In vitro protein synthesis by inner membranes of rat brain mitochondria. Prior investigation of the protein synthesizing properties of mitochondria involved the whole organelle. In order to better characterize these properties, the present study was concerned more specifically with the activity of the inner mitochondrial membranes (IMM) which recent investigation has implicated as the primary location of mitochondrial ribosomes. To further define mitochondrial protein synthesis simultaneous experimentation was also conducted utilizing cytoplasmic ribosomes thus enabling both qualitative and quantitative comparison between the two systems. Results from this series of investigations reveal a dramatic amino acid incorporating ability by the IMM fraction of the brain mitochondria. This activity, in turn, was shown to be highly independent of exogenous sources of ATP, GTP, pH 5 enzymes, and cytoplasmic ribosomes. Furthermore, the addition of an exogenous source of messenger RNA, polyuridylic acid or (poly (U)) which resulted in an increased incorporation of [14C]phenylalanine into polypeptide in the cytoplasmic system was found to have no effect on the IMM system. Upon comparison of the in vitro protein synthesizing properties of the IMM fraction with those of the cytoplasmic ribosomal system, it became evident that obvious differences existed in the degree of amino acid incorporation and in the sensitivity of this process to the various protein synthesizing inhibitors. Cytoplasmic ribosomes demonstrated a much greater [14C]leucine and [14C]phenylalanine incorporating activity than the IMM fraction. In addition, RNase and cyclohexamide had their greatest effect on the cytoplasmic system while the action of chloramphenicol was most potent on the IMM system. Although puromycin inhibited both protein synthesizing systems, this effect was greatest in the presence of cytoplasmic ribosomes.


Identification of p-hydroxydiphenylmethane as a urinary and fecal metabolite of diphenylmethane in the rat. The conversion of diphenylmethane to p-hydroxydiphenylmethane has been studied in laboratory rats. The urine of rats was found to contain 0.37 mole of unconjugated and 0.06 mole of conjugated p-hydroxydiphenylmethane. Rat feces was found to contain 0.06 mole of a mixture of unconjugated and conjugated p-hydroxydiphenylmethane.


The structure of propranolol hemisuccinate. 1-(N-hemisuccinyl-N-isopropylamino)-3-(1-naphthoxy)-2-propranolol, contaminated with a small amount of the N,O-dihemisuccinyl derivative, is formed when propranolol [1-isopropylamino-3-(1-naphthoxy)-2-propranolol] is allowed to react with succinic anhydride (pyridine, 70 degrees C, 5 hours). This conjugate, used by others for the preparation of an immunogen of propranolol for development of radioimmunoassay methodology for its sensitive quantitation, was previously assigned the O-hemisuccinate structure. The amide structure is assigned on the basis of comparison of infrared and nuclear magnetic resonance spectral data obtained on the product of succinylation of propranolol with data from the model compounds O-acetylpropranolol, N-acetylpropranolol and N,O-diacetylpropranolol.


Dopamine potentiates anaphylactic contraction of pulmonary vein of calf. Isolated strips of pulmonary vein of antigen-sensitized calf contracted to histamine, serotonin and antigen. In the presence of subthreshold concentrations of dopamine (10(-6) M), anaphylactic contractions to antigen were enhanced, whereas responses to histamine and serotonin were not.


Carbon-13 nuclear magnetic resonance identification of 2-hydroxy-3-O-methyl-6beta-naltrexol as a minor naltrexone metabolite. A carbon-13 nuclear magnetic resonance comparison of synthetic and biological samples was used to identify unequivocally 2-hydroxy-3-O-methyl-6beta-naltrexol as a minor naltrexone metabolite in humans. This study points up the increasing usefulness of natural abundance carbon-13 nuclear magnetic resonance techniques in metabolism studies.


Kinetics of pharmacologic response to cocaine. Cocaine plasma concentration-response-time data obtained from the literature were analyzed by pharmacokinetic methods. The plasma concentration-time data yield an elimination half-life of approximately 1 hour and the data suggest that only about 20% of an oral dose of cocaine is absorbed intact into the systemic circulation. Response, as assessed by means of a relative "high" rating scale, declined linearly with time as predicted by theory. The rate of decline of response was found to be 0.0221 "high"/min. The rate of decline of response is a function of the apparent first-order elimination rate constant (K) of the drug and the slope of the response-log plasma concentration curve (m). A value for m of 4.2 "high" was calculated from the response-time data which agreed well with a value of 3.9 "high" for m determined from the slope of the response-log plasma concentration curve.


The kinetics of amitriptyline following single oral dose administration to man. Amitriptyline and its metabolite, nortriptyline, were measured in the plasma of eight humans for 96 hours following oral administration of a 75 mg dose of amitriptyline hydrochloride. Based on the 8 to 96 hour post dosing plasma concentration data, the terminal exponential half life of amitriptyline +/- S.D. was 22.4 +/- 4.3 hr. Based on the 24 to 96 hour concentration data, the "apparent" terminal half time of nortriptyline +/- S.D. was 26.0 +/- 7.4 hours for seven subjects. For these same seven subjects the relative area under the plasma concentration time curve of nortriptyline +/- S.D. was only 0.88 +/- 0.34 times that of amitriptyline. One subject whose apparent nortriptyline half time was 108 hours had a nortriptyline bioavailability 3.83 times that of amitriptyline. Average steady state plasma levels for 12 psychiatric patients who had received a 50 mg oral dose of amitriptyline three times a day for an average of 32 days could be predicted from the single dose plasma clearance of amitriptyline.


Dose-dependent pharmacokinetic behavior of lidocaine in the conscious dog. The apparent steady state blood concentration of lidocaine in dogs depends on the animal's lidocaine treatment history. For example, an infusion of 50 microgram/Kg/min X 240 min followed immediately by an infusion of 125 microgram/Kg/min X 240 min yields steady state lidocaine levels which are consistent with a linear drug dispositional system. However, when the sequence of these infusions is reversed the apparent steady state level during the low infusion rate step is much greater than those predicted from the steady state level observed during the high infusion rate (assuming a linear dispositional model). These data suggest that high dose lidocaine infusion treatment alters the dog's ability to clear lidocaine during a subsequent low infusion rate treatment period.


PGE2: metabolic effects in healthy volunteers. Some metabolic and haemodynamic responses to intravenous prostaglandin (PG) were studied in five healthy male volunteers, aged 27-40. Subjects, who fasted overnight, rested supine for for 30 min before any measurements were made. Control pulse rate and arterial blood pressure were recorded and 20ml venous blood drawn for analysis. Intravenous infusion of PGE2 5 microgram/min then began and was continued for 15 min; the dose was then increased to 7.5 microgram/min. Measurements were made during the infusion at 15 and 30 min and also 15 min after infusion was stopped. Pulse rate increased but blood pressure was unaffected by the infusion. Glycerol and FFA levels rose, whereas lactate and pyruvate levels fell during the infusion. The rise in glycerol level was significant at 30 min. The changes recorded were slight in clinical terms but the study provides a baseline for the screening of other PG analogues.


Barbiturate and amphetamine activity in rats fed a magnesium-deficient diet. Hexobarbital hypnosis and d-amphetamine toxicity were observed in rats fed a commercially available rat food preparation (lab chow) and in another two groups fed complete nutritionally defined diets with or without magnesium. Neither hexobarbital sleeping time nor hexobarbital blood concentration at awakening were affected after 4, 8 or 12 days of feeding the deficient diet. However, increased sensitivity to d-amphetamine was observed after 11 days of feeding the same magnesium deficient diet to other rats. The LD50 of d-amphetamine in magnesium deficient rats was less than 0.5 that recorded for the groups fed lab chow or the nutritionally defined diet with a magnesium supplement.


Enhanced lethality and tissue levels of chloroquine in rats pretreated with pyrogen. The lethality, and concentrations of chloroquine in plasma, brain liver and heart, in control and pyrogen-treated rats were investigated. Pyrogen treatment increased the lethality, the convulsive activity, plasma and myocardial concentrations of chloroquine significantly. The results suggest that the initiation of therapy with chloroquine in acute febrile conditions may require smaller than usual dosage.


The relationship between kanamycin ototoxicity and glucose transport. The clinical utility of the aminoglycoside antibiotics is hampered by their well-known capacity to cause labyrinthine and renal damage. The mechanism by which these damages are produced is unknown. Attention was focused on the aminosugar moiety of these antibiotics by the finding of Owada (1962) which demonstrated that 3-aminoglucose is as ototoxic as its parent antibiotic, kanamycin. It is known that aminosugars compete with glucose for transport and that the sensory cells of the cochlea depend on glucose as a primary energy source. The hypothesis that grew out of these considerations was that kanamycin might be causing its ototoxicity by inhibiting glucose transport at one of several sites in the inner ear. To test this hypothesis the ototoxicity of kanamycin was determined in hyperglycemic animals. Hyperglycemia clearly and dramatically protects animals against ototoxicity as evidenced both by electrocochleographical and histological examination.


Role of phospholipids in the development of the hepatic endoplasmic reticulum associated with drug metabolism. During development from fetal to adult age in the female rat the rapid increase of hepatic drug metabolizing activity was paralleled by changes in the production of membrane bound phospholipids. Microsomal phosphatidylcholine synthesis was raised in particular, and was associated with an enhanced activity of S-adenosyl-L-methionine:microsomal phosphatidylethanolamine methyl transferase. This enzyme is responsible, in part, for phosphatidylcholine production by stepwise methylation. Phospholipid acyl components such as various unsaturated fatt acids also showed a sharp rise during development. These results demonstrated that maturation of the hepatic endoplasmic reticulum was correlated with an increased production of phosphatidylcholine that contained greater amounts of unsaturated fatty acids. It is therefore suggested that during maturation phospholipids are not only essential in providing the structural units of the membranes but they also act as organizers of enzyme function.


The membrane effects of vitamin E, cholesterol and their acetates on peroxidative susceptibility. Ox-brain phospholipid liposomes provide an organised membrane structure as well as a substrate for lipid peroxidation. Vitamin E is a poor antioxidant outside the membrane but has considerable activity within. Inclusion of its acetate derivative confirmed the dual role of vitamin E as both a stabilising structural component and free-radical scavenger. Cholesterol similarly stabilises the membrane but does not appear to significantly protect by radical scavenging. Its functions are closely related to the amount and type of phospholipid present in the membrane. Changes in oxidative susceptibility following free-radical stress provide a sensitive measure of membrane structural organisation.


