Instructional objectives for a teaching program in cancer for primary care physicians. Precise instructional objectives are critical to the success of educational programs in medicine. Adequate attention to the development of instructional objectives prompts careful consideration of course methods, helps define means of evaluation, and results in realistic long-term goals. Current curricula often focus on the teaching of facts and the diagnosis and treatment of advanced and uncommon diseases; behavioral science skills are rarely taught and, in general, content is unrelated to the kinds of problems physicians see in practice. This paper presents instructional objectives in cancer which attempt to answer these criticisms. The objectives, covering cognitive, psychomotor, and affective domains, emphasize the areas of prevention and early diagnosis.


Internal review--a fruitful family practice evaluation tool. In 1975 the Department of Family and Community Medicine, University of Toronto, initiated a system of internal review of its undergraduate and postgraduate programs. During the next six months each of the major teaching resources for the family practice component of the programs was visited by an inspection team. A detailed report with recommendations was prepared and received wide distribution. After this initial review, the internal medicine and pediatric components of the curriculum were evaluated. Again reports and recommendations were made. At the present time the surgical and psychiatric components of the program are being evaluated. This ongoing internal review has had several benefits including specific changes in programs, better organization, and a better understanding of the department and its goals. Some of the difficulties are the time and organization necessary for a valid and appropriate review.


Optimal hierarchy as a means of increasing the flexibility of a morbidity classification system. Established systems of problem or morbidity classification do not always meet special needs for higher levels of specificity in coding. Optional hierarchy is a mechanism that may be employed to achieve the desired specificity for local use while permitting recombination into parent rubrics for external comparisons. Optional hierarchy may be employed to develop subdivision rubrics when justified by the high incidence of specific problems, whether due to geographic or social circumstances or because of the special nature of individual practice(s). It may also be used to meet the sometimes esoteric needs of the researcher, the unique needs of the teacher, or the preferential needs of other individual recorders. While the development of subdivision rubrics is simple, care is required to avoid pitfalls in reversion to the parent rubric. Failure to ensure the accuracy of this reversion can destroy a fundamental purpose of morbidity classification--the intercenter comparison of data. Although this paper discusses the application of optional hierarchy to the International Classification of Health Problems in Primary Care (ICHPPC), it is equally useful in other systems of classification.


The dying child and the family.

The dying child and the family. The physician involved in the care of a child with a fatal disease has an obligation not only to give the best possible medical care to the child but also to provide emotional support and guidance for the family and the patient. Many emotional problems can be resolved or prevented by discussions with the parents and by encouraging them to express their anxieties and questions. The death of a child is the ultimate tragedy, and everything should be done to prevent further problems which add to the anguish the parents must endure. Support of the parents begins when the diagnosis is first presented, must be continued throughout the child's course, and should often extend beyond the death of the child. Understanding the child's reactions to death is important and helps the physician respond appropriately to the child's questions. Some older children wish to discuss their disease with the physician and in such cases their questions should be answered honestly, while at the same time offering hope.


Regenerative ability of double-half and half upper arms in the newt, Notophthalmus viridescens. The upper arms of adult newts (Notophthalmus viridescens) were surgically manipulated to create double-half dorsal, double-half ventral, double-half anterior, and double-half posterior upper arms, and longitudinal half-dorsal, half-ventral, half-anterior, and half-posterior upper arms. Amputation through the double-half upper arms usually failed to elicit normal distal regeneration, despite the fact that an apparently normal regeneration blastema was initially formed. Instead, regeneration in these cases was limited to the formation of a variable number of small cartilage elements. On the basis of these results it is concluded that a complete limb circumference is required for distal transformation in newts, in addition to the well-established requirements for a wound epidermis, adequate innervation and dedifferentiation leading to blastema formation. A model for the sequential generation of new parts of the limb pattern during distal transformation from a complete circumference is presented. This model can also account for the occurrence of normal early stages of regeneration in double-half upper arms. Half upper arms which were amputated immediately were shown to develop single, complete regenerates. If amputation of half upper arms was delayed three or more weeks to permit complete wound healing, a supernumerary limb from the lateral wound surface sometimes developed in addition to a complete, single limb from the distal amputation surface.


The failure of double-half forelimbs to undergo distal transformation following amputation in the axolotl, Ambystoma mexicanum. Although capable of initiating early regenerative responses, axolotl forelimb stumps which are composed of double-half limb tissues fail to undergo the events that normally lead to the replacement of missing parts. In the present study, the posterior halves of right forelimbs were exchanged with the anterior halves of left forelimbs, or the dorsal halves of right forelimbs were exchanged with the ventral halves of left forelimbs. Forelimbs were amputated through the graft region 30 days after grafting. Limb stumps bearing double-dorsal, double-ventral or double-posterior tissues either produced hypomorphic regenerates or failed to form any externally visible outgrowth. When the limb stump bore double-anterior tissues, no externally visible structures were formed. Normal and multiple regenerates were never formed by double-half limbs. These results are discussed in terms of the polar coordinate model and suggest that the regeneration blastema requires a complete circumference of positional values in order to complete distal transformation.


Timing of sperm transport, sperm penetration and cleavage in the rat. Times of sperm entry into the oviduct from the uterus, into the ampulla from the isthmus; of sperm penetration into oocytes, and of cleavage, were determined using three mating regions. Time intervals and their errors of estimation were calculated. Spermatozoa were first found in the isthmus of the oviduct no earlier than 15 minutes after coitus, but required four hours to ascend the oviduct to the ampulla. The rate of sperm arrival was equal to the rate of sperm penetration, i.e., about 3 sperms/hour. Time of cleavage in vivo was 20.6 hours after sperm penetration in ad libitum mated animals. In culture, oocytes cleaved at exactly the same time as in vivo. Delaying sperm arrival to the site of fertilization (by delaying mating) shortened the time interval between median time of sperm penetration and median time of cleavage. It was concluded that the time of cleavage of the oocyte reflects primarily the time of sperm penetration, but is also influenced by the postovulatory age of the oocyte.


Mammalian pyruvate kinase hybrid isozymes: tissue distribution and physiological significance. The purpose of this study was to examine the pyruvate kinase isozymic patterns of a wide variety of tissues from rats and mice, particularly regarding hybrid isozymes. For these studies, we employed longer electrophoresis times than used in most earlier studies in order to improve the resolution of closely spaced bands. The tissue distributions of types K, L, and M pyruvate kinases were found to be approximately the same as those reported earlier for rats and other mammals. In addition, K-M hybrids could be detected in most tissues examined in relative quantities which differed from one tissue to another in the same organism, in corresponding tissues from different species, and within a single tissue during development. Hybrid isozymes containing type L subunits occur in only a few tissues of either the fetus or the adult of either animal. In earlier studies utilizing L-M hybrid isozymes produced in vitro, we showed that the kinetic properties of a given subunit are profoundly affected by the nature of its neighbors within the tetramer (Dyson and Cardenas, ['73] J. Biol. Chem., 248: 8482-8488). Based on these altered kinetic properties, we suggest that there is little need for anorganism to suppress completely the gene activity for one subunit type of pyruvate kinase during the synthesis of larger quantities of a second subunit type.


A large-scale laboratory maintenance system for gravid purple sea urchins (Strongylocentrotus purpuratus). A large-scale laboratory facility for the maintenance of several thousand gravid sea urchins (S. purpuratus) is described. Gametes of this species provide an important research resource for studies of animal development. Methods are described for culturing adult S. purpuratus for periods up to two years or more with almost no mortality after the first three to four weeks following collection. Adult females can be maintained in a fertile state in the culture system for four to six months. When spawned, gravid females living in the culture facility will routinely regenerate normal sized populations of fertile oocytes at 1 to 2-month intervals. Such females can be used repeatedly as a source of mature gametes for laboratory research. The reproductive performance of these females can be predicted approximately by the number of late vitellogenic oocytes present in their ovaries. After several months the pool of these oocytes is exhausted and no further mature oocytes can be found for a long period. We show, however, that such females are able to carry out a complete annual cycle of oogenesis if held for a long enough period of time in the culture system.


In vitro analysis of pre- and early postimplantation development of lethal yellow (Ay/Ay) mouse embryos. Preimplantation embryos from matings between yellow heterozygous (Ay/a) mice were recovered at 56 hours post coitum, cultured for five days, and compared with the development of embryos from three control matings (Ay/a female X a/a male, a/a female X Ay/a male, a/a female X a/a male). Most embryos were at the 8-cell stage at recovery; however fewer embryos from the experimental cross had developed to the 8-cell stage than embryos of control matings, indicating a developmental lag of experimental embryos (P less than 0.01). The yellow (Ay/a) uterus did not contribute (P = 0.05) to delayed development. Experimental and control embryos were equally capable of successful development in culture to the morula stage with no distinct morphological characteristics identifying the class of Ay/Ay mutants. However, significant differences were observed in the development from morulae to blastocysts; 9.4% (10/106) of the morulae in experimental crosses failed to undergo blastocyst formation as compared with 2.5% (10/398) of morulae in pooled control crosses (P = 0.010-0.025). In the experimental cross 25.0% (24/96) of embryos that developed successfully to the blastocyst stage failed to hatch from the zona pellucida; these are presumed to include the class of lethal yellow homozygotes. Abnormalities seen in cultured embryos consisted primarily of blastomere disintegration, blastomere arrest and exclusion, and embryo fragmentation.


Studies on oocyte maturation of the medaka, Oryzias latipes. V. On the structure of steroids that induce maturation in vitro. The response of oocytes within isolated follicles (800-950 micron in diameter) to various steroids was examined with the teleost fish, Oryzias latipes. Continuous exposure of oocytes, which were removed from ovarian investments 17 hours before predicted germinal vesicle breakdown (GVBD), to C19- or C21-steroids brought about maturation in vitro but never triggered ovulation. The steroids effective in inducing maturation have in common a C=0 (or alpha-OH) group at 3C and a beta-OH group at 17C in the C19-steroids, and a C=O (or beta-OH) group at 3C and a C=O (or alpha-OH) group at 20C in the C21-steroids, in addition to an delta4- or delta5-unsaturated for 5alpha-saturated configuration. The orientation of the hydrogen at 5C seems to be critical in determining the ability of a particular steroid to stimulate oocyte maturation. Maturation of oocytes in the ovaries of hypophysectomized females was induced by administering progesterone, but the mature oocytes did not subsequently undergo ovulation. Thus the steroid hormone is capable of inducing oocyte maturation but apparently does not participate directly in the ovulation of Oryzias latipes oocytes.


