullary pressures, i.e. the mean medullary pressures obtained at the normal range of PaO2 (75--110 mmHg) with the mean medullary pressures corresponding to the range of PaO2 of less than 75 mmHg, statistically significant (P less than 0.05) decreases were seen in both epiphyseal, metaphyseal and diaphyseal medullary pressures, from 27.6 +/- 5.0 to 15.5 +/- 3.6 mmHg, from 23.5 +/- 2.9 to 13.9 +/- 2.3 mmHg and from 27.7 +/- 3.9 to 18.3 +/- 2.5 mmHg (all mean values +/- s.e. mean), respectively. Hyperoxia, hypocapnia, hypercapnia or metabolic acidosis had no effect on medullary pressures in any of the regions studied.


The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Sulfasalazine and its active components, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), are potent modulators of inflammatory reactions but with somewhat different modes of action. Investigating the effect of these compounds on normal human polymorphonuclear leukocytes in vitro, we show inhibition of different stages in the phagocytic process, such as migration (sulfasalazine and SP), superoxide production (sulfasalazine and SP), myeloperoxidase-mediated iodination and cytotoxicity (5-ASA and SP). It is thus suggested that sulfasalazine is not just a vehicle for delivering its active components in the colon, but that its therapeutic effect is ulcerative colitis and other inflammatory reactions is a result of the concurrent action of the three compounds.


[Treatment of a case of chronic obsessive troubles through combined behavioral therapy (author's transl)]. Behavior therapy of a young man, suffering from grave obsessive and compulsive troubles is the first example of combined therapy, with individual therapy, family therapy as group therapy. Two steps are find in the cure. There are benefits--trust and hope--due to psychiatric hospitalization and generous and constant affection of the sponse. The sponse was the key of reciprocal inhibition necessary to the control of anxieties due to the treatment. The aim reached was the control of obsessions and compulsions lasting for more than sixteen years.


Hepatotoxicity of salicylazosulfapyridine: a case report and review of the literature. A case report of a patient with biopsy-proven hepatitis which occurred while that patient was receiving Azulfidine which recurred after a rechallenge is presented. Toxic hepatitis, an apparent drug hypersensitivity reaction can result from Azulfidine therapy and must be considered in the differential diagnosis of hepatic abnormalities in patients with inflammatory bowel disease who are taking this drug. The literature concerning toxic reactions to the drug is reviewed.


Abnormal erythrocyte metabolism in hepatic disease: effect of NADP repletion. Erythrocytes from ten patients with severe liver disease displayed low methylene blue-stimulated hexose monophosphate (HMP) shunt activity and glucose recycling despite elevated total glucose consumption when compared to controls. Heinz body formation was increased and reduced glutathione concentration significantly decreased. After hemolysis, no differences in methylene-blue estimulated HMP shunt activity or glucose recycling could be demonstrated between patients and controls. The addition of 2- and 4-mM NADP to the hemolysates produced significantly greater HMP shunt activity and glucose recycling in the patients' hemolysates. The addition of NADPH to the incubation mixture produced no significant stimulation of either HMP shunt activity or glucose recycling, unless methylene blue was also added. Omission of NAD or phosphate from the incubation mixture produced no change in shunt metabolism. The absence of supplemental ATP resulted in extremely low shunt metabolism and refractoriness to NADP stimulation in both patients and controls. In the absence of additional magnesium, a reduction of shunt metabolism was noted. These data suggest that the defect in stimulated shunt metabolism in the intact erythrocytes of patients with hepatic disease does not result from an absolute enzyme deficiency, but rather from an unavailability of NADP or other cofactor.


[Psychological theories in the context of an interdisciplinary gerontology (author's transl)]. The integration of the different disciplines of gerontology can be promoted by pointing to the analogies in biological, medical, psychological, and sociological constructs and theories of aging. Max Bürger's construct of "biomorphosis", the functional age approach in physiology, and the principle of homeostasis can contribute to the formulation of hypotheses and theories in the behavioral and social sciences, too. A common frame of reference for this integrated interdisciplinary gerontology is a differential approach which tries to define different patterns of aging, their biological, clinical, social, and psychological conditions, the control and prediction of the aging process within the frame-work of these patterns and the prevention of adverse patterns. An important contribution of behavioral sciences to this differential gerontological is defined by cognitive theories of behavior which point to the decisive role of the perceived (vs. the "objective") situation in selection of responses of the aged.


