Combined device for measurement of the duration of the cardiac cycle and stimulation synchronized with the cardiac cycle. A simple device for measuring the momentary cardiac frequency (i.e. a value proportional t-r the length of the time interval between two cardiac contractions) is worked out using a capacitoo transducer consisting of two capacitors and an electron control circuit. The sequence of the charging, indication of the voltage and the discharge of the capacitors is effected by a relay circuit. A random signal characterizing the cardiac cycle can be used as input signal, such as: ECG, pulse signal, signal of the blood pressure transducer, etc. At a definite moment of the cardiac cycle the device produces a synchroimpulse. This makes it possible, by regulating the delay between the triggering and the stimulating impulses of an external stimulator, to realize a regime of synchronized stimulation, i.e., the stimulating impulses to coincide with a preliminarily given moment after the beginning of the cardiac cycle. The output of the device is connected with a standard recording device with sufficiently large input resistance. The transistor electronic circuit is connected to the supply or to an autonomous source. The dimensions of the device are 20 X 12 X 10 cm, its weight is about 2 kg.


Effect of elevated interstitial pressure on the renal cortical hemodynamics. The influence of renal interstitial pressure on the resistance pattern within the superficial cortical vasculature has been investigated from determinations of 1) the glomerular blood flow eith a modified microsphere technique and 2) the intravascular hydrostatic pressures. Interstitial pressure was monitored via a 50 mum PVC-catheter placed into the subcapsular interstitial space. Two conditions were analyzed viz. a) elevation of uretheral pressure to 20 mm Hg and b) venous stasis to 10-15 mm Hg. Both conditions produced an increase in the interstitial pressure from 1-2 mm Hg to about 5 mm Hg as well as an increased hilar lymph flow and protein flow of about the same size. The vascular reactions were different, however. Uretheral stasis (but not the stasis of a single nephron) produced a decreased resistance in the afferent arteriolae with a concomitant increae in the pressures in the glomerular capillaries, and the peritobular capillary network. In contrast, venous stasis produced only small changes in the parameters studied but for the obvious rise in the peritubular capillary pressure. The results suggest that factors other than the interstitial pressure are governing the afferent vascular tone; the tubular wall tension might be one of these factors.


Gastric acid secretion in a teleostean fish: a method for the continous collection of gastric effluence from a swimming fish and its response to histamine and pentagastrin. Gastric acid secretion has been measured in the codfish (Gadus morhua) equipped with a catheter draining the stomach, by titrating the water swallowed by the fish. Unstimulated acid secretion was found to be very low; in most fishes not exceeding 8 mumol H+/kg h. Intramuscular injection of histamine evokes a dose-dependent secretion of gastric acid, with a maximum acid output of 300 mumul/kg h occurring with 10 mg/kg histamine dihydrochloride. No acid response was obtained with pentagastrin.


n the mechanism of inhibitory action of vibrations as studied in a molluscan catch muscle and in vertebrate vascular smooth muscle. In previous studies longitudinal vibrations have been found to reduce active force development in smooth muscle, possibly due to a direct action on the contractile mechanism. In the present experiments the inhibitory effect of vibrations on isometric tension was studied in isolated preparations of the rat portal vein, the rabbit thoracic aorta and the anterior byssus retractor muscle (ABRM) of the Mytilus edulis. The results demonstrate that vibrations of appropriate frequency and amplitude caused prompt inhibition of contractile tension and that complete recovery of active force normally occurred after cessation of vibration in vertebrate smooth muscle as well as during  the phasic contraction of ABRM. However, in the "catch" of the ABRM there was no regain in force following the vibration induced inhibition. The contractile proteins are considered to be a locked state during the catch situation. Thus, this contracted state seems to be released by vibrations. It is therefore concluded that vibrations do interfere with the interrelationship between the myofilaments. This conclusion supports the previously forwarded hypothesis that vibrations act by increasing the rate of detachment of actin-myosin crosslinks in vertebrate smooth muscle.


Rubrospinal control of static and dynamic fusimotor neurones. Rubrospinal effects on about 60 extracellularyl recorded gamma-motoneurones were studied in anesthetized cats. All cells were antidromically identified from various muscle nerves. 23 cells were regarded as dynamic as they were activated from a mesencephalic region previously known to influence selectively muscle spindle dynamic sensitivity. The pattern of rubrospinal influence on static fusimotor neurones to different muscles closely followed that previously demonstrated for alpha-motoneurones with pr edominantly excitation of flexor neurones and excitation or inhibition in equal amounts of extensor cells. Dynamic fusimotor neurones were influenced in a strictly reciprocal manner with excitation of flexor cells and inhibition of extensor cells except for a few neurones which could not be reached from nucleur ruber. Evidence was also obtained indicating that the shortest path from nucleus ruber to static fusimotor neurones involves one interneurone.


Acylation of carnitine and glycerophosphate in suspensions of rat liver mitochondria at varying levels of palmitate and coenzyme A. Rates of acylation of carnitine and glycerophosphate in suspensions of isolated rat liver mitochondria were measured at varying levels of palmitate and coenzyme A in the presence  of ATP. Addition of glycerophosphate caused considerable reduction in carnitine acylation at low, but not at high palmitate levels. Glycerophosphate acylation was less reduced by added carnitine. These results can be explained by a lower Km(acyl-CoA) in glycerophosphate acylation than in carnitine acylation. High levels of free coenzyme A caused inhibition of carnitine acylation, while the inhibitory effect of glycerophosphate acylation was small. Competition between palmitate and acyl-CoA for binding sites on protein (e.g., albumine added to the mitochondrial suspensions) was indicated by stimulation of carnitine acylation by palmitate with palmityl-CoA added as substrate in the absence of ATP. Refeeding a carbohydrate-rich diet to previously fasted rats resulted in increased glycerophosphate acylation and decreased carnitine acylation in isolated liver mitochondria.


Thermoregulation during static work with the legs. Sustained static work with the legs, i.e., holding a weight of about 10% of maximal isometric strength for 25 min was compared to dynamic exercise on a bicycle ergometer causing the same rate of heat production. In the static work the subjective feeling of exertion was very high and the effort maximal. The pronounced increase in heart rate and blood pressure and a typical flush of the face and chest (flush areas) indicated a high sympathetic tonus. Plasma catecholamine levels were 1.3 times higher (significant at the Pless than or equal to 0.05 level) after static work than after dynamic work. Although the sustained static work was nearly maximal, the rate of increase in sweating and the change in core temperature during work were not different from the responses to dynamic work.


Vascular resistance in peripheral blood vessels at normotension and at local orthostatic hypertension in healty humans. The effect of changes in orthostatic pressure on vascular resistance in subcutaneous adipose tissue was examined in the forearm at normal tension and in the leg at local orthostatic hypertension in three normal subjects. Blood flow in subcutaneous tissue was measured by the local xenon-133 washout technique. Changes in orthostatic pressure were achieved by postural changes of the extremity. At levels above the heart where venous pressure is constant, there was autoregulation of blood flow over a wider arterial blood pressure range in leg than in forearm. When transmural pressure increased 25 mm Hg or more vascular resistance increased about 50 per cent in the dependent forearm and 300 per cent in the dependent leg. The effect of ischemia on vascular resistance was investigated in cutaneous tissue of hand and foot by means of the 131I-Antipyrine initial slope technique. Vascular resistance after maximum dilatation achieved after 20, 30, and 35 min of ischemia was less in vessels of the hand than in vessels of the foot. Thus, adaptive structural changes of vessels subjected to increased blood pressure are present in cutaneous and subcutaneous adipose tissues in normal subjects.


Synthesis of brain-specific acidic proteins in rat and mouse cerebral slices. Optimal conditions for incorporation of radioactive amiino acids into protein by slices of brain have been established. Protein synthesis continued for at least 4 h at 35 degrees. The highest incorporation of amino acids into protein was obtained with 20-50 mg wet weight per ml incubated at pH 7.1. After incubation of 500 mg of slices acidic proteins were separated by saltfractionation and electrophoresis on 14% polyacrylamide gel. The most acidic band was shown to contain S-100 protein. Indentification was solubility of the protein in 100% (NH4)2SO4, electrophoretic mobility at pH 8.9, precipitation with specific antibodies, and 2-dimensional electrophoresis in polyacrylamide gel. The protein band was insoluble in 50% methanol and contained between 0.06 and 0.2% of the radioactivity present in the total soluble proteins; while other well separated acidic proteins contained about 10 times the radioactivity of S-100 protein.


Sudden death in rheumatoid arthritis with atlanto-axial dislocation. A post mortem material of 11 consecutive cases of severe atlanto-axial dislocation (a.a.d.) with cord compression is reported. The total number of deaths from rheumatoid arthritis (RA) during the period of 5 years was 104, and all were autopsied. Neurological symptoms correlated poorly to fatal a.a.d. Hemiplegia was found in three cases, one of which, however, was caused by thrombosis cerebri. Spastic signs were transiently recorded in two patients and dysphagia in a further two. Five patients had a history of recent vomiting. A.a.d. was the sole or main cause of death in 8 cases and contributory in 2. Sudden death occurred in 7 of the cases. Only 2 cases had obtained a correct diagnosis intra vitam. The CNS findings at autopsy consisted of cord compression (11/11 cases), cord malacia (2/11) and cerebral oedema (3/11). One case had polyarteritis and renal amyloidosis and one pulmonary carcinoma with metastatic spread. Signs of active inflammation in the axial joints were present in 4 cases. This study, based on systematic post mortem examinations, revealed an unexpectedly high and not previously reported incidence of fatal medulla compression in RA patients with a.a.d. (10%).


Skeletal status in patients with rheumatoid arthritis. The total body calcium - estimated from the bone mineral content in the distal part of the forearm, measured by means of photon absorptiometry - has been determined in 15 patients with rheumatoid arthritis. None of the patients were treated with steroids and all were relatively mobile. The results indicate that osteoporosis is uncommon in such patients.


