[Nonribosomal ribonucleoprotein particles in preparations of nonhistone proteins extracted from pigeon erythroblast chromatin]. Two proteins were isolated from preparations of weakly bound nonhistone proteins, obtained from highly purified chromatin with 0.35 M NaCl. These two protein residues from chromatin RNP-particles have the buoyant density of 1.41 g/cm3 as shown by centrifugation in CsCl gradients and contain heterogeneous fast labelling nuclear RNA. According to SDS polyacrylamide gel electrophoresis the molecular weights of these proteins are 70000 and 43000 daltons.


[Amino oxyadsorbents. New type of adsorbents for affinity chromatography: purification of tRNA-methylases from rat nephron on aminooxybutylcellulose with immobilized tRNA]. A new type of sorbents for affinity chromatography is suggested and used to purify tRNA methylases. tRNA was immobilized on aminooxybutylcellulose via the oxidized 3'-end. In order to bind other enzymes specific for nucleic acids in general, e. g. nucleases, and to achieve a higher degree of purification the crude enzyme preparation was treated with rRNA immobilized on aminooxybutycellulose. The sequential application of two sorbents mentioned allows to get an approximately two hundred fold purification of total tRNA methylases. In a separate experiment the possibility of individual tRNA methylase fractionation by means of elution with a NACl gradient was shown; the degree of purification for some methylases was more than a thousand fold.


[Interaction of cardiotoxin from the venom of the cobra Naja naja oxiana with phospholipid membrane model systems]. Surface activity of cardiotoxin from the venom of cobra Naia naja oxiana and an acetylated analog of the cardiotoxin was investigated on the water-air interface. The interaction of these substances with lipid monolayers and bimolecular membrane was also studied. It was shown that on the water-air interface cardiotoxin can form two different types of monolayers with different conformations of molecules. Cardiotoxin is found to form complexes with phospholipids due to interaction of positive charges of amino groups of lysin with phosphate groups of lipid molecules. One molecule of toxin is able to complex up to 10 molecules of lipid. The complex formed has a high surface activity, much more than that of the pure protein. Cardiotoxin increases the anion conductivity of bimolecular membranes. The nature of this phenomen is studied. A hypothetical mechanism of biological activity of caridotoxin is offered. It is supposed that not cardiotoxin as that, but its complex with phospholipid is the active agent.


[Comparative theoretic analysis of an open reaction S1 goes to and comes from S2 E(R,T) in which the oligomeric enzyme E(R,T) is isosterically or allosterically activated by the product S2]. In connection with evolutionary aspects of the mechanisms of allosteric regulation of cell metabolism, a mathematical model of an open reaction leads to S1 E(R,T) in equilibrium S2 leads to involving product activation of the olygomeric enzyme E(R,T) whose protomers undergo the concerted conformational transitions R in equilibrium T, has been analysed. Two activation mechanisms, isosteric and allosteric, were considered. Both mechanisms produce qualitatively the same effects: the input characteristic of the reaction possesses hysteresis, which causes multiple steady states and self-oscillations. In the case of isosteric activation, only a small fraction of the maximum enzyme activity is utilized because of the strong competition between S1 and S2 for the active sites. In the case of allosteric regulation, this competition may almost completely be eliminated and the enzyme activity may be utilized with high efficiency, provided the affinity of S2 for the allosteric sites is at least an order of magnitude higher than for the active sites. Qualitative similarity between the two cases of product activation, in spite of their great quantitative discrepancy, favours the hypothesis that the mechanisms of isosteric regulation were the direct precursors of the homological allosteric regulatory mechanisms.


[Regulatory reversible enzymic reactions. Theoretical analysis]. A mathematical model has been derived and analysed describing the relationship between the rate of an enzymic reaction S1 E(R,T)A in equilibrium S2 and concentrations of substrates S1 and S2 and their analogue A capable of reversible binding to active sites of an olygomeric enzyme E(R, T). The conditions have been presented for the model to describe various types of kinetic curves, sygmoidal, curves with extremuma and intermediate plateau. The regions of parameter values have been estimated within which isosteric product activation can be observed in reactions S1 in equilibrium E(R,T) S2 and S1 E(R,T) in equilibrium S2. Two phenomena registered in experiments with olygomeric enzymes have been interpreted in the model terms, namely, the undirectional influence of isosteric and allosteric effectors on the rates of forward and reverse reactions and occurence of a reversible enzymic reaction in thermodynamically unfavourable direction. The results presented are shown to be valid for multisubstrate reactions catalysed by olygomeric enzyme E(R, T).


[Study of electron transfer in pigment-protein complexes of photosystem I]. The electron transfer processes occuring in SDS chlorophyll--protein complexes of photosystem I were studied by flash photolysis. Transient species with lifetime about 5.10(-5) sec were found to be produced on flash excitation of complex buffer solutions. The transient absorption spectrum of the short-lived species measured in the absence of SDS resembles that of P+700. This spectrum was similar with that of chlorophyll anion radical (chl-) when SDS was added to the solution. It is assumed that the charge separation in chlorophyll--protein complexes leads to formation of the primary reduced acceptor X-. The chl-species arised as a result of electron transfer from X- to monomeric form of chl a.


[Comparative study of slow 1H to 3H exchange in synthetic polynucleotides of A- and B-type conformations]. The rate of 1H leads to 3H exchange between water and C(8)H-groups of purinic residues in synthetic polynucleotides in wide temperature range measured. At temperatures below their Tm the rate of the exchange is shown to be lower as compared with that in corresponding mononucleotides. In the case of polynucleotides of A-conformation (poly(A).poly(U), poly(A).2poly(U) and poly(dA).2poly(dT), and poly(G).poly(C) the exchange is retarded by a factor of 5.7--7.5, whereas in the case of those of B-conformation (poly(dA).poly(dT), poly(dA--dT).poly(dA--dT) and poly(dG).poly(dC)) the exchange is retarded only by a factor of 2.3--2.5. Assuming the ylide mechanism of exchange the retardation is interpreted as a consequence of sterical hidrance in polynucleotides helical structure, which hampers contacts between purinic C(8)H-groups and OH-ions of solvent. Analysis of atomic arrangement around C(8)H-group and interatomic distances calculated on the basis of published atomic coordinates support our general conclusion that the sterical hindrance is more significant in the A-form as compared with that in the B-form. Elucidated correlation between the degree of the retardation in purine-containing polynucleotides and their conformation in solution allows to estimatf the type of conformation of polynucleotide with unknown structure on account of the slow 1H leads to 3H exchange data.


[Absorption and magnetic circular dichroism spectra of nonequilibrium states of hemoproteins. II. Myoglobin and its complexes]. Absorption and magnetic circular dichroism spectra of non-equilibrium states of myoglobin and its complexes formed by reduction oxidased forms of proteins by thermalysed electrons at 77 degrees K were studied. Mixtures of high spin and low spin ferroforms were observed for nonequilibrium states of myoglobin and its complex with fluorine, the content of the high spin form is larger in the complex. Two intense peaks were found in the alpha-band region of absorption spectra of myoglobin and its spectra with F-, OH- and imidazole. This effect is due to lowering of the active centre's symmetry. Similarity of spectral characteristics of low spin ferroforms of these complexes was explained by the strong influence of distal histidine. The low temperature reduction of azide and cyanide complexes of myoglobin led to formation of nonequilibrium low spin ferroforms whose spectra demonstrate the presence of N3- and CN- in heme iron's coordination sphere. The temperature relaxation of all nonequilibrium systems were investigated.


[Absorption and magnetic circular dichroism spectra of nonequilibrium states of hemoproteins. III. Complexes of peroxidase]. Absorption and magnetic curcular dichroism spectra of nonequilibrium states of peroxidase  and its complexes with F-, N3-, CN- produced by reduction of oxidased forms of proteins by thermalysed electrons at 77 degrees K were studied. Mixtures of high spin and low spin ferroforms were found in nonequilibrium states of peroxidase and complexes with F- and N3-, the content of the high spin ferroform increasing as follows: N3- complex less than peroxidase less than fluorine complex. Only low spin ferroforms was found after low temperature reduction of the cyanide complex. The existence of the low spin ferroform in equilibrium states of peroxidase and its complex with F- was explained by location of iron near the porphyrine plane. In the case of azide and cyanide complexes the existence of the low spin form is due to the presence of these ligands in heme iron's coordination sphere. The temperature relaxation of all nonequilibrium forms was investigated and a possible mechanism of the process is proposed.


Schooling, environment, and cognitive development: a cross-cultural study. The purpose of this study was to investigate the influence of schooling and general environmental conditions on the development of memory and cognitive skills in young children. The subjects were 824 5- and 6-year-old children living in jungle villages and in slum settlements of Lima, Peru. Half of the children in both the jungle and city were Mestizo, and half were Quechua Indians. Some 6-year-olds of each cultural group and in each location attended school; others did not. Memory tasks were presented in different modes of representation, that is, verbal, pictorial, and enactive; and cognitive tasks in "concrete" and "abstract" versions. A sample of parents in each group was interviewed concerning environmental conditions. In addition, samples of upper-middle-class children in Lima and poor children in Detroit were tested to assess the generality of the findings. Attendance at school was related to improvement in performance on all tasks. Improvement was equivalent for both locations, both cultural groups, and each social class. Attendance at school also was accompanied by reduced within-group variability on some tasks and by greater differentiation of cognitive processes within children. Location and cultural group interacted differentially by task according to a complex pattern of relations. There were no indications that the organization of memory or cognitive processes differed as a function of social class, age, location, or cultural group. The results were interpreted in terms of children's opportunities to acquire specific memory and cognitive skills from schooling and from their general experience in a particular environment.


