Factors influencing feeding elicited by intracranial noradrenaline in rats. An improved design of microcannula was used to inject noradrenaline into discrete areas of the rat hypothalamus. The area of the paraventricular nucleus was shown to be a more effective site than the midlateral anterior hypothalamus for eliciting feeding with noradrenaline (4.8 microgram). The magnitude but not the direction of the effect of noradrenaline on feeding was influenced by the day-night cycle. The facilitating effect of the drug reached significance in the light period but not in the dark period, possibly because the baseline food intake was higher by night than by day. The facilitation of feeding occurred whether the rats were maintained and tested on a diet of solid or liquid food.


The responses of Renshaw cells and spinal interneurones of the rat to L-glutamate and L-aspartate. A comparison of the potencies of L-glutamic and L-aspartic acids as excitants of Renshaw cells and of interneurones monosynaptically innervated from the dorsal roots in the spinal cord of the rat has been made. Both groups of cells were more sensitive to glutamate than to aspartate, and three different non-parametric statistical tests showed that the two populations were indistinguishable. The results differ qualitatively from those obtained in the cat, and for the Renshaw cells from another study in the rat.


Selective enhancement of the lordotic component of female sexual behavior in rats following destruction of central catecholamine-containing systems. Ovariectomized female rats received two intraventricular injections of 200 microgram of 6-hydroxydopamine (6-OHDA), a treatment which produced 66% depletion of telencephalic norepinephrine and 53% depletion of telencephalic dopamine. Compared to vehicle-injected controls, 6-OHDA-treated animals showed increased lordosis scores when treated with ovarian hormones. This effect was potentiated by additional treatment with 100 mg/kg alpha-methyl-p-tyrosine (AMT), a catecholamine synthesis inhibitor. Besides showing increased frequency and intensity of lordosis, animals treated with both 6-OHDA and AMT retained the lordotic posture significantly longer after the male dismounted than animals given either treatment alone or vehicle controls. The enhancement of lordosis following CA depletion was not prevented by a series of dexamethasone treatments which caused a marked suppression in adrenal steroid (corticosterone) levels. This suggests that normal adrenal function is not a prerequisite for the observed enhancements. It was concluded that the lordotic response is inhibited by the activity of a catecholamine system. Soliciting behavior (hop-darting) was not enhanced by any treatment, suggesting that catecholamine activity has an inhibitory influence on the stop component of sexual behavior, but not on the whole copulatory pattern.


Cell division in the vomeronasal organ of the adult mouse. Using [3H]thymidine labelling we could demonstrate the presence of a population of dividing cells in the vomeronasal neurosensory epithelium of the adult mouse. These cells are localised in the regions of the epithelium adjacent to its boundaries with the ciliated respiratory epithelium. With increasing survival times after thymidine administration, the labelled cells become situated progressively further away from the boundary region. The cluster of cells with labelled nuclei forms a loose column, consisting of labelled receptor cells, but in addition the immediately overlying supporting cell nuclei are also labelled. By 56 days after thymidine administration the cluster of labelled cells is separated from the epithelial boundary by a distance equivalent to about one-fifth of the total width of the epithelial sheet. There is little further change in position at 102 days. It is not clear to what extent this represents a turnover process as opposed to a continuing growth of the epithelium by accretion at the edges.


Identification of locally synthesized proteins in proximal stump axons of the neurotomized hypoglossal nerve. Analysis of radioactively labeled proteins was carried out on microsamples of myelin-free axons isolated from neurotomized and normal hypoglossal nerves of the rabbit after in vitro incubation with [3H]leucine. Major radioactive peaks in axonal endings of the proximal stump 18 h after neurotomy, identified by autoradiography of microelectrophoregrams, had apparent molecular weights of 52,000d, 41,000d and 18,000d. This autoradiographic pattern differed from that of axons of untransected nerve in: (1) not having a prominent 100,000d component present in the latter; and (2) having a novel 41,000d component not present in the latter. Labeling of axonal proteins in the proximal stump in vivo resulted in no apparent retrograde transport during the 5 h studied. Autoradiographic analysis of labeled proteins released by nerves into the medium during in vitro incubation revealed a major radioactive peak with an apparent molecular weight of 77,000d. Attempts to demonstrate uptake of the 77,000d component by unlabeled axons in vitro and in vivo were unsuccessful. The hypothesis was advanced that the 52,000d protein may be neurofilament protein, and the possible significance of the 41,000d component was discussed in the contexts of the pathology of the traumatized proximal stump, and of the antecedent events leading to axonal outgrowth.


The ocular following reflex in cats deprived of pattern vision from birth. An investigation of vertical ocular following reflexes evoked from retinal sites of different horizontal eccentricity was carried out on visually deprived cats. The recording was performed in pretrigeminal preparations where horizontal eye movements are absent. A light slit or a black stick (1 degrees X 4 degrees) were moved with 10 degrees/sec speed for 2 sec along the vertical meridian or parallelly up to 40 degrees in the nasal or temporal hemifield. As in previously described normally reared cats, the following reflexes were evoked from the whole area, but the pursuit movements had longer latency and lower velocity at the periphery than in the center of the retina. However, irrespectively of the place of stimulation, the latency of the pursuit movements was longer, their velocity lower and the course less regular than in normally reared cats. It therefore follows that in visually deprived cats the ocular following reflex is impaired.


Carnosine and anserine content of turkey breast and leg muscles. 1. Carnosine and anserine have been measured in samples of breast and leg muscles from three turkeys. 2. The results show that there is a large difference in the dipeptide content between the two types of muscle.


Effects of regular handling and blood sampling by wing vein puncture on the performance of broilers and pullets. 1. Broilers and pullets were regularly handled or bled by wing vein puncture over periods of 5 and 31 weeks respectively. 2. Neither procedure had any effect on body weight, food consumption nor on egg production, egg weight, shell quality or the percentage of non-marketable eggs.


An automated multi-calorimeter system: preliminary experiments on laying hens. 1. An open-circuit, automated, multi-calorimeter system for studies on the energy metabolism of the fowl is described. 2. Discontinuous observations of 10-min duration once each hour for 22 h gave good agreement with continuous observations throughout 22 h. 3. It is essential to train each hen before a series of calorimeter experiments. 4. A distinctive pattern of light-entrained, diurnal variation of metabolic rate has been observed in starving and fed birds of two laying strains.


Preservation of fowl semen in liquid nitrogen--an improved method. 1. An improved method of storing fowl semen in liquid nitrogen is described. It uses glycerol as a cryopotectant and the degree of fertility obtained with semen stored for up to 2 1/4 years was very promising. 2. The essential features of the method are a slow freezing rate, a reduction of temperature to - 35 degrees C before the semen is plunged into liquid nitrogen and insemination within 15 min of thawing and removing the glycerol from the diluent. 3. It seems likely that further improvements in the technique may be expected through better control of the injection of liquid nitrogen into the freezing chamber, thereby minimising localised, rapid temperature changes around the ampoules during freezing. 4. Preliminary results suggest that it may prove possible to select males for the ability of their spermatozoa to withstand freezing. 5. The importance of recognising differences between males in the initial quality of semen and between females in the physiology of the reproductive organs in determining the fertilising ability of stored semen is discussed.


Polyamine quantitative analysis in the developing chick embryo. 1. An improved specific and sensitive method for the separation and detection of polyamines, based on an automated ion exchange chromatography, is described. 4. The mean contents of polyamines in embryos at different stages of development are reported. The data show a direct correlation between the cellular polyamine content and the growth rate of the embryo.


Effect of dietary cereal on liver and plasma lipids in laying Japanese quail. 1. In three experiments the effect of diets containing maize or wheat on hepatic and plasma lipids in laying japanese quail were studied. In two of these diets of equal energy, nitrogen and fat contents were used. 2. Liver weight, relative to body weight, liver lipid content and plasma lipid concentration were greater in birds fed on maize-containing diets. 3. The maize-containing diet also produced more (14 : 0, 16 : 0, 16 : 1 and 18 : 1) and less (18 : 0, 18 : 2 and 20 :4) fatty acids in the liver lipid. 4. Egg production was not affected by the treatments. 5. The effect of dietary cereal on hepatic and plasma lipids may be due to altered lipogenesis and the quail may be a useful model for the laying hen with respect to hepatic lipid accumulation.


The photoperiodic effect of ahemeral light-dark cycles which entrain circadian rhythms. 1. A 27-h cycle of light and dark provides a greater gonadotrophic stimulus to the laying fowl, as judged by sexual maturity and rate of lay, than a 24-h cycle incorporating the same photoperiod. 2. An hypothesis put forward to account for these effects states that Effective Photoperiod equal p + c - b, where p = actual photoperiod, c = cycle length and b = the period of the endogenous biological clock. 3. Two experiments designed to test this hypothesis have yielded results which are consistent with it. 4. A  poultryman who use an ahemeral cycle to alter egg weight or shell thickness and then whishes to transfer his flock back to a 24-h cycle should calculate the difference between the two cycle lengths and then add this quantity to the prevailing photoperiod to find the appropriate amount of light to be used in the 24-h cycle.


Electrophoresis of avian muscle proteins. 1. The electrophoretic patterns of water-soluble proteins of avian muscle showed differences due both to species and to muscle type. 2. Each muscle pattern within a species showed a unique protein band which distinguished that species from other species.


Changes in oxygen consumption induced by fentanyl and thiopentone during balanced anaesthesia. Changes in whole body oxygen consumption due to bolus infusions of fentanyl and thiopentone given during "balanced anaesthesia" have been examined in 17 patients. It has been shown that fentanyl causes an average decrease in oxygen consumption of 4.9, 8.4, and 5.2 per cent at 5, 10 and 15 minutes after its infusion. Thiopentone causes an average decrease of 7.0, 8.8, and 1.9 per cent at 5, 10 and 15 minutes after infusion. It is believed that the effects of fentanyl and thiopentone on oxygen consumption are caused mainly by decreases in cerebral and myocardial oxygen consumption.


Effect of anaesthetic agents on the ionic composition of cerebrospinal fluid following total cerebral ischaemia. Total cerebral ischaemia in rats caused a marked increase in the cisternal CSF potassium concentration but little change in CSF sodium or chloride concentration. The anaesthetic techniques studied (pentobarbitone, halothane/oxygen and nitrous oxide/oxygen/relaxant) did not effect the potassium increase following cerebral ischaemia. We conclude that the mechanism of barbiturate protection following cerebral ischaemia is different from that of hypothermia.