Neuronal and liver protein synthesis in the developing offsprings following treatment of pregnant rats with ethanol or 1,3-butanediol. Ethanol or 1,3-butanediol ingestion during pregnancy and lactation results in a marked inhibition of neuronal protein synthesis in the 18-day-old rat progeny, however the same treatment had a stimulatory effect on the amino acid incorporation by neuronal perikarya of 8-day-old pups. Liver protein synthesis in vitro, on the other hand, was enhanced in both 8-day and 18-day-old pups as a consequence of maternal ethanol consumption. This was attributable to increased amino-acylation in the liver pH 5 enzyme fraction.


In vivo metabolism of N-alkylamphetamines in the rat--the effect of N-alkyl chain length on oxidation of the aromatic ring. In vivo metabolism of N-alkylated amphetamines in the rat produced 4-hydroxy- and 4-hydroxy-3-methoxy-metabolites. The relative quantities of the phenolicmetabolites formed were dependent upon the length of the N-alkyl substituent.


Regional localization of methaqualone in rat brain. Distribution of orally administered methaqualone-14C (25 mg/kg) in several rat brain areas was examined. Peak concentration attained at 1.5 hr. Among brain areas, highest concentration was measured in pineal gland (8.2 microgram/g). MTQ levels in the cortex, pituitary, hypothalamus and hippocampus ranged from 3 to 3.5 microgram/g, those in the mid-brain, medulla-pons, striatum and cerebellum from 2 to 2.5 microgram/g. Significant amounts of MTQ in all brain regions were still present at 3 hr. These results indicate that MTQ was somewhat uniformly distributed in various brain regions as a result of its lipophilic nature.


Effects of cholinomimetic agents on pentobarbital anesthesia in mice. We evaluated the effects of physostigmine, choline chloride, and neostigmine on pentobarbital anesthesia in mice, both when given before and after the administration of pentobarbital. Neostigmine and choline chloride had no effects. Physostigmine shortened the onset of pentobarbital anesthesia when given before pentobarbital but had no effects on the duration of anesthesia. However, when given after pentobarbital it shortened the duration of pentobarbital anesthesia. It seems unlikely that the above effects of physostigmine are dependent on the cholinergic system in the nervous system since neostigmine and choline chloride were without action. However, they may be due to the effects of physostigmine on the blood brain barrier permeability to pentobarbital.


Effect of furosemide on mesenteric blood flow in the dog. Diuretic therapy has been implicated as a possible inciting factor in nonocclusive mesenteric infarction. In view of this possibility, the effect of furosemide on superior mesenteric arterial blood flow (MBF) was investigated using electromagnetic flow probes in pentobarbital anesthetized dogs. After administration of furosemide, 1 mg/kg iv, MBF decreased by 44%. To assess the role of extracellular volume depletion induced by the diuresis in reducing MBF, volume depletion was prevented by infusing isotonic saline at a rate matching urine flow. In these experiments, MBF was not decreased by furosemide. Thus furosemide induces a marked decrease in mesenteric blood flow and this hemodynamic action involves a mechanism that is dependent upon the volume depletion induced by the drug.


Effects of ethanol and dihydroergotoxine on mouse brain myelin components. The effects of prolonged consumption of ethanol, dihydroergotoxine (Hydergine) and Hydergine-plus-ethanol on brain myelin components isolated from the medulla oblongata of mouse brain were examined. Based on protein content, the amount of myelin isolated from the brain tissue was not different with regard to the various treatments. However, there was a significant decrease (20%) in myelin phospholipid and cholesterol to protein ratios in the ethanol group as compared to controls and the Hydergine-treated group. On the contrary, the Hydergine and Hydergine-ethanol groups had higher cholesterol to phospholipid ratios than controls. In spite of the changes in membrane components, little change in acyl group composition of the phosphoglycerides was found in myelin.


Effect of hyperoxia on imipramine uptake and metabolism by the isolated, perfused rat lung. Imipramine (IMP) is a biologically active amine which is removed from the circulation by the lungs. We evaluated the effect of high partial pressures of O2 on pulmonary uptake and metabolism of IMP. Lungs from rats previously exposed to either air (controls) or 100% O2 at 1 ATA for 12-48 hr were isolated, ventilated and perfused via the pulmonary artery. Uptake of IMP was calculated from the arteriovenous difference of 14C-IMP across the lung and lung effluents and homogenates were analyzed for the presence of metabolites of IMP. IMP was avidly concentrated in the lungs of control rats by a saturable process, and this saturable uptake was not affected by 12-48 hr exposure to 100% O2. 14C-IMP was not metabolized by control of O2-exposed lungs.


Plasma amino acid response to single test meals in humans. II. Healthy young adults given synthetic amino acid mixtures. The postprandial plasma amino acid response to test meals containing different amino acid mixtures was analysed in six young adults. The amount of amino acids given in each test meal was equivalent with 3.5 g of nitrogen. Each test meal also contained a large amount of carbohydrate (mainly as wheat starch). Five different amino acid mixtures were used, and the effects on the plasma amino acid response of different dietary levels of lysine, isoleucine and methionine were studied in detail. The plasma amino acid responses were evaluated both by a modified Longenecker and Hause procedure (PAA ratios) and by the procedure proposed by Graham and Placko (percentage changes in the postprandial essential amino acid molar ratios). The plasma amino acid response of lysine was found to be less sensitive to reductions in the dietary supply than the isoleucine and methionine responses evaluated by these procedures. The influence of altered levels of dietary supply on the postprandial plasma concentrations of isoleucine and methionine seemed to be specifically great at the intake levels where these essential amino acids become limiting for protein utilization according to the amino acid score of the test mixtures. The nutritional significance of the postprandial pattern and level of essential amino acids is discussed on basis of the present results. Experimental conditions and evaluation models are examined with regard to the use of single-meal plasma amino acid responses to assess the protein quality of human diets.


[Side effects of proximal selection vagotomy on the esophagus. I. Effects on the esophageal blood circulation (author's transl)]. The influence of the proximal selective vagotomy (PSV) with following skeletisation of parts of the esophagus on its circulation was investigated in an animal experimental study. Among the 6 dogs with PSV and skeletisation of the esophagus up to the upper thorax apertura one was seen with necrosis and perforation in the distal part of the esophagus. The last 5 dogs and the 4 dogs in which after the PSV only the denudation of the distal part of the esophagus was carried out no signs of circulatory disturbance were seen. The blood circulation in human esophagus, as described in the literature, and the transfer of the results from dogs to human is discussed. An enlarged skeletisation of the esophagus in order to improve the completeness of the PSV does not harm blood circulation.


[Side effects of proximal selective vagotomy on the esophagus. II. Experimental study of effects of the esophageal motility and the lower esophageal sphincter (author's transl)]. The influence of the proximal selective vagotomy (PSV) with mobilisation of the esophagus of 6 cm or up to the upper thorax apertura on esophageal motility in a first group and mobilisation of 2 or 7 cm on the lower esophageal sphincter tone in a second group was investigated in canine experiments. The loss of coordinated peristalsis in the denuded segment causes a deterioration of esophageal passage. The degree of disturbance of swallowing depends on the length of the mobilisation. Reduction of lower esophageal pressure was observed. These reduction was not influenced by the extent of this motilisation. Acid reflux was not seen. Due to anatomical differences between these two species, these results cannot be readely transferred to human. Enlarged mobilisation of the esophagus for completion of PSV cannot be recommanded without reservation. Clinical studies are needed.


Complement system in sodium taurocholate pancreatitis in the rat. The role of the complement system was studied in Na-taurocholate pancreatitis in rats. Complement activity (CH 50) was determined at various times in the course of pancreatitis. Immediately after induction of acute pancreatitis, serum complement activity declined and massive C 3 deposits could be detected in the vicinity of acinar necroses and necrobioses. After a phase of recovery three to six hours postoperatively a second complement consumption occurred. Lethality rate increased as serum complement activity fell below 50% of preoperative values. The degree of C 3 deposition increased up to six hours. Decline of serum complement activity and deposition within the pancreas seemed to be correlated with histologically demonstrable tissue lesion. The first decline of complement activity in serum is thought to be caused by liberation of complement activating substances within the pancreas due to the detergent action of Na-taurocholate itself. The second decline, however, may be due to the liberation of complement activating and/or destroying enzymes into the blood stream.


[Contents of glycogen, glycolytic activity and contents of metabolites in the atrioventricular system of bovine hearts (author's transl)]. In the atrioventricular system (AVS) consisting of the compact node, the penetrating bundle and the branching bundles of about 250 bovine hearts there were made several studies: 1. In quickly removed and fixed specimens (distal AV-node, penetrating bundle) determination of a metabolic state with respect to glycogen, glucose, lactate, ATP, ADP, AMP, creatinephosphate, total creatine, gluc-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, dihydroxyacetonphosphate and pyruvate. 2. Determination of glycogen contents and glygolytic activity in AVS and its parts for ischemic times up to three hours. 3. The determination of metabolic contents in samples of connective tissue in atrium and ventricle of bovine hearts. The AV-nodes are poor in glycogen comparable with glycogen content of central nervous system and other ganglia. Penetrating bundles of Hiss and branching bundle belong after liver to the glycogen richest parenchyma of animal tissues. Even after ischemia of 3 h only a part of glycogen was recovered as lactate. The greater part of glycogen must be considered as a structural element of Hiss bundle and branching bundles of the ventricles.


Analysis of the effects of pulsatile capillary blood flow and volume on gas exchange. Blood flow into the pulmonary capillaries and the volume of blood within the capillary bed are both pulsatile with the cardiac cycle. We have developed a quantitative model of diffusional gas exchange in the lung to investigate the effects of coupling between these two time-varying parameters on lung O2 and CO2 exchange. For normal man breathing room air at rest, the computed results agree well with previous predictions for the constant flow and volume case, and for the case of pulsatile flow alone. When coupled time-varying pulmonary capillary blood flow and volume are included, using the best data available in the literature to define these parameters, diffusional O2 exchange is improved over the cases of pulsatile flow or volume alone, and closely approximates that obtained for the hypothetical constant flow and volume case. CO2 exchanges, and O2 exchange during hypoxia, are not affected by pulsatile flow and/or volume. These results suggest that O2 exchange is efficient in the presence of coupled blood flow and blood volume pulsations as they exist in the lung capillaries, and that these conditions may be optimal for gas exchange under certain physiological (or pathological) conditions.


