Bilateral electrodermal activity in depressive patients. Integrated bilateral skin conductance response and reactive lateral eye movements were studied in 19 depressive patients and 14 normal subjects during visual and verbal tasks and tone habituation sequence. Distinct right-left differences between depressed and normal subjects in reactive lateral eye movements were revealed. Both endogenous and reactive depression patients were classified as 'left-movers'. Marked bilateral differences were observed in electrodermal activity (EDA) in patients during verbal and visual tasks. In endogenous depression EDA was higher on the left hand compared with the right under all the conditions studied (visual and verbal, and tone habituation sequence). In reactive depression EDA was higher on the left side during the verbal task and tone habituation sequence and on the right side in the visual task. Neither result in reactive depression group attained significance. The results are interpreted as a reflection of a different pathophysiology underlying reactive and endogenous depression.


Components of skin impedance level.

Components of skin impedance level. Eighty students were trained on a maze-like ballboard over a series of 24 trials, while the skin impedance level was recorded from the palmar and dorsal sides of their fingers. A principal component analysis of the cross-products for the palmar and dorsal data treated separately resulted in two components for the palmar data (55% and 25% of variance) and one component for the dorsal data (80% of variance) and thus supported Edelberg's findings.


Measurement of the evoked cardiac response: the problem of prestimulus variability. This paper discusses the problem of prestimulus variability in cardiac activity and its implications for the measurement of evoked cardiac responses (ECRs). Two methods which have been proposed to reduce error arising from respiratory sinus arrhythmis (SA) were reviewed critically. The first approach attempts to control only for the error associated with the sampling of the prestimulus level. This is considered inappropriate since it does not take into account the continuation of SA into the poststimulus period. The second approach reviewed was time series analysis which provides an elegant statistical solution of the problem. Unfortunately, the application of time series analysis has not yet been evaluated for adult cardiac data. A third approach which utilizes an adjustment for SA by employing the actual prestimulus values of an SA cycle was proposed. The application of this technique in the case of a pseudostimulus demonstrated that correction for SA results in significantly smaller 'responses' with less variance than does a conventional procedure which does not take prestimulus variability into account.


The EEG, brain function, and Thomson's sampling theory. If the EEG is regarded as a measure of functional organisation in the brain, it may yet be possible to use it as an independent variable in psychological studies. The method of Maxwell et al. (1974) suggest how this relationship may be quantified. These authors develop the hypothesis that EEG power is proportional to p, the number of brain components involved in cognition. However, evidence is reviewed here to suggest an alternative hypothesis for the case of EEG alpha activity, namely that power is proportional to (1--p).


Plasma catecholamines, stress and aggression in maximum security patients. Investigations into the stress response of patients committed to a special hospital for criminally deviant offences have identified a group of sympathetically hypoactive patients who excrete more noradrenaline and less adrenaline in the urine than either the remaining hospital population or control subjects, during conditions of stresser anticipation. Further investigation of these patients has shown that similar differences in plasma catecholamines exist, and that the group of patients characterised by this imbalance tend to have been committed for the most physically violent crimes.


Diphasic electrodermal response, heart rate and moods. The simultaneous recording of spontaneous EDA (mono and diphasic SPR), HR and mood self-rating (Q-sort of adjectives), on 35 normal subjects, for 5 consecutive weeks has shown that: (1) The emission of diphasic SPR is significantly related to an increase in monophasic EDA (in frequency and in amplitude) and to a lesser degree with HR acceleration; (2) Such a physiological pattern is significantly associated with depressive mood, though independent from anxious mood. These results confirm the importance of morphological aspects of SPR in assessing normal mood states.


Field dependence, laterality and the EEG. There is evidence that an individual's 'cognitive style' is related to lateralization of function in the brain, and that this in turn is associated with characteristic EEG coherence spectra. We tested the hypothesis that field dependence (a measure of cognitive organization) and hand preference (a measure of functional organisation) relate to EEG coherence measures in a specific way. The predicted associations were based on the proposal that right preferent individuals have a more specific, and left preferents a more diffuse, system of functional units in the cortex. The association between alpha band resting EEG coherence (sampled on two occasions for both hemispheres from 12 right and 12 left preferent individuals), field dependence (Nyborg's criterion of frame dependence on a rod and frame test), and laterality scores (questionnaire and manual performance), was measured by Kendall's coefficient of concordance (W). Significant associations support the proposed model except for coherence within the left preferents' right hemisphere. It is argued that the right hemisphere is more specifically organised in strong sinistrals than the general model would predict. These and other results support the use of EEC coherence measures in the study of cerebral functional organisation.


Linear dichroism studies of binding site structures in solution. Complexes between DNA and basic arylmethane dyes. The interaction between B-form DNA and twelve cationic triaryl-methane dyes was studied with respect to optical properties and stabilities, using linear dichroism (LD) and aqueous two-phase partition techniques. Monovalent dyes derived from crystal violet as a rule form a single strong complex (K1 ca 10(5) M-1; site density per nucleotide base n1 ca 0.1 at 0.1M ionic strength) in which the plane of the dye is at an angle of less than 50 degrees to the local DNA helix axis. The complex with fuchsin is weaker (10(4) M-1) but can be explained by a similar orientation. For some of the dyes (those with pseudo-C2v symmetry) the angular orientations of two molecule-fixed axes can be obtained. For the divalent methyl green a second complex appears to be formed at low ionic strength. Methyl green (and to some extent 2-thiophene green and malachite green) show exciton splitting in the LD spectrum and circular dichroism assignable to exciton coupling between transition dipoles roughly parallel to the helical strands, indicating a dye-dye interaction. The optical data, supported by fitting experiments with space-filling models, suggests a general structure for the binding site. The dye is not intercalated but is bound to exposed hydrophobic regions in the major groove. The ligand is in part (the charged amino groups) in contact with the phosphoribose chain but its main surface lies against the hydrophobic base-pair stack. For a diphenylmethane dye, Michler's hydro blue, a perpendicular orientation was observed, possibly due to intercalation.


Interaction of phenosafranine with nucleic acids and model polyphosphates. I. Self-aggregation and complex formation with inorganic polyphosphates. Aggregation of phenosafranine in concentrated aqueous solutions and interaction with polyphosphates was studied by absorption and fluorescence spectroscopy. At concentrations greater than 10(-3)M phenosafranine forms dimers (Kd = 3.8 x 10(2) 1.mole-1), which are characterized by a hypsochromic shift of the visible and near ultraviolet absorption maxima accompanied by a hypochromic effect. No fluorescence could be detected from phenosafranine dimers. Analogues spectra changes were observed when a polyphosphate was titrated with phenosafranine, which indicated that with increasing saturation of the polyphosphate binding sites phenosafranine gradually became bound in the aggregated form. Full saturation of the polyphosphate binding sites with phenosafranine was reached only when an excess of free dye was present. The cooperative binding of phenosafranine to a polyphosphate could be evaluated by means of a theory proposed by Schwarz et al. At the zero ionic strength and at 25 degrees C the binding was characterized by cooperative binding constant K = 6.2 x 10(5) 1.mole-1, number of binding sites per monomeric phosphate residue g = 0.4, and cooperativity parameter q-30. Spectroscopic properties of phenosafranine in the aggregated and polyphosphate-bound states were compared with those of ethidium bromide.


A unified theory of nucleation-rate-limited DNA renaturation kinetics. DNA renaturations under nucleation-rate-limiting conditions on simple DNA such as bacterial and bacteriophage DNA show significant deviation from ideal second-order kinetics when followed by optical density measurements at 260 nm. Ideal second-order kinetics yield linear plots when the data is plotted in the standard reciprocal second-order (RSO) manner. The observed deviations from ideal second-order behavior take the form of steadily downward-curving RSO plots. In this paper, experiments are presented for E. coli and T2 DNA documenting this non-ideal behavior. Since experiments using T4, T5 and B, subtilis DNA yield identical non-ideal behavior, this behavior appears to be a property of DNA renaturation followed by optical density, not a peculiarity of a particular DNA. Identical non-ideal behavior is also seen in kinetics followed by S1 nuclease assay. A theory is developed to explain this deviation from ideal second-order kinetics. The theory also explains why kinetics followed by hydroxyapatite chromatography show nearly ideal second-order kinetics. In contrast to the approach taken by others in developing equations that describe S1 nuclease monitored reactions, our view is that nonideal second-order kinetics are fundamentally due to the reacton of free single strands to yield partially helical duplex species. Later reactions of these species tend to reduce the deviations from non-ideal second-order kinetics.


Analysis of ligand binding curves in terms of species fractions. The ligand binding curve for a macromolecular system presents the average number of ligand molecules bound per macromolecule as a function of the chemical potential or the logarithm of the ligand concentration. We show that various observable properties of this curve, for example its asymptotes and derivatives, are expressible in terms of linear combinations of the mole fractions alphai of macromolecules binding i molecules of ligand. Whenever enough such properties of the binding curve are known, the linear equations in alphai can be solved to give the mole fractions of each of the various macromolecular species. An application of these results is that a Hill plot for hemoglobin-ligand equilibrium where the asymptotes approach unit slope can be made to yield the four Adair constants by a simple algebraic method. A second use is that a knowledge of the first and second derivatives of the binding curve at points along the curve can yield the species fractions as functions of the degree of saturation without direct knowledge of the ligand binding constants. These methods are illustrated by some numerical examples.


Field-induced instabilities in two-component systems: the cell-free glycolytic system. The effects of weak static electric field on a cell-free glycolytic system, which is known to exhibit oscillatory behavior, have been studied using an allosteric model (due to Goldbeter and Lefever). Linear stability analysis is used to determine the change in the nature of stability and the consequent appearance of dissipative structures, due to the electric field. The results show that for this system all the necessary conditions for a field induced instability are satisfied. An order of magnitude calculation of the field strength shows that field strength in the range 10-100 V/cm is required to produce observable change in the system's behavior.