Cardiovascular effects of droperiodol during enflurane and enfluarne-nitrous oxide anaethesia in man. The cardiovascular effects of intravenous droperiodol 5 mg were measured in 20 patients during steady state enflurane-nitrous oxide-oxygen or enflurane-oxygen anaesthesia, droperiodol produced significant decreases in SVR and BP and increases in HR and Qt which were maximal after five minutes, somewhat less five minutes, somewhat less five minutes later, and back to control values 15 minutes after administration. SV was not significantly altered by droperiodol during enflurane-nitrous oxide-oxygen at any time after administration. During enflurane-oxygen anaesthesia droperidol reduced SVR and BP after five and ten minutes but did not significantly alter any other variable. All variables had returned to control levels 15 minutes after droperiodol during enfluarne-oxygen anaesthesia. These data demonstrate that droperidol produces a significant though transiet reduction of BP and SVR during enfluane anaesthesia which is associated with no change or an increase in Qt. Our findings suggest that droperidol causes minimal or no myocardial depression when used during potent inhalation anaesthesia and may have a place as an amnesic supplement and/or "afterload" reducer during light enflurance anaesthesia.


Stabilometry: a new tool for the measurement of recovery following general anaesthesia for out-patients. A stabilometer has been used to measure changes in the activity of postural muscles during the later stages of recovery from anaesthesia. It is concluded that stabilometry might be a useful tool with which to measure and record the extent of recovery andthat this might be especially useful for use after out-patient sugery.


Prevention of post-anaesthesia shivering. This study involves ventilation of the lungs with warmed humidifed anaesthetic gases during prolonged elective abdominal operations. Tympanic, oesophageal and toe temperatures were compared bewteen twenty warmed and twenty un-warmed patients at various times during operation and recovery. Fifty per cent (10/20) unwarmed patients shivered in the recovery room, while none of the warmed patients shivered. Our data indicate that pulmonary ventilation with warm humidified anaesthetic gases provides heat transfer by the lungs, preventing hypothermia during operation and post -anaesthesia shivering is prevented by maintaining the patient normothermic in both the operating room and the recovery room.


Succinylcholine sensitivity in a Nova Scotia family. Succinylcholine apnoea is usually the result of a delay in hydrolysis of the injected muscle relaxant due to the presence of an inherited defect in the enzyme cholinesterase. This report presents a Nova Scotia family in whom several members had "difficulty in breathing" following anaesthesia. Subsequent investigations revealed the presence of several phenotypes of the enzyme cholinesterase including individuals who were homozygous for the atypical cholinesterase genes. The frequency of occurrence and significance of the various phenotypes are discussed, together with their management and recommendations for family screening.


Catamenial pneumothorax and malignant hyperthermia. This paper presents a patient showing both the unusual syndrome of catamenial pneumothorax and a strong family history of malignant hyperthermia. The anaesthetic management is described and discussed.


Dermatomyositis, suxamethonium action and atypical plasmacholinesterase. A 19-year-old girl suffering from active dermatomyositis was given suxamethonium 60 mg during anaesthesia for termination of pregnancy. A prolonged suxamethonium action occurred which was explained by the finding of homozygous atypical plasmacholinesterase in her blood. Although no fasciculations were seen immediately after injection of the drug, a period of fasciculations progressing from the extremities to the head and trunk occurred during recovery of muscle tone. No hyperpyrexia or elevation of serum creatine phosphokinase occurred. This was ascribed to the steroid therapy she received. Plasma from four other patients suffering from dermatomyositis was also investigated and one young woman, also pregnant, was found to be heterozygous for the atypical enzyme.


Effect of coagulating and cutting current on a demand pacemaker during transurethral resection of the prostate. A case report. Electromagnetic interference from diathermy apparatus can be a real hazard in a patient with a demand pacemaker. A case is reported in which the cutting current of transurethral electrocautery deactivated an implanted pacemaker, while coagulating current did not alter pacemaker activity. Therefore frequent short bursts of cutting current were used for successful resection of the prostate. This case emphasizes the need for vigilant care of patients with demand pacemakers requiring transurethral resection.


The carcinogenic effect of dimethylnitrosamine in laboratory bred European hamsters (Cricetus cricetus). The carcinogenic effect of dimethylnitrosamine (DMN) s.c. injected at two different dose levels was studied in laboratory bred European hamsters (EH) and data compared to findings for captured EH. Malignant haemangioendotheliomas of the liver and kidney, hepatocellular carcinomas and cholangiocarcinomas were induced. In contrast to the results obtained with wild EH, a large number of the laboratory bred females additionally developed ovarian granulosa cell tumors.


Ganglioside and morphological changes in mouse embryo cells with time. Ganglioside and morphological changes were observed in C3H/10T1/2CL8 cells during a 4-year period of maintenance in the laboratory. The cellular morphology at confluency, as determined by scanning electron microscopy, changed from being polygonal and flattened to a fusiform shape with some piling up of cells. The saturation density increased about three-fold and the level of the simplest ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) increased about two-fold. While the reasons for the alterations are unknown, the data suggest a relationship among ganglioside composition, cellular morphology and regulation of cell growth. The possible implications of such biochemical and biological changes on studies comparing normal and transformed cells are discussed.


Mutagenicity to mammalian cells in culture by (+) and (-) trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrenes and the hydrolysis and reduction products of two stereoisomeric benzo(a)pyrene 7,8-diol-9,10-epoxides. The mutagenicity for mammalian cells of benzo(a)pyrene (BP) and 9 of its derivatives was tested by resistance to ouabain in Chinese hamster V78 cells. The derivatives included the (-) and (+) enantiomers of trans-7,8-diol; the racemic (+/-)trans-7,8-diol; two triols, (7/8,9)-triol and (7,9/8)-triol; and four tetrols, (7,10/8,9)-tetrol, (7/8,9,10)-tetrol, (7,9/8,10-triol and (7,9,10/8)-tetrol. Since V78 cells do not metabolize polycyclic hydrocarbons, mutagenesis was tested both in the presence and in the absence of Golden hamster cells capable of metabolizing polycyclic hydrocarbons. Neither BP nor any of its 9 tested derivatives showed mutagenicity for V78 cells in the absence of normal Golden hamster cells. However, in the presence of these cells, BP and the optically active and racemic trans-7,8-diols exhibited a mutagenic response that was dose-dependent. All other derivatives were inactive. The most active mutagenic hydrocarbon was (-) trans-7,8-diol, and activity decreased in the order (+/-)trans-7,8-diol, (+) trans-7,8-diol and BP.


Vitamin A serum and dietary vitamin A intake in lung cancer patients. Clinical and experimental evidence indicates a possible role for vitamin A deficiency in the pathogenesis of bronchogenic carcinoma. We, therefore, measured serum vitamin A levels in 67 newly diagnosed non-resectable lung cancer patients. In 43 of these patients daily vitamin A intake was also determined. Serum vitamin A levels were within the normal range of the general population of 66 of the 67 patients. Eighteen of 43 patients had daily vitamin A intakes less than 5000 IU/day while 25 patients had daily intake above this level. The serum vitamin A level did not correlate with histologic subtype, extent of disease or presence or absence of hepatic metastases. While these data suggest that vitamin A deficiency was not implicated in pulmonary carcinogenesis, more definitive conclusions await prospective evaluation of high risk individuals followed serially for many years.


Effects of N-nitrosodiethanolamine and 1,1-diethanolhydrazine in Syrian golden hamsters. N-Nitrosodiethanolamine (NDEA) and 1,1-diethanolhydrazine (DEH) were synthesized and injected subcutaneously weekly in male and female Syrian golden hamsters. The total NDEA dose per hamster was approx. 15 g/kg body wt. applied in either 7 or 27 subdoses. DEH was administered in 78 applications to two groups yielding total doses of 1.1 g and 273 mg/kg body wt. Under these conditions, DEH did not show a specific demonstrable carcinogenic effect. However, within 78 weeks after the first application, 39 out of 56 hamsters treated with NDEA developed tumors. Primarily, neoplasms of the nasal cavity and tracheal tumors were observed, as well as a few hepatocellular adenomas and sarcomas at the injection site. These findings and those of the earlier study on carcinogenicity of NDEA in rats raise concern as to the safety for human consumption or industrial use of products with the potential for forming NDEA.


Kinetic models of C3H mouse mammary tumor growth: implications regarding tumor cell loss. Three models of tumor cell loss are described. The effects of cell loss on other cellular kinetic parameters are evaluated, and experiments which may distinguish among the models are discussed. Each model is based on a different cell-loss mechanism, and equations for the cell-cycle, cell-frequency distribution, the growth of both the proliferating and non-proliferating cell population, the growth fraction (GF), and the relative rate of volumetric growth, (dV/dt)/V, are derived. The following types of data are simulated for each model: the pulse labelling index, the mitotic index, and the labeling index as a function of time after a single or a series of 3H-TdR injections. The relative volumetric growth rate has the same mathematical form for each model. The PLM curves predicted by each model for the tumor lines studied (S102F and Slow) are not appreciably different. The predicted initial labeling index and mitotic index may differ significantly among the models depending upon the tumor line. The most striking difference among the models lies in the predictions regarding the labeling index as a function of time after a single or after a series of 3H-TdR injections. These types of labeling experiments should be valuable for distinguishing the different cell-loss mechanisms in solid tumors.


Quantification of entry into and exit from the cell cycle in human lymphocyte cultures. A mathematical model is presented for the analysis of transition between cycling and non-cycling compartments by cells responding to a growth stimulus. The cellular age distribution as a function of time is derived from sequential [3H]thymidine pulse labeling indices. Rates of entry into and exit from the cycling compartment are determined on the basis of labeling indices obtained after instantaneous and long duration [3H]thymidine pulses. Analysis of an experiment involving sequential measurements over the whole lifespan of a human lymphocyte culture stimulated by phytohemagglutinin is presented as an example of the application of this method.


Dynamic stiffness of cat heart muscle in Ba2+-induced contracture. We analyzed mechanical properties of kitten papillary muscles both at rest and in Ba2+ contracture by the frequency response method. The muscle length was perturbed sinusoidally, with an amplitude less than 0.3% of Lmax over a frequency range from 0.1 to 60 Hz to determine the dynamic stiffness, F(omega)/L(omega), in which F(omega) = amplitude of the force response wave, L(omega) = amplitude of sinusoidal length wave, and omega = frequency, and the phase shift of F(omega) relative to L(omega). In resting muscles, the dynamic stiffness increased minutely with increasing frequency and the phase relation showed a small lead over the entire frequency range. In muscles in contracture at low temperature (22-24 degrees C), the stiffness first decreased with increasing frequency from about 0.2 to 1 Hz, then increased with a slope of 10-fold/decade, and finally plateaued over the range above 8 Hz. The phase relation showed a small lag between 0.3 and 0.5 Hz, but a clear lead of up to 60 degrees between 0.8 and 16 Hz. With an increase in temperature to 36 degrees C, the peculiar decrease in stiffness and the phase lag in the low frequency region decreased in size and shifted to a higher frequency region (about 4 Hz). These findings led us to two alternative, approximate analogues, which are similar to but simpler than that previously proposed for a twitching papillary muscle.


