Influence of intraocular colchicine and vinblastine on the cat iris. The effect of intravitreally injected colchicine (100 mug and 300 mug) and vinblastine (100 mug) on function and sensitivity of the cat iris was studied in vivo. Both antimitotics caused the same effects: The sensitivity to touch of the cornea disappeared after the third day. The normal sensitivity recovered, but after 1 month there was still an anesthetic island in the center of the cornea. The consensual light reflex from the injected to the normal eye declined markedly between 12 and 24 h and was abolished after 4 days. The consensual light reflex from the normal to the injected eye decreased with a similar time course and was completely abolished or strongly reduced after 4-5 days. The function of the sphincter pupillae in the injected eye was reestablished after one month. The affected iris became supersensitive to both pilocarpine and norepinephrine. The degree of supersensitivity in the cholinergic system was closely and inversely related to the degree of impaired function. The function of the dilatator pupillae could not be tested. The observed phenomena were most likely due to inhibition of exoplasmic flow in the nerves supplying the iris and cornea.


Biosynthesis of cadaverine in mice under the influence of an anabolic steroid. The content of cadaverine (1,5-diaminopentane) in the kidney and urine was investigated in mice treated with the anabolic steroid Durabolin (nondrolone phenpropionate). After administration of this steroid cadaverine was found in the kidneys, whereas this amine could not be detected in the kidney of controls. The urinary excretion of cadaverine was elevated 50 times after Durabolin administration. An enzyme catalyzing the formation of cadaverine from lysine was shown for the first time to be present in mammalian tissue, namely in the kidney of mice after Durabolin administration.


Improved left ventricular performance by the transmission of pulse waves through the pulmonary vascular bed. The influence on left ventricular performance of pulsewaves transmitted through the pulmonary vascular bed was studied in a cat lung preparation with the right heart bypassed by a pulsatile blood pump. The pump worked at a frequency slightly different from the intrinsic heart rate; transmitted pulse waves were thereby forced to arrive the left atrium at different phases of the left heart cycle. Slow fluctuations of left atrial pressure, left ventricular systolic pressure and left ventricular dP/dt were observed. Left ventricular systolic pressure and left ventricular dP/dt were maximum when the transmitted pulsewaves arrived left atrium just prior to the atrial contraction. The observed variation in left ventricular systolic pressure was found to be directly dependent on the magnitude of pulsatile hydraulic power transmitted to the left atrium.


Degeneration secretion and noradrenaline disappearance in rat salivary glands following proximal or distal axotomy. The noradrenaline (NA) content and the degeneration secretion of saliva were studied in rat salivary glands, following proximal or distal sympathetic denervation. Proximal denervation was obtained by removal of the cervical superior ganglion, which left a long stump of adrenergic axons attached to the gland. Distal denervation was achieved by crushing the perihilar tissue, including the adrenergic axons, close to the gland, leaving only short axon stumps connected with the gland. Onset of both NA decrease and degeneration secretion occurred first in the distally denervated glands and about 2 h later on the proximally denervated sides. Except for the delay of 2 h the pattern of NA decrease and saliva secretion was similar after the two denervation procedures. The length of the attached axon stumps was estimated to be about 15-20 mm longer on the proximally denervated side. Therefore, the delay of 2 h caused by this length of axons corresponds to the proximo-distal intra-axonal transport distal to the "axotomy" of some protecting factors at the rate of 8-10 mm/h. Onset of degeneration secretion was observed between 11 and 12 h after proximal denervation when the NA content was decreased by about 10%. The maximum of saliva secretion occurred about 14 1/2 h after denervation when only 45% of the NA remained in the gland. The correlation between the degeneration secretion of saliva and the decrease in NA probably was due to 1) the amount of NA leaking from degenerating nerve terminals, and 2) the inactivation of this escaped NA by the re-uptake mechanism in the membrane of still intact nerve terminals.


Intracerebroventricular glycerol: a potent inhibitor of ADH-release and thirst. Infusions of isotonic or hypertonic (0.3 or 0.5 M) glycerol into the lateral cerebral ventricle (60 min, 0.02 ml/min) of non-hydrated goats invariably induced a conspicuous and sustained water diuresis. Corresponding infusions of 0.3 M glycerol/0.16 M NaCl were almost equally efficient in this respect. A more short-lasting and less pronounced water diuresis was obtained in response to equivalent infusions of pure d-glucose, and the response to 0.3 M glucose/0.16 M NaCl was variable. Intravenous injections of vasopressin blocked the glucose-induced diuresis, but only postponed the glycerol-induced diuresis. Intracerebroventricular (IVT) infusions of 0.5 M glycerol caused a sustained, complete inhibition of the urge to drink in the 48 h dehydrated goat, whereas IVT glucose only attenuated dehydrative drinking. Twenty min after the infusions of glycerol the CSF [Na+] in the lateral ventricle was about 15% below normal. About 10% reduction of CSF [Na+] was obtained 20 min after the IVT infusion of glycerol/NaCl. The corresponding infusion of pure d-glucose reduced the CSF [Na+] by less than 5%. The glycerol and glycerol/NaCl infusions caused a moderate reduction of renal Na+ + K+ excretion. The possibility is discussed that the observed effects of IVT glycerol is a manifestation of its efficiency to inhibit choroidal and/or juxtaventricular (Na+-K+)-ATPase activity.


On the elicitation of the diving responses in ducks. Peripheral receptors signalling in both the 3 main divisions of the trigeminal nerves and in the glossopharyngeal nerves are most likely involved in the onset of the apnea in diving ducks. Since the response also takes place when ducks are submerged in mercury, these peripheral receptors are hardly specific to water. Neither any of the 3 main groups of trigeminal, nor the glossopharyngeal receptors are alone responsible for the initiation of the apnea. Most likely the apnea takes place when the total impact on the 'respiratory centre' in the brain exceeds a certain treshold value, due to activation of a certain number of both trigeminal and glossopharyngeal peripheral receptors. However, even very local stimulation of the glottal area invariably evoked apnea, indicating a higher density of receptors there than for example on the beak or in the nares. This idea is supported by the fact that not even heavy rain evokes any response at all. It is unlikely that the cardiovascular adjustments displayed by diving ducks are directly coupled to the apnea response (i.e. to stimulation of peripheral receptors). Rather they are supposed to be components in orienting and chemoreceptor reflexes.


Temperature regulation during exercise in water and air. Four healthy subjects were studied during exercise in water, using a swimming flume, and in air, on a stationary bicycle ergometer at mean skin temperatures of 30 and 33 degrees C, respectively. Measurements included rectal (Tre), esophageal (Tes), and mean skin (Ts) temperatures, metabolic energy liberation (M) and total heat production (H),  maximal aerobic power output (Vo2 max), cardiac frequency and calculated peripheral tissue heat conductance (K). The results showed that for a given M and Ts, Tes and Tre were about 0.4 degree C lower and the K values were consistently higher in swimming than in bicycling. The intersubject variability in Tes and Tre was reduced by considering relative (expressed as %VO2max) rather than absolute work load, but the differences in the body temperatures between the two types of exercise remained. It was concluded that during exercise in water where the capacity for heat dissipation is increased, the body core temperature (Tc) is maintained at a lower level due to the higher forced convective and conductive heat transfer from the skin in water. This reduces the heat storage at the beginning of exercise compared with conditions in air. The lower Tc-Ts gradient for a given H in swimming, which results in higher K values implies a greater skin circulation than during cycling in air.


Cardiovascular and metabolic actions of neurotensin and (Gln4)-Neurotensin. The actions of the tridecapeptides neurotensin and (Gln4)-neurotensin have been studied on the heart and on the blood flow in subcutaneous adipose tissue, skin and small intestine of anesthetized dogs. In addition, their possible actions have been investigated on blood glucose concentration and lipolysis in subcutaneous adipose tissue. The two peptides were found to be approximately equipotent. Intravenous infusion of 20-120 ng X kg-1 X min-1 produced slight hypotension, an initial vasodilatation in the small intestine and a delayed vasoconstriction in denervated subcutaneous adipose tissue and to a lesser extent in the skin and small intestine. At this infusion rate, neurotensin and (Gln4)-neurotensin did not elicit vasodilatation in the skin or adipose tissue and had no effect on heart rate. The delayed vasoconstriction in adipose tissue was not inhibited by local alpha-receptor blockade. Both neurotensin and (Gln4)-neurotensin increased glucose concentration in the upper dose range. No effects on lipolysis were observed, either in vivo or in vitro. These experiments show that neurotensin and (Gln4)-neurotensin have both vasodilator and vasoconstrictor actions in the peripheral vasculature but seem to be without cardiac actions. They also increase blood glucose concentration. It remains to be shown whether these actions are direct or whether some are indirectly mediated.


Experienced reality in somatic patients more that 65 years old. A comparative study of disturbed and clear, but demented states of consciousness. Eight experienced qualities of reality were examined in relation to five sorts of experience in 15 demented patients in clear states of consciousness (the CSC group), and in 15 patients in disturbed states of consciousness (the DSC group). Many more abnormal reality qualities appeared in the DSC than in the CSC group. In the DSC patients the tendency to experience non-existent fantasy items as being real was so much greater than in the CSC patients that it will be of value in differential diagnosis if it is confirmed in other patient materials. In DSC patients, furthermore, positive qualities of sensation were found attached to many experiences of items which were not present in the actual stimulus fiels - even in patients who were not clinically hallucinated. The reliability of the results was controlled by having each patient evaluated by two psychiatrists.


Lithium treatment of a patient with periodic catatonia. This case report describes successful lithium treatment in a patient with long-standing periodic catatonia. Various medical treatments had been tried with meager results. Since 1955, a number of phenothiazines had been tried, also with little improvement. The institution of lithium treatment in 1964 caused a dramatic improvement in the patient's condition. For 9 years the patient remained totally asymptomatic. Lithium treatment was terminated in 1975 because of lithium intoxication with a diabetes insipidus-like syndrome. The patient then became psychotic again and has since experienced periodic phases similar to the previous illness. The diagnostic validity of the case is discussed, and some possible explanations of the favourable response to lithium are mentioned briefly.


