The comparative feeding mechanism of gadidae and macrouridae. I. Functional morphology of the feeding apparatus. The comparative feeding apparatus of Gadidae and Macrouridae has been studied from a functional point of view. Some important modifications in macrourid species in comparison with the gadid ones were found: rostral end of the cranium, rostral ligaments and disposition of the jaw muscles. Anyways, all the modifications seem secondary, motivated by the habitat. That is true in the case of the beak, in relation with the swimming system which had been already observed by Marshall and Bourne (1964). The question of the rostral ligaments modification would be related with the protraction of the upper jaw, but a further analysis is required. Also discussed are two schemes of possible changes in the jaw musculature.


Development of myodomes and the position of eye muscles in Rasbora daniconius (ham. buch). 1. In Rasbora the anterior myodome for the oblique eye muscles is absent. 2. The attachment of M. obliquus inferior and superior closely follow the teleostean pattern. 3. The posterior myodome is well developed and both the anterior and posterior recti muscles arise from it.


[Definition of the organell concept].

[Definition of the organell concept]. Since the essential cytological functions are endergonic processes, the organelle cannot be defind without considering the necessary energy transfer. Therefore, a sensible definition may read: The Organelle is a cytoplasmatic structure capable of funtional energy consumption (Frey-Wyssling 1977).


Maternal affect-allowance and limit-setting appropriateness as predictors of child adjustment. This study sought to determine whether social competence in children is related to maternal ability to (a) respond differentially to child compliance and noncompliance; and (b) be tolerant of child affect. The study sought to validate aspects of the "reflective" view of personality socialization. One hundred and ninety-five 4-year-olds were rated on the Kohn social competence scale. Mothers were asked to role-play typical responses to childrearing vignettes. The vignettes portrayed child compliance or noncompliance and child affect or no affect. Maternal responses were scored on control level and affect acceptance. The results generally supported the hypotheses. Mothers of high socially competent children were more likely to gear their limit-setting efforts to the fact of noncompliance, regardless of whether affect was expressed. Furthermore, they were more likely to make comments supporting the expression of affect. The results, in addition to supporting a reflective approach to discipline, suggest the need for socialization researchers to adopt a more differentiated approach to the measurement of parental "control" than has been the case in previous investigations.


Induced resistance to 6-methylpurine and cycloheximide in tetrahymena. I. Germ line mutants of T. thermophila. Two new mutant lines of Tetrahymena thermophila (T. pyriformis, syngen 1), each conferring resistance to a different agent, are described. Resistance to cycloheximide and 6-methylpurine are each determined by dominant genes, ChxA2 and Mpr; the traits show phenotypic assortment. The method used to select these mutations, the critical importance of backcrossing to wild type following mutagenesis, and the utility of these marker genes in further mutagenic selection schemes and studies of the sexual cycle of Tetrahymena are noted.


Induced resistance to 6-methylpurine and cycloheximide in Tetrahymena. II. Variation within vegetative cultures of micronucleate T. thermophila and amicronucleate T. pyriformis. Resistance to 6-methylpurine and cycloheximide has been induced in both the micronucleate species Tetrahymena thermophila and the amicronucleate species T. pyriformis. Resistance follows only after mutagen treatment and vegetative growth. The frequencies with which resistant variants are induced and the independence of mutagenesis and selection are demonstrated. All evidence is consistent with the hypothesis that macronuclear subunits are assorting in both species during vegetative growth to produce new phenotypes among subclones.


[Possible role of protein damage in the development of UV-induced isochromatid breaks]. The rate of structural chromosome mutations at the second K-mitosis was studied in the primary culture of embryonic fibroblasts from BALB mice, after treating these cells with UV-rays at various wavelength during G2-phase. The action spectrum of UV-rays for chromatid aberrations, determined at 254, 265, 280 and 302 nm, was found to be closely similar to the absorption spectra of thymidine and to the spectrum of the formation of DNA crosslinks. The action spectrum for isochromatid breaks, determined at the same wavelength, was similar to the spectra of protein absorption. Caffeine (1.37 mM) increases the rate of UV-induced chromatid breaks, when the cells were treated at the S-period of the second mitotic cycle after irradiation and had no effect on other aberration types. It is suggested that various primary damages are responsible for chromatid aberrations and isochromatid breaks. Transversal DNA-DNA crosslinks, formed as a result of thymine dimerization, underlie chromatid aberrations. Chromophor of protein nature is of importance in the origin of isochromatid breaks.


[Effect of genotype on the angiotensin-forming system of plasma and the hypothalamus]. It is shown that hypothalamic renin-like enzyme of mice (lines C57B1/6 and BALB/c) consists of two forms differing from one another in their molecular weight. The allele AY determines the absence of the heavy form of renin-like hypothalamic enzyme (RLHE) and a relatively low level of activity of the blood plasma renin in intact animals. The heavy form of RLHE disappears in mice in case of a considerable dehydration.


[Temperature-sensitive mutations as a possible cause of human embryo fatalities]. Mutations to temperature sensitivity (ts') are suggested to be a casue of the embryo death. In the course of investigation of 102 cases of spontaneous abortions (sporadic and habitual) in 5 cases it was found, that cells propagate badly at 37 degrees C and die at 40 degrees C. Such cell strains could be successfully maintained only at 32 degrees C. Thus the possibility of direct identification of human embryolethals is proved. A hypothesis is advanced that ts' mutations can be a cause not only of spontaneous abortions, but of congenital malformations as well.


Lysosomal N-acetyl-beta-hexosaminidase and beta-glucuronidase activities from arterial wall. Variations with aging. Properties of two hydrolases: beta-glucuronidase and N-acetyl-beta-hexosaminidase were studied in lysosomal fractions of media-intima from arterial wall. These enzymatic activities change significantly with aging. In the arterial wall, the decrease in activities of beta-glucuronidase and N-acetyl-beta-hexosaminidase between young and old rats was highly significant while there no notable change in the activities of acid phosphatase. These data are in agreement with the metabolic slow-down and the modifications of the glycosaminoglycan distribution in the media-intima of arterial wall with aging.


Test of some aging hypotheses using two-dimensional protein mapping. We have compared the proteins from superior cervical sympathetic ganglia (SCSG) in young and old male Fischer rats. We have searched for the kinds of changes in protein size or charge which are predicted by such cellular aging theories as the error catastrophe theory, the somatic mutation theory, the cross-linkage theory, translational aging, the deamidation theory, and the autoimmune theory. SCSG from young (2 months to 1 year) and old (21-24 months) rats were labeled in vitro for 1 h with 14C-leucine prior to protein extraction for analysis. Protein analysis was on high-resolution, two dimensional polyacrylamide gels using O'Farrell's technique, with some modifications. Proteins were separated according to isoelectric point in one dimension and molecular weight in the second dimension. The changes predicted by the above aging theories were detected neither in the staining pattern, showing protein amounts, nor in the labeling pattern on autoradiographs of dried gels, showing newly synthesized proteins. The results suggest the possibility that, at least for rat, some other mechanisms for aging are present.


Hypothalamic neuron number of old female rats. Neuron density, volume of the area and total neuron number were measured in the medial preoptic area (MPOA), supraoptic nucleus (SO), paraventricular nucleus (PVN), anterior hypothalamic area (AHA), ventromedial nucleus (VMN), dorsomedial nucleus (DMN) and arcuate nucleus (ARN) of the hypothalamus in young adult female rats (3.5-5 months old) and in old female rats (over 24 months old). As age advances there is a tendency to increase in the volume of hypothalamic area and consequently decrease in the neuron density. However, loss of neuron due to aging occurs only in MPOA, AHA and ARN. The decrease in neuron number due to aging in these three areas ranged from 23 to 50%. No neuron loss due to aging was observed in SO, PVN, VMN and DMN. The physiological significance of neuron loss in MPOA, AHA and ARN is discussed.


Bidder's hypothesis revisited. Solution to some key problems associated with general molecular theory of ageing. In this paper I consider three major difficulties associated with the general molecular theory of ageing, namely: (1) How can molecular damage accumulate in the face of the constellation of repair mechanisms that is found in cells? (2) How can the obvious programmatic nature of ageing be reconciled with underlying stochastic processes? (3) How do some organisms avoid ageing? As a solution to points 1 and 2, I propose that the repair mechanisms themselves deteriorate in a programmed fashion with age. However, I argue that this programming is unlikely to be a result of direct selection for life-shortening but, rather, is more likely to be a result of an indirect selection for other characters. This idea is very similar to the theory of senescence first formulated by Bidder. The solution to point 3 is that the repair mechanisms in systems which avoid ageing, in particular cellular and molecular turnover, are not impaired with age. The rejuvenating capacities of sexual and asexual reproduction are also discussed.


Some unusual features of Paget's disease of bone. The usual features of Paget's disease of bone, e.g. large head, deafness due to involvement of the 8th cranial nerve and bowing of the legs are all well described in text books of medicine. However, some features such as platybasia with neurological deficit, involvement of the 2nd, 5th and 7th cranial nerves, hydrocephalus, dementia, dysphasia, corrugation of the skull, bone pain (with or without associated osteo-arthrosis of hips and knees), heart failure, triradiate deformity of the pelvis have either had an inadequate or no description in books. These features are unusual, but it is important to recognise them, as the advances made since the introduction of the very promising new drugs in recent years have not only provided increasing insight into the disease, but also have improved management of patients with Paget's disease of bone.


Adrenal function and ascorbic acid concentrations in elderly women. Tetracosactrin (Synacthen) tests were performed on 19 elderly women who had leucocyte ascorbic acid (LAA) levels of less than 15 microgram/108 WBC. 9 were then given a daily dose of 200 mg ascorbic acid orally for 2 weeks while the other 10 were left untreated. Following this, tetracosactrin tests were repeated in both groups. All initial plasm cortisol responses to tetracosactrin were within normal limits. Treatment with ascorbic acid produced no changes in these. This suggests that the low LAA levels often found in old people do not result in adrenal insufficiency.