The effects of ouabain on the transmembrane potentials and intracellular potassium activity of canine cardiac Purkinje fibers. Open-tip microelectrodes containing a potassium-sensitive liquid ion exchanger (Corning 477317) were used to study the effects of ouabain on the intracellular potassium activity and the transmembrane potentials of beating canine cardiac Purkinje fibers. The preparations were superfused with Tyrode's solution containing ouabain, 2 X 10(-7) M, and potassium, 4 mM, for 30 minutes. At the end of this period, intracellular potassium activity had decreased from the control value of 130.0 mM to 112.2 mM. The resting membrane potential determined through conventional 3 M KC1-filed microelectrodes decreased from -83.6 to -78.8 mV. Comparison of the decrease in the potassium equilibrium potential with the decrease in the resting membrane potential suggests that there was an accumulation of potassium at the exterior surface of the cell membrane. The effect of ouabain on the resting membrane potential, therefore, was due to a change in the transmembrane potassium ion gradient. This, in turn, resulted from a decrease in intracellular potassium activity and, apparently, from an increased potassium activity at the cell surface.


Adenosine metabolism in canine myocardial reactive hyperemia. In pentobrabital-anesthetized open chest dogs, myocardial adenosine content is elevated by 5 or 15 seconds of left coronary artery occlusion and falls exponentially to control levels during reactive hyperemia. The rate constants for adenosine dissipation are (mean +/- SEM): -0.08 +/- 0.01 and -0.034 +/- 0.007 sec-1 after 5- and 15-second occlusion, respectively. Kinetic analysis of the reactive hyperemia flow curves (Circ Res 14/15 (suppl I): 81-85, 1963) predicts rates of -0.069 +/- 0.009 sec-1 and -0.04 +/- 0.009 sec-1, indicating that changes in adenosine levels can account for the way coronary flow changes during this response. The log (dose-) response curve relating reactive hyperemia flow to tissue adenosine concentration has a steeper slope and is half-maximal at a lower adenosine concentration than the dose-response curve obtained by intracoronary infusions of adenosine in oxygenated hearts, indicating that the coronary vasoactivity of adenosine is enhanced during reactive hyperemia. This could explain why theophylline antagonizes the coronary vasocilatory effect of adenosine in oxygenated hearts but has relatively little effect on reactive hyperemia.


Quantitative determination of regional oxygen consumption in the dog heart. A micro-Fick method has been developed to measure the O2 consumption of different regions of an organ. The method was tested in isolated dog gracilis muscle and consisted of microspectrophotometric determination of arterial and venous O2 saturation in quick frozen tissue to determine O2 extraction and flow measured with 85Sr-labeled microspheres, with O2 consumption calculated from the product. This was compared to electromagnetically measured flow and O2 extraction determined by Van Slyke or CO-oximeter. The accuracy of the new measurement was at worst 8.7% for O2 consumption over the range tested in a single muscle. In the hearts of anesthetized open-chest dogs, right ventricular O2 consumption, 7.1 +/- 0.9 ml O2/min per 100 g, was significantly lower than left, 11.0 +/- 0.4. This gradient was related to a blood flow difference. Right ventricular base had a 51% lower O2 consumption than right ventricular apex. In the left ventricle, subepicardial O2 consumption, 9.5 +/- 0.7, was lower than that of the subenocardium, 12.1 +/- 0.7. This difference was related to a difference in O2 extraction.


Relative effect of CO2 on canine coronary vascular resistance. We determined the effect of alterations in coronary arterial PCO2 on coronary vascular resistance (CVR) at a constant coronary sinus (CS) PO2 and the effect of coronary arterial PO2 variation on CVR at a constant CS PCO2. A linear but opposing effect on CVR was found for both gases. The sensitivity of CVR to O2 change, represented as CVR/CS PO2, was approximately twice that of the ratio CVR/CS PCO2. (0.0852 +/- 0.006 vs. -0.0362 +/- 0.005). The entire range of CVR variation obtainable through CO2 variation was as great as that resulting from O2 variation. During randomized variation of O2 and CO2, CVR can be mathematically related in a multiple linear expression to CS PO2 and CS PCO2.


Regional myocardial blood flow after sudden aortic constriction in awake dogs. Hemodynamic and regional myocardial blood flow responses were studied 5 seconds (early) and 30 seconds (late) after abrupt proximal aortic constriction in chronically instrumented awake dogs. During the early phase, left ventricular end-diastolic pressure (LVEDP) increased and stroke volume (SV) decreased significantly. During the late phase, there was a positive inotropic response manifested by a decrease in LVEDP and increase in SV (Anrep effect). The late inotropic response was closely associated with a recovery from subendocardial underperfusion. Hemodynamic and regional flow responses after beta-adrenergic blockade with propranolol (0.4 mg/kg) were similar to those observed during control. Studies during coronary vasodilation induced by adenosine (0.75--1.0 mg/kg per minute) showed that, if subendocardial flow was elevated during the early phase, the early increase of LVEDP and decrease of SV were less than control; however, if subendocardial flow did not change from control in the early phase and did not subsequently increase, there was no late inotropic response. These data suggest that the Anrep effect in the awake dog is closely related to a recovery from subendocardial ischemia.


Recurrent sustained ventricular tachycardia. 1. Mechanisms. The mechanism of recurrent sustained ventricular tachycardia (VT) was evaluated in 21 patients. Re-entry as the mechanism for VT was suggested by a) the reproducible initiation (19) and termination (15) of the arrhythmia by programmed stimulation. The rate, ventricle of origin, and stimulation site determined the method of termination. One VPD was usually required with VT rates less than 175/min and/or ventricle of origin ipsilateral to the stimulation site, while two VPDs were usually required for VT with faster rates originating in a contralateral ventricle. The proximal His-Purkinje system (HPS) was not required for initiation or maintenance of VT. Evidence localizing the site of re-entry to a small portion of the ventricles included: a) ventricular capture by ventricular premature depolarizations (VPDs) or pacing (VP) without terminating VT (5), b) sinus capture following VPDs and/or supraventricular fusions without terminating VT (12), and c) atrial pacing normalizing the QRS and H-V intervals without terminating VT (5).


Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Endocardial ventricular mapping of 21 ventricular tachyardias (VT) in 17 patients was performed using electrode catheters. Activation at multiple left and right ventricular sites was utilized to determine the site of origin of the VT. Eleven VT had a left bundle branch block pattern (VT-LBBB) and 10 VT had right bundle branch block pattern (VT-RBBB). In all VT-RBBB the earliest site of activation was in the LV or septum. In VT-LBBB the earliest site was RV (4/11), LV (5/11) and septum (2/11). All ventricular tachycardias with QRS less than 140 msec arose in the septum. In patients with an aneurysm, the site of origin of ventricular tachycardia was always in the aneursm. All VT-LBBB arising from the left ventricle originated in an aneurysm involving the septum. QRS changes during ventricular tachycardia were associated with alterations in the patterm of ventricular activation without alteration of the site of origin. In three patients the site of origin predicted by endocardial ventricular mapping was confirmed intraoperatively by epi- and/or endocardial mapping. We conclude that endocardial ventricular mapping demonstrates the limitations of the surface electrocardiogram in localizing the site of origin of ventricular tachycardia. The method may provide important data upon which the surgical therapy of ventricular tachycardia is based.


Electrophysiologic effects of lidocaine on sinus node and atrium in patients with and without sinoatrial dysfunction. Electrophysiological studies were conducted in 13 patients with normal sinus node function and 14 with sinus node dysfunction before and after intravenous lidocaine. Mean +/- SEM sinus cycle length significantly shortened from 810 +/- 34.3 to 774 +/- 34.3 msec in patients with normal sinus node (P less than 0.001) and from 1061 +/- 67.6 to 1016 +/- 64.5 msec in patients with sinus node dysfunction (P less than 0.025) after lidocaine. Mean sinus recovery time was 1027 +/- 49.4 before and 1026 +/- 52.5 msec after lidocaine in patients with normal sinus node (NS) and 1269 +/- 97.7 before and 1170 +/- 73.8 msec after lidocaine in patients with sinus node dysfunction (P less than 0.05). Mean calculated sinoatrial conduction time was 87 +/- 9.5 before and 90 +/- 9.2 msec after lidocaine in patients with normal sinus node (NS) and 80 +/- 10.3 before and 96 +/- 10.2 msec after lidocaine in patients with sinus node dysfunction (P less than 0.001). Mean atrial effective and functional refractory periods were not significantly changed with lidocaine. Thus lidocaine shortened sinus cycle length in both groups, without affecting atrial refractoriness. Lidocaine appeared to depress perinodal tissue only in patients with sinus node dysfunction. The abbreviation of sinus recovery time in patients with sinus node dysfunction could reflect increased sinus automaticity and/or increased perinodal refractoriness, allowing entrance block to occur. This mechanism may explain why sinus arrest has been noted in some patients during lidocaine administration.


Characteristics of atrioventricular conduction and the spectrum of arrhythmias in lown-ganong-levine syndrome. Electrophysiological characteristics of atrioventricular (A-V) conduction and refractoriness were examined in 12 patients with Lown-Ganong-Levine (LGL) syndrome referred for assessment of the following arrhythmias: (group I) regular narrow QRS tachycardia 6/12 (50%), (group II) atrial fibrillation (AF) 2/12 (17%), group III) ventricular tachycardia (VT) 4/12 (33%). A-V node refractory periods were shorter, and enhanced A-V conduction more frequent (7/12, 58% vs 7/28, 25%) in LGL patients compared to similar studies in 28 normal controls. During laboratory study reciprocating tachycardia (RT) due to re-entry within the A-V node occurred in 4/12 (33%) LGL patients, and exhibited a shorter cycle length (294 +/- 60.4 msec) than did the same arrhythmia in 11/28 (39%) controls 372 +/- 51.8 msec, P less than 0.05). Similarly, RT utilizing a concealed accessory pathway had a shorter cycle length (228 +/- 3.5 msec) in 2/12 (17%) LGL patients than in 11/28 (39%) controls (314 +/- 24.3 msec, P less than 0.001). In AF, the shortest R-R intervals in 4/12 (33%) LGL patients (2 group I, 2 group II) were shorter than in 15/28 (54%) control patients (254 +/- 42.2 msec vs 325 +/- 64.2 msec, P less than 0.05). The mean R-R internvals did not differ significantly (LGL 372 +/- 89 msec vs control 428 +/- 82.6 msec). This study suggests that the characteristics of A-V conduction and refractoriness may permit development of more rapid heart rates during certain arrhythymias in LGL patients compared to normal controls. Furthermore, the occurrence of VT in patients with LGL sydrome indicates that symptomatic arrhythmias require specific diagnosis.