High pacemaker implantation rate following "cardiogenic neurology". This paper gives data on symptomatic patients with bradycardia found not at random but as the result of greatly expanded facilities for recognition of arrhythmias. The incidence of patients with symptomatic bradycardia was very high. Most patients had intermittent arrhythmias and diagnosis was often only possible after long-term ECG screening. Symptoms were as severe, and relief of symptoms with treatment was as good, as in pacemaker-treated patients described by others. Our conclusion is that indications for arrhythmia screening should be increased, as the diagnosis and treatment are very worthwhile. We refer to the systematized active diagnosis and treatment of arrhythmias in patients with cerebral symptoms as cardiogenic neurology.


Routine exercise ECG three weeks after acute myocardial infarction. In the third week after acute myocardial infarction, mean 18 days, exercise tests have been performed in 209 patients prior to discharge from the Coronary Care Unit. The exercise was done on a bicycle ergometer with electrically controlled braking, starting at the load 300 kpm/min (equal to 50 W), increasing with 300 kpm/min every 6th min, aiming at a maximal symptom-limited performance. ECG, in 3 extremity leads and 3 precordial leads, and heart rate (HR) were continuously recorded, and blood pressure (BP) was measured every minute. The most common cause for discontinuing exercise was fatigue (in 58%). Anginal pain or dyspnoea was the cause in 23.8%. Only in 9.1% was the exercise interrupted by the investigator because of rhythm disturbances or pronounced ST-T changes. Maximal work varied from 1 min exercise at 300 kpm/min to 6 min at 900 kpm/min (150 W); 18% of all patients were able to work for 6 min at 600 kpm/min (100 W). HR increased on an average from 80 beats/min at rest to 129 beats/min at maximal work load. Systolic blood pressure (SBP) increased on an average from 126 to 170 mmHg. The maximal values reached during exercise were HR 170/min, and SBP 270 mmHg. The product HR X SPB increased a little more than two-fold on an average. ST-T changes indicating myocardial ischaemia during exercise were observed in 70%. During exercise ventricular ectopic beats occurred in 42%. All rhythm disturbances provoked by exercise disappeared spontaneously shortly after work. Persistent ECG changes, reinfarction or other serious complications were not observed in connection with the exercise test. It is concluded that an exercise test under controlled circumstances is safe in patients of all ages in the third week after myocardial infarction. It is an objective measure of physical work capacity and described the reaction to physical activity. It gives a basis for advising return to normal life and is of great psychological importance to the patient.


Diagnosis of ventricular septal defect in acute myocardial infarction without cardiac catheterization. Five patients with acute myocardial infarction and a systolic murmur suggestive of ventricular septal rupture or mitral regurgitation have been examined by external vascular isotope dilution curves over the chest after i.v. injection of 125I-hippuran. In three patients these isotope dilution curves showed signs of left-to-right shunting of blood, and subsequent autopsy demonstrated the presence of ventricular septal defect. In two patients there was no sign of left-to-right shunting, and these patients recovered.


Verapamil in the treatment of atrial tachycardia with block. Atrial tachycardia (A-T) with block is easily converted as a rule to sinus rhythm by DC shock, but the recurrence rate is high. So far drug treatment of this arrhythmia has been unsatisfactory. There is no drug of choice in the treatment of A-T with block. We report on the effect of verapamil on this arrhythmia in 14 patients. Ten of them reverted to sinus rhythm, but A-T with block later recurred in 4. The best effect was found in patients with no or only minimal heart enlargement and in patients with short duration of the arrhythmia. The effect of verapamil on A-T with block may support the concept of this arrhythmia being due to atrioventricular (A-V) nodal reentry, as the main effect of verapamil is a prolongation of the effective refractory period of the A-V node.


Uriglox and quantitative urine microscopy in diagnosis of urinary tract infection. The aim of this study was to find an alternative to the sole use of abundant cultural findings as a basis for the diagnosis of urinary tract infection (UTI). For this purpose, the results obtained from the bacteriological culture of daytime urine specimens from 154 students by the dip slide method were checked against the findings from the quantitative culture, microscopy and Uriglox testing of the first morning urines voided later at home. As a diagnostic criterion, the finding of 10(5) or more bacteria/ml urine in two successive cultures had an error of 19%. For the simultaneous occurrence in the morning urine of abundant bacteria (larger than or equal to 10(5)/ml) and a subnormal glucose concentration (as revealed by the Uriglox test), this error was 1.5%. Only the latter combination showed, therefore, the presence of UTI at the confidence level of larger than or equal to 95%, or was "clinically significant". The specificity indices for the Uriglox test and the quantitative culture were 0.99 and 0.97, respectively. Microscopy of the morning urine showed 10(3) or more bacteria/ml in all the subjects with infection but the number of leucocytes was normal in a fifth of them. The specificity indices for microscopic counts of 10(3) or more organisms/ml and 10 or more leucocytes/mm3 were 0.74 and 0.94, respectively. For higher counts, i.e. 10(5) or more bacteria/ml and 50 or more leucocytes/mm3, the specificity index of positive microscopy was 1.0. This specificity level was, however, attained at the expense of the sensitivity, which for 10(5) or more organisms/ml was 0.67 and for 50 or more leucocytes/mm3 0.53. It is concluded that abundant bacterial contamination of specimens often decisively complicates the diagnostic use of urine culture, and therefore the combined use of quantitative culture, microscopy and the Uriglox test is recommended as the principal tool for the diagnosis of UTI in ordinary hospital and ambulatory health services.


Diagnosis of cardiac amyloidosis by myocardial biopsy. A case of cardiac amyloidosis with severe heart failure is presented. The diagnosis was confirmed by myocardial biopsy. The microscopical and ultrastructural changes in this biopsy are described in detail.


Iron absorption in patients with chronic renal failure not requiring dialytic therapy. Gastrointestinal iron absorption, by means of whole body counting, has been measured in 15 patients with chronic renal failure, not requiring dialysis. Whole body retention 14 days after oral administration of 10 muCi 59Fe together with a carrier dose of 10 mg Fe2+ was taken as expression of absorption. The percentage incorporation in the total erythrocyte mass of administered 59Fe (erythrocyte incorporation) and absorbed 59Fe (red cell utilization) was estimated as well. Iron absorption was 9.6+/-2.0 (S.D.)% (geometric mean) and erythrocyte incorporation 7.5+/-2.3 (S.D.)% (geometric mean) while red cell utilization averaged 80.3+/-4.8 (S.E.M.)% (arithmetic mean). None of these parameters were significantly different from those obtained in a normal control group (p greater than 0.5, p greater than 0.9 and p greater than 0.2, respectively). The correlation between iron absorption and erythrocyte incorporation was highly significant (r=1.00, p less than 0.001). Iron supplementation is often indicated in the investigated category of patients due to increased blood loss and insufficient iron intake and should be given orally in consideration of the normal gastrointestinal absorption.


Studies on some biological properties of heteroploidal cell -- PZH-1 line derived from human embryo lung. The morphological and karyological properties as well as susceptibility to virus strain of tissue culture derived from human embryo lung that underwent a transformation becoming a continuous line defined as PZH-1 were observed. The observations cover 120 passages divided into four phases: one before and three after transformation. Each of these phases was characterised by different biological strain properties. Loss of PZH-1 susceptibility to ECHO virus was the first change of biological properties preceding in time changes in growth rate, cell morphology and chromosome complement. The loss of susceptibility to ECHO virus may indicate cell transformation.


A simple device for spot counting in photomicrographs or electron micrographs. A simple apparatus for spot counting in photomicrographs or electron micrographs is described, consisting of an illuminator on which the photographic print in placed and a counting pen. By making small holes in the photograph with the specially designed spring-loaded counting pen, the spot counted can be clearly located by the light from the illuminator falling through the hole, whereas a microswitch built into the counting pen makes an electronic counting system to move one digit.


Biostatics of the tibial shaft.

Biostatics of the tibial shaft. In all, 56 tibiae from Lapps and 56 tibiae from Norwegians have been studied. These ethnic groups represent different weight bearing situations. Only measurements referring to the diaphysis are presented. The bones are studied in the AP and ML planes and at different transverse sections. The material is analyzed statistically. The distribution form is examined. Chiefly positive skewness occurs. Platykurtosis is found twice as often as leptokurtosis. A differentiated pattern of distribution seems to be the case regarding measurements in the lower extremities. This corresponds to the influence of variable hereditary and external factors. Divergencies from standard normal distribution is compared with differences between groups. In some cases differences are influenced by platykurtosis and skewness. Divergence from standard normal distribution could not be traced back to measuring errors, special features of the bone or special sex characteristics. The divergencies are not supposed to affect the results to any noteworthy extent. Female Lapps show small variances, female Norwegians great variances. In linear variables Lapps generally show smaller values than Norwegians, females smaller values than males. Regarding linear measurements, sex differences are a little more marked than differences between the two ethnic groups. The opposite is the case regarding the angular measurements and the indices. The sex differences in linear measurements are smaller in Lapps than in Norwegians. The opposite is the case regarding the length of the bone. In Lapps, angular measurements and indices show no significant sex differences. Regarding linear measurements, differences between the ethnic groups are mostly due to differences between the males. The opposite may be said about the indicnes. The variations of the tibia recorded and discussed in the present paper are the results of mechanical factors influencing the basic processes in functional bone remodelling. The periosteal ossification is particularly involved in the dimensions of the shaft, the epiphyseal cartilage in the length dimensions. Particularly important is the relation between the weight bearing line and the diaphysial axis of the bone, and the muscles activated by variation is this relation.


An electronmicroscopic study of the truncus ridges in chick embryos. In 6 days' chick embryos, an electronmicroscopical study was made of the fusion of the endocardial ridges of the truncus arteriosus. It could be demonstrated that in this fusion process not only the endothelial cells are involved, but also cells of the condensed mesenchyme of the parietal ridge. The endothelial cells form protrusions which interdigitate and show endocytosis whereas the cells of the condensed mesenchyme produce long, blunt pseudopodia containing filaments and microtubules.