Acquired antithrombin III deficiency in patients with glomerular proteinuria. Antithrombin III (AT II/III) was determined immunologically and by means of a heparin cofactor assay in plasma samples and 24-hour urine of 15 patients with various degrees of proteinuria, being predominantly of glomerular origin. In urine the AT II/III concentrations were significantly correlated to the concentrations of albumin, plasminogen and IgG. One third of the patients had AT II/III plasma levels below the normal range. The plasma levels showed a significant inverse correlation to the AT II/III and albumin clearance rates. Similarily, the plasminogen concentrations in plasma were decreased in two thirds of the patients, being inversely correlated to the renal plasminogen clearance values. It is proposed that AT II/III deficiency in the nephrotic syndrome is an important pathogenetic factor in venous thrombosis.


Soluble plasma fibrin and platelet prostaglandin endoperoxides following myocardial infarction. Following myocardial infarction, soluble fibrin in plasma is often elevated as a sign of an activated plasmatic coagulation system. Soluble fibrin in plasma is most pronounced in shock patients under catecholamine administration. With the improvement of the clinical situation the fibrin concentration declines to normal. Following incubation with N-ethylmaleimide an increased production of prostaglandin endoperoxides is observed in the platelets of patients after myocardial infarction compared to normal platelets. Plasma of patients exhibits an endoperoxide-producing effect on normal platelets. The stimulating effect of patient plasma diminishes together with the fall of soluble plasma fibrin. These phenomena may be considered as signs of a relation between the plasmatic and thrombocytic coagulation system.


Comparison of antithrombotic activity of heparin, ASA, sulfinpyrazone and VK 744 in a rat model of arterial thrombosis. Rat carotid arteries were injured electrically (350 V, 2 mA DC for 5 min) before and after the intravenous administration of heparin (1,000 U/kg), VK 744 (25, 50, 100 mg/kg) ASA (100, 200 mg/kg) and sulfinpyrazone (50, 100, 150, 200 mg/kg). Thrombus growth was quantified by recording arterial temperature change distal to the injury. Heparin completely blocked thrombus formation in most experiments. All other agents exhibited antithrombotic activity with sulfinpyrazone being most potent. None was as effective as heparin. This model may be a useful tool for screening antithrombotic drugs.


Acetylsalicylic acid and the cardiovascular effects of ADP in the rat. Acetylsalicylic acid (ASA) did not prevent the arrhythmias induced in rats by a bolus intravenous injection of ADP, an effect independent of platelets. ASA was also unable to protect the rats from the platelet-mediated cardiovascular effects and myocardial ischaemia induced by a prolonged ADP infusion. It is suggested that the release of vasoactive substances inhibited by ASA does not play a major role in the cardiovascular effects of ADP in rats.


Rigidity of red cells in essential hypertension. Both viscosity of blood and the rigidity of red cells are of consequence in the mechanism of hypertension. While the details of this mechanism are still elusive, the evidence presented might open the way for a wider inquiry into the role of blood rheology in hypertension.


[Solitary cyst of the distal radius].

[Solitary cyst of the distal radius]. One case of an aneurysmal bone cyst in the distal end of the radius of a 10 year old boy is described. These bone cysts probably develop from local hemodynamic disturbance and should be treated by evacuation and cancellous bone packing. Their propensity for recurrence is confirmed in the literature.


[Gout - a surgical problem].

[Gout - a surgical problem]. The incidence of gout has increased in recent years. For effective treatment an interdisciplinary approach is necessary. Medical therapy can be effectively supported by surgical removal of the tophi. This way normalisation of the uric-acid-pool can be achieved more quickly without additional harmful effects on the kidneys. Especially in the area of the hand surgical extirpation of the tophi can be gratifying, though it may be a difficult task. Severe restrictions in function of the hand can be corrected. This is demonstrated by the case of a 56 year old patient.


Arterial patterns in the hand and pollicisation. The arterial pattern of the human hand shows remarkable variations in so called normal individuals. In patients with congenital deformities of the hand there are also be variations based on embryonic disturbances. Therefore, the total pattern is complex. Successful transfer of fingers depends on an adequate blood supply. In some individuals there are variations in the patterns of blood supply which make a finger transfer more risky. Modern angiography makes the study of the arterial patterns of the hand possible. The authors state that angiography is essential in the pre-operative examination of a candidate for finger transfer. Three case histories illustrate this statement.


[Perilunar, transscaphoid, transcapital, transstyloid fracture-dislocation of the wrist. Operative reconstruction]. Report of a new type of fracture dislocation of the wrist and the intercarpal joints, which has not been published until now. A perilunar dislocation was associated with fractures of the scaphoid and capitate bones as well as a fracture of the radialstyloid. Open reduction and internal fixation was followed by fracture healing and slight posttraumatic arthritis. Loss of function was minimal and working capacity not reduced.


[Biomechanical aspects of arthrosis of the carpometacarpal joint of the thumb and its treatment with a special endoprosthesis]. The joint between the trapezium and the first metacarpal is anatomically like a saddle. In function, however, it is used like a ball and socket joint with the following possible movements: 1. Flexion - extension, 2. abduction - adduction, 3. opposition and circumduction. The movements in the two first planes are completely congruent, whereas in the third an incongruent motion of the joint is created by the rotation of the metacarpal on the trapezium. In this situation there is joint contact at one point only, being - biomechanically - a prearthrotic deformity as described by HACKENBROCH. Accordingly, the carpometacarpal joint of the thumb in normal use is exposed to special stress which can end in degeneration. When in arthrosis of the carpometacarpal joint of the thumb conservative measures fail, we replace the deformed joint by prosthesis having the construction of a ball and socket joint. The prosthesis (designed by FRANCOBAL) has a metallic part with body, neck and a sphereshaped head, and a polyethylene socket, which can be coupled to the head by a snap mechanism. Both parts are inserted with polymethylmetacrylate cement into the prepared bone of the trapezium and the first metacarpal. The advantages of this method are: no pain, stability of grip, and motion similar to that of a ball and socket joint. Because this motion is physiological, loosening of the implants and their insertions are avoided. The first 8 patients treated with this method show satisfying functional results. The longer follow-up time is 6 years.


[Treatment results in fractures and pseudarthrosis of the scaphoid bone]. In 258 patients with fractures and pseudarthroses of the carpal scaphoid the cause and type are given and the results of treatment are presented. It is verified that the majority of fresh fractures are united by plaster immobilisation. In fractures with delayed healing and in cases with non-union the best results are achieved by autologous bone grafting.


Group treatment of epileptics.

Group treatment of epileptics. Contrary to popular belief, in most cases epilepsy need not be a major handicap to the individual. However, epileptic patients usually have a variety of psychosocial problems, largely because of the pressures and frustrations with which they are often confronted in society and at home. The authors describe an interdisciplinary approach to the health care of these patients in which group treatment was a primary component.


Reflections for Rosalynn: mental health policy and time lag. By establishing the President's Commission on Mental Health early in his Administration and by ordering the final report to be presented by mid-1978, President Carter appears to have insured that this commission will have direct impact on mental health legislation. The authors point out how the work of previous commissions was delayed to the point of being negated by changes in the sociopolitical climate.


Medical problems of the alcoholic in nonmedical treatment. The ambivalence about chronic alcohol abuse among health and related professionals can result in their failure to appreciate medical complications frequently associated with this disorder. Data from 81 male alcoholics are presented in this article to illustrate their increased risk of physical illness and premature death. The authors point to the need for more effective screening and monitoring procedures in alcoholism programs as well as improved training of professionals.


Managing the psychosocial factor in disaster programs. In developing disaster plans, hospital administrators are not always aware that the psychosocial needs of victims and their families can be greater than their medical needs. The author outlines a program to deal with the psychosocial factor in disasters, emphasizing the role of the social work department.


Visiting aides training program.

Visiting aides training program. This article describes a hospital-sponsored service program in which mature members of the community are given a course of supervised field training in the home care of recently discharged patients. The program benefits the trainee, the patient, and the general taxpayer.


Innovative roles for social workers in home-care programs. Home care has become recognized as an effective means of preventing or postponing costly institutionalization. In order to provide more comprehensive programs, home health agencies will require the services of professionally trained social workers. The author describes several roles for social workers trained in clinical services, administration, and planning.


Attitudes toward elderly clients.

Attitudes toward elderly clients. Many studies have found that social workers often have negative feelings about the elderly. The authors review research findings in this area, offer explanations for the negative feelings of professionals, and provide suggestions for insuring appropriate attitudes among those who work with elderly clients.


Latex reaction with toxoplasma antigen.

Latex reaction with toxoplasma antigen. The technique of latex reaction with toxoplasma antigen is briefly described. The results of latex reaction are compared with those obtained by complement-fixation test, indirect fluorescence reaction and microprecipitation in gel.


Redescription of the nematode Philometra obturans (Prenant, 1886) with a key to the philometrid nematodes parasitic in European freshwater fishes. A redescription of the nematode Ph. obturans (Prenant, 1886), based on specimens from pike (Esox lucius L.) from the R. Elbe basin in Czechoslovakia, is presented. In addition to gravid, subgravid and mature females from the blood system also the male and mature female, found for the first time in the host's eye, are described. The paper is supplemented by a key for the identification of the philometrid nematodes parasitizing freshwater fishes of Europe.


On some theoretical and practical aspects of population variability in helminths. Possibilities of studies of some microevolutionary processes in helminths on the basis of knowledge of their variability are presented. The practical aspects of the study of helminth variability are also referred to. In conclusion the author states that the investigation of non-morphological characters of helminths, in relation to various morphological structures of phenotypes in the populations of parasite and host, represents a sphere in which the interests of theoretical and practical helminthology meet with one another.


Some aspects of monogenean existence.

Some aspects of monogenean existence. This paper deals with some ecology and evolution problems of monogeneans--gill parasites of fishes, such as congeneric simultaneous doublets, spatial distribution of species on the gills, interspecific restrictions of biotopes etc. The author proves competitive character of site selection in monogeneans. The role of hermaphroditism in the evolution and biology of monogeneans, and morphological adaptations (mainly androgynous) directed to increasing of mating chance are discussed. The author concentrates on analyzing the cases of monoxenous distribution and speciation and also on examining the concept of symxenity and alloxenity. He attaches great importance to ecological and evolutionary investigations of Monogenoidea.