Depression and daily temperature. A long-term study. In a long-term observation of a manic-depressive female patient, three depressive episodes and two intervals without complaints were studied. During this period, the oral temperature was measured every 3 h. The temperature values were compared with a self-rating scale of the patient. The oral temperature showed a different pattern on the depressive days as compared with the interval days. The average temperature values were higher on depressive days. During the depression, changes were found in the daily temperature rhythm which resulted in a temperature maximum earlier in the day. The changes can be explained as indicating a desynchronization phenomenon of the circadian rhythms.


Season of birth among siblings of schizophrenics. A test of the parental conception habits interpretation. Many studies have shown schizophrenics to be born with unusual frequency in the period January-April, and one interpretation of this seasonality of birth is that the parents of schizophrenics have an unusually strong general tendency to conceive offspring who will be born in January-April. This parental conception habits interpretation may be tested by studying whether the siblings of schizophrenics are also born with increased frequency in January-April. The present study investigated the season of birth of 288 full siblings and 44 half-siblings in 91 families of male schizophrenics. Approximately 5% of the siblings were known to be schizophrenic; with the schizophrenic siblings excluded from the analyses, the full siblings showed a birth pattern much closer (nonsignificant) to that of the schizophrenics than to that of the general population. Half-siblings showed January-April birth rates at or below the population level. Although the mechanisms responsible for the current results still remain unclear, the study suggests that seasonality of births of schizophrenics may be related to the parents' conception habits as well as to an etiological or triggering effect on the development of schizophrenia in the offspring.


Antivitamin B6 induced ultrastructural changes in the hippocampus of the convulsant rabbit and its biochemical correlates. In rabbits epileptiform seizures were induced by systemic application of methoxypyridoxine, an antimetabolite of vitamin B6. The regional distribution of GABA was measured in 11 brain structures, before the onset of the seizure and during the generalized convulsions. In brain regions with a high GABA level the GABA content drops already preictally, in contrast to the GABA poor structures where no preictal decrease takes place. From this it is concluded that there exist two GABA pools, a functional one containing the GABA for chemical transmission, which is exhausted already preictally giving rise to the seizure discharges, and a metabolic one, which is utilized as an additional energy-source during the convulsions. Due to the decrease of the hippocampal GABA the endings of the dentate gyrus granule cells, the giant boutons contacting the apical dendrites of the pyramidal cells of CA3 and CA4, can discharge unrestrained. An ultrastructural correlate of the increased excitation is demonstrated. The dense-core vesicles of the giant boutons fuse in an omega-shaped form with the presynaptic membrane of the spines. This fusion-phenomenon is observed in ultrathin sections as well as in freeze-fractured replicas of this region.


Formation of glutamate and GABA in epileptogenic tissue from human hippocampus in vitro. The levels of some amino acids and the incorporation rates of 14C from glucose and acetate were estimated in control human brain tissue and epileptogenic foci from human hippocampus incubated in glucose-saline medium. In the epileptogenic tissue the level of glutamine and the incorporation of radioactivity from both substrates into glutamine were lowered, mainly from acetate. These results suggest damaged glial metabolism. The relative increase of glutamate and decrease of glutamate formation in epileptogenic tissue were similar to the changes caused in rat brain slices by increased concentration of potassium in the incubation medium.


Contribution to surgical terminology in epilepsy. The classifications of the World Health Organization used in epileptology do not contain any aspects of surgical treatment. The introduction of stereotactic techniques make it necessary to include in the classification such terms as multifocal epilepsy, modified epilepsy and iatrogenic epilepsy. Epilepsy classification will most likely be affected also by the neuro-histological changes found from epileptogenic zones with bio-chemical analysis of brain structures as well as from the zone of epileptic focus.


The value of electrostimulation in epileptic focus localization. The ES is a non-physiological stimulus of the brain. However it represents an important and indispensable part of stero-EEG investigation since it is an easily adjustable method, capable of inducing typical electro-clinical seizures. From the clinical and electrical responses elicited by ES and from the data of the stimulation tresh-old, we are in agreement with other authors, we feel we can also distinguish several different reacting zones in the epileptic brain: 1. The epileptogenic zone from which the complete or almost complete electro-clinical seizure is reproducible immediately by ES or with short latency. These pathological responses show the severe dysfunction of the given structures. 2. The irritative zones from which seizure elements can be evoked, but the complete electro-clinical seizure does not. "Physiological" clinical responses can also be elicited, but by a very low threshold stimulus pointing to the pathological excitability of this zone. 3. The area reacting to "normal" stimulus threshold with a physiological response. 4. The silent area without any electro-clinical response in the functional state of the nervous system. One of the practical values of ES is that makes possible to separate these zones from each other in a given patient within certain limits, and it may help to reveal the localization, the multiplicity and the degree of the "seizure disposition" in epilepsy.


Graphic representation of the epileptic focus. On the basis of systematic examinations of electrical activity of brain deep structures in 87 epileptic patients, an experiment was carried out to replace the concept of the epileptic focus by the graph of functional grouping of structures with epileptic activity. In order to make the graph as realistic as possible, the multi-lead electrodes have to be introduced into the brain systematically and under standard conditions. In this case, the results obtained are comparable. At the same time, the graph proves to be the basis of indications for stereotactic treatment.


Centrencephalic epilepsy and suboccipital derivations. 1. The application of suboccipital electrodes provides earlier and safer detection of pathological activities within deep infratentorial structures than the standard recording techniques. 2. Spike and wave complexes are better differentiated with regard to frequency, duration and possible primary focus, which is of basic importance in determining the optimal therapy; 3. The combinations with chemical activation methods increases the number of positive findings and thus contributes to a better diagnosis. 4. The technical procedure is not complicated or dangerous for the patient. It causes less pain and inconvenience than the application of the needle in sphenoidal electrodes; 5. Suboccipital electrodes applied alone or in combination with the scalp and sometimes with sphenoidal electrodes represent the simplest technique of recording and detecting deeply located focal centres as well as electrographic changes originating in deep infratentorial structures, without damaging the meninges.


Clinical and electrophysiological effects of chronic epileptic lesion in split-brain cats. The development of the clinical and EEG manifestations of intracortical alumina cream epileptogenic lesion is described in 14 split-brain cats. In 4 animals contralateral and/or ipsilateral, cortical and subcortical secondary epileptic foci were present. The results indicate that integrity of interhemispheric transfer through the corpus callosum and anterior and posterior commissures is not necessary for the transmission of epileptic activity to contralateral hemisphere. Partial epileptic seizures of Jacksonian type were observed in 6 cats. In 1 cat grand mal epileptic seizure developed. The possible mechanisms of secondary epileptic foci and generalized type of seizure are discussed.


Determination of the functional hierarchy in multifocal epilepsy. An averaging technique of epileptic spikes, carried out on human stereoelectroencephalographic explorations, allowed the detection of morphological alterations of spikes peculiar to a given structure, associated with variations of temporal relations among spikes simultaneously recorded in different structures. On the basis of experimental data it can be supposed that these variations reflect the alternance of the functional prevalence among the different structures involved in the epileptic process.


Investigation of epileptic structure properties by transfer function. The paper deals with the possibility of applying linear control theory and the theory of statistical dynamics to the complex and quantitative analysis of electroencephalographic records. The aim is to specify signals in the brain environment, in particular sources, speed and direction of signals, and the determination from results gained of the model of signal transfer, The possibilities of applying Fourier analysis and correlation analysis are examined. The methodical approach of the transient analysis is suggested. Conditions are discussed for approximate application of linear theory. Experimental results, as well as the calculation of transfer parameters of signals are evaluated. The method of magnetic EEG records, the scanning and processing of data on analogue and digital computers are introduced. The method described of correlation and transient analysis arises from the necessity to detect epileptic structures from an evaluation of SEEG records of the deep brain structure.


The role of focal and extrafocal structures in the triggering of epileptic spikes: an experimental study. Experiments carried out in cats with a neocortical cobalt induced epileptic focus demonstrated that focal averaged spikes, obtained by a personal computer technique, can alternatively lead the caudate ones or be led by them. Defined morphological alterations of the spikes characterize the two situations.


Catecholamine levels in penicillin-induced epileptic focus of the cat cerebral cortex. In 25 cats an unilateral epileptic focus was produced by intracortical injection of potassium benzyl penicillin and on the other hemisphere, sham-operation was done by injection of the same volume of saline solution without penicillin. Catecholamine analysis was performed for each hemisphere separately. In a second series of 15 cats, the effect of catecholamines and of 1-DOPA on penicillin-induced spike activity was examined. In the first and second stage of propagation of penicillin-induced spikes, dopamine and norepinephrine significantly decreased in the focus. In the third stage no differences existed. The penicillin-induced spike activity was reduced as well by the topical application of dopamine as of 1-DOPA, whilst no inhibitory effect was observed in the topical application of norepinephrine.


Lateral-trigonal intraventricular tumors. A new operative approach. With the introduction of additional diagnostic methods, computerized axial tomography, interventricular tumors are discovered at a time when these lesions are still small and may have presented very insignificant or no clinical symptoms. If the lesion is a benign tumor as a meningioma and within the lateral ventricle of the dominant hemisphere a very difficult problem persents itself to the patient and surgeon. Shall they wait until the tumor reaches such a size to make more permanent symptoms to justify entering the ventricle by the conventional approach through the middle temporal gyrus and leaving the patient at least with a visual field defect? Or should surgery be postponed until the ventricle especially the temporal horne is enlarged due to blockage by the tumor, making the operative procedure technically easier? The authors present a method used in three atrial trigonal meningiomas of the dominant hemisphere which did not result in any neurological deficit which was not present before surgery and which abolished paroxysmal attacks of hemianopsia and severe headaches in one patient. The latter patient was believed to have suffered from migraine for 2 1/2 years.