Intersex or sex reversal amongst plant parasitic nematodes. The intersexuality amongst plant parasitic nematodes has been discussed to be an intermediate stage of sex reversal of male into female. We, hereby, suggest four possible reasons for the sex reversal, this being an intermediate stage - a so-called intersex phase: (1) gene mutation, (2) unusual numerical relationship between autosomes and sex chromosomes during fertilization, (3) effect of female sex hormone secreted by adult females alongwith the mating attractant, and (4) presence or absence of andrgenic hormone in males. The possible effect of female sex hormone on the synthesis of macromolecules which might play a role in sex reversal, is discussed in particular.


Functional significance of non-specific esterase and its involvement in the excretory mechanism of trematodes, cestodes and nematodes. The distribution of non-specific esterase in the excretory canals of nematodes, cestodes and trematodes is described. In all the cases the excretory canals are intensely positive, except in Dioecocestus fevita where the reaction is mild. In most of the cases the reaction is observed in the form of small granules, distributed throughout the canal. The distribution of the enzyme has been correlated with the excretory functions of these parasites.


The process of conditioning: an evolving concept. Various explanations of the process of conditioning and some models of the postulated connections between brain centers are discussed. Some results of research on conditioning processes at the neuronal level are reviewed. A hypothesis is put forth that conditioned behavior is a result of activation of neural patterns of associations between the sensory traces of stimuli; such neural patterns may be stored in polysensory neurons. Models based on this hypothesis are presented.


Post-consummatory arousal of drive as a mechanism of incentive motivation. A review of experimental papers on the problem of incentive motivation reveals little or no support for the hypothesis that conditioned food signals facilitate autochthonous instrumental responses (i.e., responses motivated by the same drive and rewarded by the same unconditioned stimulus). The existing data are explained most parsimoniously by assuming that reward, or its conditioned signal, inhibits the central drive process, and, that the termination of either primary (food US) or secondary (food CS) reward causes the rebound of drive which energizes instrumental behavior. This post-consummatory arousal of drive retains some specificity related to the reward and is assumed to represent a mechanism of the phenomena usually referred to as incentive motivation.


Drive-controlled reflexes: a theory.

Drive-controlled reflexes: a theory. Drive-controlled (higher) reflexes are divided in two ways: (i) according to the controlling drive into pain, fear and appetite reflexes; (ii) according to the manner of drive elimination into type A and type B reflexes. A type A reflex simply removes the evoking stimulus, whereas a type B reflex provides a drive-inhibiting stimulus. According to different functions performed in an organism, reflexes are grouped into several systems.


The biological significance of duetting and antiphonal song. Duetting plays a very important part in the signal system between male and female in a large number of bird species, in particular species that inhabit tropical regions. These elaborate song patterns show many interesting features, of which only a few have been discussed here. Perhaps the most interesting result of our investigations of duetting is the light cast on the heretofore little appreciated precision and synthesizing power of avian aural perception, the great precision of response time and the equally great exactness of control of the vocal organs. The use of these vocal powers for individual recognition is in line with observations made over the past decade by B. Tschanz, C. G. Beer, myself and others. This work has shown that in many colonial nesting birds (for example auks, terns, gulls, gannets and penguins) brief calls of a half-second duration or less can have enough acoustic detail not only to serve as labels identifying the calling species but also to label the individual caller.


Prefrontal cortex and manipulatory go left-go right differentiation to acoustic directional cues in dogs. In 20 dogs the manipulatory go left  go right differentiation to acoustic directional cues was elaborated. All dogs received total prefrontal, or dorsolateral (total or partial) or medial (total or partial) cortical ablations. All total ablations markedly affected performance of the task, whereas the partial removals produced moderate or no impairment. Thus, both the dorsolateral and medial prefrontal cortex are involved in this type of differentiation.


Effects of partial prefrontal lesions in dogs on go-no go avoidance reflex differentiation and reversal learning. The effects of prefrontal medial or lateral lesions on the retention of avoidance go  no go click-tone differentiation in dogs were studied. The acquisition of the differentiation was influenced by the quality of the stimuli since more errors were performed to the click CS(-) than to the tone CS(-). Neither medial nor lateral lesions exerted any effect on retention of the differentiation. Similarly, as during original differentiation training, the quality of the stimuli had an effect on reversal learning in normal dogs. Such an effect was markedly reduced in dogs with prefrontal lesions and more strongly in those Ss which received lateral lesions. The results were discussed relative to data obtained from cats trained under similar conditions. The dogs showed better responding on positive trials while performance in cats was better on negative trials. The stimulus quality effect was more pronounced in dogs during negative, and in cats during positive trials.


Dissociative effects of selective lesions in the caudate nucleus of cats and rats. Lesions in the neostriatal region connected to the prefrontal cortex severely impaired delayed alternation in both cats and rats, whereas no such effect was found after damage to other neostriatal regions. These results indicate that the processes mediating delayed alternation are well localized in the neostriatum of both cats and rats. Two possible models of neostriatal functioning are discussed, one of functional heterogeneity, the other of functional homogeneity.


Cortical motor representation in view of recent experiments on cortico-spinal relations. The results of recent experiments using either intracortical stimulation or stimulation of the surface of the motor cortex were reviewed from the point of view of "muscle" and "movement" cortical representation. It has been concluded that there is no satisfactory evidence for location of the pyramidal tract (PT) cells which project directly (monosynaptically) to motoneurones of one muscle in primates within small and separate cortical areas; such evidence is even weaker for PT cells which exert their effects via polysynaptic pathways in other species. The available evidence shows in contrast a very pronounced overlap of cortical areas of projection to different motor nuclei.


Spreading depression resulting from cortical punctures. In acute experiments on cats under deep Nembutal anesthesia punctures of the cortex caused a prolonged negative shift of its surface potential (up to 15 mv, 5.5 min), which was followed by a prolonged positive shift. During these shifts of the potential, both components of the direct response were depressed. The changes in potential and the depression of electric activity spread over the cortex at a mean rate of 65 micrometers/s. The phenomenon arised when the punctures are made with a pipet 20 micrometers and above in diameter. A puncture of the surface structures was critical; passage of the pipet through the middle and deep layers was ineffective. It is assumed that when cortical punctures are made the SD is caused by K(+) ions which leak out of the destroyed glial structures.


Acquired and inherent trace processes in the neuronally isolated cortex. Trace processes in the neuronally isolated cerebral cortex of one hemisphere were analysed. EEG and unit activity of the isolated cortex at different times after the operation were investigated. Temporal connections in the isolated cortex were elaborated. Neurons fixing the stimuli traces were revealed. These neurons (23 percent of reactive neurons) form a microsystem of learning neurons.


Consciousness from neurons.

Consciousness from neurons. Consciousness derives from a neural process that requires unceasing metabolic support, and probably involves only a select population of neocortical elements. The essential process must operate for roughly more than 100 ms for sensorial registration (Libet). It is highly unlikely that the essence of the process lies in its computational logic and hence it can never be produced by inanimate machines. Since the process is thus unique to neurons, and since the consciousness of the left hemisphere normally communicates with that of the right (and probably vice versa) via the forebrain cornmissures, at least some portion of the nerve impulse traffic across the commissures must possess a wholly mysterious property enabling its transcendent compilation into a unified conscious experience. Comprehending the nature of this property which couples ionic fluxions into mentality is the quintessential problem of science. The forebrain commissures may ultimately provide the clues for its solution.


Electron microscopic morphometry of the zona glomerulosa cells of the Wistar rat. Results of morphometric measurements were compared on the cells of the zona glomerulosa (ZG) of the adrenal gland of the rat. The mean area covered by the cells, the nuclei, the mitochondria and the lipid droplets, as well as the surface density of the endoplasmic reticulum membrane and of internal mitochondrial membrane indicated an inhomogeneity even in the ZG cells of the same animal, with considerable deviations in the ZG of different animals. The dark and light ZG cells were compared too. The results suggest hormonal-functional differences, both among the normal animals and among the cells of the same animals.


Blood supply of the rat hypothalamus. III. Anterior region of the hypothalamus (nucleus suprachiasmatis, nucleus hypothalamicus anterior, nucleus periventricularis). The arterial and venous blood supply of the anterior hypothalamus was studied by means of double perfusion technique. The angiotopography and cytoarchitecture of the hypothalamus were compared on serial sections by accounting for the three-dimensional coordinates. A detailed description is given of the arteries and veins contributing to the blood supply of the suprachiasmatic, the anterior hypothalamic and the periventricular nuclei. The topography of the arterial and venous trunk on the base surface of the rat diencephalon is described, as well as that of the larger branches which enter from below and pass through the anterior hypothalamus.


Effect of prostaglandin F2 alpha on the neurohypophysis. A histochemical study. Ten micrograms of PG F2 alpha in distilled water were injected intraperitoneally into thirty non-pregnant female rats and their hypophysis was studied after aldehyde-fuchsin and performic acid-alcian blue staining. A definite depletion of posterior pituitary principle was observed in the hypophysis. The role of oxytocin in relation to the oxytocic effect of prostaglandin F2 alpha is discussed.


Connective tissue alterations following neonatal thymectomy. VI. Calcium histochemical, growth-dynamical and thermoanalytical investigations on bone tissue of thymectomized rats. Thymectomy was performed in newborn rats and the changes occurring in the epiphyseal cartilage and bone were investigated by Ca histochemical and thermoanalytical methods, one, two and six weeks following operation. Formation of Ca complexes was slowed down in the epiphyseal cartilage and the rate of growth decreased. At the same time the inorganic substance content decreased considerably in the bone tissue of operated rats as compared to the controls.


Permeability of the post-ischemic rat aorta. The time course of the vascular permeability disorder following upon acute hypoxia and the fate of plasma substances entering the vessel wall in consequence of increased permeability were studied on the rat abdominal aorta rendered hypoxic for one hour by double ligature and recirculated for periods ranging from one hour to 30 days. The distribution and quantity of mural plasma inhibition were determined histochemically by means of a colloidal iron tracer and Prussian blue reaction and by photometric analysis, respectively. Plasma imbibition reached its maximum after recirculation for 24 to 48 hours and fell to an almost normal level after 10 days. Administration of the colloidal iron tracer on the second day of recirculation, when the permeability disorder was at its peak, showed plasma imbibition in every layer of the vessel wall. At seven days it was restricted to the outer third of the media and the adventitia. The endothelium is acting as the main barrier to mural plasma imbibition and in the case of a permeability disorder only the elastic lamellae constitute a temporary mechanical obstacle to the ingression of plasma.