Tissue reaction of the liver of cattle to an artificial or natural infection with Cysticercus bovis. An evaluation of the tissue reaction to Cysticercus bovis in the liver of calves with an artificial infection and that of oxen with a natural infection provided evidence for the fact that the liver of these animals responded to an infection with C. bovis with an extensive granulomatous reaction. A comparison of tissue reaction to cysticerci at an identical stage of development showed that the reaction of the liver parenchyma was much more intensive than that of the heart and the skeletal muscles. In the described cases, this intensive reaction caused the death of the cysticerci before the completion of their development. Evidence was obtained for the first time that also in the liver C. bovis was located in the lymphatic vessels.


Investigations on the fauna of beds in flats, children's sanatoria and old-age homes. An analysis was carried of the fauna found in 338 beds from two old-age homes and from flats inhabited by asthmatic children. During hospitalization of these children the fauna in the flats was compared with that found in beds used by them in sanatoria. The most abundant species proved to be Dermatophagoides pteronyssinus that is also widely spread in other countries of Europe. The bed fauna in the sanatoria is very poor, corresponding to the improved state of health of patients during hospitalization. The authors assume that the low population density of fauna is influenced by constant airing of rooms and by strict separation of bedrooms from dining halls and other premises. Also the number of mites in different padding material used in mattresses was evaluated and an analysis of the general fauna per bed was carried out.


Natural infection of the tick Dermacentor reticulatus (Fabr.) with the microsporidian Nosema slovaca Weiser et Rehácek in Slovakia. A total of 6,199 adult ticks (Haemaphysalis intermis, Dermacentor reticulatus, D. marginatus and Ixodes ricinus) collected in three localities in Slovakia were examined for microsporidian infection. The spores of Nosema slovaca were found in six D. reticulatus (0.097%). The microsporidian experimentally inoculated into the hemocele of half-engorged females of D. reticulatus caused acute infection and death of the host. The infection can be transmitted also to other tick species from the same region. The yield of spores from one tick ranges from 3 X 10(5) to 52 X 10(7) depending on the infection dose and tick species. Peroral infection of some butterfly larvae with the microsporidian pores was unsuccessful. The importance of Nosema infection in ticks in nature is discussed.


Microscopical anatomy of larva of cheladonta costulata (Acarina: Trombiculidae) II. Body tegument and digestive system. The cuticle of gnathosoma of Cheladonta costulata larva consists of a smooth and firm epicuticle and sclerotized procuticle. The cuticle of the idiosoma is elastic. The wall of the digestive system is formed by cells lying on the basal membrane. During the process of sucking, however, the intestinal cells, which were originally spherical, get an appearance of a club reaching up to the lumen of intestine. In a fully engorged larva the intestine appears to be united and fill the major part of body. The lumen of the intestine is filled with eosinophilic granules of various size, among which are minute granules with basophilic tinge. The excretory bladder is located between posterior lobes of the intestine. In an unengorged larva, the excretory bladder is conical and possesses a conspicuous wall of a cellular structure. Its lumen is empty. In a fully engorged larva, the excretory bladder is oval, covered with a thin membrane, and its lumen is filled with guanine crystals.


Improved yields of daunomycinone glycosides in developmental mutants of Streptomyces coeruleorubidus. When improving Streptomyces coeruleorubidus JA 10092, a producer of antibiotics of the daunomycinone complex, the most active variants were found among isolates of morphological types bld-1 (with a suppressed production of the aerial mycelium on organic media containing glucose) and whi (with an asporogenic aerial mycelium on glucose media and with the bald phenotype on media containing starch). Submerged cultures of the whi mutants produced increased quantities of daunomycinone glycosides in the antibiotic complex, the amount of free anthracyclinones being simultaneously decreased. The whi strains differed from the wild type also in higher demands for aeration, concentration of glucose and in an increased production capacity in starch media. The overall antibiotic activity increased more than 40 times after a six-step selection (application of UV light, gamma-radiation, nitrous acid and natural spreads) combined with an altered fermentation technology.


Mutants of Streptomyces coeruleorubidus impaired in the biosynthesis of daunomycinone glycosides and related metabolites. Mutants of Streptomyces coeruleorubidus, blocked in the biosynthesis of anthracycline antibiotics of the daunomycine complex, were isolated from the production strains after treatment with UV light, gamma-radiation, nitrous acid, and after natural selection; according to their different biosynthetic activity the mutants were divided into five phenotypic groups. Mutants of two of these groups produced compounds that had not yet been described in Streptomyces coeruleorubidus (aklavinone, 7-deoxyaklavinone, zeta-rhodomycinone and glycosides of epsilon-rhodomycinone). The mutants differed from the parent strains and also mutually in morphological characteristics but no direct correlation between these changes and the biosynthetic activity could be observed in most cases.


The replication map of the chromosome of Mycobacterium phlei. It was the aim of the present work to construct the replication map of the chromosome of Mycobacterium phlei. The method of mutagenesis of the replication point by N-methyl-N-nitroso-N'-nitroguanidine in synchronously dividing populations and the method of analysis of gene frequency were applied. The order of replication of 19 genes on the chromosome was determined by means of induction of back mutations and forward mutations in auxotrophic mutants PA leu and PA met and in double auxotrophic mutants with methionine as a reference marker.


The cytotoxic and cytocidal effect of colicin E3 on mammalian tissue cells. The plasma membrane of mammalian cells can mediate the cytotoxic and cytocidal effects of colicin E3. As little as 10(2) lethal units of purified colicin E3 per cell exert a pronounced cytocidal effect on human epithelial HeLa cells and as little as 10(4) lethal units per cell also on line L mouse fibroblasts in tissue culture. Cells in complete monolayers are rapidly killed, become spherical and shrink, they are detached from the support and finally autolyzed. The percentage of killed cells in both lines is directly proportional to the multiplicity of colicin used. The LD50 for HeLa cells is about 30 times lower than for L cells. At the multiplicity of 10(5) I.u., usually 100% HeLa and 90% L cells are killed in 2--3 days. Purified colicins E2 and D have no demonstrable cytological effect on HeLa cells, although DNA synthesis in L cells appears to be partly inhibited by colicin E2. The profound effect of colicin E3 on mammalian cells could be interpreted in a similar way as in bacteria, viz. as a specific cleavage of rRNA.


Glucose-2-oxidase activity and accumulation of D-arabino-2-hexosulose in cultures of the basidiomycete Oudemansiella mucida. Submerged cultures of the basidiomycete Oudemansiella mucida, strain III, accumulate D-arabino-2-hexosulose. The maximum yields during cultivations in shaker flasks or in a laboratory fermentor are 6--12 and 15 mg/ml, respectively (20--50% conversion of substrate glucose). The accumulation is transient, the aldoketose being again utilized after glucose exhaustion. Its production is stimulated by fluoride ions. The enzyme responsible for the C(2)-specific oxidation of D-glucose acts as an intracellular oxidase with a maximum activity in the exponential phase of growth. D-arabino-2-Hexosulose was also detected in the cultivation medium of the wood-rotting fungi Pleurotus ostreatus, Laetiporus sulphureus, and Phellinus abietis.


Studies on xylan hydrolases from different strains of Streptomyces and their mutual influences in the breakdown of xylan. A good proportion of Sreptomyces isolates from natural sources produced extracellular xylan hydrolase. Nineteen isolated showing high activity were able to completely or partially degrade wheat bran in the growth medium. Chromatographic analysis of commercial xylan degradation products suggested that the isolates produced either endo- or exo-xylan hydrolases or their mixtures. Mixed additions of culture fluids showed a highly synergistic effect, up to an increase by 200%. In a few cases antagonism was seen which, however, could be removed by dialysis of the culture fluid.


Management of innovation and change in mental health services. In recent years the mental health field has been characterized by innovation and change. All changes are not sound or necessary, and the most common approach to implementing change, that of power, can have unfortunate consequences. However, the incidence of innovation and change and the growing technology on planning for the adoption of innovations indicates that change can be managed more effectively. One approach to managing change is the decision determinants analysis model, a group of eight factors that influence whether a change will be successfully adopted; they are ability, values, information, circumstances, timing, obligation, resistance, and yield. The author discusses the factors and gives suggestions related to each for increasing the probability of successful adoption of a change.


Gold award: mental health services for the deaf--St. Elizabeths Hospital, Washington, D.C. The mental health program for the deaf at St. Elizabeths Hospital offers comprehensive services to adolescents and adults who were born deaf or who became deaf early in life. A staff of 49, six of whom have impaired hearing, provide services to about 33 inpatients and about 71 outpatients. Activity therapies that do not require oral communication, such as occupational therapy, art therapy, dance therapy, and psychodrama, play an important role in the program, as does group psychotherapy. The program provides training, field experience, and consultation for workers throughout the U.S. and from foreign countries. Some guidelines for communicating with the deaf are given.


Gold award: providing psychiatric care and consultation in remote Indian villages--Department of Psychiatry, University of Toronto, Toronto, Ontario. Faculty of the University of Toronto department of psychiatry take several trips a year to remote Indian villages in northwestern Ontario to deliver care to the Cree and Ojibway people and to provide consultation and training to the service delivery providers in the area. The program is part of a larger medical program operated by the university and financed by the Canadian government. Psychiatrists face numerous cultural and language obstacles in addition to harsh weather conditions and limited means of communication in the vast Sioux Lookout zone. When they are back in Toronto, they keep in touch via two-way radio with professional staff in the zone for ongoing consultations.


Hospital policies and procedures: even 'the system' needs a system. Hospitals need effective systems for recommending, coordinating, writing, distributing, and implementing policies and procedures. Some features of an effective system include use of a coordinator, interdepartmental cooperation, and well designed forms and manuals. Some of the benefits include better management and better coordination with regulatory bodies and requirements.


Community health education fostered by hospital program. A small, acute care hospital in Massachusetts develops its community outreach program by offering health care services to area schools and industries. The Clinton Hospital Industrial Program (CHIP) offers special first aid courses, testing and rehabilitation services, and employee health plans to the town's numerous small industries. The School Nurses Program and CPR training for high school teachers are two services the hospital offers Clinton public schools.


