[Serum enzymatic activity in neuromuscular diseases]. In 200 patients with neuromuscular diseases the author studied malonic dehydrogenase and lactic dehydrogenase activity comparing it with the activity of serum creatine kinase and aldolase. A significant rise in the values of all these enzymes was found only in the Duchenne type of muscular dystrophy, in polymyositis, and less frequently in the limb-girdle type of muscular dystrophy. Raised activity of creatine kinase and sidolase was observed in mothers and sisters of patients with Duchenne type of dystrophy, in patients with non-progressive myopathy, periodic paralysis, amyotrophic lateral sclerosis and polyneuropathy. With progression of dystrophy the activity of these enzymes decreases.


[Favorable result of carbamazepine treatment of compulsive drinking]. A case of refractory compulsive drinking in a 37-year-old female is reported. Administration of carbamazepine in doses of 2 tablets daily resulted in disappearance of excessive thirst and polyuria.


[Case of postpregnancy diencephalosis with manifestations of psudotumor cerebri]. The authors report a female patient with postpregnancy diencephalosis in whom in close correlation with premenstrual tension syndrome acute cerebral oedema developed repeatedly with signs of tentorial herniation. Owing to treatment with substitutive cyclopeptide hormones stimulating secondarily the failing hypophysis complete disappearance of these signs was obtained.


[Effect of trihexphenidyl on the excitability of alpha motor neurons of the foot plantar flexor in chemically induced parkinsoniam rigidity]. For assessment of the effect of trihexiphenidil on the excitability state of the alpha-motoneurons of the plantar flexor of the foot in patients with drug-induced parkinsonian rigidity curves of the excitability of motoneurons of the soleus muscle were plotted in two variants of experiments: I. with afferent stimulation of the Ia fibres of the soleus muscle as the conditioning and testing stimulus (tibial nerve in the popliteal fossa), II. with afferent stimulation of Ia fibres of the anterior tibial muscle (peroneal nerve behind the fibular capitulum) used as the conditioning stimulus and stimulation of the tibial nerve as the testing stimulus. These investigations were carried out on 12 psychiatric patients who received no drugs at the time of these investigations (control group), 13 similar patients treated with chlorpromazine, 12 treated with phenothiazine compounds with piperazine ring in the side chain. The investigations were repeated 30-50 min. after oral administration of trihexiphenidil 5 mg. In variant I typical excitability curves were obtained and 5 phases could be discerned in them. In patients treated with piperazine-containing phenothiazine derivatives inducting more significant parkinsonian effects phase III - depression - was significantly shortened, and the excitability was raised in phase IV. In variant II phases III and IV were reversed and in phase IV a rise in excitability was observed in place of depression. In variant II in the group of drug-induced parkinsonism as compared with controls the rise in exictability was greater in phase III and depression in phase IV was smaller. The effect of trihexiphenidil in variant I depended on the initial state. In controls and in patients treated with chlorpromazine trihexiphenidil reduced the duration of phase III of depression and decreased its intensity. In atients treated with phenothiazines containing the piperazine ring depression in phase III was weak but increased after trihexiphenidil administration and increased excitability in phase IV was decreased. The curves became similar to those obtained in controls. In variant II in the control group excitability in phase III increased after trihexiphenidil administration.


[Rare case of left vertebral artery agenesia in man]. At the post-mortem examination of 74 years old male subject it was found that his left vertebral artery was missing. A circle of Willis was formed by two carotid internal arteries and the right vertebral artery. Both cerebellar inferior posterior arteries as well as posterior spinal arteries were also missing. The vessels network of the medulla oblongata and medulla spinalis was composed of multiple cervical ramifications of the right vertebral artery. The latter one passed into the basal cerebral artery and divided in its distal segment into two posterior cerebral arteries. The other arteries of the circle of Willis were normal. There was no history of any CNS disturbances in the patient during his life.


[Carpal tunnel syndrome in a 4-year-old girl with numerous developmental anomalies]. The authors report carpal tunnel syndrome in a 4-year-old girl with multiple developmental anomalies particularly of the cervical spine. The diagnosis was difficult to establish on the basis of muscle atrophy alone since lesions of cervical nerve roots coexisted.


[Excitability curve of alpha motor neurons of the foot dorsal flexor in chemically induced parkinsonian rigidity prior to and following ethylbenzatropine administration]. For evaluation of the state of excitability of motoneurons in the dorsal flexor of the foot in patients with drug-induced muscle rigidity curves of excitability of motoneurons in the anterior tibial muscle were plotted in 10 patients not receiving psychotropic agents (controls) and 10 patients treated with chlorpromazine. Two variants of experiment wase used: in the 1st variant stimulation of the peroneal nerve  behind the fibular capitulum served as the conditioning and testing stimulus, in the 2nd variant stimulation of the tibial nerve in the popliteal fossa was the conditioning stimulus and stimulation of the peroneal nerve in the above way was the testing stimulus. The investigations were carried out before and 30-50 min after intramuscular injection of ethylbenzatropine 5 mg. In the 1st variant the curve of excitability of the motoneurons of the anterior tibial muscle showed the same configuration as the curve of excitability of motoneurons of the soleus muscle in the control group as well as in the treated group. Similarly as in the excitability curve of the soleus muscle five phases could be differentiated in it. Phase III of depression was, however, deeper and phase IV of returning excitability was more evident. In variant II in phase III depression was observed lasting only 40 msec., then in place of return of excitability its decrease was observed. These results were similar to these obtained in the case of conditioning stimulation of afferent fibres of the anterior tibialis muscle, and testing stimulation of the afferent fibres of the soleus muscle. After ethylbenzatropine injection no changes were found in variant I, on the other hand, in variant II a rise of excitability was present in phase III in the control group and in phases III and IV in treated patients. Ethylbenzatropine seemed, thus, to have no effect on the excitability of motoneurons in the dorsal flexor of the foot in the case of conditioning afferent stimulation of the dorsae flexor of the foot.


[Neuromuscular excitability and conduction in cases of hypoparathyroidism]. The patients with hypoparathyroidism were studied carrying out: a) tetanic test (PT) for assessment of the degree of neuromuscular excitability and b) double stimulus test (PBP) for assessment of the efficiency of neuromuscular conduction. In six patients low values of calcium, high values of phosphorus and normal values of magnesium were found. In the remaining patients calcium level was decreased also but the phosphorus level was normal, while that of magnesium was low. In all patients the PT was normal while the PBP showed in the first group reduced efficiency of conduction and in the remaining cases increased neuromuscular conductivility. The possible interpretation of obtained results is discussed.


The effect of testosterone and other adrenal steroids on PMS-induced ovulation in the immature rat. 17 alpha-hydroxyprogesterone (up to 200 mug/day) and 11 beta-hydroxyandrostenedione (up to 500 mug) had no effect on PMS-induced ovulation in intact immature rats. 10 mug/day of testosterone propoinate (TP) on days 28-30 of life decreased the percent of animals ovulating and the number of ova produced; this effect persisted in adrenalectomized animals with or without corticosterone replacement. Three daily doses of 10 mug TP increased the electrical threshold of the medial preoptic area in pentobarbital-blocked, PMS-stimulated animals. And TP decreased the rate of release and synthesis of FSH during the ovulatory surge, and the storage and rate of release of LH; it also inhibited the response to HCG in the PMS-primed animal, suggesting a direct target-organ effect.


[Electromyographic studies of plantar-mental reflex]. The authors investigated the electromyographic response to mechanical stimulation of the palmar skin (palmo-mental reflex) and plantar skin (planto-mental reflex) in the mentalis muscle. The palmo-mental reflex was present in EMG in all 22 healthy subjects an in 51 cases of 51 cases of limited cerebral lesions. The planto-mental reflex was absent in healthy subjects, but it was found in 14 out of 31 cases of focal brain injury and in 2 out of 20 cases with diffuse lesions. The planto-mental reflex is a pathological reflex appearing mainly in severe focal cerebral lesions. No description of this reflex was found in the available literature.


[Epidemiology of epilepsy in school children at Pruszkow and Ursus]. The purpose of the study was calculation of the prevalence rate of epilepsy in school-children (7-15 years) in Prusków and Ursus on the basis of cases recorded in specialistic medical sources and determination and description of elementary clinical and social features in the studied group of children. The calculated prevalence rate of epilepsy in the studied population is 6.73/1000. It is higher in boys (7.45) than girls (5.96) and higher in older children - above 10 years (7.52) than in younger children (5.81). Approximate evaluation of the number of epileptic children at school-age on the basis of this rate shows that in the year 1970 there were about 34000 epileptic children registered in medical institutions in Poland. The analysis of all clinical and social data and certain differences in comparison with data in the literature may show that in childhood epilepsy recorded groups of children are formed by the process of selection. Of a significant role in the formation of these groups may be clinical as well as non-clinical factors. It may be expected, thus, that the actual prevalence rate of epilepsy in children population is higher than that calculated from registered cases.


[Further studies of the state of knowledge and attitudes of the rural population toward epilepsy]. Inquiry investigations were carried out covering 657 individuals from two counties: Plock and Nowy Targ. The inquiry contained 21 questions concerning the knowledge of epilepsy and the attitudes of those questioned to epileptics. The responses were correlated with the sex, age, educational level and occupation of the questioned. Statistical significance was assessed at the confidence level 0.05. The fear of epilepsy was in the 5th place after neoplasms, tuberculosis, cardiac diseases and mental diseases. As the most shameful diseases were regarded venereal diseases, tuberculosis and epilepsy ex aequo with mental diseases. About 1/3 of the respondents answered that epilepsy is a hereditary disease; nearly half of them considered that epileptics may marry and have children. 60% of those questioned regard that they would let their children play with epileptic children, they were usually respondents with medium and higher educational level and representatives of non-agricultural workers. Most respondents stressed the significance of sudden fright in the aetiology of epilepsy and thought that observation of an epileptic seizure may cause epilepsy; the observing subject, especially a child, may be frightened. About 50% of respondents knew nothing of the causes of epilepsy. Over 1/3 of respondents regarded that epileptic children can attend normal schools. Nearly 60% of respondents regard that epileptics can work in certain occupations. The latter view is expressed by younger people below 40 years with high school and college education and representatives of non-agricultural occupations.