Effect of triiodothyronine treatment, thyroparathyroidectomy and mercaptoiminazole treatment on enchondral bone growth. Changes in the histological structure of the growth organ. Histological changes caused by triiodothyronine (T3) and mercaptoiminazole treatment as well as by thyroidectomy have been studied in the proximal growth organ of the tibia of growing rats. On triiodothyronine treatment morphometric examinations revealed an increased proliferation and resorption of cartilage associated with a transitory acceleration of linear bone growth. Administration of mercaptoiminazole and thyroidectomy inhibited cartilage proliferation and resorption resulting in a slowing down of bone growth.


Plasma elastase levels in the elderly.

Plasma elastase levels in the elderly. Plasma elastase levels were estimated in 190 patients of both sexes above the age of 65 with the exception of one male subject with prostatic carcinoma who was 51 years of age. There was no significant rise of fall in the elastase levels in subjects above the age of 65, nor was there any difference between the sexes. Higher values compared with the rest of the population were obtained in those subjects with arterial disease and/or cardiac disease. Subjects with cerebrovascular disease had higher values than those with cardiovascular disease. Very low values were obtained in patients suffering from malignant disease, especially carcinoma of the prostate.


Bed blocking by elderly patients in general-hospital wards. A point prevalence survey, using a questionnaire, was performed in three general hospitals to investigate the problem of elderly patients blocking acute-hospital beds. A total of 1010 occupied general beds were surveyed and all patients, over the age of 60 years, who had been in hospital more than four weeks, and who, in the opinion of medical and nursing staff, were no longer in need of the facilities of a general hospital, were investigated. Forty-eight patients (4.8 per cent of the total) were found to be genuinely in bed inappropriate to their needs. Rehabilitation, together with assessment of these patients, appeared disorganized and lacked consistency, and decisions regarding suitable 'disposal' appeared to be made without sufficient consultation and conformed to no detectable pattern. The main reason for the continuing bed occupancy of the patients was the length of the waiting lists for alternative residential accommodation and the main single medical factor preventing discharge home or to a hostel was the problem of mobility. By interviewing staff and patients and scrutinizing the questionnaires, it was found that 23 patients (48 per cent) were only suitable for transfer to a long-stay hospital. Of these, however, 15 (31 per cent) could be placed in specialized accommodation if some degree of nursing care, at present not available, was provided.


Reviews after one and five years in a longitudinal study of ageing persons. A simple random sample of older people composed of 215 men and 272 women aged 62 years and over was examined in Edinburgh in 1968-9. After one year, 86 per cent of the men and 79 per cent of the women were re-examined; 7 per cent of the men and 4 per cent of the women had died and the remainder were not re-examined for various reasons, mainly refusal. After five years, 53 per cent of the men and 54 per cent of the women were re-examined; 36 per cent of the men and 22 per cent of the women had died and the remainder were not re-examined mainly because of various types of refusal. Causes of death resembled in frequency and sex differences those reported by the Registrar General. Methods used in tracing and improving cooperation of subjects are described.


Control of warfarin therapy in the elderly. Eighty patients over 65 years old with satisfactory coagulation control with Warfarin were selected and analysed to determine factors predictive of dose. Age followed by urea were the important predictors. Albumin, globulin, sex, weight and T3 uptake were not significant factors. It is concluded that care should be taken when Warfarin is given to older patients, particularly those with high blood-urea levels.


Causes for reduced dietary intake in a long-stay hospital. The food and nutrient intake of 98 patients in a long-stay geriatric hospital was measured. Intakes of nicotinic acid and iron were reduced in patients requiring help with feeding because of physical disability. This was related to a reduced intake of meat and fish, bread and vegetables other than potatoes. A more generalized reduction in food and nutrient intakes was found in patients with severe mental impairment. Possible causes and remedies for these associations are discussed.


The identification of the medical and social needs of the elderly in the community: a pilot survey. A pilot study, covering 237 old people over the age of 75 years, was carried out by two Health Visitors in a Group Practice. Medical and social needs were tabulated and the amount of health visiting time calculated for such a service in a Health Board area covering a total population of 330 000.


The mechanism whereby growth hormone-release inhibiting hormone (somatostatin) inhibits food stimulated gastric acid secretion in the cat. Growth hormone-release inhibiting hormone (somatostatin) inhibits the gastric acid response to food in concious cats. We have confirmed that this tetradecapeptide blocks the food stimulated gastrin release. However, the inhibition of gastrin release is delayed relative to that of acid secretion, &howing that the inhibition of food stimulated acid secretion is by primary effect on the acid secretory mechanism. No evidence was found of potentiation of either the gastric acid output or serum concentration of gastric in response to food.


An anti-inflammatory substance in normal human plasma. A substance of low molecular weight, below 1000 daltons, has been separated from normal human plasma by a stepwise process involving ultrafiltration followed by column chromatography. The spectrum of anti-inflammatory activity of the active fraction in a variety of animal models shows that it is most active in situations in which the emigration of circulating leucocytes plays the more prominent role. The fraction exerts a selective action on the release of chemotactic factors after the activation in vitro of the complement cascade by the alternate but not by the classical pathway. The existence of the plasma fraction raises several interesting queries. Is it part of the naturally occurring control mechanisms in inflammation? What is its relevance to human disease, e.g., rheumatoid arthritis, and do conventional antirheumatic drugs interact with it? Does its lack of activity against chemical mediators of inflammation and their generating systems throw any light on the importance of these materials in inflammatory reactions?


Changes in cellular enzyme levels and the inhibition of selective release of lysosomal hydrolases from macrophages by indomethacin. Indomethacin increases the cellular levels of several lysosomal enzymes in cultures of mouse peritoneal macrophages exposed to the drug for periods of time ranging from one day to four weeks. This increase can be blocked by puromycin, an inhibitor of protein synthesis. Pretreatment of macrophages with indomethacin inhibits the selective release of lysosomal enzymes induced by a C-mucopolysaccharide peptidoglycan complex purified from the cell walls of Group A streptococci.


Inhibiting effects of morphine, chloroquine, nonsteroidal and steroidal anti-inflammatory drugs on electrically-induced contractions of guinea-pig ileum and the reversing effect of prostaglandins. Twelve different non steroidal antiinflammatory drugs (NSAID), five steroidal antinflammatory drugs, morphine and chloroquine have been added at various concentrations to in vitro electrically-stimulated preparations of guinea-pig ileum. They all inhibit the electrically-induced contractions. Prostaglandins E as well as nicotine reverse this inhibition. These reversing effects are less evident on totally inhibiting drug concentrations than on partially inhibiting drug concentrations. It is suggested that this inhibiting effect could be due mostly to nervous as well as muscular membrane permeability changes induced by these drugs and not to inhibition of prostaglandin synthesis which could be only proposed as partial explanation for NSAID effects. The reversing action of nicotine could be related to a release of acetylcholine while a sensitization of guinea-pig ileum smooth muscle to acetylcholine could explain the reversing properties of prostaglandins.


Enhancement of carrageenin foot oedema by 1,10 -phenanthroline and evidence for the bradykinin as endogenous mediator. Carrageenin oedema in enhanced by the simultaneous injection in the rat paw of 1,10-phenanthroline, a kininase inhibitor. The analysis of the time-course of this enhancement showed that the maximal effect was observed about 3 hours after the injection. This enhancement was also present when the oedema-producing agent was cellulose sulphate, a kinin-releasing compound. On the contrary, oedema induced by eggwhite as well as by dextran, which are mainly mediated by histamine and 5-hydroxytryptamine, were unaffected by 1,10-phenanthroline. These results further support the role of kinins in the pathogenesis of carrageenin oedema.


The response of the newborn rat to intraleural dextran: vascular and cellular aspects. The development of hind paw oedema, in response to dextran injected in to the pleural cavity of rats, has been shown to differ with the age of rat studied. It was found that newborn rats were less responsive than adults, with respect to oedema formation induced by dextran. Attempts to suppress the dextran-indu.ced foot oedema using mepyramine and cyproheptadine, were successful only in rats from the adult age group. A semiquantitative analysis was made of the inflammatory cellular exudate produced by the intrapleural injection of dextran into rats of different ages. In contrast to the reaction of adult rats, it was found that accumulation of polymorphs in the pleura of newborn animals was delayed. The polymorph was the dominant cell type found in exudates induced either by intrapleural saline or dextran, in rats from the 6-hour age group. This contrasted strikingly with comparable exudates induced in adult rats, whose major cell type was the mononuclear cell (after saline), and the polymorph, followed by the mononuclear cell (after dextran). Fewer cells were observed in the reaction of 6-hour-old rats, compared with 7-day-old animals following intrapleural injection of the same volume of a 6-percent solution of dextran.


Effect of calcitonin on carrageenan foot oedema. The effect of salmon calcitonin (SCT) on acute inflammation was tested in carrageenan induced foot oedema of the rat. A considerable inhibition of the oedema was obtained with 20 MRC U/kg of SCT. The injection of SCT is followed by decrease of calcemia. A hypothesis of possible inhibition of prostaglandin (PG) synthesis and/or release, caused by decrease of calcemia, is advanced.


Some special respiratory effects of CO2 in pigeons. Injections of CO2-gas have been made into an abdominal air-sac of pigeons. The resulting alterations of respiratory rate and of breathing efforts are dose-dependent and easily reproducible. The receptive zones for these effects do not seem to be located in the air-way system itself; they may be in the respiratory center. Some data provide further evidence for the assumption that the ventilation of the abdominal air-sacs is mainly one-directional, from outside to gas-exchange compartments. Panting increases the ventilation of the abdominal air-sacs.