Day care complements hospitalization.

Day care complements hospitalization. A program of day care for psychiatric patients can reduce costs and provide a more suitable environment for the treatment program. Such programs hold considerable promise for other types of programs in various types of hospitals.


Patient transfer form provides continuity of care. General Hospital of Everett (WA) took the initiative in developing a new patient transfer form that has been adopted for statewide use. By using suggestions from a wide variety of sources, a hospital committee, which consisted of professionals from local extended care facilities and nursing homes, as well as from the hospital's staff, was able to develop a useful and effective patient transfer system.


Food services merge to contain costs and enhance menu. A sharing of food service facilities between two institutions has cut costs and has benefited patients and dietary staff. It was aided by a standardization of menus, which increased the variety to the patient but simplified menu tabulation and production for the food service operation. The program's success has enhanced the image of many of the hospital's other programs.


Controlled substances registration for nonlicensed physicians. Changes in drug laws and the addition of many formerly uncontrolled drugs to the controlled substances list has caused some concern about the registration of nonlicensed physicians. The question is, how does the recent medical school graduate obtain authorization to use the controlled substances he may need in the course of his postgraduate training at the hospital? The University of Alabama Hospitals, Birmingham, have answered the question with an effective system for hospital registration of nonlicensed physicians.


Survey shows increase in hospital training programs. A 1976 AHA survey has determined that the extent of hospital-based training programs for the allied professions has increased since 1973, when the previous survey was conducted. Both surveys depict the wide range of types of such programs offered by hospitals.


System for control, monitoring ensures efficient linen use. By implementing recommendations from a short-term consulting program, a hospital regained control over the use, costs, and quality of its linen service. Long-term measures, such as use of rescheduled distribution, appropriate quotas, consistent policies, a hospital linen manager, and reports for measuring performance, have cut the costs and improved the service of the linen department.


Planning: simplistic guidelines won't work. The controversy over the national guidelines for health planning and appropriateness review is well-founded. There is no question that planning tools are required if the planning process is to have validity, but simplistic rules will only make planning chaotic. There must be room for input from the grass roots.


Study of malpractice panels notes advantages, problems, gaps in data. A special study on malpractice panel systems in four states identified the currently limited participation of non-physician hospital personnel and 14 factors that determine the effectiveness of such systems. However, more data are needed to determine whether such systems resolve cases fairly and quickly and stabilize malpractice insurance premiums.


Hospital system works to ensure risk management, quality of care. A health care corporation that includes several hospitals and other related health services conducts a wide variety of institutional and corporate activities and programs of risk management and quality assurance. Some of these efforts include board review of medical staff organization and privileges, medical and nursing audits, patient care evaluation, a risk manager and steering committee, patient education, equipment maintenance, and safety programs.


Creativity and hospital costs: it's all in the approach. Although most hospitals do consider costs before deciding to fund a new undertaking, many of them fall short of the necessary inventiveness when it comes to developing low-cost alternatives in problem-solving situations. Thus, too often, solutions to problems are found in a climate of crisis that overshadows considerations of cost. If hospitals would take a creative approach to cost containment and regard it as a philosophy or an attitude rather than a program, they might find that they have less trouble in slowing down cost increases to the annual rate of inflation.


Ambulatory surgical center lowers costs, not services. The development of ambulatory surgical centers is a recent development in the health care delivery system. This article reflects the experience of one hospital in developing and implementing an ambulatory surgical program.


The all-RN staff: why not?

The all-RN staff: why not? The emphasis on cost containment and consumer satisfaction has spurred a new upsurge in interest in all-RN nursing. Data are mounting that show that an all-RN staff doesn't necessarily cost more and that its use markedly improves the quality of patient care. Although obstacles to implementation exist, they are not insurmountable, and nurse leaders are asking, "Why not?"


We only have to ask.

We only have to ask. As a group, hospital trustees have great potential for effecting positive change in the hospital industry. Hospital administrators and hospital associations must recognize this potential, focus the commitment trustees are willing to make, and put that commitment to constructive use. Without their help, the author says, the process of making positive changes will be difficult, if not impossible.


Hospital administrators face stiff competition in job market. Career opportunities in health administration will broaden, but the career ladder will be harder to climb, according to the president of the American College of Hospital Administrators.


Landscaped campus site humanizes life for the elderly. Conceptual planning and architectural design have enabled the elderly residents at Maple Knoll Village, Springdale, OH, to live somewhat independent lives and to receive essential medical and nursing care. The landscaped campus and linked residential and health care facilities generate a community spirit, an opportunity for social interaction and individual pursuits, and a personal sense of security and physical and emotional well-being.


Program rehabilitates alcoholics, alleviates personnel problems. By establishing an employee's alcoholism program, Montefiore Hospital and Medical Center (MHMC) has reduced absenteeism, increased productivity, improved the supervisory process, and, in most instances, enabled rehabilitated alcoholics to satisfactorily perform their jobs. The rationale, policy, components, and administration of this program can be replicated in any health care institution that is committed to the personal well-being of its employees and to the quality of its services.


Clinical engineering from the administrator's perspective. Based on the results of a survey, investigators infer that hospital administrators have a "diverse, and, at times, inaccurate understanding of clinical engineering.". For instance, most hospitals would integrate their perceived clinical engineering function into their general maintenance operation. Among other things, results indicate that administrators have not fully accepted the need to have a professional person to provide these services.


Group purchasing of food items maintains quality, cuts costs. Hospital food group purchasing programs face problems that other kinds of group purchasing programs don't have. HARICOMP, a not-for-profit hospital shared services corporation, helped a group of Rhode Island hospitals solve some of these problems by using computers. The computers eliminate much of the time-consuming effort involved in making price comparisons, holding sales meetings, and doing paperwork.


Rx for health care economics: competition, not rigid NHI. While competition may serve consumers well in the production of many goods and services, it does not function equally well in all of the nation's economic sectors. And the health services sector does not fit the competitive model at all well. The market for medical care services might be restructured, however, so competition might yield more of the benefits it yields in other markets.


Sponsorship: the uneasy question.

Sponsorship: the uneasy question. The Sisters of Mercy of the Union, as part of a more general concern that their ministry meet its objectives of prophecy and service, set up a committee to investigate the issue of sponsorship. This committee defined a sponsored activity, drew up criteria for evaluating the effectiveness of such an activity, and developed an instrument for establishing whether an activity meets the criteria for Mercy sponsorship.


Dealing confidently with IRS, Part I: Preparing for IRS audits. With the IRS apparently making health care institutions the focus of a nationwide audit emphasis, hospital administrators will want to prepare themselves for confident handling of audits. Four types of audit procedures are explained, suggestions are made for getting a hospital ready for an audit, and strategies are suggested for maintaining control over the audit's progress.


Guidelines for evaluating department managers. A format is suggested for administrators' difficult, important task of evaluating hospital department managers' relationships within the department and with other departments and personnel; official relationships with personnel outside the hospital; creativity and initiative; dependability; level of supervision required; sense of loyalty and understanding of the hospital's interest; and performance as outlined in the job description.


The health care market audit.

The health care market audit. With marketing increasingly being accepted as a mechanism by which hospitals can more effectively meet community needs, a hospital can begin a marketing program by auditing its markets. This involves identifying, collecting, and evaluating information.


St. Francis Hospital and Medical Center, Topeka, KS. A fast-track project: keeping going while growing. St. Francis Hospital and Medical Center, Topeka, used careful planning, good communication, and the fast-track design and construction method in a $20-million project to nearly double the facility's size. Although keeping the hospital going while building this addition involved inconvenient trade-offs, the facility's administration "would do it again."


Developmental abnormalities of the kidney in children. The prognosis for infants and newborns with anomalies of the kidney and lower urinary tract can be improved by differentiating the disorders according to etiology and gearing treatment accordingly. In this second article of a new series on renal function in health and disease, congenital and hereditary anomalies are characterized in terms of their physiologic consequences, and guidelines for therapy are provided.


When cholecystectomy?

When cholecystectomy? The crux of the matter is to avoid being forced into cholecystectomy when the patient is acutely ill and has an increased risk of operative mortality. The rationale for performing surgery on an elective basis in patients with chronic gallbladder disease and for early medical management in most patiens with acute disease is discussed, along with the specifics of diagnosis and special considerations in the handling of problem cases.


Asthma in adults III: occupational asthma. Recognition of the disease may be difficult, since symptoms may be atypical and a temporal association with exposure is often obscure. Attention is given to the ways of differentiating the truly allergic in origin from other types of occupational asthma.


The ischemic myocardium: mechanism of early pump failure. The rapid loss of myocardial contractility that occurs after coronary occlusion may result from the absence of some critical substrate for cellular metabolism or from accumulation of toxic metabolites. In any event, for a few hours the portion of the myocardium affected by the interruption of blood flow retains its viability. Research into the mechanisms operating during this early period may open the way to reversal of the cellular changes.


Assignment of peptidase S (PEPS) to chromosome 4 in man using somatic cell hybrids. A starch gel electrophoretic procedure is described that resolves peptidase S (PEPS) as well as the peptidases A, B, and C in man-rodent, rodent-rodent, and primate-rodent interspecific somatic cell hybrids. The interspecific PEPS cell hybrid phenotype can be resolved into a pattern which suggests that PEPS is composed of five or six identical subunits. Results are presented supporting assignment of the PEPS locus to chromosome 4 in man using man-mouse and man-Chinese hamster somatic cell hybrids. Human genes coding for peptidases A, B, C, and D were assigned to chromosome 18, 12, 1, and 19, respectively, confirming previous assignments. These somatic cell genetic data demonstrate the independent genetic control of the several human peptidases.


