Lithium metabolism and intracellular electrolytes.

Lithium chloride was administered orally to swine and two different types of sheep, HK and LK. There was a pre-lithium 16-fold variation in intracellular sodium (LK greater than HK greater than swine) and a 6.5-fold variation in the intracellular potassium (swine greater than HK greater than LK). Collected plasma and erythrocytes were analyzed for lithium, sodium and potassium. The ratio of erythrocyte lithium/plasma lithium was directly related to the pre-lithium erythrocyte sodium concentration and inversely related to the pre-lithium erythrocyte potassium concentration.


Development of potentiation in the dentate gyrus of rat: physiology and anatomy.

The physiological development of potentiating processes in the rat dentate gyrus were compared to morphological development. Rapid Golgi techniques were coupled with in vitro studies of dentate granule cell frequency potentiation, post-tetanic potentiation and long-term potentiation. Frequency potentiation and long-term potentiation exhibited a developmental progression between 7 and 210 days postnatal. Posttetanic potentiation remained constant across this period. The relation of these findings to synaptogenesis and dendritic spine formation are discussed.


Effect of total amygdalectomy upon regulation of salt intake in rats.

Sodium appetite was studied in rats with lesions destroying the entire amygdaloid nuclear complex. The rats were totally aphagic and adipsic for several days following lesioning but regained nearly normal levels of food and water intake about 2 to 3 weeks postoperatively. Intake of 3% saline was observed after induction of sodium appetite by treatment with a mineralocorticoid and a natriuretic agent. Rats with amygdaloid lesions generally manifested severe but not total loss of sodium appetite. Regulation of water intake was also moderately to severely impaired. Suggestive evidence was obtained that recovery of sodium appetite in amygdalectomized rats can be enhanced by postoperative experience with sodium appetite and saline reinforcement.


Some physiologic characteristics of the electrodermal reflex in the cat.

The amplitudes of electrodermal reflexes evoked in intact cats were compared under a variety of anesthetic conditions. Electrodermal reflexes were elicited in both decerebrate and spinal preparations with and without anesthesia. Reflex amplitude was significantly depressed in the anesthetized preparation after decerebration or spinal transection. In contrast, spinal transection performed after decerebration in unanesthetized preparations significantly increased the amplitude of the reflex. The evidence presented in this study supports the concept of a primarily inhibitory lower brainstem system with regard to this reflex. The relative stability of the reflex amplitude in the anesthetized cat suggests that this reflex system could be useful in the analysis of the effects of drugs acting on the central nervous system.


Effect of a low protein diet on the anatomical development of subcortical formations.

The effects of a low protein diet during gestation, lactation, and after weaning on the anatomical development of a subcortical nucleate formation, the neostriatum, and a reticulate formation, the diagonal band of Broca, were studied. At 10, 30, and 90 days the volume of the neostriatum was decreased in the experimental rats. However, the percent of the brain volume that was neostriatum was unaffected at each of these ages. In a rapid Golgi study of individual neurons at 90 days of age there was no significant effect of the low protein diet on the dendritic length of three different types of neurons within the neostriatum. However, its heavily spined dominant neuron showed a significant decrease in synaptic spine density. In the reticular formation, there was also no significant effect on dendritic length. A minute, apparently axonless cell corresponding to the neurogliaform cell of Ramón y Cajal, showed a decrease in extent of its cell processes only in the neostriatum. When compared to cortical formations, these phylogenetically more conservative neuronal substrates appear to be more resistant to the effects of undernutrition.


Effects of septal damage and ovariectomy on feeding, drinking and body weight.

Septal destruction and ovariectomy each influenced food intake and body weight differentially. Animals sustaining septal damage ingested significantly more food than the other groups, and septal hyperphagia persisted for as long as 109 days. Ovarian hyperphagia did not occur under conditions of constant illumination. Septal destruction exerted essentially no effect on body weight, while ovariectomy substantially increased body weight. Sequential surgical manipulations provided further evidence that the ovaries and the septum influence food intake and body weight via independent mechanisms. Results indicated that the septal and ovarian effects on water intake are not mediated via independent mechanisms. Septal and ovarian hyperdipsia were found to be very robust effects occurring regardless of the lighting regimen. It was further demonstrated that ovarian hyperdipsia is not secondary to food intake but rather is primary hyperdipsia.


Olfactory pathway evoked potentials in response to hypothalamic stimulation.

Ipsilateral and contralateral stimulation of lateral, ventromedial and posterior hypothalamic nuclei produced evoked responses in the olfactory bulb and in the prepyriform cortex. No differences in the latencies were found by stimulation of each nucleus in the homo and contralateral olfactory structures. The high amplitude of the fast component (N1) was obtained with stimuli applied to the ventral zones and the slow components (N2, N3) were obtained with more dorsal stimulation. An ipsilateral pathway is indicated at the supramammillary and posterior commissure level, since severing these structures abolishes the evoked responses. A bilateral projection is proposed for the olfactory bulb.


An atlas of the deep cerebellar nuclei and subtentorial brainstem of the cat with compensation for skull-size.

The bony tentorium in the cat precludes a stereotaxic approach, in the coronal plane, to widespread areas of the cerebellum and underlying brainstem. To facilitate the application of the stereotaxic method in these areas, an atlas of the subtentorial brainstem was prepared, with plates (30 degrees from the vertical) based on an angle of entry which avoids the tentorium. In addition, a placement error regression function, based on a measure of skull size, was derived to provide atlas coordinate corrections for different brain sizes. The application of this regression function, together with the present atlas plates, can greatly increase placement accuracy.


Effects of pyrithiamin and oxythiamin on acetylcholine levels and utilization in rat brain.

Regional cerebral acetylcholine (ACh) levels and utilization rate were assessed in vivo in rats rendered thiamin deficient using the thiamin antagonists pyrithiamin or oxythiamin. ACh levels were significantly reduced in all brain regions of pyrithiamin treated rats and in the medulla-pons and striatum of oxythiamin treated rats compared to controls. ACh utilization was significantly reduced in the midbrain, striatum and hippocampus of pyrithiamin treated rats, but was reduced only in the striatum of oxythiamin treated rats compared to controls. Thus, there are some reductions in ACh levels and utilization that are unique to pyrithiamin induced deficiency and as such are distinct from oxythiamin/undernutrition related reductions. Since only pyrithiamin produces neurological symptoms, its unique ACh effects may be related to these symptoms.


Spontaneous and osmotically-stimulated activity in slices of rat hypothalamus.

Single unit activity was recorded from 400-500 mu m thick slices of rat hypothalamus, using either NaCl- or horseradish peroxidase-filled glass micropipettes. Spontaneous activity was present in the following hypothalamic loci: anterior hypothalamic-preoptic area, nucleus circularis, nucleus of the diagonal band of Broca, paraventricular accessory nucleus, paraventricular nucleus (all portions), periventricular regions of the anterior hypothalamus, and the suprachiasmatic nucleus. The supraoptic nucleus was the only major cell group studied to exhibit no spontaneous activity. Cells of the paraventricular and circularis nuclei were spontaneously active, displayed firing rates and patterns of activity similar to those recorded in vivo for magnocellular elements of the hypothalamus, and in some cases responded to increases in the osmolality of the bathing medium with altered firing rates and/or patterns of activity. Many cells in these preparations were characterized by phasic, bursting patterns of activity. Slow, irregular and regular, continuous activity was also frequently observed, as is typical in vivo. Median firing rates were in the range of 4-6 spikes/sec, somewhat faster than the rates usually reported for anesthetized in vivo preparations. These rates are more similar to those observed in unanesthetized monkeys or rats with diencephalic islands. Extracellular HRP marking provided a high degree of localization for many of the recorded cells. These results indicate that the hypothalamic slice preparation is useful for studies in which it is desirable to eliminate extrahypothalamic connections and in which it is necessary to exercise a fine degree of control over the extracellular environment of the cells.


Analysis of temporal relations among units and slow waves in rabbit hippocampus.

Arrays of triple microelectrodes were stereotaxically lowered into CA1, CA3 and dentate areas of the dorsal hippocampal formation in anesthetized rabbits. Recordings of action potentials and waves were analyzed on a PDP-11 computer using auto-, cross-, and multiple-correlation programs to determine temporal relations during 90 sec samples of spontaneous activity. It was found that temporal periods of neuronal firing and inhibition were strongly related to the pattern of waves. During periods of high amplitude synchronous waves (theta), the correlation between the activities of different groups of neurons was directly related to the periodicity of the wave. During instances of lower amplitude, desynchronous wave activity, the correlations between spikes recorded from those same cells were less periodic, varying according to the amount of wave synchrony. Variations in wave synchrony due to anatomical location, eserine effects, or spontaneous fluctuations under anesthesia produced corresponding variations in the relations between the activities of different groups of neurons. It is suggested that these relations between neuronal activity and gross waves may be implicated in processes which are at the basis of learning and memory.


Effects of post-trial reinforcing vs. subreinforcing stimulation of the substantia nigra on passive avoidance learning.

Experiments were designed to investigate the role of post-trial reinforcing and subreinforcing stimulation of the substantia nigra on memory processing. Thirty sec post-trial reinforcing stimulation (0.2 sec on/1.8 sec off) impaired learning of response suppression in a step-down task compared to control animals as well as to animals stimulated at subthreshold current level (i.e., at 25% of the current level shown to maintain optimal self-stimulation in previously performed self-stimulation sessions). In a second small-box passive avoidance experiment, i.e., the alcove-avoidance task, opposite results were attained: Subreinforcing stimulation attenuated learning whereas neither suprathreshold stimulated animals nor control animals showed impairment of learning. The conclusions drawn from these results are as follows: Post-trial stimulation of the substantia nigra interferes with memory processing. This attenuation of learning is obviously task-dependent and can additionally be influenced by the quality of the stimulation, i.e., whether it is reinforcing or not. Possible explanations to account for these task-dependent and quality of stimulation-dependent effects of post-trial substantia nigra stimulation are discussed.


Neuronal activity in the midbrain reticular formation related to behavioral habituation and sensitization.