Re-entrant ventricular arrhythmias in the late myocardial infarction period. 5. Mechanism of action of diphenylhydantoin. The mechanism of action of diphenylhydantoin (DPH) on re-entrant ventricular arrhythmias (RVA) was studied in dogs 3-7 days following ligation of the anterior descending coronary artery utilizing direct recordings of the re-entrant pathway (RP) from the epicardial surface of the infarction zone (IZ). DPH in a therapeutic dose consistently prolonged refractoriness of potentially RP in the IZ. This resulted in further impairment and/or block of conduction in the RP and was directly responsible for DPH ability to abolish RVA. On the other hand, DPH had no significant effect on conduction in the adjacent normal zone. Prior to abolition of RVA initiated by premature beats (PBs), DPH resulted in: 1) narrowing of the critical range of coupling intervals of PBs that resulted in re-entry (i.e., the re-entry zone), 2) shift of the narrowed re-entry zone to longer cardiac cycle lengths, and 3) lengthening of the coupling interval of the first re-entrant beat, as well as slowing the rate of re-entrant tachycardia. Thus DPH, similar to lidocaine, owes its antiarrhythmic action in RVS to its selective depressant effect on ischemic cells forming part of the RP.


Normalization of bundle branch block patterns by distal His bundle pacing. Clinical and experimental evidence of longitudinal dissociation in the pathologic his bundle. Clinical and experimental observations in which bundle branch block patterns (BBBP) in ECG leads were normalized by distal His bundle (H) pacing are reported. The clinical material includes four patients with acute right BBBP secondary to anterior wall myocardial infarction and three patients with chronic left BBBP. Six of the seven patients had a prolonged H-V interval (60-85 msec) including three who showed evidence of an intra-H conduction delay (IHCD) with split H (H and H'). Distal H pacing from a right-sided electrode catheter normalized the BBBP with a stimulus-to-QRS (PI-V) interval 20-35 msec shorter than the H-V interval and almost identical to the H'-V interval in the three patients with documented IHCD. In 18 dogs ligation of the anterior septal artery resulted in IHCF with split H associated with right or left BBBP. Distal H pacing from catheter and/or plunge wire electrodes normalized the BBBP in 12 experiments (67%) with a PI-V interval identical to the H'-V interval. H pacing was selective and direct stimulation of myocardium was excluded by monitoring the high ventricular septal electrogram. The clinical and experimental observations are discussed as evidence that functional longitudinal dissociation is probably only operative in the pathologic H due to selectively greater depression of conduction in the transverse interconnections.


The noninvasive diagnosis of right ventricular infarction. We evaluated scintigraphy and echocardiography for the diagnosis of right ventricular (RV) infarction. Of 26 patients with acute transmural myocardial infarction (MI), six with inferior MI had abnormal radionuclide uptake localized to the RV free wall on infarct scintigraphy or segmental akinesis of the RV free wall on gated radioangiography or both. These six patients with RV involvement (group I) were compared with the remaining nine with inferior MI (group II) and 11 with anterior MI (group III). RV/LV area ratios determined radioangiographically were significantly greater in group I than group II in diastole and systole. Echocardiographic RV enddiastolic dimension and RV/LV end-diastolic dimension ratio were significantly greater and RV stroke work index was significantly lower in group I than in group II. Predominant RV involvement in inferior MI may occur commonly. Anatomic and functional evidence of this diagnosis can be obtained noninvasively.


Cross-sectional echocardiographic characterization of aortic obstruction. 1. Supravalvular aortic stenosis and aortic hypoplasia. Cross-sectional echocardiographic and cineangiographic studies of the left ventricular outflow tract and ascending aorta were performed in five patients with supravalvular aortic stenosis (four hourglass and one hypoplastic). Visualization of the area of obstruction was possible in each patient using the cross-sectional system. In each case the echocardiographically determined diameter at the level of obstruction was within 3 mm of the similar angiographic value. Assessment of the extent of the lesion was possible in four of five cases. In three of these four cases the echocardiographic measurement was within 5 mm of the angiographic measurement while in the fourth the obstruction was felt to involve the total ascending aorta by both techniques. Determination of percent decrease in LVOT diameter from the aortic anulus to the level of obstruction was useful in defining obstruction and estimating severity. Cross-sectional echocardiography is a valuable noninvasive method for evaluating the ascending aorta in patients with supravalvular aortic stenosis.


Cross-sectional echocardiographic detection of aortic obstruction. 2. Coarctation of the Aorta. Cross-sectional echocardiographic studies of the aortic arch and proximal descending aorta were performed in 18 patients with coarctation of the aorta and 20 normal subjects. In normals the aortic arch and proximal descending aorta appeared as an arcuate, echo-free structure curving across the plane of the scan. There were no localized changes in aortic diameter and the amplitude of aortic systolic pulsation was symmetrically maintained throughout the scan plane. Visualization of this region was possible in 16 of 18 patients with coarctation. In each of these cases there was a localized area of decrease in aortic diameter in the region of the left subclavian artery which corresponded to the angiographic appearance of the coarctation. In addition prominent systolic pulsation of the aortic arch proximal to the region of obstruction was evident. Cross-sectional echocardiography may offer a useful noninvasive method for direct visualization of aortic coarctation.


Disproportionate ventricular septal thickening in the developing normal human heart. A disproportionately thickened ventricular septum containing numerous disorganized cardiac muscle cells is the most characteristic anatomic feature of hypertrophic cardiomyopathy. Since information concerning ventricular wall thicknesses and cellular arrangement in the developing heart may be pertinent to understanding the genesis of hypertrophic cardiomyopathy, morphologic observations were made in 151 normal human embryos, fetuses and term infants. Disproportionate ventricular septal thickening (septal-free wall ratio greater than or equal to 1.3) was present in 94% of embryos and young fetuses; in over one-third disproportionate thickening was particularly pronounced (septal-free ratio greater than or equal to 2.0). Disproportionate septal thickening was also present in 65% of older fetuses, but in only 12% of infants over two weeks of age. Septal-free wall ratio decreased in a curvilinear fashion with increasing age and apporixmated unity in the newborn. This phenomenon occurred because, while both ventricular septal and left ventricular free wall thicknesses increased directly with age, free wall thickness increased at a greater rate than septal thickness, particularly after birth. Marked cellular disorganization in the septum was not a feature of the hearts studied.


Failure of high doses of propranolol to reduce experimental myocardial ischemic damage. Myocardial creatine phosphokinase (CPK) activity and myocardial blood flow (MFB, 15 +/- mu microspheres) were measured at 24 hours after ligation of the left anterior descending coronary artery in nine untreated anesthetized dogs, in eight dogs pretreated with intravenous propranolol 5 mg/kg and in eight which had both pretreatment as well as infusion of propranolol (1.25 mg/kg/hour) after occlusion. Loss of CPK activity from the border and center zones of the myocardial infarct was similar in extent in dogs which had pretreatment but no infusion of propranolol as it was in the control group. Loss of CPK from the center zone was greater (P less than 0.005) in dogs receiving pretreatment followed by constant infusion of the drug. Propranolol had no significant effect on collateral blood flow to the border or center zone of the infarct. In separate experiments, there was no important difference in hemodynamic measurements, except a slower heart rate (P less than 0.01), when pretreated dogs were compared with control dogs up to 2 hours after coronary ligation. We conclude that propranolol given in this dose does not influence nyocardial damage, on the basis of regional myocardial blood flow or tissue CPK depletion values at 24 hr after coronary occlusion.


Effects of dimethyl propranolol (UM-272; SC-27761) on myocardial ischemic injury in the canine heart after temporary coronary artery occlusion. Myocardial ischemic injury after temporary occlusion of the left anterior descending coronary artery (LAD) for 90 min followed by reperfusion was estimated from the epicardial ST-segment elevation 15 min after occlusion (ST15m), changes in QRS complex, myocardial creatine kinase (CPK) activity and nitro-blue-tetrazolium (NBT) staining at 24 hours. At all sites exhibiting ST15m greater than 2 mV, there was a small development of epicardial Q waves after 90 min of occlusion (sigma deltaQ = 6.94 +/- 0.52 mV) and was maintained for 24 hours. Good correlations were obtained between CPK activity at 24 hours and the development of Q waves at 24 hours as well as at 60 min after reperfusion (r = 0.49; N = 56). Pretreatment with UM-272 significantly reduced the development of Q-waves (sigma deltaQ1hr = 2.23 +/- 0.75 mV) which was correlated with less CPK depletion and smaller infarct size as determined on the bais of NBT staining for myocardial tissue dehydrogenases at 24 hours. It appears, therefore, that the assessment of pathoologic Q wave development provides an accurate and early estimate of the extent of the ultimate cardiac damage due to ischemia and that pretreatment with UM-272 exerts a protective effect on the ischemic myocardium.


The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. In order to evaluate hemodynamic predictors of myocardial oxygen consumption (MVO2), 27 normotensive men with angina pectoris were studied at rest and during a steady state at sympton-tolerated maximal exercise (STME). Myocardial blood flow (MBF) was measured by the nitrous oxide method using gas chromatography. MBF increased by 71% from a resting value of 57.4 +/- 10.2 to 98.3 +/- 15.6 ml/100 g LV/min (P less than 0.001) during STME while MVO2 increased by 81% from a resting value of 6.7 +/- 1.3 to 12.1 +/- 2.8 ml O2/100 g LV/min (P less than 0.001). MVO2 correlated well with heart rate (HR) (r = 0.79), with HR x blood pressure (BP) (r = 0.83), and, adding end-diastolic pressure and peak LV dp/dt as independent variables, slightly improved this correlation (r = .86). Including the ejection period (tension-time index) did not improve the correlation (r = 0.80). Thus, HR and HR x BP, both easily measured hemodynamic variables, are good predictors of MVO2 during exercise in normotensive patients with ischemic heart disease. Including variables reflecting the contractile state of the heart and ventricular volume may further improve the predictability.