Analysis of DNA replication patterns of human fibroblast chromosomes: the replication map. A replication map of human fibroblast chromosomes from two diploid human female fibroblast lines, 46,XX and 46,X, del (X)(q13), was determined using the 'fluorescent plus Giemsa' (FPG) technique. Each chromosome was found to stain homogeneously dark when thymidine was incorporated for the entire S phase of that particular cell. As the duration of exposure to thymidine progressively decreased by increasing the incubation time in bromodeoxyuridine, the staining intensity of chromosomes decreased and, concurrently, gaps in the staining began to appear. These gaps coincide with R bands and represent the earliest areas to complete DNA synthesis. As these areas widen and increase in frequency, first Q and G bands appear, and finally C bands. Homologous X chromosomes were easily differentiated by either a comparison of the bands present or their staining intensity. The replication kinetics of the structurally abnormal heterocyclic X chromosome were very similar to those of the normal heterocyclic X chromosome. The X chromosome with deletion of a portion of the long arm was consistently late in replication.


Mutation rates from rare variants of proteins in Indian tribes. Recent attempts to estimate mutation rates in man have resulted in some theoretical developments. Recently, Nei (1977) provided a new formula for estimating mutation rates from electrophoretically detected rare protein variants. His formula is applied here to estimated mutation rates from such variants among the Kadars of Kerala and five tribes of Andhra Pradesh in India. The estimates seem to differ from Nei's estimate on South American Indians by an order of magnitude, although the standard errors associated with such estimates are rather large.


Incidence of 47,XYY karyotype in a consecutive series of newborn males in Tokyo. A series of 3545 newborn males, born consecutively at a maternity hospital in the western suburbs of Tokyo and with no detectable physical abnormalities, were studied for fluorescent Y-chromatin. Buccal cell smears from each infant were screened. Cases with ambiguous results were subjected to a second test by blood smears, which were found to be more reliable. After the second test, chromosomal analysis was carried out in five infants: three had a 47,XYY karyotype; one, the karyotype 46,XY-D,t(D:Y) (Iijima et al., in preparation); and one, a normal male karyotype. The XYY karyotype occurred in 0.11% of newborn males in this series.


Refined mapping of the gene for glutathione reductase on human chromosome 8. Activity of the enzyme glutathione reductase (EC 1.6.4.2) in erythrocytes and fibroblasts of a patient with karyotype 46, XY, del(8) (pter-p212:) was found to be in the normal range. With results from other laboratories, this allowed a more precise mapping of the gene for this enzyme in the region 8p2100-8p212.


Partial trisomy-5p.

Partial trisomy-5p. Two sibs with partial trisomy-5p are reported. Their father is the carrier of a balanced translocation 46,XY,t(4q+;5p-). Twelve cases of partial trisomy-5p--including our two patients--have been reported. The most common abnormalities found were mental retardation, short stature, dolichocephaly, prominent nasal bridge, prognathism, seizures, hypotonia, ear abnormalities, increased ulnar loops on the fingertips, and cryptorchidism in affected males.


Human semen as a source of epithelial cells for culture. When washed cells from human semen samples were plated out, epithelial cultures were obtained. The human ejaculates used as starting material contained, in addition to spermatazoa, 10(3) to 10(7) cells of other types, including granulocytes, macrophages, lymphocytes, spermatocytes and epithelial cells. Although no fractionation of cell types was attempted, semen samples yielded epithelial cultures uncontaminated by fibroblasts. The cultured cells appeared characteristically epithelial with a polygonal shape, interdigitating cell membranes, and desmosomes. ABH blood-group antigenic determinants of the donor were expressed with variable frequency as a surface antigen on these cells. About half the trials gave some cell attachment. Most cultures remained as small, tight colonies, but a few reached confluency in about 5 weeks and could be subcultured successfully. Cell proliferation, as monitored by (3H) thymidine incorporation into nuclear macromolecules, ceased in less than 2 months.


Normal human endometrium in cell culture. I. Separation and characterization of epithelial and stromal components in vitro. Separation of human endometrium into its epithelial and stromal components has been achieved through collagenase digestion and has permitted a study of these two cell populations under specific experimental culture conditions. The stromal cell populations showed a progesterone response, were easily handled in culture, and displayed a limited in vitro life span typical of human diploid fibroblasts. In contrast, epithelium only survived in short-term primary culture and showed no clear hormone response. High-density epithelial cultures remained viable for longer periods in culture. Comparisons between resurfacing endometrial epithelial cells in vivo and epithelial cells migrating from explants in vitro suggested that this initial epithelial migration in vitro was the counterpart of the repair response in vivo.


Cartilage tissue differentiation from mesenchymal cells derived from mature muscle in tissue culture. Under the influence of biochemical components of bone matrix gelatin (BMG), cartilage differentiates in tissue culture from the connective tissue cell outgrowths of mature muscle. Proliferation and differentiation begin within 24 hr with synthesis of hyaluronate, continue with high levels of synthesis of DNA and hyaluronidase, and culminate in production of large quantities of chondroitin sulfate. The addition of hyaluronic acid to the culture medium during the first 48 hr of culture depresses, whereas chondroitin sulfate enhances, subsequent production of cartilage. These observations on the cell biosynthetic products prior to the appearance of mature cartilage suggest that the BMG--modified connective tissue outgrowths of mature muscle exhibit the developmental potential of embryonic axial mesenchyme. Whether muscle harbors embryonic cells in a programmed but not yet activated readiness (protodifferentiated state) to differentiate into cartilage, or simply contributes a population of temporarily dedifferentiated fibroblasts, is not known, but in any event, BMG switches the pathway of further development from fibrous connective tissue to cartilage.


Spontaneous 51Cr release by isolated rat hepatocytes: an indicator of membrane damage. Radiochromium uptake and release by isolated rat hepatocytes in suspension was monitored under continuous-labeling conditions. Cell protein remained unchanged during the absorption phase, whereas the release of 51Cr correlated well with the loss of cell viability and release of cytoplasmic protein. The results suggest that under equilibrium conditions, 51Cr release represents an efflux of label from damaged or dying preparations and not an elution of radioisotope from intact cells.


Identification of hydrogen peroxide as a photoproduct toxic to human cells in tissue-culture medium irradiated with "daylight" fluorescent light. Hydrogen peroxide, lethal for human cells, is produced in Dulbecco's modified Eagle's tissue culture medium when exposed to "daylight" fluorescent light. Addition of pure H2O2 and use of the enzyme catalase demonstrate that about 40% of the toxicity in irradiated medium is due to generated peroxide. Riboflavin and tryptophan, or riboflavin and tyrosine, are the components necessary for formation of lethal levels of H2O2 during light exposure.


Protein synthesis in imaginal disks of Plodia interpunctella during development in vivo and in vitro. Wing imaginal disks were dissected from larvae of Plodia interpunctella (Hübner) at various stages during the larval-pupal transformation. The wing-disk proteins separated by electrophoresis and scanned with a densitometer changed quantitatively but not qualitatively during development in vivo. Treatment of wing disks in vitro with beta-ecdysone resulted in a 2-fold increase in synthesis of proteins after only 2 hr incubation. The maximum rate of protein synthesis was reached 16 hr after treatment with hormone. The pattern of proteins separated by electrophoresis of wing disks that were incubated in vitro with beta-ecdysone did not change qualitatively. The major features of protein synthesis during wing-disk development in vivo were similar to those observed during beta-ecdysone-induced development in vitro.


Ischemic myocardial injury in cultured heart cells: leakage of cytoplasmic enzymes from injured cells. An in vitro model of myocardial ischemia has been established with primary monolayer cultures of postnatal rat myocardial cells. Ischemic conditions were simulated in vitro by subjecting the myocardial cell cultures to various levels of oxygen and glucose deprivation. The experimental protocol consisted of treatment with 20% or 0% O2 and 1000, 500 or 0 mg glucose per 1 of medium for 4 or 24 hr. Control cultures were treated with 20% O2 and 1000 mg glucose. After the ischemic treatments, cultures of beating muscle (M) cells were evaluated for signs of injury, i.e. leakage of cytoplasmic enzymes into the culture medium. Differences were found in leakage of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) from the cultures that were exposed to partial ischemia of glucose deprivation and from those cultures that were exposed to total ischemia of oxygen and glucose deprivation. Glucose deprivation along resulted in a slight-to-moderate loss of LDH and CPK from the cells, whereas total ischemia resulted in a significant release of the two cytoplasmic enzymes. When the cultures were allowed to recover after ischemic treatment in complete medium (1000 mg glucose) and a normal atmosphere of 20% O2, they had levels of LDH leakage comparable to those of control cultures. Cell viability and total protein content of the ischemic cultures did not differ significantly from controls.


Isolation of specific and common antibodies to staphylococcal enterotoxins A and E by affinity chromatography. Specific and common antibodies to staphylococcal enterotoxins A and E (SEA and SEE) were isolated from anti-SEA and anti-SEE antisera by affinity chromatography. Anti-SEA and anti-SEE antisera were passed through a column with the cross-reacting enterotoxin coupled to a CNBr-activated Sepharose 4B matrix. Specifically bound common antibodies were eluted with NaSCN. The isolated specific antibodies reacted only with the homologous enterotoxin, whereas the common antibodies gave a reaction of identify with both enterotoxins in double gel diffusion plates. The common antibodies had a higher titer against SEE than against SEA. The significance of the isolation of antibodies common to two separate protein molecules is discussed.


Passive transfer of resistance to frambesial infection in hamsters. The immune mechanism by which hamsters acquire resistance to infection with Treponema pertenue, the causative agent of frambesia, or yaws, has not been elucidated. Serum or cells (spleen or lymph node) obtained from hamsters resistant to frambesial infection were transferred to normal syngenic recipients, who are subsequently infected with T. pertenue. The following parameters were used to measure the ability of immune serum of cells to confer resistance on recipient hamsters to frambesial infection: inhibition of the development of cutaneous lesions, decreased weight, and number of treponemes in the inguinal lymph nodes. This investigation demonstrated that immune serum conferred protection on recipient hamsters infected with T. pertenue. Discontinuation of the administration of immune serum (18 days after frambesial infection) did not result in the development of cutaneous lesions. Since the inguinal lymph nodes contained a sizeable number of treponemes (2.6 X 10(5)), immune serum failed to prevent frambesial infection. Recipients of immune spleen or lymph node cells initially developed frambesial lesions 9 days after infection. The frambesial lesions began to resolve 12 to 14 days after infection and by day 21 had completely regressed. These results illustrated that humoral factors and cells are involved in resistance of the hamster to frambesial infection.