An experimental analysis of some procedures to teach priming and reinforcement skills to preschool teachers. This Monograph reports the results of teaching preschool teachers to be successful at increasing desired behaviors of their children, thus becoming successful teachers. Five teacher-training techniques were examined experimentally under single-subject designs: written assignments, feedback from viewing graphs, on-the-spot feedback from a wireless radio (Bug-in-the-Ear), feedback from an observer, and self-counting. Those teaching procedures that included prompt and frequent information to the teacher about the behavior under study were the most effective techniques. Self-counting, in which the teacher tallied the number of times she emitted the behavior of either priming or reinforcing social or verbal behavior of a child (or children), and observer feedback, in which the observer reported to the teacher periodically during the hour the frequency of her behavior, were the most reliable teaching techniques. The other procedures, while less reliable than self-counting and observer feedback, were effective with some teachers. Maintenance of teacher behavior across settings was examined with a group of Head Start teachers, and maintenance of teacher behaviors across different child behaviors and different children was examined with three student teachers. The results indicated that teaching was more likely to maintain if it occurred in the teacher's home setting rather than at another site. In all cases, when generalization occurred across settings, time, or children, the frequency of the teacher's behavior was not as high as when the relevant behavior had been trained directly. Results supported the proposal that it is possible to define effective teacher behavior, not just characterize it, as it occurs in the classroom, and that effectiveness can be measured by defining and observing the child behaviors to which teacher behaviors are directed.


Scanning-electron microscopy of chromosome aberrations. This study is the first report of scanning-electron microscopy of isolated and purified metaphase chromosomes containing drug-induced aberrations. The technique reported allows high resolution topological examination of chromosomal aberrations which may pass undetected with conventional techniques.


Use of the beta-binomial distribution in dominant-lethal testing for "weak mutagenic activity: part 2. Experiments in Dominant-Lethal Testing have been simulated on the computer to estimate the type I error rates and the power of the Beta-Binomial test under various models. (1) The mating ratio is one; and p, the probability that an implant will die, is distributed over the couples. (2) The mating ratio is larger than one; and p is distributed over the males, the females mated to the same male being binomial observations of the value p supplied by the male. (3) The mating ratio is larger than one; and p is distributed over the females. The average rates of dead implants have been set at 0.08 and 0.10 for the control and treatment groups, respectively, and a nominal level of significance equal to 0.05 has been chosen. The type I error rate of the traditional chi-square test has also been estimated. A by-product of these simulations is the behaviour of the estimates alpha and beta of the beta-distribution parameters, which discloses that, in the actual experiments with mice, p is distributed over the females. Our results lead to the recommendations that, for a given number of animals per group, a mating ratio larger than one should be adopted and that the males should be considered as the experimental units for the calculations. With 300 and 450 animals per group, average powers of 0.72 and 0.85 are reached, respectively, for the chosen increment of 2% in the rate of dead implants. Under these models, the type I error rate of the traditional chi-square test may grow to 0.30 for the nominal level of 0.05.


Modification of UV-induced mutation frequencies in Chinese hamster cells by dose fractionation, cycloheximide and caffeine treatments. Chinese hamster (V79) cells were irradiated with a fractionated regime of ultraviolet light (UV1 + UV2). The fractionation of a UV dose always increased the colony-forming ability but reduced (or it did not change) the mutation frequencies. Treatment with cycloheximide between the two UV irradiations resulted in two types of effects, depending on the protocols used. Long exposures to cycloheximide (i.e., greater than 6 h) for the entire period between UV1 and UV2 or partial treatment of cycloheximide (i.e., 3 h) long before UV2 always resulted in reduced colony-forming ability and enhanced or unchanged mutation frequencies. Exposure to cycloheximide for the entire period in the short fractionated regime (i.e., 4 h) between UV1 and UV2 or partial treatment of cycloheximide just prior to UV2 tended to give the opposite effects. Caffeine treatment before UV2, with or without UV1, significantly increased the mutation frequencies. These results suggest that an error-free postreplication repair system exists in Chinese hamster cells which is inhibitable by particular cycloheximide or caffeine treatments.


[Complementarily addressed alkylation and cleavage of T7 phage DNA adjacent to the oligothymidylic sequences]. Effect of temperature and reagent excess on the alkylation of the T7 phage DNA by an alkylating derivative of hexaadenylate that containes a modifying group on the 3'-terminus has been studied. Under condition of saturation at 20 degrees the reagent covalently binds adjacent to the 133 5'-PuN2--4Tn greater than or equal to 4 sequences in the T7 DNA; at 40 degrees the reagent alkylates 24 5'-PuN2Tn greater than or equal to 6 sequences. DNA containing specific apurinic sites has been prepared due to elimination of the alkylated purines. This DNA has been cleaved at the apurinic sites and specific DNA fragments have been obtained. Three types of DNA fragments are formed due to alkylation at 20 degrees: one fragment with 26,500 nucleotides in length, seven fragments with 4500 nucleotides in length and 103--111 fragments with an average length of 190 nucleotides. Alkylation at 40 degrees with following apurinization and cleavage yields 21--23 fragments with the lengths: 1--31,500; 1--19,000; 3--9500 and 17--19 with 1100 nucleotides in average.


Absence of interaction between X-rays and UV light in inducing ouabain- and thioguanine-resistant mutants in Chinese hamster cells. Chinese hamster ovary cells were irradiated with X-rays at times from 0 to 17 h before being irradiated with ultraviolet (UV) light. No synergism was observed between the two radiations for the production of mutants resistant to either ouabain or 6-thioguanine. These experiments were designed to test whether X-rays induced an error-prone repair system that would increase the frequency of mutations produced by UV light, but no such system was detected.


Induction of 6-thioguanine- and ouabain-resistant mutations in synchronized Syrian hamster cell cultures during different periods of the S phase. Cells of a transformed Syrian hamster line, BP6T, were synchronized by a period of growth in low serum with a subsequent blockage of the cells at the G1/S boundary by hydroxyurea. This method provided cells with nearly 100% synchrony, although approximately 20% of the cells were non-cycling. The cells were then treated with 10(-5) M 5-bromodeoxyuridine for 1 of 5 1-h periods during the S phase and subsequently irradiated with near-ultraviolet light for 5 min. The BrdU plus irradiation treatment induced 6-thioguanine- and ouabain-resistant mutants while BrdU alone or irradiation alone was not mutagenic. 6-Thioguanine-resistant mutants were induced only during early S phase by BrdU plus irradiation treatment. Ouabain-resistant mutants, however, were induced in a biphasic pattern, during early S phase and also during late S phase. The induction of ouabain-resistant mutants at two distinct periods of S phase suggests the presence of two loci for the gene(s) of Na+/K+ ATPase.


Enhancement of repair replication in mammalian cells by hydroxyurea. The effect of hydroxyurea on DNA repair replication has been studied in Chinese hamster ovary cells. Mitotic cells were treated with UV irradiation, methyl methanesulfonate or nitrogen mustard and incuated in the presence of each of the 4 [3H] deoxyribonucleosides plus BrdUrd and FdUrd for 2 h. The amount of repair replication was quantitated on CsCl gradients and similar values were obtained for each nucleoside. In all cases addition of HU during the incubation period increased these values approximately 2-fold. Following MMS treatment, pool sizes for each of the nucleosides were estimated by varying the amount of exogenously supplied nucleoside. They were found to be insensitive to the addition of HU and it is concluded that the increased incorporation of [3H]deoxyribonucleosides in the presence of HU reflects an increased amount of repair replication.


Detection of alkylating agents by the analysis of amino acid residues in hemoglobin and urine. 1. The in vivo and in vitro effects of ethyl methanesulfonate, methyl methanesulfonate, hycanthone methanesulfonate, and naltrexone. The effect of alkylating agents on the amino acid composition of rat and human hemoglobin has been examined. Because the amino acid compositions of these proteins are well established, the changes in the molar ratios of specific amino acids could be monitored in purified hemoglobin samples. Ratios of histidine, which is readily attacked by alkylating agents, to proline, which is not, were consistent in hemoglobin purified from untreated blood samples from 14 rats and 25 human subjects. Treatment of hemoglobin in vitro or in vivo with methyl methanesulfonate, ethyl methanesulfonate, or hycanthone methanesulfonate resulted in a loss of histidine residues relative to proline or phenylalanine. The decrease in histidine content increased with treatment dose and time and reached a maximum at about 15% of total histidine. Treatment of rats with methyl methanesulfonate or hycanthone methanesulfonate resulted in increased urinary excretion of methyl histidines.


Determination of radiation equivalence of the chemical furylfuramide (AF-2) for the induction of gene conversion in diploid yeast and estimation of genetic risk to the Japanese population. Dose--effect relationships for the induction of gene conversion by AF-2 in diploid yeast have been established. On the basis of these, the rec value for AF-2 for induction of gene conversion has been calculated to be 0.085 microgram/ml.h. This compares well with the rec values obtained with other test systems and other genetic end-points. The genetic burden to the Japanese population due to consumption of AF-2 is estimated to be equivalent to 55 millirec. However, uncertainties in the consumption of AF-2 per person and its metabolic detoxication tend to lower this value to, probably, a small fraction of that due to natural background ionizing radiation.


Sister-chromatid exchange induction by sodium selenite: dependence on the presence of red blood cells or red blood cell lysate. Sodium selenite (Na2SeO3) sister-chromatid exchange (SCE) induction was studied in both short-term and long-term cell cultures. The ability of Na2SeO3 to induce SCEs was found to depend on the culture conditions employed. Concentrations of Na2SeO3 (7.90 X 10(-6) M and greater) that produced elevated SCE frequencies in whole blood cultures resulted in control level SCE frequencies (6-8 SCEs/cell) in Ficoll-Hypaque--purified lymphocyte cultures. However, whole blood and purified lymphocyte cultures were equally sensitive to SCE induction by methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and N-hydroxy-2-acetylaminofluorene (N-OH-AAF). Analysis of different whole blood components showed that the presence of red blood cells (RBCs), and specifically RBC lysate, was a prerequisite for Na2SeO3 SCE induction in purified lymphocyte cultures. The SCE frequencies of xeroderma pigmentosum (XP12RO) and normal human lymphoblastoid cell lines were also found to be unaffected by Na2SeO3 concentrations that produced elevated SCE frequencies in whole blood cultures. Incubation of these latter two cell types with Na2SeO3 and RBC lysate resulted in SCE frequencies comparable to those in Na2SeO3-exposed whole blood cultures.


Colicin K acts by forming voltage-dependent channels in phospholipid bilayer membranes. The bactericidal action of colicins K, E1, Ia, and other functionally related colicins involves disruption of active transport and leakage of ions from the cell. We show that a single colicin K molecule can form a voltage-dependent, relatively nonselective, ion-permeable channel of a few picosiemens conductance in a planar phospholipid bilayer membrane. In a membrane containing many of these channels, the ratio of the number of conducting to nonconducting channels changes e-fold per 3.7 mV. We suggest that the physiological effects of colicin K and functionally related colicins result from their ability to form ion-permeable channels in the bacterial plasma membrane.