Effects of seven anthracycline antibiotics on electrocardiogram and mitochondrial function of rat hearts. Daunomycin, adriamycin and 5 semisynthetic anthracycline antibiotics inhibited oxygen consumption or ATP production of rat heart mitochondria in vitro. The no-effect levels varied depending on the substrate used and ranged from 1 nmole per mg mitochondrial protein. Mitochondrial functions were also studied in hearts of rats treated with repeated i.p. injections of the 7 antibiotics. Decrease in oxygen consumption without change in ATP production was observed with adriamycin and NSC-149584. Daunomycin, NSC-164011, NSC-143496 NSC-143114 affected primarily ATP production. The most potent compounds were daunomycin and adriamycin which damaged mitochondrial function at cummulative doses of approximately 10 mg/kg. ECGs were monitored in groups of equally treated rats. Cardiotoxicity manifested itself by progressive widening of the QRS complex often followed by the development of a S-wave trough. The most toxic compounds also induced intraventricular block, bradycardia and heart failure. The development of the ECG changes showed a good correlation with the impairment of mitochondrial function.


The systematic appraisal of cellular injury. From a study of the ultrastructural effects of numerous injuries agents on cultured kidney and liver cells, a check-list has been drawn up which summarizes all of the changes observed in subcellular components. The checklist resembles a multiple-choice test. Its use would permit greater standardization among workers reporting ultrastructural alterations observed in injured cells. It would also increase the objectivity with which cell injury can be assessed by electron microscopy. The checklist is suitable for use in computer-based programs designed to characterize types of cellular injury and for seeking correlations in ultrastructural changes arising from different forms of treatment.


A new mass sensor for respirable dust measurement. A new portable instrument measures mass concentration in the 100 mug/m3 range of airborne dust particles smaller than 10 mum. An electrostatic precipitator desposits particles as small as 0.01 mum onto a piezoelectric micro-balance sensor. The instrument utilizes digital readout and a built-in sensor cleaner.


Elevated urinary phenol levels not related to benzene exposure. Two common over-the-counter medications may elevate urinary phenol to levels exceeding 75 mg/liter (ppm). This study presents data indicating that it is invalid to correct urinary phenol levels to specific gravity of 1.024. Animal studies indicate that having elevated urinary phenol levels secondary to phenyl salicylate ingestion are not harmful.


The rapid counting and sizing of fibers in a mixture using an IITRI-modified coulter counter. Fibers can be counted and sized in the presence of other particle shapes using a modified Coulter Counter tube. With the modifications, only particles of a pre-selected projected area reach the sensor. Since particle volume is sensed, particles with volumes greater than the unit volume corresponding to the projected area are fibers.


An extractive method for determination of benzene in blood by gas chromatography. A gas chromatographic procedure has been developed using toluene extraction for the analysis of benzene in hemolyzed blood. No sample incubation is required and only small quantities of blood (0.2 to 0.5 g) are needed. Levels as low as 0.5 mug benzene per gram of blood have been determined.


Community noise criteria.

Community noise criteria. In the fields of community noise abatement and municipal planning, there are new requirements to define an environment of varying noise level by a single number rating method that correlates well with the subjective response of human beings. Typical criteria, either in use of proposed, are LN numbers (noise levels exceeded N% of the time), Leq (the equivalent sound level in dB(A) ), LNP (the Noise Pollution Level), and Ldn (the day-night average sound level in dB(A) ). Instruments available include an environmental noise classifier, a statistical distribution analyzer/recorder combination, and a digital sampling system for field measurements for subsequent interrogation by a programmable calculator.


An aerosol generator of high stability.

An aerosol generator of high stability. This paper reports on the use of a syringe pump to provide a constant liquid flow to an atomizer to obtain an aerosol generator of high stability. This syringe-pump atomizer has also been used with a vaporizer-condenser to generate monodisperse DOP (di-octyl phthalate) aerosols in the 0.032 to 1 mum diameter range.


Calibration of mercury vapor monitors by permeation. The permeation system described provides constant concentrations of mercury in air. They can be selected at will and introduced into one or more of the instruments to be calibrated. The concentration of mercury in the permeation stream is simultaneously reocrded by a reference ultraviolet photometer.


Control of cobalt exposures during wet process tungsten carbide grinding. Pneumoconiosis has been reported in tungsten carbide manufacture; past studies have suggested that adverse cobalt exposures may occur from wet process tungsten carbide grinding. This study shows that wet process tungsten carbide grinding without local exhaust can cause adverse cobalt exposures. Controls are summarized.


Steady state respiratory responses to tasks used in Federal testing of self-contained breathing apparatus. A portion of Title 30, Part II, CFR calls for a Man Test, which is a series of regimens performed with a breathing apparatus. The respiratory responses to the tasks in the Man Test were established on coal miners and students. Based on these responses, the minimal metabolic requirements were derived for the use of breathing apparatuses with a service life of 30 minutes or more.


A piezoelectric crystal dosimeter for monitoring mercury vapor in industrial atmospheres. A personal dosimeter for mercury vapor in air based on the use of a piezoelectric sensor with a selective coating has been developed and evaluated. The sensor is a gravimetric device which indicates an integrated total exposure to mercury vapor.


Effects of fluorocarbons 11 and 12 on tracheobronchial particle deposition and clearance in donkeys. Donkeys were exposed to trichlorofluoromethane (FC11), dichlorodifluoromethane (FC12) and an equivolume mixture of the two to determine their effects on tracheobronchial particle deposition and mucociliary clearance. There was no statistically significant evidence of changes beyond those variations observed in corresponding air control tests.


A statistical analysis of asbestos fiber counting in the laboratory and industrial environment. The reproducibility of standard fiber counts in the laboratory and four industrial plants is discussed in detail. Under field conditions the standard deviation of the results varied between 0.4-1.2 f/ml. Under ideal laboratory conditions the standard deviations of the counts were approximately 0.2 f/ml. It is concluded that the standard method is sufficiently precise for industrial measurements.


Cortical cytoplasm and configurational changes of RGC-6 cells exposed to cytochalasin B. RGC-6 cells, grown to confluency in monolayer cultures, are typically fusiform. In sections of these cells, fixed in situ and examined in the electron microscope, a discontinuous zone of cortical cytoplasm (5-4 nm wide), was found subjacent to the plasma membrane of the free surface. It was composed largely of 5-7 nm microfilaments distributed in an apparently irregular network and appeared to comprise a discrete zone separating the plasma membrane from the underlying endoplasm. Following incubation with cytodhalasin B (5 mug/ml), the configuration of the cells changed markedly. The perikaryal cytoplasm appeared to swell, while the cellular processes became attenuated and often terminated in flower-like tips. Although more discontinuous and somewhat less dense, the fine structure of the cortical cytoplasm appeared little affected by incubation with cytochalasin B for one hour. By 48 hours no zone of cortical cytoplasm was found. Subplasmalemmal microfilaments were no longer identifiable and endoplasmic organelles were found in direct contact with the plasma membrane of the free surface, which appeared to have collapsed onto the underlying endoplasm. The change in cell configuration resulting from exposure to cytochalasin B occurred at 37 degrees C but not at 4 degrees C, suggesting a dependency on metabolic activity. It did not, however, appeared related directly to protein synthesis. Whereas incorporation of 3H-leucine was decreased to 46.9% and 62.9% of control values after one hour or two hours exposure to cytochalasin B, respectively, no change was found after 24 or 48 hours. It is suggested that the effect of cytochalasin B on cell form, which appeared not to be a direct effect on either protein synthesis or subplasmalemmal microfilaments, may represent a primary response of the cortical cytoplasmic matrix.


A light and electron microscopic study on the embryonic development of the rat carotid body. The embryonic development of the rat carotid body was studied with electron microscopy. In the 11 mm embryo a cell aggregation consisting of undifferentiated cells and unmyelinated nerve fibers appears on the anterior wall of the third branchial artery. Granule-containing cells appear in the 12 mm embryo and continue to increase in number as the cellular aggregation increases in size and becomes separated from the wall of the third branchial artery. Synapse formation and the appearance of fenestrated capillaries occur almost simultaneously at the 17 mm stage. There are two types of synapses, one with membrane densification and vesicles clustered inside the nerve endings, the other with dense material and vesicles inside the granule-containing cells. At the 20 mm stage the undifferentiated cells send enveloping cytoplasmic processes toward adjacent granule-containing cells and the carotid body anlage displays rudimentary lobules.


Scanning electron microscopy of normal rat liver: the surface structure of its cells and tissue components. Scanning electron microscopy (SEM) allows the surface ultrastructure of intrahepatic cells and other tissue components of liver to be delineated. Excellent depth of focus of the SEM makes it possible to visualize surfaces of intact cells in their native configurations. This report details the surface characteristics and inter-relationships of hepatocytes and hepatic plates, sinusoidal endothelial cells and sinusoids, presumed Kupffer cells, vessels, bile ducts, connective tissue, and the capsule of rat liver. Hepatocytes present three structurally distinctive faces--the intercellular face containing flat surfaces and bile canaliculus, the sinusoidal face, and the connective tissue face which abuts portal tracts and hepatic veins. Sinusoidal endothelium is penetrated by large (1 to 3 mum) and small (0.1 mum) fenestrae, the latter occurring in clusters of up to 50. The width of bile canaliculi and distribution of large fenestrae vary proximodistally along hepatic plate or sinusoid. The cells of portal bile ductules contain microvilli located in linear rows and sparse cilia. Endothelium of hepatic artery and of portal vein is sparsely fenestrated.


Morphological diversity of oocytes released from the adult mouse ovary. This study was designed to classify and differentiate the population of oocytes released from the mouse ovary by mechanical means. Liberated oocytes were classified on the basis of their number, size and by the nature of the attachment of follicle cells to these oocytes. Microscopical examination of oocytes mechanically released from the ovaries revealed three distinct morphological classifications of oocytes: (1) those completely devoid of follicle cells, (2) those encased in follicle cells and (3) those in the process of degeneration. Ooxytes ranged in size from approximatley 30mu to 119mu. Those oocytes surrounded by follicle cells could be further subdivided into two groups depending on whether the follicle cells could be mechanically removed from the oocyte. These data demonstrate that the adult ovary contains a variety of classes of oocytes which differ in size and in the extent to which the follicle cells are attached to the oocytes. It is suggested that the metabolic activities and meiotic potnetials of the various oocyte populations differ and as a result, care should be employed to insure a uniform population of oocytes when conducting further studies sith mechanically liberated oocytes.