Ultrastructural evidence for adrenergic innervation of the interstitial gland in the guinea pig ovary. Fluorescence microscopy has shown that the guinea pig ovary contains not only vasomotor adrenergic nerves but also many nerve terminals running within endocrine structures. Electron microscopy of the interstitial gland confirmed the presence of adrenergic nerves distinguished by administration of the false transmitter, 5-hydroxydropamine. Axon varicosities, denuded of their Schwann cell ensheathing, innervated the endocrine cells in the interstitial gland, with a synaptic distance of approximately 400 A. This suggests that the interstitial gland participates in a neuroendocrine transducer mechanism.


Effect of intraventricular neonatal 6-OH dopamine or 5,6-dihydroxytryptamine adminisration on the circadian periodicity of plasma corticosteroid levels in the rat. The extent of circadian variation in plasma corticosteroid levels at 30 days of age was normal in rats who received either intraventricular 6-OH dopamine or 5,6-dihydroxytryptamine on day 3 of life. A 4-h advance in the time of peaking was present in this latter group. At the time of study the depletion of 8.00 a.m. and 8.00 p.m. levels of norepinephrine was significant in the cortex (--49%), hypothalamus (--58%), hippocampus (--65%), and amygdala (--44%) of the 6-OH dopamine-treated animals, as was a similar depletion of serotonin in these areas in the 5,6-dihydroxytryptamine-treated animals. There was no difference between 8.00 a.m. and 8.00 p.m. levels of either amine in any of these areas, in contrast to the variation seen in uninjected animals in whom 8.00 a.m. levels of both amines were higher in all areas than 8.00 p.m. levels. The female 6-hydroxydopamine-treated animals had significantly increased adrenal weights. No other significant changes were noted in the adrenals or gonads of either treated group. Body weights were not significantly altered in any of the animals. These data demonstrate that the circadian variation in plasma corticosteroid levels can develop in the presence of either marked norepinephrine or serotonin depletion in CNS areas that have been implicated in the regulation of such periodicity.


[Morphological studies of the brain in rats receiving meta-bromophenylsuccinimide]. Morphological evaluation of changes in the brain of rats receiving orally metabromophenylsuccinimid (4-m) - original Polish antiepileptic drug - 1/20 of DL50 per day during a period of one month, has been performed. The dose of the preparation per one kg of the body weight was approximately nine times higher than the therapeutic dose applied at present in human. Neuropathologic changes were found only occasionally; they were not specific, degenerative in character. Both parenchymal and mesenchymal components of the nervous tissue were involved. In neurones the lesions characteristic of chronic disease could be seen; they were more conspiecuous in the cortex of the cerebral hemispheres and in the cerebellum. The damage of the neurones was accompanied by a marked glial cells reaction, progressive in character. Morphological changes of the vessels with consecutive oedema of the white matter were limited to endothelium. Sporadic and not extensive character of the changes as well as their mild intensity seem to provide an evidence that the neurotoxic effect of the tested preparation m-4 is relatively small.


[Lactic dehydrogenase isoenzymes (LDH) in the serum of patients with progressive muscular dystrophy]. Using agar-gel electrophoresis a highly statistically significant decrease in the fractions LDH-4 and LDH-5 and a rise in the LDH-1 and LDH-2 fractions were demonstrated in the serum of patients with dystrophy. Analogous shifts in LDH isoenzyme pattern were found in the serum of 80% of mothers confirmed carriers of the dystrophy gene.


[Hypoxia of high altitudes as a theoretical method of treatment of angina pectoris. Influence on cardiac metabolism]. The stages of myocardial metabolism under normal conditions and in hypoxia are examined. Reference is made to changes in heart metabolism induced in the experimental animal by hypoxia and to the results of a study of such metabolism in persons living permanently at high altitudes (Moret et al.). Hypoxia in decompression chambers is proposed as a hypothetical means of treating angina, since it is capable of causing changes in myocardial metabolism. Note is taken on the fact that hypobarism is not comparable to other techniques on account of its multiple and complex action; this acts at various levels and primarily influences the cardiovascular apparatus.


[Effect of low-molecular dextran on leukergy and thrombergy in cases of cerebral infarct]. In cases of thrombotic cerebral infarction the leucergic and thrombergic tests were done on the 2nd and 3d days of the disease and after 48 hours from the first dextran loading. Fleck's test tube method was used in the leucergy test. The proportion of agglutinated platelets was calculated from a smear stained by Papanicolau method. The results were processed statistically. An inhibitory effect of dextran on aggregation of white blood cells and platelets was observed in the blood of patients with cerebral infarction. The inhibitory effects of dextran was greater in relation to aggregation of platelets than white blood cells. However, in our investigations the effect of this agent on both processes was transient.


[Transport of patients by airlines].

[Transport of patients by airlines]. The problems of transporting patients on normal flights are examined.  The first section describes the conditions of the plan's microclimate which might affect the health of passengers conditions which are obsolute contraindications for flying are also listed.  More detailed analysis is applied to problems regarding the air transport of pregnant women, immature children and heart cases.  The effect of hyperventilation and the anxiety state on flight passengers is then studied.  To conclude, statistics on patients transported on airline flights and on the influence of flying on the course of diseases are reported.


[Aeromedical problems in cranio-vertebral injuries]. Impact between the brain and the cristae of the base normally results as a consequence of inertia when an obstacle is hit, followed by contusion, or intra-, sub- or extradural haematoma. The skull itself may be briken (usually at the interpilasters or the weak points of the pilasters) or dented. Denting resulted in the depression of a circular fragments or fragments, with compression of the dura mater or brain; this, in turn, may be contused, lacerated or even crushed. Spinal crash fractures usually involve the lumbar region. Neck fractures are rare. The picture may be one of clinical silence (local pain) or marked neurological involvement. Damage to the cord is expressed in the form of shock, complete flaccid para- or tetraplegia, complete loss of sensation below the lesion, loss of deep and superficial reflexes, urinary retention and rectal incontinence. Treatment is rendered complicated by profuse scalp haemorrhages, respiratory insufficiency requiring orotracheal intubation and assisted respiration, convulsions, which should be handled with care, since ordinary anti-epilepsy products may mask the onset of hypertension and haematoma. Swelling should be reduced with cortisones. Diuretics may be too brusque and lead to intracerebral haematoma. In the case of spinal injuries, particular care should be excercised in shifting the patient and conveying him to hospital. Where high neck lesions are suspected, the possibility of damage to the originating segments of the phrenic nerve must be borne in mind.


[Medico-social aspects of the post-infarct state. Clinical, functional, psychological and return-to-work studies of 100 patients with myocardial infarct treated in the coronary unit]. To determine whether intensive care unit are able to improve long term as well as immediate prognosis of acute myocardial infarction, one hundred patients, aged 40 to 60 years, six months to three years after discharge have been studied. All patients were examined with ergometric test, psychological assessment and medico-social survey. Comparison was made with patients treated in general medical wards. Correlations between clinical picture, psychological pattern, functional capacity and return to work prove that treatment in a coronary care unit positively affects the future of these patients. The importance of a rehabilitation program and its principles are also discussed.


Treatment of clear cell adenocarcinoma in young females. Eight cases of clear cell adenocarcinoma treated at The M. D. Anderson Hospital are reviewed. Six such lesions were primarily vaginal carcinomas and 2 involved the cervix. Five patients with early carcinomas were treated entirely with a transvaginal cone or interstitial irradiation and 4 are living and well, 2 to 8 years after completion of therapy. We believe that this experience justifies further treatment of early clear cell carcinomas with conservative radiation. This form of therapy is particularly important since the DEX-exposed patients represent an identifiable high-risk group which should augment the chances for early diagnosis.


Cancer metastatic to the ovary: factors influencing survival. In the period 1950 through 1966, 357 patients with cancer metastatic to the ovaries were treated at the Mayo Clinic. The majority of primary tumors arose in the gastrointestinal tract. Factors influencing survival included the site of the primary cancer, histologic grade of the neoplasm, menstrual status, and the type of treatment. Patients whose cancers originated in the genital tract had the lowest mean death rate. Although analyses of survival confirm the observation that cancer metastatic to the ovaries has a poor overall prognosis, 21 of the 357 patients were still living at 10 years and 7 of these patients survived for at least 20 years. The continued development of improved technics of radiation therapy and of more effective chemotherapeutic agents should facilitate intensive therapy for patients with metastatic cancer of the ovaries and result in improved survival.


Appendicitis complicating pregnancy.

Appendicitis complicating pregnancy. Thirty-four pregnant women with acute appendicitis presented at Parkland Memorial Hospital during a 15-year period. Abdominal pain, usually accompanied by nausea with or without vomiting, was the most common presenting symptom. Anorexia was less constant, and its occurrence decreased with advancing gestation. Physical findings usually included direct abdominal tenderness and, less often, rebound tenderness. Leukocytosis and/or a "left shift" were common laboratory findings, and the urinalysis was normal in most cases. Diagnosis was increasingly difficult as gestation progressed. This was reflected both by the increasing severity of the disease process found at surgery and by increasing fetal loss. If the diagnosis of appendicitis is suspected in the gravid patient, immediate surgical intervention is indicated to prevent the catastrophic complications associated with procrastination in diagnosis and treatment.


Gestational variation of fatty acid composition of human amniotic fluid lipids. The amount of total lipids of the amniotic fluid of normal human subjects increases progressively with gestational age and is found to be maximum in labor at term. The lecithin/sphingomeylin ratio, which invariably increased with gestational age, is 2:1 or greater beyong 34 weeks of pregnancy and becomes maximum at term labor. No definite correlation exists between the palmitic acid content of total lipids and gestational age; but the palmitic acid content of the lecithin fraction increases with gestational age and this increase is markedly accelerated near the 34th week of pregnancy. Also it is observed that the arachidonic acid of cholesterol esters increases with gestational age. Therefore, it is suggested that both the palmitic acid level of lecithin and the arachidonic acid level of cholesterol esters might serve as more reliable indices that current methods being employed for the assessment of fetal lung maturity.


Contraction stress test for antepartum fetal evaluation. The contraction stress test (CST) was used to attempt determination of fetal reserve prior to labor by evaluating the response of the fetal heart rate to spontaneous or induced uterine contractions. Testing was performed by using an external fetal heart rate monitor and tocograph. The CST was employed 189 times in 120 high-risk patients who either had hypertensive disorder of pregnancy or had completed at least 42 weeks of gestation. Testing was begun as early as 34 weeks' gestation and repeated at weekly intervals; it was not used in the clinical management of the patient. The maximum number of tests performed on one patient was 8. A negative CST appears to be a most reliable guide to the ability of the fetus to tolerate labor if it ensues within 1 week. A positive test suggests that the fetus is at increased risk, but death is not necessarily imminent. Results of the present study warrant use of the CST in controlled studies to determine its effect in improving perinatal outcome.