Induced formation of asters and cleavage furrows in oocytes of Xenopus laevis during in vitro maturation. We have previously reported that injection of purified basal bodies or sperm into unfertilized eggs of Xenopus laevis induced the formation of asters and irregular cleavage furrows. Fully grown oocytes were found to be unable to form asters or cleavage furrows. In this paper we show that the oocyte acquires the ability to form asters upon basal body injection at the time of germinal vesicle breakdown during in vitro maturation. Our evidence indicates that aster formation requires progesterone-stimulated changes in the oocyte and mixing of cytoplasm and germinal vesicle plasm. The ability of the oocyte to form cleavage furrows arises six to eight hours after germinal vesicle breakdown. We infer that some maturational change in the cell cortex occurs to enable the egg surface to furrow. Experiments on the relationship of aster formation to furrow initiation indicates that asters stimulate furrow formation. However, some furrowing could be induced without aster formation in mature oocytes and unfertilized eggs by an activation stimulus, showing that asters are not essential for cleavage initiation. The significance of these observations are discussed in the light of our current understanding of meiotic maturation, cell cleavage and aster growth.


Selective incorporation of selenium-75 into a polypeptide of the rat sperm tail (1). Selenium is necessary for normal sperm tail development in the rat. The biochemical locus of this requirement was investigated by intratesticular administration of (75Se)SeO3-2. Sperm were labeled primarily in tail keratin, a disulfide-stabilized fraction obtained by extracting isolated tails with sodium dodecyl sulfate (SDS). By incubation in 1% SDS-0.2 mM dithiothreitol, followed by sonication and centrifugation, the 75Se was separated from a residue rich in S and Zn, composed of dense fibers and connecting pieces. The extracted 75Se-labeled material was non-dialyzable, sensitive to pronase, retained most of its bound isotope following carboxymethylation, and displayed only one radioactive component, of 17,000 daltons, during SDS-polyacrylamide gel electrophoresis. It is suggested that the labeled moiety is a selenopolypeptide whose function is critical for normal assembly of the sperm tail.


Visual pigment and photoreceptor sensitivity in the isolated skate retina. Photoreceptor potentials were recorded extracellularly from the aspartate-treated, isolated retina of the skate (Raja oscellata and R. erinacea), and the effects of externally applied retinal were studied both electrophysiologically and spectrophotometrically. In the absence of applied retinal, strong light adaptation leads to an irreversible depletion of rhodopsin and a sustained elevation of receptor threshold. For example, after the bleaching of 60% of the rhodopsin initially present in dark-adapted receptors, the threshold of the receptor response stabilizes at a level about 3 log units above the dark-adapted value. The application of 11-cis retinal to strongly light-adapted photoreceptors induces both a rapid, substantial lowering of receptor threshold and a shift of the entire intensity-response curve toward greater sensitivity. Exogenous 11-cis retinal also promotes the formation of rhodopsin in bleached photoreceptors with a time-course similar to that of the sensitization measured electrophysiologically. All-trans and 13-cis retinal, when applied to strongly light-adapted receptors, fail to promote either an increase in receptor sensitivity or the formation of significant amounts of light-sensitive pigment within the receptors. However, 9-cis retinal isin. These findings provide strong evidence that the regeneration of visual pigment in the photoreceptors directly regulates the process of photochemical dark adaptation.


The influence of external cations and membrane potential on Ca-activated Na efflux in Myxicola giant axons. In microinjected Myxicola giant axons with elevated [Na]i, Na efflux was sensitive to Cao under some conditions. In Li seawater, sensitivity to Cao was high whereas in Na seawater, sensitivity to Cao was observed only upon elevation of [Ca]o above the normal value. In choline seawater, the sensitivity of Na efflux to Cao was less than that observed in Li seawater whereas Mg seawater failed to support any detectable Cao-sensitive Na efflux. Addition of Na to Li seawater was inhibitory to Cao-sensitive Na efflux, the extent of inhibition increasing with rising values of [Na]o. The presence of 20 mM K in Li seawater resulted in about a threefold increase in the Cao-activated Na efflux. Experiments in which the membrane potential, Vm, was varied or held constant when [K]o was changed showed that the augmentation of Ca-activated Na efflux by Ko was not due to changes in Vm but resulted from a direct action of K on activation by Ca. The same experimental conditions that favored a large component of Cao-activated Na efflux also caused a large increase in Ca influx. Measurements of Ca influx in the presence of 20 mM K and comparison with values of Ca-activated Na efflux suggest that the Na:Ca coupling ratio may be altered by increasing external [K]o. Overall, the results suggest that the Cao-activated Na efflux in Myxicola giant axons requires the presence of an external monovalent cation and that the order of effectiveness at a total monovalent cation concentration of 430 mM is K + Li greater than Li greater than Choline greater than Na.


Contractile activation phenomena in voltage-clamped barnacle muscle fiber. Tension development in voltage-clamped barnacle muscle fibers occurs with depolarizing pulses so small as not to activate the potassium and calcium conductance systems. Peak tension and the tension time integral appear to be graded by both amplitude and duration of the depolarizing pulses. Subthreshold depolarizing conditioning pulses shorter than 500 ms potentiate the response to a given test pulse. This effect diminishes and reverts when the duration of the conditioning pulse is increasingly prolonged. The relationship between fiber membrane potential and tension developed in response to depolarizing pulses is described by an S-shaped curve. The tension saturates at a membrane potential of about +10 mV (inside positive). For a given pulse duration the saturation value remains constant even when the fiber interior reaches a value of +230 mV, which is well above what may be estimated to be the equilibrium potential of calcium ions (Eca = +120). In the presence of 5 mM external procaine, the shape of the tension-potential curve changes; the maximum value tension besides being diminished is not sustained by falls when the potential approaches the estimated value for Eca. These results suggest that under physiological conditions the contractile activator is probably released from an internal store, and that the calcium entering the fiber as inward current does not play a direct major role in contractile activation.


Properties of internally perfused, voltage-clamped, isolated nerve cell bodies. The membrane properties of isolated neurons from Helix aspersa were examined by using a new suction pipette method. The method combines internal perfusion with voltage clamp of nerve cell bodies separated from their axons. Pretreatment with enzymes such as trypsin that alter membrane function is not required. A platinized platinum wire which ruptures the soma membrane allows low resistance access directly to the cell's interior improving the time resolution under voltage clamp by two orders of magnitude. The shunt resistance of the suction pipette was 10-50 times the neuronal membrane resistance, and the series resistance of the system, which was largely due to the tip diameter, was about 10(5) omega. However, the peak clamp currents were only about 20 nA for a 60-mV voltage step so that measurements of membrane voltage were accurate to within at least 3%. Spatial control of voltage was achieved only after somal separation, and nerve cell bodies isolated in this way do not generate all-or-none action potentials. Measurements of membrane potential, membrane resistance, and membrane time constant are equivalent to those obtained using intracellular micropipettes, the customary method. With the axon attached, comparable all-or-none action potentials were also measured by either method. Complete exchange of Cs+ for K+ was accomplished by internal perfusion and allowed K+ currents to be blocked. Na+ currents could then be blocked by TTX or suppressed by Tris-substituted snail Ringer solution. Ca2+ currents could be blocked using Ni2+ and other divalent cations as well as organic Ca2+ blockers. The most favorable intracellular anion was aspartate-, and the sequence of favorability was inverted from that found in squid axon.


The calcium current of Helix neuron.

The calcium current of Helix neuron. Calcium current, Ica, was studied in isolated nerve cell bodies of Helix aspersa after suppression of Na+ and K+ currents. The suction pipette method described in the preceding paper was used. Ica rises to a peak value and then subsides exponentially and has a null potential of 150 mV or more and a relationship with [Ca2+]o that is hyperbolic over a small range of [Ca2+]o's. When [Ca2+]i is increased, Ica is reduced disproportionately, but the effect is not hyperbolic. Ica is blocked by extracellular Ni2+, La3+, Cd2+, and Co2+ and is greater when Ba2+ and Sr2+ carry the current. Saturation and blockage are described by a Langmuir adsorption relationship similar to that found in Balanus. Thus, the calcium conductance probably contains a site which binds the ions referred to. The site also appears to be voltage-dependent. Activation and inactivation of Ica are described by first order kinetics, and there is evidence that the processes are coupled. For example, inactivation is delayed slightly in its onset and tau inactivation depends upon the method of study. However, the currents are described equally well by either a noncoupled Hodgkin-Huxley mh scheme or a coupled reaction. Facilitation of Ica by prepulses was not observed. For times up to 50 ms, currents even at small depolarizations were accounted for by suitable adjustment of the activation and inactivation rate constants.


Studies on the mechanisms of vaccinia virus cytopathic effects. II. Early cell rounding is associated with virus polypeptide synthesis. Vaccinia virus-induced morphological lesions were studied in LLC-MK2, HeLa and L cells. In LLC-MK2 cells, cell rounding occurs within 30 to 60 min after infection with 300, 900 or 2700 particles/cell and the time of appearance of these changes is dependent on the multiplicity of infection (m.o.i.). When cycloheximide (300 microgram/ml) is added to cultures at the time of infection, early cell rounding is prevented regardless of the m.o.i. However, cell rounding does occur when cycloheximide is removed, and its time of appearance and extent depends upon the time of removal of the compound and the m.o.i. Upon removal of cycloheximide at I or 2 h after infection early cell rounding occurs, and virus polypeptide synthesis is evident in cells infected at all three multiplicities. However, when the drug is removed at 4 hr after infection, cell rounding and virus polypeptide synthesis occur only in cultures infected at 300 particles/cell. Early morphological changes are also prevented in HeLa and L cells infected at 300 particles/cell in the presence of cycloheximide. These changes occur only if the compound is removed up to 2 h after infection in HeLa cells and up to 40 min after infection in L cells. Early morphological lesions are not seen if the compound is removed at later times. The occurrence of early morphological changes in HeLa and L cells is also correlated with the synthesis of virus polypeptides. All cell types, when infected at 2700 particles/cell in the presence of cycloheximide, or inhibitors of RNA synthesis, display cell fusion. Thus, whereas early morphological changes require virus protein synthesis to become manifest, cell fusion occurs in the absence of virus RNA or protein synthesis and may be mediated by a component of the virion.