[Co-carcinogens or modulators of carcinogenesis. New aspects of the etiology of human tumors and of the molecular mechanisms of carcinogenesis]. Within the last 10 years numerous new and typical exogenous cocarcinogens were identified chemically as well as biologically and characterized biochemically as initiation or tumor promoters. They are highly irritant diterpene esters of plant origin. Promoters of this type were recently detected also in the Euphorbiacea Croton flavens L., the multiple use of which for stimulants according to local habits was previously held responsible for the unusually high rate of esophageal cancer on Curacao. This detection confirms for the first time that in the etiology of human cancer besides solitary carcinogens (first-order carcinogenic risk factors) also cocarcinogens of the promoter type have to be considered (second-order carcinogenic risk factors). -- The active principles of the diterpene ester type are the strongest promoters known so far; they are noninitiators and nonmutagens. Of the manyfold biochemical activities of these promoters the three most actual are: the TPA molecule does not require activation by metabolic alteration, it releases very  rapidly prostaglandin E2 from cellular membranes and it activates latent DNA-viral genoms.


Development of inactivated vaccine for Akabane disease. Virus inactivated by formalin or beta-propiolactone was superior to that inactivated by ether and heating in immunogenicity to mice. There were no significant differences in the antibody response of mice among such adjuvants as aluminum phosphate gel, aluminum hydroxide gel, and sodium arginate gel. When cattle were immunized with vaccine inactivated by formalin and adsorbed to aluminum phosphate gel, an excellent effect was obtained by injection with two doses of 3 ml each given at a 4-week interval. It was also suggested that mice and guinea pigs might be available for the potency test of vaccine. When calves and pregnant goats were injected with vaccine in the same manner as mentioned above, they were prevented from viremia and fetal infection caused by challenge virus. Even when stored at 4 degrees C for 12 months, vaccine was found to retain its stabilized immunogenicity. When pregnant cows were injected with vaccine in the field, the positive rate of neutralizing antibody was 88.5% in the 2 months after the first injection. When other pregnant cows were injected twice with vaccine, this rate was 34.6, 100, 65.4, and 45.8% in the 1, 2, 6, and 10 months, respectively, after the first injection. In another experiment, the antibody levels attained declined rather rapidly in several months. A single dose of vaccine given one year later provoked a rapid antibody response. The vaccination caused no clinical symptoms, abnormal birth, or decrease in milk yield in these cows.


The effect of acute and chronic desipramine and amitriptyline treatment on rat brain total 3methoxy-4-hydroxyphenylglycol. The effect of acute (single dose), short-term (4 days), and chronic treatment (21 days) with two tricyclic antidepressants desipramine and amitriptyline on brain 3-methoxy-4-hydroxyphenylglycol (MHPG) was examined in the rat. Amitriptyline had no effect on brain total MHPG irrespective of the duration of the treatment and did not interfere with the lowering effect of clonidine on brain total MHPG. Acute and short-term desipramine treatment decreased brain total MHPG in rats, while chronic desipramine treatment increased it. The differential effect of acute and chronic treatment of desipramine on the brain total MHPG was further demonstrated by the lack of interference with the lowering effect of clonidine on brain total MHPG by one single dose of desipramine; partial interference after 4 days and complete interference after 21 days of desipramine treatment.


Neurotensin and its amide analogue [Gln4]-neurotensin: effects on brain monoamine turnover. Intracerebroventricularly administered neurotensin and [Gln4]-neurotensin (50-200 microgram) increased the formation of Dopa in different brain regions of rats after inhibition of the aromatic L-amino acid decarboxylase. For both neuropeptides these increases were dose dependent (20-150%). In the corpus striatum [Gln4]-neurotensin was twice as active as neurotensin and it tended to be more active also in other brain regions. The brain tyrosine concentrations were also increased. [Gln4]-neurotensin (100-200 microgram) following inhibition of the aromatic L-amino acid decarboxylase, increased the accumulation of 5-hydroxytryptophan in all brain regions by 30-60%. In contrast, neurotensin was completely inactive. In both cases the brain tryptophan concentrations were increased. Both neurotensin and [Gln4]-neurotensin also accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. These results show an increased brain monoamine turnover induced by both neuropeptides.


The effects of a permanent and selective depletion of brain catecholamines on the antinociceptive action of morphine. 6-Hydroxydopamine was given to newborn mice. After 60 days their brains were deficient in noradrenaline and dopamine while morphine's antinociceptive action was reduced. 6-Hydroxydopa was administered to adult mice. This depleted brain noradrenaline and reduced morphine's antinociceptive action. Newborn rats received 6-hydroxydopa. After 60 days morphine's antinociceptive action was potentiated, brain noradrenaline was reduced while dopamine had increased. Adult rats were treated with 6-hydroxydopa. This reduced brain noradrenaline but did not affect morphine's antinociceptive action. Guanethidine, which depletes noradrenaline in the peripheral nervous sytem, was given to newborn animals of both species. It had no effect on morphine's antinociceptive action. It is concluded that in the mouse the antinociceptive action of morphine relies in part on normal brain noradrenaline function and dopamine is not directly involved. In the rat morphine's action is affected by neurotoxic drugs which alter brain dopamine function.


A possible reason for the phalloidin tolerance of hepatoma cells. In contrast to normal liver cells, AS-30D hepatoma cells are insensitive to phalloidin. The lack of the typical phalloidin response in the latter cells is not due to a deficiency of contractile proteins. Actin prepared from hepatoma cells is able to form filamentous structures and is stabilized in a manner similar to muscle actin. Isolated liver cells were exposed to a medium containing phalloidin and removed after 20 min by centrifugation. The supernatant was incubated again with fresh cells. The procedure was repeated four times. The phalloidin response decreased to about 19% of the control because of the uptake of phalloidin during each incubation. When the same procedure was carried out with AS-30D hepatoma cells, and aliquots of the supernatants were tested with hepatocytes no marked decrease of the phalloidin response was seen. This indicates that hepatoma cells do not consume the toxin as do normal liver cells.


Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats. Pretreatment of rats with spironolactone caused an fourfold increased cleavage rate of the sugar chain of digitoxin (dt-3) in vitro yielding digitoxigenin-bis-digitoxoside. This was due to an enhanced, cyt. P450 dependent, formation of 15'-dehydro-dt-3, the intermediate which has to be formed before the terminal sugar can be split off. The second reaction catalysed by microsomal monoxygenases, the 12-beta-hydroxylation, was only increased by a factor 2. In contrast to the effects of spironolactone no increase of metabolism could be observed after phenobarbital pretreatment. From our results it may be concluded that the enhanced dt-3 metabolism in vivo is mainly caused by spironolactone inducible monoxygenases which catalyse the oxidation of the terminal sugar.


Cell proliferation kinetics and nuclear morphology in endometrial cancer under progesteron treatment. Cell proliferation kinetics by using the double labeling with 3HTdR--14CTdR, and nuclear morphology were studied in 20 patients with endometrial cancer who were given progesteron as a preliminary therapeutic measure. Results of these studies indicate that we have to face the fact that in all histological types of endometrial cancer considerable variations in the amount of tumor cells undergoing secretory conversion occur due to the primary heterogeneity of the tumor cell population.


Antilymphoid activity of leptospiral exoproducts. Intraperitoneal application of supernatant fluid of L. patoc caused a pronounced and transient fall in peripheral lymphocyte count of Syrian hamsters. Pathogenic and possible cancerologic aspects of this findings are discussed.


Cytotoxic and cancerostatic effect of 1,4-dithiaanthraquinone-2,3-dicarbonitrile. 1,4-Dithiaanthraquinone-2,3-dicarbonitrile (DTA) has been found to exert a considerable cytostatic effect especially on some of the investigated types of eukaryotic cells, concretely on the HeLa cells, moulds, yeasts, protozoa and algae. In cells of the Ehrlich ascites carcinoma (EAC) DTA after a short exposition causes a parallel inhibition of incorporation of 14C-adenine and 14C-valine, in proportion to its rising concentration. The inhibition of biosynthetic processes thus made manifest, is probably a consequence of the primary DTA intervention into the energy metabolism of EAC cells, particularly in glycolysis. The effect of DTA in concentrations capable of bringing about full inhibition of glucose consumption or lactate formation in EAC cells also results in a loss of their transplantability. On the other hand, DTA also exerts a cancerostatic effect on the Ehrlich ascites carcinoma in mice.


Cellular mechanisms of the radiomodifying effect of hypothermia. The irradiation of experimental tumors with a dose of 2000--2500 rad (20--25 J/kg) under hypothermia promoted an inhibition of the growth to a greater degree than the irradiation under normal conditions. In Guerin's tumor the inhibition of DNA and RNA synthesis was more expressed after the irradiation under hypothermic conditions than under the irradiation, and/or hypothermia alone. After the irradiation of the Guerin's tumor under hypothermia the cells were synchronized during the presynthetic phase of the cycle (block G1-S), and the effect of synchronization was more expressed in the tumor than in the normal tissue. The irradiation under hypothermia decreased the proliferative pool to a greater degree than the irradiation and/or hypothermia alone.


Some characteristics of karyotype changes in the NK/Ly ascites tumor during its growth. The NK/Ly ascites tumor has been studied with respect to the karyotype and its changes during tumor growth. The numeric stem line of the tumor cells is 43. The chromosome markers are as follows: a large metacentric chromosome, a large submetacentric chromosome with the long arm divided or, in a few cases, not divided by achromatic space, a large telocentric chromosome with a well-visible achromatic space which divides its long arm into two sections, and 1--2 extremely small chromosomes. The combination of the large metacentric chromosome, the large submetacentric chromosome with achromatic space, and of 1--2 extremely small chromosomes is modal. With the NK/Ly tumor growth, the number of modal cells decreases, while the variability in the number of chromosomes in the cells increases, i.e. their number is diminishing, and so is the percentage of cells with the modal combination of chromosome markers. On the 12th day of tumor growth, no clearly visible stem line can be noticed. The observed karyotype changes may be considered, alongside with other causes, to be due to longer period of the cell cycle during the NK/Ly ascites tumor growth.