Single units of the midbrain reticular formation (MRF) were recorded in the active rat (N = 10) during the presentation of repetitive trains of clicks or flashes. The movement and orienting behavior elicited by the stimuli, measured by direct observation and in terms of electrical disturbances in the recording cable, showed habituation in 14 cases, sensitization in six cases, and no decrement in nine cases. Of the 18 MRF units recorded during at least one of these behavioral conditions, seven were classed as congruent, i.e., they showed activity that paralleled the behavioral response. The majority of MRF units were behaviorally incongruent; in the most frequently observed case, their activity failed to change reliably when behavior habituated. Although the activity of congruent units generally showed moderate correlations with behavior that followed stimulation, disassociations between the two responses were commonly found. While the data are consistent with a role for the MRF in behavioral habituation and sensitization, they provide little evidence that the region is closely linked to the systems in direct control of behavior.


Disulfiram alters dopamine metabolism at sites in rat's forebrain as detected by push-pull perfusions.

The effect of tetraethylthiuramdisulfide (disulfiram) on the catabolism of dopamine within discrete regions of the brain was investigated in the unrestrained rat. After a guide cannula had been implanted stereotaxically, a given subcortical site was radiolabeled with 14C-dopamine (DA) by microinjecting 2.0 mu Ci in 2.0 microliters. Successive push-pull perfusates collected from each tissue were assayed by paper electrophoresis for the separation of DA metabolites. When disulfiram, a potent aldehyde dehydrogenase (ALDH) inhibitor, was given intragastrically in a clinically efficacious dose of 200 mg, the formation of the acids DOPAC and HVA was inhibited within perfusates of the caudate nucleus and nucleus accumbens. However, following disulfiram treatment, the proportion of alcohol metabolites did not differ from the control level in the untreated rat. The level of ALDH decreased by approximately 50% in these subcortical nuclei following the inhibition of the enzyme by disulfiram. Conversely, in samples of perfusate obtained from 14C-labeled sites within inferofrontal cortex, periform cortex, diagonal band of Broca, lateral-posterior caudate nucleus, tuberculum olfactorium, lateral olfactory tract or the olfactory nuclear complex, the proportion of DA metabolites remained stable. Generally, a low rate of deamination of the exogenously injected DA occurred within perfusion sites in the ventrobasal forebrain, whereas an intermediate rate of deamination was noted in samples collected at more dorsal loci. Thus, clearcut regional differences in DA catabolism occur in the brain of the living animal, which may depend upon the characteristics of the dopaminergic-rich area of the rat's brain.


Biological activity of neurotensin and its C-terminal partial sequences.

A hypothalamic tridecapeptide, neurotensin, and its C-terminal partial sequences down to the dipeptide were synthesized. These peptides were assayed for smooth muscle contracting and blood pressure lowering properties using preparations of isolated stomach fundus, uterus and duodenum of the rat, isolated guinea pig ileum and rabbit carotid artery. Sequences of 6 or more terminal amino acids produced a strong stomach fundus contracting effect, the potencies of the fragments being approximately equivalent to or slightly more than that of the parent tridecapeptide. These fragments also elicited the ileum contracting activity, but the potencies were only one fifth to one tenth that of neurotensin. The tetra- or dipeptide hardly stimulated either the fundus or the ileum. The stimulating effect on the uterus or relaxing effect on the duodenum of neurotensin was not consistent. Rabbit blood pressure was lowered markedly by neurotensin and weakly by its dodecapeptide. From these results, the arginine or arginine-arginine residue down to the C-terminal leucine appears to be essential for the smooth muscle contracting activity of neurotensin. The full length sequence may be needed for the hypotensive effect.


Movement-dependent and movement-independent changes in hippocampal RSA in cats.

EEG was recorded from the dorsal hippocampus of cats during walking in situations intended to elicit a minimum of orienting or attentional behavior. The situations included walking in an alley for food after prolonged overtraining, and ad lib walking in an observation chamber after 24 hours habituation. In virtually all (82-100%) cases of sustained walking RSA was present in the dorsal hippocampus; however, the amplitude of the RSA during walking was quite variable and in many cases quite small. The results suggest that in the cat motoric factors may influence the occurrence of RSA and non-motoric factors may influence the amplitude of RSA.


Effects of urethane on hippocampal unit activity in the rat.

The effect of urethane on hippocampal single unit activity in rats paralyzed with gallamine triethiodide was examined to determine possible influences of urethane as an anesthetic for electrophysiological recordings. With intravenous injections of urethane (1.0 g/kg body weight), hippocampal units responded initially with a substantial decrease in spontaneous firing rate. Activity in some cells recovered partially after a period of approximately 45 min. The activity of the remainder of cells recorded remained depressed for periods of time up to 1.5 hr. Longer periods of depression were observed in some cells. The difference in susceptibility to urethane in the population of hippocampal cells may offer a selective alteration in patterns of spontaneous activity in the hippocampus and systems efferent to the hippocampus. A knowledge of such alterations may prove important in interpreting the results of electrophysiological recording in preparations under urethane anesthesia.


Stereotaxic implant microinjection and temperature recording system for rabbits.

Modification of standard rabbit stereotaxic apparatus to allow adjustment of the tooth bar in the vertical plane may be accomplished by simple machining of a standard laboratory clamp and aluminum rod. The modification greatly increases speed of head positioning for implant surgery. Machining the chrome and brass luer hub of standard stainless steel hypodermic needles to the described configurations produces improved guide tubes for brain temperature recording and cannulae for brain microinjections. Data from hypothalamic injection of prostaglandin E1 and records of resulting changes in brain temperature support the effectiveness of the methods described.


Similar effects of estrogen and lateral hypothalamic lesions on feeding behavior of female rats.

Many similarities exist between the inhibitory influence of estrogen on food intake (FI) and body weight (BWt) in female rats and the effect of lateral hypothalamic (LH) lesions on energy balance. Thus, a possible interaction of small electrolytic LH lesions (0.8 mA/10 sec) with hormone-dependent changes in FI, BWt and feeding patterns of female rats was examined. Relative to sham operated controls, rats with LH lesions showed a transitory period of anorexia and initial loss of BWt. Subsequently, FI and BWt gains of lesioned rats returned to control levels although a small chronic reduction in mean BWt was observed relative to sham animals. Daily changes in FI and BWt during 4-day estrous cycles as well as post-ovariectomy increases in FI and BWt were comparable for lesion and sham animals. Also, both groups showed a similar decrease in FI and BWt following a SC injection of estradiol benzoate (EB). Possible effects of LH lesions were further examined by analyzing feeding patterns. Feeding behavior was continuously monitored with photodetectors and recorded on an Esterline Angus event marker before and after a single SC injection of 6 micrograms of EB. Relative to shams, LH animals showed an exaggerated diurnal distribution of meals, ate smaller meals of shorter duration and had larger intervals between meals during the light period. EB was found to shift the feeding patterns of sham animals towards the meal patterns shown by the lesioned rats (exaggerated diurnal distribution of meals, etc.). However, the lesioned rats also showed a normal change in feeding patterns following EB, albeit these changes occurred from a markedly different baseline level.(ABSTRACT TRUNCATED AT 250 WORDS)


[Consequences of a high-placed jugular bulb for the inferior ventilation pathway of the middle ear].

The evaluation and the correlation between the healthy and inflamed system of the mucosal folds of the middle ear demonstrate that there is a second "bottle neck" of the aeration pathways (the first being the Eustachian tube) in the region of the tympanic diaphragm with the tympanic isthmi - anterior and posterior -, the latter is more important for the ventilation of the epitympanum and antrum. Anatomical variations in this lower air-pathway as a high placed jugular bulb into the middle ear cavity endanger of course the undisturbed ventilation of the epitympanum and antrum in case of the infected and swollen mucosa and its folds.


[Behavior of the middle ear mucosa in cholesteatoma and following tympanoplasty. An experimental histological study in rabbits].

After operation three consecutive phases can be observed: 1. thickening of epithelial cell layer with development of edema in the submucosa, 2. metaplasia of epithelium with formation of ciliated and goblet cells, concomitantly round cells are found in the submucous tissue, 3. regression of inflammation and epithelial metaplasia. After 6 months goblet and ciliated cells disappear and eventually a slightly irregular monolayer epithelium is seen. If cholesteatoma is present the second phase persists. Remarkably epithelial and subepithelial changes are not concentrated in the vicinity of cholesteatoma but are seen in the whole middle ear. By autoradiography it was demonstrated, that the subepithelial tissue of cholesteatoma has a normal metabolic rate. It can be concluded that high metabolic activity postulated by other authors cannot be responsible for inflammation.


A rapid method for blood alcohol determination by headspace analysis using an electrochemical detector.

A method for the determination of blood alcohol concentration by headspace analysis using an electrochemical detector is described. A determination can be made within 2 min, and only 0.1 ml of blood is required for each analysis. The detector response was linearly related to ethanol concentrations up to 3.0 mg/ml. The standard deviation of a single determination was +/- 0.014 mg/ml. The accuracy of the method based on comparison with an enzymatic (alcohol dehydrogenase) technique was high, the mean recovery being 102.2% of the attributed concentration. The ease of the operation and fast analysis time make the method ideal for serial determinations, for example during mass screening of biological samples for ethyl alcohol in forensic and toxicology laboratories.


Heroin abuse and a gas chromatographic method for determining illicit heroin samples in Singapore.

The abuse of heroin (diacetylmorphine) in Singapore escalated sharply in 1975 and 1976, as indicated by the 35-fold increase in the number of heroin seizures and the 20-fold increase in the urine samples containing morphine since 1974. A rapid and simple GC method has been described to estimate diacetylmorphine (and caffeine). Monoacetylmorphine and acetylcodeine may be ascertained by an additional step involving acetylation. All gas chromatograms of a large number of samples analyzed consistently had the same pattern, indicating that they possibly had a common origin. This GC "fingerprint," together with the quantitative data, appears to be characteristic of the illicit Asian or Chinese type of heroin found in Singapore. The proportions of the four major ingredients in some twelve typical samples have been tabulated. Statistical data confirming the accuracy and reproducibility of the analytical method have also been presented.


Correlation of antemortem and postmortem digoxin levels.

Postmortem serum digoxin levels from any source routinely exceed antemortem values. Variation resulting from site of sampling gave a mean postmortem to antemortem ratio of 1.96 for heart, 1.63 for subclavian vein, and 1.42 for femoral vein samples. No correlation could be made between the postmortem interval and the increase in post-mortem serum values, irrespective of the site of sampling. A combination of femoral venous serum and vitreous humor values gave the best information for determining possible antemortem digoxin toxicity.