DNA and histone synthesis in reovirus-infected cells. Reovirus infection inhibits the incorporation of 3H-thymidine into cellular DNA. We have now investigated several aspects of this inhibition in L-929 cells early (8 h) after infection at high multiplicity (200 to 250 p.f.u./cell). Using equilibrium sedimentation analysis of DNA sequentially labelled with density and radioactive analogues of thymidine, we find a 52% reduction in the amount of DNA synthesized with no change in rate of replication fork movement in infected cells. Gel electrophoresis of histones labelled with 3H-lysine shows that infection inhibits their synthesis by 76% several hours before overall cellular protein synthesis is inhibited. There is also a reduction of nearly 50% in the size of the thymidine triphosphate pool, as measured by enzymic assay. The proportion of exogenous nucleotide in the pool is the same as in uninfected cells since there is no change in the buoyant density of DNA labelled during a short pulse with 3H-bromodeoxyuridine. The uptake of thymidine is reduced, but its phosphorylation to thymidine triphosphate is normal. The findings provide direct evidence that DNA synthesis is inhibited early in infection. This inhibition is accompanied by other derangements of thymidine and chromatin metabolism suggesting that there is an early and specific attack by reovirus on nuclear function in infected cells.


Cleavage defect in the non-structural polyprotein of Semliki Forest virus has two separate effects on virus RNA synthesis. When Semliki Forest virus ts-4 mutant infected cultures are grown at the permissive temperature (28 degrees C) and shifted to the restrictive temperature (39 degrees C), two different defects in RNA synthesis are manifested: (i) the synthesis of 26S RNA is stopped within 60 min (Saraste et al. 1977) and (ii) the increase in RNA synthesizing activity ceases, in contrast to cultures maintained at 28 degrees C, indicating that no new active RNA polymerase is formed at 39 degrees C. Accumulation of a non-structural precursor protein with an apparent mol. wt. of about 220 000 (ns220) was demonstrated in ts-4 infected cultures shifted to 39 degrees C. NS220 was labelled during short pulses given immediately after release of protein synthesis from hypertonic initiation block, suggesting that genes coding for ns220 are located near the initiation site at the 5'-end of the 42S RNA. The viral specificity of ns220 was shown by its disappearance after a shift to 28 degrees C and by labelling in the presence of sucrose, when no host cell protein synthesis is detectable. The two functional defects can be explained if the polypeptides responsible for the RNA polymerizing activity and that responsible for the synthesis of 26S RNA are components of the same non-structural polyprotein. A mutation in the latter polypeptide which prevents cleavage of the polyprotein would thereby prevent the further formation of active RNA polymerase. If cleavage of the polyprotein has taken place at the permissive temperature, the RNA polymerase would remain active also at 39 degrees C, whereas the polypeptide responsible for 26S RNA synthesis would become inactive due to the mutation.


The sizes of RNA subunits isolated from high and low leukaemogenic Friend virus. The sizes of non-covalently linked RNA subunits isolated from highly leukaemogenic Friend virus derived from the plasma (PV, plasma virus) of leukaemic mice were compared to the RNA subunits isolated from low leukaemogenic Friend virus grown in tissue culture (TCV, tissue culture virus). Histograms derived from electron microscope measurements showed that about one-half of the plasma virus RNA was 1.4 to 2.5 micron in length, corresponding to a mol. wt. range from 1.8 X 10(6) to 3.2 X 10(6) and the other half less than 1.4 micron. In contrast, approx. 50% of the TCV RNA was only 0.7 to 1.6 micron in length (mol. wt. 0.9 X 10(6) to 2.0 X 10(6)) and the remainder less than 0.7 micron in length regardless of whether the virus RNA was isolated from 3, 9, 36 or 72 h cultures. The histograms suggest size classes for both TCV and PV derived RNA subunits. Data obtained from sucrose gradient sedimentation of heat-denatured FLV RNA agreed with the electron microscope length measurements. The smaller sizes of the TCV RNA subunits are hypothetically related to the limited biological activity of Friend leukaemia virus produced from leukaemic cells in culture. Comparable results were obtained using two different RNA extraction procedures. Contamination of TCV nucleic acid preparations by cellular DNA was observed even when the virions were harvested from short term cultures and purified by isopycnic sucrose gradient centrifugation. Consequently, preparations of intact virus were treated with DNase prior to sucrose gradient purification of the virions.


The genome of human coronavirus strain 229E. The genomic RNA of human coronavirus strain 229E (HCV 229E) migrated on polyacrylamide gels as a single peak with a mol. wt. of 5.8 X 10(6). Denaturation of the genome with formaldehyde did not alter its electrophoretic mobility, which suggests that the HCV 229E genome is a single-stranded molecule. At least 30% of the genomic RNA was shown to contain covalently attached polyadenylic acid [poly(A)]sequences by binding the RNA to an oligo(dT)-cellulose column. These poly(A) tracts were shown to be about 70 nucleotides in length by measuring the resistance to digestion of HCV 229E RNA with pancreatic and T1 RNases. Finally, the genomic RNA was shown to terminate at or near the 3'-terminus on the basis of its susceptibility to polynucleotide phosphorylase.


A classification of feline calicivirus isolates based on plaque morphology. Isolates of feline calicivirus (FCV) can be divided into four groups according to plaque size under an agar overlay. All isolates classified as minute plaque, along with certain other isolates, are sensitive to inhibitors present in agar.


Trait ambiguity and impression formation sufficiency tests of the meaning change model. Two experiments tested the meaning change model's prediction for the effect of trait ambiguity on impression formation. Participants were all college students, 43 males and 29 females in Experiment 1 and 20 males and 28 females in Experiment 2. Standard impression formation tasks were used. The results revealed greater context effects for high as compared to low ambiguous traits and greater influence on description ratings for low as compared to high ambigous traits, supporting the meaning change model. When ratings of descriptions and of individual traits were clearly separated, context effects were observed only for low ambiguous traits. The implications of this finding for meaning change and information integration models of impression formation are discussed


Autokinetic movement of an induced afterimage. Thirty-two female Ss participated in an experiment in which autokinetic movement (AKM) direction change frequency of an induced afterimage was assessed as a function of stimulus afterimage color (yellow or blue-green) and the presence or absence of eye strain. Afterimage color was found not to affect AKM frequency reports. However, eye strain significantly (p less than .002) affected such reports, with the fewest AKM direction changes reported when strain was present. These results were explained in terms of an error signal and noise analysis of AKM.


Negative and positive incentive contrast effects with saccharine versus sucrose. Forty male white rats received 19 sessions of bar press training with sucrose (16% or 4%) as reward followed by a shift from 4% to 16% and from 16% to 4%. Three dependent measures indicated positive and negative contrast effects. In Experiment II, 70 male white rats received 14 sessions of bar press training with (1.2%, 1%, .10%, or .01%) saccharine, and water followed by a shift from 1.2% to .10%, 1.2% to .01%, 1 to .1%, and .10% to .01%. Three of the four measures indicated negative contrast effects. In Experiment III, 40 male white rats experienced 16 sessions of bar press training with 1%, .10%, .05%, or .01% of saccharine followed by an increase from .1%, to 1%, .05% to 1%, and .01% to 1%. Three of the measures indicated positive contrast effects. Confounding inherent in the use of solid food or sucrose did not appear to account for negative and positive incentive contrast effects.


Spontaneous recovery in rabbit eyelid conditioning. Spontaneous recovery of the classically conditioned rabbit eyelid response increased in a negatively accelerated function with an increase of postextinction rest from .17 to 24 hr. The data were obtained from six groups of male New Zealand rabbits which received an extinction session separated by rest intervals of varying duration from a spontaneous recovery test.


Intensity of motion sickness symptoms as a function of apparent autonomic balance. Twenty volunteer male college students were exposed to motion picture films which reliably elicit symptoms of motion sickness. Those Ss with relatively higher apparent sympathetic nervous system dominance showed significantly smaller autonomic reactions to the film. It was concluded that increased sympathetic tone tended to the film. It was concluded that increased sympathetic tone tended to reduce autonomic reactions to motion sickness stimuli. It was suggested that the sympathetic nervous system symptoms that usually occur in motion sickness are actually defensive reactions rather than symptoms of nausea.


Using neuropsychological and personality tests to assess the likelihood of patient employment. This study assessed the ability deficits and personality disturbances associated with three levels of employment in patients referred for neuropsychological testing. Highly significant group differences were found, with the unemployed group consistently showing greatest pathology on the tests, the full time employed group performing relatively normally, and the part time employed group earning intermediate scores. A discriminant function which used both neuropsychological and personality measures was found to discriminate unemployed from full time employed patients satisfactorily. Classification rates achieved by the function for validation and cross-validation samples support its clinical utility in identifying new patients who are at high risk for unemployment. It appears that psychological tests commonly used in neurological and psychiatric diagnosis can also help predict some aspects of patients' abilities to function in everyday life.


The relationships of some information-processing factors to severely disturbed behavior. Thirty-five psychiatric inpatients with heterogeneous diagnoses were given four tasks: Mueller-Lyer Illusion, Wisconsin Card Sorting Text, Object Sorting, and Rokeach dogmatism questionnaire. Tasks were chosen to represent a broad sampling of paradigms, spanning levels of information processing, involving perceptual, conceptual and attitudinal processes. Subjects' behavior was assessed by the Inpatient Multidimensional Psychiatric Scale (IMPS). Each IMPS scale was analyzed in turn as a function of perceptual/cognitive variables, in multiple regression analysis. To provide basis for comparison, traditional clinical measures were included as independent variables (MMPI scales) and dependent variables (intelligence, chronicity, and premorbid adjustment). Results showed that different patterns of disordered behavior were predicted by different perceptual/cognitive variables. MMPI scores were predicted primarily by traditional measures. Interrelationships of all variables suggested three subject groups: chronic, process-type schizophrenics with perceptual abnormalities, paranoid patients with conceptual abnormalities, and affectively disordered patients with predominantly attitudinal abnormalities.