Sterilization of the operating microscope. Sterilization of the operating microscope and its equipment with formaldehyde (10 g for 10 hours) in a specially developed container provides sterility and ideal storage, and secures immediate availability in daily operating theatre practice.


Extracranial metastases of anaplastic cerebral gliomas. Seven cases are reported of anaplastic cerebral gliomas with metastases outside the neuraxis, seen among about 1500 gliomas. There were two children with anaplastic ependymomas, one adult with oligodendroglioma, and four young to middle-aged adults with astrocytomas grade III and IV. All patients had one or more craniotomies, and four had radiotherapy prior to the appearance of distant tumour deposits. The survival times ranged from 7 to 31 months in cases with gliomas grade II, and from 8 to 18 months with high grade astrocytomas. All seven tumours showed invasion of the meninges, ventricular walls, or both, and in four cases they transgressed the dura and surrounding bone or soft tissues. In six autopsy cases there was widespread dissemination of gliomas through the CSF pathways. Distant metastases involved regional or distant lymph nodes in six patients, the lungs in two, and the vertebrae, pleura, liver, or mediastinum in one patient each. The possible pathways for distant spread or intracranial gliomas and the factors which are considered responsible are briefly discussed.


[Intramedullary oligodendroglioma with meningocerebral dissemination (author's transl)]. A 28 year old woman suffered from lumbar radicular signs and sensory deficit for three years before death. A progressive illness with increased intracranial pressure, cerebellar signs, and multiple cranial nerve palsies appeared one year after the onset of symptoms, but craniotomy of the posterior fossa was negative. After development of spastic paraparesis, an intramedullary oligodendroglioma of the lower thoracic cord was partly removed. Death occurred two months later from raised intracranial pressure. At autopsy a diffuse oligodendroglioma was found involving the periventricular regions of the brain, the entire subarachnoid space, the cerebral parenchyma, and the whole length of the thoracic cord. There was a small lumbar syrinx. It is suggested in this case that the dorsal intramedullary oligodendroglioma was the source from which tumour spread diffusely through the cerebrospinal fluid pathways and secondarily invaded the cerebrum. The diagnostic difficulties of diffuse meningeal gliomatosis are discussed.


[Unusual recurrence of an IC--PC aneurysm after neck clipping--any structural weakness of the clip? (author's transl)]. Recurrence of an IC--PC aneurysm after a successful neck clipping (Heifetz' clip) is reported. This was caused by breaking of a clip blade at its proximal end. It is suggested that some structural weakness was present in the clip metal.


Educating the future mental health executive: a public health approach. The mental health program we are developing at the Yale School of Public Health has as its basic element a broad introduction to the concepts and principles of public health and mental health administration and is rooted in conern for community well-being. It is our belief that this combination of public health - mental health training will produce administrators for mental health, psychiatric and human resource agencies who will be able to design, implement, manage, and evaluate programs that improve mental health and help communities evaluate and structure the human services they need.


Teaching mental health administration to psychiatric residents. Methods for teaching mental health administration within the framework of the regular psychiatric residency are described. The basic principles of social systems analysis and social systems management are the framework for both the field experience and the didactic curriculum. Emphasis is placed on student participation in the teaching process. The student engages in multiple exercises within the actual working processes of mental health administration. In essence, we attempt to teach mental health administration by providing learning experiences where the student performs the tasks and engages in the conceptual work that form the basis for social systems management.


Physical attractiveness, physical effectiveness, and self-concept in late adolescents. The differential role of various body attitudes in predicting the self-concepts of late adolescents (124 males and 218 females), enrolled in introductory psychology courses, was assessed. Subjects rated 24 body characteristics in terms of 1) how physically attractive they assumed these parts of their bodies were, and 2) how physically effective they assumed them to be; subjects also responded to a short self-concept scale. In accordance with the theory of Erikson (1968) and of McCandless (1970), it was expected that attractiveness attitudes should contribute more to the self-concepts of females than should effectiveness attitudes, while a reverse pattern of interrelatedness was expected for males. Results indicated a higher correspondence between what are seen as attractive body parts and what are viewed as effective body components for males than for females. Moreover, findings from step-wise multiple regression analyses of each sex group's ratings of the body parts for attractiveness and effectiveness, respectively, each with the criterion variable constituting mean self-concept score, were consistent with expectations. For females, the multiple correlation between attractiveness ratings and self-concept was greater than the multiple correlation between effectiveness ratings and self-concept, and more attractiveness variables than effectiveness variables were significant predictors of self-concept. The converse of these findings were obtained with the males' data. The relevance of these results for theories of personality development were discussed.


RES blockade: effects on immunity and tolerance. Reticuloendothelial cell blockade has been studied for decades in regards to physiological and immunological effects. "Overloading" of RE cells with inert colloidal particles, such as carbon or other particulate substances, has often been used to analyze the role of phagocytic activities in antibody formation, often with contrasting results. In the present studies the effects of colloidal carbon treatment of mice on immunologic responsiveness to sheep erythrocytes was investigated. Pre-treatment of mice with carbon shortly before either primary or secondary immunization with SRBCs markedly suppressed the expected antibody response, as shown by depressed numbers of hemolytic antibody plaque forming cells. Carbon treatment did not affect antibody forming cells per se as shown by lack of an effect on plaque forming cells when carbon was given after SRBCs, either in vivo or in vitro. Carbon injection before primary immunization prevented development of "immunologic memory," as shown by an altered secondary immune response. Mice given carbon and SRBC several weeks before secondary immunization with RBCs developed a primary type antibody response characterized by appearance of 19S antibody with little or no 7S hemolysins, characteristic of a secondary response. Furthermore, by appropriate treatment of mice with carbon and SRBC, immunologic unresponsiveness to SRBCs could also be induced, as evident by absence of both 19S and 7S antibody formation after subsequent challenge immunization with sheep erythrocytes. The mechanisms involved in RE "blockade" induced aberrations of normal immune responses may be related to effects on macrophages or soluble humoral factors, or both. It is unlikely that carbon treatment affects immunocytes directly. Further studies concerning the nature and mechanism of RE blockade on cellular and humoral components of the immune response mechanisms seem warranted and should provide more insight concerning the role of macrophages in antibody formation.


Trauma induced histamine synthesis and RES activity. The histidine decarboxylase activity of the lung and spleen was determined in animals made resistant to tumbling trauma, either by prior sublethal exposure or by injection of extracts prepared from the spleens and plasma of trauma resistant rats. The data describe the post-traumatic period in the normal animal as being associated with an increased histidine decarboxylase activity. In addition, the increased histidine decarboxylase activity was paralleled by an increased phagocytic activity of the reticuloendothelial elements of the spleen. In trauma resistant animals, changes in the enzyme activity and phagocytic capability were prevented or curtailed. The administration of spleen and plasma protective extracts were similarly effective in impeding these changes following trauma. It is suggested that the active humoral factor elaborated during conditioning and associated with the RES may act by inhibiting the activation of histidine decarboxylase.


The role of transport processes in the distribution and disposition of prostaglandins. Currently available evidence shows that some cell membranes represent a barrier to passive diffusion of PGs. In contrast, an active transport of PGs was demonstrated across the wall of the rabbit vagina in vitro. Evidence has been obtained indicating that similar carrier-mediated PG transport processes in vivo mediate the uptake of PGs from the circulation into the lung and the removal of these autocoids from the brain and the eye, across the blood--brain and blood--aqueous barriers. It was shown that probenecid, a known inhibitor of PG transport, enhances the effect of PGE1 on the brain, and in general, it appears to alter the distribution and rate of excretion of PGs. The existence of such barriers to the free diffusion of PGs and the saturable, and possibly rate-limiting, transport of these autocoids across some other membranes must be taken into consideration in the design of experiments and in the interpretation of results. Furthermore, the importance of this consideration is emphasized by the observation that many nonsteroidal antiinflammatory agents and PG antagonists are effective inhibitors of PG transport (17,18); hence, they can be expected to affect the distribution and disposition of PGs.


Biosynthesis and catabolism of prostaglandins during animal development. Catabolism of [9beta-3H1]prostaglandin F2alpha (PGF2alpha) was investigated in several organs (lung, kidney, brain, and liver) of the rat and lamb with respect to the product-type formed as well as the capacity of the observed enzymes. Biosynthesis of PGE2alpha and PGF2alpha in the same tissues was measured by dual ion mass fragmentography after incubation of the tissue homogenate with excess exogenous arachidonic acid (100 mug/g tissue). Further confirmation of the products was obtained through computer-operated multiple ion mass plots for each compound investigated. The results demonstrate that 1. Total PG-catabolizing activity in most organs is not constant but varies with animal age; highest activity (10-60-fold greater than the adult) being observed at certain stages of organ development. 2. The diverse catabolizing enzymes are dissociated in their activity, some enzymes being most active in immature animals (15-PGDH, 13PGR) and others being most active in the adult (9 PGDH, beta-oxide). 3. The activity profile for PG catabolism is both organ and species-specific. 4. PB biosynthesis in developing animals does not change significantly. The observed higher activity of PG catabolism with little change in PG biosynthesis strongly suggests an important need for the rapid inactivation of prostaglandins at certain critical stages of development serving as a protective mechanism likely in the control of cell differentiation and against the potentially harmful vasocative properties of prostaglandins during organogenesis.


Prostaglandin action on transmitter release of adrenergic neuroeffector junctions. The results presented here indicate that 1. The inhibitory action of the endoperoxides on NE release can be at least partly explained in terms of formation of degradation products, presumably mainly PGE2. 2. PGA2 is less active and the PG analogue 16,16-dimethyl-PGE2 more active than PGEs on transmitter release from adrenergic nerves. 3. PGF2alpha seems to enhance vascular responses to renal nerve activity solely by a postjunctional action. 4. PG synthesis inhibition augments NE turnover in a number of rat organs, thereby increasing the probability of PGs being involved in the control of adrenergic neurotransmission in vivo. 5. Prolongation of the duration of the impulse and action potential counteracts the effect of PGE on NE release, thereby strengthening the view that PGs operate on NE release from adrenergic nerve terminals by interfering with Ca2+ influx.