The postmortem diagnosis of magnesium deficiency: studies in an animal model for the human infant.

Weanling rats were studied as a model for the human infant to determine the optimal tissue in which to assess the status of magnesium after death. Control rats were fed laboratory chow or purified diets that provided a surfeit of magnesium and accommodated a normal rate of growth. Other rats were fed diets that resulted in two degrees of magnesium deficiency: one that might result in spontaneous death within one week, and the other, within two weeks. These times may correlate with six months and one year in the human infant, the period during which the sudden infant death syndrome usually occurs. There was no consistent difference between the magnesium concentration found in the vitreous humor, liver, heart, or skeletal muscle of magnesium-deficient and control rats. However, bone accurately reflected the level of dietary magnesium. There was a significant difference between the magnesium concentration of the anterior and posterior halves of the ribs, indicating irregular distribution of magnesium within the bone. Significant differences were found in the magnesium concentrations of different bones from the same animals. Therefore one entire bone, such as the sternum or the rib, should be studied. The need to match control and study subjects for age was apparent.


Determination of group specific component phenotypes in dried bloodstains by immunofixation on cellulose acetate.

Group specific phenotypes in dried bloodstains can be rapidly and reliably determined by immunofixation on cellulose acetate membranes. Up to 16 samples, can be analyzed simultaneously in less than 60 min, and the cellulose acetate electrophoretogram is retained as a permanent record.


Gunshot wounds: visual and analytical procedures.

Visual examination of clothing and tissue from gunshot wounds provides information pertaining to the range of discharge of a firearm. Identification of powder grains or soot is evidence of close range discharge by a handgun. Analyses of tissue by EDX and FAAS technics are shown to supply corroborating data to visual examination in estimation of range. These methods are of particular value in differentiating contact and distant wounds when decomposed bodies are examined and when multiple layers of clothing are present.


Sleeping arrangements of sudden infant death syndrome victims in the District of Columbia--a preliminary report.

The recent decline in the incidence of the SIDS in the District of Columbia has permitted identification of what appears to be two separate groups of cases within the generic SIDS population. While deaths of bed-sharing victims remained relatively constant throughout the study period, a greater than fourfold decrease was seen in non-bed-sharing SIDS fatalities. The implications and preliminary nature of these findings are discussed in an attempt to stimulate further inquiry into the possible safety hazard of the practice of bed-sharing in the SIDS age group and its potential influence on the incidence of the SIDS.


The postpericardiotomy syndrome then and now.

The postpericardiotomy syndrome is a febrile illness with pericardial and pleural reaction that either persists or appears beyond the 1st postoperative week. We believe that it begins in the 1st week after intrapericardial cardiac surgery, and that clinical signs of illness correlate with appearance of AHA and with significant rise in titer to AVA. Our present working hypothesis is that myocardial damage with bleeding into the pericardial sac at the time of surgery combines with concurrently acquired or reactivated viral illness to set the stage for the syndrome. The immune response is triggered by viral invasion of traumatized myocardium and an immune response is mounted, not against autologous myocardium per se but against the neo-antigen, the virus-infected myocardium. The illness is self-limited. It sometimes recurs but it seems to leave no sequelae other than the bad memory of a painful postoperative complication that prolonged hospitalization and delayed the realization of the full benefits of that heart operation.


The correction of hypospadias.

Hypospadias can be divided into Type I deformities, in which only construction of the distal urethra is necessary, and Type II deformities, where the penis must first be straightened. In 200 consecutive repairs of Type II hypospadias there were no fistulae.


Behavioral role of the mammillary efferent system.

The present study examined the effects of lesions of the mammillary system on spatial memory and arousal. Destruction of the medial mammillary nucleus or the mammillotegmental tract produces impairments on a delayed alternation task and greatly increases activity in the open-field. Lesions of the mammillothalamic tract produce a differential effect in that the spatial alternation deficit is accompanied by a general lethargy and unresponsiveness. It is suggested that the mammillary system plays a crucial role in the short-term storage of proprioceptive information necessary for the successive execution of maze choices. It also appears to play a role in the arousal state of the animal.


Studies on the mechanism of sprouting of noradrenergic terminals in rat and mouse cerebellum after neonatal 6-hydroxydopa.

The effect of various pharmacologic agents on the noradrenergic innervation of rat cerebellum was observed. It was found that the neurotoxin 6-hydroxydopa (6-OHDOPA), when given to rats at birth, caused a 46% reduction at 5 weeks of age in tyrosine hydroxylase activity in the locus coeruleus, the nucleus of origin for noradrenergic fibers innervating the cerebellum. At the same time, however, both tyrosine hydroxylase activity and NE content were elevated by 50% in the cerebellum. By treating gravid mice with the 6-OHDOPA, which crosses the placental barrier to affect the brains of developing pups, a dissociation has been shown between the elevated cerebellar NE levels and reduced telencephalic NE content. None of the other assorted pharmacological agents--namely amphetamine, metaraminol, apomorphine, alpha-methyl-p-tyrosine. L-dihydroxyphenylalanine and tyramine--when given at birth, caused a permanent elevation in cerebellar NE content. This series of studies suggests that a reduced number of noradrenergic perikarya are providing a greater innervation of the cerebellum than in control rats. Also, alteration of the telencephalic noradrenergic fibers, which are also derived from the locus coeruleus, does not appear to be a necessary event for the initiation of sprouting of noradrenergic fibers in the cerebellum. Because none of the acute-acting pharmacological agents caused a permanent elevation of NE in the cerebellum, it appears that damage, and not mere stimulation or blockade, is a necessary event for initiation of sprouting.


A meshed aluminum foil wound dressing system.

A minimally adherent dressing of meshed aluminum foil has been designed and tested. The theoretical and practical advantages of this dressing are described.


[Hemodynamic effects of various doses of a new inotropic: amrinoma].

The hemodinamic effects of Amrinone, bipiridine derivate with positive inotropic effects in animals, were studied on eight patients under right and left heart catheterization. The cardiac index, stroke volume, dP/dt and stroke work index were increased; the pulmonary pressure and the left ventricle end diastolic pressure were decreased all with statistical significant values. There were no changes in mean aortic pressure. These effects are mainly due to an increase in contractility and, partially, to vasodilation and tachycardia. The intrinsic mechanism of action of this compound is not known. Its place in cardiac therapy must be established with additional clinical investigations.


H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemiblock). Clinical, electrocardiographic and electrophysiologic correlations.

Electrophysiologic studies were performed in 119 adults with chronic bifascicular block manifested by right bundle branch block and left anterior hemiblock. The H-V interval was normal in 86 patients and prolonged in 33. The following clinical variables were more frequent (P less than 0.05) in patients with a prolonged H-V interval: cardiac third sound, mitral systolic murmur, cardiomegaly on chest roentgenogram, congestive heart failure and cardiac functional class III or IV (New York Heart Association criteria). The following differences in the electrocardiographic and electrophysiologic findings were found: Patients with a prolonged H-V interaval had a longer mean P-R interval, QRS duration and A-H interval (P less 0.02). All patients were followed up prospectively in a cardiac conduction disease clinic after initial evaluation. The mean follow-up periods were (mean plus or minus standard error of the mean) 514 plus or minus 49 and 563 plus or minus 34 days for the patients with a prolonged and normal H-V interval, respectively. Progression of conduction disease occurred in three patients (4 percent) with a normal H-V interval and in four (12 percent) with a prolonged interval. The cumulative 3 year mortality rate for the entire group was 25 percent. The patients with a prolonged H-V interval had a higher cumulative 2 year mortality rate than those with a normal H-V interval but the difference was not statistically significant. In summary, a prolonged H-V interval was often associated with  serious myocardial dysfunction and a high mortality rate. The risk of progression of conduction disease was slight with either a prolonged or a normal H-V interval during this relatively short follow-up period.


Cor triatriatum: study of 20 cases.

Twenty cases of cor triatriatum are reported. The diagnosis was confirmed by necropsy in 16 cases and at the time of operation in 4. The lesion occurred as an isolated anomaly in 7 cases; in 13, other associated cardiac anomalies were present. Three anatomic types of cor triatriatum were identified in the cases studied at necropsy: diaphragmatic (10 cases), hourglass (3) and tubular (3). The diaphragmatic type was also present in all four cases in which the diagnosis was confirmed at operation. Associated anomalies were found in five cases of the diaphragmatic type and in each case of the hourglass of tubular types. In isolated cor triatriatum the clinical findings were characteristic of pulmonary venous and arterial hypertension. In two cases, one with a communication between the right atrium and the accessory left atrial chamber and one with partial anomalous pulmonary venous connection associated with cor triatriatum, the clinical findings suggested a large left to right shunt with pulmonary arterial hypertension. The clinical findings varied in the cases with associated anomalies, and it was difficult to determine the cause of disturbance of the circulation.


Nonobstructive hypertrophic cardiomyopathy mimicking mitral stenosis. Documentation by echocardiography, phonocardiography and intracardiac pressure and sound recordings.

The physical findings in hypertrophic cardiomyopathy with left ventricular outflow tract obstruction are well described. In the absence of outflow tract obstruction the findings are less distinctive. There have been several reported cases in which the cardiac findings have suggested the diagnosis of mitral stenosis, In this report we describe a patient whose auscultatory and roentgenographic findings more closely mimicked mitral stenosis. The patient had a loud first heart sound, mitral opening snap and an apical presystolic murmur; left atrial enlargement was present. Noninvasive studies, including phonocardiography, echocardiography and apex cardiography, strongly suggested the correct diagnosis of nonobstructive hypertrophic cardiomyopathy. The diagnosis and unusual auscultatory findings were confirmed by results of cardiac catheterization and intracardiac phonocardiography. The importance of recognizing this syndrome and the use of noninvasive methods to establish the diagnosis are stressed.


Anatomically corrected malposition of the great arteries (S, D, L).

Two autopsy-proved cases are presented of a rare form of congenital heart disease, anatomically corrected malposition (S, D, L). Anatomically corrected malposition means that despite the abnormal relationship between the great arteries, the aorta arises nonetheless above the anatomically left ventricle and the pulmonary artery originates above the anatomically right ventricle. (S, D. L) briefly indicates the segmental set or combination: situs solitus of viscera and atria (S), ventricular D-loop (D), AND L-MALPOSITION OF THE GREAT ARTERIES (L). These are the first cases of anatomically corrected malposition (ACM) in whom the presence of a subaortic muscular conus only has been documented pathologically. This established that ACM can occur with a subaortic conus, as well as with a bilateral conus. From the diagnostic standpoint, the distributions or epicardial courses of the coronary arteries are recommended as a helpful approach to ventricular identification. This diagnostic method has widespread angiocardiographic and surgical applications. Symbolic terminology, exemplified by anatomically corrected malposition (S, D. L) is brief and accurate. This approach may conveniently be applied to many other forms of comples congenital heart disease, and it considerably facilitates computer data processing.