Growth characteristics of the RL-67 lung tumor -- a new model for experimental therapy of metastatic processes. Implantation of the RL-67 tumor in to the limb muscle of C57Bl strain mice resulted in the tumor growth at the site of implantation and the metastatic process became manifest predominantly in the lungs of all animals. A direct correlation was established between the primary tumor and its metastases. The number of metastases on the 20th day after the transplantation amounted to about 60. The mean survival time of the tumor-bearing mice was approximately 24 days. Seven different substances were administered intraperitoneally to tumor-bearing animals and their effect on the tumor and its metastases was established. It was found out that heparin and carboxymethyldextran led approximately to a 50% decrease in the number of lung metastases in comparison with the controls. A certain "prophylactic" effect on metastases was achieved with Bleomycin. The data of the biological and histological studies suggested that the RL-67 lung tumor may be used as a suitable model for investigation of the factors influencing the tumor metastases.


Protein synthesis in tumor host. I. Enhanced peptide elongation in transplantable tumors and host liver. Protein synthesis was significantly enhanced in subcellular systems containing ribosomes and cytosol from the liver of Walker tumor-bearing rats from the second week following the tumor transplantation and this enhancement persisted for the whole period of tumor growth. Homologous systems from Zajdela hepatoma and host liver showed a markedly increased poly(U)-dependent peptide elongation when compared with normal liver tissue. A stimulation of polyphenylalanine synthesis resulted from the addition of cytosols from tumors or host liver to ribosomes from normal rat liver. Similar results were found for the binding of phenylalanyl-tRNA to ribosomes. Ribosomes from tumors and host liver are more active in peptide elongation than particles from normal liver tissue. A more than 10-fold stimulation of phenylalanine polymerization resulted from the addition of poly(U) to ribosomes from Zajdela hepatoma whereas only less than 2-fold enhancement was found when using ribosomes from normal or host liver. Hepatoma ribosomes apparently contain only a low proportion of polyribosomes carrying natural message. Enhanced protein synthesis in tumors and host liver is apparently due, in particular, to an increased activity of soluble factors required for protein synthesis and less due to an increased activity of ribosomes.


Differences in uptake of aminoacids by patients with various forms of cancer. The serum concentrations of alphaaminonitrogen (AAN), lysine, valine and leucines were determined before and within the period of 24 hr after the administration of Trophysan (10% solution of glucose containing a mixture of aminoacids) in 100 patients with cancer (17 with gastrointestinal carcinoma, 34 with uterus carcinoma, stages I to III; 8 with breast carcinoma, stages II and III; 15 with bronchogenic carcinoma, 10 with various localizations and 15 with metastatic cancer) and in 22 patients with benign tumors. A significant decrease in the serum content of AAN, valine and lysine was noted in patients with cancer (stages I to III) at 24 hours after the administration of Trophysan. This effect was absent for the patients with benign tumors. The enhanced uptake of aminoacids found in patients with cancer is probable the result of the negative nitrogen balance associated with the malignant state.


Effect of cytostatics on some platelet functions in vitro. VI. Vinblastine. The influence of vinblastine upon principal functions of blood platelets in vitro (adhesion, aggregation, platelet release reaction, membrane stabilization) has been followed using an extended system of laboratory examinations. The authors have found that the concentration of vinblastine which is higher than the average therapeutic dose (10(-5)M) inhibits the functional ability of platelets so that it may cause a thrombopatic disorder.


Influence of heparin and defibrase on transplantability of syngeneic tumors in mice. It had been previously demonstrated that fibrin clot might have an important role in the growth of malignant tumors and in metastasis formation. For this reason an attempt had been made to find out whether inhibition of fibrin formation by heparin or fibrinolysis induced by defibrase could limit tumor growth. Male mice of inbred strain were challenged with suspension of tumor cells. For anticoagulation and/or fibrinolytic therapy two different schedules were used. The treatment was started either simultaneously with the tumor transplantation, or one week prior to the injection of tumor cells. The size of tumors was bigger in the group of treated animals, when compared with the controls. However, the difference was not statistically significant. On the other hand, frequency of implanted tumors was significantly higher in animals with heparin and defibrase treatment or pretreatment.


Estrogenic effect in vaginal smears in cancer of the uterine cervix. Values of karyopyknotic index (KPI) in a series of 37 uterine cervix cancer patients were significantly increased when compared with the same groups of 61 healthy women. Radiosensitivity of the tumors was accompanied by subsequent decreasing in the KPI values while in all radioresistent cases as well as in all early recurrences persistence of initial high KPI values could be proved. Significant differences in the kinetics of KPI changes during and after radiation in the group of praemenopausal and postmenopausal patients support suggestion for non ovarian origin of this estrogen like activity.


Factor VIII procoagulant activity in children with nephrotic syndrome and post-streptococcal glomerulonephritis. Plasma factor VIII procoagulant activity has been shown to be significantly elevated in 32 children with the nephrotic syndrome. This increase is more marked in those with obvious glomerular lesions on histology than in patients with minimal change nephropathy. Fluctuations in factor VIII levels corresponded to changes in the clinical condition of the nephrotic syndrome. In 28 children with post-streptococcal glomerulonephritis, 4 patients with the highest factor VIII levels recovered between 7 and 60 days of onset of disease whereas the remainder did so in less than 7 days. Factor VIII levels may reflect the extent of immunopathological injury to glomerular capillaries and be useful in management of children with glomerular disease.


Screening uremic 'toxins' using bromsulfophthalein clearance by the isolated perfused rat liver. The kinetics of bromosulfophthalein clearance from plasma, secretion into bile, and, by difference, storage in hepatic cells, were determined, using normal livers and blood from normal rats in the isolated perfused rat liver system. Two suspected uremic 'toxins', urea and guanidinosuccinic acid, were then administered in order to determine if either of these substances would independently alter the kinetics under study. Results indicated that these two compounds have little or no  effect on liver function on an acute basis. However, because of the excellent reproducibility obtained, it is believed that this method can be of significant use in the further screening of substances from uremic patients which may be interfering seriously with liver functions.


Changes in copper and ceruloplasmin in chronic renal insufficiency treated by hemodialysis and peritoneal dialysis. Serum copper and ceruloplasmin as well as other parameters in 68 patients with chronic renal insufficiency were studied. It was found that chronic renal insufficiency increases neither the serum copper nor the serum ceruloplasmin. In the group on hemodialysis, there is a progressive increase of copper and ceruloplasmin in serum due to a liberation of 44.44% of the copper content of the membranes. In the group on periodic peritoneal dialysis, there is also an increase of serum copper during the dialysis. We do not have an explanation for this finding.


Spontaneous retroperitoneal hemorrhage in chronically hemodialyzed patients. Patients maintained on chronic hemodialysis have an increased incidence of spontaneous bleeding from various parts of the body. In this paper we describe 5 patients who developed spontaneous retroperitoneal hemorrhage. All patients were receiving anticoagulants (Coumadin and/or heparin) at the time of bleeding. Clinically, retroperitoneal hemorrhage was evident in the interdialytic period. Presenting symptoms and signs included sudden and progressive onset of pain in the abdomen, flank, back, thigh or hip associated with a drop in blood pressure and hematocrit in the absence of obvious blood loss. Subsequently ecchymosis, swelling and/or mass were observed. Abdominal X-rays showed absent psoas shadows. Treatment included blood transfusions, discontinuation of Coumadin and/or heparin, the use of regional heparinization for hemodialysis and occasionally peritoneal dialysis. Surgical exploration was not required in any case and all 5 patients recovered. Anticoagulation therapy and platelet dysfunction may be contributory causes.


Hemosiderosis secondary to chronic parenteral iron therapy in maintenance hemodialysis patients. Autopsy data on 24 chronic maintenance hemodialysis patients who had received varying doses of parenteral iron as the iron-dextran complex were reviewed for evidence of iron overload (hemosiderosis) and tissue fibrosis or organ dysfunction (hemochromatosis). Hemosiderosis was frequent in patients who received high total doses of iron but absent in those who received little or no iron. The degree of tissue iron did not increase with increased iron administration above a total of 2.5 g. Hemochromatosis or organ dysfunction secondary to tissue iron deposition was not noted in any patient. Chronic parenteral iron administration may improve anemia and result in tissue iron deposition but does not lead to hemochromatosis.


Effect of arginine or creatinine administration on the urinary excretion of methylguanidine. The metabolic pathway of methylguanidine (MG) is mainly speculated from the change in urinary excretion of MG in the arginine (Arg)-injected normal rat, the creatinine (Cr)-injected normal rat, and the Arg-injected uremic rat. 15N-Arg was ingested to 2 uremic patients. Arg administration resulted in marked increase in urinary MG excretion both in the uremic rat and patient, but not in the normal rat. In the first phase of the 15N-Arg ingestion experiment, a rapid rise of 15N atom percent excess of urinary MG was observed in the uremic patient. In the second phase of this study, after 24 h of 15N-Arg ingestion, the 15N atom percent excess of urinary Cr and that of MG closely paralleled. These findings imply that there might be two metabolic origins of MG: one is a formation of MG from Arg itself or an Arg metabolite other than Cr, the other a pathway producing MG via Cr. The former is compatible with the hypothesis by Cohen.


Modular single-needle haemodialysis; ultrafiltration characteristics. In vitro and in vivo work has been carried out examining a modular single-needle system for fistula haemodialysis. Ultrafiltration characteristics of the single-needle system are defined and conclusions upon flow patterns are reached. Applying the mean blood pressure formula to the extracorporeal system pressures, the transmembrane pressure can be calculated and the ultrafiltration rate forecast. High transmembrane pressures can be modified, with sacrifice of blood flow, by amendment of the blood flow phase durations.


Bleeding in renal failure: altered platelet function in chronic uraemia only partially corrected by haemodialysis. Bleeding time, blood loss and platelet retention by glass beads, measured by standardized techniques, were significantly altered in  a group of 30 non-thrombocytopenic patients with chronic renal failure undergoing maintenance haemodialysis. Bleeding time or blood loss did not correlate with platelet retention either before or after haemodialysis. No correlation could be found between the above tests and a number of biochemical parameters characterizing the uraemic condition. Haemodialysis only partially corrected the abnormal bleeding time, blood loss and platelet retention. These tests were still significantly different after haemodialysis from those of 30 normal subjects. It is suggested that some non-dialyzable material could play an important role in the aetiology of uraemic bleeding.