Luteinizing hormone, adrenal androgenesis, and polycystic ovarian disease. Seven oophorectomized patients were administered a total of 60,000 units of human chorionic gonadotropin over a 3-day period, and plasma testosterone levels were obtained. One of the 7 patients demonstrated a definitive response to the hormone but repeat testing proved to be negative. The potential role of luteinizing hormone in the pathogenesis of polycystic ovarian syndrome is discussed and current evidence linking LH to adrenal androgenesis is reviewed. Modifications that may be employed for future study are suggested.


Aging and X chromosome loss in the human ovary. A study of the incidence of X chromosome loss from the mitotic complement of human ovary has demonstrated a small loss beginning between ages 36 and 45 years and increasing additively to age 75. This was earlier and less than has been shown for blood. In ovarian tissue, autosomal chromosomal loss declined with age while X loss increased. Though no correlation of X loss could be demonstrated with the clinical state of the menstrual cycle, there was a greater loss of all chromosomes in normally cycling subjects than in perimenopausal and postmenopausal subjects. The possibility that the menopause is initiated in the ovary is raised by findings of these correlates of aging.


Renal carcinoma in pregnancy.

Renal carcinoma in pregnancy. A gravid patient presented with gross hematuria in the last trimester of pregnancy but did not permit diagnostic measures. After delivery a large abdominal mass, which proved to be renal cell carcinoma, was found. Previously reported cases are reviewed, and the importance of adequate workup of hematuria during pregnancy is emphasized.


Intravascular hemolysis: a complication of midtrimester abortion: a report of two cases. Intravascular hemolysis occurred twice in a series of 1582 consecutive intraamniotic midtrimester saline abortions. The hemolysis was associated with consumption coagulopathy and acute renal failure. Both patients made a complete recovery after a prolonged hospital stay; one required peritoneal dialysis. The pathogenesis of this serious complication of saline abortion is discussed but no satisfactory explanation has been reached.


Manometric evaluation of labor.

Manometric evaluation of labor. A practical method of monitoring uterine contractility during labor is described utilizing a water manometer technic. Comparison of manometric measurements of uterine activity with electronic monitor values reveals that the manometric technic provides an accurate assessment of pathologic intrauterine pressures.


A safer uterine curette.

A safer uterine curette. A new uterine curette is described, with features designed to help eliminate some of the instrumentation hazards in the operation of uterine curettage. An analysis of the disadvantages of the traditional curette is presented together with a description of how these have been minimized or eliminated in the new instrument. The fundamental difference in the new instrument is its tip. It has features to minimize the likelihood of perforation, deep gouging, and unnecessary injury to the basilar endometrium. Prototypes of the new instrument have gone through an evolutionary and testing period of 25 years, during which the instrument has been used by many operators. There have been no serious accidents or complications reported, and there has been no need for repeat curettage.


Medicine and the law.

Medicine and the law. 1. Public and private benefits offering security for life if the need is of sufficient magnitude inhibits optimum restoration of the patient. 2. The physician frequently does not recognise nor is concerned with the premorbid attitude, goals or life-style of the patient and does not effectively deal with the future temporal needs of the patient, thereby contributing to less than satisfactory levels of restoration. 3. The law and its objectives as practised by the lawyers often develop into an intense adversary posture, threatening the security of the patient and jeopardising a satisfactory level of restoration. 4. Administration of the law by judicial and quasi-judicial judges and juries is manipulated to give the highest award possible, therefore the plaintiff will not be restored to the satisfactory level of which he is capable. 5. There is hostility and little communication between physician and lawyer again contributing to the patient's failure in restoration. 6. The adversary system is accused of creating conditions contributing to unsatisfactory restoration but can be utilised as a motivational force with innovative and creative thinking on the part of the professions to meet the real needs and goals for security of the patient and motivate his restoration. 7. Communication and role-playing exchange between the professions and the patient as his condition will require, promote a successful and acceptable restoration. 8. The counsel involved develop the process for prompt financial disposition without involving the patient in the adversary process or in trial.


The experimental contusion injury of the spinal cord in sheep. The validity of reproduction of the controlled contusion injury to the spinal cord in the experimental animal is questioned. The dynamic pathology involving the microvasculature within the first two hours is illustrated using light microscopy. After 15-30 minutes swelling of axons and disruption of myelin sheaths become evident in most areas of white matter. After four hours microcysts have formed in the columns of white matter and are evidence of irreversible damage. Swelling of the cord following injury results from congestion, extravasation and intracellular swelling of neurones, rather than from any demonstrable increase in extracellular fluid. Oedema was only demonstrated with perfusion fixation. Isotope and contrast myelography were compared in the identification of the degree and extent of spinal cord swelling. Significant improvement in motor power was found in a group of paraplegic sheep treated with alpha-methyl paratyrosine. There was no significant improvement in the degree of recovery of motor power or sensation in those animals treated with intrathecal methyl prednisolone (Depo-Medrol). The histopathology in the crushed spinal cord tissue of the treated and untreated animals at various intervals of time was compared. Some possible explanations for the different patterns of clinical recovery in the treated animals are discussed.


Ferritin turnover in plasma: an opportunistic use of blood removed during exchange transfusion. The concentration of plasma ferritin was measured in serial samples of blood removed from six preterm neonates undergoing exchange transfusion for hyperbilirubinemia. The average plasma ferritin concentration in the infants was 218 ng/ml compared with 47 ng/ml in the donors. The mean concentration of ferritin decreased an average of 62 ng/ml during the exchange transfusions. The plasma ferritin half-life was computed to be 2.5 and 5.5 min in the two infants weighing 2,000 and 2,500 g compared with a half-life of 4 min in the rat. In four infants weighing between 1,000 and 1,180 g, the half-life ranged from 9.1 to 34 min. These data support the concept of a rapid plasma ferritin turnover and indicate that ferritin may transport a large amount of iron through the plasma compartment in spite of its low concentration.


In vivo D-glucose absorption in the developing rat small intestine. Solutions containing D-glucose (1--20 mg/ml) were perfused in situ through the jejunum + ileum of anesthetized rats 7-8 and 14-15 (suckling), 21-23 (weanling), 35-36, and 70-73 days old. The amounts of glucose absorbed, expressed as percentage of load perfused (normalized for intestinal weight, milligrams per hour per gram wet weight), were greater in the weanling than in the suckling pups. Rate of glucose absorption increased with increase in glucose concentration in the perfused solutions and reached a plateau when concentration exceeded 3 mg/ml in the suckling and 10 mg/ml in the weanling rats. Based on intestinal weight, absorption rates (milligrams per hour per gram wet weight) from solutions containing 10 mg/ml glucose were 2 times greater in the 21-23 than in the 7-8-day-old pups (64 versus 30; P less than 0.01). Glucose absorption rates (milligrams per hour per gram wet weight of the perfused intestine) from the 20 mg/ml solution were similar in the 21-23 (64), 35-36 (60), and 70-73 (58)-day-old rats. The above results suggested that under the experimental conditions in rats the ability of the small intestine to absorp glucose per unit weight about doubles at the time of weaning as compared with the suckling period with no further enhancement thereafter.


Production of the features of Reye's syndrome in rats with 4-pentenoic acid. 4-Pentenoic acid, an analog of hypoglycin which is believed to cause Jamaican vomiting sickness, was administered intraperitoneally to rats in an attempt to produce the features of Reye's syndrome in rats. Mean ammonia levels in plasma were found to be elevated approximately four-fold after injection of 200 mg/kg pentenoic acid in fed rats. Pentenoic acid caused hypoglycemia in fasted rats and hyperglycemia in fed rats. In chronic experiments rats were injected intraperitoneally every 4 hr with 50 mg/kg body weight of pentenoic acid for 10 doses, followed by a single dose of 200 mg/kg. The livers of the treated group were enlarged and yellow and showed extensive fatty degeneration. The blood-urea-nitrogen (BUN) was significantly higher and the free fatty acids (FFA's) significantly lower in these rats. This study shows that pentenoic acid administered to rats produces findings similar to those of Reye's syndrome and Jamaican vomiting sickness.


In vitro studies of effects of light and riboflavin on DNA and HeLa cells. The widespread use of phototherapy for neonatal hyperbilirubinemia has caused some concern since substances other than bilirubin may be photoactivated. The toxic properties of these photoactivated substances might prove to be more harmful to the neonatal infant than bilirubin. The purpose of the present study was to investigate the effect of photoactivated riboflavin in low concentration, on purified DNA. The results demonstrate extensive changes in the structure of DNA (see Table 1) manifested by (1) a change in the peak absorbance in the ultraviolet, (2) a decrease in the temperature of the thermal helix-coil transition, (3) a slight decrease in the sedimentation coefficient, and (4) an increase in the buoyant density values (1.704-1.709). These observations are consistent with the interpretation that there has been an alteration of one of the base moieties with minimal cleavage of the phosphodiester linkages. Results with human cells in tissue culture indicate that a similar photodynamic effect of riboflavin on the DNA occurs in living cells.


Detection by electron microscopy of photo-induced denaturation in lambda DNA. We have used an electron microscope to study localized denatured regions in ultraviolet-irradiated DNA. DNA from bacteriophage lambda was UV-irradiated and then prepared for electron microscopy after fixing in buffered (pH 9.5) formaldehyde solutions at 25 degrees C. The denatured regions observed corresponded to those described by Inman and Schnös (1) who used alkaline denaturation to preferentially destroy thymine-adenine base pairing. In UV-irradiated DNA, pairs of neighboring thymine residues are converted into photodimers; hence, loss of hydrogen bonding most likely occurs in thymine-rich regions and denaturation results. Conceivably, photo-induced denaturation may under some circumstances represent a more convenient method than alkaline denaturation for mapping thymine-rich regions in DNA.


Further characterization of the polynucleotide phosphorylase of Micrococcus luteus. The purification of polynucleotide phosphorylase from Micrococcus luteus by chromatography on phosphocellulose colums is described. This procedure offers several advantages over previous procedures. Previously determined molecular weights for Form-I enzyme and Form-T enzyme derived from Form-I by limited tryptic hydrolysis were confirmed as 2.7 and 2.3 times 10-5, respectively. Form-I appears homogeneous in the ultracentrifuge, but multiple active protein species are separable by polyacrylamide gel electrophoresis. The multiple species are probably the result of proteolysis. On polyacrylamide gel electrophoresis under denaturing conditions, Form-T yielded a single size of subunit of 71,000 daltons, and Form-I yielded several bands of different molecular sizes. These results differ from earlier determinations. The amino acid compositions of Form-I and Form-T are reported. Form-I contains only between 8 and 10 cysteine residues per molecule and Form-T half that many.