Hemodynamic effects of nitroprusside and hydralazine in experimental cardiac tamponade. Cardiac tamponade is associated with decreased cardiac output and increased systemic vascular resistance. Thus, vasodilator drugs might lower systemic resistance and increase cardiac output. Three groups of dogs were studied during tamponade. Group I received nitroprusside only; group II received blood transfusion and then nitroprusside; group III received hydralazine. In group I, nitroprusside lowered right artrial pressure and systemic resistance; cardiac output was unchanged. In group II, transfusion raised right atrial pressure but not cardiac output. Then nitroprusside raised cardiac output significantly. Hydralazine decreased right atrial pressure less than nitroprusside but decreased vascular resistance and raised cardiac output. Both nitroprusside and hydralazine decreased systemic vascular resistance during tamponade, but only hydralazine raised cardiac output probably because of its lesser effect upon the capacitance vessels. Nitroprusside maintained cardiac output during tamponade despite lowered right atrial pressure but increased cardiac output only after transfusion.


Effects of a cardiac glycoside in combination with propranolol on the ischemic heart of conscious dogs. The effects of coronary occlusion and of subsequent propranolol and ouabain administration were examined in 12 conscious dogs. Overall left ventricular (LV) function was assessed by measurement of LV pressure and dP/dt, and regional myocardial function was assessed by measurements of segment length (SL), velocity of SL shortening and regional myocardial "work," i.e., pressure-length loops in normal and moderately and severely ischemic zones. Regional intramyocardial electrograms were measured at the same sites as function along with regional myocardial blood flow as determined by the radioactive microsphere technique. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones, along with graded flow reductions and graded elevation of the ST segment. Propranolol, 1 mg/kg, depressed overall LV function and function in the normal zone more than in ischemic zones. Propranolol reduced flow to the normal zone and increased flow to ischemic zones, while not affecting ST-segment elevation significantly. In the presence of occlusion and propranolol, ouabain, 20 microgram/kg, improved overall LV function as well as regional function in the normal, moderately ischemic and severely ischemic zones. In addition, ouabain reduced ST elevation and increased blood flow further in moderately and severely ischemic zones. Most strikingly, ouabain returned normal systolic shortening to eight severely ischemic segments which were previously akinetic.


Beneficial effect of physical training on blood flow to myocardium perfused by chronic collaterals in the exercising dog. To determine the effect of physical training on collateral blood flow, we measured regional myocardial blood flow (MBF) by injecting 15 mu radioactive microspheres at rest and during exercise in 14 dogs with chronic coronary occlusive lesions. Seven dogs subsequently trained for 6 weeks while the other seven remained in kennels. Training effect was documented by decrease in heart rate during exercise that averaged 35 beats/min. MBF studies were repeated after 6 weeks. Myocardial samples were obtained from normally perfused zones (NZ) and from regions supplied via collaterals (collateral dependent zones or CZ). Initially, endocardial blood flow in CZ averaged 1.110 ml/min/g (83% of NZ, P less than 0.05) at rest and 1.36 ml/min/g (69% of NZ, P less than 0.05) during exercise, indicating relative underperfusion. Epicardial blood flow was equal in NZ and CZ. After 6 weeks MBF was not significantly changed in control animals. After training, however, MBF to underperfused endocardium of CZ during exercise was 39% greater than it had been prior to training. The epicardial portion of CZ (not exhibiting underperfusion) showed no change in MBF during exercise after training. Our data suggest that beneficial effects of training in coronary disease may include improvement in MBF to underperfused collateral-dependent portions of myocardium.


Reduced left ventricular myocardial blood flow per unit mass in aortic stenosis. Myocardial blood flow (MBF) per unit mass was measured in 10 patients (pts) with severe aortic stenosis (AS) and no significant aortic insufficiency, normal ejection fractions, and normal coronary arteriograms, using xenon-133 and a multiple crystal scintillation camera. MBF per unit mass was reduced in AS (53 +/- 13 mg/100g.min) in comparison to a group of seven normal control patients (69 +/- 12 ml/100g.min) (P less than 0.05). When normalized for heart rate. MBF remained depressed in aortic stenosis (0.65 +/- 0.11 ml/100 g.beat). MBF/beat was strongly related to peak left ventricular wall stress in both groups (r = 0.97). Individual values of MBF/beat were normalized for peak stress using an analysis of covarience; the adjusted mean values were 0.62 +/- 0.03 ml/100g.beat for the AS patients and 0.84 +/- 0.03 ml/100 g.beat for the control patients. There was no overlap between groups in adjusted MBF per beat. Values of MBF per beat and peak stress for a group of ten cardiomyopathy patients with depressed contractility were observed to fall close to the regression line for AS patients. The results suggest that variability in resting MBF in these AS patients is due primarily to differences in LV stress and that reduction in MBF per beat in this group may be due to reduced contractility.


Exploration of the cause of the low intensity aortic component of the second sound in nonhypotensive patients with poor ventricular performance. This investigation was undertaken to explore the cause of the diminished second sound (S2) that may occur in normotensive patients with poorly performing ventricles. Intra-aortic sound and pressure were measured in 16 patients with angina; eight had normal ventricular performance (ejection fraction greater than or equal to 60%) and eight had poor performance (ejection fraction less than 50%). The amplitude of S2 was lower in patients with poor ventricular performance as was negative d/dt. Aortic pressure was conparable in both groups. The ampitude of S2 was linearly related to the rate of change of the pressure gradient that developed across the aortic valve during diastole (r = 0.82). The latter also correlated with negative dp/dt (r = 0.82). These observations indicate that in patients with poor ventricular performance, isovolumic relaxation may be compromised. This would cause a reduction of the rate of development of the diastolic pressure gradient, which would result in a diminished S2.


Spectral energy of the first heart sound in acute myocardial ischemia. A correlation with electrocardiographic, hemodynamic, and wall motion abnormalities. First heart sound (S1) energy spectra in isovolumic systole, hemodynamics, and angiographic left ventricular wall motion (LVWM) at rest and with atrial pacing were compared in 27 patients who underwent diagnostic cardiac catheterization and angiography because of chest pain. Eighteen patients were found to have coronary artery disease (CAD) and nine patients, normal coronary arteries. Eleven of the 18 CAD patients (61%) had a mean reduction in the spectral energy of S1 of 6.5 +/- 1.4 (SEM) dB below control (-52%), during interruption of ischemic stress of rapid atrial pacing, compared to only one of nine patients without CAD (P less than 0.05). Only five CAD patients (28%) had an abnormal rise (greater than or equal to 5 mm) in left ventricular end-diastolic pressure (LVEDP) either during or upon interruption of pacing, and six (33%) had ischemic ST-segment depression greater than or equal to mv in the ECG. Similarly two patients free of CAD (22%) had an abnormal increase in LVEDP, and none had ECG evidence of ischemia. Seventeen CAD patients (94%) had segmental LVWM abnormalities at rest or with interruption of pacing, while three patients with normal coronary arteries (33%) had abnormal angiographic LVWM (P less than 0.01). Thus, reduction is S1 spectral energy is a common accompaniment of myocardial ischemia. In the present study, it was more frequently observed than abnormalities in either the ECG or LVEDP, but was not was consistently seen as segmental left ventricular wall motion abnormalities.


Changes in plasma catecholamines and dopamine beta-hydroxylase after corrective surgery for coarctation of the aorta. In six patients within 12 hours of surgical correction of aortic coarctation there was a 750% increase in plasma noradrenaline concentrations accompanied by an increase in systolic and diastolic blood pressures. The magnitude of the postoperative increase in noradrenaline concentrations was related to the preoperative level of the pressure gradient across the coarctation. Six months after operation plasma noradrenaline concentrations were still significantly elevated. In nine patients who underwent other types of major surgery there was a small increase in plasma noradrenaline concentrations and a return to levels within the normal range within 24 hours. Various explanations for the rise in plasma noradrenaline concentrations are considered. In particular the possibility is raised that after surgical correction of aortic coarctation the increased levels indicate a marked increase in sympathetic nervous system activity; this may be mediated by baroreceptor mechanisms and may persist for up to six months after surgery.


A guide to the radiographic identification of prosthetic heart valves. To facilitate the radiographic identification of prosthetic heart valves, radiographic silhouettes of various aortic, mitral and tricuspid valve prostheses were analyzed and shematized. Forty different prosthetic valve models (heterograft and mechanical) were obtained from seven domestic manufacturers. Each prosthesis was positioned to approximate the aortic, mitral or tricuspid valve anulus plane. The valves were then radiographed and photographed as they would appear in posteronanterior and left lateral chest radiographs. The radiographic silhouettes were examined and a scheme was designed to enable easy, yet accurate, differentiation of the many heart valve prostheses. Illustrations of the various valve types are presented as they would appear in routine chest radiographs.


Echocardiographic diagnosis of ruptured aortic valve leaflet in bacterial endocarditis. Aortic valve rupture, secondary to aortic valve endocarditis, was diagnosed echocardiographically and closely followed preoperatively. The ruptured left coronary cusp of the aortic valve was seen as dense irregular echoes, located anteriorly during ventricular diastole, and protruding into the left ventricular outflow tract in an otherwise normally appearing aortic valve. These echocardiographic findings, when correlated with changes in the clinical status of the patient, prompted immediate cardiac catheterization and aortic valve replacement. Early echocardiographic detection of abnormal aortic cusps and variation from normal aortic root echo features should alert the physician to proceed to cardiac catheterization, and aortic valve replacement if necessary.


Inexcitable right ventricle and bilateral bundle branch block in Uhl's disease. A 29-year-old female with Uhl's anomaly developed complete atrioventricular (A-V) block. His bundle studies revealed block distal to the His bundle recording site with narrow QRS complexes. Right ventricular capture could not be obtained and despite successful left ventricular epicardial pacing, the patient died. Autopsy revealed absence of myocardium in most areas of the right ventricle and the right side of the ventricular septum with a normal tricuspid valve. Conduction system examination revelaed total destruction of both bundle branches. This is the first case where bilateral bundle branch block is shown to be present in Uhl's anomaly. Narrow QRS complexes probably reflected the absence of right ventricular forces.