Effect of chemoreceptor denervation on the pulmonary vascular response to atelectasis. Six dogs anesthetized with 30 mg/kg pentobarbital were ventilated after differential cannulation of the main stem bronchi. Following sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta (QT). Following 10 min of bilateral 100% O2, QL was 37.4 +/- 5.8% of QT. When left lung atelectasis was induced while the right lung remained on 100% O2, PaO2 remained above 75 mm Hg and QL fell to 26.1 +/- 5.0% of QT. However, when the right lung was ventilated with room air while the left lung remained atelectatic, PaO2 fell to 50.0 +/- 2.6 mm Hg and QL rose to 36.7 +/- 6.2% of QT. Six dogs which had undergone peripheral chemoreceptor denervation prior to these experiments showed a similar decrease in perfusion of the atelectatic left lung when the right lung was ventilated with 100% O2, but did not increase blood flow to the atelectatic lung during systemic hypoxemia. Thus, the increased blood flow to the atelectatic lung which occurs during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.


Dead space and tidal volume of the giraffe compared with some other mammals. The ventilation, tidal volume and anatomical dead-space were measured in a living giraffe and compared with similar measurements in a camel, red deer, llama and man. The giraffe had a resting tidal volume of about 3.3 litres with a dead-space/tidal-volume ratio of 0.34. The giraffe breathes slowly, apparently because of the unusually small diameter of its trachea relative to its length, compared with known measurement in other mammals.


The contribution of the reflex hypoxic drive to the hyperpnoea of exercise. Oxygen breath tests have been applied to six normal subjects at rest and during steady state exercise on a bicycle ergometer (200, 400 and 600 kpm) to estimate the contribution of the reflex hypoxic drive to total ventilation. The subjects were changed without their knowledge from air to 100% oxygen for 4--5 breaths, the fall in ventilation was recorded and expressed as a percentage of total ventilation (hypoxic drive). The average reflex hypoxic drive was 16.2% (SE +/- 2.6; n = 35) this remianed unaltered during all levels of steady state exercise. The maximum fall in ventilation occurred earlier in exercise (P less than 0.0005). At rest the maximum fall occurred on average 31.2 s (SE +/- 2.6) from the start of the first breath of oxygen. During the first level of steady state exercise the maximum fall occurred 19.4 s (SE +/- 0.5) from the start of the first breath of oxygen. It is concluded that the contribution of the reflex hypoxic drive to the total ventilation is unaltered by exercise although a substantial part of the hyperpnoea can be accounted for by the presence of this drive.


Permeability and diffusion coefficient of oxygen in membranes for oxygen electrodes. Oxygen diffusion coefficient and permeability in thin membranes of low-density polythene and laminated polytetrafluorethylene (PTFE) are measured over the temperature range of about 20 to 30 degrees C. The diffusion coefficient is estimated from the time response of a large area platinum electrode covered with the membrane material and exposed to a sudden change in PO2. outside the membrane. The electrode is operated at a very low polarising voltage so that consumption of oxygen at the cathode surface is made negligible. This method is considered to be more reliable than that based on operating the electrode at more normal polarising voltages at which the boundary condition for oxygen tension at the cathode surface is often ill-defined. Oxygen permeability is estimated from the flux of oxygen across an area of membrane separating a nitrogen gas stream from one containing oxygen, the oxygen being measured with a platinum/zirconium oxide reversible cell. Diffusion coefficient in the membranes is very temperature dependent, whereas oxygen solubility is only weakly so. The diffusion coefficient at 25 degrees C is 0.28 +/- 0.06 . 10(-6) and 1.0 +/- 0.2 . 10(-6) cm2 . sec-1 for PTFE and polythene respectively. The corresponding values for permeability are 0.80 +/- 0.08 . 10(-7) and 0.43 +/- 0.04 . 10(-7) ml O2 atm-1 . cm-1 . sec-1.


Theory of gas exchange in the avian parabronchus. To understand the distribution of oxygen and carbon dioxide in the avian lung, a theoretical treatment of gas exchange in the parabronchus of the avian lung is described. The model is modified after Zeuthen (1942). In addition to bulk flow through the parabronchial lumen, diffusion through the air spaces of both the parabronchial lumen and air capillaries is treated. The relationship of PO2 and PCO2 within the blood capillaries, air capillaries, and parabronchial lumen to parabronchial blood flow and ventilation is graphically shown. The results indicate that the variations of PO2 and PCO2 along an air capillary are less than one torr under resting conditions. Removal of diffusion resistance within the air space of the air capillaries increases calculated parabronchial gas exchange by less than 0.1% at rest. At high or resting ventilation rates the partial pressure profile along the parabronchial lumen calculated considering bulk flow only agrees well with the profile calculated considering bulk flow and axial diffusion, but as the ventilation rate decreases there is increasingly large disagreement. Forward diffusion of O2 toward the parabronchus reduces pre-parabronchial PO2 and backward diffusion of CO2 from the parabronchus increases PCO2. Neglecting diffusion within the air spaces of both the lumen and the air capillaries increases calculated parabronchial gas exchange by less than 2% (CO2) or 6% (O2) at rest.


[Systematic screening of hemoglobinopathies in blood donors in Guadeloupe (French West Indies)]. We report the results of a systematic survey carried on 8.961 healthy Guadeloupean blood donors, where we looked for hemoglobinopathies. The results are expressed in regard of the race and site of living (urban or rural) of the subjects. Of these 8.961 subjects, aged 18 to 60, 7.75% were sickle cell trait carriers, 2.36% were heterozygous for Hb C and 0,2% had a significant elevation of Hb F. Were also report some less frequent phenotypes : three Hb AD, five Hb SC, one Hb CC, two Hb SF, one Hb CF and one case of isolated Hb, A2 elevation. Two rare hemoglobinopathies are reported: a case of Hb Korle Bu associated with Hb S an a case of Hb N-Baltimore. Our datas regarding race and sex of Hb S and Hb C carriers are evaluated. These results are compared to previous studies carried on healthy blood donors in Guadeloups. Problems related to the detection of hemoglobin abnormalities in a blood transfusion center are reviewed.


[Lewis antigen and diabetes].

[Lewis antigen and diabetes]. The Lewis negative (Le a--b--) red blood cell phenotype was observed three times more frequently in 170 diabetics (29%) irrespective of their clinical type and in 27 non-diabetics low insulin responders to glucose than in 100 controls (10%). This difference could not be accounted for by factors influencing the serological typing ("ABH secretion and ABO groups) nor by the geographic origin of the populations tested. The Lewis substances are primarly soluble antigens present in blood, saliva, others fluids and absorbed on red blood cells. In 50 diabetics saliva was also analysed. Blood cell and saliva results were concordant allowing to interpret the Lewis negative blood cell phenotype as reflecting the absence of Lewis antigen. The higher frequency of Lewis negative phenotype was not related to the severity or the duration of the diabetes and therefore was unlikely to depend on metabolic factors. The similarity between the results for juvenile and maturity onset diabetes seems to indicate that these two clinical types of diabetes are genetically related. Furthermore, the same results obtained in low insulin responders afford additional support for considering these subjects as potential diabetics. It probably indicates, in the diabetic population, an increased frequency of le/le genotype or of one or several genes inhibiting the expression of Le.


[Detection of antitetanic antibodies. Technics (electrosyneresis, Laurell, latex) applied to a high-antibody population]. The human serum of about twenty years old men, recently vaccinated has been tested by Laurell's method (Mesnier and Piquet variant). Purified antitetanic equine serum from Pasteur Institute (P.I.) has been taken as reference. With 5 Lf tetanic toxoid from P.I. concentration we can trust in the results until 50 antitetanics I.U. For richer serum, a 10 Lf toxoid concentration must be used. Correspondance between Pasteur Institute serum and gamma TS (human specific immunoglobulins) is indicated. Technics of Laurell, latex and electroimmunodiffusion are compared. The way to obtain plasma pool with higher antitetanic titre than 8 I.U. from poor and rich plasma is mentionned. The highest rate of titre antibody after the first typhoid diphteria tetanic vaccinal injection is observed between the 11th and 21th day.


Physiotherapy: its prescription and implementation for orthopaedic out-patients. During a three-month period, 1462 (29%) of the new out-patients seen by 18 orthopaedic surgeons were prescribed physiotherapy. The rates of referral among the surgeons ranged widely, from 15% to 56%, and the differing characteristics of the patients did not account for these variations. For specific conditions examined, physiotherapy appeared to be one of a range of possible therapies. The majority of prescriptions gave clinical details and specified the type of treatment, but its duration was specified in less than half; the frequency and aims of treatment were hardly ever given. Nearly 90% of the patients completed their course. Fourteen different types of treatment were applied, but only four of these--heat, exercises, electrical stimulation, and traction--were applied to more than 3% of the patients. Physiotherapists nearly always carried out the treatments prescribed and augmented them in nearly a quarter of cases, usually with heat and/or exercises.


Copper--an index of erosive activity?

Copper--an index of erosive activity? Using atomic absorption spectrophotometry the copper content of synovial fluid has been compared in rheumatoid and osteoarthrotic synovial fluids. Synovial fluid caeruloplasmin has been determined by single radial immunodiffusion. Both are significantly increased in the rheumatoid group. Serum copper, similarly estimated, shows a trend to greater elevation with increasing degree of rheumatoid erosion as assessed radiologically.


The synovial changes in post-traumatic synovitis and osteoarthritis. The histopathologic appearances of post-traumatic synovitis and synovitis of osteoarthritis cover a limited range of changes and have features in common. Electron microscopy yields information complementary to that given by light microscopy. With these techniques, based on sufficient material, histological analysis linked with clinical observation will permit some degree of differentiation between the two conditions.


Indomethacin or prednisolone at night in rheumatoid arthritis? Indomethacin, 100 mg orally, was compared with prednisolone, 5 mg, as addititional therapy at night, in a two-week, double-blind, between-patient study in twenty-four in-patients with rheumatoid arthritis. Both therapies proved equally effective, and significantly lessened morning stiffness and increased grip strenght. Two patients with dyspepsia were discontinued from the indomethacin group. Using indomethacin at night avoided the central nervous system side-effects frequently seen with this compound.