An analysis of rod outer segment adaptation based on a simple equivalent circuit. This model of rod outer segment adaptation is based on the hypothesis that transmitter substance released by bleached rhodopsin closes sodium channels in the outer segment plasma membrane, leading to hyperpolarization of the receptor. The outer segment adaptation processes of the model are associated with the transmitter release, the transmitter background concentration and the plasma membrane leakage. Changes in the three model parameters correspond to the three types of outer segment adaptation process. According to the model the stimulus-response function is in every adaptational state U/Umax = I/(I + IH). The model predicts how each adaptation process affects IH and Umax. Specifically, when the number of liberated transmitter molecules per isomerizing quantum decreases, the amplitude Umax remains constant but IH increases. A short description of this model has been published in a paper reporting experimental results on background adaptation (Hemilä, 1977).


Flash photolysis of rhodopsin in rabbit. Flash photolysis of rhodopsin in rabbit's retina has been analysed theoretically, and the results are found to be in good agreement with the experimental results of Hagins (1957). We have also obtained the variation of relative concentrations of rhodopsin, lumirhodopsin, isorhodopsin and metarhodopsin I during the period of the flash corresponding to two different intensities of the flash. It has been found that the quantum efficiencies of conversion of lumirhodopsin into rhodopsin and isorhodopsin will lie in the range 0.24--0.45 and 0.20--0.44 respectively; quantum efficiency of conversion of metarhodopsin I into rhodopsin and isorhodopsin are found to have values greater than 0.52 and 0.45 respectively and the quantum efficiency of conversion of isorhodopsin into lumirhodopsin has been found to be approximately 0.865. Also the maximum value of the rate constant of the reaction metarhodopsin I leads to metarhodopsin II at 37 degrees C has been determined in decerebrated eye and it has been found that it is of the same order as found by Pugh (1975) in the case of human eye.


Cross bridge slippage induced by the ATP analogue AMP-PNP and stretch in glycerol-extracted fibrillar muscle fibres. Glycerol-extracted insect fibillar muscle fibers in rigor exhibited both an elastic and a plastic phase in the length-tension diagram. The transition between these phases took place at a critical tension, the "yield point" or elastic limit. In the plastic phase the apparent static elastic modulus became zero, whereas the immediate elastic modulus (measured by rapid length changes completed within 4 ms) exhibited no abrupt change at the yield point. The tension value of the yield point (but not immediate stiffness) was lowered by addition of AMP-PNP and was partially restored by washing out AMP-PNP. The dependence of the critical tension at which plastic flow begins on cooperative cross bridge behaviour is discussed in terms of breaking and reforming acto-myosin linkages. Evidence is presented that addition of AMP-PNP induces slippage of cross bridges on the actin filament by affecting the interaction between myosin and actin.


Unmaintained remissions in multiple myeloma. Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.


Polyamine synthesis in bone marrow granulocytes: effect of cell maturity and early changes following an inflammatory stimulus. Enriched fractions of mature and immature neutrophil granulocytes, isolated from guinea pig bone marrow, were assayed for ornithine decarboxylase activity and polyamine content. The results show that immature granulocytes contain at least ten times more ornithine decarboxylase activity and two times more spermidine than mature granulocytes. The incorporation of 14C-ornithine into putrescine and spermidine of intact immature granulocytes was three to four times and ten times, respectively, that of mature granulocyte preparations. Six hours after an inflammatory stimulus, transient increases of 14-fold and 3-fold in the activities of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, respectively, were observed in immature bone marrow granulocytes. At this time the incorporation of 14C-ornithine into putrescine and spermidine in bone marrow granulocytes from stimulated animals was 14 times that of cells from controls. A maximum increase in DNA synthesis in these cells during the inflammatory response occurred 6 hr after the maximum increase in the polyamine synthetic activity. Together these data suggest that polyamine synthesis in the granulocyte compartment of the bone marrow is associated chiefly with immature proliferating cells and that increased polyamine synthesis precedes increased granulocyte proliferation in the bone marrow following an inflammatory stimulus.


Acquired IgG antibody occurring in a thrombasthenic patient: its effect on human platelet function. In subagglutinating amounts, an IgG antibody isolated from the plasma of a polytransfused thrombasthenic patient (L) inhibited ADP-, epinephrine-, collagen-, and thrombin-induced aggregation of normal human platelets. The inhibition of ADP-induced aggregation was strongly diminished following the prior incubation of the antibody with control human platelet stroma but not with the stroma prepared from the platelets of two different thrombasthenic patients. The IgG(L) did not affect the binding of 14C-ADP to control human platelet membranes and did not inhibit the ADP-induced shape change. Bovine factor VIIIVWF-induced agglutination and ristocetin-induced aggregation of control human platelets were not inhibited in the presence of the antibody. The IgG(L) strongly inhibited ADP-induced retraction of reptilase clot and thrombin-induced clot retraction. This antibody therefore induced a thrombasthenialike state in normal human platelets, suggesting that the antigenic site recognized by the antibody plays a central role in the later stages of the mechanism of platelet aggregation induced by physiologic aggregation-inducing agents.


Role of the hypophysis in erythropoietin production during hypoxia. Hypophysectomized or sham-operated male rats were exposed to hypoxia (0.42--0.40 or 0.37--0.35 atm for 6, 12, or 24 hr) applied 2 wk to 7 mo after surgery. Erythropoietin (Ep) levels in rat serum were evaluated on the basis of the exhypoxic polycythemic mouse assay. Ep activity evoked by hypoxia was significantly lower in hypophysectomized rats than in sham-operated controls. Progressive increase of the EP response to hypoxia correlated with extension of the time interval between hypophysectomy and hypoxia from 2 wk to 2--4 mo apparently mediated by the simultaneous inverse decline of red cell mass (RCM) values, i.e., of the "relative plethora" induced by a low O2 demand associated with relatively high RCM values. However, after 3--7 mo hypoxic Ep activity was still lower than in sham-operated controls. In these ablated animals the relative plethora became negligible or absent; accordingly, the Ep response apparently had reached plateau levels. These studies indicate that hypophysis (hypophyseal and target hormones, with the exception of estrogens) modulates Ep production under hypoxic conditions, possibly via a permissive enhancement of renal Ep activity.


Diamond-Blackfan syndrome: evidence against cell-mediated erythropoietic suppression. The profound anemia of Diamond-Blackfan syndrome (DBS) is due to marrow red cell failure, but the pathogenesis is not understood. Studies by others indicated cell-mediated erythropoietic suppression in this condition. To explore this mechanism further, Ficoll-Hypaque--separated peripheral blood lymphocytes (PBL) from four anemic untreated patients with DBS, or from normals were cocultured with control marrow in vitro and the growth of erythropoietin-responsive stem cell colonies (CFU-E) was dermined. CFU-E numbers obtained from cultures with added normal PBL were not significantly different from the number without PBL. Similarly, CFU-E from cultures with added DBS PBL were not significantly different from the number without PBL (215 versus 220, 229 versus 220 and 84 versus 60, 74 versus 94/10(5) cells, respectively). Mixing marrows from a control and one DBS patient in ratios of 2:1, 1:1, or 1:2 prior to culture failed to disclose a decrease of colony growth. We could not show cellular inhibition of erythropoiesis in these patients with DBS. The mechanism of anemia in this disorder remains an open question.


Marrow culture in diffusion chambers in rabbits. II. Effect of competing demands for red cell and white cell production on cell growth. Studies were done of cell production by marrow in diffusion chambers implanted in the peritoneal cavity of rabbits subjected to various stimuli to hematopoiesis. In chambers in neutropenic hosts and in hosts injected with endotoxin, animals presumed to have an increased stimulus to granulopoiesis, there was increased production of granulocytes but there was also increased production of red cells. Although red cell production was decreased in chambers in polycythemic hosts, granulocyte production was not different from that in controls. Stimulation of erythropoiesis by erythropoietin injections or by exposure to hypoxia increased red cell production by marrow in the implanted diffusion chambers without diminishing granulopoiesis. Only in chambers in hosts made anemic by bleeding was there an increase in red cell production accompanied by a decrease in granulocyte production. In these anemic hosts induction of neutropenia led to an increase in granulopoiesis without any depression of erythropoiesis.


Separation of rabbit marrow precursor cells by combined isopycnic sedimentation and electronic cell sorting. Separation of developing cells into fractions of differing stages of maturity is critical to effective biochemical study of the process of cellular differentiation. Density gradient techniques utilizing rate-zonal or isopycnic separations have permitted partial separations based on cell mass or cell density. In this study the separation of various rabbit marrow cells was improved by high-speed flow analysis and sorting in a Coulter Two-Parameter Cell Sorter. After preliminary isopycnic separation of marrow cells in Ficoll-Hypaque, cells were sorted into lymphoid and myeloid elements, utilizing light-scatter (LS) profiles to determine sorting. Characteristic LS patterns were present for erythrocytes, lymphocytes, devitalized cells, and granulocytes. When erythrocytes and their precursors were removed by hypotonic lysis, the remaining granulocytes could be sorted to give samples with much greater purity with respect to developmental stage than was possible with density gradients alone. Thus the combination of techniques represents a significant improvement in the ability to study the mechanisms of normal or altered cellular maturation.


Marked reduction of spectrinin hereditary spherocytosis in the common house mouse. In contrast to the disease in humans, hereditary spherocytosis in the common house mouse produces an extreme spherocytosis. The cells show a broad distribution in size ranging from microcytic to macrocytic. Of particular interest is the finding of a substantial reduction in the major membrane polypeptide called spectrin, supporting a critical role for this protein in the control of erythrocyte shape and membrane stability.


Hormone-stimulated heme synthesis by isolated mitochondria. Erythropoietin (Ep), insulin, and prostaglandins E1 and A1 (PGE1, PGA1) enhanced heme synthesis by mitochondria isolated from embryonic and adult mouse liver cells. The combination of Ep with PGE1 had an antagonistic effect, while that of Ep with PGA1 gave an additive result. The capability of isolated human platelet mitochondria to synthesize heme was also shown. This activity was stimulated by Ep.