Metacarpal cortical thickness in uremic patients on regular hemodialysis. Metacarpal cortical thickness was measured in 83 patients with chronic renal failure undergoing periodic hemodialysis. Patients were dialyzed twice weekly, 8--9h per session, with a calcium concentration in dialysate of 6.5 mg/dl. Supplements of calcium, vitamin D (5,000 I.U. a day), steroid anabolic hormones, and aluminium hydroxyde were administered to all patients. They were on a normal protein intake and unrestricted physical activity. The results show that the young males have a reduction in cortical thickness as compared to age-matched controls, and that there is a progressive loss in cortical width as the length of dialysis increases. This bone loss is statistically significant in males during their first 18 months of dialysis.


Serum erythropoietin concentration in anephric patients. In 13 bilateral nephrectomized patients serum erythropoietin (SEp) activity could be measured quantitatively by use of the highly sensitive fetal mouse liver cell assay. SEp concentration in the majority of the cases was below the mean of normal controls. There was a significant positive correlation between SEp levels and hematocrits, suggesting erythropoietin (Ep) deficiency to be a causative factor in the anemia of the anephric state. Androgen therapy stimulated extrarenal Ep production in all of 5 anephric patients studied.


Nephroptosis and kidney function.

Nephroptosis and kidney function. We have investigated the influence of renal mobility on both renal blood flow and glomerular filtration, in order to evaluate its role as a potential intermediate cause of hypertension. In 25 untreated patients we compared between recumbent and upright position the relative change in the following five parameters: effective renal plasma flow (ERPF), glomerular filtration rate (GFR), renal mobility, peripheral plasma renin activity (PRA) and blood pressure. We found a positive correlation between the degree of renal mobility and an observed decrease in ERPF. On the other hand, no relation was found between the former and an observed decrease in GFR. The PRA appeared to rise following the decrease of the ERPF. These observations suggest that renal mobility adds to the orthostatic reduction in renal blood flow.


Treatment of the nephrotic syndrome with indomethacin. In 25 patients with nephrotic syndromes of different origin, indomethacin caused an immediate decrease in glomerular filtration rate (GFR) and urinary protein excretion. This effect of indomethacin on GFR and proteinuria was more pronounced when the renin-angiotensin system was stimulated by a low-sodium diet and 50 mg hydrochlorothiazide daily, and resulted in a significant rise in serum albumin. Withdrawal of indomethacin after 1--3 years of administration was followed by an increase in proteinuria to pretreatment levels in 9 out of 15 patients. A harmful renal effect of long-term indomethacin administration was found to be unlikely. The results suggest that the steroid-resistant nephrotic syndrome can be treated symptomatically by indomethacin.


Evidence of possible association of nephrolithiasis and nephroptosis. Two separate populations, one consisting of 100 patients with renal stones and one consisting of 81 patients with nephroptosis were examined to determine whether an association may exist between excessive renal mobility and renal stone formation. The statistical analysis of the data suggests a direct relationship between nephroptosis and the occurrence of renal stones.


Charcoal hemoperfusion for chronic renal failure. 16 patients with end-stage renal disease were treated with a fixed-bed, uncoated-charcoal hemoperfusion device, used either alone or in series with a hemodialyzer. 3 patients had one of their thrice weekly dialyses replaced by one 3 hour combined treatment for up to 6 months, and 3 patients had 150-min combined treatments thrice weekly for up to 5 months. The procedure was well tolerated. Transient hypotension occurred and interfered with fluid removal by ultrafiltration. Platelet counts were reduced, but there was no clinical bleeding. Pretreatment of the device with albumin provided no advantage over heparinized saline, and dextran caused a more severe reduction in the platelet count. The changes in platelets, white blood cells, and hematocrit were transient and noncumulative. Considerable amounts of creatinine and uric acid were removed. Regular charcoal hemoperfusion appears to be safe, and long-term studies of clinical efficacy are indicated.


Chronic hemodynamic effects of propranolol treatment in dialysis-refractory hypertension. The hemodynamic mechanism of the hypotensive effect of propranolol was studied by quantitative radiocardiography in 8 patients with dialysis-resistant hypertension. Propranolol treatment brought about a decrease in mean arterial pressure and peripheral vascular resistances. The cardiac index was slightly reduced only in the early stage of the treatment. No significant difference was found between patients on treatments lasting longer than 3 months and patients with dialysis-controlled hypertension. The results show that propranolol can be used safely as the sole antihypertensive agent in patients with dialysis-resistant hypertension.


Glomerular injury in malignant nephrosclerosis. Electron microscopic analysis of subendothelial and mesangial alterations in the glomeruli was performed in 15 cases of malignant nephrosclerosis (MNS). 8 cases showed segmental or diffuse subendothelial accumulation of proteinaceous 'fibrinoid' material associated with thickening of glomerular basement membranes. 2 of these cases also showed similar deposits in the mesangium. When severe, this mesangial insudation resulted in almost complete replacement and destruction of the mesangial matrix. Endothelial injury with alteration of glomerular microcirculation and secondary intravascular coagulation is believed to play a role in the development of the glomerular lesions in MNS.


Renal lesions in chronic pancreatitis.

Renal lesions in chronic pancreatitis. Many patients with chronic pancreatitis (CP), even in the absence of intrinsic renal disease, are found to have abnormal urine, with persistent proteinuria, cylindruria, microhematuria and leukocyturia. The kidneys of 12 necropsy cases with CP showed mild to moderate arterial and arteriolar nephrosclerosis and no other significant changes. Renal biopsies were performed in 10 patients with CP without evidence of systemic disease or intrinsic renal disease, but with persistent urinary abnormalities. By light microscopy, mild arterial and arteriolar nephrosclerosis was present in 5 instances. In 1 patient, evidence of the reparative phase of acute tubular necrosis was noted. In 5 biopsies, electron microscopy revealed minimal to mild increase in mesangial matrix. Mild thickening of the glomerular basement membrane (GBM) was found in three instances but there was no clear-cut evidence of diabetic glomerulosclerosis. The presence of subendothelial electron-lucent material in 3 cases suggests the possibility of previous subclinical episodes of intravascular coagulation. The most consistent finding was the presence of lipid material in the cytoplasm of glomerular and tubular cells. The renal lesions associated with CP are mild, nonspecific and nonprogressive. Various pathogenetic factors can be invoked to account for their presence and for the urinary abnormalities found in patients with CP.


Effects of in vivo and in vitro dialysis on plasma transaminase activity. The effects of dialysis on plasma glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were investigated. GOT was measured using Autoanalyzer (SMA) and kinetic (Karmen) methods. Hemodialysis of uremic subjects was associated with a significant increase of GOT (SMA) and GPT (SMA). In contrast, hemodialysis had no effect on GOT (Karmen). However, the SMA method is influenced by substances affecting the blank value. Therefore, the results suggest that the increase in transaminase activities measured by the SMA method are not due to true increases in enzyme activities. Plasma from dialysis patients, obtained prior to hemodialysis, was also dialyzed in vitro. In vitro dialysis of uremic plasma significantly increased GOT (SMA), GOT (Karmen) and GPT vitro dialysis of uremic plasma significantly increased GOT (SMA), OGT (Karmen) and GPT (SMA). The results suggest that an inhibitor of transaminase activity may accumulate in renal failure. In vitro dialysis may remove this inhibitor and thus increase true transaminase activity.


Calcium and sodium excretion in rats in response to prolonged treatment with polythiazide. The hypocalciuric response to prolonged polythiazide (PTZ) administration has been investigated in intact and thyroparathyroidectomized (TPTX) rats. After 3 control days, PTZ was given for 6 days (0.1 mg/100 g body weight . 24 h p.o.). In both groups, calcium excretion fell on day 1 of PTZ and remained depressed thereafter. In the intact rats, this decrease was associated with increased sodium excretion and urine output on treatment day 1. In the TPTX rats, hypocalciuria occurred without change in sodium excretion or body weight; urine output increased on the first 2 days. Thus PTZ can reduce calcium excretion in the absence of parathyroid hormone, changes in sodium excretion, and changes in body weight (an estimate of body fluid balance with constant food intake).


Indomethacin and lysine acetylsalicylate in rats with autologous nephrotoxic serum nephritis. Biochemical and morphological studies. The effects of indomethacin and lysine acetylsalicylate (L-ASA) were compared in rats in which autologous nephrotoxic serum nephritis had been induced. The aim of this study was to offer support to the hypothesis that indomethacin might reduce proteinuria through increased synthesis of glomerular basement membrane by the podocytes. Both drugs were injected intraperitoneally at the dosage of 4 mg/kg body weight daily during a 6-day period into 40 rats rendered nephritic by rabbit nephrotoxic serum injection. Rats treated with indomethacin showed a marked decrease of proteinuria (tested by the 3% sulfosalicylic aicd method) and a clear ultrastructural picture of hyperplasia and hypertrophy of podocytes. Rats given L-ASA showed only a slight correction of proteinuria and less specific ultrastructural modification. These observations suggest that indomethacin decreases proteinuria in nephritic rats not only through its anti-inflammatory activity, but possible also by a peculiar mechanism, namely an increase in podocytic basement membrane synthesis.


Effect of experimental chronic renal failure upon the synthesis of thyroid hormones in rats. The authors utilized two groups of adult male rats to study the effect of chronic-uremic toxemia on the synthesis of thyroid hormones. The control group was sham operated, while the other group had about 70--80% of the left kidney tissue surgically excised and a total right nephrectomy performed 10 days later. At the 90th day after the second operation, 8 muCi of 131I were injected intraperitoneally and 24 h later the thyroid was excised and hydrolyzed enzymatically for a period of 14 h at 37 degrees C. The percentages of iodinated components were then calculated after radiochromatographic separation on paper. The group of experimental rats by this time showed significant increases of plasma urea and creatinine, and an absence of acidosis. The results suggest that monoidotyrosine concentration is increased and diiodothyronine decreased in the experimental group of rats with renal failure. This might indicate a toxic metabolic blockage in the transformation of monoiodotyrosine to diiodothyronine.