Self-destructive behavior on an inpatient ward. Suicidal and self-destructive behavior on a psychiatric inpatient service are said to be related to the degree of staff demoralization and dissension. Staff factors that may permit or encourage self-destructive acts include poor communications, staff disagreements, scapegoating of patients, poor staff judgment, staff self-preoccupation, and reversal of staff-patient roles. However, it is also possible that a major contributory factor is not individual patient or staff psychopathology, but rather the destruction of the underlying traditions and values of the ward which occurs at times of major change. The thesis is presented that the ritualization of ward values, when operative, provides a coherent world-view which renders the therapeutic activities, and life itself, meaningful, and that such ritualization can provide a framework of stability in times of critical staff turnover. Without such tradition and ritualization, however, therapeutic activities become hollow and meaningless, and fail to provide self-destructive patients a reason to view their life more positively.


Soft neurological correlates of compulsive eaters. Thirty patients with the syndrome of episodic compulsive eating (binge eaters) were given a neurophysiological evaluation which included a complete electroencephalogram (EEG) and a structured interview. The interview was designed to elicit 10 "neurological soft signs" (rage attacks, frequent headaches, dizziness, stomach aches, nausea, parethesias, history of convulsions, perceptual disturbances, other compulsions, and a family history of epilepsy). Afterwards, 23 patients received an adequate trial with phenytoin. The sum of the 10 neurological soft signs and the EEG (as an 11th sign) was significantly correlated with improvement. No single sign or other combination of signs was significantly a predictor of improvement. These results lend support to the thesis that in some episodic compulsive eaters, a neurophysiological substrate may be involved.


Telephone transmission of all-night polysomnographic data from subjects' homes. All-night sleep recordings, essential for obtaining measurements of sleep and for diagnosing various sleep disorders, have been restricted primarily to laboratory settings. Described here is a system to complete all-night-sleep recordings in subjects' homes. Eight electroencephalogram channels can be fed into a portable transmitter (which contains a preamplifier and frequency modulator), and transmitted over telephone lines to a receiving polygraph at a remote laboratory. No polygraph is required at the transmission site. Evidence of good signal quality is presented. The clinical and research implications of this methodology are discussed.


Perphenazine-induced systemic lupus erythematosus-like syndrome. A small number of cases have been presented in the world literature in which treatment with phenothiazines resulted in clinical and laboratory manifestations of systemic lupus erythematosus (SLE). The clinical picture of such patients tends to be "symptom poor". A 26-year-old patient is presented who had a 7-year history of treatment for a schizophrenic illness and developed clinical as well as laboratory evidence for SLE. The differential diagnosis included: a) phenothiazine-induced SLE; b) SLE presenting with psychosis as a symptom; and c) SLE and sychosis occurring independently. The patient had a complete medical and neuropsychiatric work-up and was followed for 12 months. This challenging diagnostic problem is discussed. Phenothiazine-induced SLE was the most likely diagnosis. Although the possibility of two diseases occurring independently in the same person did not explain the clinical and laboratory data, it is difficult to rule out this possibility completely. SLE presenting with psychosis as a symptom could be ruled out by the work-up and history.


Reversible mental symptoms in temporal arteritis. Mental symptoms are common in temporal arteritis. Reported here is a case in which a deficit in nonverbal memory documented with psychological testing resolved after a course of steroids. Besides the global confusional states commonly seen in temporal arteritis, focal intellectual impairment may be seen. It seems possible that some patients presenting with dementia as well as focal mental signs may have temporal arteritis. The diagnosis can easily be made by performing an erythrocyte sedimentation rate and temporal artery biopsy.


Conduction through demyelinated plaques in multiple sclerosis: computer simulations of facilitation by short internodes. Clinical and laboratory observations both suggest that it may be possible for action potentials to traverse, in a continuous manner and without interruption, demyelinated zones along some axons. This continuous mode of conduction requires the presence of sufficient numbers of sodium channels in the demyelinated region. One of the factors which will tend to prevent such conduction is the impedance mismatch at sites of focal demyelination, which may result in a reduction in current density sufficient to cause conduction failure. As  part of an effort to examine the conditions which would promote conduction into, and beyond, the demyelinated region, we examined, using computer simulations, the effects of reduction in length of the proximal internodes closest to the demyelinated region. Our results indicate that reduction in length of the two internodes closest to the demyelinated region. to approximately one-third of normal length or less, will facilitate conduction beyond the plaque. The results suggest that reductions in internode length, which have been histologically observed along some demyelinated fibres, may have functional significance in terms of facilitating conduction past focally demyelinated zones.


Analysis of heart rate variations in patients with multiple sclerosis. A simple measure of autonomic nervous disturbances using an ordinary ECG. A simple method requiring only an ordinary ECG apparatus and a ruler has shown a hitherto unknown abnormality of the autonomic nervous sysyem in patients with multiple sclerosis. The main findings were that both long-term and short-term variations in heart rate were reduced in patients wirh multiple sclerosis. The reduction was comparable with that observed in other patients with autonomic abnormalities-for example, long-term diabetics-but in addition patients with multiple sclerosis presented unexpected large shifts in pulse rate levels, lasting from a few to 10 or 20 beats.


Comparative simultaneous measurement of cerebrospinal fluid 5-hydroxyindoleacetic acid and blood serotonin levels in delirium tremens and clozapine-induced delirious reaction. Cerebrospinal fluid 5-hydroxyindoleacetic acid and total blood serotonin levels were measured simultaneously in 11 female patients with delirium tremens and nine schizophrenic women with clozapine-induced acute delirium. Both groups had significantly raised levels of 5HIAA in CSF and significantly reduced blood 5HT levels as compared with normal control subjects, symptom-free alcoholics, or clozapine-treated schizophrenics. The two delirious groups were not distinguishable from each other in respect of their CSF 5HIAA or blood 5HT values. After clinical recovery both values returned to normal levels.


Long-term effects of partial limb amputation in man. Ten patients with amputation of part of one arm have been studied electrophysiologically. In each patient the ulnar nerve was stimulated electrically in the amputation stump and at a corresponding level in the intact limb. Control observations were also made on 15 normal subject. In the partially-amputated (PA) limbs the amplitudes of the centripetal ulnar nerve compound action potentials, after maximal stimulation of fast-conducting fibres, were markedly reduced in comparison with the results in control limbs. A small decrease in the mean impulse conduction velocity was observed in the population of PA limbs. In comparison with control observations, stimulation of the ulnar nerve in a PA limb evoked responses in the contralateral somatosensory cortex which were significantly diminished. Simulation of PA limbs caused reflex excitation and inhibition of triceps motoneurones similar to that observed in control subjects. In the intact limbs of the amputees, however, inhibition was reduced, possibly as a consequence of overuse. It is concluded that the receipt of an input from the periphery is essential for the functional integrity of most motor and sensory nerve axons, and probably for fibres in the dorsal column-medial lemniscus pathway.


Surgical relief of progressive upper limb paralysis in Arnold-Chiari malformation. Two cases of delayed progressive paralysis of the upper limbs in an adult and a teenage patient, without neurological deficits in other regions of the body, are presented. In both cases, the pathology appeared to be a traction lesion of the middle cervical and lower cervical nerve roots, due to abnormal angulation of the nerve roots, which first ran up and then downward in the neural foramina and canal. Re-routing of the nerve roots by removing part of the floor of the neural canal, or by a facetectomy, appeared to offer extensive improvement or full recovery.


Median and ulnar nerve conduction determinations in the Erb's point--axilla segment in normal subjects. Twenty-one median and 22 ulnar nerves were tested in 12 patients for motor nerve conduction velocity (MNCV) and motor nerve conduction time (MNCT) in the segments from Erb's point (N) to axilla (A) bilaterally. It was found that on this segment for both nerves, MNCV values equal to or smaller than 51 m/s or conduction times equal to or longer than 4 ms are to be considered abnormal. For comparative studies and for checking the normality of the tested nerves in their entire length, the more distally located segments in the same nerve were also tested. For diagnostic purposes, the differences between right and left MNCV or MNCT values determined in the same person on N-A segments of homologous nerves were analysed. Motor nerve conduction velocity or MNCT determinations on the N-A nerve segment are expected to replace MNCV determinations on the longer N-AE (AE=100 mm above elbow) nerve segment, which is now in use, for diagnosis of the thoracic outlet syndrome.


Delayed visual evoked potentials with bilateral disease of the posterior visual pathway. A man of 51 years presented with sudden onset of a confusional state and marked visual deterioration. The computerised transaxial tomogram showed a mass in the corpus callosum which had spread to involve both cerebral hemispheres. The visual evoked potential to pattern stimulus was delayed by about 20 ms. Necropsy confirmed the presence of an astrocytoma of the corpus callosum involving the optic radiation and occipital cortex on both sides. The anterior visual pathway was normal.


Long-term recovery of visual reaction time after closed head injury. A follow-up study covering two years after a closed head injury was carried out on a group of 57 young males. Their reaction time was tested on both a simple and a four choice visual reaction task. The group was divided into three subgroups according to length of unconsciousness after the injury. Reaction time discriminated between subgroups, and a highly significant improvement during follow-up was shown. Choice reaction time discriminated better and continued to do so throughout the whole period of follow-up. Some relations of reaction time with clinical variables and outcome are discussed. The choice reaction in particular seems to have some value for monitoring recovery and predicting final outcome.


Stiff-man syndrome associated with nocturnal myoclonus and epilepsy. A case of stiff-man syndrome associated with primary generalised epilepsy is reported. In addition, nocturnal polygraphic recording revealed a nocturnal myoclonus. Detailed examination of the central nervous system did not show specific changes. There is no direct proof as to a spinal or supraspinal origin of the stiff-man syndrome. The absence of specific anatomical lesions may indicate a functional rather than a structural disturbance in its physiopathogenesis.