Effect ofprostaglandins E1 and E2 on hypothalamoneurohypophyseal--Neurosecretory systems of rats: a histochemical study. PGE2 increases NSM in the neurosecretory neurons and posterior pituitary store of HNNS. It stimulates acid phosphatase and TPPase activities in HT, indicating increased synthesis of NSM. PGE2 also increases AChE and BuChE activities. PGE1 shows very little effect on NSM distribution and enzyme activities. It is concluded that PGE2 causes increased HNNS activity by stimulating AChE-mediated and Ca2+-dependent "stimulation secretion coupling mechanism".


Comparison of the effects of prostaglandins A, E, F, and B on the canine pulmonary vascular bed. The present data show that prostaglandins of the A, E, F, and B series have a wide spectrum of effects on the canine pulmonary vascular bed. PGF2alpha and PGB2 were very potent pulmonary pressor substances. Both of these agents increased pressure in the lobar artery and small vein. Since blood flow was constant and left atrial pressure did not rise, the increase in lobar arterial pressure reflects an increase in resistance to flow in the lung. The rise in venous pressure and the increase in pressure gradient between lobar artery and vein indicate that these substances increase pulmonary vascular resistance by constricting lobar veins and upstream vessels presumed to be small arteries. PGE1 and PGA1 both dilated the pulmonary vascular bed and the decrease in resistance was due to dilation of veins and upstream vessels. In the dog, both PGE2 and PGA2 were found to be modest pulmonary pressor substances. The increase in resistance with both agents was similar in blood and dextran-perfused lung lobes, hence interaction with formed elements contribute little, if anything, to these responses.


Prostaglandins: a possible regulator of muscle tone in the ductus arteriosus. We have shown that E-type prostaglandins are potent relaxant of the lamb ductus arteriosus at low, but not high, oxygen tensions, and that their effect is possibly controlled by the rate of endogenous PG synthesis. These findings, together with the demonstration of the contractile effect of PG synthesis blockers on the hypoxic ductus in vitro and in vivo and of the relaxant effect of GSH in vitro, strongly suggest that E-type prostaglandins are responsible for maintaining ductus patency during fetal life. The endoperoxide intermediates may act in concert with PGEs. While our findings argue against the idea that PGF2alpha mediates the oxygen-induced constriction, they suggest that suppression of PGE activity in a high oxygen environment might be important to the initiation of ductus closure at birth. An extension of this concept is that continued patency of the ductus after birth results from either the excessive formation of PGEs or from the persistence of a "fetal-like" response of ductal muscle to endogenous or bloodborne PGEs, or both. The present scheme of PGE action is amenable to practical applications. Our work and that of Elliott et al. (15) prove that PGEs can be used to reopen a constricted ductus in children with cyanotic congenital heart disease, thus improving their change of survival during subsequent corrective surgery. Conversely, treatment with blockers of PG synthesis is envisaged as an alternative to surgery for closing a persistent ductus.


Antiarrhythmic effects of arachidonic, linoleic, linolenic, and oleic acid, and the influence of indomethacin and polyphloretinephosphate. Intravenous application of arachidonic and linoleic acid induced strong antiarrhythmic effects demonstrated on three models of experimental arrhythmias. In contrast, linolenic and oleic acid were poorly effective. The antiarrhythmic action of the unsaturated fatty acids required 10- to 1000-fold higher doses in comparison with the most effective prostaglandins. Indomethacin decreased the antidysrhythmic action of arachidonic and linoleic acid; PG efficiency remained unaffected. Polyphloretinphosphate markedly reduced the improvement of aconitine arrhythmia by PGs, the decrease of the antidysrhythmic effects of arachidonic and linoleic acid was without statistical significance. The results suggest an important role of PG synthesis for the antiarrhythmic effect of polyunsaturated fatty acids.


Aspects of prostaglandin action in asthma. Eight patients with type I allergic bronchial asthma were given specific allergens by inhalation until symptoms and signs of asthma attacks were provoked. In some of these patients the provocation was repeated with premediciation of heparin, theofyllamin, small doses of cortisone (beclomethasone inhalations) or pretreatment within indomethacin. Before and after the provocation as in the three patients with exercise-induced asthma, peripheral venous blood sampled and analyzed for 15-keto-13,14-dihydro-PGF2alpha using combined gas--liquid chromatography-mass spectrometry. The allergen or exercise-provoked asthmatic attacks were associated with an up to eightfold increase in 15-keto-13,14-dihydro-PGF2alpha, the main metabolite of PGF2alpha in plasma. The increase in PGF2alpha metabolite which could be demonstrated within a few minutes after starting the provocation or finishing the exercise test seemed to be correlated to the severity of the attack in the allergic asthma but not clearly in exercise asthma. Pretreatment with different drugs did not give significant change in allergen sensitivity or plasma metabolite of PGF2alpha, except after pretreatment with indomethacin where one patient showed a fairly unchanged allergen sensitivity but a marked decrease in the plasma level of the PGF2alpha metabolite. The role of prostaglandins, their precursers and intermediates in prostaglandin synthesis, in the pathogenesis of asthma is indeed complex.


Involvement of endoperoxides and thromboxanes in anaphylactic reactions. Our recent work on prostaglandin endoperoxides in the lung has shown that: 1. The endoperoxides were 5 to 10 times more potent than PGF2alpha in an in vitro preparation of respiratory smooth muscle, i.e., the guinea pig trachea. 2. The endoperoxides were 5 to 10 times more potent than PGF2alpha in causing an increase in tracheal insufflation pressure in the anaesthetized, artificially ventilated guinea pig. 3. Endoperoxides formed from exogenous arachidonic acid in homogenates of guinea pig lung and in intact guinea pig lung were converted to a large extent into metabolites different from the classical prostaglandins, i.e., thromboxane B2 (8-(1-hydroxy-3-oxopropyl)-9-12L-dihydroxy-5,10-heptadecadienoic acid) and HHT (12L-hydroxy-5,8,10-heptadecatrienoic acid). 4. Injection of antigen into sensitized guinea pig lungs caused a significant release of the endoperoxide metabolite, thromboxane B2. PGF2alpha has previously been implicated to be involved in anaphylaxis (14). The findings described above show that the prostaglandin endoperoxides are important not only as precursors of PGF2alpha but also through their own effects on airway smooth muscle. Furthermore, the release of thromboxane B2 indicates that its immediate precursor, the biologically active thromboxane A2 is also formed in this system (15). This compound, which has a half-life of 30 to 40 sec causes platelet aggregation and contraction of the isolated rabbit aorta (15). Work is in progress to study the respiratory effects of thromboxane A2 and its possible role in anaphylactic reactions.


Nocturnal asthma and sudden death.

Nocturnal asthma and sudden death. Asthmatics may develop a considerable increase in airways obstruction during the night or early hours of the morning. In most patients, this causes only mild symptoms. In others, the effects may be severe, resulting in sudden death. Greater awareness of the potential severity of nocturnal asthma, together with actual measurement of airways obstruction at the time of symptoms, might prevent some of these catastrophes. If patients are not getting relief with their regular therapy, they should be admitted to the hospital for organized management.


Flutter of left ventricular structures in patients with aortic regurgitation, with special reference to patients with associated mitral stenosis. Echocardiography was performed in 45 patients with aortic regurgitation. Forty showed a high frequency diastolic flutter of the mitral valve, which was holodiastolic in all but the patients with associated mitral stenosis. Of four patients with coexisting mitral stenosis, mitral flutter was absent in two; in the other two, in atrial fibrillation, mitral flutter occurred, but only during a fixed interval after mitral valve opening, irrespective of cycle length. A fine flutter of similar frequency was observed on the left ventricular aspect of the ventricular septum in 12 patients. In six of these it was of slight degree and restricted to early diastole and the high septum; in four others (three of whom had associated mitral stenosis), the septal flutter was more marked, holodiastolic, and present over all parts of the septum scanned; in two, it was holodiastolic over the high septum but early diastolic at lower septal levels. Aortography performed in 19 patients showed that septal flutter was present in seven of 12 patients in whom the regurgitant aortic jet was directed forward to the ventricular septum, whereas in the other seven patients with no septal flutter, the jet was directed away from the septum. Septal flutter is useful as an echocardiographic sign of aortic regurgitation, especially in the presence of mitral stenosis when mitral flutter may be absent or exceeded by septal flutter in both amplitude and duration, and when the mitral valve has been replaced by a prosthetic valve. Vibration of the septum appears to be attributable to the regurgitant aortic jet impinging on it and may contribute to the production and radiation of the characteristic diastolic murmur of aortic regurgitation.


Hypoxemia and lung water in acute myocardial infarction. Pulmonary extravascular volume or lung water (PEV), arterial blood gases, and cardiac hemodynamics were measured in 88 patients with acute myocardial infarction. A progressive increase in PEV and a decrease in arterial oxygen tension (PaO2) were observed from Class I (uncomplicated) patients to Class III (frank pulmonary edema) patients. Heart rate and pulmonary wedge pressure (Pw) rose and cardiac index declined with increasing severity of heart failure by clinical classification. There was a significant correlation between PEV and Pw independent of clinical class (r = 0.47, p less than 0.01). PaO2 had a negative correlation with Pw (r = -0.28, p less than 0.01) as well as PEV (r = -0.26, p less than 0.02). We conclude therefore that increased pulmonary hydrostatic pressure secondary to pulmonary venous hypertension in patients with acute myocardial infarction is a major determinant of interstitial edema. At higher values of PEV, PaO2 was lower. The mechanism of hypoxemia in the presence of excessive lung water may be due to multiple factors, including small airway dysfunction and intrapulmonary shunting.