Ultrastructure of crista supraventricularis muscle in patients with congenital heart diseases associated with right ventricular outflow tract obstruction.

Ultrastructural studies were made of operatively resected crista supraventricularis muscle in 59 patients with congenital heart diseases, or whom 54 had obstruction to right ventricular outflow. Relationships of anatomic diagnosis, age, peripheral arterial oxygen saturation (PAO2), peak right ventricular systolic pressure gradient and right ventricular end-diastolic pressure (RVEDP) to hypertrophic changes, abnormalities of cellular and myofibrillar orientation, and degenerative alterations were determined. Changes directly related to hypertrophy were: cell diameters greater than 20 mu, irregular cell shape, lobulated nuclei, multiple intercalated discs, dilated T tubules, abnormal Z bands, and increased numbers of ribosomes. Abnormalities of cellular or myofibrillar orientation were focal in distribution and occurred in 12 patients, most of whom had elevated RVEDP, decreased PAO2, markedly enlarged cells, and interstitial fibrosis. Interstitial fibrosis was prominent in 19 patients and was associated with cellular hypertrophy, elevation of RVEDP, and increased age of the patients. Degenerative changes (myofibrillar lysis, abnormally small mitochondria, myelin figure formation, and proliferation of sarcoplasmic reticulum in cardiac muscle cells ocurred in six patients and correlated with increased age, decreased PAO2, and elevated RVEDP. Mitochondria containing glycogen deposits were present in 17 patients, most of whom had decreased PAO2. The variability of morphologic manifestations of chronic cardiac hypertrophy and the relationships of hypertrophic changes to orientation abnormalities and degenerative alterations are discussed.


Agranulocytosis caused by Chinese herbal medicines. Dangers of medications containing aminopyrine and phenylbutazone.

Four non-Chinese patients, middle-aged or older, developed agranuloctyosis while taking Chinese herbal medicines for relief of arthritis and back pain. All four developed life-threatening infections with bacterial sepsis; one died. The herbal medicines were shown to contain substantial amounts of undeclared aminopyrine and phenylbutazone, drugs that are well-known causes of agranulocytosis. These Chinese herbal medicines are widely available over the counter throughout the United States.


Hypoplastic enamel, onycholysis, and hypohidrosis inherited as an autosomal dominant trait. A review of ectodermal dysplasia syndromes.

A syndrome consisting of a hypocalcified-hypoplastic enamel, onycholysis with subungual hyperkeratosis, seborrheic dermatitis of the scalp, and hypofunction of the sweat glands with rough dry skin is inherited as an autosomal dominant trait in a kindred of Caucasian ancestry.


Recent developments in gastrointestinal endoscopy.

Endoscopic findings can be extremely valuable in directing or altering specific treatment. Endoscopy also has therapeutic applications, such as removal of polyps (gastric or colonic), coagulation of bleeding sites in cases of upper gastrointestinal bleeding, and the removal of foreign objects from the gastrointestinal tract. Laparoscopy is an easily performed procedure with minimal risk. On of its greatest values is in investigating diseases of the liver. Coloscopy has many uses, including evaluation of equivocal x-ray findings and histologic confirmation of cancer. Endoscopic retrograde cholangiopancreatography (ERCP) is a new, highly sophisticated procedure that offers a major advantage in investigating pancreatic disease and evaluating jaundice.


Transplantation of islets of Langerhans in diabetic rhesus monkeys.

Islets of Langerhans from unrelated donor rhesus monkeys were transplanted into the portal vein of five rhesus monkeys which had been made diabetic by partial pancreatectomy and Streptozotocin. There was definite improvement of the diabetic state with an increase in the mean KT1/2 from 0.71 to 1.52 percent per minute. The islets were isolated by a more efficient digestion-filtration process than previously had been described. This process has allowed, for the first time, successful isolation of large masses of islets permitting islet transplants in subhuman primates.


Survival for 18 days with a Jarvik-type artificial heart.

This is a report of an experiment wherein a calf had its natural heart replaced with an artificial heart and survived for 18 days and 20 hours. All measured physiologic parameters remained normal until the fourteenth day. Thereafter a gradual persistent rise in venous pressure and signs of a decreased cardiac output occurred. However, the animal outwardly appeared normal until the eighteenth day. During the nineteenth day it became comatose and was killed. At autopsy large thrombi were found in both atria, impairing ventricular filling, resulting in venous congestion and diminished cardiac output. This extended survival time and our ability to understand and eliminate the problems associated with artificial heart implantation give support to our hope that artificial hearts for man will be possible in the not too distant future.


Femorofemoral grafts for unilateral occlusion of aortic bifurcation grafts.

Femorofemoral bypass grafts were performed in 10 patients who developed thrombosis of one of the limbs of previously placed aortoiliac or aortofemoral bifurcation grafts. There were no operative deaths or significant postoperative morbidity, and no amputations had to be performed following the bypass. Nine of the 10 patients have patent grafts from 5 to 70 months (average 33 months) following operation. Of these nine, eight are asymptomatic and one has mild claudication on the side of the unoccluded limb. Because of its simplicity, low operative risk, and encouraging late success rate, we feel that femorofemoral bypass grafting for late unilateral occlusion of a prosthetic bifurcation graft is the procedure of choice.


The effect of shock on the inflammatory response. A reevaluation of the role of platelets in the active arthus reaction.

The active Arthus reaction can be inhibited by hypovolemic shock or the infusion of catecholamines. A reevalution of previous work with platelet antiserum indicates that shock rather than thrombocytopenia was responsible for preventing the active Arthus reaction. Immunofluorescent studies of the inhibited Arthus sites reveal that immune precipitates are not present in the extravascular tissues. Since leukocyte aggregates can be seen within venules at the inhibited sites, and they phagocytize BSA-anti-BSA complexes, their failure to migrate out of the vessels is due to the absence of complexes in the extravascular spaces. (Am J Pathol 78:159-170, 1975)


Ultrastructural and histochemical study of the adrenal medulla in normal and cold-stressed Syrian hamsters.

The effect of 24 and 48 hours' cold stress on the hamsters' adrenomedullary follicles and on the medullary ATPase activity was studied by light and electron microscopy. Only norepinephrine cells were depleted after this stress, and exocytosis seemed to be the mechanism involved in the release of catecholamine. Follicles containing these cells expanded and their lumina became narrow. A few other cellular and follicular changes also occurred and are described. ATPase activity was apparent in control organs along the endothelial linings, in neural elements and macrophages, and in approximately 40% of the linings of follicular lumina. Cold stress did not alter this pattern. These results have been compared with previous findings and the possible functions of the follicular lumina are discussed. It is concluded that they are unlikely sites for catecholamine storage or release.


Glycosaminoglycans of brain during development.

The concentration of hyaluronic acid, chondroitin sulfate, and heparan sulfate was measured in rat brain at 2-day intervals from birth to 1 month of age, and in 40-day-old and adult animals. The levels of all three glycosaminoglycans increased after birth to reach a peak at 7 days after which they declined steadily, attaining by 30 days concentrations within 10% of those present in adult brain. The greatest change was seen in hyaluronic acid, which decreased by 50% in 3 days, and declined to adult levels (28% of the peak concentration) by 18 days of age. Only heparan sulfate showed a significant change in metabolic activity during development (a fourfold increase in the relative specific activity of glucosamine), most of which occurred after 1 week of age. In 7-day-old rats almost 90% of the hyaluronic acid in brain is extractable by water alone, as compared to only 15% in adult animals, and this large amount of soluble hyaluronic acid in young rat brain is relatively inactive metabolically. On the basis of our data we propose that the higher amounts of hyaluronic acid found in very young brain may be responsible for the higher water content of brain at these ages, and that the hydrated hyaluronic acid serves as a matrix through which neuronal migration and differentiation may take place during early brain development.


Hepatitis B surface antigen and its subtypes in an institution for the mentally retarded.

The prevalence of hepatitis B surface antigen (HBsAg) in 155 patients with Down's syndrome (DS) and 209 with other types of mental retardation (OMR) at Huronia Regional Centre, Orillia, Ontario was 34.8 and 5.3%, respectively. There was no significant difference in prevalence between males and females in either group of patients. In 75 matched pairs (DS-OMR) the HBsAg prevalence was 45% in DS and 8.3% in OMR males; in females 40% of those with DS were HBsAg-positive, whereas all the OMR residents were negative. The prevalence of HBsAg in both DS and OMR  groups was higher in those admitted in early childhood and in those who had resided in the institution for more than 10 years. In all 54 HBsAg-positive DS patients the antigen subtype was ad. Among the 11 HBsAg-positive OMR patients the subtype was ad in 10 cases and ay in 1.


Genetic characterization of adenine-3 mutants induced by 4-nitroquinoline 1-oxide and 4-hydroxyaminoquinoline 1-oxide in Neurospora crassa.

Specific locus mutations induced by the chemical carcinogens, 4-nitroquinoline 1-oxide (4NQO) and 4-hydroxyaminoquinoline 1-oxide (4HAQO), have been characterized to obtain a presumptive identification of the genetic alterations at the molecular level. One hundred eighty-four 4NQO-induced and 219 4HAQO-induced ad-3 mutants of Neurospora crassa obtained in previous studies were studied with a series of genetic tests that permits determination of their genotype and the frequencies of point mutations and multilocus deletions. These tests have shown that the spectrum of ad-3 mutations among 4NQO-induced mutants is similar to that of 4HAQO-induced mutants. None of the 4NQO- or 4HAQO-induced mutants is a multilocus deletion mutant. The ratio of ad-3A to ad-3B mutants is the same in the two samples, as well as the frequencies of complementing ad-3B mutants. These data suggest, then, that the mechanism of mutation induction by 4NQO in N. crassa is identical to that of 4HAQO. It is not clear, however, whether 4NQO is mutagenic per se or reduction of 4NQO to 4HAQO is the first step involved in the mutagenesis of this compound in Neurospora. The heterotaryon tests have shown that the relatively high frequencies of 4NQO- or 4HAQO-induced ad-3B mutants show allelic complementation and that most of the complementing ad-3B mutants (74% of 4NQO induced and 71% of 4HAQO induced) have nonpolarized complementation patterns. From this we conclude that both agents induce predominantly base-pair substitution mutations in N. crassa. The results are in agreement with our other studies which show that potent chemical carcinogens induce predominantly base-pair substitution mutations in N. crassa.