Phenytoin dosage in ambulant epileptic patients. Ambulant patients with recently diagnosed generalised or psychomotor seizure disorders or both were randomly assigned to two dosage regimens of phenytoin. Drug compliance was evaluated with subsequent blood phenytoin levels four to eight weeks after initial enrollment into the study. Although the two groups had similar mg-kg daily dosages of phenytoin, the mean blood levels were statistically different between the two groups, favoring the simplified dosage regimen. Once or twice a day dosage regimens of phenytoin had a beneficial effect on drug compliance when compared to more frequent regimens as measured by phenytoin blood levels.


Neurological involvement in the epidermal naevus syndrome. The case of a left handed girl aged 18 years suffering from the "epidermal maevus syndrome" is described. She presented with dysphasia, transient left hemiparesis, and sensory symptoms due to an occlusion of the right internal carotid artery. Arterial occlusion, abnormal retinal vessels, and Raynaud's phenomenon have not been previously documented. The neurological complications of this syndrome are discussed. It is suggested that the arterial occlusion may have been caused by a dysplastic artery.


Hemispheric asymmetries of affective processing as determined by the Minnesota Multiphasic Personality Inventory. Patients with left hemisphere disease have been noted to be depressed while those with right hemisphere disease appear indifferent. While patients with left hemisphere disease frequently have a greater cognitive deficit, patients with right hemisphere disease have difficulty in expressing affectively intoned speech. The Minnesota Multiphasic Personality Inventory (MMPI) can demonstrate underlying affective experience and is not dependent on affectively intoned speech. The purpose of this study was to determine whether a difference in affective moods, as assessed by the MMPI, was related to laterality of lesion in patients matched for severity of cognitive and motor dysfunction. Seven of the 16 subjects with left hemisphere dysfunction and none of the eight subjects with right hemisphere dysfunction showed an elevation on the depression scale. This observation not only confirms previous clinical observations but also demonstrates that these asymmetries cannot be ascribed completely to hemisphere-related differences in cognitive deficits or expressive abilities.


Cervical cord compression by solitary osteochondroma of the atlas. A 28 year old woman presented a syndrome of slow spinal compression evolving over four and a half years at the level C1--C2 vertebrae due to a solitary osteochondroma of the posterior arch of the atlas which was excised by laminectomy. Radiographys of the skeleton did not show the presence of other osteogenic tumours. This is the fifth case of solitary osteochondroma to be published. Elsewhere, in six cases out of 14, the vertebral lesion formed part of generalised exostoses.


Deformation of isolated neurofilaments and the pathogenesis of neurofibrillary pathology. Experimental structural alterations were studied in neurofilaments isolated from rat peripheral nerve. Structural alterations were induced in vitro by prolonged incubations of neurofilament-rich fractions in 0.1 M KCl prior to fixation and examination of neurofilaments by negative staining techniques. Neurofilaments appeared to retain their structural integrity during the first week of incubation. Subsequently, a progressive reduction in the numbers of intact neurofilaments coincided with the increasing appearance of neurofilamentous breakdown products. During the period of neurofilament breakdown, an increasing number of altered neurofilaments were observed. These abnormal neurofilaments were characterized primarily by axial enlargements with diameters frequently occurring in the 150-200 A range but measuring up to 250 A. Enlarged neurofilaments also showed a greater irregularity of their lateral margins and less ridigity in their linear course. A striking feature of enlarged neurofilaments was their tendency to display twisting deformations along their longitudinal axes. Twists occurred most frequently along neurofilaments of greatest diameter. The largest abnormal neurofilaments reveal multiple periodic twists, sometimes occurring at 800-1000 A intervals. These enlarged and twisted neurofilaments resembled the abnormal filaments described in neurofibrillary tangles and plaques. The demonstration of neurofilament plasticity as well as the resemblance of neurofilaments deformed in vitro to the abnormal filamentous structures of neurofibrillary tangles and plaques has led to the suggestion that the latter structures may be derived from alterations of normally-formed neurofilaments. Furthermore, it is proposed that the enlarged and twisted filaments of neurofibrillary pathology may arise from alterations in the turnover of neurofilaments or, more specifically, from deficiencies in the degradative processes by which these organelles are broken down.


Treatment of mouse muscular dystrophy with the protease inhibitor pepstatin. Dystrophic mice were treated for 5 weeks beginning at 3 weeks of age with 20 ugm per day of pepstatin, a potent inhibitor of cathepsin D. Mortality was less and weight gain greater in pepstatin treated mice than in controls. Muscle bulk was greater and hind lamb contractures were reduced in treated mice. Mean muscle fiber mass was significantly increased by pepstatin treatment. Inhibition of muscle protease may be the mechanism by which pepstatin slows the tempo of progression of mouse muscular dystrophy.


Gliofibroma. A peculiar neoplasia of collagen forming glia-like cells. A tumor of highly unusual composition was found in the lower medulla oblongata of a 3 year, 9 months old girl. Light microscopy of the lesion showed an intimate intermingling of astroglial processes with collagen fibers, both projecting congruent to the pattern of preexisting fiber tracts. Electronmicroscopy disclosed a mosaic formed by the intimate apposition of collagen bundles, of glial processes filled with glial fibrils, and of scattered myelinated fibers, all abutting upon each other, often without intervening basement membranes. This well differentiated mass within the medulla adjoined a dedifferentiated endophytic extension of the tumor into the fourth ventricle which had seeded into the cerebellar cortex and the cauda equina. The dedifferentiated portion of the neoplasm also displayed intimate apposition of collagenous and glial elements. The tumor was tentatively identified as a gliofibroma or a desmo-plastic glioma.


Laminar scars in cerebral white matter: a perinatal injury due to edema. Branched plate-like demyelinated lesions were present in the gyral and central white matter of two individuals, 3 and 54 years of age. The degenerated areas contained very few axons and were densely gliotic, and in the older case, contained connective tissue fibers and were continuous with a large parenchymal cyst. The lesions were covered on both sides by normally myelinated white matter, often representing only the subcortical arcuate white matter, occasionally being considerably broader. In some of the latter zones, there was a central area of less severe degeneration which, however, spared the arcuate zone which remained normal. It is suggested that these lesions represent the effects of edema induced by birth injury, under circumstances which permitted the continued formation and maturation of white matter after the edema had subsided. The edema is thought due for the most part to diffuse hypoxia and acidosis, but other mechanisms, such as infection, venous stasis and trauma, may have contributed to the pathogenesis of the edema, and to the lesions directly.


The role of edema in diffuse sclerosis and other leukoencephalopathies. The pathologic changes associated with broad zones of demyelination of the cerebral white matter, the diffuse sclerosis group, are analyzed with respect to the contribution of cerebral edema to their pathogenesis. The characteristics of cerebral edema in general are reviewed, and the interpretation offered that only one type of cerebral edema, that characterized by an extracellular accumulation of fluid, occurs in man. In the diffuse sclerosis group, edema is most readily recognized by the tendency for the arcuate zone of the white matter to be spared when the deeper white matter is severely degenerated. Edema is demonstrated in metachromatic leukodystrophy, globoid cell leukodystrophy, adrenoleukodystrophy, disorders of amino acid metabolism, trauma, hypertensive disease, radiation effect, diffuse hypoxia with acidosis, and other conditions, i.e., both in disorders of myelin metabolism and in conditions in which normal myelin is injured by extrinsic influences. These groups cannot be consistently distinguished morphologically, in part because the injury by edema often obscures any primary morphologic change which may have been present. A familial tendency does not necessarily denote a metabolic abnormality specifically related to the chemistry of a myelin constituent, since the lesions might result from edema induced by some other type of familial process. Such familial processes might be metabolic, but are not specifically related to myelin formation or catabolism, as might be true of diseases like phenylketonuria or maple syrup urine disease. Edema may also occur in instances in which a familial disease induces diffuse hypoxia and acidosis, as exemplified by two instances of severe white matter degeneration in subacute necrotizing encephalomyelopathy; one of these is an additional instance of apparent "crib death" by this cause.


Peripheral nervous system pathology in relapsing experimental allergic encephalomyelitis. A recurrent type of primary demyelination was found in the anterior roots and dorsal root ganglia of strain 13 guinea-pigs with relapsing experimental allergic encephalomyelitis. Single nerve fibre studies revealed a predominant nodal--paranodal distribution of the destruction of myelin in these nerves. Damage of the Schwann cell--axolemmal junction was found in the majority of the abnormal nodes of Ranvier. This was accompanied by the formation of supernumerary adaxonal Schwann cell processes which further altered the normal myelinating cell--axon relationship. It is concluded that variations in antigenic composition may play a role in the selective involvement of the anterior roots. The pathogenesis of the observed nodal changes is discussed.


Synaptogenesis in the basilar papilla of the chick. Synaptogenesis was studied in the basilar papilla of chicken embryos from days 7--21 of incubation. On the 9th day of incubation differentiating hair cells first appeared and a few growing nerve tips made contact with them, although no membrane specializations were apparent at this stage. Synaptic bodies associated with presynaptic membrane specializations were first observed on the 10th day. They lay opposite either supporting cells or afferent nerve processes; in the latter site slight membrane thickenings were occasionally found. During subsequent stages synaptic bodies and the surrounding vesicles increased in number. Synaptic bodies associated with presynaptic membrane specializations, but devoid of contact with afferent nerve endings, were often observed on the 14th day, whereas almost all the synaptic bodies associated with presynaptic specializations were in contact with afferent nerve processes by the 21st day. The efferent synapses were first recognized on the 14th day. These results suggest that in the hair cells of chicken basilar papilla the synaptic bodies and presynaptic membrane specializations appear first and after the synaptic sites are determined by the position of the synaptic bodies, the growing nerve tips seek out and establish synaptic contact at the pre-existing synaptic sites.