The gout patient in general practice.

The gout patient in general practice. A study of the clinical profile of gout-diagnosed patients was undertaken within general practice in Great Britain. At the time of the first attack of acute gouty arthritis, the mean age was 52.3 years and 15.6% of the total 1077 patients were female. Males had an earlier clinical onset than females and the average frequency of attacks of acute gouty arthritis was 0.91 per patient year. Ten per cent of the cases were believed to be secondary gout, with diuretic therapy the most frequent cause. The sample showed a highly significant association between gout and the higher social classes, a family history among blood relatives in 23% of cases, tophi were noted in 4.6% of cases where sought and 38.2% of cases were 10% or more overweight and significantly heavier than a non-gouty population. The great toe joint was most frequently involved, both in the first episode and in all acute episodes combined. The most frequently occurring associated chronic condition was hypertension which was present in 27.8% of cases. Renal stones occurred in 6.1% and renal impairment in 2.2%. Only 20.4% of the patients were referred to hospital, with the younger being referred more frequently than the older. Those with joint involvement other than the great toe had a greater chance of being referred, as did those who also had angina pectoris, myocardial infarction and hypertension. Allopurinol appeared to be the drug of choice for long-term control therapy and phenylbutazone for the acute attack.


Azapropazone and renal function.

Azapropazone and renal function. Renal concentrating ability was measured in two groups of arthritic patients. The first had received long-term therapy with azapropazone and the second with other nonsteroidal anti-inflammatory drugs. Even after long periods of treatment, azapropazone did not adversely affect renal concentrating ability.


A comparison of axillary, elbow and Canadian crutches. Crutches can be used by patients with injuries to the lower extremities in order to perform 'swing-through' gait. Because axillary crutches have been associated with axillary artery thrombosis and crutch palsy, they have to a large extent been superseded by elbow crutches. Canadian crutches combine many of the features of axillary and elbow crutches, and a study of the three types suggests that they have advantages in terms of energy cost.


Standardization of anticoagulant control. Oral anticoagulant treatment is widely administered, particularly for the management and prophylaxis of thrombo-embolism. Anticoagulant dosage requires laboratory monitoring. An international system of standardization of laboratory control is necessary. A system based on the provision of a standardized tissue extract of thromboplastin (British Comparative Thromboplastin) is described. This is used in laboratories in seventy countries including a representative group of Italian hospitals and is now recommended as the international reference preparation.


Immunological mechanisms of human platelet involvement. Several immunological mechanisms of platelet involvement in inflammation are described. Basophils degranulate and release a platelet-activating factor (PAF) when challenged with anaphylotoxins, cationic proteins (CP) from polymorphonuclear cells (PMN) as well as with specific antigens from atopic patients. PAF is a newly-discovered mediator of anaphylaxis present in rabbit and human basophils. This factor is a small phospholipid, probably a lyso-1-phosphatidylcholine with a significant aggregating activity on rabbit and human platelets. PAF is released, together with a small amount of arachidonic acid, from basophils in the presence of anaphylotoxins, CP and specific antigens from atopic patients. The already well-known direct interaction between immune complexes (Ics) and human platelets is compared here with the mechanism of PAF-induced aggregation. It is shown that the latter process of aggregation differs from the former. Human platelet aggregation starts more rapidly in the presence of PAF than of Ics. PAF-induced aggregation is ADP-independent as it is not affected by ADP inhibitors. On the contrary, Ic-dependent aggregation is brought about by endogenous ADP release and therefore inhibited by ADP inhibitors. The interaction between Ics and platelets leads to the release of CP. The latter produce a cascade reaction involving basophils which degranulate and release PAF. A self-maintaining mechanism of tissue injury is thus triggered.


Non-specific count subtraction in radioimmunoassay (a criticism). The radioimmunoassay (RIA) blank (Blk) value (as calssically determined) does not represent the real aspecific portion of the radioactivity because of the lack of both antigen and antiserum and the consequent total availability of free tracer, and is, therefore, unlike the standard and unknown tubes. Gastrin-RIA with bound-free separation by charcoal adsorption was chosen as example for providing evidence that the subtraction of such an empirical constant (Blk) from the dependent variable (the response) of a function (response versus dose) is analytically incorrect. Antigen-recovery and parallelism (serum dilution) tests were carried out, and the results obtained by the so-called "Blk subtraction procedure" (BS values) were compared with the corresponding values without Blk subtraction (BNS values). In the recovery test, the BS values were higher than the BNS values, but the former were higher than the expected values, whereas the latter showed a quantitative recovery. The same result was also found in the serum dilution test: the BNS values gave dilution curves more parallel to the BNS standard curve than did the BS values to the BS standard curve. It is concluded that the Blk subtraction procedure must be avoided in processing RIA results.


Collagen, elastin and sugar content in primary varicose veins. The collagen, elastin and total sugar content was evaluated in 32 samples of saphenous varicose veins and in 34 controls. A significantly lower collagen and elastin content was found in the varicose samples. In addition, the total sugars and the soluble non-scleroproteins were found to be increased in varicose samples. The results are more significant when expressed as mg per unit surface of endothelium. Our findings support the hypothesis that the decrease in collagen and elastin content is a primary rather than a secondary change.


[Comparison of computer tomography with ultrasound in renal disease (author's transl)]. The following has been established in examinations under optimal conditions: 1. Ultrasound and CT scan appear to be of equal value in respect of validity and significance of information on the nature of findings, especially in connection with spaceoccupying processes, hydronephrosis and pyonephrosis. However, CT supplies a better anatomical and topographical overall view of the situation. 2. CT scanning, is definitely superior in respect of significance of information on the extension and behaviour in respect of neighbouring organs. This is particularly evident in the visualisation of relapses after hyponephromas and in perirenal processes. 3. Computer tomography is clearly superior in the identification of renal aplasias and hypoplasias.


[Possibilities of errors in the sonographic diagnosis of renal tumours (author's transl)]. Artefacts or not completely visualised renal contours can lead to the erroneous diagnosis "renal tumour". This false diagnosis is mostly avoidable by means of accurate examination technique. Further radiological examination will be required only in exceptional cases. Incompletely visualisable parenchymal ridges with socalled incomplete multiple kidneys frequently create the impression of an intrarenal tumour and indicate the need for further clarification. There is a relatively high degree of uncertainty in intrarenal space-occupying processes below 2.5 cm diameter, as far as structural analysis is concerned. In such cases, provided a sufficiently strong clinical and roentgenological suspicion is sustained, angiography and, if necessary, exposure, should be recommended on a rather liberal basis.


[Sonographic renal diagnosis in paediatrics (author's transl)]. Sonography is a method without risk but of high diagnostic value. Hence, it is extremely well suited for paediatric examination. In our opinion, this method should rank first among all other examination methods when clarifying inflammatory conditions of kidneys and of the efferent urinary tract, whereas in all other problems sonography continues to rank second behind the urogram. Both examinations together, which account for a diagnostic safety of more than 95%, are employed to decide whether and to what extent other and more invasive and complicated measures will have to be taken.


[Direct antegrade cholangiography and percutaneous transhepatic drainage of the biliary tract (author's transl)]. Direct antegrade cholangiography via transjugular access or as transcutaneous, transhepatic fine-needle cholangiography reduces the examination risk involved in the direct visualisation of the bile duct via needles of thick calibre. The article reports on the results obtained with 83 patients. Direct puncture of the bile duct by means of a fine needle is superior to transjugular antegrade cholangiography in respect of the required technical equipment and cost, and also as far as the proportion of accurate results is concerned, since visualisation of cholangiectasis will always be successful, whereas the visualisation of undilatated bile ducts can be effected in 50% of the examinations. Transvenous access should be chosen in such cases where liver tissue biopsy is necessary. Dilatation of the transcutaneous, transhepatic bile duct access via the temporary transcutaneous, transhepatic bile duct drainage, is necessary in those situations where the bile flow cannot be ensured by surgery, or where surgery is ruled out on account of the patient's general condition.


[Initial X-ray manifestations of bronchial carcinoma. Possibilities and limitations of early diagnosis (author's transl)]. Problems of defining "early diagnosis" and difficulties, arising from multiform clinical and radiological manifestations in bronchial carcinoma are discussed. Different types of manifestations offer unequal chances for early detection. In demonstrating some typical cases, auxiliary diagnostic means and possibilities for more efficient radiological diagnosis are discussed.


[Circumscribed intrapulmonary densities following thoracic trauma (author's transl)]. Intrapulmonary hematoma caused by blunt trauma to the chest may appear as round opacities of various size. The diagnosis depends on an exact case history and radiological follow up. 4 relevant cases are being presented. The incidence and pathogeneses are being discussed.


The endocrine syndrome of occult tuberculosis. Based on clinical observations made in the "C.I. Parhon" Institute of Endocrinology and in a clinic of catching diseases in Bucharest, the authors have isolated an endocrine syndrome of occult tuberculosis. The disease shows signs and symptoms of endocrine glands involvement. The paper presents the pathogenesis, epidemic spread and endocrino-tuberculostatic management.


Inhibitory action of pineal extract on LH and FSH. The influence of melatonin-free pineal extract on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was studied. Administration of bovine pineal extract in intact rats was found to induce a statistically significant decrease of serum LH and FSH. The pineal extract also inhibited the 24-hour-post-castration rise of serum and pituitary LH and FSH in mature male rats. The stimulating effect of gonadotropin-releasing hormone (GnRH) on pituitary LH and FSH was also inhibited in intact animals. The antigonadotropic activity of melatonin-free pineal extract, melatonin and arginine-vasotocin (AVT) is discussed.


Changes in plasma lipids in hirsute women. The changes in blood cholesterol, triglycerides, total lipids and lipoproteinograms were examined in 40 women with hirsutism compared to 40 normal women of similar ages as control. The results show a significant increase in cholesterol, triglycerides and total lipids in hirsutism. The lipoproteins, analysed according to Frederickson's classification show that while only 12% of the normal women came within type II A, in hirsutism the proportion was 50%. A proportion of 5% of normal women came within type II B whereas in hirsutism there were 28%. In conclusion, both types of blood lipoprotein alteration with atherogenic potential are significantly better represented in hirsutism cases.