Different mechanisms in testosterone action on glycogen metabolism in rat perineal and skeletal muscles.

Testosterone affects glycogen levels in perineal and skeletal muscles by two distinct mechanisms. Both of them show similar sensitivity to androgens (0.1 mg/rat/day of testosterone being effective) and to antiandrogen administration. However, they differ because of the pattern of glycogen increase (early after the androgen injection in the perineal muscles; slowly and with a linear function of time in the skeletal muscles), and because of the different sensitivities to adrenolectomy, diabetes and hypophysectomy. Also, the biochemical changes induced by testosterone in muscles differ. The rate of sugar uptake and phosphorylation is increased in the perineal muscle only; the rate of glucose incorporation into glycogen is increased in the perineal but depressed in the skeletal muscles. Therefore, in the former case glycogen accumulation depends mainly on increased synthesis; in the latter, it is probably the result of a glycogen sparing effect.


Effects of increased ambient pressure and nitrogen on man's monosynaptic reflexes.

Neurological signs during dives may result from altered excitability of central neurons. The present study assesses the effect of an increase in pressure from 1 to 3 ATA on the excitability of muscle spindles and alpha motoneurons by comparing the EMG amplitudes of the mechanically and electrically elicited monosynaptic reflexes of the gastrocnemius-soleus muscle in 10 normal adults breathing a normoxic oxygen-nitrogen gas mixture. At the surface the amplitude of the electrically elicited H response was matched to that of the mechanically elicited Achilles tendon reflex (ATR), but at depth these amplitudes became significantly different. In every subject the amplitude of the ATR, which depends upon the excitability of both muscle spindles and the alpha motoneurons, was reduced on an average of 38% (with a range of 12-75%). The H response bypasses the muscle spindles and hence, depends primarily upon alpha motoneuron excitability. Its amplitude was unaltered in four, reduced in three, and increased in three subjects. Since the ATR was always depressed despite the direction of change in the H response, we have concluded that an increase in ambient pressure (i.e., pressure per se, or nitrogen, or both) must have decreased the responsiveness of muscle spindles to the tendon tap via a reduction in fusimotor activity.


Influences of clinical factors on marginal adaptation and residual mercury content of amalgam.

Clinical factors affecting residual mercury and marginal adaptations of amalgam restorations in a private practice environment were investigated. Findings, converted to ridit values, indicated that influencing factors are the training level of the dental assistants, type of amalgamator, accuracy of the timing device, and method of condensation.


Parotid saliva enzymes in Down's syndrome.

The parotid saliva in persons with Down's syndrome was analyzed for three enzymes: acid phosphatase, nonspecific esterase, and amylase. The results have shown a statistically significant elevation of esterase activity in persons with Down's syndrome whereas no statistical differences were observed with the other enzymes. The current investigation has provided further insight into salivary gland metabolism and may have yielded some information pertaining to the genetic control of the processes regulating the electrolyte concentration of human saliva.


Patent ductus arteriosus complicating the respiratory distress syndrome in preterm infants.

In 46 preterm infants with RDS the patency of the ductus arteriosus was established by single film aortography or by clinical diagnosis and confirmation at surgery. The estimated left-to-right shunt through the PDA by aortogram correlated well with the heart size and the clinical diagnosis of heart failure. In 14 infants massive cardiomegaly and heart failure with a PDA occurred before the appearance of a heart murmur. Twelve infants had severe RDS and 34 had mild or moderate RDS. Massive cardiomegaly occurred significantly earlier in infants with severe RDS. It is suggested that ductal ligation is indicated when an infant with massive cardiomegaly requires IPPV and whose aortagram shows that all of the contrast material is in the pulmonary arteries and none in the aortic arch. A heart murmur may or may not be present.


Incidental ectopic pregnancy.

Three cases of incidental ectopic pregnancy are described in which the patients were found to have unsuspected ectopic pregnancy when operated for an elective gynecologic procedure.


Epidemiology of burns. The burn-prone patient.

Predisposition to burning was identified by history, by conversation with the family, or by physical examination. Factors that decreased the patient's ability to respond appropriately were considered as predisposing. A consecutive series of 155 hospitalized, burned, adult patients was reviewed. Approximately 50 per cent of the entire series showed predisposition to burning; among the more severe burns, this fraction was 57 percent. Among women, predisposition was more prominent in all categories than among men. Among women, those predisposed to burning had larger burns and a greater likelihood of dying. Alcoholism led the list of predisposing factors, with senility, psychiatric disorders, and neurological disease following in order. The patient's own home was usually the site of the burn in those predisposed, with the initial ignition being in the patient's hair or clothing, the mattress, bedclothes, or an overstuffed chair. All of the burns occurring in hospital or mental institution patients were among those predisposed to burning.


Surgical aspects of regional myocardial blood flow and myocardial pressure.

The surgical technique of cardiopulmonary bypass with either an empty beating or an empty fibrillating ventricle produces marked changes in the regional blood flow and oxygen demand of the left ventricle. This paper describes the changes which occurred in the regional perfusion of both the normal and the hypertrophied left ventricle during these conditions and relates them to the known changes in oxygen demand. It also correlates the changes in flow with the measurable changes in myocardial tissue pressure-systolic when the heart is beating and continuous when fibrillating. The various types of filbrillation had identical effects on both regional tissue pressure and regional flow. The subendocardial blood supply was adequate or more than adequate under each of these conditions so long as the coronary perfusion pressure was maintained at an adequate level. A low perfusion pressure during ventricular fibrillation of any type led to a marked reduction in flow to the subendocardial portion of the left ventricle: The presence of ventricular hypertrophy accentuated this danger.


Hypoventilation secondary to chronic upper airway obstruction in childhood.

A 6-year-old child manifested symptoms and signs of alveolar hypoventilation and signs of cor pulmonale caused by obstruction of the upper airway. These symptoms and signs disappeared after tonsillectomy and adenoidectomy. The relationship of upper airway obstruction to hypoventilation and cor pulmonale is discussed in the hope of renewing interest in this problem and alerting physicians to think of this possiblity early in the evaluation of such patients.


Effects of streptozotocin on glucose metabolism, insulin response, and adiposity in ob/ob mice.

To determine whether hyperglycemia in the obese hyperglycemic (ob/ob) mouse is related to enhanced activity of the pancreatic beta cell, streptozotocin (175 mg/kg) was injected into lean and ob/ob mice at 8 wk of age. The influence of this injection upon glucose metabolism, adipose cellularity, pancreatic morphology and immunoreactive insulin (IRI) release from isolated pancreatic islets was measured. The plasma glucose levels before and after an oral glucose load were elevated in lean and decreased in ob/ob mice 2 wk after treatment with streptozotocin. By 5 wk after this treatment, a reduced pancreatic islet size, beta cell number and a decreased pancreatic islet IRI release were present in both lean and ob/ob mice. At this time, plasma glucose was still elevated in lean, but depressed in ob/ob mice and the insulin responsiveness in muscle and adipocytes was unchanged. Hyperglycemia abates in the ob/ob mouse as hypersecretion of insulin is diminished, but these observations may not be directly related, since streptozotocin affects key metabolic activities of the livers as well as the pancreatic beta cell. The progression of obesity and status of adipose cellularity are not directly related to hyper-insulinemia, since they are not altered following streptozotocin treatment.


The chemical composition of idiopathic nonarteriosclerotic cerebral calcifications.

Calculi from a case of cerebral idiopathic nonarteriosclerotic calcification (Fahr's disease) were examined. The stone consists of hydroxyapatite and possesses a typical structure: the calcification process seems to be initiated by the formation of small round bodies that are cemented to each other to form the final stone. Calcified vessels are also present, but seem to be a secondary effect. From a comparison with other calcifications, it is concluded that no pathologic significance should be attached to the relatively high levels of trace metals such as zinc, iron, copper, magnesium, lead, and others, with the possible exception of manganese. The organic matrix of the stone contains large quantities of protein. On hydrolysis of this fraction, an important unidentified ninhydrin-positive peak was found. No mucopolysaccharides were found.


Fetal monitoring: is it worth it?

The current trend to fewer births per family, a lower birth rate, and a national commitment to reduce mental retardation calls for evaluation of methods which will optimize perinatal outcome individually and in a collective sense. Based on the assumption that continuous fetal heart rate monitoring during labor can reduce perinatal mortality and morbidity by 50%, a cost analysis is constructed. The cost for total monitoring of 3000 deliveries per year is compared with the potential savings due to prevention of one-half of the mental retardation that would develop from the same group were they not monitored.


T-cell reconstitution by thymus transplantation and transfer factor in severe combined immunodeficiency.

Reconstitution of cell-mediated immunity was achieved in a 5-month old female infant with severe combined immunodeficiency by fetal thymus transplant given simultaneously with two units of transfer factor. Thymus was obtained from a 15-week gestational age male fetus, and the two units of transfer factor from the lymphocytes of 500 ml of peripheral blood. Three weeks after transplantation, two nel HL-A antigens were detected on the infant's lymphocytes, one of which was present in the mother of the thymus donor; at the same time, some of the infant's own HL-A antigens disappeared. Thereafter, the percent of rosette-forming cells (T-cells) increased and the in vitro response to phytohemagglutinin and allogeneic lymphocytes became normal, and delayed skin tests became positive. Karyotyping of peripheral blood lymphocytes posttransplantation reveals an XY (male) pattern. These results suggest lymphocyte re-population as a result of the thymus-transfer factor therapy. Five months after transplantation, the patient has normal cellular immunity but persistent hypogammaglobulinemia. She is free of infection and growing normally on gammaglobulin injections.


The incidence and properties of beta axons to muscle spindles in the cat hind limb.