Failure of the alpha-thalassemia gene to decrease the severity of sickle cell anemia. A 15-yr-old black male with homozygous sickle cell disease was severely growth retarded and had a chronic hemolytic anemia requiring transfusions. Globin chain synthetic studies of both peripheral blood reticulocytes and bone marrow cells revealed a ratio of alpha to betas globin synthesis (alpha/betas ratio) of 0.5, indicating the presence of an alpha-thalassemia gene. Messenger RNA isolated from the bone marrow of the patient was translated in the wheat germ cell-free system, and the globin synthesized had an alpha/betas ratio of 0.7. The hemolysate prepared from incubated bone marrow cells was fractionated on a Sephadex G100 column. The results showed that there was a peak of radioactivity that eluted after the hemoglobin peak. When this pooled peak was analyzed by CMC chromatography, the alpha/betas ratio was 0.9. These globin intermediates, probably dimers, may have contributed to the hemolysis in this patient.


Monovalent cation composition and ATP and lipid content of irreversibly sickled cells. Discontinuous Stractan gradients were used to separate heterogeneous populations of sickle cells into discrete subpopulations containing varying proportions of reticulocytes, mature discoid cells, and irreversibly sickled cells (ISC). The improved homogeneity of these preparations, together with an enhanced yield of ISC, allowed us to distinguish effects of cell maturation from those of irreversible sickling. With these cell preparations we have begun to define physical properties of ISC. We confirmed the marked abnormalities in cation composition of native ISC. Measurements of ATP in ISC did not substantiate prior reports of ATP deficits. Finally, no evidence for substantial loss of membrane lipids during the process of ISC formation could be demonstrated.


[Comparison between cytochemical and gelelectrophoretic demonstration of acid phosphatases from leukocytes (author's transl)]. The cytochemical and gelelectrophoretic demonstration of acid phosphatases with substrates alpha-naphthyl phosphate and naphthol AS-BI phosphate and with couplers fast garnet GBC and hexazotized pararosanilin is described. Cytochemically best results are achieved wit naphthol AS-BI phosphate and pararosanilin, electrophoretically however with alpha-naphthyl phosphate and pararosanilin. This discrepancy ist explained by a different substrate affinity and membrane penetration of substrates.


Effects of petroleum hydrocarbon solvents on alkaline phosphatase of rats. After administration of benzene, gasoline, IOMEX or petroleum ether, liver alkaline phosphatase showed over 200% increase in activity whereas kidney alkaline phosphatase activity was depressed by 50%. The pattern of separation of isoenzymes of alkaline phosphatase in liver, kidney and serum indicated involvement of one of the isoenzymes. A simple method of detecting the incipent toxicity is described.


Mirex and behavior in the Long-Evans rat. In two experiments, adult male Long-Evans rats were fed chow containing mirex (1.78 ppm and 17.8 ppm in Experiment 1, 17.8 ppm in Experiment 2) over a several week period and were tested on a variety of behavioral tasks. No differences in behavior were seen between control and experimental animals tested in an open-field apparatus, on VI 30-sec and DRL 20-sec operant paradigms, or on a discrimination-reversal task motivated by escape from footshock.


The clinical reliability of brain stem auditory evoked responses. Auditory evoked responses thought to originate in the brain stem were investigated in patients with and without good evidence of brain stem pathology, and in healthy volunteers. The purpose of the investigation was to find a method of quantifying these evoked responses which would be clinically useful. The best quantitative measure was the latencies of certain peaks in the evoked response considered in combination. This measure indicated abnormal brain stem evoked responses in 64% of patients with good independent evidence of brain stem pathology; 23% of patients with equivocal independent evidence of brain stem pathology; and 0% of healthy volunteers.


The availability of statistics relating to deafness in the United Kingdom. Statistics concerning the prevalence of deafness in the United Kingdom are constantly being requested. Authoritative figures do not exist concerning the adult deaf population. However, a variety of statistics is available and an attempt has been made to collate these in order that some assessment of the size of the problem may be made.


Selection of hearing aids for severely deaf children. Procedures are described for selecting the gain and frequency response of hearing aids for deaf children and for evaluating aided hearing. These include a comparison of aided thresholds with the speech spectrum to determine how much of the frequency range is functional for each child. This provides a basis for deciding whether to select an aid having a "conventional" (C) response, which de-emphasises the low frequencies, or a low frequency (LF) response which provides more low frequency gain, although not necessarily low frequency emphasis. It is concluded that, for optical aid fitting, some children require "C" responses for both ears, others "LF" responses for both ears and others a "C" response for one ear and an "LF" response for the other. These three possibilities are all required sufficiently commonly that exclusive use of any one would inevitably result in relatively ineffective amplification for many deaf children.


Tolmesoxide, a drug that lowers blood pressure by a direct relaxant effect on vascular smooth muscle. 1 The blood pressure of conscious, deoxycorticosterone acetate (DOCA) hypertensive and 1 kidney Goldblatt hypertensive rats and renal hypertensive and normotensive cats was reduced by tolmesoxide (4,5-dimethoxy-o-tolyl methyl sulphoxide). 2 Tachycardia accompanied the hypotension. In rats the increase in heart rate was abolished by concurrent administration of propranolol. Tachycardia did not occur in pithed rats. 3 Vascoconstriction induced by sympathetic stimulation, noradrenaline, tyramine, angiotensin or vasporessin was antagonized by tolmesoxide. 4 The antagonism of vasoconstrictor responses produced by tolmesoxide was unaffected by beta-adrenoceptor, muscarinic or histamine antagonists. 5 It is concluded that the lowering of pressure produced by tolmesoxide results from a defect relaxant effect on vascular smooth muscle.


The effects of D-pencillamine and levamisole on leucocyte chemotaxis in the rat. The administration of D-penicillamine (25 mg/kg) or levamisole (5 mg/kg) had no effect on leucocyte emigration into the exudates formed in inert sponges implanted in normal rats. 2 In rats, previously sensitized to Bordetella pertussis and implanted with sponges containing pertussis vaccine, an increased leucocyte migration into the exudates occurred; this was significantly enhanced by the administration of the drugs. 3 Neither drug in vitro affected the chemotaxis of rat polymorphonuclear leucocytes although random migration was significantly increased by levamisole (2 microgram to 1 mg/ml). Neither drug affected the chemotaxis of rat mononuclear cells although levamisole (25 microgram/ml) significantly increased that of human monocytes. 4 It is concluded that both drugs produce similar effects in an animal model of delayed hypersensitivity and that their clinical antirheumatic actions may have common elements.


Effects of some pyrazinecarboxamides on sodium transport in frog skin. 1 The inhibitory effect of amiloride (N-amidino-3,5-diamino-6-chloropyrazinecarboxamide) on sodium transport in isolated skin of frog has been compared with 17 of its analogues. The dissociation constant of amiloride for passive sodium channels was 181.9 +/- 8.9 nM, and the maximal percentage inhibition of sodium transport was 101.3 +/- 0.4% (means of 123 measurements) when measured at a sodium concentration of 111 mM. 2 The N-benzylamidino and N-o-chlorobenzylamidino compounds had affinities approximately 20 times larger than those for amiloride, and produced maximal inhibition of transport. 3 Substitution of chlorine in the 6-position by other halogens showed that the bromo-compound was equally active to amiloride, whereas the iodo derivative had an affinity equal to 15% of that for amiloride. 4 Substitution in the 5-amino group in 10 compounds reduced the affinities to less than 1% of that of amiloride, without affecting their ability to produce complete inhibition of transport. 5 N-Amidino-3,5-diaminopyrazinecarboxamide was unique in that it produced an unusual concentration-response relationship.


The uptake and release of [3-H]-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthlane (ADTN) by striatal nerve terminals. A study has been made of the uptake and release of [G-3H]-2-amino 6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) by crude striatal synaptosomes of the rat. 2 Uptake was rapid, temperature-dependent and could be suppressed by a variety of metabolic inhibitors. 3 The Michaelis-Menten kinetincs indicated the presence of two distinct transport systems in the striatum which were of much higher capacity than those found in the cerebellum, which lacks dopaminergic innervation. 4 Uptake of [3-H]ADTN was strongly inhibited by dopamine and the two potent dopamine-uptake inhibitors, benztropine and nomifensine, but only weakly by imipramine and amphetamine (the latter in non-reserpine-treated animals). 5 Accumulated [3-H]ADTN could be released from striatal slices by elevated K+. A similar release was evoked upon the addition of the ionophore, A23187. 6 The most potent releaser of [3-H]ADTN was (+)-amphetamine. This effect occurred at concentrations inactive against ADTN uptake. The neuroleptic cis-flupenthixol produced an inhibition of the spontaneous release. 7 It is concluded that [3-H]ADTN is accumulated preferentially into areas of the rat brain rich in dopamine. The pharmacological specificity of the uptake suggests that it is a good substrate for the dopamine carrier. Following uptake, [3-H]-ADTN may be released by K+ and a calcium ioniphore, which raises the possibility that ADTN might act as a false transmitter.


Tachyphylaxis to ethacrynic acid in the isolated atrium of guinea-pig and its relation to noradrenaline stores. 1 The isolated electrically-paced atrium of the guinea-pig developed a dose-dependent increase in the force of contraction in response to ethacrynic acid (12-100 microgram/ml) which was blocked by pretreatment of the animals with reserpine but was unaffected by desipramine or colchicine added to the bathing medium. 2 There was a rapidly developing tachyphylaxis to repeated doses of ethacrynic acid which was not reversed by rest or incubation of the tissue with noradrenaline. 3 There was no cross tachyphylaxis between ethacrynic acid and tyramine, amphetamine or nicotine. 4 Ethacrynic acid (200 microgram/ml) decreased the noradrenaline content of the atria by 32%. 5 It is concluded that ethacrynic acid exerts its effects indirectly through the release of endogenous noradrenaline and that the mechanism of release seems to be different from that of other known indirect sympathomimetic drugs.