The pathogenetic significance of intravascular coagulation in experimental acute renal failure. Serum and urine fibrin(ogen) degradation products (FDP), FDP clearances, and serum urea nitrogen (SUN) concentrations of rats challenged with glycerol-induced myohemoglobinuria were measured serially over a period of 4 days. The results obtained in animals that developed acute renal failure (ARF) were compared with those obtained in rats made refractory to renal failure by long-term salt loading or recent recovery from prior renal failure. Only the rats susceptible to ARF experienced a major rise in serum FDP concentration. Urine FDP excretion rose most markedly in the same rats but, being elevated in all groups. showed the utilization of fibrinogen whether serum FDP values increased or not. The results obtained might reflect differences in the degree of intravascular coagulation which are pathogenetically important. It is possible, however, that increased serum FDP concentrations found exclusively in rats with ARF are the results rather than the cause of impaired filtration, and that reduced tubular absorption may at least partly account for the high urinary FDP excretion observed in this model of experimental acute renal failure.


Synthesis and degradation of glomerular basement membrane in rats with nephrotoxic nephritis. Degradation and synthesis of the collagen portion (CLP) of the glomerular basement membrane (GBM) in glomeruli of rats with nephrotoxic nephritis (NTN) were determined in vivo and in vitro. Degradation of CLP in rats with NTN was only increased during the first 24 h after induction of NTN. After 24 h, the half-life of CLP in NTN rats (16.9 days) was not significantly different from that in the controls 15.6 days). The loss of CLP during the first 24 h is accompanied by an increased synthesis, measured in vivo and in vitro. The increased synthesis, however, does not seem to be sufficiently high to result in accumulation of CLP-like material in NTN. Since degradation and synthesis of CLP was not altered during the later phase of NTN, it is unlikely that chronic proteinuria is the result of an ongoing abnormal turnover of CLP.


Natriuresis-induced protection in acute myohemoglobinuric renal failure without renal cortical renin content depletion in the rat. The interrelationships of renal cortical renin content RCRC, sodium chloride excreting and the severity of renal failure were studied in the glycerol-induced acute myohemoglobinuric renal failure model in the rat. Protocols were designed to increase sodium chloride excretion without necessarily resulting in RCRC depletion. Our data fail to demonstrate a relationship between RCRC and severity of renal failure, but they demonstrate an excellent inverse correlation between the sodium chloride excretion of the animals in the 24 h prior to glycerol administration and the severity of resulitng renal failure. The protection of long-term saline-drinking animals should properly be ascribed to the associated natriuresis which develops much before RCRC depletion during the time course of saline drinking. The exact mechanism by which natriuresis exerts its protective effect needs further elucidation, but our data argue against a major role for RCRC in the pathogenesis of acute experimental renal failure.


Elevation of rat erythrocyte nucleotide levels following acute renal failure induced by glycerol or mercuric chloride. Biochemical changes in the blood following induction of renal failure by glycerol or mercuric chloride have been studied in 16 rats. Plasma creatinine, urea and Pi levels indicated that renal impairment followed the same time course in both renal failure models, with the severest effects on day 3 and returning to normal by day 7. Erythrocyte ATP and guanine triphosphate (GTP) levels were significantly elevated above contorl values on day 1 and remained elevated in both models. ATP/ADP and GTP/GDP ratios also increased in both models. In renal failure the increased purine 'salvage' in the erythrocyte may be attributed to accumulation of purine metabolites in the serum associated with increased P-ribose-PP levels due to elevated cellular Pi. Nucleotide changes in both these models are analogous to those found in chronic renal failure in man.


Morphometric studies on glomeruli in the congenital nephrotic syndrome. Morphometric studies were performed on glomeruli in two kidneys of a 13-month-old patient with congenital nephrotic syndrome of the Finnish type (CNF) and two control kidneys from an 11-month-old child. The mean diameter of the glomeruli in the diseased kidneys was abnormally large for the patient's age and the mean glomerular volume about twice the normal. The number of glomeruli, counted using a statistico-geometrical method, was 74% higher than in the control kidneys, a finding which is in accordance with a previous result obtained using a different counting method. The total glomerular volume per kidney in the CNF patient was about 3 times the normal for that age, almost equalling that in a 7-year-old individual.


Polkissen cells and their possible role in renin secretion. An electron microscopic study of the renal polkissen cells revealed evidence of their participation in the renin angiotensin system. An unusual feature of the cell is the presence of polar nuclear bags (vacuolization) with attached ribosomes. Significantly, a good correlation was observed between vacuolization and plasma renin activity. The latter was created by differing experimental settings, namely restricted sodium intake, hemorrhage, or reduced renal perfusion pressure. These data, plus the finding of secretory granules in these cells, are interpreted as evidence that the polkissen cells are in some way concerned with the regulation of secretion of renin.


Intravenous urography in experimental acute renal failure. Nephrograms and pyelograms in saline-loaded rats. We studied renal opacification during intravenous urography in 20 rats subjected to glycerol-induced acute renal failure, with and without prior saline loading. Animals drinking saline suffered less severe renal impairment (mean plasma creatinine 175 mumol/l) than those drinking tap water (mean 341 mumol/l). Nephrograms occurred during intravenous urography in 19 rats at all levels of renal impairment, but were only followed by pyelograms in 8 with mild plasma creatinine elevation (mean 84 mumol/l). The occurrence of a pyelogram was determined not by whether an animal was drinking saline or tap water, but only by the level of renal impairment. The presence of the nephrogram throughout the range of functional impairment in acute renal failure argues against glomerular filtration as the principal route by which contrast medium reaches the nephron to produce this clinically very useful sign.


Chromic acid poisoning treated with acute hemodialysis. Poisoning with chromium compounds is rare, but often serious. The symptoms are quite characteristic, the most dramatic of these being circulatory collapse, hepatic and renal failure. A case is reported where an 18-year-old woman ingested 5 g of chromic acid. She was treated with acute hemodialysis and forced diuresis, and survived with surprisingly few symptoms of poisoning.


[Neurotraumatology of sportive origin (author's transl)]. In our Statistics, accidents in sports represent only 2,3% of the trauma cases hospitalized in the neurosurgical service of Marseille La Timone; of these cases 57% are cranio-cerebral injuries, 43% are vertebral or spinal cord injuries. The type and severity of trauma are of course directly related to the type of sport concerned. Cranio cerebral and spinal cord injuries occur with the same frequency in rugby. Horse back riding and foot-ball are responsible for severe cranio-cerebral injuries (respectively 90% and 92% of the total number of these accidents). Diving is the cause of spinal cord injuries in 79% of the cases. Close supervision of accident victims and systematic and technical analysis of accidents related with sports practice should improve the safety for both amateurs and professionals.


[Traumatic atlanto-axial dislocation. (About two cases with late clinical manifestations) (author's transl)]. Two cases of atlanto axial dislocation with late neurological manifestations are reported and the very few cases of the literature are reviewed. The clinical signs are non specific. Excellent lateral tomography must demonstrate the abnormal space between atlas and axis. Surgical treatment includes bone fusion after reduction of the dislocation by cautious skull-traction. The results are excellent if the operation is performed before the onset of severe neurological deficits.


[4 cases of traumatic cerebral aneurysms are reported (author's transl)]. Among them: one aneurysm of the meningeal artery and 2 cases of aneurysm of cortical arteries. The delay between trauma--mild or severe--is variable: eight days to 3 weeks. Cerebral angiography is the only diagnostic procedure which can identify these traumatic aneurysms. Surgical treatment is discussed.


[Radicular artery thrombosis after cervical anterior approach for cervico-brachial neuralgia (author's transl)]. An anterior cervical approach completed by a bone graft is performed on a man suffering from cervico brachial neuralgia which did not improve by medical treatment and rest. During four months, the post operative course is excellent, with complete disappearance of pain and regression of the pre-existing neurological deficit. At the end of this period, the appearance of a major deficit within the field of the concerned root led to a selective brachial angiogram which revealed the existence of a radicular artery thrombosis.


Effect of calcium on brain metabolism in vitro. In attempts to distinguish between direct and indirect effects of Ca on brain cell metabolism, respiration, glycolysis, ATP, phosphocreatine, incorporation of [14C] leucine into protein, and accumulation of 45Ca was determined in brain slices. Incubation was carried out in normal salt-balanced medium, in high-potassium-or ouabain-containing medium under aerobic and anaerobic conditions. Calcium ions inhibited slightly glycolysis and respiration in normal medium and activated amino acid incorporation into proteins. Levels of ATP and phosphocreatine remained normal. The effects were interpreted as due to a stabilization of plasma membranes by Ca ions to prevent their spontaneous depolarization. Incubation of slices in high-potassium and ouabain media in aerobic conditions in the presence of Ca resulted in activation of respiration and glycolysis, decrease of ATP and phosphocreatine levels, and inhibition of amino acid incorporation into proteins. The disturbances in energy metabolism, caused by the respiration-linked Ca uptake in brain mitochondria and concomitant inhibition of oxidative phosphorylation, may lead to the inhibition of amino acid incorporation into proteins. An increase in Ca levels in the cytoplasm may only be expected in anaerobic conditions during the incubation in high-potassium and ouabain media. This is manifested by a direct inhibition of glycolysis by Ca ions and a drastic decrease of ATP and phosphocreatine in slices. The results suggest that stimulation of aerobic glycolysis and inhibition of anaerobic glycolysis by Ca may explain the unknown mechanism of the so-called "reversed Pasteur effect" of brain slices incubated in high-potassium media.


A possible mechanism for cholesteryl ester formation during demyelination: lecithin:cholesterol acyltransferase (LCAT) activity in rat brain. Lecithin:cholesterol acyltransferase (LCAT) activity has been examined in the rat by using a brain homogenate preparation as the phospholipid substrate and blood plasma as the enzyme source. LCAT activity was detected on using 60 mul of serum onwards. Successive experiments have also shown that LCAT activity is present in the edematous rat brain tissue homogenate when incubated with inactivated rat plasma as substrate. The results are discussed in relation to cholesteryl ester accumulation in brain during demyelinating diseases.


Increase of ornithine decarboxylase activity elicited by reserpine in the peripheral and central monoaminergic systems of the rat. Ornithine decarboxylase activity was increased about tenfold in adrenal glands and in brain regions preponderantly containing aminergic neurons, by a single dose of 16 mumol/kg of reserpine. Maximal enzyme activity in the adrenal glands was observed at about 8 hr after reserpine administration. The ornithine decarboxylase activity-time curves in the brain regions showed a concomitant polyphasic course, with the highest maximum at 12 hr postinjection. Ornithine decarboxylase induction is discussed as an early event in the cascade of molecular events preceding the induction of cell typic enzymes.