The distribution of beta axons to muscle spindles in the tenuissimus and abductor digiti quinti medius (A.D.Q.M.) muscles of the hind limb of the cat was determined by testing the action of single motor axons, capable of producing extrafusal contraction, isolated in the ventral spinal roots on the discharges of individual muscle spindle primary sensory endings recorded in the dorsal spinal roots. The proportion of spindles with beta innervation was 41% in A.D.Q.M. and 30% in tenuissimus. The proportion of fast motor axons that were beta axons was 28% in the A.D.Q.M. and 11% in tenuissimus; usually each beta axon innervated a single spindle while no spindle received more than two beta axons. The beta axons were dynamic in nature and those to any one muscle tended to have slightly lower conduction velocities than the alpha axons though some overlap did occur. The extent to which beta axons can account for the fact that in isolated spindles axons selective to either nuclear bag or nuclear chain fibres are found in about equal proportions whereas a ratio of three static to one dynamic gamma axons is found electrophysiologically is discussed. An explanation for the low incidence of beta innervation previously found electrophysiologically and the considerably higher incidence found histologically is given.


Factors contributing to the development of low back pain in industrial workers.

A survey to elicit information on factors related to the causes of low back pain in industrial workers was made. Questionnaires were sent to 1000 workers in various industrial occupations including hospital workers, and 509 responses were received. In this population, back injuries were more frequent among women, as were absences for other illness.  Most employees sustaining back injury subsequently returned to their original job. This survey serves as a pilot study indicating areas from which objective results may be obtained and directions of improvement in future questionnaires.


Preparation of mixtures of humidified air with CO, SO2, NO2, NH3, NH2CH3, Cl2, and HCl to measure respirator cartridge and canister service life.

Four systems have been fabricated to measure the effective service life of respirator cartridges and canisters. The four systems employ carbon monoxide, sulfur dioxide/nitrogen dioxide, ammonia/methylamine, and chlorine/hydrogen chloride as contaminants. Each system produces test concentrations in the low percentage range (typically 0.05 to 3.0%) at flow rates of 32 and 64 liters/min and at relative humidities between 20 and 95%. Suitable anlyzers have been provided to measure the downstream concentration from 1 to 500 ppm as a function of time. Holders have been designed to accommodate the wide size variation of commercially available cartridges and canisters.


Train-of-four nerve stimulation in the management of prolonged neuromuscular blockade following succinylcholine.

Four patients, all possessing an atypical form of plasma cholinesterase, developed prolonged paralysis following succinylcholine administration. The clinical management of all four cases was facilitated by monitoring the train-of-four stimulus. All patients showed marked "fade" of the train-of-four ratio, the initial ratios of the fourth to the first twitches being 50 per cent or less, indicating variable degrees of nondepolarizing neuromuscular blockade. Reversal of paralysis with anticholinesterase agents was completely successful in three cases, but only partially effective in the fourth because of the probable presence of a mixture of both depolarizing block and nondepolarizing block. In such a situation, caution in the interpretation of the train-of-four ratio is necessary, since this test measures only the nondepolarizing component of the block. Whether or not reversal with anticholinesterase drugs is attempted, clinical estimates of neuromuscular function, such as head lift, vital capacity, and inspiratory force, must be carefully correlated with train-of-four values. If reversal is attempted, the brief action of edrophonium provides a useful clinical trial.


On acid glycosaminoglycans (mucopolysaccharides) in pleural effusion.

The concentration of acid glycosaminoglycans (mucopolysaccharides) in pleural fluid was found to be in the range of 4.0 to 60.3 mug per ml. By chromatographic analysis and by electrophoresis of the eluates, in combination with enzymatic digestion, it was found that pleural fluid contained protein-free hyaluronic acid, protein-bound hyaluronic acid, undersulfated chondroitin sulfate A(C), chondroitin sulfate A(C), protein-bound chondroitin sulfate A(C), and dermatan sulfate. The composition of acid glycosaminoglycans in pleural fluid seems to reflect the metabolism of the pleural cavity.


Isolation, subunit structure, and proteolytic modification of bovine factor VIII.

A new method has been described for the isolation of factor VIII. The method results in a high yield of factor VIII that is homogeneous by several different criteria. The purified protein is very stable and is not dissociated in the presence of 1 M NaCl or 0.25 M CaCl2. The highly purified protein is readily activated and inactivated by various proteolytic enzymes, such as thrombin, plasmin, and trypsin. The molecular events that lead to the activation reaction, however, have not been established.


Molecular structural studies of human factor VIII.

Neither normal nor hemophilic factor VIII protein enters a 5% sosium dodecyl sulfate gel; on reduction, however, a single 195 000-molecular-weight peptide is observed. Hemophilic and normal factor VIII contain carbohydrate and appear identical in subunit molecular weight, electrical charge, and major antigenic determinants. Thrombin activation and inactivation of factor VIII does not detectably change the subunit molecular weight. Trypsin causes similar activity changes and obviously cleaves the factor VIII subunit. Human plasmin destroys factor VIII procoagulant activity and degrades the factor VIII subunit to 103 000-, 88 000-, and 17 000-molecular-weight peptides. Both normal and hemophilic factor VIII as well as thrombin-inactivated factor VIII support ristocetin-induced platelet aggregation. Purified factor VIII chromatographed on 4% agarose in 1.0 M sodium chloride shows no dissociation of the procoagulant activity from the void volume protein. Gel chromatography on 4% agarose in 0.25 M calcium chloride results in a procoagulant activity peak removed from the void volume protein; both peaks contain protein which does not enter a 5% SDS gel, but on reduction a 195 000-molecular-weight subunit band is observed for each. Both the void volume protein peak and the procoagulant activity peak from the 0.25 M calcium chloride-agarose gel column support ristocetin-induced platelet aggregation. After removal of calcium, a small amount of procoagulant activity is present only in the void volume peak. These data suggest that both the procoagulant and von Willebrand activities are on the same molecule. Thus our previous conclusion remains the same: human factor VIII is a large glycoprotein composed of identical 195 000-molecular-weight subunits jointed by disulfide bonds and is responsible for both antihemophilic and von Willebrand activities in human plasma.


Human tissue reaction to sutures.

Tissue reaction to sutures was studied in 666 specimens obtained from patients from one day to 23 years after operation. Reaction to catgut depends on the stage of absorption and is mainly histocytic in type. Nonabsorbable sutures are encapsulated by a rim of connective tissue, while near the suture histocytes, giant cells and lymphocytes are found. This is most marked with silk and cotton, less so with Dacron, and least with nylon and wire. Tissue infiltration into the suture interstics is variable. The reactions resemble the findings in experimental animals.


Managing the complications of plasma cell myeloma.

Management of some diverse complications of plasma cell myeloma is reviewed with respect to prevention when possible and prompt treatment when necessary. A series of 102 patients from the Duke University Medical Center was surveyed to ascertain the approximate frequency with which renal failure, hypercalcemia, infection, hyperviscosity syndrome, and neurologic disorders occur. Selected patient studies and additional data from the literature emphasize aspects of these complications amenable to therapy aside from that directed at plasma cell growth.


Idiopathic (asymptomatic) monoclonal gammopathies.

Asymptomatic forms of monoclonal gammopathies (MG) are recognized with increasing frequency; their recognition and differentiation from the symptomatic forms of MG appear imperative, since the therapeutic approaches are different. Available clinical and laboratory indexes lack specificity required for useful and practical discrimination; presently, we must still rely on the timecourse monitoring of such laboratory values as hemoglobin levels, M-protein concentrations, and presence of Bence Jones proteins. Elucidation of histocompatibility A and W antigenic profiles, as well as the functions and kinetics of B-lymphocytes from such patients, appear most promising. Evidence of the causative role of extrinsic and intrinsic antigenic stimulation in MG production is increasing; segregation into two distinct concentration ranges of M-proteins in the asymptomatic and symptomatic groups suggests two control levels of the expression of immune response (Ir) genes, due to partial or complete derepression of the latent Ir gene function, reflecting "partial" (asymptomatic, benign MG) and "complete" (symptomatic, malignant MG) monoclonal immune responders.


Reticulum cell sarcoma of the heart.

The association of a primary cardiac lymphoma in a 53-year-old man with a previously documented myocardial infraction was found. The patient was initially thought to have a recurrent myocardial infraction, but failed to respond to aggressive treatment. The enigma of the clinical course was solved at autopsy by the identification of a primary reticulum cell sarcoma of the heart.


Actin-activated ATPase from human erythrocytes.

A fibrillar protein complex, possessing ouabain-insensitive Ca2+-ATPase activity was isolated from human erythrocyte membranes by using a low ionic strength extraction procedure. Mg2+-ATPase activity was revealed upon addition of rabbit skeletal muscle actin, thus demonstrating the presence of a myosin-like protein in the crude extract of the erythrocyte membrane. Upon sodium dodecylsulfate gel electrophoresis, the extract showed mainly the doublet of subunit molecular weight bands of 230 000 and 210 000, and more than 10 faster moving bands. Gel filtration of the erythrocyte membrane extract on Sepharose 4B furnished 4 fractions. Fraction I, containing the doublet and 80 000, 60 000 and 46 000 subunit molecular weight bands was 5-fold purified with respect to Ca2+-ATPase activity, but was devoid of actin-activated Mg2+-ATPase activity. Fraction II, containing only the doublet, was devoid of Ca2+ and actin-activated Mg2+-ATPase activity. The 210 000 subunit molecular weight protein could be phosphorylated in the presence of Mg2+ in the crude extract and Fraction I but not in Fraction II.


Activation of rabbit brain microsomal (Na+ plus K+)-dependent ATPase by a leukocytic product.

The properties of a (Na+ plus K+)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) activator contained in leukocytic extracts was investigated. Intact polymorphonuclear leukocytes release the activator in a time- and temperature-dependent process. It is non-dialyzable through cellophane; inactivated by protease, trypsin, or phenol; contains essential sulfhydryl groups; and is heat and acid labile. Treatment of ATPase with the activator and subsequent removable of the activator from mixtures did not reverse the ATPase activation.


The hydration of proteoglycans of bovine cornea.

The water sorptive and retentive capacities of three corneal proteoglycans with different keratan sulfate/chondroitin-4-sulfate compositions were investigated. The calcium salt of a predominantly keratan sulfate containing proteoglycan had hydration properties similar to that of calcium keratan sulfate. The proteoglycan containing predominantly calcium chondroitin-4-sulfate side chains sorbed water to a greater extent than pure calcium chondroitin-4-sulfate but its retentive power was somewhat less. The proteoglycan containing about twice as much keratan sulfate as chondroitin-4-sulfate, on a dissaccharidic molar basis and had hydration properties which were closer to the behavior of chondroitin-4-sulfate than keratan sulfate. The results are discussed in terms of structure and polymer interaction in the proteoglycan matrices.