Fat cell size--body weight correlation in newborn. Authors investigated the mean diameter of fat cells in 30 newborns weighing between 1500 g and 5400 g. A gradual increase of the mean diameter paralleling the body weight was observed. The highest values of the mean diameter exceeding 180 mu were found in overweight newborns from diabetic mothers.


Occurrence of megakaryocytes in various vessels and their retention in the pulmonary capillaries in man. A total of 17 patients with hypertension undergoing renal vein or adrenal vein catheterization were investigated in order to ascertain the number of megakaryocytes in blood from the inferior vena cava, the femoral artery and a cubital vein. On an average 11.9, 3.8, and 4.5 megakaryocytes per ml were found, respectively. In blood from the inferior vena cava, 30% of the megakaryocytes had copious cytoplasm, while megakaryocytes in arterial and cubital venous blood had sparse or no visible cytoplasm. It was demonstrated that 2/3 of the megakaryocytes were retained in the pulmonary circulation and that at least 70% of the platelets could derive from megakaryocytes in central venous blood or the pulmonary circulation. It was found that megakaryocytes pass through a life cycle in which the differentiation take place in the bone marrow, platelet release occurs mainly in central venous blood and in the pulmonary circulation and the destruction of the megakaryocyte nucleus take place outside the bone marrow, especially in the pulmonary circulation.


Effects of prednisolone in 6 cases of glucocorticoid receptor-positive CLL. The effect of treatment with prednisolone on clinical and laboratory variables was studied in 6 patients with chronic lymphocytic leukaemia (CLL). The laboratory variables analyzed on the leukaemic cells were surface immunoglobulin (S-Ig), sheep red blood cell receptors (SRBC), proliferative activity (PI) and glucocorticoid receptor (GR). In all cases the CLL was of B-cell type and the leukaemic cells contained a significant amount of GR. 4 out of 6 patients had a progressive disease with increased PI. On treatment they went into clinical remission, which was paralleled by a reduction in the leukaemic B-cell number and in PI. The amount of GR was unaffected. In 2 patients with nonprogressive disease, prednisolone produced no clearcut effect on clinical or laboratory variables.


Studies on human preleukaemia. IV. Clinical and prognostic significance of sideroblasts in aregenerative anaemia with hypercellular bone marrow. The prognostic significance of the bone marrow sideroblasts found in aregenerative anaemia with hypercellular bone marrow was evaluated particularly to see if the sideroblasts might be a preleukaemic sign. The study includes 32 patients with abnormal sideroblasts; 14 had mainly ringed sideroblasts while 18 had mainly the intermediate or ferritin type. Basic erythrokinetic data (59Fe erythrocyte incorporation and erythroblast labelling indices) were similar in the two groups. The colony forming capacity (CFUc) was abnormal in 2 of 5 patients with ringed sideroblasts compared to 12 of 13 in the intermediate sideroblast group. Patients with mainly ringed sideroblasts had significantly longer duration of disease state, higher platelet and leucocyte counts, no increase in the percentage of bone marrow myeloblasts and did less often develop acute leukaemia. Thus aregenerative anaemias can be divided according to the type of abnormal sideroblasts in two groups with different risk of development of acute leukaemia. The ringed sideroblastic anaemia seems not to be a preleukaemic stage in the prospective sense in contrast to aregenerative anaemia with mainly intermediate sideroblasts.


Inhibition of myeloid differentiation by mature granulocytes can be reversed by humoral factors. Human mature granulocytes added to in vivo diffusion chamber (DC) cultures of murine bone marrow cells (BMC) led to a late reduction of CFU-C, day 5, and proliferative granulocytes, day 6. Cell free DC fluid harvested on day 4 from chambers with BMC and mature granulocytes slightly reduced granulocyte formation in new DC cultures, but not more than DC fluid from control cultures (BMC). Mice which had carried chambers of either group for 4 d, were not different when used as hosts for new DC cultures. However, they were less able to stimulate cell growth in DC than untreated mice. Tranfer of DC to new host mice on day 2 completely reversed the inhibition by mature granulocytes which otherwise could be detected in numbers of CFU-C on day 5 and proliferative granulocytes on day 7. However, CFU-S numbers were reduced on day 5 following reimplantation indicating an increased differentiation of CFU-S. Transfer of DC as late as day 4, rapidly restored the granulocyte numbers in the granulocyte co-culture group suggesting that also more differentiated granulocytes were stimulated to further growth and differentiation. It is proposed that factors from mature granulocytes reversibly inhibit myeloid differentiation. Differentiation can again be induced by factors which reach the DC shortly after intraperitoneal implantation in a mouse.


Response to doxorubicin in hairy cell leukaemia. A case of hairy cell leukaemia (HCL) treated by single-agent chemotherapy after the failure of splenectomy is reported. The patient was treated with doxorubicin 50 mg on 4 occasions over an 8-day period. After 2 weeks of profound pancytopenia, substantial blood and bone marrow improvement ensued. This case demonstrates that HCL may in some case be treated successfully by intensive chemotherapy.


Relations between accelerated sexual maturation and menstrual disorders. The author demonstrates that the phenomenon of acceleration of sexual maturation is more frequent in urban areas. The factors having a part in determining this process are multiple: psychoemotional and audio-visual ones, and have an important role. The acceleration of sexual maturation has rather negative consequences, due to the significant increase of puberal menstrual troubles.


Destruction of sensitized erythrocytes by human monocytes in vitro: effects of cytochalasin B, hydrocortisone and colchicine. The purpose of this study was to characterize the destruction of sensitized erythrocytes by human blood monocytes in vitro. The incubation in vitro of human monocytes with 51Cr-labelled human erythrocytes sensitized with IgG rhesus alloantibodies anti-D (EAIgG anti-D) resulted in release of 51Cr from the erythrocytes (lysis) as well as uptake of 51Cr-labelled erythrocytes by the monocytes (phagocytosis). The lysis of EAIgG anti-D by monocytes was not dependent on phagocytosis, because cytochalasin B, which inhibited phagocytosis of EAIgG, enhanced lysis. In contrast, hydrocortisone and colchicine inhibited lysis, but had no effect on phagocytosis. These agents did not affect binding of EAIgG anti-D to monocytes. The effect of these agents on lysis corresponded to their effect on release of lysosomal enzymes by monocytes. The release of lysosomal enzymes, when induced by EAIgG anti-D, was, likewise, enhanced by cytochalasin B and inhibited by hydrocortisone and colchicine. A significant correlation was found between lysosomal enzyme release and lysis. Together, these results strongly suggest that lysosomal enzymes, released by the monocytes when incubated with anti-D-sensitized erythrocytes, are responsible for the cytotoxic activity of these cells towards sensitized erythrocytes. The action of these enzymes only occurs over a short range, probably at the site of attachment of the erythrocyte, because only erythrocytes that were bound to the monocytes were lysed. The finding of other investigators that removal of monocytes from suspensions of human mononuclear leucocytes results in a strong reduction in the cytotoxic activity of these leucocytes towards sensitized erythrocytes in vitro. was confirmed.


De novo balanced translocation: 46, XX, t(13;20)(q34;p 11). The authors present a family in which the father has brachymetacarpy and brachymetatarsy and the mother has a 13/20 translocation. A baby was born with multiple malformations similar to the trisomy syndrome for the short arms of chromosome 20. The genetic consequences of the translocation are discussed.


Acetylcholine receptor antibody in myasthenia gravis: purification and characterization. Acetylcholine receptor antibody was measured in serum and IgG fractions from patients with myasthenia gravis using different analyses for antibody interfering with the toxin binding site and for antibody directed against other sites. No correlation was found between the concentration of receptor antibody as measured with the two assays. The different antibody activities also showed different isoelectric spectra. Receptor antibody was purified about 1000 times from IgG by affinity chromatography on a partially purified human skeletal muscle receptor preparation. The purified antibody was homogeneous in SDS-gel electrophroesis and showed a polyclonal pattern in agarose gel electrophoresis and isoelectric focusing. Both kinds of light chains were demonstrated. The results imply that the acetylcholine receptor antibody found in myasthenia gravis is heterogeneous and of multiclonal origin.


Demonstration of high-affinity binding sites for C3a anaphylatoxin on guinea-pig platelets. 3H-serotonin release from guinea-pig platelets was demonstrated to be the consequence of C3a binding to these cells. A Scatchard analysis of dose-response data of the 125I-C3a binding pattern to guinea-pig platelets pointed to the existence of binding sites with high and low affinity for the C3a molecule (HA and LA receptors). HA receptors are specific for C3a with intact C-terminal arginine. whereas C3adesarg only interacts with LA receptors. The release of serotonin may be induced by a combined reaction of C3a with HA receptors and LA receptors on the platelet membrane.


Biological homogeneity, symptom heterogeneity, and the diagnosis of schizophrenia. Much biological research is directed at using biological variables to predict traditional symptom-based psychiatric categories. In this article, the authors discuss the need for a research strategy in which biological variables actually define psychiatric groups.


The diagnostic ambiguity of postpsychotic depression. A clearly differentiated episode of depression in the aftermath of acute psychosis reportedly occurs in approximately 25 percent of all patients hospitalized with a diagnosis of acute schizophrenia. A comparison of premorbid functioning, symptomatology, and clinical course in patients with a postpsychotic depression following acute schizophrenic episodes and patients in the depressed phase of bipolar depressive illness suggests a high congruence between the two disorders. The results support the growing evidence that bipolar depressive illness is frequently misdiagnosed as acute schizophrenia.


Psychotherapy with schizophrenics requires relevant training. Secondary sources continue to cite a one-page preliminary note about the Michigan State Psychotherapy Project, ignoring fuller reports in print. Relevant experience and training are critical to quality control of psychotherapy in schizophrenia research. This investigation is unique in that "experienced" meant that the therapist had worked over 10 years specifically with schizophrenics, poor patients, and black patients. These relevantly experienced therapists supervised inexperienced therapists. Evaluations were "blind," and thought disorder was objectively measured. Psychotherapy produced better overall functioning, less thought disorder, and shorter hospitalization, particularly in the long run, than medication. Adjunctive medication facilitated behavioral control, but slowed change in the thought disorder.