Uptake and release of meta-tyramine, para-tyramine, and dopamine in rat striatal slices. The uptakes of high-affinity concentrations (10(-8)M) of meta-tyramine (m-TA), para-tyramine (p-TA), and dopamine (DA) into rat striatal slices have been shown to be inhibited by DNP and ouabain. We now demonstrate that cocaine (5 x 10(-6)M) and low concentrations of sodium ion (26 x 10(-3)M) also reduced these uptakes. The spontaneous efflux and the release [induced by an elevated concentration of potassium ion (5 x 10(-2)M)] of each of the previously accumulated amines were studied in the presence and absence of added calcium ions. The spontaneous efflux of each amine (especially the tyramines) was enhanced by the absence of calcium ions. Part of this enhancement seemed to be due to an inhibition of a calcium-dependent reuptake. The elevated concentration of potassium ion proved to be an effective releaser of each amine; and for DA, such release was decreased by the removal of calcium. For m- and p-TA, however, the removal of calcium either did not reduce or completely abolished the releases depending upon the duration of the calcium removal. The significance of these findings is discussed.


Cholinergic systems in muscle and brain in vitamin E-deficient rats. Rats fed a vitamin E-deficient diet for 7--8 weeks postweaning showed no change in brain weight or the activity in brain of various enzymes involved in neurotransmitter synthesis and metabolism. Body and muscle weights were markedly reduced. Muscle choline acetyltransferase and acetylcholinesterase activities were significantly elevated on a protein basis, but the total amount of choline acetyltransferase/muscle was essentially normal and total acetylcholinesterase activity was slightly reduced. Total carnitine acetyltransferase and butyrylcholinesterase activities were markedly decreased. The results are quite different from those found in hereditary murine muscular dystrophy and suggest a myogenic etiology for the vitamin E-deficiency-induced condition.


Transcallosal approach to the anterior ventricular system. Using an anterior transcallosal approach, we operated upon 25 patients with lateral and 3rd ventricular lesions. The facility of this route is discussed, and the operative technique is presented.


Human malignant gliomas treated with chemotherapy: a pathological study. Twenty-one malignant cerebral tumors treated with chemotherapy after operation or clinical diagnosis were studied. The brains were cut in coronal slices that were embedded in paraffin. The histological picture of the whole tumor and of the adjacent normal tissue was carefully investigated, and it was compared with the histological features noted on biopsy. The general characteristics of glioblastoma, including wide central necrosis, were present in all of the cases. No specific alterations referable to chemotherapy were found. The increase of monstrous cells and the decrease of mitoses, although observable in some areas, were not of general importance. There was a statistical relationship between the occurrence of reactive astrocytes with bizarre nuclei and repeated chemotherapy or length of time after radiotherapy.


Pediatric posterior fossa tumors: hazards of the "preoperative" shunt. Many neurosurgeons recommend a "preoperative" shunt for children with posterior fossa tumors. It has been reported that the definitive surgery is simplified and the postoperative course is more benign as a result of the cerebrospinal fluid diversion. The present report documents complications as a result of upward herniation and hemorrhage within the tumor after shunt placement. On the basis of this experience, we conclude that a shunt is potentially hazardous and should be restricted to that selected group of patients who are acutely ill from increased intracranial pressure that is refractory to temporizing pharmacological management.


The development of paediatric neuroradiology. The development of paediatric neuroradiology is a specific persuasion within neuroradiology and has increased in scope and significance throughout the last ten years. The emergence of computed tomography has altered the indications for types of neuroradiological procedures in infants and children. The sophistication, accuracy, and safety of standard neuroradiological procedures have been increased by the accuracy and safety of computed tomography, particularly in the premature infant. There is a growing need for education and instruction in paediatric neuroradiological techniques and paediatric neuroradiological diseases within the neuroradiological fraternity as a whole.


The role of computed tomography in the diagnosis of brain tumors in infants and children. CT has considerably facilitated the diagnosis of intracranial tumors, especially in infants and children. The authors review their experience with a series of 260 children with proven brain tumors. In most cases CT is so conclusive that other diagnostic techniques are no longer often needed. Pneumoencephalography in particular has largely been replaced by CT in recent years in the authors' departments, and the frequency of central ventriculography with contrast material has decreased substantially. Particular diagnostic difficulties with regard to tumors near to or within the caudal brain stem, some posterior fossa tumors, small vermian tumors, and tumors of the cerebral hemispheres are discussed.


Colonic ileus complicating laminectomy.

Colonic ileus complicating laminectomy. Colonic ileus is an unusual form of adynamic ileus that often mimics true intestinal obstruction and that, if not recognized and adequately treated, may be fatal. We have encountered three patients in whom this syndrome followed apparently uncomplicated laminectomy for herniated disc or spinal stenosis. Two of our three patients required abdominal exploration for diagnosis and treatment of the complication. At operation, a large distended colon without volvulus or tumor was found. Cecostomy was performed in both patients. The third patient was treated conservatively. All three patients recovered without sequelae. The pathogenesis of the illness is unknown, but the most widely held view is that ileus results from increased sympathetic activity that inhibits the bowel. Conservative management consisting of correction of any fluid or electrolyte abnormalities, continuous gastric suction via nasogastric tube, and placement of a rectal tube may relieve the symptoms. Patients should, however, be followed carefully and, if distention of the cecum exceeds 12 cm, a decompressive operation is indicated.


Magnification angiography of the small vessels in cerebrovascular disease in advanced age. Vascular changes in the cerebral arterioles (150 - 500 mu) were demonstrated by means of magnification serial cerebral angiography (focal spot 0.15 mm) in a consecutive series of 25 hypertensive patients of advanced age suffering from cerebrovascular disease. The changes identified were: (a) arteriosclerotic lesions, (b) arteriolar occlusion, and (c) miliary aneurysms. The enhancement of vascular details obtained is essential to arrive at exact diagnosis and accurate clinical management.


Subdural empyema in Africans in Rhodesia. Subdural empyema was encountered in 44 African patients in Rhodesia during the period from 1970 to 1974. Subdural empyema seems to be a relatively frequent occurrence in Africans. Sixty-eight per cent of the patients were below the age of 20 years, and males predominated. More than half of the patients had either a history or evidence of an infectious process outside the central nervous system, and about 60% demonstrated focal neurological signs. The diagnosis was confirmed by either surgery or postmortem examination. Cultures of available specimens were positive in 50%. The predominant organisms identified were Streptococcus, followed by Staphylococcus. Surgical treatment consisted mainly of multiple burr holes, drainage of the empyema, and irrigation. The mortality rate in this study was 59%, and some recognizable contributing factors are elaborated. In the discussion the authors compare these observations with pertinent reviews from the literature. Some of these findings correlate well with other reports, whereas other observations are attributed to factors partly inherent in the socio-economic structure of the African population in Rhodesia.


An automated tumor resection device for neurological surgery. A pneumatically activated cutting probe has been designed for the neurosurgical removal of nervous system tumors or diseased tissue. The hand-held probe is formed of concentric slender tubes, one reciprocating inside the other. A scalpel-sharp edge on the tip of the inner tube moves in a shear motion past a stationary port on one side near the distal end of the outer tube. The reciprocating motion of the inner tube is provided by a pneumatic power source housed in a separate control console.


Angiography of the external carotid to internal carotid anastomosis. The EC/IC bypass is being performed more and more, and angiography is essential as part of the postoperative evaluation. This review of 41 patients points out the need for selective external carotid angiography in those cases where intracranial vessels fill spontaneously at the same time as the shunt. However, 8 of 11 cases showed the superficial temporal artery to be larger on the selective external carotid angiogram than in the common carotid study done during the same session. In two cases undergoing staged occlusive procedures as treatment for giant aneurysm, the external carotid artery leading to an EC/IC was occluded as an angiographic complication without neurologic sequelae.


Giant intracranial aneurysms of the anterior circulation: clinical characteristics and diagnosis by computed tomography. The computed tomography (CT) characteristics and clinical features of giant (globoid) aneurysms of the anterior circulation are reviewed. These lesions appear on the CT scan as smoothly encapsulated ovoid masses, within which a partially patent lumen is seen after the infusion of iodinated contrast material. With careful analysis of the CT scan it may be possible to differentiate giant internal carotid artery, anterior cerebral artery, and middle cerebral artery aneurysms from other parasellar and hemispheric lesions.


Syndrome of inappropriate antidiuretic hormone secretion after spontaneous subarachnoid hemorrhage: a reversible cause of clinical deterioration. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) developed approximately 7 days after a spontaneous subarachnoid hemorrhage in a 63-year-old woman with an anterior cerebral artery aneurysm. The hyponatremia associated with this syndrome resulted in a deterioration of the patient's clinical condition and focal neurological signs, which simulated the clinical deterioration after spontaneous subarachnoid hemorrhage that is often caused by other intracranial pathological conditions. The focal neurological signs in particular are likely to be interpreted as indicating one of these other conditions. Prompt recognition and treatment of the SIADH resulted in prompt improvement, and we were then able to proceed with the planned craniotomy for the aneurysm. The syndrome and its importance are discussed.


Infarction and circulation in cerebrum. Effect of recanalization and/or collateral circulation on the lesion and prognosis. Findings of computed tomography (CT) and angiography in supratentorial cerebral infarction associated with complete stroke were compared with regard to prognosis. It was found that the extent of low-density areas on CT was perfectly in accordance with the areas of occluded arteries on angiograms. However, the low-density areas on CT were always smaller than the areas involved angiographically when early recanalization and/or collateral circulation were carried out within 2 to 3 days of onset. It was also found that smaller low-density areas only had favorable effect. We concluded that the prognosis was better with early recanalization and/or collateral circulation, despite the general acceptance of its poor prognostic implication.


Comparison of angiographic and CT findings between patients with multi-infarct dementia and those with dementia due to primary neuronal degeneration. The CT and angiographic appearances in multi-infarct dementia have been compared with those of primary neuronal degeneration. It was possible to make a CT or angiographic diagnosis of multi-infarct dementia in about 40% of patients diagnosed by the ischaemic scoring method of Hachinski et al.