Effects of physical training on several glycolytic enzymes in rat heart.

In response to a program of daily swimming for 16 weeks, the activities of pyruvate kinase and lactate dehydrogenase increased significantly in the hearts of young male rats. The isozyme composition  in M of cardial lactate dehydrogenase increased from 28.5 to 32.7% in the trained animals. Phosphofructokinase activity and glycogen content were unchanged. The hearts of the exercising animals were 28% heavier than those of sedentary paired weight controls.


Changes in enzyme pattern of Ehrlich ascites tumor cells following serial cultivation in media with increased (hypertonic) NaCl content.

Adaptation of Ehrlich ascites tumor cells to serial cultivation in media with progressively elevated (hypertonic) NaCl content ("high NaCl"-tolerant cells) has resulted in progressive increases of the cellular activities of NAD-dependent glycerol-3-phosphate dehydrogenase (EC 1.1.1.8), NAD-dependent malate dehydrogenase (EC 1.1.1.37), glutamate--oxalacetate transaminase (EC 2.6.1.1), NAD (P)-dependent glutamate dehydrogenase (EC 1.4.1.3), NADP-dependent isocitrate dehydrogenase (EC 1.1.1.42). The activities of glutamate-pyruvate transaminase (EC 2.6.1.2.) and of glycolytic enzymes as phospho-fructokinase (EC 2.7.1.11), glyceraldehydephosphate dehydrogenase (EC 1.2.1.12) and lactate dehydrogenase (EC 1.1.1.27) were only slightly and not in progressive manner (in response to the progressive increase of the environmental NaCl concentration) affected. These changes are discussed with respect to a metabolic pattern of these "high NaCl"-tolerant cells which is compatible with increased energy requirements, especially for active cation transport. It is suggested that these increased cellular enzyme activities reflect an increased transfer of reducing equivalents across mitochondrial membranes (via the "glycerophosphate cycle and the malate-aspartate shuttle") and possibly a stimulated lipid metabolism. These alterations in the level of enzyme activities must be regarded asan adaptive cellular response to the "high NaCl" environment, since readaptation to growth in regular isotonic media resulted in a reversion to the enzyme pattern characteristic of the parent cells.


Regulation of the amount and of the activity of phosphofructokinases and pyruvate kinases in Escherichia coli.

Two isozymes of fructose-6-phosphate kinase and two isozymes of pyruvate kinase have been detected in Escherichia coli under a wide variety of growth conditions. Their kinetic behavior has been characteriized with respect to different effectors and substrates. The conclusions reached on one hand by Malcovati and Kornberg (Biochim. Biophys. Acta (1969) 178, 420-423), on the other hand by Fraenkel, Kotlarz and Buc (J. Biol. Chem. (1973) 248, 4865-4866) have been found to be true in aerobiosis as well as in anaerobiosis. The biosynthesis of the four proteins is sensitive to the nature of the carbon sources as well as to the shift from aerobic to anaerobic conditions. Kinetics of depression after a shift to anaerobiosis have been followed and found to be of the order of the doubling time.


[The mechanism of blood cell sedimentation. XVIII. Sedimentation effect of fibrinogen plasminolysis products].

Various high molecular weight plasmin degradation products of fibrinogen were isolated by chromatographic procedures and investigated to what extent they influence the sedimentation rate of erythrocytes in heparinized serum. Among the early plasminolysis products Fragment X accelerated the sedimentation rate considerably although it was less effective than fibrinogen. Fragment Y showed a weaker but clearly demonstrable agglomerine activity. The late plasminolysis products D and E were ineffective, if applied alone and in concentrations equivalent to the fibrinogen content of plasma. However, they promoted the sedimentation effect of fibrinogen. If present in considerably higher concentrations are Fragments D and E, in absence of fibrinogen, also accelerated the sedimentation rate of erythrocytes significantly. A mixture of D and E was not more effective than the single compounds.


Defective antibody response to bacteriophage phichi 174 in Down syndrome.

Antibody responses to bacteriophage phichi 174 were studied in 17 institutionalized patients with trisomy 21 and in six mentally retarded control patients with normal karyotype. Primary antibody response was significantly impaired in 11 of the 17 patients. Secondary immune response was normal in one, moderately impaired in seven, and very low in nine patients. Tertiary immunization further differentiated the two groups: those with moderately impaired secondary immune responses developed normal serum titers of predominantly IgG antibody; patients with low secondary immune responses had extemely impaired tertiary immune responses consisting mainly of serum IgM antibody.


Alopecia areata, autoimmunity, and Down's syndrome.

Alopecia areata occurs more often in Down's syndrome than would be expected by chance, sixty cases being found among 1000 patients with this syndrome compared with one case among 1000 subnormal controls.  Because  alopecia areata is associated with some organ-specific autoimmune disease and thyroid antibodies are often found in Down's syndrome sera from affected patients were examined for the presence of fluorescent autoantibodies.  Antibodies against thyroid components tended to be present in female mongols with alopecia areata in comparison with females in a normal population but not in male mongols.  Futhermore, eight out of 23 female mongols (35%) with alopecia areata had antibodies against thyroid components compared with two out of 23 female mongols (9%) without alopecia areata.


Determination of sensitivity of Mycoplasma hyosynoviae to tylosin and selected antibacterial drugs by a microtiter technique.

A microtiter technique was used for determination of the sensitivity of Mycoplasma hyosynoviae to antibiotics and other drugs. Use of a biphasic agar-broth medium in microtiter plates allowed direct visualization of growth. Results were more reproducible with this system than when broth alone was used and evaluation based on color change was required. Attempts to adapt the test for use with Mycoplasma hyorhinis were not successful. Minimal inhibitory concentrations of 12 drugs and drug combinations for 12 strains of M. hyosynoviae are presented. Drugs with the lowest minimal inhibitory concentrations were tylosin (0.37 mcg/ml)and lincomycin (0.88 mcg/ml), both of which have been used for treatment and control of M. hyosynoviae arthritis. Comparison of the minimal inhibitory concentrations of tylosin for 43 isolates of M. hyosynoviae obtained in 1959 and 1960 and from 1966 through 1971 indicated the possibilty of decreasing sensitivity to the drug although differences between recent isolates and earlier ones were not statistically significant.


Streptozotocin therapy in 22 cancer patients.

Twenty-two cancer patients were treated with streptozotocin (SZN) in six weekly intravenous doses of 1.0-1.5 g/m2. The results of the initial courses of therapy include 3 complete and 2 partial responses, 11 patients with no change, 4 with progression, and 2 deaths due to tumor progression. Three additional deaths also due to tumor progression occurred in previously responding patients. All responses were in patients with pancreatic tumor. Toxicity consisted of transient proteinuria in 11/15 patients, transient azotemia in 11/18 patients, marked reduction of creatinine clearance in 1 patient, burning pain at site of injection, nausea, and vomiting in 20/22 patients, change of FBS from pretherapy to post-therapy of at least 10 mg/100 ml in 11/17 patients, significantly decreased platelet count in 1/22 patients, decreased Hgb in 2/22 patients, and duodenal ulcer in 2/22 patients. A reduced dosage schedule and combination with other drugs known to be effective in pancreatic tumors deserves further investigations.


Metastatic atypical fibroxanthoma of skin.

A case is presented of postirradiation atypical fibroxanthoma of the skin, metastatic to cervical lymph node, in a young female. Although such skin tumors characteristically have a malignant microscopic appearance, and although they occasionally recur following surgical excision, they have previously been noted for their consistently benign clinical behavior. This is thought to be the second recorded instance of metastasis from an atypical fibroxanthoma of skin.


Familial atrioventricular heart block; an autosomal dominant trait.

A family of 28 individuals spanning four generations was investigated because of a finding of complete heart block in five members and the existence of a low degree of atrioventricular (A-V) heart block in a sixth member. The disorder was characterized by 1) adult onset in all, 2) complete A-V heart block in five and first degree A-V heart block in one, 3) sinus bradycardia in three, 4) atrial fibrillation in five, 5) abnormal QRS complex in five, 6) ventricular tachycardia in three, 7) left ventricular enlargement in all, and 8) mitral insufficiency in five. Proximal location of the A-V heart block was suggested by the fact that atropine caused acceleration of the ventricular rate and by the presence of a His bundle potential preceding the QRS complexes. Involvement of the distal conducting system was indicated by the widened QRS complex and a prolonged H-V interval. Pathologic examination in one case showed extensive sinus node fibrosis and interruption of the A-V node-His bundle connection. This disorder is probably due to an autosomal dominant trait.


Genesis of high frequency notching of QRS complexes in an in vivo cardiac model.

High frequency notching of the QRS complex is associated with transmural infarction, cardiomyopathies, and ventricular hypertrophy from any cause. The mechanism producing notching is unknown; but the presence of a discrete anatomic lesion is not an essential feature. The hypothesis that notching was produced by activation across, rather than along, myocardial fibers was investigated by stimulation at 12 points around a clock electrode attached to the epicardium while mapping isoschronous lines in the area activated. All fibers at the subendocardial layer beneath the clock electrode were ligated by a pursestring suture. Propagation direction, as measured by isoschronous maps, produced more notched QRS compleses when the path was across, rather than paralled with, the myocardial fibers. Using grouped data and a 5 times 6 table, notches versus the angle formed between fiber direction and orientation of the direction of travel were shown to be related (P less than 0.001). The hypothesis that cross-fiber activation enhances notching was confirmed. retrograde activation did not increase notching nor did ligation of subendocardial fibers.


Dynamic determinants of letf ventricular diastolic pressure-volume relations in man.