Speculating about cognitive experiments using schizophrenics. Several models of selective attention are reviewed, emphasizing how breakdowns in various parts of each model could result in certain attentional deficits. It is concluded that some evidence suggests that the ability to mobilize attention may not be as impaired in schizophrenia as is the ability to choose which stimuli are appropriate for attention. If so, then in any cognitive experiment involving schizophrenics, any schizophrenic subject would be particularly distracted by certain extraneous stimuli, while other schizophrenic subjects would be particularly distracted by other stimuli. The importance of this possibility for cognitive research in schizophrenia is discussed.


Dopamine supersensitivity, endorphin excess, and prostaglandin E1 deficiency: three aspects of the same schizophrenic elephant. The author presents a hypothesis relating prostaglandin E1 (PGE1) deficiency to schizophrenia. The hypothesis is consistent with the importance of prolactin-stimulating properties in currently used antipsychotic drugs, the effect of prolactin on PGE1 synthesis, and the deficiency of PGE1 regulation in schizophrenic platelets. The author relates the PGE1 deficiency hypothesis to theories implicating dopamine and endorphins in the etiology of schizophrenia. A clinical trial in chronic schizophrenics has suggested the possible therapeutic efficacy of penicillin, a drug without dopamine-blocking actions which can stimulate PGE1 synthesis directly.


Social networks, the family, and the schizophrenic patient: introduction to the issue. This article is an editor's introduction to the theme of a special issue of the Schizophrenia Bulletin. The origin of the social network concept is described. Ideology, morale, structure, and the larger social context are identified as aspects of the social network to be examined in future research. Consumer organizations of schizophrenics and their families are described, and their potential for network formation and cooperation with organized psychiatry is discussed.


Social networks and schizophrenia.

Social networks and schizophrenia. This article suggests that social network concepts and methods can provide a unifying framework for social research on schizophrenia. A selective review of the literature indicates that a social network perspective is not only consistent with a range of other research approaches and findings, but may help resolve some basic and persistent methodological and conceptual problems. A theoretical model is briefly described which attributes a critical role in the onset and recurrence of schizophrenia to social network processes. Some examples are given of the potential contribution of social network variables to research and therapy in schizophrenia.


Schizophrenia and social networks: ex-patients in the inner city. A high level of social contacts has been recognized as one of the main predictors of outcome in schizophrenia. However, a variety of issues concerning the sociability of schizophrenics still need to be clarified. Focusing on ex-mental patients residing in a large Manhattan hotel, an analysis is made of the relationship between several social network variables, psychopathology, and rehospitalization. The findings indicate that: (1) Schizophrenics have significantly fewer linkages than nonpsychotics, but even the most impaired schizophrenics are not totally isolated. (2) Within the schizophrenic spectrum there are differences with respect to network size, complexity, directionality, and interconnectedness. (3) Rehospitalization is dependent upon two factors, degree of psychopathology and hotel network size.


Support systems of schizophrenic and nonschizophrenic Puerto Rican migrant women in New York City. Analysis of the social networks and support systems of patients with varying degrees of emotional disturbance reveals models of naturally occurring support systems that can be used by mental health professionals for fostering, redeveloping, or building supports for chronic schizophrenic patients in their natural communities. As a demonstration, analysis is made of the social supports of 55 Puerto Rican migrant women with five degrees of emotional disturbance. Seven patterns of social support with associated family and emotional status variables emerge. These support system patterns range on a continuum from one which reflects the ideals of the culture found primarily among women who are symptom-free, through four variations that appear to be adaptations to deficits in the core support system (e.g., absence of husband, extended kin, or both) found predominantly among the nonschizophrenic but disturbed women, to two culturally deviant forms found almost exclusively among the schizophrenics. The salient finding of this analysis is that there is greater reliance upon neighbors, friends, and other non-kin than upon family among the schizophrenic women who lead their lives relatively successfully within the community. It is suggested that these non-kin supports be used in natural network therapy to reintegrate or maintain chronic schizophrenic patients in the Puerto Rican migrant community and that similar analyses be made of the support systems of patients from other communities.


Restructuring parental attitudes--working with parents of the adult mentally ill. The Thresholds parents group gives the parents of clients an opportunity that has rarely been presented to them. They are able to discuss openly, with their peers, many issues that have not been expressed previously except in the greatest privacy. Often their children's mental illness has been a well-kept secret or has been handled in a guilty and shamefaced way. They do not find it easy, as a rule, to discuss mental illness in the same way they might discuss diabetes or congenital heart disease. It is an enormous relief to be open about their problems with others who are in similar circumstances. The main issues addressed in the group are a redefinition of good parenting to include mutual disengagement, emancipation, and separation; reduction of parental guilt, with its consequent implications of parents getting more out of their own lives, and a reduction of manipulation; and the handling of management issues such as money, medication, visiting, parental expectations, holidays, siblings, and parents' united front. Parents of the emotionally ill are a much maligned group. Too often they are regarded by the mental health community as enemies and not allies. Too often the suffering that they have endured is ignored. Too often parents' strengths are overlooked by mental health professionals treating their offspring. And, finally, too often basic change in the parents is demanded as a prerequisite for meaningful change in the member.


Efference copy and corollary discharge: implications for thinking and its disorders. Many motor commands in the nervous system are associated with corollary discharges which alter the excitability in both sensory and motor systems. These discharges may assist in the distinction between self-generated and externally produced movements; they also allow (or represent) monitoring of the motor commands before the effector response has occurred. Here, I hypothesize that this mechanism of control and integration is also present in thinking, which as Hughlings Jackson pointed out, may be considered the highest and most complex form of motor activity. I speculate that if corollary discharges are normally part of the motor mechanisms of thought, their derangement could produce many of the symptoms of schizophrenia.


[Electroencephalographic periodicity with asynchronous  variations in period duration in both hemispheres following acute cerebral anoxia]. The periodicity of paroxysmal wave complexes in EEG after acute cerebral anoxia with special reference to the dynamics of period duration (alteration of Zeitmass) is described in case 20 hours before isoelectric tracing. The completely asynchronous feature of paroxysmal events within certain limits of period duration in both hemispheres is a rare condition. Late and pure cortical electrogenesis is suggested. Short and long EEG- periods in similar and different pathological processes and functional states are compared with respect to topography of lesions. Subcortical interactions and extraneuronal influences upon periodicty are discussed. The parameters "complex wave and periodicity" in EEG and the dynamics respectively are a matter of serial investigations for better understanding pathophysiology and prognostic value.


[Possible explanation of the high degree of IQ variability in subjects with classical phenylketonuria]. Descriptions of cases of PKU presenting the plain metabolic defect but little or no brain damage are becoming more and more frequent. The author admits the existence of a genetic enzyme system independent of the PKU gene (X). It is probably acting in the brain cells, restoring more or less normal aminoacid balance at this level. Full enzymatic activity and optimal protection against the deleterious effect of phenylalanine would result from the homogenous gene (XX), somewhat lower activity from the heterozygous gene (Xx). Homozygous xx-individuals would lack the protecting enzyme and therefore be highly exposed to damage by phenylalanine. Hydroxylation of phenylalanine in brain tissue has been reported for several animal species by a series of authors who incriminate either a brain isoenzyme of phenylalanine hydroxylase or tyrosine hydroxylase. The main aim of this paper is to suggest search for such types of enzyme in human brain cells to all the workers having access to human brain tissue.


[So-called internuclear ophthalmoplegias. Electro-oculographic study]. A study is presented of three patients suffering from internuclear ophthalmoplegia without diplopia. The components of the nystagmus and the dysmetry of the oculomotor changes, as well as the difference in the respective speeds during abduction and adduction toward the side opposite to the lesion were recorded. A dysmetric component was found in the saccadic low amplitude movements (reading movements).


Cell regulations of the cerebrospinal fluid in diseases of the central nervous system. After a survey of the composition and the possibilities of the differentiation of the liquor cytogram, the author reports upon the reaction types of the cerebrospinal fluid. Following the functional mechanisms of the cerebrospinal fluid cells (phagocytosis, digestion, thesaurismosis, formation of antibodies) are to be mentioned.


[Cerebrospinal fluid spread of ependymomas]. A series of twentyseven ependymomas, four of which made subarachnoid implantation, is reported. Two of these were malignant, having their origin in the posterior fossa and two benign, having their origin in the spinal cord. The cytology in the cerebrospinal fluid of these cases is described.


Kinetics of 99MTc-pertechnetate uptake in healthy and arthritic knees. 99mPertechnetate (99TcO-4) was injected intravenously in 7 healthy subjects and 30 patients with rheumatoid arthritis (RA). The uptake of isotope (99Tc) in both knee joint regions was traced continuously for 30 min from the time of injection. The isotope showed more rapid accumulation with increasing arthritic involvement of the knee, and the rate of uptake of 99TcO-4 in the knee region tallied with the clinical findings before and after treatment (14 RA patients). The findings indicate that the rate of 99TcO-4 uptake could serve as a useful complement to the more commonly used quantitative uptake of isotope. The two measures may possibly reflect different features of synovial inflammation.


Cardiac involvement in polymyositis.

Cardiac involvement in polymyositis. Sixteen cases of polymyositis (PM) were treated at the Central Hospital, Jyväskylä. Features of cardiac involvement were observed in 11 cases (69%). The heart diseases which developed or worsened after the onset of PM were grouped as follows: (1) Sole disturbance of conduction--one case, (2) congestive heart failure--four cases, (3) coronary heart disease with or without congestive heart failure--six cases. Three patients suffered an acute myocardial infarction. Electrocardiography revealed arrhythmias in eight cases and disturbances of conduction in three. In one patient complete atrioventricular block and congestive heart failure necesssitated installation of an intracardiac pacemaker. In four patients congestive heart failure progressed to death. In two autopsied cases changes suggestive of PM were found in the heart muscle. Involvement of the heart in PM was prognostically a bad sign.


Treatment of rheumatoid pachymeningitis involving the entire thoracic region. A 67-year-old woman developed a spinal cord compression syndrome due to rheumatoid pachymeningitis with a roentgenological block from T2 to T11. The dura was surgically split from T1 to T12 and carefully dissected away from the spinal cord and then left open without grafting. The patient imporved and 3 years after the operation the spinal subarachnoid space and the circulation of cerebrospinal fluid were normal.