Organ culture of osteopetrotic (ia) rat bone: evidence that the defect is cellular. Calvarial bone from osteopetrotic (ia) rats and normal littermates has been cultured in a chemically defined medium supplemented with homologous serum to test for the presence of inhibitors or the absence of promoters of bone resorption in mutant serum. In addition, the response of mutant and normal bone to parathyroid extract and hydrocortisone was tested in vitro. The results indicate that mutant and normal serum do not differ with respect to their ability to support bone resorption and that ia bone responds to hydrocortisone but not parathyroid extract in organ culture. These data indicate that the skeletal defect in ia rats is not humoral but cellular.


Junctions between sinusoidal endothelial cells in fetal rat liver. During a freeze-fracture study of tight junctions in fetal rat liver (Montesano et al., '75) unusual patterns of intramembranous particles were observed in regions of contact between sinusoidal endothelial cells. These patterns were mainly represented by arrays of particles, often associated with linear elevations or crests in the membrane A-face; they may represent abortive forms of tight junctions.


Ultrastructural evidence for the uptake of 5,6-dihydroxytryptamine in the frog's gustatory cell. The fungiform papillae of the frog were examined electron-microscopically after a single injection of 5,6-dihydroxytryptamine (5,6-DHT). Thirty minutes after 5.6-DHT injection, numerous vesicles partially occupied with dark material were found in the cytoplasm of gustatory cell processes. Three days after the drug treatment, the majority of vesicles were completely filled with dark material so that their limiting membrane became obscure, while the terminal portions of gustatory cells showed no evidence for fine structural alteration indicative of drug retention. In addition, clear vacuoles, suggesting a degenerative change induced by the uptake of the neurotoxic agent, occurred in the cytoplasm of gustatory cell processes. It is suggested that the uptake of 5.6-DHT in gustatory cells may reflect the presence of an indoleamine, probably 5-hydroxytryptamine (serotonin).


Vinblastine-induced microtubular paracrystals in prolactin cells of anterior pituitary gland of lactating rats. Vinblastine sulfate in physiological saline was injected directly into the pituitary glands of lactating rats. Injections were made through the ear canal using a syringe equipped with a 24-gauge needle. The animals were killed at 2, 4, or 6 hours after the injections. When the anterior pituitary glands were examined by electron microscopy, many microtubular paracrystalline deposits were seen in the prolactin and growth hormone cells. The usual cytoplasmic microtubules and microfilaments were not seen in the cytoplasm of these cells. Granular extrusion (exocytosis) was markedly depressed, and an accumulation of secretory granules was definitely observed in the prolactin cells after the administration of vinblastine.


The resurgence of heroin abuse in the District of Columbia. Prospectively collected drug abuse trend surveillance data suggest that the rate of heroin use in Washington, D.C. is rising following a two year decline in the magnitude of this problem. Supportive data include increased potency of street level heroin, increased numbers of heroin-related deaths, increased detection of heroin positive urine specimens in the D.C. Superior Court arrestee population, increased demand for addiction treatment services and rising property crime rates. Increased prevalence of heroin use has not yet been associated with an increase in incidence, suggesting that former heroin users have begun to use once again following a period of abstinence. Analysis of heroin specimens seized across the United States suggests that cities formerly dependant upon European (white) heroin have now developed a new heroin distribution system which supplies Mexican (brown) heroin. This has offset the reduction in heroin use observed during 1972-1973 concomitant with the East Coast heroin shortage and widespread introduction of addiction treatment services.


Social sanctions and rituals as a basis for drug abuse prevention. This paper will report on preliminary findings of an on-going study of "controlled" use of marihuana, psychedelics, and opiates which point to the possibility of minimizing the social costs of illicit drug use via social control. This study, sponsored by The Drug Abuse Council, Inc., a non-profit private foundation, shows that despite the lack of larger cultural support for controlled illicit drug use and other obstacles, users are able to develop and maintain moderate, long-term, nonabusive, i.e., controlled, drug-using patterns. We will show that these patterns are primarily supported by the development of social drug-using situations in which sanctions and rituals permit use while condemning abuse. In the discussion, we will compare the management of controlled use in our sample to the larger culture's handling of alcohol.


Psychiatric evaluation services to court referred drug users. This paper reports on the description and outcome of one hundred youthful drug abusers referred from family court for psychiatric evaluation and treatment recommendation. The average referral, both male and female, was a 16-year-old white Catholic from a middle class background who was diagnosed as having a personality disorder. Significantly more males than females showed pathology in early childhood such as behavior problems in school and hyperactivity. Follow-up data collected up to 6 months after evaluation and treatment recommendation indicated that approximately half of the clients showed improvement in terms of work and/or school adjustment, social relations, and drug use.


Simulations in drug training.

Simulations in drug training. A simulation over a five-day period allowing clinicians to become patients and apply what they experience is presented as a vehicle from which important learning can take place to help clinicians function better within clinical work environments. The simulation gave clinical trainers and trainees in the drug field mutually shared experiences that were understood and applied to real work situations through discussions, lectures, and presentations. Clinicians had the opportunity to understand how therapeutic structures affect individuals through experiencing the structures as recipients of service.


The impact of peer pressure on the verbally expressed drug attitudes of male college students. Peer pressure was shown to have a powerful influence on the verbally expressed drug attitudes of the undergraduate male sample. Subjects exposed to a group which consistently espoused either conservative (anti-drug) or liberal (pro-drug) attitudes toward the personal use of drug were highly likely to conform to the groups' attitudinal norms (p less than 0.001). Effects of natural peer groups are discussed along with recommendations for primary prevention programming and further research.


Problem drinkers among patients on methadone. Among 212 former heroin users maintained on methadone, the authors identified 27% as problem drinkers. The problem drinkers were found remarkably similar to other patients on methadone in personal and treatment characteristics. They differed significantly from other patients in only three respects: the problem drinkers worked more frequently at manual labor, they had more evidence of liver disease, and they appeared more depressed. All subjects showed more depression than normal controls. This finding with evidence from other studies of depression among opioid users suggests that depression may serve as an important etiological factor in chronic opioid use.


Plasma testosterone levels in healthy male marijuana smokers. Plasma testosterone, FSH, and LH levels were obtained from 25 healthy consecutive heterosexual male mauijuana smoking university students. All values were within the range of normal and the means did not differ significantly from those of 13 normal controls. These data suggest that the casual marijuana smoker (at least one time weekly with an average of 5.1 joints per week) may have plasma testosterone levels which are normal for the time of day and the laboratory.


Two autopsy cases of diffuse gastrointestinal polyposis with ectodermal changes. Cronkhite-Canada syndrome. Two autopsy cases of Cronkhite-Canada syndrome were reported. The caused of hypoproteinemia, electrolyte imbalance and ectodermal changes were discussed with reference to previously reported cases. The mechanism of protein loss was probably due to outflow into the intestinal lumen of the mucous substance in the cystically dilated glands, directly and/or indirectly followed by loss of mucosal surface. Electrolyte imbalance probably developed from gastrointestinal loss as well as poor substitution. The ectodermal changes were probably not a subsequent part of the emaciation or hypoproteinemis, but an inherent part of this disease. Therapy, whether substitution or surgical procedure, should be selected in order to control the general condition of the patient.


Leiomyosarcoma of the colon exclusive of the rectum. Five cases of leiomyosarcoma of the colon are presented along with a review of the literature. In our cases the presenting symptoms and signs included abdominal pain, diarrhea, weight loss, blood in stools and abdominal mass. Anemia was present in four cases. Roentgenologically, an intraluminal tumor with obstruction was found in two cases, paralytic ileum in one and two cases were reported as "negative". At surgery there were peritoneal implants in three cases, metastases to the liver in two cases and perforation of the tumor in one case. Only diagnostic or palliative surgery was performed in all cases. All patients died of tumor within 15 months. The clinicopathological findings are similar to those reported by others in patients with extensive disease.


Gastrointestinal phytobezoars in Africans. Fourteen gastrointestinal phytobezoars are presented. There have not been previous reports in Africans. Eleven were gastric and mimicked wither peptic ulceration or carcinoma of the stomach. The classical barium meal appearance of a mobile filing defect was present in the majority but a confident diagnois of carcinoma of the stomach was made in two cases in whom fiberoptic endoscopy established the correct diagnoisis. The bezoars were composed of vegatable material from either a tuber or rhizome. Three ileal bezoars presented with acute intestinal obstruction; two were probably the result of incompletely masticated maize porridge.


Enzymatic softening and endoscopic destruction of a phytobezoar in an unoperated stomach. A phytobenzoar formed in an intact stomach due to the excessive intake of citrus fruit. This was successfully treated by the combined use on a multienzyme preparation to soften it followed by its endoscopic destruction.


Potential economic effets of a brand standardization policy in a 1000-bed hospital. The potential economic effects of a brand standardization policy on 50 multiple source, nonproprietary drugs in a 1000-bed hospital which uses a unit dose drug distribution system were studied. Inpatient drug usage cost and inpatient drug inventory cost for the year 1974 were compared under the existing nonformulary system and a simulated formulary system of brand standardization. Drug usage cost was defined as expenditures made by the study hospital for drugs which were administered. Drug inventory cost was defined as the dollar value of drug inventory being stored for use in the hospital. Potential saving in excess of $35,000 for drug usage cost and $9,000 for drug inventory cost could have been realized with a brand standardization policy on 50 nonprietary drugs. The differences in costs were significant at the 0.005 level. It is concluded that a brand standardization policy can be effective means of reducing drug usage cost and drug inventory cost in a large hospital.


Recommended system for surveillance and reporting of problems with large-volume parenterals in hospitals. Recommendations regarding the detection, confirmation and notification of problems associated with the use of large-volume parenterals at the hospital level are presented. The recommendations are given in a stepwise manner, and include graphic outlines of the evaluation and reporting processes for both product- and patient-signaled problems associated with large-volume parenterals. It is recommended that each hospital appoint a product control officer who would coordinate the hospital's reporting of large-volume parenteral problems.