Serum cholesterol analysis in the C.B. Heart Project. Intra-and inter-laboratory continuous quality control. Standardization and quality control of measurements are of crucial importance in large medical surveys. In the C.B. Heart Project serum cholesterol analyses in the central laboratory were extensively controlled with regard to precision as well as accuracy. All measurements are carried out in side-by-side duplicate, the maximum difference allowed being 0.3 mmol/l. Bench control, aiming at maintaining linearity and precision with control limits, requires insertion of standard solutions and several serum controls into every run. Control values must fall within 2 S.D. limits from the established mean values, e.g. 4.1 +/1 0.25 mmol/l and 8.2 +/- 0.25 mmol/l. A very reliable check on the precision was obtained by blind introduction of duplicate patient specimens. Repeatability (within-run precision) as calculated each month has S.D. values of approx. 0.10--0.20 mmol/l, whereas reproducibility (long-term precision) S.D. values are 0.15--0.25 mmol/l. Accuracy is checked in the Cooperative Standardization Programme of the WHO Regional Lipid Reference Centre in Prague. This makes the C.B. Heart Progject results comparable with other standardized studies. Our bias approximates +3% and usually remains within WHO "narrow limits".


Thyroid hormone concentrations in a large scale community survey. Effect of age, sex, illness and medication. Total thyroid hormone concentrations have been measured in the course of a large scale community survey to determine the distribution of these variables in the normal population and to assess the effect of age, sex, previously undectected thyroid disease and medication upon these parameters. 2779 subjects were studied. Serum T4 concentrations were normally distributed. A progressive increase in T4 levels with age was noted in the males, and a smaller increase in females which was concealed by the raised T4 values secondary to oral contraceptive therapy in females under the age of 45. Serum T3 levels were also normally distributed. There was a small reduction in T3 with age in the males but this fall was not seen in the females. T3 values were relatively higher in females under the age of 45 but this increase was not noted after exclusion of subjects taking an oral contraceptive. The changes in thyroid hormone concentrations with age are relatively minor (particularly with respect to T3) in a randomly selected sample from an English town. It is suggested that the changes reported by other authors reflect the process of selection used, and the high frequency of undetected thyroid disease, other illness and medication in hospital-based communities.


Mitochondrial fraction of serum glutamic-oxaloacetic transaminase in Duchenne muscular dystrophy. The mitochondrial fraction of serum glutamic-oxaloacetic transaminase was measured in the serum of 50 patients with Duchenne muscular dystrophy by an immunoadsorbent method. The enzyme activities in patients in the early, midstage, and late stages of the disease and controls were 21.8 +/- 7.4 (N=9), 12.2 +/- 3.7 (N=38), 6.4 +/- 1.2 (N=3) and 4.2 +/1 1.2 units/ml (N=15), respectively. The enzyme level in the early stage was significantly elevated (p less than 0.01, vs. control, p less than 0.05 vs. mid stage). As the disease progressed, the levels gradually declined, but mid-stage values were still higher than the late stage (p less than 0.01) or control values (p less than 0.01). In the late stage, enzyme activity was within the control range.


Multiple forms of renin substrate in human plasma. Renin substrate (angiotensinogen) in unfractionated human plasma has been shown to exist in multiple forms by DEAE-cellulose chromatography and isoelectric focusing. Two major and 5 to 6 minor peaks were resolved by using a descending pH gradient elution from DEAE-cellulose columns. The two predominant forms were eluted at or near pH 4.8 and 4.4 and usually accounted for 40--50% of the recovered substrate activity. The elution pH values of the various forms were nearly constant among plasmas from normal males and females and in diabetes, early and late pregnancy and estrogen substitution therapy. The relative distribution of components was not affected by prior freezing of the plasma or by dialysis against the column buffer. Eight renin substrate forms were clearly resolved during isoelectric focusing of plasma from a woman on estrogen substitution therapy. Four of these focused at pH 4.79, 4.88, 4.94 and 5.02 in 1% (w/v) ampholytes pH 3.5--5 and were nearly equal in substrate amount. Together these 4 forms constituted 66% of the total recovered activity. A similar pattern but with decreased amounts of each form of substrate was obtained with normal plasma.


The labelling of urinary acids after oral doses of deuterated L-phenylalanine and L-tyrosine in normal subjects. Quantitative studies with implications for the deuterated phenylalanine load test in phenylketonuria. Oral doses of L-[2H5]-phenylalanine (25 mg/kg) and L-[2H2]-tyrosine (12.5 mg/kg) were given separately to three normal subjects and together to a fourth. Blood samples were analysed for deuterium labelled phenylalanine and tyrosine, and urine for labelled o-and p-hydroxyphenylacetic, p-hydroxyphenyllactic and p-hydroxymandelic acids. The labelling patterns of the urinary metabolites indicated that the para-compounds all originated in both hepatic and extra-hepatic tissues. The plasma tyrosine did not appear to be in equilibrium with the tyrosine in the liver. It is concluded that a simple quantitative relationship between the labelling of these metabolites and the synthesis of labelled tyrosine from labelled phenylalanine in liver is unlikely.


Loads versus tracers for assessing phenylalanine hydroxylase activity using plasma phenylalanine decay curves. Consideration of the flow of phenylalanine within the body shows that classical phenylalanine load tests for assessing phenylalanine hydroxylase activity cannot usefully be replaced by tracer techniques.


Fluorimetric determination of free hydroxyproline and proline in blood plasma. A selective and sensitive assay of hydroxyproline in blood plasma is presented. The technique uses ion exchange chromatography followed by reaction with 7-chloro-4-nitrobenzofurazan (NBD choloride) and continuous recording of the resulting fluorescence (gamma ex=465 nm, gamma fl=535 nm). Proline and prolyl-and hydroxyprolyl-peptides can also be measured by this system. For hydroxy proline, the method is more sensitive than procedures using ninhydrin or p-dimethylaminobenzaldehyde.


Automated continuous flow determination of urine albumin by competition with dye-detergent binding. A continuous flow automated method for urine albumin was developed based on the ability of albumin to displace bromophenol blue from a bromophenol blue detergent complex. The method is almost specific for albumin, giving a slight response with an alpha-globulin fraction from serum. Results agreed closely with rocket electrophoresis albumin estimates on urine samples, but significantly less closely with "total urine protein" estimates by an acid protein precipitation, followed by biuret colour reaction, procedure. This method is being used to replace the indefinite "total protein" test for most routine purposes.


The misleading presence of glucose in lipid extracts from human liver. Lipid extracts of two out of three liver samples examined contained appreciable quantities of an apparent glycolipid migrating with a chromatographic mobility intermediate between a tetrahexosylceramide standard and sphingomyelin. The substance was subsequently identified as free glucose. Its presence in the lipid extracts was probably related to the high levels of endogenous carbohydrate in the samples. To prevent possible confusion with glycolipids, care should be exercised in the interpretation of chromatographic data when organs containing high levels of endogenous carbohydrate are being examined.


Spontaneous abortion, sex ratio and facial cleft malformations. In family and reproductive data combined from five treatment centers, relating to 861 index cases with cleft lip (with or without cleft palate, CL+/-P), maternally recognized spontaneous abortions were found to be significantly less frequent in sibships including two or more cases of CL+/-P than in sibships including only one case. In data relating to 379 index cases with cleft palate (CP), maternally recognized spontaneous abortions were reduced to a degree short of formal significant in sibships including two or more cases of CP by comparison with sibships including only one case of CP. The sex ratio among the sibs of parents of CL+/-P index cases was elevated when the index case was the only affected child and reduced when the index case had one or more affected sibs. Considered in combination with the results of other investigations, these findings indicate the existence of inherited factors reducing abortion frequency in the sibships of CL+/-P index cases. These factors appear to be unrelated to those for liability to CL+/-P.


Partial 2p trisomy (p21 leads to pter) in two siblings of a family with a 2p-:15q+ translocation. Partial 2p trisomy was diagnosed (by the G-banding method) in two sibs with multiple congenital defects. Their father showed a balanced translocation 46,XY,rcp(2;15)(p21;q26) (so the patients were the result of a paternal adjacent-1 meiotic segregation). The clinical features of the two affected cases are compared with other cases previously reported of partial 2p trisomy in order to individualize the syndrome.


Arginase deficiency in multiple tissues in argininemia. A 5 9/12-year-old Mexican female with argininemia presented at 4 years of age with severe growth retardation, microcephaly, mental retardation, loss of ability to walk, spasticity and epileptiform electroencephalogram. At follow-up, blood ammonia was elevated only twice out of 30 determinations. Blood arginine was 544 to 1,074 mumol/l (normal 61 to 173); cerebrospinal fluid arginine was 88 mumol/l (normal 6 to 29); and urinary arginine, citruline and argininosuccinic acid were consistently elevated. Arginase activities in tissues from the propositus were 0.01 mU/mg hemoglobin in erythrocytes (normal 29.8 to 96.1); 9 mU/mg protein in liver (normal 1,522 to 5,491); and 5 mU/mg protein in stratum corneum (normal 2,856 to 7,556). The demonstration of arginase deficiency in liver and stratum corneum suggests a generalized deficiency and helps to explain the elevation of blood arginine. Therapeutic trials of orally administered lysine to enhance dibasic amino acid competition and of enzyme replacement using erythrocyte transfusion did not result in significantly decreased blood arginine or clinical improvement.


Developmental abnormalities associated with long arm deletion of chromosome No. 6. A patient is reported who had a partial terminal deletion of the long arm of chromosome No. 6. His clinical findings included development delay, failure to thrive, neurologic abnormalities, and multiple congenital malformations. Among the malformation were unusual facial features, cleft palate, atrial septal defect, and abnormalities of the external genitalia. The patient's features are compared with others who may have material deleted from the long arm of chromosome No. 6.


Glutaric aciduria in progressive choreo-athetosis. The clinical symptoms in a 10-year-old girl with progressive dystonic cerebral palsy are described. The biochemical findings were dominated by large amounts of glutaric acid in the urine. The disorder is caused by impairment of the degradation of glutaryl-CoA. A survey is given of the clinical and biochemical symptoms, based on the five cases reported so far. It is concluded that patients with progressive dystonic palsy should be examined for disorders in the metabolism of organic acids.


Benign hereditary chorea. Clinical and genetic aspects. Five patients from two families in Wales are described who have a benign disorder characterized by lifelong, non-progressive choreic movements, but without mental deterioration or other features of Huntington's disease. The clinical picture and natural history of this specific disorder are discussed, with particular emphasis on its distinction from Huntington's disease. Genetic data from previously reported kindreds are reviewed, and it is concluded that the disorder follows autosomal dominant inheritance, with reduced penetrance in the female. The importance is stressed of recognizing this disorder and not confusing it with Huntington's disease, if serious errors in prognosis and genetic counseling are to be avoided.


Fetal mitral valve movement recording by pulsed ultrasound. A technique for the recording of the fetal mitral valve is described and evidence to confirm the origin of the echoes is presented. Our results based on over 500 recordings, and their potential clinical values are discussed.