Rheumatoid arthritis contributing to lumbar spinal stenosis. Neurogenic intermittent claudication. Two patients with rheumatoid arthritis affecting the lumbar spine showed the clinical, roentgenological, and operative characteristics of lumbar spinal stenosis, which is a neurological complication of rheumatoid arthritis that can be treated by surgery. The clinical history is a prerequisite for suspicion of the syndrome, and lumbar myelography including roentgenograms of the extended lumbar spine may verify the diagnosis.


Changing pattern of clinical features and prognosis in systemic lupus erythematosus. The changing pattern of clinical features of and prognosis for 206 patients with SLE were studied. SLE patients with Raynaud's phenomenon and minimal change and focal proliferative glomerulonephritis observed by means of renal biopsy tended to increase in C (1972--76) group compared with A (1955--68) and B (1969--71) groups. SLE patients with lupus nephritis and central nervous system lupus treated with large doses of steroids or combined therapy of steroids and immunosuppressive agents also increased in the order C, B, and A group. The prognosis for group C patients was better than that for A and B group patients. However, there appeared to be an increasing incidence of complications unrelated to SLE, namely infection and perforated peptic ulcer.


Comparison of chemical, radiation and surgical synovectomy for knee joint synovitis. In 66 patients with rheumatoid knee joint synovitis and hydrops and with only slight radiological destruction, local treatment of the knee was randomly performed either with osmic acid, radioactive yttrium or surgical synovectomy. After a one-year follow-up the clinical and radiological results were slightly better in patients who underwent surgical synovectomy than in other treatment groups. However, radiological osteoarthrosis had progressed more in synovectomized patients than in others. In 2 patients with radioactive yttrium a relapse requiring surgical synovectomy was seen. Because osmic acid is almost as effective as surgical synovectomy, is very cheap and easy to perform, it can be recommended as the first choice for local therapy in patients with corticosteroid-restant knee joint synovitis, in the early stage of the disease.


Release of lysosomal enzymes from human polymorphonuclear leukocytes by soluble intermediate immune complexes. The efficacy of soluble immune complexes (1C) of different sizes prepared in vitro or present in RA sera and synovial fluids to induce the release of beta-glucuronidase (BG) and neutral protease (NP) from PMN has been examined. Immune complexes of human HGG-rabbit anti-human HGG prepared in 5, 10 and 20 times excess of antigen equivalence were fractionated into three pools, PI (22S--13S), PII (13S--7S) and PIII (7S) using Sephadex G-200 column chromatography. NP and BG-releasing activity was mostly associated with PII. Similar fractions were obtained from RA sera and synovial fluids. BG-releasing activity was again predominantly associated with PII. PII fractions from normal sera and from 2 non-RA IC disease sera showed less BG-releasing activity than the RA PII fractions. Negligible NP release was observed with all three serum pools. Further investigation demonstrated the presence of NP inhibitor(s) in PI and PII from human sera.


Pneumothorax in the Ehlers-Danlos syndrome: consequence of coincidence? A 25 year-old man, known to suffer from Ehlers-Danlos syndrome, developed a left-sided pneumothorax. At thoracotomy, pulmonary blebs and bullae were found at the apex of the lung. Bullectomy with removal of adjacent lung tissue was performed. The histological and ultrastructural findings in the lung tissue must be regarded as non-specific. These findings do not reflect a direct cause-and-effect relationship, even in the presence of the inheritable connective tissue disorder.


Transbronchial lung biopsy with fiberoptic bronchoscope. Transbronchial lung biopsy (TBB) was performed during fiberoptic bronchoscopy under fluoroscopic guidance in 133 patients with diffuse or peripherally localized lung diseases without endobronchial lesions. Histological diagnosis consistent with the clinical course and roentgenographic appearance was obtained in 96 patients (72%). In four cases specimens were inadequate for histological evaluation (3%). In 33 cases a diagnosis was not possible even though the specimens were adequate for histological examination. The low complication rate in this series seems due to the selection of patients and the technique used.


Pleural plaques in a health survey material. Frequency, development and exposure to asbestos. All cases of pleural plaques discovered at mass X-ray screening in Uppsala County during 1970-1976 were collected. Case histories, including the history of exposure to asbestos and smoking habits, were taken. A total of 508 cases, 492 males and 16 females, were found. Eighty per cent were smokers, which was more than expected, and 80% confirmed exposure to asbestos. The frequency of pleural plaques was found to increase steadily with the years parallel to the increase in the use of asbestos which had started 30 years earlier. The pleural plaques showed gradual development and many finally calcified.


Associations between housing conditions, smoking habits and ventilatory lung function in men with clean jobs. In 218 men, who had minimal occupational exposure to dusts, fumes, temperature variability, or physical exercise, the relation between housing conditions throughout life and lung function was analysed. The number of years spend in dwellings without central heating was significantly inversely associated with the level of FEV1 and MMEF, and significantly directly associated with closing capacity in per cent of TLC, CC%. Significant dose-response relationships between smoking habits and FEV1, MMEF, CC% and slope of the alveolar plateau (phase III) were found, whereas closing volume, CV%, was only correlated to age. The association between dwelling conditions and ventilatory capacity was independent of smoking habits. Tobacco smoking, however, moderated the association in as much as it was strengthened after standardisation for tobacco consumption. These data support the hypothesis that poor dwelling conditions during childhood and adolescence are associated with development of peripheral airways disease and expiratory airflow obstruction at middle age, and that comparisons of lung function between different occupational categories are incomplete and may be misleading if lifelong housing conditions or other factors reflecting socio-economic status are not taken into consideration.


Clinical features, mortality and survival of patients with asbestosis. This paper describes the characteristic clinical features, mortality and survival rate of 202 patients diagnosed as having asbestosis by the Institute of Occupational Health between 1934 and 1976. One hundred and thirty-three patients were subjected to a clinical reexamination. Major findings included breathlessness in 118 (88.7%), persistent sputum in 95 (71.4%), crepitations in 77 (58.0%) and finger clubbing in 43 (32.3%). Of the 95 patients with persistent sputum, 19 (20.0%) were nonsmokers. Of the 174 men registered as having asbestosis, 56 had died, whereas the expected  number of deaths among men of the same age in the Finnish general population was only 23.4. The respective figures for lung cancer were 19 observed and 2.1 expected. No excess mortality was found for other malignomas. Among men with asbestosis, the life expectancy was shorter for smokers than for non- and exsmokers.


Radiographic and physiological findings in patients with asbestosis. Radiographic and respiratory functional findings are reported for a series of 133 Finnish patients with asbestosis. Of these patients, 65 (49%) were found to have radiographically mild diffuse pulmonary fibrosis (profusion 0/1, 1/0 or 1/1), 48 (36%) moderate fibrosis (1/2, 2/1 or 2/2) and 20 (15%) diffuse fibrosis in an advanced stage (2/3 or more). The type of fibrosis was mostly irregular (110 = 83%). Fibrosis was typically the most advanced in the lower zones of the lungs. Of the 133 patients, 88 (66%) showed pleural changes and 78 (59%) pleural calcifications. The more severe the fibrosis, as seen in the radiographs, the greater the decrease in vital capacity (VC) and expiratory volume in 1 s (FEV1.0). Transfer factor was generally impaired only in advanced cases of asbestosis (fibrosis 2/3 or more). In general, obstruction was not observed in this series. Pleural changes seemed to decrease VC and FEV1.0 when the fibrosis was mild (0/1, 1/0 or 1/1). They had no effect on diffusion capacity (TLco).


Sputum cytology of asbestosis patients.

Sputum cytology of asbestosis patients. One hundred and fourteen patients with asbestosis, 59% of whom were chronic cigarette smokers, were subjected to a cytological sputum examination which showed: 36 workers (31.6%) with squamous metaplasia, 20 (17.5%) with benigh columnar cell atypia, 5 (4.4%) with benign dysplasia, 2 with suspicious cells for carcinoma, and 1 with anaplastic (microcellular) carcinoma. Clinically and histologically five lung cancers were verified, two of which were cytologically false negatives. All asbestosis patients with lung cancer were chronic smokers. Of the 114 asbestosis patients, 49 (43.0%) had ferruginous bodies in their sputum. The workers from an asbestos quarry more frequently had ferruginous bodies in their specimens than the other patients. Radiographically moderate and severe asbestosis cases showed squamous metaplasia more frequently than those with radiographically slight asbestosis. Most of the detected cellular atypias represented reversible alterations of the respiratory epithelium. It is, however, important to screen the sputum of older (greater than 40 years of age) smoking asbestos workers with benign and suspicious cellular atypias regularly because these alterations may represent the first step int he pathway to bronchogenic cancer. The results of this study did not answer the question of whether bronchial cancer of patients with asbestosis is curable if detected early with cytological methods.


Psychological dysfunctions in lead-exposed workers. Relation to biological parameters of exposure. Insidious neurotoxic effects of lead have been studied in a population of 42 lead-exposed workers and a reference group of 22 comparable workers with no lead exposure. The age of the individuals ranged from 18 to 50 years. The complete Wechler Adult Intelligence Scale, as well as psychomotor and memory tests, was included in the test battery. The exposure was assessed by means of the lead concentration in blood and hair and the ratio between zinc protoporphyrin and hemoglobin in the blood. Significant differences were found between the two groups of workers, especially concerning long-term memory, verbal and visuospatial abstraction, and psychomotor speed. Decreased performance in these tests was in most cases associated with indices of increased lead exposure, not only in the total population studied, but also within the lead-exposed group alone. Blood lead and zinc protoporphyrin appeared to correlate better with the intellectual impairment than did hair lead, and thus these analyses are probably better predictors for neurotoxic effects of lead. Age and exposure time were not found to be significant confounding factors in this study.