Interaction of pentobarbitone and gamma-aminobutyric acid on mammalian sympathetic ganglion cells. 1. Interactions of bath-applied pentobarbitone and gamma-aminobutyric acid (GABA) on neurones in isolated superior cervical ganglia of the rat have been examined with intracellular microelectrodes. 2. Pentobarbitone itself (30 micrometer-1 mM) showed no clear or consistent GABA-like effects: changes in resting input conductance and membrane potential were small and variable. 3. Pentobarbitone (100 micrometer) strikingly enhanced the conductance increases produced by GABA and 3-aminopropanesulphonic acid, and reversed the depression of GABA-evoked responses by bicuculline. 4. It is concluded that reversal of bicuculline action at the membrane conductance level might be explained by augmentation of GABA-action. This augmentation cannot be attributed to 'partial agonist' properties of pentobarbitone or to interference with glial transport processes.


Effects of propylbenzilylcholine mustard on injection into the liquor space of cats. In unanaesthetized cats the effects were examined of propylbenzilylcholine mustard (PrBCM) on injection into the cannulated cerebral ventricles and cisterna magna. Extreme motor excitation, vocalization, shivering leading to fever, tachypnoea, panting, piloerection and salivation were produced on ventricular, vigorous scratching bouts on cisternal, injections. The sites of these actions are discussed. None of the effects was produced by atropine similarly injected. All effects were suppressed by anaesthetizing doses of pentobarbitone sodium injected intraperitoneally.


Role of platelets in aspirin-sensitive bronchoconstriction in the guinea-pig; interactions with salicylic acid. 1 The bronchoconstriction caused in the guinea-pig by arachidonic acid (AA), bradykinin, adenosine diphosphate (ADP) and adenosine triphosphate (ATP) was correlated with effects on platelets. ATP and ADP produced a brief thrombocytopenia and AA a more prolonged one. Bradykinin had no effect on platelets.2 Aspirin inhibited bronchoconstriction and thrombocytopenia produced by AA and part of the bronchoconstriction produced by ATP, but had no effect against ADP. Thrombocytopenia produced by ADP and ATP was not affected by aspirin or indomethacin.3 Platelet depletion by antiserum prevented bronchoconstriction in response to ADP and to ATP, but not in response to bradykinin or to AA, showing that platelets are not involved in aspirin-sensitive bronchoconstriction. Infusions of ADP reduced bronchoconstriction and thrombocytopenia in response to ADP itself and to ATP, but not to AA. Bronchoconstriction by ADP or ATP involves an action on platelets. Only that due to ATP is partially dependent on the activity of prostaglandin synthetase.4 ATP induced aggregation in vitro in guinea-pig platelet-rich plasma (PRP). Rabbit PRP responded only when ATP was first incubated with guinea-pig plasma. The aggregating compound formed was probably ADP, since it was destroyed by apyrase. Its formation was not inhibited by aspirin or indomethacin, indicating that aspirin inhibits ATP-induced bronchoconstriction by a different mechanism.5 The aggregating effect of ATP on guinea-pig platelets was inhibited by concentrations of apyrase that block ADP-induced aggregation, and potentiated by lower concentrations of apyrase.6 Adenosine 5'-tetraphosphate did not aggregate platelets in vivo or in vitro. In vitro aggregation occurred when apyrase was added, suggesting transformation into ADP. Adenosine 5'-tetraphosphate and apyrase inhibited aggregation due to ADP, but failed to affect that due to AA. This suggests that aggregation involving products of prostaglandin synthesis does not require ADP.7 Salicylic acid did not interfere with bronchoconstriction or aggregation due to AA, but prevented inhibition by aspirin when the weight ratio, salicylic acid:aspirin was 4:1. Salicyclic acid may be useful in studies of potential inhibitors of thromboxane A2 synthesis and of thromboxane A2-dependent processes in vivo and in vitro.


Inhibition by morphine of prostaglandin-stimulated fluid secretion in rat jejunum. 1 Anesthetized rats (225 to 300 g) were used to study the inhibitory effect of morphine on fluid secreted by the small intestine. 2 Small intestinal fluid secretion was stimulated by infusion of prostaglandin E1 (PGE1) into the aortic arch, the jejunum being more sensitive than the ileum. Infusion of PGE1 2 microgram/min caused maximal net fluid secretion in the jejunum but inhibited net fluid absorption in the ileum. 3 Morphine caused a dose-related inhibition of maximal PGE1-stimulated fluid secretion in the jejunum. At the higher doses of morphine used (5 to 20 mg/kg) the fluid transporting function of the jejunum was restored almost to normal net absorption. 4 The inhibitory effect of morphine on PGE1-stimulated fluid secretion was antagonized by naloxone. Naloxone caused a parallel shift to the right of the dose-response curve for morphine. 5 Two other narcotic analgesics were assayed relative to morphine and their descending order of potency was oxymorphone greater than morphine greater than pethidine. 6 It is suggested that the antisecretory effect of morphine in the small intestine may contribute to its efficacy as an anti-diarrhoeal drug. Further studies on the rat jejunum may show it to be a useful model for predicting narcotic drug activity and as such, may give some insight into the mechanisms of action of these drugs.


Hyperthermic responses to central and peripheral injections of morphine sulphate in the cat. 1 The effect of morphine on body temperature was studied in conscious, unrestrained cats provided with implanted third or lateral cerebral ventricular cannulae, jugular venous catheters and retroperitoneal thermocouples.2 Intraventricular injections of 2.5-50 mug and intravenous injections of 1-10 mg/kg morphine sulphate produced dose-related hyperthermic responses. Similar mean increases in body temperature after administration of a given dose were elicited in cats which had not previously received morphine and, provided that tolerance was avoided by spacing injections at least 72 h apart, in cats which received a series of injections of morphine. Morphine was at least 850 times more potent when injected into the third ventricle than when given intravenously. Increasing the dose of morphine sulphate injected into the third ventricle to 1250 mug only prolonged the hyperthermia. Morphine did not produce hypothermia at any dose tested.3 Injection of 10 mug morphine sulphate into the third ventricle produced similar hyperthermias at ambient temperatures (tas) of 4-6, 21-23 and 33-36 degrees C. The increase in body temperature was associated with shivering at the lower tas. At the highest ta, shivering was not evoked, but respiratory rate decreased after morphine if it was initially elevated. These results suggest that morphine increased the level at which body temperature was regulated.4 Neither metiamide nor indomethacin antagonized morphine so histamine and prostaglandins were apparently not required for the hyperthermic effect.


Central adrenoceptors and cholinoceptors in cardiovascular control. 1. In cats anaesthetized with chloralose, adrenoceptor and cholinoceptor agonists and antagonists were localized to the posterior hypothalamus (PH), lateral medullary pressor area (LMPA) and spinal autonomic loci to delineate the role of central cholinoceptors and adrenoceptors in cardiovascular control. 2 All along the neuroaxis, the alpha-adrenoceptors seem to subserve an inhibitory and the beta-adrenoceptors a facilitatory role in cardiovascular control. There appear to be a predominance of alpha-adrenoceptors at the medullary level and beta-adrenoceptors at the hypothalamic level. 3 The nicotinic cholinoceptors at the hypothalamic, medullary and spinal levels were facilitatory, whereas muscarinic cholinoceptors were inhibitory for cardiovascular control. However, muscarinic receptors were undetectable at the posterior hypothalamus. 4 The central cardiovascular effects of nicotine are attributed to nicotinic receptor activation and release of central catecholamines. 5 There appears to be a relationship between central cholinergic and adrenergic mechanisms in cardiovascular control.


Interpersonal distance as a function of situationally induced anxiety. Two experiments were conducted to investigate the effects of situationally induced anxiety on interpersonal distance in a two-person conversation. In the anxiety-arousing situation subjects were asked to discuss an interesting incident while their social competence was assessed from behind a one-way screen. The briefing and debriefing periods were used for control purposes. Analysis of speech disturbance rates showed that the anxiety manipulation was successful. A significant increase in interpersonal distance was found in the anxiety-inducing situation relative to the low stress situation. The implications for the controversy concerning the effect of anxiety on the need for affliation are discussed.


Retrieval from long-term memory in presenile dementia:two tests of an hypothesis. Recent experimental studies have suggested that patients with presenile dementia might have diffculty in retrieving information from memory as well as a reduced ability to acquire new information. The hypothesis that this retrieval difficulty might be due to an inability to inhibit the recall of irrelevant information was tested by two investigations. Free recall data failed to give clear support for the hypothesis but a prediction based upon recognition testing was confirmed.


Reducing multiple problem behaviours in a profoundly retarded child. The purpose of the present paper is to describe two behaviour management programmes developed for a profoundly retarded child in a special education classroom. The target behaviours were:(1)inappropriate object contract,(2)wild running about the room, and(3)consistent refusal to eat. Literature was reviewed in an effort to fine information which would help in the management of these behaviours. However,only a limited number of studies were found to be directly relevant. Salzberg & Napolitan(1974)modified inappropriate object contact through physical restraint. Neumann & Gaoni(1975)increased food consumption in a woman suffering from anorexia nervosa by using preferred foods. No literature was found which demonstrated the suppression of wild running behavior.


Controlled drinking training with a female alcoholic. Controlled drinking training based upon an avoidance conditioning paradigm (Mills, Sobell & Schaefer, 1971) has previously been demonstrated to offer an alternative to abstinence for some alcoholics. This paper describes the treatment and outcome of controlled drinking training as applied to a 33 year old female who had previously attempted abstinence and who could engage in sexual intercourse only after drinking.