Absence of mRNA for casein in free polysomes of lactating ewe mammary gland. Total polysomal RNA or poly A- containing RNA extracted from free polysomes of lactating ewe mammary gland was unable to direct a significant synthesis of alpha-s- and beta-casein. Polyacrylamide gel electrophoresis of poly A- containing RNA revealed that the two major peaks of mRNA isolated from membrane-bound polysomes were not observed in mRNA isolated from free polysomes. Purified 125-I anti-alpha-s-casein could bind significantly to membrane-bound polysomes only. These data suggest that casein synthesis occurs almost exclusively on membrane-bound polysomes and that this specificity may be attributed to the presence of casein mRNAs on these polysomes and their absence from free polysomes.


Heterogeneity of mitochondrial DNA from Saccharomyces carlsbergensis. Denaturation mapping by electron microscopy. Electronmicroscopic observation of the denaturation pattern of 130 partially denaturated linear mitochondrial DNA molecules from Saccharomyces carlsbergensis was used to investigate the distribution of AT-rich sequences within the mitochondrial genome. The molecules were observed after heating to 43 degrees C in the presence of 12% formaldehyde. These conditions resulted in an average denaturation per molecule of 21%. The average length of the molecules was 10 mum, and a few molecules had a length corresponding to the size of the complete genome. The undenaturated regions varied in length from 0.1 to 5.0 mum with denaturated regions of length 0.02 to 0.1 mum in between. A denaturation map was constructed by use of one of the long molecules (28.7 mum) as a master molecule for positioning of all other molecules. This map shows distinct regions corresponding to the position of easily denaturated sequences in the mitochondrial DNA. These sequences which presumably correspond to the very AT-rich regions, known to exist in the yeast mitochondrial DNA, were found at intervals of about 0.5 - 3 mum on the map.


Correlation of anti-inflammatory activity with inhibition of prostaglandin synthesis activity of nonsteroidal anti-estrogens and estrogens (38532). Diethylstilbestrol, clomiphene, ethamoxytriphetol and triparanol were 0.18, 1.0, 0.02 and 0.01 times as potent in the in vitro inhibition of prostaglandin synthetase, respectively as was indomethacin.  In the in vivo carrageenan-induced rat paw edema studies, diethylstilbestrol was more potent as an anti-inflammatory agent than was clomiphene, and ethamoxytriphetol and triparanol were only marginally effective.  The most potent of the compounds tested was indomethacin.  The results reported demonstrate that the nonsteroidal anti-inflammatory agents and the nonsteroidal estrogens and anti-estrogens share the property of inhibition of prostaglandin synthetase.


Effects of metyrapone on reproductive organs of house mice (38533). The effects of chronic administration of metyrapone, a specific adrenal 11beta-hydroxylase inhibitor, were examined on the reproductive organs of house mice. In one experiment, immature (30 days old) mice of both sexes received daily injections of either metyrapone (100 mg/kg) or saline ip for 30 days. In a second experiment, mature mice (90 days old) were treated in like manner either with metyrapone (100 mg/kg) or saline for 21 days. Twenty-four hours after the last injection, mice were killed, fixed in formalin, and organs were weighed and examined by light microscopy. There was significant impairment of ovarian and uterine development in the young female metyrapone-treated mice with the incidence of corpora lutea being reduced 82%. Seminal vesicle and body weights were significantly reduced in juvenile males. Among mature animals, a 14% decrease in adrenal gland weight from adult females was the only signigicant effect of prolonged treatment with metyrapone. These data support the hypothesis that increases in pituitary-adrenocortical function may impair development of reproductive organs in small rodents.


Effect of pinealectomy on rat brain myelin (38534). Analysis of purified myelin from the respective brains of both sexes of 40-day-old rats revealed that neonatal pinealectomy results in decreased myelin formation.


Ferritin in formed blood elements (38539). The ferritin concentration of the formed elements of the blood has been measured. Nearly equal amounts were found in plasma, red cells, granulocytes, and in the mononuclear (monocyte and lymphocyte) cell fraction. Platelets contained a negligible amount. Concentrations of ferritin were greatest in blood leukocytes, amounting to approximately 24 mug/ml. Changes occurring with iron depletion and iron overload were consistent with those expected in body tissues in general. With infection, increased levels of ferritin were observed in the mononuclear cell fraction, consistent with that which occurs in RE cells.


Host resistance mechanisms to Newcastle disease virus in immunodeficient chickens  (38540). In order to assess the mechanisms of host resistance to Newcastle disease virus (NDV), the susceptibility of young adult normal, T cell deficient and agammaglobulinemic chickens to an avirulent live vaccine (Bl) and a mesogenic strain of NDV was studied.  All animals, regardless of immunological status resisted the vaccine strain.  Most normal birds resisted mesogenic NDV, HOWEVER T cell deficient birds were much more susceptible and agammaglobulinemic chickens were extremely susceptible.  There was no difference in the kinetics and levels of hemmagglutination-inhibition activity of plasma between normal, control-irradiated and T cell deficient birds nor between dying and surviving birds.  Agammaglobulinemic chickens could be partially protected against an otherwise lethal challenge following immunization with avirulent NDV, low doses of mesogenic NDV inoculated intranasally or im injection of beta-propriolactone inactivated NDV mixed in complete Freund's adjuvant.  The possible mechanisms for this protection together with the relative roles of humoral, cell mediated and non-specific immunity are discussed.


Cirrhosis of choline deficiency in the Rhesus Monkey.  Possible role of dietary cholesterol (38541). One of five rhesus monkeys fed a diet deficient in choline and protein for 31 mo developed signs of cirrhosis at 26 mo.  Five other monkeys were fed the same diet for 14 mo, at which time cholesterol comprising 2% of the diet was added.  Three followed a sharp rise in hepatic lipids.  One monkey developed marked hypercholesterolemia and showed signs of cirrhosis 2 mo after cholesterol supplementation. The findings indicate that the rhesus monkey is susceptible to choline-deficiency cirrhosis.  They suggest that cholestrol supplementation accelerates this process.


Experimental manipulation of preleukemic change in whole-body irradiated RFM/Up mice (38542). Radiation which induces leukemogenesis in the unirradiated mouse, inhibits leukemogenesis if given again to the previously irradiated, but not yet leukemic mouse. The objective of this experiment was to identiry nonmalignant late radiation in jury in the bone marrow, the modification of which by a second exposure may account for postponement of radiogenic leukemia. To this end, leukemogenically irradiated RFM/Up mice were reirradiated under conditions known to bring about postponement of the leukemias due to the first radiation exposure. Quantitative analysis of the femoral pone marrow of these mice shows that leukemia incidence is positively correlated with the number of immature myeloid cells, and negatively correlated with the percentage of the mature myeloid cells in the entire myeloid series. The implications of this for the understanding of preleukemic change are discussed.


Effect of cholestyramine on tissue pools of cholesterol a preliminary report. Four Type II Hyperlipoproteinemic subjects were investigated before and after treatment with cholestyramine. Plasma cholesterol was significantly reduced (365 plus or minus 23 vs 273 plus or minus 34 mg/100 ml) and triglycerides significantly increased (149 plus or minus 55 vs 181 plus or minus 59 mg/100 ml) on cholestyramine treatment. The daily turnover of cholesterol, as determined by the method of Goodman and Nobel, was nearly doubled by the treatment (0.813 plus or minus 0.11 vs 1.595 plus or minus 0.176 g). Although previous workers have already suggested that cholestyramine does not decrease tissue cholesterol pools, we observed a significant increase in tissue pools in each of the three subjects given cholestyramine alone (10.1 plus or minus 1.4 vs 16.2 plus or minus 6.9 g) for Pool A - EXCLUDING PLASMA; AND 27.2 PLUS OR MINUS 4.6 VS 43.7 PLUS OR MINUS 6.4 G FOR Pool B). Treatment for the fourth subject consisted of a combination of cholestyramine and clofibrate. This combination appeared to prevent increases in the size of Pool B and in the size and production rate of Pool A. These preliminary observations suggest that the hypocholesterolemic effect of cholestyramine may be enhanced and its effects on tissue cholesterol prevented by giving it in combination with other agents such as clofibrate.


Effect of mirex on induced ovulation in immature rats (38550). PMS-induced ovulation  was significantly inhibited in 28-day-old immature rats by acute administration of the chlorinated  pesticide Mirex.  Numbers of ova recovered were reduced by 40-80% from controls with dose levels of Mirex ranging from 0.4 to 50 mg per animal.  When injections of Mirex 48 hr after PMS were followed by HCG the inhibitory effect of the insecticide was overcome, suggesting that the ovary is not the primary site of action.  Injections of Mirex at intervals preceding the PMS-induced LH surge resulted in an inhibition of ovulation.  Administration of the insecticide after the expected release of LH was ineffective.  There was no indication of a premature or delayed release of LH due to injection of Mirex.  TPHE DATA SUGGEST THAT Mirex inhibits PMS-induced ovulation by an unknown effect upon neural mechanisms controlling the release of LH.


Inability of angiotensin to stimulate RNA SYNTHESIS IN ISOLATED RAT ATRIA (38551). Contrary to a previous report by other investigators, angiotensin was shown not to increase the incorporation of (3H)uridine into RNA of rat atria in culture.


The effect of vasectomy and oviduct section on mouse behavior (38554). The spontaneous movement of vasectomized adult Swiss Webster male mice was 60% less than sham-operated controls 45 days after the operation. A similar trend was recorded for tubectomized frmales. Exploratory behavior as measured by the open field test was not significantly influenced by either surgical proceedure.


Degradation of particulate lipid by the large-granule fraction of rat liver (38555). Radiolabeled particulate lipid administered intravenously was cleared from the circulation and localized primarily with in the liver. The phagocytized 131I-triglyceride was degraded with the subsequent release of free 131I-triglyceride emulsion in vitro with different hepatic subcellular fractions revealed that the lysosome rich large-granule fraction contained the highest specific deiodinative activity. This observation coupled with the findings on latency of activation and an acid findings on latency of activation and an acid pH optimum, support the concept that the lysosomes are critically involved in the degradation of the particulate phagocytized lipid in the liver.