Distribution of endotoxin (lipopolysaccharide) in the tissues of lipopolysaccharide-responsive and -unresponsive mice. We examined the distribution of bacterial lipopolysaccharide (LPS) in LPS-responsive (C3H/St) and LPS-unresponsive (C3H/HeJ) mice. The results reported here demonstrate that the rates of removal of an immunological or a toxic dose of LPS from the circulation are the same in both strains of mice. C3H/St spleens accumulated significantly more LPS than C3H/HeJ spleens after the intravenous injection of either an immunogenic or a toxic dose of LPS. There was also a greater amount of LPS associated with cells teased from C3H/St spleens compared to those from C3H/HeJ spleens. After a toxic dose of LPS, there was more LPS in C3H/St lymph nodes, adrenals, lungs, kidneys, and heart than in the corresponding C3H/HeJ tissues. The accumulation of more LPS in tissues from C3H/St mice compared to C3H/HeJ mice suggests that these tissues are involved in the pathophysiological and, ultimately, the toxic effects of LPS. The differential accumulation of LPS in the tissues of these two strains may be the reason for the decreased responses of C3H/HeJ mice to LPS.


Antibody-mediated recovery from subcutaneous herpes simplex virus type 2 infection. Young adult mice infected with 3 X 10(6) plaque-forming units of herpes simplex virus type 2 (HSV-2) died within 9 to 12 days after spread of the virus from the sites of infection to the spinal cord and brain. Administration of HSV-2-neutralizing antisera prepared in syngenic mice or in rabbits inhibited spread of the virus from the footpad of infected animals and prevented death. A single intraperitoneal inoculum of antiserum (virus-neutralizing titer of 1:128) was effective in protecting mice when the antiserum was given at 8 to 48 h, but not at 72 h, after virus inoculation. Immune sera absorbed with HSV-2-infected cells no longer protected mice from subcutaneous infection, whereas absorption with noninfected cells had no effect. Thus, HSV-2-specific antibodies appeared to be responsible for the protection observed. If the mice were given a sublethal dose of irradiation (390 rads) at 24 h before antibody transfer, protection was no longer obtained. This suggested that the mechanism of protection probably was not solely due to in vivo neutralization of virus, but required the participation of a radiosensitive component which has not yet been defined.


Structural analysis of the cellular constituents of a fresh clinical isolate of Staphylococcus aureus, and their role in the interaction between the organisms and polymorphonuclear leukocytes in the presence of serum factors. The in vitro interaction of a fresh clinical isolate of Staphylococcus aureus and polymorphonuclear leukocytes was investigated. The importance of the various cellular constituents as host immunological factors was analyzed, and the results suggested that two components, namely, an acidic polysaccharide consisting of a predominance of aminogalacturonic acid and a strain-specific mucopeptide complex, may be involved in impeding in vitro opsonization of the organism by leukocytes. Immunochemical analysis indicated that the acidic polysaccharide possessed the same immunodominant aminogalacturonic acid residues as the antiphagocytic acidic antigen of the encapsulated prototype Scott strain. Antisera derived from rabbits immunized with strain D contained two types of opsonins, those with acidic polymer specificity and those with mucopeptide complex specificity.


Intestinal distribution of Vibrio cholerae in orally infected infant mice: kinetics of recovery of radiolabel and viable cells. Kinetics of distribution of Vibrio cholerae in the gastrointestinal tract of orally challenged infant mice were examined by determining recovery of input dose from the whole gut and from individual segments of stomach, upper bowel, and lower bowel. The strains studied were 569B, CA401, and VB12 (a rough CA401). Recovery was determined as a percentage of either input radiolabel using 35S-labeled cells or input colony-forming units. We found clearance of radiolabel and viable cells from the stomach into the intestines by 2 h. Early whole-gut clearance of label was greater for 569B and heat-killed CA401 than for CA401, VB12, or Formalinized CA401. At early times postchallenge, significant differences occurred between strains in the upper bowel, with greater recovery of label and viable cells for CA401 than for 569B or VB12. Beginning at 8 h postchallenge, radiolabel accumulated in the lower bowel with all experimental groups except CA401-challenged mice, where diarrhea was noted and label disappeared from the intestines. In vitro evaluation of mucosal association of these strains with bowel sections was also done. CA401 and VB12 associated to a greater extent than 569B or heat-killed or Formalin-killed CA401.


Influence of iron on Corynebacterium renale-induced pyelonephritis in a rat experimental model. Growth of Corynebacterium renale in vitro on low-iron medium (1.34 micron) was only slightly less than that on high-iron media (7.16 and 9.85 micron). However, studies on C. renale-induced pyelonephritis using the rat as an experimental model revealed that C. renale cultivated in high-iron media was capable of producing pyelonephritis, but when grown on low-iron medium, these bacteria were noninfective. This apparent avirulence of the bacteria cultivated on low levels of iron could be reversed by injecting the rats intramuscularly with ferric ammonium citrate.


Inhibitory effects of extracellular products from oral bacteria on human fibroblasts and stimulated lymphocytes. Extracellular products of 12 strains of Streptococcus mutans and 5 additional species of oral bacteria were analyzed for their ability to inhibit proliferation of fibroblastoid cells (HeLa and AV3) and blast transformation of human peripheral blood lymphocytes obtained from normal individuals. Products from S. mutans strains AHT and BHT, Streptococcus intermedius, and Actinomyces viscosus inhibited [3H]thymidine uptake by fibroblastoid cells and phytohemagglutinin-stimulated lymphocytes. Products from S. mutans E49, Streptococcus salivarius, and Actinomyces naeslundii inhibited blast transformation of human lymphocytes but did not significantly inhibit the growth of fibroblastoid cells. Preparations from S. intermedius gave the greatest inhibitory activity against both target cell types; initial characterization of this preparation suggested a single factor active in both assays, in that the heat lability and Sephadex G-200 elution profile were similar for the inhibitory activity seen with the two cell types. The molecular weight of the inhibitor, estimated by gel filtration on Sephadex G-200 and Ultragel AcA34, was approximately 160,000. The results strongly suggest that oral bacteria produce heat-labile substances that interfere with fibroblast proliferation and alter the lymphocytic immunological response.


Interaction of inflammatory cells and oral microorganisms. VII. In vitro polymorphonuclear responses to viable bacteria and to subcellular components of avirulent and virulent strains of Actinomyces viscosus. Both virulent (V) and avirulent (AV) strains of Actinomyces viscosus T14 are capable of colonizing the oral cavity of gnotobiotic rats, but only T14-V causes destructive periodontal disease. The basis for this difference in in vivo pathogenicity has not been adequately defined. In the present study we compared the capacities of T14-AV and T14-V to provoke in vitro extracellular release of lysosomal constituents from human polymorphonuclear leukocytes (PMNs). In serum-free cultures, viable T14-V but not T14-AV stimulated discharge of PMN lysosomes. The release response was correlated with PMN phagocytic activity; thus, PMNs readily ingested T14-V but not T14-AV. To explain these differences in PMN-bacteria interactions, subcellular fractions of T14-AV or T14-V were incubated with PMNs. A crude, insoluble sonic extract derived from T14-V caused PMN lysosome release, but a similar fraction from T14-AV was inactive. However, following extensive washing and treatment with deoxyribonuclease or sodium dodecyl sulfate, cell wall fractions of T14-AV stimulated lysosome release. These procedures apparently removed an extracellular polysaccharide slime which is synthesized by T14-AV but not by T14-V. There was a significant reduction in the capacities of viable T14-V or cell wall fractions of T14-V or T14-AV to provoke PMN lysosome release when these agents were preincubated with a slime material isolated from T14-AV. This inhibitory influence of slime was overcome by the addition of fresh or heated (56 degrees C, 30 min) serum to the PMN-bacteria cultures. The data suggest a relationship between the abilities of the avirulent and virulent strains of A. viscosus T14 to act as periodontal pathogens in vivo and to serve as stimuli for PMN lysosome release in vitro.


Purification of tritium-labeled cholera toxin. Cholera toxin was labeled with tritium by the Wilzbach technique, and highly purified radiolabeled toxin was obtained by Sephadex column chromatography and disc gel electrophoresis. 3H-labeled cholera toxin retained its biological activity and chemical stability and had a specific activity of 405.9 muCi/mumol. The methods utilized in extraction and purification of 3H-labeled toxin may be advantageous for preparation of other biologically active radiolabeled proteins.


Disruption of the permeability barrier (zonula occludens) between intestinal epithelial cells by lethal doses of endotoxin. A freeze-fracture technique was used to examine the most apical intercellular junctional complex between intestinal epithelial cells (the tight or occluding junction) in mice after challenge with endotoxin. Some of these junctions were disrupted after challenge and may be a site for leakage of microbial agents from the lumen.


Effect of phorbol myristate acetate on cellular metabolism and lysozyme release from alveolar macrophages and polymorphonuclear leukocytes. Phorbol myristate acetate stimulated oxidative metabolism in alveolar macrophages and blood neutrophils. This compound also stimulated lysozyme release from neutrophils but not from alveolar macrophages. These findings suggest that the regulation of lysozyme release from alveolar macrophages is different than for polymorphonuclear leukocytes.


Cyclophosphamide effects on murine cryptococcosis. BALB/c mice were given cyclophosphamide and challenged with Cryptococcus neoformans. Delayed-type hypersensitivity was transiently depressed, and survival was either unaffected or shortened by cyclophosphamide.


Ability of Streptococcus mutans and a glucosyltransferase-defective mutant to colonize rodents and attach to hydroxyapatite surfaces. A mutant of Streptococcus mutans forming little or no cell-associated glucosyltransferase attached to the teeth of rats and to saliva-treated hydroxyapatite comparably to its parent.