An investigation of the role of 'hypnosis', hypnotic susceptibility and hypnotic induction in the production of age regression. In response to criticisms of the methodology of Barber's(1969)experiments, a 2x2 factorial design, varying hypnotic susceptibility and hypnotic treatment, was used to study the role of 'hypnosis' in the production of age regression by suggestion. Twenty subjects of high hypnotic susceptibility and 20 subjects of low hypnotic susceptibility were randomly allocated to one of two treatment conditions:hypnotic induction procedure or motivational instructions. Both  treatments were followed by suggestions to regress to the age of seven years. Two measures of age regression were taken:the Draw-A-Man-Test and a subjective rating of the reality of the experience. The results showed significant effects of both variables, with high suceptibility and induction treatment producing better regression on both measures than low susceptibility and motivation treatment. Hypnotic susceptibility was the stronger of the two variables. The ranking of the four conditions corresponded with predictions of hypnotic depth from the state theory of hypnosis, but the findings were not inconsistent with the non-state theory. The drawings of all regressed groups were more mature than the norms for the age of seven and the drawings of a group of seven year old children.


Attention, eye tracking and schizophrenia. Two experiments are reported. The first experiment successfully replicated the finding that Smooth Pursuit Eye-Tracking(SPET) performance recorded using electronsystagmographic techniques statistically differentiates between groups of clinically diagnosed shizophrenic patients and normal controls. Ratings taken of spontaneous patient behaviour during testing indicated that behaviour which on a priori grounds was thought to preclude optimum attention to eye tracking was related to greater impairment of schizophrenic performance. The second experiment investigated the effect of experimentally induced distraction on SPET performance by normal controls. It was found that competing tasks of increasing levels of difficulty produced increasing degrees of impairment in SPET performance. The results of the two experiments were interpreted as evidence that SPET performance is sensitive to superficial inattention, and that deficits in schizophrenic SPET performance are best explained by attentional deficits in the schizophrenics.


Sixth interim progress report of the British Institute of Radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx. The results are reported of the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx. 687 patient records have been analysed with respect to survival rates, recurrence-free rates and laryngectomy-free rates. For the group as a whole these analyses show no difference between the two fractionation regimes. Analysis of the sub-group which had early disease confined to the vocal cords does, however, show a better recurrence-free and laryngectomy-free rate for those patients treated with 5F/week, though the survival rate for the two groups remains similar. Acute and late normal tissue reactions are reported for up to six years after treatment. It appears that treatment with 3F/week can be given safely to patients with advanced disease. The differences between the two treatment groups who had early disease of the vocal cords are discussed, but until more data become available in the future the problems raised cannot be resolved.


Ioglycamide (Biligram) studies in man--plasma binding, renal and biliary excretion studies in jaundiced and anicteric patients. When five patients with varying degrees of hepatic impairment and a T-tube in situ were given intravenous ioglycamide at a rate of 2 mg/kg/min for two hours the mean biliary excretion in the first two hours was only 3.2% of the administered dose. In contrast, in five T-tube patients with relatively normal liver function the mean biliary excretion over the same time interval was 20.6%. The mean plasma concentration of ioglycamide achieved at the end of a two-hour intravenous infusion at 2 mg/kg/min was 1427 +/- 187 microgram/ml in six anicteric patients and 1262 +/- 82 in six jaundiced patients. Despite these very similar plasma levels the 24-hour urinary excretion of ioglycamide was 42.3 +/- 3.8% of the administered dose in the patients with jaundice compared with only 18.1 +/- 2.4% in the anicteric group. These differences probably reflect the fact that the percentage of unbound contrast agent in the plasma of the jaundiced group (11.9 +/- 1.9%) was significantly higher than that of the anicteric group (6.4 +/- 0.9%). It is suggested that bilirubin and possibly other substances in the plasma are competing with ioglycamide for binding sites on albumin. These factors need to be borne in mind when performing intravenous cholangiograms on jaundiced patients.


Endoscopic and radiological assessment of recurrent ulceration after peptic ulcer surgery. One hundred and eighteen patients with dyspepsia after peptic ulcer surgery were assessed by a double contrast barium meal and fibre-optic endoscopy, for the possibility of recurrent ulceration. There was overall endoscopic-radiological agreement in 89%. It is concluded that the two techniques are complementary and that a double contrast barium meal performed and interpreted by an experienced radiologist can demonstrate the presence or absence of a recurrent peptic ulcer with an acceptable degree of accuracy.


Protection of the eye during carotid angiography. An eye shield was developed for use in neurological examinations in projections in which it does not interfere with the information sought. Use of this shield in A.P., oblique, 30 deg Towne's and 12 deg carotid Towne's projections reduced the corneal dose to approximately 5% of the unshielded value. For lateral projections, doses were reduced to approximately 5-15%. Use of the shield resulted in corneal doses of the order of 0.5 mrad/mAs and 1.0 mrad/mAs for standard and magnified projections respectively, with the exception of the lateral projections for which the corresponding values were approximately 0.3 mrad/mAs and 0.7 mrad/mAs. Corneal dose for a typical carotid angiogram was estimated to be reduced from 6.2 rad to 0.33 rad by the use of the shield.


A computer simulation study of optimal thyroid radiation protection during investigations involving the administration of radioiodine-labelled pharmaceuticals. The administration of iodide for thyroid blocking is now known to carry its own risks, at least in certain categories of patients. We have therefore made a theoretical study by computer simulation of the efficacy of various thyroid blocking regimes. In the case of injected 125I- or 131I-iodide, substantial thyroid protection may theoretically be achieved by a single oral dose of inorganic iodide, for example a 90% reduction in radiation dose is produced by only 20 mg iodide. Repeating the initial blocking dose is of little value. A single blocking dose, however, affords poor protection against radioiodine released from labelled plasma proteins. Both for short-lived proteins such as fibrinogen, and for the longer-lived proteins such as albumin, the optimum dosage schedule appears to be stable iodide given daily for two to three weeks. For instance, 10 mg daily for a fortnight will reduce thyroid irradiation by a factor of ten following injection of 125I-fibrinogen.


Display of cross sectional anatomy by nuclear magnetic resonance imaging. High definition cross-sectional images produced by a new nuclear magnetic resonance (NMR) technique are shown. The images are a series of thin section scans in the coronal plane of the head of a rabbit. The NMR images are derived from the distribution of the density of mobile hydrogen atoms. Various tissue types can be distinguished and a clear registration of gross anatomy is demonstrated. No known hazards are associated with the technique.


Rectilinear bone scanning: differentiation between metastases and degenerative spinal disease. Criteria have been developed for radioisotope scanning of bone with an eight-colour-display rectilinear scanner, to differentiate metastases from degenerative spinal disease. If the area of increased uptake is two or more colours "hotter" than normal, this is probably due to metastases even if degenerative spinal disease coexists. The positivity of a scan due to degenerative spinal disease is a function of the degree of sclerosis adjacent to the intervertebral discs and apophyseal joints; it is not related to the degree of osteophyte formation.


Central airways obstruction in carcinoma of the bronchus treated by radiotherapy: a study of pulmonary function. A battery of lung function tests was performed on 28 patients with carcinoma of the bronchus, before radiotherapy, six weeks later, and at three months. Twenty-five had evidence of ariways obstruction, though only five had a forced expiratory ratio of less than 50%. Nine were shown to have obstruction to a main or lobar bronchus, while 11 definitely did not, but the only significant difference in lung function between groups was in the residual volume calculated from single breath helium dilution. Eight of ten cases of squamous cell carcinoma were central, and seven of these obstructive. Of seven cases with undifferentiated cells only two were central (p less than 0.05) and one obstructive. Breathlessness on presentation was significantly more common in patients with central tumours (6/12) than those with peripheral lesions (1/8), and all six breathless patients with central tumours claimed that this symptom improved after radiotherapy. Radiotherapy may have a palliative effect for breathlessness in patients with central airways obstruction due to tumour.


Response of selected tumour cell populations separated from a fibrosarcoma following irradiation in situ with fast neutrons. We have characterized selected populations of fibrosarcoma cells separated on density gradients of Renografin with respect to distribution in the cell cycle, clonogenic ability, and response to radiation. The latter two parameters have been observed to be related to the density of the cells, the denser populations being less clonogenic but more resistant to both low and high LET radiation. We have determined that these cells effectively repair potentially lethal damage if allowed to remain in situ following exposure to low LET radiation. This repair ability is not observed, however, following neutron irradiation. In addition, cells left in situ are relatively more sensitive to low doses of either low or high LET radiation. This difference in response is believed to be due to differences in the expression of damage by cells left in situ as compared to those assayed immediately. These data reflect the usefulness of cell separation methods in the study of solid tumour systems. Specifically, these methods reduce the heterogeneity found in the solid tumour by allowing for the isolation of subpopulations which then can be studied either individually or in relation to the entire tumour.


Hyperthermic sensitization of mouse intestine to damage by X rays: the effect of sequence and temporal separation of the two treatments. Adult mice were irradiated with between 7 and 15 Gy of X rays to the abdomen either before or after immersion of the lower half of the body in water at various temperatures. The thermal enhancement of X-irradiation damage to the intestine was estimated using survival at five days as the endpoint. Thermal enhancement ratios (defined as the ratio between the dose of X rays and the dose of X rays plus heat to produce the same level of damage) were calculated at the 50% survival level. If only a few minutes separated the application of heat and irradiation, the values obtained were similar to those reported for other normal tissues. There was only a slight dependence on the sequence of the two treatments. As the time interval between the two treatments was increased the effect of heat was reduced and a normal irradiation response was obtained when the separation was greater than about four hours. The results are compared with those for other normal tissues and tumours and the relevance of these findings in the design of optimal therapeutic schedules of combined heat and X rays is discussed.