Presence of radial glia in foetal mouse cerebellum. The ventricular layer (VL) of foetal mouse cerebellum at days 13--15 of gestation was studied by light and electron microscopy. In Golgi-stained material, round or ovoid cells are located in the VL. These cells have ascending processes, which extend to the pial surface. Ultrastructurally, the ascending processes are electron-lucent, contain microfilaments, some smooth endoplasmic reticulum and scant free ribosomes. They appear to be immature glial processes, oriented radially away from the ventricle. The perikarya of these glial cells lie either in the ventricular or subventricular zones. Juxtaposed along the length of these radially oriented glial processes are unidentified cells, some of which are attached to the immature glial fibres by puncta adhaerentia. These cells are elongated or ovoid with a thin rim of cytoplasm containing few organelles. These unidentified cells may represent neuroblasts (Purkinje cells, Golgi cells, cells of the deep cerebellar nuclei) or glioblasts, (precursors of astrocytes and/or oligodendrocytes) at very early stages of development.


AMg2+ -dependent class of thick filaments and correlated nuclear chromatin condensation in catfish photoreceptors. Photoreceptor cells of excised catfish retinae show morphological differences when incubated in Ringer's solutions of varying ionic composition. Two striking changes were observed in photoreceptor cells incubated in a high Mg2+ (25 mM) Ringer's: (1) Thick filaments appeared in the cytoplasm of receptor terminals and myoids; (2) A pronounced condensation of nuclear chromatin occurred in certain nuclei in the outer nuclear layer. The filaments occurred in lattices or bundles. The bundles had a diameter of approximately 0.05--0.2 micrometer and had either tapered or frayed ends. They were observed with somewhat higher incidence in tissue incubated in a 25 mM Mg2+ Ringer's with EGTA added to chelate Ca2+. A common basis for the cytoplasmic and nuclear changes may lie in a redistribution of fibrous protiens brought about by the increased Mg2+ concentration.


A comparison of similar ionic responses to gamma-aminobutyric acid and acetylcholine. 1. Fast Na+-, Cl-, and K+-Conductance increase responses to gamma-aminobutyric acid (GABA) show times to peak similar to the comparable ionic responses to acetylcholine (ACh). 2. On some identified neurons, both putative transmitters elicit responses due to the same conductance change. For example, in cell R2 both substances cause an increase in Cl- conductance. Receptors for GABA and ACh on R2 do not cross desensitize and therefore are distinct. The ACh but not the GABA response is blocked by alpha-bungarotoxin and strychnine. 3. In R2 both responses reverse at -58 mV, and the Cl- ionophore (for both responses) appears to be partially permeant to propionate and isethionate, but impermeant to acetate, sulfate, and methylsulfate. 4. The Cl- responses but not the Na+ responses to both ACh and GABA are blocked by both picrotoxin and bicuculline, the classical GABA antagonists. 5. These results are compatible with the hypothesis that the ionophores associated with receptors to different neurotransmitters but mediating the same ionic conductance change have many common properties and may, in fact, be identical. Bicuculline and picrotoxin may be specific blockers of the Cl- ionophore, not the GABA receptor.


Neuronal mechanisms underlying physiological tremor. 1. Tremor force was recorded during stationary isometric contractions of intrinsic hand muscles of normal subjects. Subjects maintained a steady force level between their thumb and forefinger for 30 s. The force level varied from weak (0.2 kg) to strong contractions (7 kg). These experimental conditions were the same as those in two preceding studies, where single motor-unit activity (14) and the correlation between the discharges of two simultaneously recorded motor units and physiological tremor (11) have been investigated. 2. Two alterations of the power spectra were observed at successively stronger contractions: increase of tremor amplitude and changes in the shape of the power spectrum. At all force levels, the power spectra of tremor force show the well-known decay of tremor amplitude from the lower to the higher frequencies with a local peak at 6--10 Hz. This peak does not show a significant change with respect to frequency when the force level is varied. It is shifted toward lower frequencies in a pathological condition (Parkinsonism) where the recruitment firing rates of the motor units are significantly lower than in the normal. 3. Higher frequencies (greater than 20 Hz) are barely present in the power spectrum during the very weak contractions. They become significant as the contractions become stronger. 4. The steep decay of the power spectrum toward higher frequencies has a similar slope (--43 dB/decade) as the reduction in amplitude of the unfused part of the muscle contractions with increasing stimulus rates (--38 dB/decade). The cutoff of the power spectrum above 25 Hz parallels the achievement of total fusion of muscle twitches above this rate. 5. The results are consistent with the hypothesis that the power spectrum over the range of 6--25 Hz is mainly caused by the unfused parts of the twitch contractions of motor units firing between recruitment (6--8/s) and total fusion of the twitches (25--30/s). The decline of the power spectrum toward higher frequencies can be explained by mechanical damping, which results from increasing fusion of the twitch contractions. The low-frequency part of the power spectrum is assumed to be the result of the slow force deviations produced by changes in the net output of the motoneuron pool. 6. These assumptions were supported by additional animal experiments where the number and rate of force-producing elements could be controlled. Bundles of ventral root filaments innervating cat soleus and gastrocnemius muscles were stimulated synchronously and asynchronously at a number of different rates. The force output of the strain gauge was recorded, filtered, and analyzed in the same way as the human force records. 7. Stimualtion of one nerve bundle at one fixed frequency led to a sharp peak in the power spectrum at that frequency plus peaks of decreasing height representing the harmonics of the stimulation frequency. The height of the peaks decreased at --37 dB/decade. 8...


Electrotonic properties of neurons: steady-state compartmental model. 1. If a neuron is represented by a network of resistively coupled isopotential regions, the passive flow of current in its dendritic structure and soma is described by a matrix differential equation. The matrix elements are defined in terms of membrane resistances and capacitances and of coupling resistances between adjoining regions. 2. A uniform cylidrical dendrite can be represented by a chain of identical regions. In this case, a closed-form mathematical expression is derived for the voltage attenuation factor of the dendrite at steady state in terms of the ratio of membrane resistance to coupling resistance. A numerical method is given to determine the coupling resistances, which in turn yield a specified attenuation factor. Related expressions are given for a dendrite coupled to a soma. Formulas are also derived for the input resistance in these configurations. 3. For more complicated neuronal structures, matrix manipulations are described which yield values for input resistances in all regions, attenuation factors between all pairs of regions, and values of applied voltages necessary to attain specified steady-state potentials. 4. Dynamic solutions to the differential equation provide voltage transients (PSPs). Comparison of the shape paramenters of these transients with those of experimental or cable-theoretical PSPs establishes the number of regions necessary to achieve a given degree of approximation to the transients predicted by cable theory.


A single-unit analysis of inferior colliculus in unanesthetized bats: response patterns and spike-count functions generated by constant-frequency and frequency-modulated sounds. 1. Single-unit activity evoked by constant-frequency (CF) and frequency-modulated (FM) sounds was recorded from the inferior colliculus of unanesthetized Mexican free-tailed bats. The FM bursts were designed to mimic the natural orientation cries emitted by this species. 2. The feature of greatest concern in this study is the response patterns evoked by acoustic signals. Four major types of response patterns are recognized: a) the phasic on patterns where up to 4 spikes were evoked with a total firing duration occurring within a period of about 5 ms, b) the on-off patterns characterized by a phasic on-response followed by a silent interval with a brief burst of impulses occurring to the off-set of the signal, c) the phasic burst patterns where the unit typically fired 3-7 spikes over a 5-10 ms (or longer) duration with the same response pattern being evoked by a wide range of signal durations, d) the tonic or sustained patterns characterized by a sustained firing whose duration faithfully followed the signal duration. 3. Constant frequency and FM signals were not equally effective for eliciting the various response patterns. While all of the major response categories and most of the subtypes were evoked with CF stimulation, FM signals, which mimicked the natural echolocation cries, evoked predominantly phasic on-responses and a much smaller number of phasic bursters. Tonic and on-off patterns were never observed with FM signals. 4. Many units exhibited a particular response pattern with CF signals which differed from the pattern evoked by FM signals. This finding demonstrated that utilizing  CF signals to investigate encoding features relevant for echolocation is an inappropriate approach and can result in misleading conclusions. 5. In many electrode penetrations most units, and in some cases all units, had the same response pattern. This was observed for phasic constant-latency responders (pELRs), phasic erratic-latency responders (pELRs), phasic burst, and tonic units, and provides evidence that units having a particular response pattern are organized in vertical arrays within the volliculus. 6. Several of the response patterns were strongly correlated with a particular spike-count function. The pCLRs almost always had a steeply rising monotonic function, phasic bursters were always nonmonotonic but never upper threshold, while the tonic units typically had monotonic functions. The pELRs were heterogeneous with regard to spike counts having monotonic, nonmonotonic, and upper-threshold functions. Upper-threshold functions were observed only in pELRs.


Response properties of vibrissa units in rat SI somatosensory neocortex. 1. Glass microelectrodes were used to record extracellular responses from 308 SI cortical neurons to deflections of the contralateral vibrissae in 21 unanesthetized, paralyzed rats. Controlled deflections of individual hairs were produced by means of an electromechanical stimulator. Fast green dye marks were made to aid histological reconstructions of electrode tracks. 2. TS) were observed throughout layers II--VI; "fast" cortical spikes (FS) were less frequently encountered and largely restricted to layer IV. Although both types of potentials had similar negative-positive waveforms. FSs were distinguished from RSs by their comparatively rapid time course, about half that of RSs. RS units (RSU) discharged spontaneously at rates of less than 1--15/s, whereas FS units (FSU) displayed rates of 15--50/s. The amplitudes of FSs, which were generally smaller than those of RSs, often decreased during high-frequency discharges. 3. With sinusoidal oscillations of a vibrissa FSUs responded more reliably and over a broader range of frequencies (3 to at least 40 Hz) than did RSUs , particularly in layer IV. In addition, FSUs typically responded to whisker deflections over a range of 360 degrees, whereas many RSUs in layer IV displayed sharp spatial-tuning charcteristics, responding over a restricted range of less than 90 degrees. 4. Of all units, 58% responded preferentially to stimulus transients (vibrissal movements), 32% displayed sustained responses to stimulus stead-states (fixed vibrissal displacement). For the remaining 10% of units the appropriate stimulus could not be specified; these units were particularly common in layer V. 5. Computation of quantitative stimulus-response relations showed that many units increased their rate of discharge with increasing stimulus intensities. 6. Most units were directionally selective, responding preferentially to deflections of a whisker in one or more of four quadrants. 7. In radial penetrations through the cortex there was a columnar patern so that units were activated at least by the same (i.e., the "principal") whisker. In a number of cases these could be directly correlated with the barrels. Of all units, 55% responded to deflections of single vibrissa only, the remaining 45% to 2--12 adjacently situated vibrissae. For most multiple-whiser units the responses elicited by deflection of any one hair activating the neuron was qualitatively similar to those elicited by deflection of any other hair activating it. The principal whisker of the penetration was typically associated with the most vigorous responses. 8. In layer IV, 85% of neurons responded to deflections of one hair only, the remaining 15% to two or more hairs. In layers II and III 39% of units were activated by more than one vibrissa; in layers V and VI multiple-whisker units predominated (64%). Whisker configurations in the deep layers were larger than those in other layers. 9...