Percutaneous transhepatic cholangiography with the Chiba Needle. Percutaneous transhepatic cholangiography using the Chiba needle has been performed on 102 patients. There was an overall success rate of 86 out of 102 cases (84%). Dilated bile ducts were successfully demonstrated in 61 out of 65 patients (94%) and non-dilated ducts in 25 out of 37 patients (70%). Gallbladder filling was achieved in 40 out of 70 cases (67%). The hepatic lymphatics were filled in 32 cases but dilated lymphatics were mainly seen in patients with biliary cirrhosis, inflammatory liver disease or lymphoma. It is suggested that an excessive radiation dose may be given to the radiologist's fingers unless the fluoroscopy diaphrams are kept well coned down. Complications requiring active medical intervention occurred in three cases and emergency surgery in one case.


Selection of tumors with a poor prognosis in operable carcinoma of the endometrium. A retrospective review of 405 patients with operable cancer of the endometrium tested the hypothesis that histological grading might serve to select patients with a poor prognosis for additional external radiation. Deaths from disease by the fifth anniversary were 10 times higher (28/109 - 26%) among patients in the poorly differentiated group - who made up 27% of those assessed. There were 7/288 deaths (2.5%) in the well-differentiated group. A sample of 114 curettage specimens from the above cases, graded without knowledge of the clinical findings, gave a similar result. The FIGO grading system has the advantage of having well-defined dividing lines between grades 1, 2 and 3. However, its value in clinical practice is limited, since the prognostic watershed between well-differentiated and poorly differentiated cases falls well within grade 2. The separation between grade 1 and hyperplasia is also poorly defined and may affect the interpretation of oestrogen studies in relation to endometrial cancer incidence.


Carcinoma of the larynx - results of primary radiotherapy. Results for 180 patients with carcinoma of the larynx treated by radiotherapy at Belvidere Hospital in Glasgow between 1958 and 1968 are presented. The policy of treatment was primary radiotherapy with surgery for recurrences. All the patients have been followed up for more than five years. Overall crude five-year survival is 57%. For stages I and II it is 70%. Surgical rescue was successful in 50% of fit patients.


Distant metastases in nasopharyngeal carcinoma. Three hundred and fifty-two consecutive cases of nasopharyngeal carcinoma were analysed to determine the pattern of distant metastases. Diagnosis of distant metastases was made wholly on clinical signs and radiography. Ninety-nine patients developed distant metastases, an incidence rate of 28.1%. There did not appear to be any difference in "risk" by age or sex. The predilection of this cancer to develop skeletal metastases is further confirmed. Pulmonary and hepatic involvement were the next commonest. Both extent of primary tumour (T) and cervical lymph node status (N) exerted a significant influence on the probability of metastases developing. Thus significant differences in metastatic rate were observed between T0/T1, T2 and T3/T4 and N0, N1, N2 and N3 groups. 65.6% of metastatic cases had control of local disease (nasopharynx and cervical lymph nodes). When metastases are diagnosed the prognosis is gloomy with a median survival under four months and a fatality rate of 91% within a year of first metastasis.


The radiological changes in infections of the spine and their diagnostic value. This study describes the early radiological changes which occur in infections of the spine, by examination of the initial radiographs in 45 patients with proven spinal infection. The commonest radiological change in infection of the spine was a symmetrical lesion involving the adjacent surfaces of two vertebrae, with a variable degree of reduction in height of the disc space. A paravertebral abscess was a common associated finding. No radiological pattern was completely reliable in distinguishing tuberculous from non-tuberculous infections, but in white patients the formation of new bone strongly suggested a pyogenic lesion. The presence or absence of a paravertebral abscess was not helpful in distinguishing the variety of infection.


Osteoblastic bone metastases secondary to adenocarcinoma of the pancreas. The incidence of bone metastases secondary to adenocarcinoma of the exocrine pancreas is unknown since radiological studies of the bones during life, routine bone scintigrams or extensive examination of the skeleton at autopsy is rarely undertaken in the absence of specific clinical indications. Symptom-producing bone metastases are relatively uncommon; a review of the literature suggests that the vast majority are osteolytic in nature with only a few isolated case reports of purely blastic deposits. In the authors' experience osteoblastic bone metastases are commoner than is generally recognised. Of 12 patients with symptom-producing bone deposits secondary to adenocarcinoma of the pancreas, five (41.6%) were purely blastic in nature. The clinical, radiological and pathological findings in these five cases are reported in order to emphasise that the pancreas is a potential source of purely blastic bone metastases and should be considered as a possible primary site in patients who present initially with osteoblastic bone deposits of unknown origin.


The radiology of bone changes in rhabdomyosarcoma. Rhabdomyosarcoma usually presents as a soft tissue mass, which may invade adjacent bone. However, the patient presents occasionally with bony metastases. Recognition of these is important for staging and management. Fifty-eight cases have been reviewed; 14 of these had local bone invasion by the soft tissue tumour. All bones involvel were flat bones; 12 showed permeated bone destruction and two showed geographic destruction. Bone expansion was seen in half the involved bones. Twelve of the 58 cases showed secondary bone deposits, which were the presenting feature in five. Although 10 cases had permeated bone destruction, two were very well defined with a wide range of radiological appearances. The radiological differential diagnosis includes neuroblastoma, leukaemic infiltration, lymphoma, histiocytosis X, solitary and multifocal osteosarcoma and other deposits.


The role of diagnostic radiology in the diagnosis and management of rhabdomyosarcoma in young persons. Rhabdomyosarcoma is a rare tumour of mesenchyme-like tissue in which differentiation of rhabdomyoblasts has occurred. It is found mainly in infants and children. The prognosis, until recent years very grave, has been improved by a combination of chemotherapy and radiotherapy occasionally with surgery. Survival depends on the extent of the disease at the time of diagnosis. Diagnostic radiology has an important role to play in the demonstration of this, illustrations of which are given from a series of seven cases. The primary tumour has no pathognomonic appearances and is demonstrated essentially as a soft tissue mass lesion which displaces adjacent soft tissue structures such as arteries, veins, bladder and colon, or erodes adjacent bones whether in the extremities or the skull. The main role of diagnostic radiology is the detection of metastases. Chest radiography and skeletal survey are mandatory. Lymphangiography may reveal filling defects in regional lymph nodes but these are indistinguishable from any other metastases. Arteriography as well as revealing displacement of larger vessels, may show typical tumour neovascularity in the lesion. Serial skeletal radiographs are of help in assessing response of metastases to therapy.


Widening of the radial notch of the ulna: a new articular change in haemophilia. A new radiological sign has been observed in 14 of 236 elbows of haemophiliacs examined. This finding is a widening of the radial notch of the ulna, which may become extremely large.


The abdominal aorta in spina bifida cystica. The features of abdominal aortography in a small group of severely affected children with spina bifida cystica and kyphosis are presented. The examination was done to spinal fusion as earlier surgical reports had indicated a close relationship between the aorta and the vertebral bodies forming the apex of the kyphosis. The abdominal aorta was shown to bridge the apex of the kyphosis, thus it was outside the field of surgery and was not a potential hazard. Three vascular abnormalities emerged. First, the position of the aortic bifurcation, as judged by the vertebral level, was shown to be rather lower than usual, although lumbar kyphosis masked a relative aortic shortening. Second, the aorta was abnormally small in calibre with hypoplastic limb vessels. Third, abnormal segmentation of lumbar arteries was found in four of the eight in whom they were visualised, and correlates with the presence of vertebral body maldevelopment as opposed to neural arch maldevelopment. The possible pathogenic significance is discussed.


Radiological features of vascular compression of the duodenum occurring as a complication of the treatment of scoliosis (the cast syndrome). The application of a body cast or the surgical correction of scoliosis is occasionally associated with acute obstructive vascular compression of the duodenum. The clinical and radiological manifestations observed in 10 such patients are described. All cases manifested abdominal distension and vomiting, while epigastric pain was present in 50%. Plain radiographs of the abdomen demonstrated duodenal distension with little gas in the remainder of the bowel in three cases. Barium studies in nine patients demonstrated an intact mucosal pattern and a duodenum dilated proximal to the site where the superior mesenteric vessels crossed it. All cases recovered with non-operative treatment which included nasogastric suction, intravenous fluids, change in position, particularly nursing in the prone position, and, occasionally, cast removal. The obstruction may sometimes persist or recur and then duodenojejunal side-to-side anastomosis is the surgical procedure of choice. The term "cast syndrome" is a misnomer as vascular compression of the duodenum may also occur in patients who are undergoing treatment for scoliosis without the use of a body cast.


Comparative pelvimetric measurements in Nigerian and Welsh women. The authors compared the pelvic measurements of a group of Nigerian women with those of a similar group of Welsh women. The Nigerian pelvis is smaller than the Welsh especially when account is taken of the Nigerian women being taller. Base-line data for radiologists working in Nigeria are provided.


Pharyngoesophageal manifestations of epidermolysis bullosa. Two cases of a rare hereditary disease, epidermolysis bullosa, congenital and acquired, are presented. The disease manifests by vesicular eruptions over the skin and mucous membrane of the oropharynx and oesophagus, alternating with sympton-free periods. The recurrent crops of vesicles heal by scarring and progressive stenosis of the pharynx and oesophagus. Although mucosal involvement is a less common and a late manifestation of the disease, it may occur in relatively mild cases and relatively early in the course of the disease. It is important that the radiologist be familiar with the pharyngoesophageal manifestations since the patient may present with dysphagia during an interval free of cutaneous lesions. The barium swallow appearance of stricturing with obstruction is illustrated.


Isolated mesenteric desmoids (mesenteric fibromatosis). The so-called desmoid tumour is an important member of a group of conditions termed "the fibromatoses" which are characterised by an infiltrating fibroblastic proliferation without features of an inflammatory response. While desmoids most frequently arise in the anterior abdominal wall, they may also be extra-abdominal or intra-abdominal in location. Mesenteric desmoids are relatively rare. They may occur in association with Gardner's syndrome, especially following colectomy, or as an isolated abnormality in otherwise normal patients. In the present paper the authors describe the clinical, radiological and pathological findings in two patients with isolated mesenteric desmoids. The radiological differential diagnosis is also briefly discussed.


Analysis of a new corticosteroid aerosol in treatment of contact dermatitis. In multicentric clinical trial involving twelve investigators and 271 patients, betamethasone dipropionate (0.1 percent) aerosol was found to be significantly more effective than its vehicle in the treatment of moderate to severe contact dermatitis. Statistical tests determined this significance at a value of less than 0.0001. Betamethasone dipropionate was favored numerically not only in the combined results but also in ten of the twelve individual centers.