The therapeutic advantage of combined heat and X rays on a mouse fibrosarcoma. The response of an experimental fibrosarcoma to combined heat and X rays has been assessed using delay in tumour regrowth. No thermal sensitization was observed for one hour of heating at 41.5 degrees C. A thermal enhancement ratio of 1.4 to 1.5 was seen for one hour of heating at 42.5 or 43.5 degrees C immediately after irradiation. The importance of the sequence and time interval between the two modalities was tested using a constant heat treatment of 42.5 degrees C for one hour. Heating was most effective when given after irradiation, with little change in TER for an interval of a half to six hours. When heat preceded the irradiation the pattern was more complex, with no sensitization at half, one, and six hours, but with a significant effect at two and three hours. The degree of sensitization often depended upon the X-ray dose, being lower below X-ray doses of about 20 Gy. The therapeutic advantage of the combined treatment was assessed by comparison with previously published results for skin reactions. No therapeutic benefit was found for treatments when heat and X-rays were separated by one hour or less. A therapeutic gain factor of about 1.3 was observed for heat given two to six hours after irradiation of this fibrosarcoma.


Causes of failure in the surgical treatment of primary hyperparathyroidism: lessons from 51 successful reoperations. A review of 51 successful reoperations for persisting hypercalcaemia due to primary hyperparathyroidism shows that inadequate anatomical knowledge, inadequate surgical technique and unusual localizations of the parathyroids are the most frequent causes of failure of the primary operation. The majority of these failures are therefore preventable. There is a frequent need for cervical thymectomy in parathyroid surgery. Sternotomy is only very rarely necessary.


Diabetic autonomic neuropathy in patients with vascular disease. An attempt has been made to determine the effect on vasomotor tone and sweating of peripheral neuropathy in the feet of diabetics with vascular disease. There was a loss of vasomotor tone in 48 per cent of patients with peripheral neuropathy and in 12 per cent of those without neuropathy (P less than 0.01). Complete loss of sudomotor activity was rare in both groups.


Intestinal ischaemia associated with ileal carcinoid tumours. A case of intestinal infarction due to multiple ileal carcinoid tumours is presented in which abdominal pain due to intestinal ischaemia was the first manifestation of the underlying tumour. It is postulated that intestinal ischaemia may be of more importance in the production of abdominal pain by carcinoid tumours than has been generally accepted, and that it is the result of functional and structural changes in the around the mesenteric blood vessels, caused by substances secreted by the carcinoid tumour.


Abdominal apoplexy.

Abdominal apoplexy. Two cases of the rare condition of abdominal apoplexy are described. The two main clincial presentations of this condition are discussed as is the aetiology. It is suggested that selective visceral angiography might prove helpful in preoperative diagnosis.


Abdominal apoplexy.

Abdominal apoplexy. Seven patients with abdominal apoplexy have been treated between 1975 and 1977 and their clinical features and management are reviewed. Accurate preoperative diagnosis is difficult but the condition should be considered in patients with abdominal pain and vomiting or diarrhoea who have signs of shock, peritonism or a falling haemoglobin level. Urgent laparotomy to identify and ligate the bleeding artery offers the best chance of survival.


Roux diversion for bile reflux following gastric surgery. Regurgitation of bile into the stomach after gastric surgery often causes severe and distressing symptoms, though the onset may be delayed for some years. We have used a Roux loop diversion as a secondary procedure for bile reflux in 36 patients, making the anastomosis from 18 to 40 cm below the stomach. There were no deaths and the clinical results were good in 20 of 27 patients followed up from 1 to 10 years. Vagotomy was omitted in 13 patients, 2 of whom subsequently developed jejunal ulceration. One patient developed an unexplained gastric ulcer and 2 operations failed because the loop was too short. The optimum length may well be 40 cm and vagotomy should be added in all cases. In 3 patients with associated dumping the upper 10 cm of the Roux loop was reversed.


Parietal wound drainage in abdominal surgery. A prospective randomized study of wound drainage in 250 surgical abdominal wounds was undertaken to determine (a) what effect wound drains had on clean surgical wounds; (b) whether wound drains reduced infection in potentially contaminated wounds; (c) whether wound drainage was an acceptable alternative to the use of topical antibiotics in frankly contaminated wounds. Ten per cent of clean wounds which had been drained became infected, compared with 2 per cent of control wounds in the same group (P less than 0.002). Infection was also more common in potentially and frankly contaminated wounds in the presence of a drain. Skin organisms were grown from 8 drained and 2 nondrained wounds in this group (P less than 0.005), suggesting contamination by the drains. Drains were, however, associated with a lower infection rate in 23 obese patients with frankly contaminated wounds.


A prospective study of the clinical value and accuracy of grey scale ultrasound in detecting gallstones. The accuracy and possible clinical value of grey scale ultrasonography in the detection of gallstones has been prospectively studied in 100 unselected patients presenting with recurrent biliary colic, acute cholecystitis or acute pancreatitis. Adequate visualization of the gallbladder was obtained in 79 cases, with 3 false positive  and no false negative reports. Oral cholecystography remains the initial investigation of choice in patients presenting with recurrent biliary colic, but grey scale ultrasound has been shown in this study to be a reliable means of detecting gallstones in the 'acute' situation, when conventional contrast radiology is of limited value.


Non-operative removal of retained stones in the common bile duct. A method of removal of retained common bile duct stones under radiological control is described and its use in 16 patients reported. The ease of the method, the minimal associated morbidity and the inexpensiveness of the equipment suggest that this should be the primary method of removal of retained stones when a T tube has been placed into the common bile duct.


Drug therapy in intermittent claudication: an objective assessment of the effects of three drugs on patients with intermittent claudication. It has been suggested that, by reducing the viscosity of blood, flow through capillaries is increased with consequent improvement in the symptoms of patients with peripheral vascular disease. We examined the effects of treatment with drugs purported to reduce blood viscosity to test the validity of this claim. Measurements of viscosity and the rate of blood flow to the leg were made in a group of patients before and after treatment with three different drugs--tetranicotinoylfructose (Bradilan), oxypentifylline (Trental) and cinnarizine (Stugeron). All patients had intermittent claudication in one leg and the distribution of arteriosclerosis was similar in each patient. After treatment there was little or no change in blood viscosity and no change in the rate of flow recorded in the symptomatic legs. We did not find any objective evidence to support the use of these drugs in patients with intermittent claudication.


The treatment of early colorectal cancer by local excision. An analysis is presented of 143 patients with early colorectal carcinoma treated by local excision between 1948 and 1972 at St Mark's Hospital. The tumours are considered in three groups; colonic tumours, pedunculated rectal tumours and non-pedunculated rectal tumours. The importance of careful clinical assessment and accurate pathological examination is emphasized. Local excision of the tumours, using various operative techniques, gave good results and this method of management can be recommended in the carefully selected case.


Balloon catheter contol of a ruptured abdominal aortic aneurysm in a patient with Cullen's sign. A patient with Cullen's sign due to a ruptured abdominal aortic aneurysm is reported. At operation a balloon catheter was used to stop severe retroperitoneal bleeding and the aneurysm was replaced with a graft.


Popliteal vein entrapment.

Popliteal vein entrapment. A case of popliteal vein entrapment by an abnormal 'third' head of the gastrocnemius muscle is reported. Complete relief of disabling symptoms was obtained by dividing the abnormal muscle band.


A new method of nerve repair: repair of a lesion of the radial nerve with a branch to the triceps muscle. Regeneration of the radial nerve following a new technique of nerve anastomosis in the humeral spiral groove is reported. Neurorrhaphy was performed by anastomosing a branch supplying the medial head of the triceps to the distal cut end of the radial nerve at the level of the lateral intermuscular septum. The progress of the nerve is detailed and has been confirmed by electromyographic studies showing regeneration of the radial nerve 3 years after operation and 4 years after injury. This technique for repair of the radial nerve has not been previously described.


Factors influencing the incidence of neonatal jaundice. A retrospective study of 12 461 single births confirmed an association between maternal oxytocin infusion and neonatal jaundice. The effect of oxytocin on jaundice was independent of gestational age at birth, sex, race, epidural anaesthesia, method of delivery, and birth weight, each of which was significantly associated with neonatal jaundice. The effect of oxytocin was, however, small, producing a calculated mean increase in peak plasma bilirubin concentration of 8.6 mumol/1 (0.5 mg/100 ml); this excess was independent of sex and less than the effect of the baby being born one week earlier.


High prevalence of hyperuricaemia and gout in an urbanised Micronesian population. The prevalence of hyperuricaemia and gout was investigated in the Micronesian inhabitants of the highly urbanised central Pacific island of Nauru. Sixty-four per cent of men and 60% of women aged 20 years and over had hyperuricaemia--the highest prevalence rates yet reported for a population. The hyperuricaemia in men was accompanied by a high prevalence of clinical gout (6.9%). While the hyperuricaemia is probably genetic, the high prevalence of gout may be related to the environmental change from the traditional island style of living to one of almost complete Westernisation.


Mechanism of action of insulin in diabetic patients: a dose-related effect on glucose production and utilisation. Six insulin-requiring diabetics were studied after insulin had been withheld for 24 hours. On three separate occasions each received a two-hour infusion of insulin at a low dose (2.6 U/h) and a high dose (10.6 U/h) and an infusion of saline as control. The rates of production and utilisation of glucose were measured isotopically. The rate of fall of plasma glucose concentration was faster on the high-dose infusion of insulin than on the low, whereas the fall in plasma free fatty acids, glycerol, and keton bodies was the same on both insulin infusions. The mechanism whereby the two rates of insulin administration lowered plasma glucose concentration differed: during the low-dose infusion the decrease in the glucose concentration was produced entirely by a fall of hepatic glucose output, whereas during the high-dose insulin infusion the glucose concentration fell because both the rate of glucose production fell and the rate of glucose utilisation rose. In all experiments there was a direct relation between a fall in serum potassium concentration and the fall in plasma glucose concentration irrespective of the mechanism that reduced the glucose concentration.These results indicate that in uncontrolled diabetics low-dose insulin infusions lower the blood glucose concentration entirely by reducing glucose production from the liver and that the effect of insulin on potassium transport is independent of its effect on glucose uptake.