Effect of corynebacterium parvum on bone marrow cell cultures (38557). The effect of C. parvum on in vitro colony-forming cell was evaluated.  A single ip injection of the vaccine had no effect during the first 4 hr either on colony stimulating factor or on colony-forming cells.  The enhancement of the colony-forming capacity of the bone marrow by C.parvum occurred after two injections of the vaccine within 48 hr.  The stimulation of colony formation by C. parvum was time related function and occured 5 days after the initiation of the cultures.  The results of this study indicate that C. parvum appears to be stimulant of bone marrow cells capable of proliferation and may be used as a valuable adjuvant against myelosuppressive agents.


Ability of several cations to promote secretion of thyrocalcitonin in the pig-1-2 (38559). Various ions were tested to see whether or not at pharmacological plasma levels they affected TCT secretion from the pig thyroid gland in vivo.  Test solutions were infused either systemically (femoral vein) or directly into the thyroid artery for brief (10-12 min) periods.  Infusions of large doses of magnesium, potassium, strontium and barium, as well as calcium, produced increases in TCT in thyroid venous plasma ranging from two- to tenfold.  Blood analyses reveled that levels of these stimulatory cations produced in plasma during the infusions indeed were high.  In contrast, infusions of sodium and phosphate suggested that neither hypernatermia nor hyperhosphatemia directly altered TCT secretion.  The findings are in accord with previous suggstions that although cations other than calcium are capable of increasing TCT secretion, probably only calcium plays an important role in the physical regulation of TCT secretion.  Neverthless, other effective agents, such as those reported here, may consitute useful pharmacological tools for studying the mechanisms involved in secretion of TCT.


Effect of diftalone and other nonsteroidal anti-inflammatory agents on synthesis of prostaglandins (38560). Diftalone and its metabolites 7, 14-Dihydroxyphthalzino  (2,3-b)phthalazine-5, 12 (7H,  14H)-dione, 7-Hydroxyphthalazino (2, 3-b)phthalzine-5,12 (7H, 14H)=DIONE, AND 12 (1(2H)-oxo-2-phthalazinyl)methylbenzoic acid inhibited prostaglandin synthesis in bovine seminal vesicle microsome preparations.  Diftalone was the most active of these compounds but less active than indomethacin although more active than phenylbutazone or asprin.  The magnitude of the concentration of arachidonic acid influenced the velocity of the reaction in the synthesis of prostaglandins; the highest concentrations inhibited the rate of reaction.  The results of the in vitro inhibition of prostaglandin synthetase studies correlated well with those obtained in the in vivo carrageenan edema inhibition studies in the rat.  The relative potencies for Diftalone, indomethacin and phenylbutazone were similar with both experimental procedures.


The dependence of the hemoglobin (beta plus gamma)/alpha chain synthetic ratio on the degree of anemia in beta-thalassemia (38561). The peripheral blood hemoglobin (beta plus gamma)/alpha chain synthetic ratio in three homozygous beta-thalassemic subjects was shown to increase towards unity as their hematocrits were raised by stepwise transfusion.  The observation that the chain synthetic ratio can vary in a given individual is discussed in relation to current understanding about the regulation of hemoglobin synthesis.


Release of cholecystokinin by acid (38562). In dogs with pancreatic fistulas, the amount of CCK released by acid in the intestine was estimated by determining how much exogenous CCK had to be fiven to mimic the pancreatic protein response. Duodenal infusion of 16 mmole/hr of HCl with a high background dose of intravenous secretin stimulated pancreatic protein secretion to about the same degree as 0.5 unit/kg-hr of exogenous CCK; the same acid load without secretin background gave a response equivalent to about 0.7 unit/kg-hr of CCK. Expressed as fractions of their respective doses for half maximal response, acid releases almost five times more secretin than CCK.


Safety assessment of poly I:C in NZB/NZW mice (38565). The present report confirms the findings by Steinberg et al. (9) that repeated intraperitoneal injections of poly I:C (3 mug/g, three times per wk, 40-52 doses) enhanced the incidence and severity of glomerular lesions that occur spontaneously in NZG/NZW mice and also increased the development of circulating antibody against nucleic acids. This effect was minimal when only six intraperitoneal doses were given in 1 mug/g amount at weekly intervals. Intranasal administration of poly I:C (0.2 mug/g, three times per wk, 40 doses) or six doses of the drug (1 mug/g weekly) caused no apparent potentiation of glomerular response. ICR/Ha mice, which do not suffer from the spontaneously occurring disease, were uneffected by poly I:C treatment except for occasional development of antibody against poly I:C or DNA.


Tolerance of isolated cardiac muscle to hypoxia: force-frequency interrelationships (38566). The  preformance of isolated left ventricular muscle preparations during 60 min of hypoxia (95 percent N-2, 5% CO-2) and 30 min of reoxygenation (95% O-2, 5% CO2) was examined at differing stimulation rates (1, 12 and 60 stimuli/min).  Since a change in inotropic state accompanies a change in cardiac rate, studies were carried out in two species with different force-frequency relationships over the heart rate range examined the rat and the guinea pig.  Preparations were studied at the apices of their length tension curves while contracting isometrically 12 times a min at 28 degrees.  At increasing stimulation rates, under oxygenated conditions, isometric tension fell in rat ventricular muscle while the reverse is true in the guinea pig.  Despite the differing force-frequency responses, both species demonstrated progressively poor performance during hypoxia at increasing stimulation rates.  This was manifested by a more rapid and greater decline in mechanical activity, more severe contracture during hypoxia and and slower recovery upon reoxygenation.


Migration of peripheral leukocytes in the presence of carcinoembryonic antigen.  Studies in patients with chronic inflammatory diseases of the intestine and carcinoma of the colon and pancreas (32568). The leukocyte migration technique was employed to study in vitro cell-mediated immune responses to purified CEA in patients with Crohn's disease and active ulcerative colitis and in those with colonic and pancreatic carcinoma. No significant inhibition of leukocyte migration was demonstrated by CEA, with the exception of one patient with pancreatic carcinoma.  Thus, with the leukocyte migration technique, no consistent in vitro cell-mediated immunity to CEA was demonstrated supporting the hypothesis that CEA is not the antigen toward which cell-mediated host response phenomena are directed.


Efficiency of energy utilization by the Zucker hereditarily obese rat "fatty" (38569). The hereditarily obese rat "fatty", with food intake restricted to approximately normal, laid down excessive fat at the rate of 0.56 g rat per day for up to 74 days on experiment, producing an energy denser, but lighter weight, carcass than the normal control.  The "fatty" retained over 20% of the energy supplied, in its carcass, the control less than 10%.


Failure to demonstrate circulating endotoxin in malaria (38572). The possibility that endotoxin or an endotoxin-like substance plays a role in malaria has been suggested by the clinical similarity between human malaria and the febrile reaction to endotoxins, as well as the occurrence of endotoxin tolerance in humans infected with malaria.  However, endotoxin or endotoxin-like activity was not demonstrable, using the Limulus test, in the plasma of humans or monkeys infected with plasmodia.  The data indicate that the febrile paroxysm of malarial infection is not associated with detectable levels of endotoxin in the blood.


Effect of hemoglobin and hematin on plasma clearance of hemopexin, photo-inactivated hemopexin and albumin  (38575). The plasma half clearance time (T1/2) of isotope-labeled rabbit hemopexin was 35.5 plus or minus 1.9 hr in rabbits. After intra-and extra-vascular equilibration of 125I-hemopexin and 131I-albumin, injection of either hematin, hemoglobin or methemoglobin (12.5 mg of heme/kg body wt) resulted in the rapid removal of 60-80% of circulating hemopexin (T1/2 = 7.2 plus or minus 0.6 hr) but did not affect albumin catabolism. After selective photo-inactivation of hemopexin, the T1/2 of this hemopexin was comparable to that of the native molecule. However, its plasma disappearance curve was not appreciably affected by administration of hematin. These findings demonstrate that hemopexin is cleared and catabolized at an enhanced rate during states of plasma heme load, and that modification of critical histidine residues of hemopexin eliminates its biological function in plasma heme disposal.


Transplacental passage of methylmercury and its uptake by primate fetal tissues (38576). Radioactive methylmercury given to rhesus monkeys in late pregnancy crossed the placenta slowly from mother to fetus.  The maternal-fetal ratio in both plasma and erythrocytes was as low as 10:1 serveral hours after maternal administration.  Transfer from fetus to mother was even slower with the concentration gradient remaining above 25:1. Organic mercury was generally distributed throughout fetal tissues in a similar manner regardless of the routine of administration.  The placenta and blood-brain barrier each appear to represent partial impediments to acute transfer of organic mercury, probably because of extensive erythrocyte binding.  While the hemochorial placenta, by virtue of its limited permeability to organic mercury, appears to afford the fetus some degree of protection of acute mercury poisoning the fact that mercury moves out of the fetel circulation even more slowly than into it probably accounts for the fetal hazard with chronic exposure.


In vivo hemolytic potency and binding of chlorpromazine to plasma protein and erythrocytes of rat and dog (38579). It was demonstrated by equilibrium dialysis that dog red cells have a greater ability to bind chlorpromazine than rat red cells.  Dog plasma was shown to have a greater ability to bind chlopromazine than rat plasma although this difference was not statistically significant.  In the presence of CPZ (10-3M), the 50% hemolysis time of dog red cells suspended in homologous plasma or in 0.9% buffered NaCl solution was much greater than that of rat red cells treated in the same manner.  The 50% hemolysis time of dog red cells suspended in homologous plasma was considerably shortened when they were suspended in rat plasma.  Conversely, an increase in the 50% hemolysis time was obtained when rat red cells were suspended in dog plasma.  Several possibilities for the slower rate of CPZ-induced hemolysis of dog red cells as compared to rat has been discussed in the present report.


The synthesis of tautine from sulfate VIII. The effect of potassium (38580). The in vitro and in vivo influence of K+ on the activity of rat heart and liver PAPS-sulfotransferase (P1) was tested. The P1 activity was optimal with 0.5 mumoles K+ per mug protein. The P1 activity was decreased by mild dialysis and lost by extended dialysis. The enzyme was stable when dialyzed with K+ and tests with other ions indicated K+ specificity. Rats fed purified diets with low, normal or high levels of K+ had significantly different heart taurine concentrations and P1 specific activities. These P1 specific activities became comparable to those from the rats receiving the normal K+ diet by the addition of KCl to the assay mixture.