Disaster alert plan for a hospital pharmacy. A disaster alert plan for the department of pharmacy of a large hospital is described. The plan is intended to effectively and efficiently alert and mobilize pharmacy personnel in the event that the hospital should re required to deal with mass casualties.


Antihypertensive therapy with hydralazine and propranolol: a case history. Rapid control of arterial blood pressure through use of the interacting drugs hydralazine and propranolol is discussed. A case history illustrating the treatment is described, and various aspects of this therapy are discussed, including mechanisms of action and side effects.


Systematic approach to drug information requests. A five-step systematic technique used for answering drug information requests is described. Step 1 is classification of the request. Step II involves determination of exactly what information is being requested and why, and ensuring that all pertinent background data are obtained. Step III is a systematic search of the literature, beginning with general references and progressing through secondary sources to primary articles. Step IV is formulation of the accumulated data into an appropriate writtern of verbal response. Step V involves reclassification of the request which may be necessary if there is a change in its scope.


Changes in serum total protein values occurring in clinical samples during shipment. Total protein and protein electrophoresis determinations were performed on paired serum samples before and after shipment of the samples via parcel post. After shipment, one serum from each pair of samples was analyzed at the same laboratory that had performed the initial analysis; the other sample from the pair was analyzed after its receipt by a referral laboratory. The results indicate that, due to some factor or a combination of factors occurring during shipment, statistically significant apparent increases were observed in 86 per cent of the total protein values and in 66 per cent of the albumin values. Experimentally, both mechanical agitation and bacterial contamination are capable of causing slight elevations similar in pattern to those observed in the shipped samples. The significance of these findings relative to clinical interpretation and to analytical quality control programs is discussed.


Parathyroid hormone responsiveness in hypoparathyroidism with hypomagnesemia. The failure to respond normally to parathyroid hormone (PTH) administration has been reported in patients with severe hypomagnesemia. A patient with hypoparathyroidism and a markedly decreased serum concentration of magnesium (0.7 mEq/liter), but a normal red blood cell magnesium level, is described who increased serum calcium concentration and decreased per cent renal tubular reabsorption of phosphate when parathyroid extract was given. It is suggested that PTH responsiveness in hypomagnesemic patients may, at least in part, be dependent upon the adequacy of intracellular magnesium stores. This interpretation is supported by the normal cellular (red blood cell) magnesium concentrations observed in this patient and in comparable studies in which PTH responsiveness in the presence of hypomagnesemia was demonstrated. In addition, a failure of optimal renal conservation of magnesium was noted to occur in this patient since, despite hypomagnesemia, urinary magnesium excretion was greater than the 1 mEq/day loss that is seen when magnesium conservation is induced by means such as dietary restriction.


Acute bacterial meningitis: an analysis of factors influencing prognosis. Three-hundred and forty-nine cases of acute bacterial meningitis treated during a 25-year period (1949 through 1973) were reviewed to determine the prognostic significance of initial historical, physical and laboratory findings. A poor prognosis was associated with age greater than or equal to 40 years (p less than 0.01), presence of predisposing illness (p less than 0.01), associated illness (p less than 0.01), absence of nuchal ridity (p less than 0.05), and derangement of cerebral function (p less than 0.01). The effects of predisposing illness and moderate cerebral dysfunction were dependent upon age. In contrast, the effects of associated illness, mild or severe cerebral dysfunction, and absent nuchal rigidity were independent of age. Laboratory studies associated with a poor prognosis included an elevated cerebrospinal fluid (CSF) protein (p less than 0.05), a positive CSF smear (p less than 0.05), or culture (p less than 0.01), or bacteremia (p less than 0.01). No prognostic significance could be attributed to race (p greater than 0.05), sex (p greater than 0.05), prior antibiotic therapy (p greater than 0.05), duration of illness before institution of adequate therapy (p greater than 0.05), CSF leukocyte count (p greater than 0.05), frequency of polymorphonuclear leukocytes in CSF (p greater than 0.05), CSF sugar less than or equal to 40 mg/100 ml (p greater than 0.05), or a CSF sugar-simultaneous blood sugar ratio less than or equal to 0.40 (p greater than 0.05).


Aplastic anemia in Isreal: evaluation of the etiological role of chloramphenicol on a community-wide basis. A nationwide study of aplastic anemia in Israel revealed a mean yearly incidence of 7.1/1,000,000 in males and 8.7/1,000,000 in females. Twenty-five per cent of the cases reported had an apparent chloramphenicol etiology. Ten patients, five treated with chloramphenicol and five without it, developed acute leukemia. The median survival was 11 months in males and 28 in females. Survival was particularly inferior in chloramphenicol-related cases, suggesting that this group constitutes a specific entity.


Bone marrow 99m Tc sulfur colloid distribution and marrow cellularity. The relationship between marrow distribution as imaged with 99mTc sulfur colloid and histologic estimate of bone marrow cellularity was examined in 101 patients. The patients were divided into three groups according to marrow cellularity: normocellular, hypercellular or hypocellular marrow. The marrow distribution of these patients was graded as extended, not extended or not visualized. A general association between marrow cellularity and marrow distribution was found. Seventy-seven per cent of patients with normocellular marrow had limitation of marrow within normal sites and a similar number of patients with reactive hypercellular marrow had marrow extension. On analysis of the patients that were exceptions to this generalization the following observations were made. In patients in whom the marrow is hypercellular and infiltrated with abnormal cells or tissue the marrow distribution may not be visualized with radiocolloid. Stimulation of hematopoiesis may result in marrow hypercellularity without marrow extension beyond the usual sites. Stimulation of one or more hematopoietic cell lines may result in marrow extension without marrow hypercellularity, suggesting an impairment of hematopoietic cell response. Peripheral marrow extension as observed with radiocolloid, therefore, is not simply a reflection of marrow hypercellularity but probably represents a response of the bone marrow stroma to situations in which one or more hematopoietic cell lines is stimulated.


The prediction of glaucoma from ocular biometric data. Part 1. An application of multiple regression analysis. Two sets of multiple regression equations (prediction systems) were derived from the analysis of ocular biometric data obtained from glaucoma patients (16 open angle; 16 angle-closure) and 75 normal subjects. Discriminant scores were established for both sets of equations which minimised the number of false negatives. One set, the 'Glaucoma Equations' was applied to the data to segregate the glaucoma from the normal subjects. The other prediction system, the 'Classification Equations,' was then applied to the group defined as glaucomatous to discriminate between patients in the angle-closure and open angle categories. The performance of these equations, obtained by comparing the predicted and actual classifications for this sample, was such that between 9 and 12% of false positives and 0 and 3% false negatives were found on the 'Glaucoma Equations' and between 6 and 12% of false positives with no false negatives on the 'Classification Equations.'


The prediction of glaucoma from ocular biometric data. Part 2. An evaluation. A method of glaucoma prediction from ocular biometric data has been described previously. A study was undertaken to evaluate the performance of the existing multiple regression equations (prediction systems) on data obtained from an independent sample consisting of 22 angle-closure glaucoma, 29 open angle glaucoma and 44 normal subjects. This performance, found by comparing the predicted and actual classification for this sample, was such that between 2 and 7% false positives and 12 and 27% false negatives were found on the equations differentiating glaucoma from normal subjects; and between 14 and 27% false positives, with 10 to 14% false negatives on the equations classifying the glaucoma subjects as angle-closure or open angle. From these results the efficiency of glaucoma prediction from ocular biometric data would appear to be equal to that of the combined tonography and provocative tests, provocation with corticosteroids and visual field screening.


Citrobacter diversus at Grace Hospital, Detroit, Michigan. Over a six-month period from December 1973 to June 1974, isolations of Citrobacter diversus were obtained from nine patients at Grace Hospital. Our initial experience was with a patient who developed pneumonitis and a massive fatal empyema due to this organism. Seven of the nine patients were 50 years of age. Three patients had an underlying malignancy. Four patients experienced significant clinical infections. Isolations in three patients were considered to be commensal, and two isolations were of indeterminate significance. Our Citrobacter diversus isolates, which can be confused with Escherichia coli, were uniformly resistant to ampicillin and carbenicillin and sensitive to the cephalosporins, tetracyclines, and gentamicin. These results agree with previous reports. Citrobacter diversus appears to be capable of causing serious clinical disease. Patients most at risk are elderly compromised hosts and infections are usually hospital acquired.


Relationship between changes in corneal configuration and thickness. The experiment was conducted on a sample of 26 subjects including both males and females and a control group of five. Their mean age was a little over 24 years. Corneal thickness and configuration were measured before and after the subjects had been wearing rigid and flexible contact lenses for three hours; measurements were also taken on control subjects at two different sessions, before and after a three-hour period. The statistical analysis showed a low but significant correlation between corneal thickness and corneal shape.


Effect of hemodialysis on red cell organic and inorganic phosphates. Red cell 2,3 diphosphoglyceric acid (DPG), total nucleotide phosphate, inorganic phosphate, and plasma inorganic phosphate were measured at the onset and termination of 22 hemodialyses performed for chronic renal failure in 19 patients. Plasma inorganic phosphate decreased from a mean of 2.05 mM/liter +/- 0.14 to 1.26 mM/liter +/- 0.09 (p less than 0.005) while intracellular inorganic phosphate fell from 1.76 mM/liter +/- 0.12 RBC water to 1.21+/-mM/liter (p less than 0.005). Mean DPG was 6.37 mM/liter RBC +/- 0.23 at the start of the dialysis and 6.08 mM/liter +/- 0.24 at the termination (p=n.s.). Mean nucleotide concentration was 5.90 mM phosphorous content/liter RBC+/-0.26 at the start and 5.95 mM/liter 0.21 at the end (p=n.s.). Although there were significant decreases in intracellular and plasma inorganic phosphate concentrations immediately following dialysis, neither the DPG nor nucleotide phosphate concentrations were significantly altered by this short-term procedure. Red cell water inorganic phosphorous rapidly attained identical concentration with plasma water inorganic phosphorous.