Clinical considerations concerning detection of venous air embolism. Venous air embolism during neurosurgical procedures (detected by Doppler Ultrasound and aspiration via a right atrial catheter) was noted in 100 of 400 patients in the sitting position, 5 of 60 patients in the lateral position, 7 of 48 patients in the supine position, and 1 of 10 individuals monitored in the prone position. We confirmed venous air embolism in many of these cases by using serial technetium-macroaggregated albumin lung scans. Gravitational gradients from the venous portal of entrance to the right side of the heart were as small as 5.0 cm, with aspiration of 200 ml of air occurring. Doppler ultrasonic air bubble detection and aspiration through a previously inserted right atrial catheter are critical factors in the diagnosis and treatment of this condition.


Basiparallel cut by pneumoencephalotomography and cerebellar atrophy. The basiparallel cut is a nearly horizontal slice of the posterior fossa used in air study and the structures are observed on a plane parallel to the clivus. Total shrinkage of the cerebellum, with or without fourth ventricle dilatation, was found in cases of olivopontocerebellar atrophy, some intoxications, and a few senile subjects. Some atrophy of paleocerebellar portions was seen in Holmes-type degeneration. Another pattern was symmetric shrinkage of neocerebellar lobules and relatively specific for the cases of 'multiple system atrophy' such as progressive supranuclear palsy, striatonigral degeneration, Marie's ataxia, etc. Loss of the superior cerebellar peduncle was clearly demonstrated in this view.


The CT scan appearance of the brain in the normal elderly population: a correlative study. Atrophy of the brain as depicted on CT scan was correlated with social and psychological testing in 100 selected volunteers with no known neurologic or psychiatric impairment. The data indicated cognitive impairment based on psychometric test results in those with atrophy, independent of its severity. No organic or biochemical changes could be found that could explain these findings. Repeat examinations at 1-year intervals are planned to evaluate the evolution of these findings.


Cerebellar atrophy: the differential diagnosis by computerized tomography. Seven patients with cerebellar atrophy were studied by computerized tomography. The radiographic findings were varied. They included enlargement of the lateral cisterns, loss of superior cerebellar vermian substance with prominence of the superior cerebellar cisterns, and fourth ventricle enlargements. The patterns of posterior fossa atrophy may suggest the etiology.


The evaluation of occipital lobe atrophy by computerized tomography before consideration of vertebral artery reconstructive surgery. Occipital lobe atrophy can be identified on CT. In a review of 90 selected cases with brain ischemia symptoms, 45 cases were found to have hindbrain ischemia with symptoms of vertigo and/or 'blurred vision.' Ten cases (22%) had normal CT studies and 35 cases (78%) had abnormal CT studies. The CT brain scan of the cerebellum and occipital lobes has a place in determining whether a patient with clinical hindbrain ischemia is a candidate for angiography and vertebral artery bypass surgery.


Computed tomography in meningitis.

Computed tomography in meningitis. Computed tomography in 34 cases of meningitis has revealed a spectrum of findings. In acute cases these include enlargement of the subarachnoid spaces, generalized contrast enhancement of the meninges and ependyma, sterile and pyogenic subdural collections, cortical infarction, and cerebral necrosis.


A statistical method for determining the proportions of gray matter, white matter, and CSF using computed tomography. The brain may be considered as a collection of volume elements (voxels) containing unknown proportions of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). If one assumes that (1) the attenuation coefficients for voxels with the same proportions of GM, WM, and CSF follow a Gaussian distribution whose mean is a weighted average of the mean attenuation coefficients of pure GM, WM, and CSF and (2) the voxel-to-voxel variation in proportion follows a Dirichlet probability distribution, then the overall proportions of GM, WM, and CSF can be calculated by optimizing the parameters of a compound Dirichlet-Gaussian distribution. This approach permits a quantitative analysis of the compartmental composition of the brain and may be useful in the evaluation of patients with cerebral edema, hydrocephalus, and leukoencephalopathy.


Cerebrovascular Doppler examination and cerebral angiography--alternative or complementary? Obstructions in the extracranial cerebral arteries can be detected noninvasively by directional Doppler ultrasound technique using 'indirect' and 'direct' criteria. The indirect criteria are based on measurement of flow in the common carotid and in the terminal branches of the ophthalmic artery before and after the common carotid artery and branches of the external carotid artery are compressed. With the direct criteria, internal and external carotid artery are differentiated by diastolic flow, and local inhomogenetics of flow (turbulence) are detected. Flow in the vertebral artery is picked up transorally in the oropharynx. The Doppler examination was used in 2230 patients of whom 436 underwent angiography. The results of Doppler and angiography correlated in more than 90% of the cases.


Doppler ultrasound evaluation of extracranial cerebrovascular disease. Carotid Doppler examination was compared with arteriographic findings in 125 patients. The results demonstrated exact correlation in 87% of vessels studied. Clinically significant errors occurred at a rate of 4.5%. Clinically insignificant errors (8.5%) were usually the result of wall disease being mistaken for nonhemodynamically significant stenosis.


Intracranial aneurysms in geriatric patients: angiographic features and angioautotomographic analyses. The angiographic investigation of intracranial aneurysms in geriatric patients was made by conventional cerebral angiography and angioautomography. Analyses were based on 49 aneurysms in 38 patients aged over 60 who had 24 (49.0%) large aneurysms of maximum diameter over 100 mm. This contrasted strongly with the aneurysms of patients aged under 60, only 14.4% of which were large. Cerebral angioautotomography had a particular diagnostic value for such large aneurysms, revealing not only the stalks and the whole shapes of aneurysms, but also the normal parent arteries which were hidden on conventional cerebral angiography.


The clival-perpendicular or modified Water's view in compound tomography. The air gap type of CT scanner with tilting gantry allows the use of head positions other than the standard semi-axial. The modified Water's or clival-perpendicular position is especially useful in the diagnosis of posterior fossa disease. The position offers a view that is approximately coronal to the clivus and tentorium. The clival-perpendicular view easily separates the supra- and infratentorial compartments. It also helps to differentiate extra- and intra-axial lesions and to locate the fourth ventricle, and it gives far better vertical orientation of posterior fossa pathology.


An angiographic study of brain swelling in cerebral infarction. In order to assess the characteristics of brain swelling due to infarction, 322 angiograms in patients with cerebral infarction have been reviewed. The rate of incidence of swelling related to time from onset, sequential angiographic changes, and factors contributing to the phenomenon are presented. Some clinical and differential diagnostic aspects are discussed.


The diagnosis of cerebral atrophy on the basis of cerebral angiogram. An increased distance between brain surface, represented by the terminal arterial branches, and skull causes the appearance of a broad avascular band in the carotid angiogram, which--apart from other criteria--has been valued as a sign of cerebral atrophy. We investigated 54 patients (ages 60-79 years) suffering from cerebrovascular disease. Carotid angiographies of the afflicted hemispheres were carried out within 4 to 90 days after the stroke. The distance between vessels and skull was measured in frontal and lateral projection. We evaluated statistically the impact on this distance of alterations in extracranial vessel walls, number of attacks, severity of stroke, and patient's age. The results are compared to those of CAT. Only limited correlations have been found between the above-mentioned parameters and the distance between vessels and skull. Thus the distance is only of limited diagnostic value for the verification of senile cerebral atrophy on a vascular basis.


Comparative study of intracranial aneurysms in advanced age. A correlative angiographic and clinical analysis of 108 intracranial subdural aneurysms in patients from 60 to 84 years of age is presented. Angiographically defined spasm was present in about 54% of the cases. Spasm grades I and II had no apparent influence on clinical course, and grades III and IV were in some instances associated with arterial occlusion and infarction. There was no clear evidence that the spasm was related to hypertension, and no relationship could be established between preoperative and postoperative spasm. Atherosclerotic alterations in some cases were combined with a persistent narrowing of the arterial lumen.


Evaluation of cerebral infarction by computed tomography with special emphasis on microinfarction. Computed tomography has proved to be the most effective mode of evaluating cerebral infarction in 143 documented cases. This was especially true when multiple focal infarcts were present. The incidence of contrast enhancement in acute infarcts was 88%. Concomitant acute and old infarcts were observed in 20% of cases. In the acute stage of stroke, radionuclide studies are preferable to contrast angiography since the latter may aggravate the pre-existing focal ischemia. Follow-up CT and radionuclide scans were extremely useful in confirming the diagnosis and demonstrating various postinfarction sequelae.


Classification of hypertensive intracerebral hemorrhage by means of computed tomography. This classification concerns the size and site of the intracerebral hematoma and the existence and degree of the intraventricular hemorrhage examined in 144 cases, with regard to the prognosis quod vitam et functionem.


Comparative study of computed tomography (CT) and carotid angiography (CAG) in stroke patients. The findings in CT and CAG were compared in 173 stroke patients to evaluate dependability in the localization of cerebral arterial occlusion and of infarction by CT, and to test the reliability of the angiographic and clinical diagnosis of a space-occupying lesion in patients diagnosed clinically as stroke cases.


[Topographic correlation of angiographic and CT findings in cerebrovascular disease (author's transl)]. Problems of correlating ischemic lesions of the brain with the cerebral vessel involved originate in the axial scanning direction. It is almost impossible to line out precisely the borders of the cerebral lobes--far less are we able to describe exactly the areas supplied by the cortical branches of the anterior or middle cerebral artery. Using a method based on detailed perception of the base of the skull and physiological calculations, it is possible to reconstruct the individual baseline of the scan and to project the outlines of the slices upon the lateral view of the angiogram. Thereby a reliable topographical association between CT findings and angiogram is given.


CT and arteriography in cerebral ischemia. A preliminary note. Sixty patients with cerebral ischemia were studied by both CT and angiography. The results are: 1. Thrombosis of the internal carotid artery: CT shows a hypodensity lateral to the frontal horn. 2. Thrombosis of the middle cerebral artery: the hypodensity occupies the convexity of the frontal, parietal, and temporal lobes. 3. In thrombosis of the posterior cerebral artery there is an occipital hypodensity, while in thrombosis of the vertebral artery the hypodensity occupies a cerebellar hemisphere. 4. Circulatory disturbances without occlusion of the major cerebral vessels: there is a disproportion between the serious CT lesion and paucity of the angiographic findings.