[Possibilities and problems in the rehabilitation of aged patients with mental illness (author's transl)]. In the Federal Republic of Germany as in other Western Countries institutions suitable for the rehabilitation of aged patients with mental illness are lacking. As long as "psychiatry of the higher age" is synonymous to "psychiatry of demented patients" the term "rehabilitation" means only a slogan, not a maxime. Jurisdiction in the Supreme Court though, has shown the way of going on. It will depend also on the attitude of the doctors in charge of the patients to fulfill the expectations posed in that jurisdiction and to reach so the far set marks in the interest of the patients. Big institutional deficits have to be ameliorated as far as possible; of prime importance here is the necessity to place the opportunities for the employment of qualified employees. Rehabilitation instead of custodial care here is synonymous for efficiency and humanity. The change from an obsolete and nonorganized "system" of care to a modern network of rehabilitation should be obtained by voluntary cooperation and by voluntary coordination of medical and social institutions. So an integration of all possibilities of help to a network could be reached.


[Medical data from a gerontological field-study and its value with regard to the conception of a psychogeriatric service (author's transl)]. 1114 people were investigated by a sociological interview. A representative subgroup got a medical check-up mostly by psychiatrists, a few of them by the family doctors. It revealed a refusal-group of 28% out of 625 persons. Our medical data did not confirm the rate of morbidity from 10 to 20% of the elderly. Whereas the sociological date of the refusal-group maybe identify the expected crisis-population so that we did not gain enough information for planning a psychogeriatric service by this field-study.


Variables related to affective mental disorders in the elderly. Social life, somatic and mental health at the age of 70 and 75. It is reported about a population study of 70-year-old people in Gothenburg with the special concept of suffering from loneliness. The aim was to study factors that might cause or be the consequences of loneliness. In this study 12% of males and 25% of females suffered from loneliness. The lonely women felt sick more often and visited physicians more frequently than the other women, whereas diseases such as coronary insufficiency had no obvious relationship to feeling of loneliness. Together with other symptoms is the feeling of loneliness one symptom in a syndrom of depression of mood and low life satisfaction.


[Psychological problems of incurable patients in old age (author's transl)]. Biological functions are regulated by feedback mechanisms. In old age disorders occur in this regulation by insufficiency of biochemical transmitters. The synthesizing enzymes of Tyrosine Hydroxylase, Tryptophan Hydroxylase, Dopa Decarboxylase and 5-Hydroxytryptophan Decarboxylase are diminished in old age. Minus symptoms as depression, or exhaustion and disorders of circulation occur. A substitution by biogenic transmitters is not possible, because these don't pass the blood-brain-barriere. Therefore a medication of psychopharmacological drugs is necessary. For instance Anxiety--tranquilizer, exhaustion--anti depressive drugs.


Alterations of two parameters of cellular immunity in the aged men. There were two parameters of cellular immunity in 46 old and 34 adult (control) individuals investigated. These reactions were delayed type hypersensitivity of the skin and the in vitro leukocyte migration inhibition test. PPD was used as antigen for both reactions. According to our investigations there was no correlation between them neither in the aged nor in the control group. But the statistical analysis of data revealed a significant difference between skin responses of aged and control groups. In spite of this we consider cellular immunity unaltered in old men, because there was no difference in migration inhibition between aged and adult men and according to our earlier experiments in guinea pigs this test is much more reliable than skin response.


Premedication for elective Caesarean section. Four coded, but otherwise unidentified, premedicants were prescribed in randomised order for 219 patients who were to undergo elective Caesarean section. Seventy-six (35%) of these patients affirmed at the pre-operative visit that they were not anxious. Diazepam 5 mg and lorazepam 1 mg appeared to be superior to the placebo and to 10-6 ml of 90% alcohol in inducing calmness and/or drowsiness, although the differences were not statistically significant. The incidence of awareness or unpleasant dreams was considerably higher in the placebo and alcohol series (6.2% and 7.5%) than in the diazepam and lorazepam series (nil and 2.1%). There was no remarkable difference in the condition of the immediate newly-born related to the premedicant received by the mother, any small differences being much less impressive than that related to the duration of the U-D interval. No notable differences were observed in the long term conditions between the infants in the placebo, alcohol and diazepam series but the incidence of "reluctance to feed". If relief from preoperative anxiety-and possibly a reduction in the likelihood of awareness-without undue effect upon the infant is considered desirable, diazepam 5 mg is the preferred choice from the four drugs investigated.


[Enzyme immunoassay for the detection and identification of dengue viruses from infected mosquitoes (author's transl)]. The authors deal with a "double sandwich" enzyme immunoassay for the detection and identification of dengue viruses 1, 2 and 4. They use ground glass-beads (7 mm diameter) coated with human heterospecific anti-dengue antibodies, to bind viruses obtained from infected mosquitoes (Toxorhynchites amboinensis). The mouse antibodies bound to the viruses coated on the beads are revealed by anti-mouse 7S immunoglobulins labelled with peroxydase. The method is practical, sensitive and confident. The standard curves obtained with each type show significant differences from one another until very high dilutions of the viral suspension. Inhibition tests by human immune antibodies and dengue antigens demonstrate the specificity of the reaction. This method is certainly applicable to others arboviruses and allows a large scale epidemiological survey.