Acute and chronic effects of sulpride on serum prolactin and gonadotropin levels in castrated male rats (38581). The effect of the acute or chronic administration of sulpiride on serum prolactin and gonadotropin levels was studied in castrated male rats. Sulpiride administered in acute intravenous injections induced a quick increase in serum prolactin levels and no significant changes in serum gonadotropins. The peak in serum prolactin was observed 30 min after the injection of sulpiride, with a decrease of serum prolactin levels at 60 and 120 min. The subcutaneous administration of sulpiride for 13 days induced a significant increase in serum prolactin levels at the end of the treatment, and no significant changes in serum FSH and LH levels.


Direct effects of hypoosmolality on vascular resistance and myocardial contractile force (38587). Hemodialysis was used to study the direct effects of acute hypoosmolality upon the resistance to blood flow through the gracilis and coronary vascular beds and upon left ventricular contractile force in the dog. When sodium chloride was removed from the blood perfusing the gracilis vascular bed, resistance increased linearly over the range 300-225 mOsm/kg. A 10% decrease in osmolality produces a 20% increase in resistance. When the removed sodium dhloride was replaced with mannitol such that plasma osmolality did not change, resistance rose slightly but failed to regularly return to the control value. Hypoosmolality also raised coronary vascular resistance and this was associated with an increase in left ventricular force. Thus direct effects of hypoosmolality on peripheral vascular beds and perhaps myocardium may participate in the compensatory mechanisms that tend to stabilize blood pressure during hypoosmotic states such as acute salt depletion.


The effects of prostaglandin E on fetal pulmonary vascular resistance (38588). The effects of PGE on pulmonary vascular resistance were investigated in fetal goats using an isolated perfusion technique on otherwise intact unventilated lobes.  PGE decreased perfusion pressure in the left pulmonary artery under conditions of monary vascular resistance by vasodilatation of tonically contracted vascular smooth muscle. In our preparation, intrapulmonary PGE infusion did not alter femoral arterial pressure which suggests that PGE is inactivated in the fetal lung.  Implications for PGE in the newborn with respiratory distress and increased pulmonary vascular resistance are discussed.


Erythrocyte 2,3-diphosphoglycerate concentrations in hibernating, hypothermic, and rewarming hamsters (38589). Hematocrit, hemoglobin and erythrocyte 2,3-DPG concentrations were examined in normothermic control, hibernating, and helium-cold hypothermic hamsters. Hematocrit was not signigicantly different (P greater than 0.05) between groups, but did reflect alterations reported for hemoglobin. Hemoglobin concentration did not change from control values during 12 hr at Tre 7 degrees; however, approximately a 20% decrease occurred in hibernators (48 hrs) and animals hypothermic (24 hr). 2,3-DPG concentrations declined 39.1 and 33.9% from control values in the hibernating and 24 hr hypothermic groups, respectively. No change was observed in animals hypothermic for 12 hr. Both parameters were studied in the aroused animal. Hemoglobin returns to control values immediately after the animals reached a stable Tre approximately equal to 37 degrees. Although 2,3-DPG levels increased during arousal, they were still 10% lower than control values in both metabolically depressed groups. 2,3-DPG remained approximately 10% less than controls in rewarmed hypothermic animals studied 2 hr after reaching stable Tre approximately equal to 37 degrees. The data are discussed in terms of cold depression of erythrocyte glycolysis.


Oxygen consumption in fetal rabbit ductus arteriosus (38590). Oxygen consumption in fetal rabbit ductus arteriosus and descending aorta was studied after human umbilical artery tissue was used to standardize the technique. A steady state of oxygen consjmption persisted for 90-100 min after dissection, and a tissue dry weight of greater than 15 mg was necessary to obtain reliable data, necessitating pooling of rabbit fetal tissue from 25.75-26.5 day gestation had an oxygen consumption of 2.05 plus or minus 0.22 (4) mul oxygen/10 mg dry wt/hr, and at 27.5-29.5 it was 5.69 plus or minus 0.28 (7) (P less than 0.001). There was no change with gestational age in the oxygen consumption in the descending aorta (2.15 plus or minus 0.23 mul oxygen/10 mg dry wt/hr).


Blood and urine gold levels during chrysotherapy for rheumatoid arthritis. In this study the value of undertaking routine blood and urine estimations was assessed in relation to achieving maximum efficacy and safety in chrysotherapy. It was found that a favourable response to gold was forthcoming in approximately two-thirds of patients and occurred irrespective of the patients' disease duration or severity, or the mean serum gold level or the mean urinary gold excretion, estimated immediately before the next gold injection was due. The presence of rheumatoid nodules and the patients' advancing age were associated with a less favourable clinical response to gold. Those patients who derived a marked benefit from chrysotherapy did so significantly earlier in their course than those who derived only moderate benefit. A frequent correlation was seen in individual patients between serum gold levels and urinary gold excretion. This was most marked in those patients showing a favourable response to gold.


Carcinoembryonic antigen in rheumatic diseases. In an earlier study, the mean plasma carcinoembryonic antigen (CEA) level of patients with seropositive rheumatoid arthritis (RA) was found to be significantly higher than that of normal, control subjects. Levels of CEA in patients with seronegative RA and ankylosing spondylitis, however, did not differ from normal. In this study it was shown that the mean CEA level of 16 patients with Sjögren's syndrome was also significantly higher than normal (P equals 0.001), whereas in a group of 23 children with Still's disease the mean level fell within the normal adult range. Despite the apparent association between rheumatoid factor and raised plasma CEA, no correlation was found between titre of rheumatoid factor and CEA levels. Gel filtration studies indicated that the CEA in rheumatoid arthritis was of a similar molecular weight to that found in cancer of the colon and that there was minimal contribution by the known cross-reacting antigen CCEA2. The mean CEA level in rheumatoid synovial fluids was found to be significantly higher than in osteoarthrotic fluids. A preliminary study has also shown that CEA can be extracted from rheumatoid synovial membranes but was not detected in a normal synovium, further indicating that the source of this antigen in RA may be the inflamed synovium.


Ankylosing rheumatoid arthritis.

Ankylosing rheumatoid arthritis. The study concerns the clinical, haematological, serological, radiological and histocompatibility antigenic status of eleven in-patients suffering from long-standing sero-positive rheumatoid arthritis at the Royal Hospital and Home for Incurables in London. The study revealed a striking degree of widespread bony ankylosis affecting the peripheral joints and cervical spine. In large part, this bony ankylosis accounted for the disability but it is considered that the cervical spine ankylosis may protect the spinal cord from damage. The absence of the histocompatability antigen HLA 27 is a useful pointer in the exclusion of Ankylosing Spondylitis. Despite the clinical impression that the disease was inactive, the elevated sedimentation rate (23-66, mean 41 mm) suggests that the rheumatoid process remains active.


Vertical atlanto-axial subluxation in rheumatoid arthritis. In a prospective survey of 476 hospital in-patients with rheumatoid arthritis, vertical atlanto-axial subluxation (AAL) was found in 13 patients (3.7 per cent). All were women with severe rheumatoid arthritis. Neurological signs were found in ten patients, and in seven they appeared to be due to vertical AAL. The signs caused by vertical AAL were diminished pain and temperature sensation in the upper divisions of the trigeminal nerve, sensory loss in the areas supplied by C2, nystagmus and pyramidal lesions. Disabling involvement due to vertical AAL was not found although it may occur and the lesion may be fatal. The lower cervical spine was involved in all patients and severe lesions were seen in nine. The most severe neurological lesions appeared to be due to subaxial subluxation. Corticosteroid therapy may have been a contributing factor in four patients.


Preliminary studies in measuring range of motion in normal and painful stiff shoulders. This study has been prompted by the need to provide basic data for prospective studies in the management of the painful stiff shoulder. We have used a hydrogoniometric technique of proven accuracy to measure passive movement at the gleno-humeral joint in a normal population, patients currently attending with a painful stiff shoulder, and a retrospective group. We have shown that there are significant age and sex differences in the range of motion of normal and affected groups. A significant number (42 per cent) of patients had persisting limitation of range of the gleno-humeral joint six years after the onset of the disability. The study indicates the importance of matching patients for age and sex, and the need for long-term follow-up for meaningful results.


N-acetyl-beta-d-glucosaminidase activity in synovial fluid. N-acetyl-beta-D-glucosaminidase activity in the synovial fluid of different articular diseases was studied and statistical investigations were carried out after logarithmic transformation of the data. The enzyme activity in the synovial fluid of rheumatoid arthritis is increased when compared with osteoarthrosis and traumatic effusions. The enzyme activity in traumatic effusions is also increased in comparison with osteoarthrosis. A linear relation was found between the enzyme activity in cell-free fluid and the polymorphonuclear leucocyte (PMN) count in rheumatoid arthritis osteoarthrosis and in miscellaneous synovitis. The activity per PMN cell was determined and found to be relatively constant in the synovial fluid of inflammatory diseases (rheumatoid arthritis, chondrocalcinosis, miscellaneous synovitis). The N-acetyl-beta-D-glucosaminidase activity per PMN cell in serum was found to be significantly lower than in synovial fluid.


Chromosomal damage after intra-articular injection of different colloids of yttrium 90. Chromosomal damage to circulating lymphocytes occurs following injection of intra-articular radio-isotopes. Differences in the degree of chromosomal damage have been shown with various colloidal forms of yttrium 90, and the severity of these changes has been shown to correlate with the degree of leakage of radio-isotope to the draining lymph node rather than with whole-body irradiation. The long-term significance of these changes is not yet known, but it is clearly prudent to use the colloidal form least associated with chromosomal damage.


On the fate of DNA synthesizing lymphoid blood cells in Hodgkin's disease. Autotransfusions of the DNA synthesizing blood cells from 2-2.5 liters of blood, labelled in vitro with 3H-thymidine, were performed in 2 patients with Hodgkin's disease. The fate of the labelled lymphoid cells was followed up for 5 min to 60 h in the circulating blood and occasionally in the lymph node tissue. The data indicate that 1) circulating DNA synthesizing large lymphoid cells leave the blood in less than 2 h; 2) they produce by mitosis large and medium sized lymphocytes, which mainly appear in blood and lymph nodes and 3) their generation time, in agreement with other estimates, is about 25 h.