How much physical therapy for patients with stroke? The use of physiotherapy, occupational therapy, and speech therapy for patients with stroke was investigated, and the three treatments were compared. Out of 135 patients with stroke surviving at two weeks, 107 received physiotherapy, but only 35 received occupational therapy and 19 speech therapy. Those who received most physiotherapy were the most severely disabled and had the worst prognosis, and, although almost no recovery occurred after six months, 30 patients continued with treatment beyond this time. Stiff and painful shoulders were present in 21 of the patients by two weeks and had developed in a further 37 by one year. Physiotherapy did not prevent this. The objectives of physiotherapy for patients with stroke need careful definition, with emphasis on treatment in the early months. Alternative treatment, possibly carried out by volunteers or more simply trained personnel, merits further consideration.


Subarachnoid haemorrhage: long-term follow-up results of late surgical versus conservative treatment. During 1964-9, 178 patients with subarachnoid haemorrhage from a single intracranial arterial aneurysm were allocated at random to receive operative or conservative treatment at an average of seven weeks after bleeding. During the follow-up fatal rebleeding episodes occurred in six of the 86 patients treated surgically and 16 of the 92 treated conservatively. This difference was significant. Fatal rebleeding occurred on average 40 months after the first episode. Deaths from all causes occurred in 17 of the 86 patients treated surgically and 22 of the 92 treated conservatively. Life-table analysis of the chances of surviving 1, 5, and 11 years gave probabilities of 95 and 91%, 87 and 86%, and 76 and 75% in the two treatment groups respectively. Of the 139 patients alive after a mean follow-up of nine years, 130 (94%) were fully independent in their daily lives, and only 43 (31%) were unable to work. The method of treatment did not affect the quality of survival.The results show that fatal rebleeding may occur even many years after the first episode. Nevertheless, if the patient is in good condition seven weeks after a haemorrhage from a single intracranial arterial aneurysm the outcome is good irrespective of whether operation is performed at this late stage.


Vision screening in children tested at 7, 11, and 16 years. Distant vision screenings of a national sample of children were performed at the ages of 7, 11, and 16. Many children with normal vision at one screening showed defects at later screenings, and altogether 18% of children with normal vision at the age of 7 had defects by the time they were 16. Twelve per cent of those with normal vision at 7 and 11 had developed a visual defect by the age of 16. Apparent improvements between screenings probably resulted largely from technical difficulties inherent in testing young children. The results clearly indicate the importance of regular vision screening during the school years and the need for comprehensive but flexible back-up services.


The consultation and the therapeutic illusion. At 45 general-practice surgery sessions 200 patients in whom no definite diagnosis could be made were randomly selected for one of two procedures. Either they were given a symptomatic diagnosis and medications, or they were told that they had no evidence of disease and therefore they required no treatment. No difference in outcome was found between these two methods as judged by the return or not of the patient within one month and his statement that he did or did not get better.


Intermittent claudication: factors determining outcome. Two groups of patients were followed up for four to eight years after first referral or admission to hospital for intermittent claudication (IC) in a study of the natural history of the disease and of factors determining its outcome. In one series of 60 patients, those who stopped or reduced smoking after referral had a much improved prognosis. Thus even after the diagnosis of IC it is extremely important that patients should be encouraged to stop smoking, since this correctable factor appears to be of greater importance in determining outcome than other medical risk factors for the disease that are less amenable to treatment. In the second study, 160 patients were followed up for eight years after first hospital admission. They had a total of 480 hospital admissions and had spent 11 190 days in hospital; their life expectancy after the age of 60 was about half that of the general population. Age, coronary artery disease, cerebrovascular disease, and diabetes were associated with an adverse outcome.


Intermittent claudication: prevalence and risk factors. Risk factors for intermittent claudication (IC) were studied in 54 patients--that is, all patients with IC on the lists of two general practices--and 108 controls. Smoking was the factor most strongly associated with the development of IC, but systolic and diastolic blood pressures and concentrations of triglyceride, urate, and fibrinogen were all significantly higher among the patients with IC than the controls. The presence of more than one factor appeared to be associated with a multiplicative increase in risk. Cholesterol, an important risk factor for ischaemic heart disease, was not associated with an increased risk of IC. IC was present in about 2% of the men and 1% of the women, who were aged 45-69 years. These findings suggest that IC, a common and disabling manifestation of atheroslcerosis, may be largely preventable.


Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man? Small doses (1-10 microgram daily) of 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders or mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH)2D3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH)2D3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent.


Simplified oesophageal transection for bleeding varices. Thirty patients with bleeding oesophageal varices were treated by oesophageal transection using the SPTU gun. Any form of shunt was contraindicated in all the patients. Twelve operations were done as urgent procedures within 36 hours of haemorrhage. The overall operative mortality rate was 10%, and there were two late deaths during follow-up, which has so far extended from two months to two years. Three of the patients had recurrent bleeding, and residual varices were probably the source in two. There were no cases of portal systemic encephalopathy. Although the follow-up is too short to allow any definite conclusions, these early results suggest that oesophageal transection with the SPTU gun may be useful in the large proportion of patients in whom injection sclerotherapy, shunt surgery, or conservative treatment is inappropriate.


Dietary fibres, fibre analogues, and glucose tolerance: importance of viscosity. To define the type of dietary fibre of fibre analogue with the greatest potential use in diabetic treatment, groups of four to six volunteers underwent 50-g glucose tolerance tests (GTT) with and without the addition of either guar, pectin, gum tragacanth, methylcellulose, wheat bran, or cholestyramine equivalent to 12 g fibre. The addition of each substance significantly reduced blood glucose concentration at one or more points during the GTT and generally reduced serum insulin concentrations. The greatest flattening of the glucose response was seen with guar, but this effect was abolished when hydrolysed non-viscous guar was used. The reduction in the mean peak rise in blood glucose concentration for each substance correlated positively with its viscosity (r = 0.926; P less than 0.01), as did delay in mouth-to-caecum transit time (r = 0.885; P less than 0.02). Viscous types of dietary fibre are therefore most likely to be therapeutically useful in modifying postprandial hyperglycaemia.


How patients use domiciliary oxygen.

How patients use domiciliary oxygen. Forty-five patients in Southampton who received domiciliary oxygen were visited at home to find out how they used and coped with their oxygen. Generally, the organisation and administration of supplies presented no problems, nearly all the apparatus complied with the drug tariff, and most patients coped well with the equipment. Only two patients were taking oxygen for prescribed periods; the others were taking it when necessary for symptomatic relief. No patient received oxygen for over five hours daily. Most patients thought that they were helped by oxygen, but only four said that it allowed them to increase their level of activity, and the overall benefit seemed slight. This was partly because oxygen was usually limited to one room, so patients used oxygen after rather than during exercise. The amount of oxygen consumed differed widely, ranging from three and a half cylinders a week in three patients to less than one cylinder in six months in 17 patients. The average yearly cost of oxygen per patient ranged from 500 pounds in patients consuming one cylinder or more per week, to 15 pounds in those consuming less than one cylinder in six months. The main cost of domiciliary oxygen is determined by the number of cylinder refills, so patients who use it infrequently are a relatively small drain on resources.


Prevalence of retinopathy in a diabetic clinic. In a prospective study lasting 14 months an attempt was made to measure the visual acuity and examine the fundi, after mydriasis, of all patients attending the diabetic clinic of a district general hospital. Of 704 patients, 160 (22.7%) had some evidence of retinopathy, and 52 (7.4%) of these were already attending an ophthalmologist. A further 18 (2.6%) were known to have retinopathy and were being followed up in the diabetic clinic. Ninety (12.8%) new patients with diabetic retinopathy were discovered. Most had minimal changes, but 30 (4.3%) were considered to have changes severe enough to be referred to an ophthalmologist. Twenty-two (2.1%) underwent, or were awaiting, photocoagulation, and half of these had had no visual symptoms when first seen. Although some of these patients were already being treated or observed for retinopathy, it is encouraging that relatively few new patients needing treatment for retinopathy were discovered. If retinopathy could be detected early enough physicians might be able to deal with it and so ease pressure on ophthalmological services.


Plasma arginine vasopressin concentrations and antidiuretic action of carbamazepine. Twelve subjects given therapeutic doses of carbamazepine showed no change in their plasma electrolyte concentrations. Ten of the 12 had abnormal water metabolism, however, their ability to excrete water loads being decreased. Plasma arginine vasopressin (AVP) concentrations fell while the subjects were taking the drug, indicating that the mechanism is unlikely to be increased secretion of antidiuretic hormone. We suggest that the water-retaining property of carbamazepine is a physiological effect of the drug, mediated by increased renal sensitivity to normal plasma concentrations of AVP and resetting of osmoreceptors.


Haemophilia A home therapy in the United Kingdom 1975-6. Data on home treatment for patients with haemophilia A (factor VIII deficient haemophilia) were compiled for 1975 and 1976 from questionnaires answered by directors of haemophilia centres throughout the United Kingdom. There were 48 haemophilia centres in 1975 and 71 in 1976. The number of patients on or in training for home treatment increased from 267 to 488 in the two years, and a further 241 haemophiliacs were considered suitable for home therapy by the end of 1976. Apart from a small (but increasing) number of haemophiliacs on prophylactic treatment, most patients were on low-dose (250-500 units) on-demand regimens, using a mean of 20 000 factor VIII units per patient per year in 1976. An estimated 55% of the blood product used for home therapy in the UK in 1976 was imported from commercial sources. Despite the fact that the numbers of patients on home treatment have increased, so that about 60% of the potential population were receiving or being considered for home treatment in 1976, inadequacies in the service still remain. In some centres follow-up is clearly inadequate; about 15% of patients still rely on cryoprecipitate; and too little money has been invested in making the NHS self-sufficient in factor VIII production.


Circulating immune complexes in pre-eclampsia. Sixteen patients with severe pre-eclampsia had more IgG-containing and C1q-binding circulating soluble immune complexes than did 16 matched women with normal pregnancies. The clinical features of preeclampsia may be explained by damage due to such complexes, although raised complex levels were also present in a few women with normal pregnancies. As immune complexes are so heterogenous in terms of the type of antigen, class and subclass of immunoglobulin, size, and complement-binding capacity, further investigations are needed to determine their role in normal and pre-eclamptic pregnancies.