A comparative analysis of pulmonary perfusion scans with pulmonary angiograms. Pulmonary angiograms and pulmonary lung perfusion scans on 162 patients with pulmonary embolism were comparatively analyzed. Among the expert angiographic panel members who independently evaluated the studies there was consistent agreement on the diagnosis, size of the emboli, and severity. Consistency of agreement among the expert pulmonary lung perfusion scan panelists was considerably less. These data demonstrate that, in addition to the lack of specificity of the lung perfusion scan for the diagnosis of pulmonary thromboemboli, there is a considerable problem of interpretation in this patient population.


Lupus cardiomyopathy: cardiac mechanics, hemodynamics, and coronary blood flow in uncomplicated systemic lupus erythematosus. Right and left heart pressures, left ventricular volumes, indices of contractility, myocardial wall stiffness, and coronary blood flow were determined in five young women with systemic lupus erythematosus (SLE) during diagnostic right and left heart catheterization. Examinations revealed (1) increases of right and left ventricular enddiastolic pressures; (2) decreases of cardiac output, stroke volume, ejection fraction, contractility indices, diastolic left ventricular volume inflow; (3) decreases of pharmacologically induced coronary vasodilation in SLE. The results demonstrate impaired pump function, reduced contractility, increased myocardial wall stiffness, and decreased coronary vascular reserve in SLE. It is concluded that lupus cardiomyopathy associated with an impairment of left ventricular function may be apparent in young women with SLE who have no clinical signs of cardiac dysfunction.


Non-bacterial thrombotic endocarditis: clinicopathologic correlations. Sixty-five cases of nonbacterial thrombotic endocarditis (NBTE) were discovered at autopsy during a 10 year period--an incidence of 1.6 per cent in the adult autopsy population. In 51 cases, one or more malignant neoplasms were associated; adenocarcinoma represented the most frequent histologic type of related neoplasm. Coagulation abnormalities suggestive of disseminated intravascular coagulation (DIC) were present in 18.5 per cent of the cases. It is possible that both the valvular and peripheral intravascular thromboses in at least some cases of NBTE represent the abnormal coagulation of DIC. Arterial thrombosis with infarction occurred in many peripheral organs. Splenic and renal were most frequent, but cerebral and cardiac consequences were the most significant.


Effect of dextran loading on left ventricular performance in chronic obstructive pulmonary disease. The status of left ventricular function in patients with chronic obstructive pulmonary disease remains controversial. With a radionuclide technique left ventricular ejection fraction, left ventricular end-diastolic volume, cardiac output, and stroke volume were measured at rest and following infusion of dextran in 23 men with severe COPD. Resting, mean LVEF was normal in 19 subjects with COPD alone; four with COPD and coronary artery disease had a depressed mean LVEF. Left ventricular end-diastolic volume index and pulmonary capillary wedge pressure were both normal at rest indicating that the left ventricle was not volume underloaded. There was a normal response to dextran infusion (750 ml.) with no deterioration in LVEF and a significant increase in cardiac index, stroke volume index, LVEDVI, and PCW. These data suggest that at rest and following volume loading with dextran left ventricular function is normal in patients with COPD.


Reactive hyperemia: an index of the significance of coronary stenoses. Coronary arterial stenosis of varying severity and length were created in open-chest dogs. The reactive hyperemic responses (RHR) to 15 second occlusions were used to produce flow increases and judge the physiological significance of the narrowings. RHR are sensitive indices of functional impairment when resting flow is unchanged. It was demonstrated that the length as well as the severity is important in assessing physiological significance by evaluation of narrowings 3 to 9 mm. long.


Coronary occlusion site as a determinant of the cardiac rhythm effects of atropine and vagotomy. We have previously demonstrated that atropine pretreatment increases the incidence of fatal ventricular arrhythmias induced by left anterior descending coronary artery (LAD) occlusion. The purpose of the present study was to determine whether the deleterious effect of atropine also applies to arrhythmias induced by right coronary artery (RCA) occlsusion. Occlusion of the RCA resulted in ventricular arrhythmias in all 20 animals studied, followed by ventricular fibrillation in three animals (15 per cent). Right coronary occlusion also resulted in bradycardia (-30.3 +/- 5.1 beats per minute) and hypotension (-23.1 +/- 4.9 mm. Hg). Pretreatment of 15 animals with atropine caused no significant increase in the incidence of ventricular fibrillation (i.e., 20 per cent). In addition, atropine pretreatment had no effect on the fall in heart rate and hypotension associated with RCA ligation. Sectioning the vagus nerves produced results similar to atropine pretreatment with the exception that a significant portion of the bradycardia was prevented. These results indicate that the increase in deaths after atropine observed in animals undergoing experimental LAD occlusion in not demonstrated with RCA occlusion. The results also indicate that the potential for deleterious effects of atropine in acute infarction might depend on the anatomic location of the involved myocardium.


An approach to the treatment of essential hypertension. The efficacy and side effects of the combined administration of propranolol and phenoxybenzamine were examined in 19 patients with moderate and moderately severe essential hypertension. By titrating the dosage of both drugs against pulse rate and blood pressure response, propranolol was given between 80 and 160 mg. and phenoxybenzamine between 20 and 50 mg. per day in divided doses. There was a substantial reduction in both systolic and diastolic blood pressure in both recumbent and upright positions without orthostatic hypotension. Normal blood pressure (140/90 mm. Hg or less) or near normal (150/100 mm. Hg or less) was attained in 14 of the patients in the recumbent and 17 in the upright position. Pulse rate also decreased significantly, whereas body weight increased but not significantly so. Except for a reduction of ejaculation in three out of six male subjects, no symptomatic side effects were detected, and no changes in the liver or renal function or in blood count were observed. Despite the short duration of therapy, 3 to 10 weeks, this study clearly demonstrates that propranolol and phenoxybenzamine given together in individualized doses are very effective in lowering arterial blood pressure with minimal side effects.


Computer simulation of the precordial QRS complex: effects of simulated changes in ventricular wall thickness and volume. The cardiac electric field generated by depolarization of the human ventricle is simulated with a computer model which utilizes 1,500 dipoles. The configuration of the ventricles utilized in the model assumed that the cross-sectional shape of the left ventricle was circular and the right ventricular free wall was a portion of an ellipse. The torso was assumed to be homogeneous and infinite. The activation sequence was based on the measurements of Durrer. The depolarizational wave was simulated by dipole layers. The output of the model is presented as a standard multilead precordial ECG. The ECG complexes generated by the model closely resemble the precordial QRS complexes of normal man. Simulated increases in wall thickness (1 to 2.2 X control) were associated with changes in the calculated precordial QRS complexes which were characteristic of left ventricular hypertrophy. Voltage (R in V5 or V6 and S in V1) and QRS duration increased linearly as a function of calculated left ventricular mass. Increases in ventricular activation time were related nonlinearly to changes in left ventricular mass and did not occur in the absence of a simulated increase in wall thickness. The effects of simulated changes in left ventricular volume (0.6 to 3.0 X control) on the QRS complex were mainly dependent on the resultant increase in left ventricular mass. This model may be useful in simulating the precordial QRS complexes that result from isolated or combined changes in ventricular volume or wall thickness or other disorders of the heart. Furthermore, it may be useful whenever a simulation of a QRS generator is needed.


Effectiveness and hazard of endomyocardial biopsy in dogs: comparison of two methods. Two different methods of endomyocardial biopsy were evaluated. Compared to the Konno bioptome, a technique using a biopsy forceps originally designed for fiberoptic bronchoscopy and bronchial biopsy, passed through a No. 9 Fr. end-hole catheter, was easier to perform. The biopsy device is smaller than the Konno bioptome, has sharper teeth, and is easier to clean. The two techniques did not differ in arrhythmogenicity, hemorrhagic changes in the myocardium, or distortion of the specimens. Ventricular tachycardia as defined by three beats in a row was observed in 34 per cent. Epicardial hemorrhage was seen in nine of 14 animals, and the specimen distortion rate was 43 per cent. In one animal, perforation of the right ventricle and hemopericardium occurred.


Dissection of the aorta complicating intra-aortic balloon counterpulsation. A 61-year-old man with recent myocardial infarction complicated by a ventricular aneurysm and recurrent ventricular tachycardia underwent intra-aortic balloon counterpulsation prior to angiography and left ventricular aneurysmectomy. A dissecting aneurysm of the descending aorta adjacent to the position of the balloon catheter was found at autopsy. No intimal tear or cystic medial degeneration of the aorta was present to account for the dissection. The authors suggest that lateral and shearing forces generated by inflation of the balloon could result in dissection of the aorta.


The pathogenesis of the two forms of hypertensive pulmonary vascular disease. Autopsy observations suggested that lesions of hypertensive pulmonary vascular disease (HPVD) due to elevated venous pressure differ from those with arterial hypertension only. Clinical and pathologic features were reviewed in patients from the Hopkins autopsy files with proved pulmonary hypertension; 50 had venous HPVD due to left-sided congestive heart failure, 50 had arterial HPVD due to congenital malformations, and 15 had idiopathic pulmonary hypertension (IPH). The two forms of HPVD have consistent distinctive histologic changes. In venous HPVD intimal fibroelastosis (IFE) develops in veins and arteries with retention of normal lumen diameters. Intensity of IFE correlates with severity and duration of venous hypertension. Arterial HPVD has IFE in conducting arteries, but the characteristic lesion is cellular intimal proliferation in regulatory arterioles, producing progresssive irreversible lumenal narrowing. Glomoid and angiomatoid lesions appear with prolonged severe arterial hypertension. They do not occur in venous HPVD. Hypertensive arteritis may develop with either form of HPVD. IPH has arterial-type HPVD. IFE of venous HPVD appears to be a response to increased mural tension. Arteriolar intimal cellular proliferations seen in arterial HPVD may be produced by blood flow boundary layer separations. IPH may be explainable as protracted inappropriate pulmonary arteriolar constriction.