Heterogeneous nuclear rna from lymphocytes of chronic lymphocytic leukaemia: adenylate-rich and double-stranded regions. Rapidly labelled high molecular weight nuclear RNA from lymphocytes of chronic lymphocytic leukaemia was analysed for ribonuclease-stable adenylate-rich and double-stranded regions. The polyadenylate content corresponds to 0.4-0.5 percent and the content of double-stranded sequences to 2-4 percent of the total nucleotides. Partial association of polyadenylate segments with double-stranded regions was found by comparative analysis of (3H)-adenosine and (3H)-uridine labelled ribonuclease-stable RNA before and after thermal denaturation. Comparison with normal lymphocytes shows lower proportions of polyadenylate-containing RNA binding to poly(U)-Sepharose in leukaemia cells than in normals. Partial degradation of rapidly labelled high molecular weight RNA was found in leukaemia cases with low white cell counts.


The effect of adrenaline, noradrenaline, isoprenaline and salbutamol on the resting levels of white blood cells in man. Adrenaline, noradrenaline, isoprenaline and salbutamol were infused at the rate of 7 mug/min for 30 min into 5 healthy subjects. Pulse rates showed a marked increase after isoprenaline, a moderate increase after adrenaline and salbutamol, and a consistent decrease after noradrenaline. The total leucocyte counts increased in response to adrenaline and noradrenaline but remained unchanged after isoprenaline and salbutamol. The absolute lymphocyte counts showed significant increases after all the four agonists. Neutrophils increased in response to adrenaline and noradrenaline but remained unchanged after isoprenaline and salbutamol. 'Stress' lymphocyte counts rose in response to adrenaline, isoprenaline and salbutamol but not to noradrenaline. From these and other reported observations it is suggested that both alpha- and beta-receptors are involved in the mobolization of lymphocytes, while neither has any specific role in the mobilization of neutrophils.


Extramedullary plasmacytoma of stomach.

Extramedullary plasmacytoma of stomach. A single case of gastric plasmacytoma showing unusual clinical and pathological features is described. The patient had gluten sensitive enteropathy, and showed increased circulating IgA levels prior to gastrectomy. Progression of the disease was associated with both K and L light chain proteinuria, hypoalbuminaemia, and vasopressin resistant polyuria. Pathological investigation revealed the coexistence of IgA secreting soft tissue plasmacytoma, with IgG secreting myeloma. The significance of these findings is discussed.


The interaction of the protein and phospholipid components of tissue thromboplastin (factor III) with the factors VII and X. The protein and phospholipid components of tissue thromboplastin have been isolated and their interactions with factor VII and factor Xa have been studied by gel filtration, centrifugation and heat inactivation. As expected, the phospholipid fraction bound both factors in the presence of Ca2+. No evidence for an interaction of apoprotein III with factor VII or Xa was obtained.


Folic acid deficiency in sickle cell anaemia. Megaloblastic anaemia responding to folic acid has been reported in a number fo patients with sickle cell anaemia. The incidence of reduced serum and erythrocyte folate levels in such patients remains unclear, however. Serum and erythrocyte folate contents were measured microbiologically in patients with sickle cell anaemia as well as in two control groups with sickle cell trait or normal haemoglobin pattern. Low serum and erythrocyte folate values were significantly more common in 61 sickle-cell patients than in each of the two socio-economically-matched control groups including 61 subjects with Hb AS and 69 blacks with Hb AA. There was no correlation between serum folate and haematocrit or reticulocyte count. The erythrocyte folate, measured before and after removal of reticulocytes, remains a reliable indicator of deficiency of folic acid in sickle-cell patients despite variable degrees of reticulocytes. Folate therapy resulted in higher haematocrits in three of four sickle-cell patients with low serum and low erythrocyte folate values, but in only one of 12 patients with low serum folate and normal erythrocyte folate. These findings are consistent with other observations that folate requirement may be increased in chronic haemolytic disorders and suggest that erythrocyte folate values should be obtained in sickle-cell patients suspected of having folate deficiency.


[Diagnosis of pyloro-duodenal ulcer by means of radiology and endoscopy]. Study of 100 cases of duodenal ulcer has revealed disagreement between radiologic and endoscopic findings. In 20 percent of cases the disagreement was minor (e.g. deformed duodenum - ulcer, deformed duodenum - scar, etc.). In 5 percent of cases they were major (e.g. normal - ulcer). The percentage of discrepancies, which were to the advantage of endoscopy, was lower than in the reports of JENNI and KAWAI, probably because our heterogeneous radiologic material was reviewed beforehand by two radiologists. The specific merit of endoscopy is that it makes it possible to observe superficial and sub-radiologic lesions of the mucosa, localize the ulcer with greater precision and detect deformation of the pylorus. Radiology affords better evidence of certain deformations.


[Treatment of early syphilis under conditions of penicillin intolerance]. In the presence of penicillin allergy early syphilis can be treated with tetracyclines, erythromycin and thiamphenicol. Treatment with semisynthetic penicillins or cephalosporins should not be attempted in view of possible cross-sensitivity. From comparison of different antibiotic treatment schedules in the literature a time-dose relationship seems evident: within therapeutic limits, treatment with a high daily dose of antibiotic requires a relatively short duration, and vice versa. Results of various treatment schedules with different antibiotics suggest that preference should be given to doxycycline by oral route, 100 mg twice daily for 12 days.


[Radiology within the framework of general medicine]. The concept of radiology as an independent basic discipline in medicine has provided a forceful stimulus for the development of this branch of medicine. Due to possible hazards the task of administering ionizing radiation to human subjects should in principle be in the hands of the medical radiologist. Medical radiology must assume the trusteeship for human genetics in the field of ionizing radiation. Although the doubling of the genetically significant dose in Switzerland from 22.3 mr in 1957 to 42.9 mr in 1971 is still within acceptable limits, extreme caution is required. If appropriate precautions are taken,the danger can be controlled without loss of medical effectiveness. The measures involve not only technical aspects; education directed at the thinking of the physicians concerned is also deemed essential. Radiologic procedures will become even more efficient as training is improved and as estensive coordination with other medical disciplines is achieved. Special attention must be paid to the shortage of trained radiologists and technical personnel.


[T-infarct in exercise electrocardiography]. In a study of 60 patients with negative T-waves in the ECG following a first myocardial infarction it was found that during milk to moderate exercise the T-wave vector turned towards normal in 36. It is assumed that during exercise the T-vector points towards the region of maximum ischemia, i.e. the border of the recent infarction. The conclusion is drawn that unexpected transitory normalization of the T-wave after myocardial infarction means "worse" not "better". It is recommended that follow-up ECGs after myocardial infarction should always be taken at complete rest.


[Multiple leiomyomatous hamartoma of the lungs]. Leiomyomatous hamartomas of the lungs are very rare lesions. As far as we know only 14 cases (including ours) have been published so far. In contrast to chondromatous hamartomas, they are exclusively found in women and as a rule are multiple. They are frequently an incidental finding in chest roentgenograms, where they appear as multiple round nodules which are often mistaken for metastases. However, as these lesions remain virtually the same size for long observation periods, differentiation is easily possible. This fact is well shown in our patient, in whom multiple nodules in the lungs were diagnosed at the age of 45 years and observed over a period of 35 years. They were first identified as leiomyomatour hamartomas at autopsy. No therapy is indicated as these lesions have no tendency to become malignant and only rarely and insignificantly interfere with respiratory function. Thoracotomy with biopsy for histological diagnosis is however indicated, since only thus can metastases be definitely ruled out.


[Measurement of carbohydrate oxidation by means of indirect continuous calorimetry in normal and diabetic subjects]. The use of continuous indirect calorimetry in the course of a 100 g OGTT in 10 normal subjects has shown that carbohydrate oxidation rises with the secondary fall in blood glucose, suggesting that it could result from glucose stored under the influence of insulin. The experimental increase in FFA by a neutral fat infusion in 8 normal subjects decreased this oxidation in spite of the insulin rise. In a group of 5 non-obese, non-ketotic insulin-deficient diabetics, carbohydrate oxidation was found to be normal and directly correlated with plasma glucose levels. On the other hand, in 7 obese diabetics with high plasma insulin levels carbohydrate oxidation was found to be low, suggesting that carbohydrate intolerance could result from the non-oxidation of glucose. This study shows heterogeneity of diabetes, since glucose intolerance could result from non-oxidation of glucose as well as from insufficient pancreatic secretion.


[Possibilities and limits of pre-therapeutic neoplasm sensitivity cytostatics tests under short-term conditions]. The following cytostatic agents were tested for activity in vivo and in vitro inWalker carcinosarcoma 256 of the rat: cyclophosphamide, triaziquon, 5-fluorouracil, methotrexate, adriamycin, dactinomycin, daunorubicin, hydroxyurea, procarbazin and vincritine. With the exception of vincristine, the results of therapy in vivo could be predicted by using a rapid in vitro test system. This involved, for cyclosphosphamide, triaziquon, adriamycin, and daunorubicin, the measurement of 3H-uridine or 3H-thymidine incorporation. The activities of methotrexate and 5-fluorouracil could be determined from 3H-deoxyuridine incorporation and that of dactinomycin from 3H-uridine incorporation. The results of short-term tests (uring adriamycin, daunorubicin, and dactinomycin) in roughly 100 human tumors were compared with data in the literature on therapy with the same cytostatic agents. Good agreement was found between the results of in vitro tests and the literature data on clinical therapy.


[Incidence of medullary thyroid gland carcinoma in unilateral and bilateral pheochromocytoma]. In the autopsy material of the Departments of Pathology in Zürich and Winterthur the frequency of cases with unilateral or bilateral pheochromocytoma and combinations of pheochromocytoma with additional medullary thyroid carcinoma with amyloid has been studied. 56 cases (0.084 percent) of pheochromocytoma, 50 unilateral and 6 bilateral, were found in a material of 66782 autopsies. Three of the 6 patients with bilateral pheochromocytomas had an additional medullary thyroid carcinoma with amyloid deposits, while no patient with unilateral pheochromocytoma exhibited this type of thyroid tumor. In families with Sipple's syndrome, however, combinations of unilateral pheochromocytoma with medullary thyroid carcinoma do occur. No typical coincidence of pheochromocytoma with other malignant tumors could be demonstrated in our material, although this possibility is discussed in the literature.


[Procedure to be followed in cases of suspected changes diagnosed by means of mammography]. As a rule the diagnosis of larger focal lesions of the breast can be easily confirmed by biopsy. Intraoperative localization is more difficult, however, in lesions of below 5 mm diameter as measured by mammography or malignant alterations only indirectly indicated by mammography. Experience to date in 64 patients shows that specimen radiography provides immediate confirmation of large lesions detected by mammography and localizes the area for histologic examination. So far it has been found that precisely those biopsies that are performed as a result of indirect signs of malignancy or of small lesions are the most valuable contributing factor in the early diagnosis of breast cancer.