Protection of mice against tick-borne encephalitis by different classes of immunoglobulins. The protective capacities of IgM and IgG immunoglobulins from fractionated human or mouse sera were investigated in tests with tick-borne encephalitis virus. Mice were resistant to challenge with tick-borne encephalitis virus if previously inoculated with specific immunoglobulins but not nonspecific immunoglobulins. The protective ability of IgM, whether derived from mouse or human sera, was only about 1/40 of that of IgG preparations adjusted to the same haemagglutination inhibition or neutralising titres.


Binding of sisomicin and streptomycin to human albumin. The aminoglycosides of the kanamycin and neomycin series are displaced from their protein binding by very low Ca++ ion concentrations, whereas streptomycin is displaced only by very high Ca++ ion concentrations. For streptomycin, therefore, the binding mechanism must differ from that for the other aminoglycosides. The displacing reaction cannot be described by the law of mass action, combining the binding equations. Several possible reasons, such as complex formation and changes in the conformation of albumin, are discussed. Complex formation between sisomicin and the lanthanide ion Nd+++, which has the same ionic radius as the Ca++ ion, could be excluded by recording the difference absorption spectrum. The displacement of the aminoglycosides from their protein binding by Ca++ ions (as well as the pH dependence of the protein binding) suggests that ionic bonds are involved in the interactions between aminoglycosides and serum proteins.


The concentration of thiamphenicol in severely diseased human kidneys. The concentration of thiamphenicol in serum and renal tissue was determined in 17 patients with severly diseased kidneys after an intravenous injection of 1000 mg of the drug. Two hours after the administration the renal tissue concentrations ranged in patients with hydronephrotic kidneys from 38.0-63.5 microgram/g, in patients with cirrhotic kidneys from 17.9-42.7 microgram/g, in patients with pyonephrosis from 9.8-17.6 microgram/g and in patients with renal carcinoma from 37.7-64.2 microgram/g. The patient with the renal sarcoma had a level of 138.7 microgram/g. At the same time the serum concentration ranged from 4.6-15.2 microgram/ml. The highest renal tissue/serum concentration ratios of thiamphenicol were observed in patients with hydronephrotic kidneys and renal tumours, the lowest in cases of pyonephrosis. The influence of severe renal disease on the renal tissue/serum concentration ratios of thiamphenicol is discussed. The high renal tissue levels of thiamphenicol in patients with severely diseased kidneys fulfill an important condition for the antibacterial chemotherapy of kidney infections.


Protective isolation and antimicrobial decontamination in patients with high susceptibility to infection. A prospective cooperative study of gnotobiotic care in acute leukaemia patients. III: The quality of isolation and decontamination. In a cooperative study, the quality of protective isolation and of antibiotic decontamination of the digestive tract was studied in patients with acute leukaemia by (bio)-typing of Enterobacteriaceae species, Pseudomonas aeruginosa and Staphylococcus aureus isolated from oral washings and faecal samples. These samples were collected before and during treatment of 82 patients who were either isolated and decontaminated for which latter purposes a combination of neomycin, polymyxin, bacitracin and nystatin was used (group A); isolated without decontamination (Group B) or treated on the ward without decontamination (Group C). The results indicated that protective isolation had only been completely successful during the entire (remission induction) treatment period in one of the 32 patients in Group B. In Group A patients, who underwent antibiotic decontamination in addition, successful isolation was achieved in 57% of 28 patients. Successful antibiotic decontamination of the digestive tract for the entire treatment period as far as all potentially pathogenic species are concerned, was realized in 4 (14%) of the 28 patients of Group A. Bacteriologically confirmed infections occurred in 50% of Group A patients, in 59% Group B patients and in 64% of Group C patients. It is concluded that the quality of isolation had in general been insufficient but that it was improved by oral nonabsorbable antibiotics and, furthermore, that the antibiotic decontamination procedure also requires improvement.


The use of an in vitro haemoperfusion circuit to evaluate the blood compatibility of albumin-coated Amberlite XAD-7 resin. We have developed an in vitro haemoperfusion circuit, which closely simulates the conditions encountered in a clinical haemoperfusion, for testing the blood compatibility of new adsorbent materials. Fresh heparinised human blood is perfused for 2 hours over two model columns arranged in parallel closed circuits. The present study was performed to investigate the blood compatibility of human serum albumin-coated Amberlite XAD-7 resin. Mean platelet losses over 2 hours were greater following perfusion of the uncoated resin (44 +/- SE 5.6%) than the albumin-coated resin (17 +/- SE 2.2%) (p less than 0.01). Mean white cell losses were similar (55%) for both resins. No rises in Swank screen filtration pressure, which detects the presence of cellular aggregates in blood, were observed. Coating of XAD-7 resin with HSA therefore improves its blood compatibility with respect to platelet losses and we thus intend to use this preparation in a clinical trial of resin haemoperfusion in fulminant hepatic failure.


Bile acid clearance and biocompatibility of XAD-4 haemoperfusion. The clearance of bile acids from human blood or human albumin solutions obtained by perfusion through 100 g XAD-4 at 100 ml/min was (in ml/min): 21 for taurocholic acid, 3 for taurochenodeoxycholic acid, 18 for glycholic acid and 2 for glychenodeoxycholic acid. Saturation effects were absent up to 7 mumole bile acid bound per gram XAD-4. Haemoperfusion (100 g XAD-4, 100 ml/min) of cholestatic dogs resulted in the removal of up to 400 mumole bile acid in 3 hours. The calculated amount of bile acid stored in tissue depots was large with respect to the amount present in the circulation. A steady state between the mobilization of the tissue pool of bile acids and the removal of bile acids from the blood was established during the perfusion. Measurements of electrolytes enzyme activities and cellular elements showed severe losses of thrombocytes and leucocytes only. Contact with XAD-4 was the cause of the platelet loss where as omission of the resin from the perfusion system did not effect the leucocyte loss. The thrombocyte loss was reduced by the addition of citrate. Differentiation of the leucocytes showed that primarily the segmental granulocytes were sequestrated.


Coated charcoal hemoperfusion for the removal galactose in rats. Microencapsulated activated charcoal has been used in this report to remove galactose from aqueous solution in-vitro and from blood of galactosemic rats. Coconut charcoal is not effective in removing galactose, whereas petroleum-based activated charcoal is very effective.


Activated carbon for haemoperfusion.

Activated carbon for haemoperfusion. Some features of activated carbon are consisted and the grades of the adsorbent used in haemoperfusion are examined. Aspects of the activation process and the properties of the resultant carbons are discussed.


Serum chromatographic pattern in different dialysis strategies. In different dialysis strategies (hemodialysis with Gambro 1.5 m2, RP6 1 m2, Vita 2 1.2 m2), sequential ultrafiltration with RP 6 (1 hour ultrafiltration followed by 3 hours of hemodialysis and hemoperfusion with Absorba 300 C) serum chromatographic pattern and medium size molecules were studied with Sephadex G 15 chromatography. The removal of the studied medium size molecules is not different from one dialyzer to another. Serum levels were generally halved by the dialysis. In the ultrafiltration fluid a considerable amount of medium size molecules was found. There is no difference between RP 6 in open or in closed system. The absorbing capacity of the Absorba 300 C was blocked after one hour for medium size molecules in the patient under study.


MIST: a medical information storage system. A simple but flexible storage and retrieval system for medical data is described. It functions by providing the user with a proven set of FORTRAN IV subroutines. It has been found that for a wide range of clinical data processing the user only needs to apply three FORTRAN subroutines.


Logic-based program system for predicting drug interactions. This paper deals with the application of an AI language, based on mechanical theorem prover (PROLOG), to deduce drug interactions. One hundred and thirty-one drug interactions were predicted by logical deduction with a program system comprising about 52 drugs in practice and 32 independent possibilities of deduction. The database of the system contains the chemical and pharmaceutical characteristics of the active components of the drug preparations, and the deductions are based on general pharmacokinetic, pharmacodynamic or other biochemical relationships concerning interactions.


A preprocessor for less basic BASIC.

A preprocessor for less basic BASIC. BASIC, originally developed primarily as a teaching tool, has many extensions to allow its application to regular production programming. Naming restrictions of variables and line number references, however, are less satisfactory for longer programs making a program more difficult to read and maintain. The solution described is a program code preprocessor which accepts, long, meaningful variable names and line labels and converts the code to executable BASIC code. In addition, automatic library inclusions and a means of isolating sections of code for variable and label resolution facilitate creation and use of general purpose routines. Use of the preprocessor does not interfere with the capability to debug programs interactively which is one of the most helpful characteristics of interpretive implementations of BASIC.


[Pulmonary gas exchange model: influence of the heterogeneity of distribution on the ventilation-perfusion and diffusion-perfusion ratios of oxygen transfer]. The purpose of this pulmonary gas exchange model is to study the effect produced by an inhomogeneous distribution of the ventilation-perfusion (V A/Q) and diffusion-perfusion (D/Q) ratios on the oxygen transfer. We calculate partial pressures of oxygen and carbon dioxide in venous blood, in capillary blood and alveolar gas of each element as the unique solution of a non-linear system, the parameters of which are the local values of ventilation, perfusion and diffusion. We show that an inhomogeneous distribution of any ratio leads to a decrease of the mixed arterial concentration of oxygen and that the greater the inhomogeneity, the greater the decrease. We show by numerical stimulation that if two inhomogeneities (V A/Q) and (D/Q) are associated, the oxygen arterial concentration decrease is rather less important if the diffusion-ventilation ratio has a distribution almost homogeneous, i.e. if the V A/Q and D/Q inhomogeneities are almost identical.


Quantification of EEG variability.

Quantification of EEG variability. This paper presents a method of segmenting the EEG based on the well-known power spectrum analysis. This procedure is applied to the EEG recordings of two normal subjects in order to determine the temporal EEG variability. These results are compared with a more classical approach.


Demonstration of segmentation techniques for EEG records. In this paper three different techniques for segmenting EEG's are presented. The principles of these techniques (the Kalman filter approach, the power spectrum analysis and the texture matrix approach) are explained and the results obtained summarised. The segmentation is used in an interactive EEG interpretation system.