Assessment of airborne hazards in the thorium processing industry. Airborne thorium thoron and its decay products contribute significantly to the hazards in the thorium industry. These have been assessed and compared with the standards. Assessment also included the unattached fractions of the decay products, the thoron working levels and the aerodynamic particle size distribution of airborne thorium.


Kidney, liver, hair and lungs as indicators of cadmium absorption. Cadmium absorption in four human tissues, kidney, liver, hair and lungs was assayed and the intertissue correlations were determined. All the correlations were positive. The correlations of the kidney cadmium level and the levels in the other tissues were the weakest. The intertissue correlations besides being indicative of the physiological similarities between the tissues also suggest the existence of 1) a preferential scheme for the deposition of cadium from the recipient sites and 2) cadmium flow steady state. The kidney-liver and kidney-hair cadmium ratios were found to have exponential age associations.


Data inversion method and error estimate for cascade centripeters. Although centripeters ("virtual impactors") have fewer substrate problems than impactors, their small secondary flows from the impaction regions complicate data analysis. It is shown here how to use data inversion to achieve substantial data improvement. The success of such methods depends upon data error and instrument response. The condition number, which measures error magnification, is defined, discussed, and evaluated for three-stage and five-stage centripeters.


The effect of high level sound exposure on the loudness difference limen. Currently used threshold audiograms fail to detect the early stages of noise-induced hearing impairment. Threshold shifts may reach 10 to 15 dB before the impairment is detected. Loudness difference limen and critical band phenomena may provide an earlier and more sensitive test for such hearing impairment. Data is reported which shows that the difference limen shift (DLS) due to noise persists longer than temporary threshold shift (TTS). These findings suggest that DLS may be a more feasible tool for industrial use than either TTS or monitoring audiometry.


Accreditation of occupational health programs: development and validation of criteria. Defined standards and a mechanism for evaluation of performance can help promote new and improve existing occupational health programs. Criteria must be based on sound principles, be comprehensive, discriminating and attainable. They should apply to small and large establishments with varying hazards. A successful program requires a multi-disciplinary effort involving physicians, nurses, industrial hygienists, health physicists, safety professionals, managers, technicians and labor. Assessment by on-site peer review is necessary. The criteria and process for their use must be accepted by the professions, labor and management. The Occupational Health/Safety Programs Accreditation Commission plans to use the document entitled Standards, Interpretations and Audit Criteria for Performance of Occupational Health Programs in its accreditation activities. The development and validation of this document and its use are described.


Preparation of vinyl chloride standards using a permeation tube. Vinyl chloride permeation tubes have been utilized to provide a convenient and accurate standardization procedure for charcoal tube monitoring of atmospheric vinyl chloride. The procedure circumvents the need of determining charcoal desorption efficiencies and eliminates the handling of free vinyl chloride in the laboratory preparation of vinyl chloride standards.


A comparison of cotton dust sampling techniques. The standard high volume sampler, multistage cascade impactor, and modified vertical elutriators were evaluated for total cotton dust sampling. The effects of changes in performance parameters is reported. Mass median dust diameter found in four textile operations for several cotton grades are reported.


Acute oral testing for determining antiarrhythmic drug efficacy. I. Quinidine. Acute oral drug testing with quinidine was used in 18 patients with high grade ventricular arrhythmia. This method involves administering a single large dose of the antiarrhythmic agent, monitoring heart rhythm by means of programmed trendscription and determining blood drug levels at selected intervals. After quinidine was given in a dose of 0.6 g, 10 patients had a positive response, defined as a 50% or greater reduction in ventricular premature beats and abolition of repetitive ectopic beats. Drug action began a mean of 88 minutes after administration, and the mean peak blood quinidine level was 3.2+/-0.5 (standard error) mug/ml. Four patients had a paradoxic increase in arrhythmia. In nine patients the response to acute drug testing was compared with the response to maintenance quinidine therapy with doses of 1.2 and 1.8 g/day. The presence of arrhythmia was assessed with 24 hour ambulatory monitoring and exercise stress testing. With both techniques, seven of nine patients showed results concordant with those of acute testing. Disparity in results of the two methods of drug administration was explained by the serum concentration of quinidine. Acute oral drug testing provides a new approach for determining expeditiously whether quinidine is effective or hazardous in an individual patient.


Undesirable cardiac arrhythmias associated with rate hysteresis pacemakers. The introduction of the ventricular inhibited pulse generator with the feature of rate hysteresis has been associated with a variety of rhythm disturbances, some causing serious concern. This pulse generator has two different pacing rates: (1) the automatic rate, which is the interval between two successive paced beats (usually 860 msec or 70/min), and (2) the hysteresis interval, which results in a 1,000 msec delay between a sensed cardiac contraction and the next pacemaker discharge. The hysteresis interval after a sensed signal may result in long pauses that may predispose to the development of serious cardiac arrhythmias. Two examples of this type of complication were recently observed. One patient had bigeminal rhythm with mechanically ineffective cardiac contractions and an effective cardiac rate of 35/min; he experienced dyspnea and weakness during these prolonged episodes. Another patient had repeated episodes of ventricular fibrillation. The cardiac arrhythmias were not controlled by antiarrhythmic agents, and both patients required replacement of the pulse generator. The proposed advantages of pulse generator hysteresis are (1) prolongation of battery life, and (2) maintenance of effective atrial transport; these advantages may be outweighed by undesirable cardiac arrhythmias that may be associated with this mode of pacemaker function. Rate hysteresis cardiac pacemakers should be reserved for patients having predominantly sinus rhythm without ventricular irritability. In patients with frequent ectopic ventricular activity, atrial fibrillation or high degree atrioventricular block, the rate hysteresis pacemaker offers no advantage over the conventional demand pacemaker. For patients with frequent ectopic ventricular activity not easily controlled by antiarrhythmic agents, consideration should be given to the use of a permanent demand pacemaker with external rate control, which may provide greater flexibility in arrhythmia management.


Propranolol-induced reduction of signs of ischemic injury during acute myocardial infarction. The effect of intravenous administration of propranolol (3 to 10 mg) was studied in 12 patients with acute anterior transmural myocardial infarction within the first 8 hours from the onset of pain. Criteria for inclusion in the study were persistence of ischemic pain, S-T segment elevation of 0.3 or more mg in at least two standard precordial leads, heart rate of 80 or more beats/min, mean arterial pressure of 75 or more mm Hg and cardiac index of 2.5 or more liters/min per m2. Within 30 minutes of administration of propranolol, the sum of S-T segment elevations from leads V1 through V6 (sigmaST6) and the average S-T segment elevation over the left precordium recorded from multiple unipolar leads (ST) decreased significantly by 40 and 39%, respectively. At the same time, there was a significant reduction in heart rate (from 100+/-3 [standard error of the mean] to 79+/-4 beats/min), mean arterial pressure (from 112+/-6 to 95+/-5 mm Hg) and cardiac output (from 6.1+/-0.3 to 4.1+/-0.3 liters/min). Pulmonary capillary wedge pressure remained unaltered. Four hours later the hemodynamic variables had returned to control level, but the beneficial effect on myocardial injury persisted. These electrocardiographic changes were accompanied by resolution of ischemic pain and cessation of ventricular arrhythmias. The effects of propranolol were more pronounced in patients with angiographically demonstrable flow to the affected area of myocardium. Thus, administration of propranolol in the early hours of myocardial infarction can significantly reduce the signs of myocardial ischemic injury without excessively depressing myocardial function.


Propranolol therapy in patients undergoing myocardial revascularization. The records of 185 consecutive patients having myocardial revascularization were reviewed with regard to preoperative administration of propranolol and intraoperative or postoperative complications. Tachycardia and hypertension before cardiopulmonary bypass were slightly more common in patients never taking propranolol or those who had discontinued it for more than 48 hours before operation. There was no statistically significant difference in the incidence of postbypass hypotension among patients who took propranolol within 24 hours of operation, those who discontinued it more than 24 hours before operation, and those who never took the drug. Operative mortality was not significantly different among patients who received propranolol within 48 hours of operation (3%), those who never took it and those who discontinued it more than 48 hours before operation (4%). Early in the series, five patients had an acute myocardial infarction within 48 hours after routine preoperative withdrawal of propranolol. Because complete withdrawal of propranolol in patients with unstable angina pectoris may lead to acute myocardial infarction, we recommend gradual withdrawal of the drug during 48 hours before operation. If this is not possible because anginal pain recurs or intensifies, then reduced doses may be given safely up to 10 hours before revascularization, provided that the patient is a satisfactory candidate for bypass and that adequate myocardial revascularization can be accomplished.


Effect of lithium on cardiovascular performance: report on extended ambulatory monitoring and exercise testing before and during lithium therapy. To assess the effect of long-term lithium therapy on cardiac arrhythmias and cardiovascular performance, extended ambulatory electrocardiographic monitoring was performed in 12 patients, and rest and exercise electrocardiograms in 10 of 12, before and during lithium therapy. Lithium increased the frequency of premature ventricular contractions in three patients, decreased it in one, and produced no change in eight. Three of four patients with atrial arrhythmias showed improvement during lithium therapy. Exercise performance was unchanged. Although 7 of the 12 patients manifested T wave flattening in the resting electrocardiogram, none had S-T segment displacement at rest or on treadmill exercise. Before lithium therapy, arrhythmias on exercise included premature atrial contractions in four patients, ventricular arrhythmias in four (premature ventricular contractions in four, with couplets in two and with ventricular tachycardia in one). During lithium therapy, exercise did not provoke premature atrial contractions or ventricular tachycardia in any of the patients, but three patients had premature ventricular contractions (with couplets in one case). We conclude that lithium at therapeutic levels may precipitate or aggravate ventricular arrhythmias. When administered to patients with heart disease, factors that interfere with renal clearance of lithium (heart failure, salt restriction, long-term diuretic therapy) must be recognized and doses must be adjusted accordingly. Careful follow-up and electrocardiographic monitoring are advisable if lithium is to be used in the presence of ventricular arrhythmias. Cardiovascular performance as assessed by treadmill exercise testing was not affected by long-term lithium therapy.