Neurophysiological effects of long-term exposure to a mixture of organic solvents. Neurophysiological effects of long-term exposure to a mixture of organic solvents was studied among 102 car painters from 27 car repair garages in Helsinki. The reference group consisted of 102 age-matched railroad engineers from the Finnish State Railways. The mean age was 35 years and the exposure time ranged from 1 to 40 years (mean 14.8, SD 8.5). According to measurements the mean concentration of the solvent mixture was relatively low in the garages, namely, 31.8% of the Finnish threshold limit value (TLV), the range of separate components varying from 4 to 212% of the respective TLVs. The main components of about 20 organic solvents of the mixture were toluene, xylene, butyl acetate and white spirit. Electroencephalograms (EEGs) of all the 102 exposed and 102 nonexposed subjects were studied, but electroneuromyographic measurements were made of only 59 car painters and 53 referents with a similar age distribution. Motor (MCV and CVSF) and sensory conduction (SCV) velocities, as well as motor distal latencies, were recorded from nerves in the upper and lower extremities. Abnormal EEGs were encountered in 32 car painters and 37 referents. The frequency of abnormal EEGs was in both groups higher than expected on the basis of EEG literature (about 10%). Twenty-six car painters had a complex of four common symptoms of disturbances in the central nervous system; the same symptom complex was found in 12 engineers. Forty-six percent of the car painters with this symptom complex had an abnormal EEG, while only 26% of those without this symptom complex had an abnormal EEG. Railroad engineers did not show such a tendency. Abnormally slow MCVs or SCVs and/or prolonged motor distal latencies were found in 12 of the 59 car painters but in none of the 53 engineers studied. Other authors have stressed that many solvents primarily cause neuropathy, while objective signs of central nervous involvement have been minor, if any. Our findings are similar; they showed slight positive signs of slowed nerve conduction velocities among the car painters and no increase in EEG abnormalities in comparison to the reference group of railroad engineers.


Biological indicators of exposure in styrene polymerization workers. Styrene in blood and adipose tissue and mandelic and phenylglyoxylic acids in urine. The concentrations of mandelic and phenylglyoxylic acids, urinary metabolites of styrene, and styrene in blood were determined for 491 styrene polymerization workers. Styrene in subcutaneous fat was determined for 25 workers. The levels of styrene exposure were estimated to be less than 10 ppm, and urinary metabolite and blood styrene concentrations indicated that significant recent exposure (within 4 h) had occurred among workers in areas of styrene polymerization and styrene monomer production. Styrene analysis of subcutaneous fat suggested that the monomer may have been present for as long as 3 d after exposure, a time when urinary metabolites and blood styrene were almost invariably undetectable. All three biological parameters were correlated with recency of exposure and estimated intensity of exposure within job categories.


Effects of long-term oral administration of styrene to mice and rats. Styrene monomer dissolved in olive oil was given orally to female O20 mice (1,350 mg/kg), C57 Bl mice (300 mg/kg) and BD IV rats (1,350 mg/kg) on the 17th day of gestation. Their offspring were treated weekly with styrene by stomach tube from the time of weaning throughout their life-span. The weekly doses used were 1,350 mg/kg for O20 mice, 300 mg/kg for C57 Bl mice, and 500 mg/kg for BD IV rats. Following the continuous oral administration of styrene for over 100 weeks, an increased and earlier appearance of lung tumors was observed in O20 mice. A few tumors rarely seen in controls were observed in BD IV styrene-treated rats, and a slightly increased incidence of liver tumors was found in C57 Bl mice. In both cases, however, the total incidence of tumors was not significantly different from that of the controls. The present results provide weak evidence of the carcinogenicity of styrene in one of the two strains of mice tested, when it is given at a high dose level.


Embryotoxic and teratogenic effects of styrene derivatives on sea urchin development. The effects of styrene and some of its derivatives on the fertilization and differentiation of sea urchins was investigated. When one of the gametes was pretreated for a few minutes, it was ascertained that the test substances act on the haploid nucleus, producing specific changes in the differentiation of the embryo. By this test system directly acting, weak mutagens may be detected.


Monitoring of styrene exposure in the polyester industry. Obtaining reliable results of exposure to styrene in field studies requires an appropriate methodology not only for analytical methods but also for the main strategy of conducting the surveys. This paper briefly describes how and why analytical methods for styrene in air, for its main metabolites in urine (mandelic and phenylglyoxylic acids) and for critical biological function tests were either chosen from the literature or adapted or developed to fit our criteria of convenience and reliability. In a second step of the preparation of field studies, experimental exposures to styrene were carried out on volunteers so that the best indicators of exposure could be determined and data could be obtained on the elimination kinetics of the urinary metabolites and the quantitative relationships between exposure and the urinary concentrations of mandelic and phenylglyoxylic acids. Finally field investigations, including air and biological monitoring, complete industrial hygiene surveys and medical examinations, have been organized and are being carried out in the Swiss polyester industry. Preliminary results concerning biological monitoring are given.


Cytogenetic effects of styrene and styrene oxide on human lymphocytes and Allium cepa. Styrene and styrene oxide induce cytogenetic effects already at very low concentrations (0.01% v/v or even less); the effects are similar in both in vitro human lymphocytes and in vivo onion root tip cells (Allium cepa L.). It is characteristic that styrene treatment is more potent in causing chromosome breakage in both systems. In Allium styrene induced inhibition of mitotic spindle action as revealed by a strong c-mitotic effect. Also the number of micronuclei and nuclear bridges increased in both test systems, especially after styrene oxide treatment. Furthermore, the metaphase chromosome morphology in the cells treated with styrene oxide was strongly affected. In both systems, chromosome destruction was observed, or else the chromosome material was decondensed and resulted in a characteristic fuzzy appearance of Allium chromosomes or a banded appearance of human lymphocyte chromosomes. A specific effect of styrene oxide on the chromosomal proteins is thus suggested. The data obtained from the autoradiographic studies with Allium support the idea that [7--3H] styrene oxide binds irreversibly to the cytoplasmic and nuclear macromolecules.


Acute biotoxic effect of styrene on rat liver. Correlation with enzyme-mediated mutagenicity of benzpyrene and acrylonitrile. Styrene is commonly used in western Europe for the manufacture of plastics suitable for packaging foodstuffs. This report demonstrates that, injected intraperitoneally at a dose as low as 10 mg/kg, styrene modifies the catalytic properties of aryl hydrocarbon hydroxylase by reducing its KM value. A similar effect is reported for two potent chemical carcinogens, 3-methylcholanthrene and benzo(a)pyrene. Ethylbenzene and benzo(e)pyrene and phenobarbital do not produce the same effect. Pretreatments of the rats with chemicals which modify aryl hydrocarbon hydroxylase also increase the capacity of the liver enzymes to activate benzopyrene to a mutagenic intermediate in vitro, as measured by the Ames test for mutagenicity. Exposure to both styrene and the other modifiers of the xenobiotic-metabolizing enzymes could thus influence the carcinogenic and toxic effects of chemicals which are activated by these enzymes. This hypothesis needs further investigation.


Neurotoxicity of styrene in occupational and experimental exposure. Occupational styrene exposure caused an increased frequency of abnormal electroencephalograms which correlated to degree of exposure. No dose-response relationship could be shown concerning a slowing of nerve conduction velocities in workers exposed to styrene. Experimental exposure of rats to 300 ppm of styrene caused a transient increase in the nerve conduction velocity in 6 weeks, but in a comparison to control rats no difference was found in measurements performed on rats exposed for  8  and 11 weeks.


Neurophysiological observations after chronic styrene exposure. Thirty-three styrene exposed workers from three different industrial sites were examined with electroencephalography and motor and sensory neurography. The three groups had respective styrene exposures of clearly above the threshold limit value (50 ppm), at about this level, and clearly below it. The neurophysiological results were compared with those of a group of normal controls and a group of 17 patients judged to suffer from sequelae after long-term heavy exposure to organic solvents (mainly painters). Ten subjects in the styrene group presented signs of a mild sensory neuropathy with polyphasic sensory responses of a low amplitude. The same pattern was commonly found among the reference group heavily exposed to solvents. The ten subjects in the styrene group with mild polyneuropathy had a significantly higher age and significantly heavier styrene exposure than the rest of the group. Age difference could not explain the difference in the neurophysiological parameters, and therefore the contributing role of styrene exposure has to be considered. The electroencephalographic analysis showed no changes of the dominant alpha frequency. An increased amount of diffuse slow activity was seen in many of the heavily exposed mixed-solvent cases and was seen in some of the styrene-exposed cases without a clear relation to degree of exposure. An increased occurrence of fast activity in central and precentral areas of the brain was found in the styrene group, as well as in the mixed-solvent group. This pilot study indicates that the same type of neurophysiological changes from the strictly normal are seen among workers exposed to styrene as those found among a group of patients judged to suffer from sequelae after chronic exposure to various organic solvents. The neurophysiological "profile" is (a) sensory nerve responses with low amplitude and long duration, (b) somewhat low sensory conduction velocities, (c) close to normal motor neurographic findings, and (d) an increased amount of fast activity in central and precentral regions in the electroencephalogram in combination with normal occipital alpha activity.


Alcohol consumption and tolerance of workers exposed to styrene in relation to level of exposure and psychological symptoms and signs. A group of 98 male workers occupationally exposed to styrene was interviewed for information on the amount and frequency of alcohol consumption and changes in consumption frequency and tolerance. Alcohol consumption and changes in consumption were not compared to any reference data, but the changes in tolerance were. The styrene-exposed workers revealed a lowered tolerance somewhat more often than the unexposed group. Neither the duration nor the intensity of styrene exposure was related to any of the alcohol "behavior" variables. The amount of over-time work in exposure had a slight relationship to high alcohol consumption, but the interpretation of this relationship remains undecided. Subjective symptoms, like hand tremor and difficulties in staying asleep, were associated with the alcohol "behavior" variables, but these two symptoms were unrelated to intensity of styrene exposure. Of the psychological functions studied, lowered visuomotor speed showed a slight relationship to high alcohol consumption. Visuomotor inaccuracy, which had proved to be related to a high intensity of styrene exposure, revealed no connection with the alcohol "behavior" variables. It was concluded that alcohol consumption among styrene-exposed workers is not related to the same psychological symptoms and signs as styrene exposure.


Morbidity among persons employed in styrene production, polymerization and processing plants. BASF has been producing styrene and polystyrene since 1931. An investigation of morbidity was undertaken for 84 workers employed in the styrene plant and exposed for 1--36 years and 93 workers employed in the polystyrene plant and exposed for 1--38 years. In all groups the concentration of styrene in the atmosphere was measured at various points of the workplace. All workers underwent a thorough physical examination and also extensive laboratory tests, including the determination of urinary mandelic acid. The absenteeism and accident rates were also taken into consideration in both plants. Blood samples were also taken and mandelic acid tests made on a small group of 16 persons employed in polyester processing plants not attached to the BASF.