Effect of photoperiod reversal on twenty-four hour patterns for GABA levels in rat brain. GABA levels were measured in various areas of rat brain at 3 or 6 hour intervals for a period of 24 hours in animals adapted for 3 weeks to a programmed-lighting schedule. On the normal cycle rats were illuminated from 08 to 20 hours; on the reverse cycle, from 20 to 08 hours. The cerebellar pattern is unimodal with a peak in the dark at 06 hours and a trough in the light at 18 hours which coincides with maxima and minima of motor activity in the nocturnal rat. The cortical pattern also peaks in the dark at 06 hours but is less well-defined. On the reverse illumination cycle both patterns peak significantly in the dark at 18 hours. Only the cerebellum displays significant differences when averaged GABA levels for light and dark phases are compared. A circadian pattern peaking in the dark described for GABA levels of the corpora quadrigemina which is partly-reversed by reversing the photoperiod. The rhythm in thalamus-hypothalamus which peaks in the dark is complex, consisting of an ultradian rhythm super-imposed on a circadian one. The former rhythm appears to be endogenous and unaltered by a change in the illumination cycle; the latter exogenous since it varies with the illumination cycle. Lower GABA levels in rat brain were found after photoperiod reversal.


On temporal structure of human hiccups: ethology and chronobiology. During a study on the phylogeny and ontogeny of human hiccups, essentially all hiccups to occur over continuous periods of 3m - lly were recorded from 20 healthy people of either sex and various ages. Hiccups displayed considerable structure in time. If more than a few occurred together, they became "established" and a hiccup bout ensued, which did not stop until a certain "minimum" number of hiccups had occurred. For many subjects, two or more bouts frequently occurred on the same hiccup day, even though days on which bouts occurred were weeks apart. Number of hiccups was correlated with age, sex, reproductive status and stage of menstrual cycle, time of day, length of time since previous hiccup day, length of time since previous hiccup bout, and length of hiccup-hiccup intervals within a bout. Findings support the hypothesis that human hiccup is a "fixed action pattern" (FAP)--a central theoretical concept in ethology--and provide leads for further studies aimed at learning the biological function(s) of human hiccup and its possible homologues in other species.


Contingency contracting with heroin addicts. The purpose of this study was to compare three conditions in a single-subject reversal design: no contract and no contingencies, a contract without contingencies, and a contract with contingencies. There were eight subjects who remained long enough in the halfway house environment to provide sufficient data for comparison across conditions. The results indicate that managerial behaviors (such as keeping a daily log and using a sign-in sheet) came under experimental control only during the "contract with contingencies" condition. Drug use did not come under control during any condition, apparently because adequate competing reinforcers were unavailable in this study.


Admission characteristics of Indian and white alcoholic patients in a rural mental hospital. A group of 58 American Indian alcoholic admissions and a group of 211 White alcoholic admissions to a California State Mental Hospital were interviewed utilizing a 141-item interview scale. The two groups were compared as to their responses to the interview items by a series of one-way analyses of variance. Statistically significant differences were found on demographic, socioeconomic, hospitalization, drinking and friendship pattern variables. The results are discussed with reference to data reliability, and socioeconomic and cultural factors. The study's findings are also related to an apparent need for the education of police and native Americans in the area concerning treatment resources available to native American problem drinkers.


Occupation and alcoholism: cause or effect? A controlled study of recruits to the drink trade. Some occupations have higher alcoholism rates than others. It is unknown whether "high risk" occupations attract problem drinkers or create them through job pressures. One hundred and fifty male manual recruits to Scottish breweries and distilleries were interviewed and compared with similar men in lower risk jobs. The alcohol producers reported poorer employment records and were significantly heavier drinkers than the controls. The alcohol producers were also more likely than the controls to have drunk more since recruitment. These results suggest that the drink trade attracts a disproportionate number of people likely to develop alcohol-related problems and indicates that drinking habits may be strongly influenced by work environment.


Behavioral correlates of age at first marijuana use. Relationships between age at initial marijuana use and selected behavioral measures representing education, arrests, employment, alcohol use, and other drug use were examined for a sample of 370 male veterans. Younger age at marijuana use was found to be associated with less education, more arrests, and more other drug use prior to entering the service. A factor analysis of the correlates of age at initial marijiana use suggested three factors of delinquent activities: drug use, school delinquency, and other propensities for delinquency.


Rehabilitation experiences of women ex-addicts in methadone treatment. In-depth interviews were conducted with 16 female "hard-core" heroin addicts on a methadone maintenance treatment program 1 year or longer to learn what the rehabilitation process is like for women and how their life-styles had changed since being in treatment. The paper describes the adjustments and special difficulties experienced by women through patients' own accounts. Behavioral changes were verified by clinic records and staff. Cessation of criminal behaviors, regulation of daily living patterns on methadone, increased social productivity, and adoption of new social values were noted. Persisting problems include loneliness, motivational difficulties, and an incomplete transition to ordinary society.


Pre- and posthospitalization alcoholic arrests in a rural state. Arrest rates of 180 male alcoholics admitted to the Wyoming State Hospital in 1969 were compared with the general Wyoming population during 1965--1973. Results indicated: (1) 67% of the alcoholics had no arrests before or after hospitalization; (2) prehospitalization arrest rates of alcoholics were higher than the general population for robbery, assault, sex offenses, theft, public intoxication, drunk driving, traffic offenses, and vagrancy; (3) following hospitalization, alcoholic arrest rates were reduced significantly in all categories except robbery and embezzlement and fraud; and (4) posthospitalization alcoholic arrest rates were lower than the general population for all offenses except robbery, public intoxication, and DWI.


The use of computers in pharmacokinetics. A review of computer applications is presented, and several examples of the use of analog and digital computers are given. Special attention is given to fitting the time concentration data to the one, two or more exponential equations, for estimation of pharmacokinetic parameters, for dosage regimen of drugs and for evaluation of bioavailability.


Hepatic activity in the generation of somatomedins: effects of administration of a liver extract. The problem of the generation of growth factors (somatomedins) (SM) is at present a matter of investigation. The liver has been proposed as the primary site of production of SM. In order to verify this hypothesis, SM activity has been assayed in patients with impairment of liver function. The subjects have been divided into three groups according to the severity of the hepatic damage, assessed with conventional diagnostic tests. In every group, somatomedin A (ASM) has been assayed by means of a biological procedure, in basal conditions and after treatment with a liver extract. The results show that the ASM activity is reduced in proportion to the degree of hepatic damage. The administration of liver extract restores the production of the ASM in the first two groups of patients, i.e. in those with mild and moderate hepatic involvement.


The distribution of sodium salicylate in the human fetus. The distribution of sodium salicylate was investigated in the fetuses of 18 mothers in the fifth or sixth month of pregnancy which had to be interrupted for medical reasons. Ninety-six min after drug administration, the salicylic acid levels in mother and fetus blood are almost equal. The highest drug levels in fetus tissue were found in the kidney, the lowest in the brain. In amniotic fluid, only traces of salicylic acid were estimated. A limited number of suitable cases made the exact statistical evaluation impossible.


Individualization of drug dosage during long-term treatment with phenprocoumon (Falithrom). Pharmacokinetic studies were carried out with 3H-phenprocoumon (3H-PPC) during long-term treatment with phenprocoumon (PPC, Falithrom) in 10 female and male patients with thromboembolic diseases. Additionally, 12 mg 3H-PPC were administered per os to 6 male volunteers. Half-life and pattern of urine metabolites were measured and compared with those in patients. The radioactivity decreased independently of the total PPC plasma concentration, which was estimated fluorometrically. An exponential regression with a high coefficient of determination was found between the mean maintenance dose (PPC) and the area under plasma concentration curve of radioactivity. This procedure is considered to be a method to improve long-term treatment with PPC.


The relative bioavailability and pharmacokinetics of carbamazepine. Differences in the bioavailability after administration of two pure carbamazepine samples that were different in particle sizes have been found. Carbamazepine was given to each of 3 healthy male volunteers in a single oral dose of 400 mg in gelatin capsules. The other carbamazepine sample was administered after a three-week time interval. Plasma was collected during the following 96 hr. Quantitative determination of carbamazepine was performed by gas liquid chromatography. By comparing the areas under the various curves for each volunteer, the relative bioavailability of one of the carbamazepines in relation to the other one was found of approximately 70%. There were no differences in the half-life time.


On the problem of optimum digitlaization in man. The low therapeutic index of cardiac glycoside requires an optimum individual digitalization. This is also a difficulty in the case of known serum glycoside concentrations because individual differences of biochemical and physiological factors (which influence both therapeutic and side effects) are important. As a rule the physician's criterion for an optimum digitalization is that side effects are avoided. This investigation attempted to find a measure for the effect of glycosides by noninvasive recording of parameters of myocardial contractility (systolic time intervals, STI). The measurements were made under oral digitalization with digoxin (Dilanacin). The serum glycoside concentration was determined by the radioimmunoassay method. The changes in STI were investigated in the rage of 1 to 3 ng digoxin per ml serum. In this concentration a significant correlation was demonstrated between STI shortening and glycoside level. It was found that the shortening of STI was maximum at the lowest concentration (1 ng/ml). It appears that the control of STI is for the physician a useful aid for an optimum digitalization in man.


Dosage monitoring through measurement of serum level--a task of clinical pharmacology. Dosage monitoring or "pharmacokinetic therapy service", respectively, covers blood level governed therapy schedule or blood level controlled dosage for certain types of therapy. It is also advantageous in applying drugs of a small therapeutic range or in "risk" patients such as children, old men and patients suffering from elimination disturbances. With the blood level data known, physicians can follow an optimum therapy schedule. The principle of this service is detailed using therapy with antiepileptics as an example. Through substantiation is given.


Keloidal blastomycosis (Lobo's disease) in Panama. A 58-year-old Panamanian man had diagnosis of keliodal blastomycosis (Lobo's disease) by the scarring nodules on his ears and the fungi seen on histologic section.


[Serum carotenoids and vitamin A in melanodermic and albino subjects in Cameroon]. Vitamin A nutritional status as assessed by carotenoid and vitamin A assays in sera collected in various parts of Cameroon prooved to be of good value. Palm oil rich diets lead to high seric carotenoid concentrations and tissular accumulation which is particularly visible on the palms and soles of melanodermic and albinos subjects.