Radioactive tracers in congenital heart disease. Radionuclide angiocardiography is a useful method in the evaluation of patients with congenital heart disease, safely and nontraumatically. Physiologic variables such as transit times, cardiac output, left ventricular ejection fraction, stroke volume, end-diastolic volume can be measured accurately with this technique. An important application of radionuclide angiocardiography in children with congenital heart disease is in the detection, localization and quantification (pulmonary to systemic flow ratio) of intracardiac shunts and shunts between the great vessels. This technique has been found useful in the evaluation of the newborn infant with cyanosis, the patient with a cardiac murmur and the patient who has had cardiovascular surgery. Newer mobile gamma camera-computer systems permit the performance of radionuclide angiocardiography in several ill premature and newborn infants and patients during the early postoperative period. Specially designed magnifying collimators and the development of ultrashort-lived radionuclides should result in an overall improvement in the diagnostic capabilities of this technique and in a further reduction in the radiation dose.


Clinical appraisal of current nuclear and other noninvasive cardiac diagnostic techniques. At a time of rapid increases in the cost of medical care and the application of complex invasive procedures to cardiovascular diagnosis, the use of noninvasive methods has aroused interest. This report discusses the usefulness and limitations of various noninvasive diagnostic methods including nuclear medicine techniques, echocardiography, exercise electrocardiography and determination of systolic time intervals. Emphasis is placed on the applicability of these methods to specific disease processes (such as ischemic heart disease, cardiac valve disease, pulmonary embolic disease), their relative merits, future potential and present shortcomings.


Common procedures for the noninvasive determination of regional myocardial perfusion, evaluation of regional wall motion and detection of acute infarction. A brief description is given of imaging techniques to record and analyze the myocardial perfusion scan, study changes in segmental wall motion, measure ejection fraction and ventricular volumes and detect acute myocardial infarction. Attention to the details of collimation, pulse height analyzer settings, intrinsic resolution of the imaging device and quality of the tracers utilized for these studies will permit information of high quality to be obtained from subjects with use of these noninvasive techniques.


The nuclear stethoscope: a simple device for generation of left ventricular volume curves. Initial evaluation has begun of a system for displaying left ventricular time-activity curves, relating the intraventricular content of radioactivity with the cardiac cycle as determined by the patient's electrocardiogram. Major problems include proper positioning of the detector, correction for background radioactivity outside the ventricle and calibration of the device to permit conversion of measurement of radioactivity to measurement of ventricular volumes.


Pathophysiologic studies of the pulmonary and coronary circulations in man. Studies of the pulmonary circulation in normal man, performed with external radiation detectors, have shown that pulmonary blood volume is about 10% of total blood volume. Pulmonary blood volume was unchanged in patients with acute or chronic left atrial hypertension and in normal persons during expansion of total blood volume in spite of marked increases in pulmonary vascular pressures. However, pulmonary blood volume was greatly increased in patients with polycythemia rubra vera and a large total blood volume and in patients with a left to right shunt but normal pulmonary intravascular pressure. Studies of regional myocardial perfusion with injection of xenon-133 solution into the left coronary artery revealed localized areas of ischemia distal to stenotic lesions even when the patient was at rest. During angina produced by pacing, more severe ischemia occurred, thus suggesting that functional factors reduce local perfusion below resting levels. In patients with "variant" angina, intravenous injection of thallium-201 chloride during spontaneous attacks has revealed large cold areas in myocardial scintigrams not present under control conditions, thus suggesting severe transmural reduction of perfusion in heart muscle corresponding to S-T segment elevation in the electrocardiogram.


Organization of cardiovascular nuclear medicine units. Progress in the development of cardiovascular nuclear medicine can be accelerated by close cooperation between cardiologists and nuclear medicine physicians in the planning, performance and interpretation of diagnostic tracer studies. The special needs of patients with acute cardiovascular disorders often require supplementation of the hospital's central nuclear medical facility with one or more satellite units in or near the coronary care unit, cardiac operating suite, postoperative intensive care unit or emergency room. Newly emerging noninvasive cardiac diagnostic laboratories should be equipped to perform certain nuclear medicine procedures. Selected nuclear diagnostic procedures also can provide useful supplemental information during cardiac catheterization and angiography.


Increased plasma catecholamines in high renin hypertension. Plasma catecholamines, indexes of sympathetic nervous tonicity, were measured simultaneously with renin both supine and after standing plus furosemide in patients with primary hypertension and normotensive volunteers. Seventy percent of hypertensive patients with high renin levels had increased catecholamines compared with a 14% incidence in the combined group with low and normal renin (P less than 0.001). Basal  catecholamines were related directly to renin in the hypertensive patients and to blood pressure in the normal (P less than 0.05), but not in the high and low renin subgroups, and inversely to percent increase of catecholamines after standing plus furosemide in hypertensive and normotensive patients (P less than 0.01). Sympathetic nervous hypertonicity may be responsible for the elevation of blood pressure and for the activation of the renin-angiotensin system in patients with high renin hypertension.


Renin and aldosterone suppression in the antihypertensive action of clonidine. In 18 hypertensive patients receiving a constant (100 mEq/day) sodium diet, treatment with clonidine (0.3 mg/day for 5 days) decreased blood pressure in 11 patients with high and normal renin levels and 7 with low renin levels. The high and normal renin group had early and rapid reductions in blood pressure and plasma renin activity. In contrast, the low renin group had a more gradual hypotensive response and only a small absolute decrease in plasma renin. For all patients, pretreatment renin levels were related to the initial decrease in blood pressure but not to the reductions measured after 5 days. Thus, two mechanisms of action of clonidine are possible, one related to acute inhibition of the renin-angiotensin system in patients with high and normal renin levels and another that is independent of renin mechanisms and occurs in all hypertensive patients. In six additional patients with high renin levels induced by prior sodium depletion (10 mEq/day sodium diet), clonidine did not reduce blood pressure or renin, thus indicating that the suppressive action of this agent on renin pressor mechanisms occurs only in patients whose elevated renin levels are intrinsic to hypertension and unrelated to sodium depletion. Of the 18 patients receiving a normal sodium diet, 13 were classified as responding to treatment (decrease in both systolic and diastolic pressures of at least 10%). The five nonresponders had greater weight gain and higher values for aldosterone excretion. For all patients, there was a significant correlation between decrements in blood pressure and in aldosterone, suggesting that the countervailing effects of fluid accumulation on blood pressure in nonresponding patients resulted from a failure of aldosterone to be suppressed. Changes in aldosterone, in turn, correlated significantly with changes in renin. Thus, the antirenin effect of clonidine enhances its antihypertensive action not only by acutely ablating renin-angiotensin pressor mechanisms, but also by inhibiting aldosterone production and thereby minimizing longer-term reactive volume retention during treatment.


Left ventricular performance in mitral regurgitation assessed with systolic time intervals and echocardiography. Among 22 patients with isolated mitral regurgitation of various origins, systolic time intervals (preejection period [PEP] index, left ventricular ejection time [LVET] index and PEP/LVET) and echocardiographic measures of left ventricular performance (end-diastolic diameter [Dd], end-systolic diameter [Ds], and the percent change in minor axis diameter [% delta D]) were calculated. The patients were classified into two groups, those with a normal or supernormal % delta D (group I, 15 patients) and those with a decreased % delta D (group II, 7 patients). On group analysis, prolongation of the preejection period, shortening of the left ventricular ejection time and an increase in PEP/LVET was generally characteristic of patients with mitral regurgitation. These changes were accentuated when mitral regurgitation was complicated by echocardiographic evidence of diminished left ventricular contractile performance (% delta D less than 30 percent). An increase in PEP/LVET to greater than 0.05 was consistently associated with abnormal left ventricular performance, whereas a normal PEP/LVET ratio reflected normal or supernormal left ventricular performance. An inverse linear relation was found between PEP/LVET and % delta D. When compared with previous data on the relation of these variables among patients without valve insufficiency, PEP/LVET proved to be increased for any level of % delta D in mitral regurgitation. The state of digitalization did not appear to influence the relation between PEP/LVET and % delta D. The use of echocardiographic measurements augments the determination of systolic time intervals in the analysis of left ventricular performance in patients with mitral regurgitation.


Echocardiographic and clinical spectrum of mitral anular calcification. To establish the reliability of echocardiography in making the diagnosis of mitral anular calcification 10 consecutive patients with dense echoes at the mitral anular area were examined fluoroscopically, using an image intensifier. Nine of these had distinct mitral anular calcification. The echocardiographic reliability thus confirmed, 30 cases with similar findings were reviewed and the total group of 40 cases were used to define the echocardiographic spectrum of mitral anular calcification. This lesion extended variably from the anulus to involve the posterior left ventricular wall, mitral valve leaflets, aortic root, aortic valve and interventricular septum. The pleomorphic echocardiographic findings introduce difficulties in the diagnosis of pericardial effusion and mitral stenosis. Echocardiography is a reliable method of diagnosing mitral anular calcification, but care must be taken to avoid confusing this condition with others it resembles.


Favorable effects of oral maintenance digoxin therapy on left ventricular performance in normal subjects: echocardiographic study. Left ventricular performance was assessed with echocardiography in 10 normal subjects before and during maintenance therapy with digoxin (0.5 mg/day orally) in the basal state and after acute pressure loading with intravenously administered phenylephrine. During digoxin therapy, despite a decrease in mean heart rate of 5 beats/min in the basal state, mean left ventricular ejection fraction increased from 74 +/- 2 to 79 +/- 1 percent (standard error, P less than 0.03); percent shortening of a left ventricular minor dimension increased from 37 +/- 2 to 41 +/- 1 percent (P less than 0.04) and the mean rate of left ventricular dimension shortening increased from 5.66 +/- 0.22 to 6.31 +/- 0.23 cm/sec (P = 0.05). During acute pressure loading with phenylephrine there was no change in mean heart rate after digoxin and mean ejection fraction increased from 69 +/- 3 to 75 +/- 2 percent; mean percent shortening increased from 33 +/- 2 to 38 +/- 2 percent; mean rate of shortening increased from 5.46 +/- 0.32 to 6.48 +/- 0.33 cm/sec and mean normalized rate of shortening increased from 1.11 +/- 0.06 to 1.29 +/- 0.05 sec-1 (all P less than 0.01). In a few subjects the response to digoxin did not coincide with the mean data for the whole group. This variability was largely due to difficulties in exactly matching heart rate between the control and digoxin studies. These data (1) support the concept that long-term oral digoxin therapy exerts a positive inotropic effect on the normal left ventricle, and (2) demonstrate the usefulness of echocardiography in nonivasive assessment of the effects of drugs on left ventricular performance.