Comparison of the tine and Mantoux tuberculin tests. Report of the Tuberculin Subcommittee of the Researched Committee of the British Thoracic Association. Intracutaneous (Mantoux 5 TU) and tine tuberculin tests were performed on the opposite arms of 307 people. The results of each test were read by two independent observers at either 48 or 72 hours. Positive readings were recorded in 59% of the Mantoux tests; induration was 10 mm or more in 34.7% of cases. Positive readings were recorded for 3.9% of the tine tests, and a further 15.5% were recorded in the doubtful category. The tine test is unsuitable for epidemiological use because of the high proportion of negative and doubtful results in people positive on the Mantoux test. For the same reasons its usefulness in clinical practice is very limited.


Evidence for intestinal origin of transcobalamin II during vitamin B12 absorption. The plasma binding of newly absorbed, radioactively labelled vitamin B12 was studied during a urinary excretion (Schilling) test. Vitamin B12, after being absorbed from the gut, enters blood attached to transcobalamin II, which seems to be derived from the ileal enterocyte. The absorbed B12 re-enters the blood stream after the transcobalamin II-B12 complex is cleared by the liver and it is then excreted into the urine during the Schilling test.


Cost of carrying out clinical diagnostic tests. The total cost of performing diagnostic tests in a hospital laboratory during one year was assessed. The largest single item of expenditure was the cost of the salaries of the technical staff, while the cost of reagents (including radiopharmaceuticals) was relatively small. The total costs of carrying out diagnostic tests are much higher than is often recognised by those who request them. The use of relatively expensive, commercially available assay kits saves time and gives good value for money. It may be worth taking this into account when planning hospital budgets.


Synapse development within the spinal trigeminal nucleus. Pars interpolaris of the spinal trigeminal nucleus of kittens has been studied with the electron microscope at birth and at several subsequent ages during the first month of life. Attention has been given to ultrastructural maturational changes that occur in this neuropil, especially events in synaptogenesis. The results of this investigation include the following observations: (1) the neuropil, even at the earliest ages studied (three-hour-old kittens), is strikingly mature, necessitating a quantitative assessment in order to determine subtle developmental changes in synaptic patterns; (2) the number of axoaxonic contacts at birth are few, and their emergence is essentially a postnatal phenomenon; (3) it appears that the immature Gray type II or symmetrical synapse possesses distinct cleft material and dense, parallel membrane specializations. Synaptic vesicle accumulation at this contact appears to occur after the membrane specializations have formed. A previous study by Kerr26 has shown a reduced potential for primary afferent reorganization with the spinal trigeminal nucleus when kittens are subjected to trigeminal rhizotomy after three days of age. Our observations on the development of axoaxonic synaptic arrangements in the neonatal period may provide an explanation for these earlier results.


Properties of cells projecting rostrally from the superficial layers of the cats superior colliculus. Cells projecting rostrally from the cat's superior colliculus were identified by antidromic activation from the posterior thalamus. These cells occurred principally in the stratum griseum superficiale and stratum opticum, although some were also encountered in deeper laminae. The rostrally projecting neurons of the superficial laminae formed a heterogeneous group with respect to axonal conduction velocity, receptive field dimensions and special response properties, such as directional and velocity sensitivity. No correlation was detected between receptive field size and estimated axonal conduction velocity in these units. Cells with the smallest receptive fields, were rarely excited antidromically from the thalamus.


Properties of X- and Y-type retinal ganglion cells in Siamese cats. There is ample evidence that the visual system of the Siamese cat is different from common cats. These abnormalities suggest possible retinal origins, although no documentation exists. In the present study, single unit recordings were made from 91 misrouted and 209 normally-routed optic tract fibers in Siamese cats. Electrophysiological responses of the misrouted fibers did not differ from those found in the normally-routed fibers of the Siamese cat with the exception of depressed responses to contrast reversal stimuli. X/Y classification of units and experiments on receptive field center sizes, intensity-response functions, and responses to flicker failed to demonstrate significant differences between the misrouted and normally-routed fibers in Siamese cats. These results were not affected by different degrees of interocular misalignment exhibited by the Siamese cat studied. Response properties of retinal ganglion cells in Siamese cats, however, were found to be quite abnormal when compared with common cats. Only 14% (42/300) of all units studied were Y-cells in Siamese cats in comparison to 35% (60/170) in common cats. The percentage of Y-units also was correlated with the severity of interocular misalignment in Siamese cats, i.e. the greater the misalignment of the eyes, the lower the percentage of Y-cells. Experiments on response to contrast reversal stimuli, intensity-response functions and responses to flicker revealed that the ganglion cells in Siamese cats are not as responsive as those in common cats.


The electromicrophysiology of delta waves induced by systemic atropine. Delta waves in the EEG can be induced by the intravenous administration of atropine. In cats we have investigated with several computer averaging programs the relationship of extracellular unit discharge to the EEG on the surface and within the cortex. We have also studied the laminar profiles and the vertical current density profiles of these slow waves. Our results indicate that surface-positive delta waves are related to events associated with excitation of cortical neurons, while surface-negative delta waves are related to a decreased probability of unit firing suggesting the possibility of inhibition. Laminar analysis of atropine-induced slow waves indicated that these were probably generated by pyramidal cells in a similar way to delta waves induced by brain lesions. These results suggest that a disturbance in cholinergic input to the cortex might be responsible for delta waves in the EEG.


Quantitative effects of methylzoxymethanol acetate on Purkinje cell dendritic growth. A quantitative analysis was made of alterations in the dendritic organisation of Purkinje cells in the cerebellum of the rat following the administration of the degranulating agent, methylazoxymethanol acetate (MAM). This drug depleted the granule cell population of the cerebellar cortex and disturbed Purkinje cell alignment such that a number of Purkinje cells became inverted and grew in the white matter. The quantitative changes that occurred in the dendritic trees of these cells (increase in segment length, decrease in segment numbers, trichotomy and branching probability) were similar to those seen following other degranulation procedures. The size of the Purkinje cell dendritic tree was found to be related to the number of parallel fibres present in the molecular layer. These results were discussed in relation to current theories of neuronal development and were shown to lend further support to the filopodial attachment hypothesis of dendritic growth.


Drug-induced differentiation of a rat glioma in vitro: II. the expression of S-100, a glial specific protein and steroid sulfatase. Amethopterin and 5-bromodeoxyuridine (BUdR) were used to induce morphological changes in cloned rat glioma (C6). The expression of S-100 protein, an acidic protein localized in glial cells, and steroid sulfatase, an ubiquitously distributed enzyme found in high concentration in glial cells, were followed during cell growth, from subculture to well into the stationary phase of control and drug-treated cultures. Amethopterin and BUdR differed in their effects on glioma morphology and in the expression of the biochemical parameters. Amethopterin coordinately stimualted both the production of S-100 protein and steroid sulfatase activity when cell division was inhibited during early logarithmic growth phase. BUdR stimulated steroid sulfatase activity but repressed production of S-100 protein. The results are discussed with respect to the mechanism of regulation of the differentiated state of tumor cells.


Analgesia from rostral brain stem stimulation in the rat. Rats implanted with bipolar stimulating electrodes in the rostral medial brain stem were tested for brain stimulation-produced analgesia using tail-flick, pinch and hot-plate tests. Potent analgesia across all three tests was obtained from stimulation of sites in the gray matter surrounding the aqueduct and the caudal portion of the third ventricle, the posterior hypothalamus, the midline area of the caudal thalamus and the pretectal region of the meso-diencephalic junction. The analgesia obtained from these sites was comparable to that produced by stimulation of the previously studied caudal periaqueductal gray matter: it outlasted the period of brain stimulation, was not due to a generalized motor debilitation of the animal, and was not correlated with changes in electrographic activity. Stimulation of sites in the caudal thalamus and pretectal area yielded analgesia without stimulation-induced aversive reactions, confirming the potential of these sites for use in the relief of clinical pain in man.


Centrally programmed feeding in Helisoma: identification and chracteristics of an electrically coupled premotor neuron network. (1) The oscillatory network underlying centrally programmed feeding in the fresh water pulmonate, Helisoma trivolvis, was studied using intracellular recording and staining techniques. These premotor neurons have been termed cyberchron neurons. (2) Intracellular staining with Procoin yellow has allowed the construction of a soma map and tentative identification of axonal projections of the cyberchron neurons. (3) Cyberchron neurons form a tightly electrically coupled network. Coupling coefficients range from 0.15 to 0.5, and electrotonic junctions allow the passage of Procion dye from cell to cell. Electrical synapses act as low pass filters, and allow spatial and temporal summation. (4) Burst generation within the network is the result of network interaction manifest as regeneration positive feedback from neuron to neuron via attenuating electrical synapses. (5) Decreased coupling between cyberchron neurons during and immediately following a burst is observed, and is discussed as a possible mechanism for burst termination.


Self-stimulation at the lateral hypothalamus and locus coeruleus after specific unilateral lesions of the dopamine system. A group of rats was trained to press levers for electrical stimulation from bipolar electrodes aimed at the lateral hypothalamus (LH), and another group was trained to self-stimulate from electrodes in the locus coeruleus (LC). All rats in both groups were subjected to unilateral injections of 6-hydroxydopamine into the substantia nigra and midbrain ventral tegmentum. The lesions produced profound depletions of dopamine from the ipsilateral frontal cortex, nucleus accumbens/olfactory tubercle, and corpus striatum. Pretreatment with desmethylimipramine prevented loss of noradrenaline in excess of that caused by electrode implantation. The destruction of the dopamine projections produced a persistent and pronounced deficit in intracranial self-stimulation from ipsilateral electrodes in both the LH and LC groups, but only transient effects on self-stimulation from contralateral electrodes at these sites. These results suggest that an intact dopamine system is required for the expression of self-stimulation behaviour.