Discharge properties of pontine reticulospinal neurons during sleep-waking cycle. 1. Reticulospinal neurons were identified by antidromic invasion from spinal cord electrodes chronically implanted at C4 in cats. 2. Most of the neuronal population studied lay within the medial portion of the giant cell field from the anterior pontine and to the anterior medullary reticular formation (FTG). A few cells were found in the tegmental reticular nucleus (TRC) which has not previously been known to project to the spinal cord. 3. Extracellular action potentials from the neuronal somata of the identified neurons were recorded continuously throughout naturally occurring sleep-waking cycles. 4. The identified reticulospinal neurons shared three properties, suggesting a generator function in desynchronized sleep (D) (with previously recorded but unidentified FTG neurons): selectivity (or concentration of discharge in D); tonic latency (or firing rate increases beginning several minutes prior to D); and phasic latency (or firing rate increases occurring prior to eye movements within D). 5. The location, discharge properties, and spinal projections of FTG neurons are, thus, all consistent with the hypothesis that they may directly mediate some of the descending excitatory and inhibitory influences on spinal reflex pathways in desynchronized sleep.


The histopathology of experimental spinal cord trauma. The effect of systemic blood pressure. The early sequential histopathological alterations following a concussive paraplegic injury to the posterior thoracic spinal cord in cats were studied. The lack of significant progression of hemorrhages over a 4-hour period after injury indicates that most hemorrhages probably occur within the first hour. The marked enhancement or retardation of hemorrhages in the post-injury period, when the blood pressure was increased or decreased, respectively, demonstrates the loss of autoregulation of spinal cord vasculature at the trauma site after a concussive paraplegic injury. Progressive edema formation was evident over a 4-hour period following injury, and it could be enhanced or retarded by elevation or reduction of the systemic blood pressure.


Subarachnoid hemorrhage and papilledema due to a cervical neurilemmoma. Case report. An unusual case of a cervical neurilemmoma is presented. A 67-year-old man developed papilledema on two occasions in association with the symptoms and signs of a subarachnoid hemorrhage (SAH). He proved to have an otherwise asymptomatic cervical neurilemmoma. It is suggested that both acute and subclinical bleeding from such tumors may sometimes underlie the development of raised intracranial pressure occasionally encountered. The clinical clue to the spinal origin of the SAH was an acute onset with root pain. This case is discussed with reference to similar cases in the literature.


Delayed traumatic intracerebral hematomas. Report of three cases. Three patients are reported who developed delayed intracerebral hematomas following closed head injuries. Two patients showed hematomas within 24 hours after a normal computerized tomogram. All three were treated surgically, and two had good results.


Moyamoya syndrome as a complication of radiation therapy. Case report. A case is reported with occlusion and stenosis of the internal carotid arteries in association with basal telangiectasia. Fifteen years after postoperative irradiation for an optic glioma, radiological signs typical of the moyamoya syndrome were observed. Radiation therapy is discussed as the cause of the vascular damage in this case.


Preoperative diagnosis of a ruptured intracranial dermoid cyst by computerized tomography. Case report. A case of ruptured intracranaial dermoid cyst in the right middle fossa is reported. A definitive diagnosis of the lesion and the fact that it had ruptured was made possible by specific computerized tomographic findings. The findings were confirmed at surgery.


Pulsatile cerebral echo in diagnosis of brain death. Conclusive diagnosis of brain death can be made by the demonstration of prolonged cessation of cerebral blood flow. This report describes a simple method to determine the presence or absence of the blood flow in the brain by recording the pulsatile midline echo on one channel of the electroencephalogram (EEG) or on any four-channel monitoring system in the intensive care unit. A firm transducer holder has been developed to eliminate artifacts caused by transducer motion, The pulsations of the midline echo are assumed to be the result of displacement of the midline structures by the arterial injection of each cardiac systole. Thus, the absence of these midline pulsatile echoes correlates with the absence of cerebral blood flow and, if the absence persists over 30 minutes in the presence of normal blood pressure, then the result is brain death. Twenty-eight cases of clinical brain death with electrocerebral silence of EEG and 18 obtained patients with various types of cerebral pathology were examined by the echo-pulsation technique. Twenty-six of the 28 cases showed no pulsation of the midline echo. The validity of the technique was documented in four cases by four-vessel cerebral angiogram.


Occipital to posterior inferior cerebellar artery bypass surgery. The results, complications, and technical aspects of occipital to posterior inferior cerebellar artery (PICA) bypass surgery are reviewed. Patients were divided into two groups: those considered to be a high risk for posterior circulation infarct but not disabled by the symptoms or deficits (eight patients), and those moderately or severely disabled at the time of admission (eight patients). Postoperative angiography revealed that 15 of the 16 grafts were patent. In 10 of the 15 patent grafts, the bypass graft served as a sole or major blood supply of the vertebral basilar system; in five patients, flow was limited to the distribution of the PICA. Eight patients achieved full employment or normal activity, six were improved but did not return to full employment, and two patients were unchanged. Ataxia was the major residual deficit in these patients.


Interrelationship of aneurysm clips and vascular tissue. Various straight-jawed aneurysm clips were tested for occluding capabilities on a vascular tissue model. Occluding pressures varied markedly among the clip styles and were altered by changes in the lumen and tissue composition of the model. Mechanical characteristics are highly variable between clip styles, but fall within a narrow range for clips of a similar style. The complex interplay of the unique aspects of clip design and force generated by the spring in conjunction with tissue characteristics and precise clip placement upon the tissue are major variables in the apparent ability of a particular clip to occlude the neck of an aneurysm.


Surgery of the superior sagittal sinus in parasagittal meningiomas. The management of 21 parasagittal meningiomas is described; three were located in the anterior third of the sinus, 14 in the middle third, and four in the posterior third. Of these, four meningiomas were attached only to the lateral wall, two invaded the external layer of only one sinus wall, two involved the lateral recess of the sinus, and seven invaded one or two sinus walls. The remaining six tumors invaded the three walls of the sinus, which was completely blocked. There was bilateral meningiomas in four cases. Complete excision of the meningioma with preservation of the venous flow in the sinus and its collateral veins was attempted in each case. In the first eight cases it was possible to preserve the patency of the sinus without graft. In six of the next seven cases the removal of the two invaded walls permitted preservation of the third healthy wall and entailed the repair of the two involved walls by a partial graft, either dural graft (three cases) or venous graft (three cases). In one of the last six cases, a total vein graft was performed after complete excision of the invaded sinus. Two cortical veins were sutured to a collateral branch of the autogenous vein graft. The surgical technique of the partial and the total vein graft is described and clinical results and angiographic controls are discussed.


The microscopic effects of ventricular dilatation without increase in head size. Eleven brains were studied from patients in whom there was some degree of ventricular dilatation due to obstruction of the cerebrospinal fluid pathways. Six further cases from the files of the Department of Neurosurgery were reviewed. Very few microscopic changes were seen in the gray or white matter even in the presence of marked ventricular dilatation. These findings, although surprising in view of the gross apparent reduction in white matter, are in accordance with the known beneficial results of shunting procedures for relief of ventricular dilatation due solely to obstruction. This study provides a pathological anatomical background for the good prognosis in patients with ventricular dilatation without other neurological disease.


Treatment of experimental cerebral infarction in rats with levodopa or with glycerol. Administration of large amounts of levodopa did not improve survival rates of rats after acute cerebral infarction induced by injection of carbon microspheres. However, when 10% glycerol was used, the number of rats that survived after cerebral infarction was significantly greater than in the control or in the levodopa-treated rats. Combination of levodopa and glycerol therapy also significantly improved the survival rate of beneficial effect. Pathological findings (gross or microscopic) indicate striking changes in brain tissue after embolization. Development of brain edema of the infarcted left hemisphere corresponded to the type of treatment and to the length of animal survival. Brain-tissue histology indicates that glycerol-treated animals developed less severe edema and had less tissue disruption than control animals. The results suggest that treatment of edema should be one of the primary steps in therapy after acute cerebral infarction.


Evaluation of the central canal of the spinal cord in experimentally induced hydrocephalus. The central canal of the spinal cord has been proposed as a significant compensatory alternative pathway of cerebrospinal fluid (CSF) flow in hydrocephalus. Ten dogs were made hydrocephalic by a relatively atraumatic experimental model that simulates the human circumstance of chronic communicating hydrocephalus. The central canal was studied by histopathology and compared with 10 normal control dogs. In both groups the central canal of the spinal cord was normal in size, configuration, and histological appearance. In this experimental model dilatation of the canal and increased movement of CSF does not appear to be a compensatory alternative pathway.


Elasticity of the spinal cord, pia, and denticulate ligament in the dog. The longitudinal elasticities of the dog spinal cord, pia, and denticulate ligaments were obtained by measuring the load-elongation curves. Both pia and denticulate ligaments were moderately elastic, but the spinal cord substance showed an upward curve, which indicated a predominantly viscous character. In situ, the spinal cord and pia were moderately strained. A 40-mm segment of the cord with dorsal and ventral roots severed and denticulate ligaments removed became 1 mm shorter when the cord and pia were transected at both ends. It was estimated that the cord and pia in situ were stressed by a force of 2 to 3 gm, the denticulate ligaments with 3 to 5 gm, and the dura with 50 to 70 gm. The elastic moduli of the spinal cord substance were 1.68 X 10(5) dynes/sq cm for loading between 5 and 10 gm and 1.19 X 10(5) dynes/sq cm between 30 and 35 gm.