Left ventricular (LV) diastolic pressure (P), volume (V), and rate of change of volume (dV/dt) were determined at 16.7 msec intervals in 17 patients (simultaneous micromanometer and single plane volume angiography). Four patients had mitral stenosis with atrial fibrillation and 13 patients (three normal, two congestive cardiomyophathy, three LV hypertrophy, and five coronary artery disease) were in normal sinus rhythm. Maximum early diastolic filling rates (max dV/dt) in the normal and cardiomyopathy patients were similar and ranged from 269 to 370 cc/m-2/sec; in coronary artery disease and LV hypertrophy, max dV/dt ranged from 197 to 290 cc/m-2/sec and 213 to 255 cc/m-2/sec respectively; in mitral stenosis, max dV/dt ranged from 215 to 270 cc/m-2 sec. The peak filling rate during atrial systole ranged form 60 to 240 cc/m-2/sec in the 13 patients with sinus rhythm. The instantaneous diastolic P-V data were fit by an exponential equation (P = be-kV) and the P-V relation throughout diastole was represented by the best fit line. The rate constant (k) in the equation was highest in the patient with IHSS and lowest in those with large dilated hearts. In mitral stenosis with atrial fibrillation the fit of the equation to the P-V data appeared better than in the patients with normal sinus rhythm. Peak ventricular filling rate during atrial systole varied directly with LV volume distensibility at the onset of atrial systole (r = 0.64). Data suggest that dynamic mechanical properties of the LV influence the diastolic P-V relations and that pressure "deviations" (deltaP) from the best fit line during atrial systole may be related to viscous drag. In a given ventricle the velocity dependence of deltaP appears to be modified by the volume distensibility of the ventricle. Variable rates of filling may preclude the assumption of an exponential relation between P and V throughout diastole and therefore may limit estimates of diastolic distensibility or compliance which rely on such an assumption.


Heart norepinephrine levels after exercise training in the rat.

Rats exercise trained by swimming one hour daily five days per week for three months developed cardiac hypertrophy. The NE concentration (0.469 mug/g) and total NE content (0.741/mug) of the hypertrophied hearts were not significantly different from levels in hearts of unexercised control rats.


Trifluoroperazine for the symptomatic treatment of chorea.

Ten consecutive patients with chorea of different etiologies were treated with trifluoroperazine, 7 were adults and 3 children; all the patients received symptomatic benefit from the medication, the effective dose ranged from 4 to 16 milligrams. The medication was well tolerated and proved to be effective a long period of time. Biochemical and pathophysiological aspects of chorea and its relations to the medication are discussed.


[Comparison of laparoscopic and scintigraphic findings in chronic hep-titis, liver cirrhosis and liver tumours (author's transl)].

Results of laparoscopy and scintigraphy were compared and contrasted with ultimate clinical diagnosis in 94 patients with chronic hepatitis or liver cirrhosis and 38 with liver tumours. The findings agreed in 77 cases of chronic hepatitis and cirrhosis and 33 of liver tumour. In the remainder either laparoscopy or scintigraphy gave the wrong results. In one case each of cirrhosis and liver metluded that (1) laparoscopy and scintigraphy are methods complementing but not replacing other clinical tests; (2) if diffuse liver disease is suspected clinically the diagnosis can essentially be done only by laparoscopy and selective biopsy or blind liver biopsy but not scintigraphy; (o) if a circumscribed condition is suspected, scintigraphy is among the most important screening tests, but cannot replace laparoscopy, biopsy or angiography for confirming the diagnosis; (4) liver scan is an important method, of little stress to the patient, in following the progress of chronic hepatitis and liver cirrhosis, additional to clinical examination, enzyme tests, laparoscopy and histology.


Structural relationship between "glutamic acid" and "lysine" forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography.

Urokinase digestion of maleinated plasminogen results in cleavage of the single peptide bond Arg-68-Met-69, which is one of the bonds normally cleaved during the first step of the activation procedure. The inactive intermediate compound formed in this way was subjected to NH2-terminal amino acid sequence analysis, which clearly demonstrates the structural relationship between the forms of plasminogen with different NH2-terminal amino acids. It is thus shown that lysine-78 and valine-79 in the "glutamic acid" plasminogen actually are the NH2-terminal amino acids in "lysine" and "valine" plasminogen respectively. The forms with glutamic acid in NH2-terminal position are called plasminogen A, while all other forms lacking the NH2-terminal part of the molecule and which can be activated in a single step are called plasminogen B. By affinity chromatographic studies of the NH2-terminal activation peptide on insolubilized plasminogen B, it was demonstrated that this peptide has specific affinity for plasminogen B. It was also shown that this noncovalent interaction is broken by 6-aminohexanoic acid in two concentration. The tryptic heptapeptide (Ala-Phe-Gln-Tyr-His-Ser-Lys) which occupies the positions number 45 to 51 in the NH2-terminal activation peptide (as well as in the intact plasminogen molecule) is importance for the conformational state of the plasminogen molecule.


[The variations in postion and form of the thoracic part of the thoracic duct. Its skeletal relations].

The postion of the thoracic duct and its relationship to the spine was examined during the course of 100 autopsies on subjects aged 48 to 95 years. Four variants in its position and two variants in shape were found, with a percentage incidence of left-sided 36%, mid-line 20%, oblique 17%, rightsided 6%, bowed 14%, angulated 7M. The midline, oblique and right-sided positions are variants related to age or consitution, left-sided postion is regarded as related to age. The variations in shape are regarded as pathological changes due to displacement of the aorta.


[Contrast retention in retroperitoneal lymph nodes after lymphography; the effect of lymph node abnormalities, radiotherapy and contrast quantity].

The rate of contrast loss from retroperitoneal lymph nodes after lymphography was studied radiologically over a prolonged period in 302 patients. It varied remarkably, even in normal persons who were not receiving any treatment. Lymph nodes empty more quickly if only a small quantity of contrast has been used. Irradiation accelerates contrast transport, not only in the irradiated, but also in the neighbouring, group of nodes. This effect is dose dependent. There is evidence that pathological lymph nodes empty more quickly than normal ones.


[Chylous reflux and chylous ascites in lymphatic dysplasia, with the lymphographic demonstration of mediastinal and retroperitoneal lymphatic cysts].

Two patients with congenital dysplasia of the lymphatic system and with chylous ascites are described. In one 24-year old woman with this rare condition, it was possible to demonstrate for the first time numerous mediastinal lymphatic cysts during lymphangiography. Both patients showed an abnormality of the retroperitoneal lymphatics, consisting of lymphatic dilatation and cysts. In the investigation of chylous ascites, direct lymphangiography must be regarded as a valuable and necessary investigation.


[Atelectatic pseudo-tumours of the lung (round atelectases)].

Following the publication of the paper by Hanke, a round atelectasis was diagnosed on six occasions in five of our patients (two radiologically and pathologically, four radiologically only). On the basis of this material, the radiological features of round atelectases are discussed. Hanke's findings are critically reviewed and a comparison with our material shows a number of differences. The term "atelectatic pseudotumour of the lung" is suggested.


[Radiographs of the thorax in acute myocardial infarction].

Radiographs of the thorax were evaluated in 240 patients during the acute phase following a myocardial infarct. Following the acute infarct, 53% of the patients showed some cardiac enlargement, in a quarter this was marked. Congestive lung changes were found in 53% of patient following the infarct, interstitial pulmonary oedema in 22% and intra alveolar oedema in 9%. Patients with marked cardiac enlargement and those with congestive lung changes showed a bad prognosis, particularly if the congestion did not regress rapidly. Even advanced pulmonary congestion and interstitial oedema may be missed by clinical examination. Radiography of the thorax following acute myocardial infarction is of value in treatment and prognosis.


[Calcification of the left atrium in mitral disease].

Calcification in the wall of the left atrium is a certain sign of rheumatic heart disease; in nearly all cases it is associated with combined mitral valve disease and auricular fibrillation. The cause of the calcification is probably repeated attacks of endocarditis. Similar to the cases described in the literature, four out of five our own patients were in the end-stages of chronic rheumatic heart disease. In four patients there was clinical evidence of mitral valve disease, whereas in the fifth patient, the clinical findings suggested a ventricular septal defect. Calcification in the dilated left atrium indicated the presence of an additional mitral valve abnormality. The typical appearances of atrial calcification are illustrated. The importance of its pre-operative demonstration is discussed on the basis of the relevant literature.


[Laevo-cardiography for the functional evaluation of the ventricle. I. The normal left ventricle].

The possibility of evaluating left ventricular function from lateral laevo-cardiogram has been investigated. A planimetric comparison of the end-diastolic and end-systolic areas of a normal left ventricle shows a 50 to 60% reduction of the systolic area, compared with the diastolic value. Assuming concentric contraction of the left ventricle, the systolic/diastolic reduction in area is proportional to the ejection fraction. This provides a measure for the quantitative evaluation of myocardial function.


[The angiographic demonstration of a primary sarcoma of the pulmonary artery].

Following the findings of a primary sarcoma of the pulmonary artery and its angiographic demonstration, a search was made of the literature for this rare condition. Angiography is usually performed because a pulmonary embolism is suspected. It is best to inject contrast medium into the right atrium or ventricle. If an unusually large defect is demonstrated in the pulmonary artery, a primary malignant neoplasm should be considered in the differential diagnosis, particularly if the mass projects into the outflow tract of the right ventricle.


[Scintigraphic radio-spirometry. Methods and indications].

Scintigraphic radio-spirometry combines conventional spirometry with the advantages of a functional isotope technique, thereby providing a clinically useful method for the study of pulmonary function. The advantage of the method consist principally in the ability to estimate physiological values separately for the two lungs, and also for selective portions of each lung. The apparatus, method and quantitative evaluation of the results are discussed in detail and the method is critically evaluated. Indications for radiospirometry are given.


[67Ga scanning in sarcoidosis].

The value of 67Ga scans in selected cases of sarcoidosis was studied at various stages in order to assess its value as a supplement to clinical, radiological and perfusion studies. During stages I and II, radioactive gallium is taken up by the granulomatous nodes in the hilum and mediastinum and in the interstitial focal pulmonary infiltrates. After complete regression of the hilar and mediastinal lymphadenopathy or of the pulmonary infiltrates, radio-active uptake can no longer be demonstrated. Gallium scans are valuable in showing whether there is active granulomatous infiltration into the lungs when there is known scarring resulting in abnormal perfusion conditions. The gallium scan may indicate that further treatment is desirable. A comparison of serial radiographs and the 67Ga scan provides an indication of the activity of the granulomatous disease; a comparison of the radiological findings and of perfusion scans shows the severity of perfusion abnormalities caused by fibrosis. The investigation has shown that the granulomatous lesions persit even though radiological, clinical and functional investigations have indicated the presence of fibrotic scarring. Radiography, perfusion and gallium scans provide an understanding of the dynamics of this disease.