Regulation of gonadotropin response in testicular feminization syndrome. The effects of hormonal manipulation on gonadotropin, androgen, and estrogen concentrations in a patient with testicular feminization syndrome (TFS) were studied to clarify the feedback regulation of gonadotropins. Baseline serum LH concentrations were normal to high and FSH concentrations were normal despite markedly elevated plasma testosterone concentrations, implying the lack of a reciprocal control relationship, and fluoxymesterone administration failed to alter gonadotropin or androgenic steroid levels. Clomiphene administration resulted in a rise in both LH and androgen levels, while moderate doses of exogenous estrogens effected a diminution in testosterone but did not significantly alter the levels of gonadotropins. Following gonadectomy, these same doses of estrogens produced a dramatic fall in the very high postoperative levels of gonadotropins. These results suggest that gonadotropin regulation is mediated by estrogens and not directly by androgens in TFS.


Bone and joint infection with Arizona hinshawii: report of a case and a review of the literature. The Arizona group of gram-negative enteric microorganisms is closely related to the genus Salmonella. Arizona infection is common in avian and reptilian species. Whereas Arizona intestinal infection has been observed in humans, extraintestinal disease has infrequently been described. A case of a 23-year-old woman with systemic lupus erythematosus and sickle cell trait who acquired Arizona hinshawii osteomyelitis and septis arthritis is presented. The patient recovered after treatment with ampicillin and cephalosporins. Three previously described cases of bone and/or joint infection with Arizona are summarized. Because Arizona species frequently ferment lactose, it is possible that they are discarded from fecal isolates by bacteriology laboratories. It is conceivable that many intestinal and extraintestinal infections are either overlooked or mistakenly identified.


Binocular summation and peripheral visual response time. Six males were administered a peripheral visual response time test to the onset of brief, small stimuli imaged in 10 degrees arc separation intervals across the dark adapted horizontal retinal meridian under binocular and both monocular viewing conditions. This was done in an attempt to verify the existence of peripheral binocular summation using a response time measure. The results indicated that from 50 degrees arc right to 50 degrees arc left of the line of sight binocular summation is a reasonable explanation for the significantly faster binocular data. The stimulus position by viewing eye interaction was also significant. A discussion of these and other analyses is presented along with a review of related literature.


Changes in the contrast sensitivity function induced by contact lens wear. Contrast sensitivity functions (i.e. minimum contrast required to resolve a sine wave grating as a function of spatial frequency) were determined for subjects when wearing normal spectacle corrections and when wearing either hard or soft contact lenses. Corections provides a more definitive evaluation of visual performance with contact lenses than do the conventional clinical procedures.


Overwhelming pneumococcal sepsis 25 years after splenectomy. In a 47-year-old healthy male, the syndrome of overwhelming pneumococcal sepsis, associated with diffuse intravascular clotting, appeared 25 years after a post-traumatic splenectomy. Although no other disease was present, the course was fulminant and the outcome fatal. Splenectomy for any condition and in all ages, augments the risk to severe  pneumococcal infection.


Luminance changes of the fundus reflex.

Luminance changes of the fundus reflex. A recording retinoscope was developed to measure the luminance of the fundus reflex during problem-solving tasks. 10 students were used as subjects. The luminance of the reflex was recorded while the subjects read 5 passages of graded reading material and performed an addition task. A reversal design was used to determine the effects of pupil changes and accommodation on changes in the luminance of the reflex. Relatively large changes in the luminance of the reflex were recorded. These were due to accommodation. The subjects' comprehension of the reading material did not appear to affect the luminance of the reflex in the manner predicted by previous studies. However, a change in task from simple reading material to an addition task appeared to increase the luminance of the reflex.


Retinal and post-retinal components of visual illusions. A technique is presented permitting control of input to each hemiretina and each hemisphere, of the various elements of a visual illusion. When the retinal effects and post-retinal effects are added, the result is greater than the total illusory effect. This is believed due to the mixing between hemispheres via the corpus callosum, and suggests a possible means of assessing the role of the corpus callosum.


Ultrastructural studies of perivascular cuffing cells in multiple sclerosis brain. Perivascular cuffs in brains taken at autopsy from 6 patients with multiple sclerosis (MS) were examined by electron microscopy. Light and electron microscopy of brain revealed acute and chronic types of cuffs. The acute type of cuffs, consisting of many lymphocytes and lymphoid cells and a few lipid-laden macrophages, was usually seen in the nondemyelinated white matter or in the margin of the plaques, and infrequently within a plaque. The chronic type consisted mainly of macrophages, plasmacytoid cells, and plasma cells and was always seen within the plaques. In the parenchymal tissue of the white matter, macrophages participated in phagocytosis of myelin and axons, but no peeling or stripping of myelin sheath by inflammatory cells was observed. So-called paramyxovirus-like fuzzy filaments were observed in the nuclei of the mononuclear cells of perivascular cuffs obtained from 5 patients. The filaments were found predominantly in the acute rather than chronic type of cuffs. Specific antigens of measles and 6/94 viruses and intranuclear RNA corresponding to the filaments could not be demonstrated in the perivascular inflammatory cells by the immunofluorescence technique or acridine orange staining.


Economy of effort in electron microscope morphometry. Statistical techniques known as the analysis of variance make it possible for the electron microscopist to plan work in such a way as to get quantitative data with the greatest possible economy of effort. This paper explains how to decide how many measurements to make per micrograph, how many micrographs per tissue block, how many blocks per experimentally treated organ, and how many organs per experimental treatment group.


Sclerosing alveolitis induced by cyclophosphamide. Ultrastructural observations on alveolar injury and repair. Adult rats received, intraperitoneally, 20 mg/100 g body weight of cyclophosphamide and were killed 1, 2, 3, 4, 7, 14, 21, and 28 days thereafter. Lung samples were studied by light and electron microscopy. Light microscopy revealed septal and intraalveolar hemorrhages at 2 days and hyaline membranes at 4 days. At 1 to 2 weeks the alveoli were reepithelialized; beyond these intervals there was septal thickening with increased septal cells and interstitial substance. Electron microscopy showed capillary endothelial blebs, membranous pneumocyte injury and sloughing, and severe septal edema at 1 to 2 days. At 4 days some granular pneumocytes appeared altered. At 1 week the alveoli were reepithelialized by prominent granular pneumocytes. Beyond these intervals there was septal thickening with abundant septal cells, debris, collagen, elastin and microfibrils. Some septal elements showed features consistent with "contractile interstitial cells." There was also alveolar collapse indicated by "trapped" granular pneumocytes surrounded by septal cells and fibers. Occasional granular pneumocytes showed large intracytoplasmic cavities. Cyclophosphamide can induce severe injury involving all alveolar components. The partly denuded alveoli are reepithelialized by proliferating granular pneumocytes, thus confirming their importance in alveolar repair. The subsequent development of sclerosing alveolitis suggests that cyclophosphamide may offer a useful experimental model for the study of alveolar injury and repair. The role of the septal "contractile interstitial cells" in the development of septal fibrosis and the possibility that these lesions are reversible remain to be clarified.


Isolation and partial characterization of human eosinophil granules. Comparison to neutrophils. Human blood eosinophils obtained from untreated patients with large numbers of circulating eosinophils were purified and lysed. An eosinophil contains 2.65 times as much peroxidase, 2.44 times as much beta-glucuronidase, approximately two times as much acid beta-glycerophosphatase, and 1.2 times as much protein as a neutrophil. Lysate filtration allowed isolation of eosinophil granules by isopycnic ultracentrifugation in sucrose. The granules had a mean density of rho 1.24 g/ml, and contained peroxidase, beta-glucuronidase, and acid beta-glycerophosphatase. They totally lacked muramidase and alkaline phosphatase. Electron micrography confirmed the isolation.


Biochemical characterization of Australia antigen. Evidence for defective particles of hepatitis B virus. Australia antigen exists in the sera of chronic carriers in several particulate forms, one of which may represent the virion of hepatitis B. This report describes the existence of subpopulations of these 43-nm particles, the Dane particles, on the basis of the staining properties of their internal cores and banding characteristics in cesium chloride (CsCl) density gradients. These data suggested that only a minor proportion of Dane particles contained an intact viral genome and represent the standard infectious virus of hepatitis B. The bulk of the Dane particles appeared to be deficient in viral nucleic acid and, as defective interfering particles, may specifically interfere with the growth of standard virus. Such defective interfering particles could thereby play a role in the persistence of HBV infection in man.


Mid-sagittal dimensions of cervical vertebral bodies. A series of lateral radiographs of the cervical spinal column was evaluated in order to determine vertebral body dimensions. The sample included males (N=30) and females (N=31) 18 to 24 years old, comprising three stature percentile ranges (1-20; 40-60; 80-99) of the U.S. adult population. A two-dimensional analysis of vertebral body height (average distance between superior-inferior surgaces), depth (average distance between anteriorposterior surfaces), and area (average height X average depth) revealed minimal effects due to stature. In all subjects, average depth exceeded average height for vertebral bodies C3 through C7. Upon combining stature groups, both sexes revealed maximum average values for these dimensions at the seventh cervical vertebral body. Minimum average height occurred at C5 whereas minimum average depth was found at C3. Significant correlation (alpha greater than 0.05) was found for males between ponderal index and height and depth of the C7 vertebra. Male head weight correlated significantly with C3, C4, C5 and C6 vertebral body height and with C3, C5 and C6 vertebral body depth. For females, C7 height and C6 depth correlated significantly with ponderal index and head weight respectively. Probable biomechanical relationships of specific cervical vertebral bodies are noted


Early prenatal attainment of adult metacarpal-phalangeal rankings and proportions. As shown in 56 human embryos and fetuses between 15 and 104 mm in crown-rump length, "adult" metacarpal-phalangeal length rankings are attained by the seventh intrauterine week and near-adult bone-to-bone ratios or proportions by the theirteenth week. Micrometric measurements of optically-projected histological hand sections show relative elongation of the distals between the 15-29 mm and 30-44 mm crown-rump range, and relative reduction to radiogrammetrically-determined adult proportions by the 90-104 mm CRL.