Origin of somatosensory evoked responses recorded from the cervical skin surface. Somatosensory evoked response from the cervical skin surface over the spine (the cervical SER) was recorded, and compared with the cord dorsum potential (CDP) simultaneously recorded from the posterior epidural space at the same segment. The cervical SER evoked by segmental nerve stimulation consisted of an initially positive spike (P1), the peak latency being the same as that of the P1 of the CDP, followed by a smaller negative wave with two peaks. The latency of the second peak of the negative wave (N1) coincided with that of the N1 of the CDP. Subsequent to this negative wave, a slow positive wave (P2) with peak latency similar to that of the P2 of the CDP, could be noticed in some subjects. The cervical SER could not be evoked even by strong stimulation of the cauda equina. Thus, the cervical SER might reflect a segmental phenomenon rather than the conducted potential along the cord, and originate from the spinal root and cord in the same way as the segmentally evoked CDP.


Evaluation of experimental spinal cord injury by measuring spontaneous spinal cord potentials. The relationship between the spontaneous spinal electrogram and the degree of spinal cord injury was studied in anesthetic-free, surgically decerebrate cats that received experimental blunt trauma by the graded weight-drop method. It was found that the characteristic spontaneous slow negative potential of the spinal electrogram showed a frequency dependency that correlated positively with the intensity of the injury (impulse expressed in gm-sec). Graphs of the frequency of occurrence of the slow negative potentials as a function of time following initial injury indicated that both the slope and shape of the curve were dependent on the severity of the injury measured in gm-sec at the time of the injury and confirmed histologically. These results indicate that the spontaneous spinal electrogram may serve as a sensitive indicator of the degree of spinal cord injury and may be useful in the assessment of various treatment modalities.


Traumatic intracranial internal carotid aneurysm due to gunshot wound. Case report. This patient developed an intracranial carotid artery aneurysm after a bullet wound. A review of the related literature, and the pathogenesis of traumatic false and true aneurysms are presented.


Chronic extradural hematoma presenting 33 years after penetrating cranial trauma. Case report. A case is reported of a 53-year-old normotensive man who presented, 33 years after a penetrating cranial war injury, with dysphasia of 10 month's duration, which proved to be due to a chronic extradural hematoma. The pathogenesis and symptomatology are discussed, and it is proposed that the lesion had been present since the original injury.


Malignant transformation in benign cerebellar astrocytoma. Case report. The authors give follow-up information on Case 59 of Cushing's 1931 series of cerebellar astrocytomas. The patient died with a malignant cerebellar astrocytoma 48 years after partial removal of a previously benign astrocytoma at the same site. Including the present one, there have been only five reported cases in which this has occurred. Ordinarily, juvenile pilocytic astrocytomas are of extremely genign character, and it is well established that even with incomplete resections patients have survived for years without progression of the tumor. Not all of the cases so reported can be wholly accepted as respresenting malignant transformation of the tumor, but may instead be instances of recurrence of an inherently benign glioma since the presence of features such as endothelial hyperplasia or nuclear atypicality in a juvenile pilocytic astrocytoma does not warrant is being classified as malignant. Features truly suggestive of malignancy are hypercellularity, frequent mitoses, necrosis, and, in some instances, a diffusely infiltrative growth pattern; all of these features were found in the present case.


Traumatic cerebrospinal fluid fistula simulating tears. Case report. A young child developed delayed cerebrospinal fluid (CSF) rhinorrhea and CSF leak from the eye presenting as tears. The "tears" were CSF which had tracked from the cribriform plate through the ethmoidal air sinuses to the medial aspect of the left orbit. There was marked chemosis and it was considered likely that the tears had leaked through damaged conjunctiva.


Inversion of the cerebral mantle as a complication of ventricular shunting. Case report. The authors report a case of inversion of part of the cerebral mantle into the frontal horn of the lateral ventricle following ventriculoperitoneal shunting for noncommunicating hydrocephalus. The abnormally positioned cerebral mantle continued to grow and caused no detectable neurological dysfunction.


Unilateral septal technique for transsphenoidal microsurgical approach to the sella turcica. Technical note. A modification of the transseptal, transsphenoidal appraoch to the sella turcica is described; it consists of a unilateral separation of the nasal mucosa from the nasal septum. Experience with the technique in 215 cases has indicated that it is a useful, practical appraoch. The advantages are that the septum is spared, reoperation is made easier, and the procedure is quicker than the bilateral septal procedure. Asymptomatic nasal septal perforations (less than 3 mm) were seen in eight of 215 cases, and represented the only complication related to the operation.


A safe technique for the precise localization of carotid-cavernous fistula during balloon obliteration. Technical note. The authors report a technique to precisely localize a fistulous opening in the carotid artery. The patient is heparinized and a Prolo catheter is introduced into the internal carotid artery and inflated distal to the approximate site of the fistula. Heparinization allows the balloon to be inflated long enough to obtain and analyze high-quality angiography film without fear of thromboembolism generated by the temporary balloon occlusion. Contrast material injected through the Prolo catheter proximal to the balloon reveals a small segment of cavernous carotid artery between the inflated balloon distally and the fistula proximally. The venous structures are now only faintly opacified and cannot obscure the morbid anatomy of the exact fistulous tear in the carotid artery. If the balloon is placed exactly opposite to the site of the fistula, a standing, stagnant column of dye forms a cast of the cavernous, petrous, and cervical carotid artery. Once the fistula is localized with this method, it may be obliterated by any therapeutic means preferred. If the Prolo catheter is used for intraluminal occlusion, then a transfemoral contralateral carotid angiogram is done before the heparin is reversed to confirm that the balloon has not been placed proxial to the fistula.


Occlusive arteriopathy and brain tumor.

Occlusive arteriopathy and brain tumor. Four cases with the association of occlusive arteriopathy and brain tumor are presented. A clinical analysis of these cases and cases reported in the literature revealed that occlusive arteriopathy at the base of the brain was often associated with a slowly growing basal tumor in children. Possible causes of occlusive arteriopathy in these cases were compression of the circle of Willis by a slowly growing basal tumor, secondary artial occlusive changes by radiation therapy for a basal tumor, or vasculopathy associated with neurocutaneous syndrome. Symptoms of sudden onset or episodic nature suggest the presence of occlusive arteriopathy rather than the mass effect of a tumor. Cerebral angiography is mandatory whenever computerized tomography (CT), performed to rule out recurrence of a basal tumor, shows an ischemic lesion with low-density areas without any evidence of mass effect of the tumor. Cerebral angiography is also necessary when a basal tumor is suspected in children, particularly in cases associated with neurocutaneous syndrome and a basal tumor. Care should be taken not to scarify the abnormal vascular network at the base of the brain at the time of operation, because it is considered to be functioning as collateral circulation. The potential hazards of radiotherapy to radiation-induced occlusive changes of the circle of Willis must be considered in treating a benign basal brain tumor in children. Even in adults, repeated large doses of irradiation could cause occlusive arteriopathy.


Functional treatment of acromegaly by transsphenoidal microsurgery. The authors have analyzed the results from 41 acromegalic patients who underwent transsphenoidal surgery. In 31 patients, postoperative growth hormone (GH) levels fell and remained below 10 ng/ml. This represents an endocrinological "cure" of 78%. In the remaining 10 cases, postoperative GH values have not stabilized below 10 ng/ml, although seven show some clinical improvement. The results were particularly good in those cases of localized adenomas, which allowed a selective removal while maintaining pituitary function within normal limits in 65.5% of cases. The postoperative GH level in this group fell and remained below 10 ng/ml in more than 90% of cases. Four patients required reoperation to normalize the GH levels which had not been sufficiently modified after the first operation; only one of them remained with plasma GH levels above normal limits. There were no deaths in this series. Rhinorrhea occurred as a postsurgical complication in four cases. In three this disappeared with bed rest and lumbar drainage; in the other, surgical repair was necessary. The occurrence of surgical complications has decreased as our experience has increased, and the need for reoperation has been unusual after the first year of our study.


Suprasellar germinoma.

Suprasellar germinoma. The clinical features of 18 cases of suprasellar germinoma were reviewed, and the following points stressed: 1) The incidence of intracranial germinoma and teratoma seems to be much higher in Japan than elsewhere. 2) Germinomas in the pineal region, the third ventricle, and the lateral ventricle were observed to be predominant in males. In suprasellar germinoma, however, males were not affected predominantly and the male:female ratio was 1:1. 3) Suprasellar germinomas caused three symptoms: diabetes insipidus, visual disturbances, and pituitary dysfunctions. 4) Pituitary functions were disturbed to various degrees. Some cases showed hypopituitarism but some showed an elevation of plasma concentrations of cortisol or luteinizing hormone and follicle stimulating hormone. 5) Some abnormalities showing a suprasellar mass were usually found on neuroradiological examination. 6) Suprasellar germinomas were very sensitive to radiotherapy and some of them rapidly disappeared on follow-up computerized tomography scanning after irradiation with as little as 1200 rads.


Carotid-cavernous fistula. Demonstration of asymptomatic vascular "steal". Abnormal distribution of cerebral vascular flow was studied in a patient who had a traumatic carotid-cavernous sinus fistula. Serial studies were performed using a method for determining relative cerebral vascular flow:99mtechnetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) was injected intravenously and flow data were processed by a digital computer. Serial studies documented the occurrence of a vascular "steal" during temporary carotid occlusion; postoperative studies showed disappearance of the steal and obliteration of thiling arterial structures and capillary filling in the brain, and in demonstrating alteration in the cerebral circulation.


Interhemispheric steal. An experimental study. In 21 cats the pressure in the occluded middle cerebral artery (MCA) was recorded by way of a catheter, introduced in the most proximal portion of this artery by way of the transorbital approach. The effect of temporary occlusion of the ipsilateral and contralateral common carotid artery on the pressure in the occluded MCA was studied. The results seem to prove the existence of the so-called "interhemispheric steal" syndrome.