Chest pain as a predictor of coronary artery disease in patients with obstructive aortic valve disease. To clarify the association between chest pain and significant coronary artery disease in patients who have aortic valve disease, 76 consecutive candidates for aortic valve replacement were evaluated prospectively with use of a historical questionnaire and coronary arteriography. Of the 76 patients, 19 (25 percent) had no chest pain, 21 (28 percent) had chest pain that was not typical of angina pectoris and 36 (47 percent) had chest pain typical of anigina pectoris. In 18 of 19 patients the absence of chest pain correlated with the absence of coronary artery disease. The single patient without chest pain who had coronary artery disease had evidence of an inferior myocardial infarction in the electrocardiogram. Thus, absence of chest pain and the absence of electrocardiographic evidence of infarction predicted the absence of coronary disease in all cases. The presence of chest pain did not predict the presence of coronary artery disease, but the more typical the pain of angina pectoris the more likely were patients to have significant coronary artery disease. Of the 21 patients with atypical chest pain, 6 (29 percent) had coronary artery disease, but of the 36 patients with typical angina pectoris 23 (64 percent) had significant coronary artery disease. In addition, when patients with chest pain not typical of angina pectoris also had coronary artery disease, the diseased vessels usually supplied smaller areas of the left ventricle than when the pain was typical of angina pectoris. In 21 of 23 patients (91 percent) with typical angina pectoris and significant coronary artery disease, lesions were present in the left coronary artery. There was no systolic pressure gradient across the aortic valve that excluded the presence of coronary artery disease, although all patients with a calculated aortic valve area of less than 0.4 cm2 were free of coronary artery disease. Patients with severe left ventricular dysfunction were more likely to have normal coronary arteries.


Coronary steal: its role in detrimental effect of isoproterenol after acute coronary occlusion in dogs. Using epicardial electrograms others have established that infusion of isoproterenol increases myocardial injury after acute coronary occlusion. To define the contribution of alterations in collateral blood flow to this increased ischemia, isoproterenol was administered to 10 dogs. After pretreatment with practolol in doses that successfully block inotropic but not vascular effects of beta adrenergic stimulants, intracoronary isoproterenol continued to enhance the magnitude of S-T segment elevation in ischemic areas. Thus, vasodilation induced by isoproterenol appears to divert flow from the ischemic area. To test this hypothesis, intracoronary adenosine was given to cause coronary vasodilation without enhancing inotropy. S-T segment elevation at ischemic and adjacent sites was significantly increased. Neither agent had systemic effects, but each increased coronary blood flow while concomitantly decreasing collateral flow as evidenced by a reduction in retrograde coronary flow and peripheral coronary pressure. In addition, adenosine significantly diminished the rate of xenon-133 clearance from the ischemic myocardium. Thus, isoproterenol, in addition to its positive inotropic effect, increases myocardial injury by its vascular action. Collateral blood flow to acutely ischemic myocardium is diminished by the production of a coronary steal. Intravenously administered isoproterenol additionally diminishes collateral flow by decreasing coronary perfusion pressure. It is postulated that any agent that causes either a primary or secondary coronary vasodilation may cause a coronary steal and subsequently enhance myocardial injury.


Preceding His-atrial interval as a determinant of atrioventricular nodal conduction time in the human and rabbit heart. This investigation shows that atrioventricular (A-V) nodal conduction time (A-H interval), both in the human and in the isolated rabbit heart, is determined mainly by the length of the preceding His-atrial (H-A) interval. The A-H intervals obtained during atrial extrasystolic stimulation at different basic rates, during Wenckebach cycles and during both transient and steady state responses to stepwise increases in stimulation frequency were plotted against the corresponding H-A intervals. The A-H intervals were found to have nearly the same duration provided they were preceded by the same H-A interval. The only important difference appeared in the short H-A interval range as a shortening of the A-H interval at faster basic rates. This facilitating effect of frequency, which was found in the majority of cases, is compatible with the similarly frequency-dependent shortening of the functional refractory period of the A-V node.


Double outlet left ventricle. Morphology, cineangiocardiographic diagnosis and surgical treatment. In double outlet left ventricle,both the pulmonary artery and the aortaarisefromthemorphologicleft ventricle. This paper presents the anatomic and cineangiocardiographic features of five patients who had this condition proved at surgery or autopsy. The condition of the first patient was incorrectly diagnosed as transposition of the great arteries with pulmonary stenosis and ventricular septal defect; the anatomic features were correctly interpreted at operation in 1966 and appropriate repair was made, but the patient died postoperatively. The condition of the other four patients was correctly diagnosed. The second patient had Ebstein's malformation of the tricuspid valve and hypoplastic right ventricle in addition to double outlet left ventricle; her condition was not considered operable. Two patients, one with visceroatrial situs solitus, concordant d-loop and dextrocardia, were surgically treated with good long-term results. The fifth patient died 2 years postoperatively and is the first patient reported to have double outlet left ventricle with visceroatrial situs inversus, a discordant d-loop and levocardia. The segmental approach to the classification and diagnosis of connection disorders is discussed and the radiologic criteria by which double outlet left ventricle may be diagnosed considered in detail. The importance of using the radiologic projection (usually left anterior oblique) that profiles the ventricular septum is emphasized because the diagnosis can be established only by delineating the relations of the origins of the great arteries to the ventricular septum. The surgical significance of other anatomic features, including the number, size and position of ventricular septal defects and conal malformations, is also discussed.


Congenitally corrected transposition of the great arteries: morphologic study of 32 cases. The detailed anatomy of the heart is described in 32 autopsy cases of congenitally corrected transposition of the great arteries.Tis condition is defined as the combination of atrioventricular (A-V) discordance and transposition of the great arteries. Examples of primitive (single) ventricle with "inverted" (that is, left-sided in situs solitus) outlet chamber are excluded. Six hearts with A-V discordance and pulmonary atresia are described in an appendix. In 29 cases of corrected transposition the heart was in situs solitus; in 3 it was in situs inversus totalis. Only 5 of these 32 hearts had no potential for intracardiac shunting. Anomalies of the tricuspid valve (91 percent of cases), ventricular septal defect (78 percent) and pulmonary outflow tract obstruction (44 percent) occurred with sufficient frequency to be considered part of the basic malformation and are described in detail. The precise anatomy and disposition of the A-V valve tension apparatus, the coronary arteries and the conducting tissues are described with special reference to possible surgical approaches for repair of the anomalies. In two hearts with situs solitus the aortic valve was right-sided with respect to the pulmonary valve. This finding is important for both diagnosis and nomenclature.


Candida myocarditis without valvulitis.

Candida myocarditis without valvulitis. Thirty-one patients with systemic candidiasis at postmortem examination were found to have Candida involvement of the myocardium without valvulitis. Retrospective examination of their clinical course demonstrated that a new conduction disturbance was seen in 10, supraventricular arrhythmias in 5,QRS changes mimicking myocardial infarction in 3, and pronounced T wave changes in 13. Hypotension or shock was seen in 13 patients and could not be explained by coexistent bacteremia or blood loss in 8. One patient died suddenly. Of 19 patients with systemic candidiasis without myocardial invasion, 4 had minor T wave changes and one had a supraventricular arrhythmia. Candida invasion of the heart significantly complicates the clinical course in systemic candidiasis and should be suspected when a young person without preexistent heart disease has cultures positive for a Candida organism, a significant arrhythmia, conduction distrubance or other dramatic QRS change. The effect of therapy on Candida invasion of the heart is unknown.


Intramuscular clindamycin for therapy of infective endocarditis. Report of 23 cases and review of the literature. Twenty-three patients with infective endocarditis received intramuscular clindamycin (Cleocin) for treatment. Thirteen had acute Staphylococcus (S.) aureus endocarditis but none had involvement of the aortic valve. Eleven of these 13 infections were heroin-related and involved the tricuspid valve.Twenty-one patients were successfully treated. Two patients with heroin-related S. aureus infection failed to respond to intramuscularly administered clindamycin, but responded to retreatment with methicillin. There have been 34 reported cases of endocarditis treated with clindamycin. Although 80 percent of all cases due to staphylococci responded favorably, almost all were heroin-related tricuspid valve infections. In addition 91 percent of cases due to aerobic streptococci responded but, surpisingly, treatment failed in three of four cases of anaerobic endocarditis. Although clindamycin can be useful in streptococcal endocarditis and in some cases of heroin-related S. aureus tricuspid endocarditis, caution should be exercised in its use. It is "less" bactericidal than the penicillins or cephalosporins, and organisms have become resistant during treatment. Furthermore, patients with anaerobic endocarditis have not responded well, and data are not available to recommend administration of clindamycin for acute S. aureus infections engrafted on the aortic or mitral valve.


Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases. A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome;16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.


Afterload reduction in the management of postinfarction ventricular septal defect. The primary goal in the medical management of ventricular septal defect complicating myocardial infarction is to support cardiac function and control symptoms, if possible, for a period of 4 to 6 weeks. If the patient survives this period, surgical correction of the defect is technically easier and safer. In many cases, However, cardiac function is severly compromised, intractable biventricular failure develops,early operation is necessary and the likelihood of successful repair is diminished.