Pyoderma gangrenosum--a literature review. Pyoderma gangrenosum is an ulcerative skin disorder with typical clinical characteristics. Histologic and laboratory findings are nonspecific. Pyoderma gangrenosum is associated with internal disorders including inflammatory bowel disease, paraproteinemias, leukemias, and arthritis. The pathogenesis of pyoderma gangrenosum is unknown, although a partial defect of cell-mediated immunity may exist. Treatment includes bedrest, local care, sulfonamides, sulfones, and corticosteroids.


Methotrexate toxicity in the treatment of generalized pustular psoriasis. In a sixty-seven year old woman with a seventeen-year history of psoriasis, generalized pustular psoriasis of von Zumbusch developed. She was treated with parenteral methotrexate in two divided doses over a one-week period. Severe acute granulocytopenia developed with a drop in the white blood cell count from 27,000 to 400. We postulate that the pustular psoriasis stimulated rapid proliferation of the granulocyte series with a high percentage of the precursor cells in the bone marrow in the S-phase of the cell cycle. The subsequent dose of methotrexate resulted in a blockage of DNA synthesis in these cells and subsequent failure of maturation beyond the mitotic compartment in the bone marrow. Caution is recommended in the use of methotrexate in patients with acute generalized pustular psoriasis.


A person's boundaries: a meaning of skin disease. This report attempts to broaden understanding of the psychological meaning of skin disease by describing patients' fantasies of healthy vs diseased skin. All disease states have emotional concomitants in ideas, attitudes, and fantasies--much at variance with what the clinician views in an "objective" focus. Skin disease particularly is invested with affectively charged ideas. The issue of "dirt" contained, in fantasy, by healthy skin is explored. Skin lesions are particularly difficult for many patients to master emotionally, because such lesions engender a sense of dirtiness--a feeling of lack of control over body contents.


Verrucous carcinoma.

Verrucous carcinoma. The various clinicopathologic forms of verrucous carcinoma of skin and mucous membrane are reviewed. It is found that the histology and natural history of these well differentiated types of squamous cell carcinoma are remarkably similar. It is concluded that verrucous carcinomas of the head and neck, giant condyloma acuminatum of the genitalia, and carcinoma cuniculatum of the lower extremity are but variants of the same neoplastic system.


Diseases of the oral mucosa.

Diseases of the oral mucosa. The dermatologist is often called upon to evaluate diseases of the oral mucosa. He should be prepared to give expert advice based on sound knowledge of oral diseases. This may be aided by biopsy study if the principles and pitfalls of obtaining and interpreting a biopsy specimen are followed. These are discussed and examples are given to illustrate some of the more common and important problems that may be encountered.


Heterogeneity in Chinese hamster ribosomal DNA. A discrete heterogeneity has been detected in Chinese hamster ribosomal DNA after Eco R1 digestion of total DNA followed by a Southern transfer and hybridization with [125I]18S or [125I]28S ribosomal RNA. Digestion with Eco R1 produces three fragments, 4.3, 6.0 and 9.5 x 10(6) daltons respectively, which hybridize with 18S RNA. The smallest fragment also hybridizes with 28S RNA. Either length heterogeneity or sequence heterogeneity (i.e. presence of an additional Eco R1 site in some of the rDNA molecules) must be invoked to account for the two larger Eco R1 fragments that contain 18S but not 28S sequences. Eco R1 and Hind III maps, consistent with either length or sequence heterogeneity, are presented. The data at this time, however, do not distinguish between the two alternatives.


[Acute drug-induced agranulocytosis: comparison between openward treatment and antimicrobial decontamination in a plastic isolation bed system (retrospective study of 30 cases) (author's transl)]. Thirty patients with severe drug-induced agranulocytosis were admitted to the Ulm University Hospital between January, 1968 and October, 1976. All of 13 already infected patients treated with antimicrobial decontamination in a plastic isolation bed system survived. But nine of 17 patients treated in the open ward died. The cases were not randomised and there was a difference in age between the two groups, but nevertheless the results suggest that antimicrobial decontamination and isolation is superior to treatment in an open ward.


[Post-traumatic diabetes insipidus syndrome (author's transl)]. Post-traumatic diabetes insipidus was observed in 14 among 702 patients with severe trauma. The cause of the abnormal vasopressin secretion may be cerebral oedema, cerebral contusion near the hypothalamus, pull on the hypophyseal stalk by displacement or gross destruction of the brainstem. The hormonal hypofunction disappears once the cerebral damage has regressed. Treatment consists of exact balancing of water and electrolyte loss, using salt-free solutions. Drug treatment with vasopressin and with ADH-secretion stimulators has given unsatisfactory results, but should be used. Seven of the 14 patients died of their injuries. The symptoms of the diabetes insipidus syndrome regressed in the survivors.


[Toxic rhabdomyolysis after alcohol and drug intoxications (author's transl)]. The clinical picture of toxic rhabdomyolysis after alcohol and drug intoxications is characterized by severe pain, swelling, and inability to move the affected muscle group. The disintegration of necrotic muscle tissue leads to hyperkalaemia, excessive increase of creatine kinase in serum, and a myorenal syndrome with anuria. Pathogenetically the combined effects of toxic vascular damage and local pressure and cold influence are assumed to occur. In anuria, resistant to conventional medication, early and repeated plasma exchanges are considered to be a therapeutic alternative to haemodialysis.


[Cortisol substitution in adrenal insufficiency (author's transl)]. Both in patients with primary (n = 15) and secondary (n = 10) adrenal insufficiency a conventional substitution with 30 mg cortisol daily (3 single doses of 15, 10 and 5 mg) leads to an unsatisfactory adjustment in most cases. Plasma maximal values after the morning dose were obtained only between 9 and 11 a.m. and were 3.5 times higher than cortisol values of healthy probands (n = 35). The half-life of cortisol in plasma (t1/2 = 0.8-3.2 hrs) varied to such an extent that some patients had subnormal values relatively quickly or that concentrations above normal were found permanently. The same also applies to free cortisol in plasma. The amount of free cortisol in urine cannot be used as a parameter of a physiological substitution of cortisol. The individual adjustment of the treatment plan can thus be only established according to cortisol concentrations in plasma.


Correlations between EEG and multiple unit activity of cortifugal axons at the onset of drug induced seizures in cats. The onset of sustained multiple unit activity (MUA) in corticofugal axons was found to precede the onset of tonic EEG activity in 91 of 92 seizures produced by administering pentylenetetrazol, strychnine, or dieldrin to cats. Latency differences from 0-8 sec were observed with a mean of 3 sec. A trend was noted for shorter latencies with subsequent seizures in the same subject. No differences in latency were seen for spontaneous as compared to evoked seizures. Much variation was encountered in the pattern of MUA and EEG development at seizure onset. In general seizures with well-defined EEG components of desynchronization, tonic and clonic activity had the greatest latency differences and the least correspondence between MUA and EEG. Seizures with the abrupt emergence of tonic or clonic activity had the smallest latency differences and the best correspondence between MUA and EEG. Large changes in the activity along corticofugal axons were observed without EEG correlates. The evidence supports the concept that the degree of synchrony within the cortical (pyramidal) cell population is critical to the emergence and development of EEG during the tonic and clonic phases of a seizure. The data suggest that, in some cases, important changes in corticofugal output may contribute to and reinforce the activity in subcortical loci implicated in generalized seizure onset.


Manipulation of cerebral monoamines in the treatment of human epilepsy: a pilot study. The effects of L-DOPA, L-tryptophan, monoamine oxidase inhibitor (MAOI), and MAOI plus L-tryptophan, each for 3 months, have been assessed in 10 severe, adult epileptics with placebo control. There was no overall reduction in seizure frequency, but 2 patients with minor partial seizures improved, 1 with L-DOPA, MAOI, and MAOI plus L-tryptophan, and the other with L-tryptophan and MAOI plus L-tryptophan. We have not been able to demonstrate an increased turnover of cerebral serotonin (5-HT), as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid, after treatment with L-tryptophan for 3 months. This observation casts doubt on the ability of L-tryptophan to alter the long-term metabolism and functional activity of brain 5-HT. The importance of further exploration of manipulation of cerebral monoamines as a possible approach to the treatment of epilepsy is emphasized.


Antiepileptic and prophylactic effects of tetrahydrocannabinols in amygdaloid kindled rats. The antiepileptic and prophylactic effects of delta9-tetrahydrocannabinol (delta9-THC) and delta8-THC were examined in rats that developed generalized seizures in response to intermittent electrical stimulation of the amygdala (kindling). Both isomers of the THC were able to acutely suppress kindled seizures, but consistent antiepileptic effects were obtained only with high, toxic dosages. Tolerance to the antiepileptic effects of THC developed very rapidly when the drugs were give repeatedly, and there was evidence that the repeated administration of a high dosage of delta9-THC resulted in a state of acute physical dependence. Administration of the isomers of THC during seizure development resulted in a suppression of kindling, suggestive of a prophylactic effect. The rate of rekindling after withdrawal of the drugs was not significantly different from that of vehicle-treated control rats, however, indicating that a genuine prophylactic effect was not obtained.


Convulsive disorders in the first year of life: neurological and mental outcome and mortality. Mortality and neurological and mental outcome were studied in infants 28 days to 1 year of age with afebrile seizures not due to an acute postnatal injury. Cases were divided into four seizure types: infantile spasms: status epilepticus; and "others" (patients without spasms or status), generalized and partial. Mortality was studied in 334 cases, mental and neurological prognosis in 313 infants followed 1 year or more. Globally the prognosis was very poor even outside cases of infantile spasms. Mortality was higher and mental and neurological sequelae were more common in symptomatic than in cryptogenic cases. The highest mortality and greatest number of neurological defects were in status epilepticus and in "others" partial groups. Severely retarded subjects were more common in infantile spasms and "others" partial. The proportion of mentally normal patients, however, was no different according to ictal type. Mental and neurological prognosis was less unfavorable when the first seizure occurred at or over 6 months. A family history of epilepsy or febrile convulsions (21% of the cases in the whole series) was more common in the "others" subgroups, especially in the cryptogenic "others" (42%). The less unfavorable outcome obtained in cryptogenic "others" generalized with a positive family history.


Epilepsy in rural Kentucky: prevalence in a population of school age children. Seizure prevalence among school age children residing in a rural western Kentucky area (Hardin County) was determined utilizing a method designed to minimize false positives and to allow estimation of false negatives. The observed prevalence of epilepsy is 5.7/1,000 and of febrile seizures 17/1,000. Because of the high rate of false negative responses detected by random sample interview, the true rate of febrile seizures is believed to be closer to a projected rate of 31/1,000.