[New procedure in the diagnosis of maldigestion. Studies with 3-H palmitic acid and 14-C tripalmitate in normal subjects and patients with chronic pancreatitis]. 3H-palmitic acid and 14C-tripalmitate dissolved in 1.0 g indian corn oil/kg body weight were administered to 29 patients with chronic pancreatitis and 25 control subjects. For the following 8 h 3H and 14C radioactivity in serum lipids and 14CO2 in expired air were measured at 2-hour intervals. Triglyceride absorption was significantly lowered in the pancreatitis group, while the wide dispersion in healthy subjects precluded reliable information on 14C-triglyceride absorption alone in individual cases. When related to palmitic acid absorption, however, reduced triglyceride absorption was much more evident and could be clearly demonstrated in 21 of the 29 patients with chronic pancreatitis. Since none of them had severe pancreatic insufficiency, the new double isotope method presented here appears to offer a very sensitive means of detecting maldigestion or slowed triglyceride hydrolysis. Compared with the 3H-fatty acid absorption, a relatively reduced triglyceride absorption was found in many cases without steatorrhea or otherwise demonstrable pancreatic insufficiency. Additional measurement of 14CO2 appears to be worthless, since in our patients specific activity of 14CO2 in the expired air was not reduced even in cases with mild steatorrhea.


[Medical and psychological problems relating to emergency shelters in case of war]. Modern warfare requires protection of the entire civilian population, and a main feature of Swiss planning is the provision of adequate shelter space for every inhabitant. The medical and psychologic problems of prolonged shelter living are considered, with reference to the literature on experience in other countries. The study centers on description of a shelter occupancy experiment. 25 men with an average age of 37 years spent 7 days in a closed shelter during the hottest part of the year. Floor space was 1.2 m2 and room volume 2.5 m3 per person. The experiment revealed that in-shelter climatic conditions remained tolerable. Initially several members of the group suffered from insomnia and nausea, while sleep disturbances, headache and gastrointestinal symptoms also occurred in the course of the stay. Daily self-rating of condition with appropriate scales showed a positive correlation of "irritability" with air humidity and a negative correlation of "vitality" with room temperature. Good shelter management and a trained leader are essential prerequisites for prolonged shelter occupancy.


[Physiopathology of accidental drowning]. The first phase of accidental drowning begins with asphyxia, due to either laryngospasm (10-15 percent of cases) or water aspiration. The second phase is characterized by water and electrolyte changes in the blood. The physiopathological modifications caused by drowning in fresh water differ from those of drowning in sea water. The hypotonic fresh water quickly diffuses in the bloodstream. The consequences are, in many cases, hypervolemia with pulmonary edema, hemolysis, hyperkalemia with risk of ventricular fibrillation, diminution of hemoglobin, and a relative decrease in plasma concentration of Na, Cl, Ca, and albumin. Further, inactivation and washing out of the anti-atelectasis factor from the alveoli by fresh water facilitate the formation of atelectasis. In cases of accidental drowing in sea water the osmotic gradient is in inverse: the electrolytes of aspirated salt water diffuse in the circulation, whereas the blood serum and the plasma albumin pass into the alveoli. Acute pulmonary edema often follows these pathological changes. Hypovolemia with circulatory collapse, hemoconcentration with rise in hemoglobin, hematocrit, sodium, potassium and albumin, and, finally, an elevated risk of thromboembolism due to increased blood viscosity, represent further complications. On the other hand, ventricular fibrillation is rare, hemolysis is absent and atelectasis usually does not occur.


[Skeletal scintigraphy. Its diagnostic possibilities and indications as compared to x-ray studies]. The properties of bone-seeking nucleids in current use are reviewed and the diagnostic potentialities of skeletal scintigraphy discussed. Osseous lesions are recognized earlier on bone scans than on roentgenograms. They are more precisely delimited and the possibility of healing can be evaluated. Roentgenographic bone survey should be replaced by whole body scans, but since a positive scintigraphic finding may be caused by different osseous processes, a specific roentgenographic check is necessary. The indication for bone scanning has been widened and depends on the clinical situation or on previous X-ray findings.


[The consumption of alcohol, drugs and the smoking habits of 4,082 healthy young Swiss men as evidenced by a random study]. By means of written questionnaires and (with every third or fourth subject, selected at random) standardized interviews, 4082 recruits from various regions of Switzerland were asked about their alcohol and drug consumption and smoking habits in civilian life. To estimate the consumption pattern during military training all recruits still available towards the end of military service (64.3 percent) were questioned again regarding intake of alcohol, tobacco and drugs during military service. The inquiry showed that in civilian life only 10.4 percent were alcohol abstainers, 39.8 percent were non-smokers and 77 percent had no drug experience. 8.6 percent reported a weekly alcohol consumption of more than 350 g alcohol 100 percent (an amount corresponding to 9 1 beer, 41/2 1 wine, 1 1 brandy), 17.4 percent had smoked more than 24 g tobacco per day (corresponding to more than 24 cigarettes daily), and 10.6 percent had taken drugs more than 6 times in their lives. The study was also designed to demonstrate the relations between family or socioeconomic data and intake of alcohol, tobacco and drugs. It was found that French and Italian speaking recruits indicated a higher alcohol consumption, that the lower socioeconomic class was exposed to be greater risk with regard to alcohol and tobacco consumption and the separately interviewed group of pupils to the greatest risk of drug experinece. Sons of divorced or separated parents, of parents married after the subject's birth or of parents who are heavy alcohol, tobacco or medicament consumers represent a higher percentage among the highest consumption class for alcohol, tobacco and drugs than subjects who had grown up in stable families or whose parents had been non-consumers or only moderate consumers of alcohol, tobacco or drugs. Finally, a correlation was also found between use of leisure time and alcohol, tobacco and drug consumption. It was in the groups of recruits who spent their spare time rather passively that the highest percentage of subjects in the upper consumption classes for alcohol, tobacco and drugs was observed. During military training consumption patterns withregard to alcohol and tobacco hardly changed, and only a small number of subjects (7.7 percent of 2587) took drugs during this time.


[Early diagnosis of lung cancer].

[Early diagnosis of lung cancer]. 268 patients with suspected lung cancer were examined over the period 1 January 1972 to 31 May 1974. On the basis of the 735 investigations performed, a 6-8 h workup program has been established including physical and functional examination, standard X-rays and hilar tomography, endoscopy and biopsy for cytologic or histologic study. Several biopsy technics are described and their indications tabulated according to their efficiency in relation to the radiologic aspect of the lesion. The number of cases and the yield for each technic are summarized in Table 2.


[Behcet's disease and toxic megacolon].

[Behcet's disease and toxic megacolon]. The gastrointestinal symptoms of Behçet's disease are ancillary manifestations of this disorder reflected principally in the form of diarrhea, abdominal pain, meteorism, nausea, and loss of appetite. If radiological changes can be detected they generally appear as dilatation of the small intestine or ulceration at different levels of the digestive tract. In our patient the intestinal symptoms started with dilation of the ileum and then toxic megacolon developed. At later follow-up examinations the radiological picture resembled Crohn's disease and ischemic colitis of the entire organ. It has been repeatedly, and wrongly, stated that there is an association between Behçet's disease and Crohn's disease or ulcerative colitis. Rather, it should be assumed that the intestinal manifestations of Behçet's disease correspond to those of Crohn's disease and ulcerative colitis without these diseases being actually present. The evolution towards toxic megacolon may be the consequence of a transmural infection across the colonic wall deriving from the mucosal ulcerations of colon and sigmoid, and proves that toxic megacolon is not a pecific complication of ulcerative colitis but may appear in the course of any acute inflammatory ulcerative lesion of the colonic wall.


[Functional changes in embryonal heart]. Intracardiac pressure in the developing chick was measured throughout the embryonic and fetal period. Amplitude and heart rate were used to estimate cardiac output and power of the heart. In addition, the cardiac performance per milligram dry weight was calculated. Initially, the cardiac tube displays a peristaltic movement which results in a continuous pressure within the vascular lumen. Switch to rhythmic atrial and ventricular contractions occurs between the 6th and the 9th developmental day. This change is directly correlated with differentiation of the conduction system. The simultaneous formation of the cardiac septa and valves is of only minor importance for this change in function. Between the 4.5th and 5.5th day, functional development is found to halt temporarily. This could be due to the enormous growth of the extra-embryonic vascular network. During this period, the risk of damage to the embryo by endogenous or exogenous factors is highest. In the human embryo, this developmental stage corresponds to the period between the 28th and 34th day. After this change in function the heart is able to build up a reserve of power, since it has less work to perform per unit weight.


[Methylphenidat (Ritalin) as a psychotropic drug in children with minimal brain dysfunction and epilepsy]. In the USA children with minimal brain dysfunction and with epilepsy have been treated with stimulants for some years now, whereas this type of treatment is not current in Switzerland and western Germany. The problems of treatment with amphetamines in children are discussed on the basis of 2 years' experience with methylphenidate (Ritalin). In children with minimal brain dysfunction methylphenidate acts against excessive motor and affective impulsivity and inability to concentrate. In epileptic children amphetamines act against drowsiness or irritability. There is no danger of addiction in the pediatric age group. No toxic side effects occur, except for growth inhibition when high doses of amphetamines are administered. Drug interaction with anticonvulsants occurs only in the case of hydantoins. Methylphenidate is given in 1-3 daily doses; treatment is commenced with small doses, and after 2-4 days the dosage is increased until behaviour changes. Dosage must be adapted to the individual, the recommended daily dose being 0.3-1.0 mg/kg. Depressive or autistic behaviours are symptoms of overdosage. In childhood treatment with amphetamines should be considered only if other types of treatment have failed. drug therapy should be accompanied by continuous advice to parents on educational and school problems. It should not be attempted if the parents are not wholly reliable.


Precision of radioimmunoassay with emphasis on curve-fitting procedures. Direct curve-fitting methods using a digital computer have been employed to analyze the calibration curves of commercial kits for the assay of digoxin, digitoxin, insulin, B12, and renin activity (angiotensin). Inconsistencies have been revealed that suggest some improvements in the commercial kits are desirable. It is not suggested that the use of these kits would yield data of uncertain clinical value, but it is suggested that improvements in consistency would enhance the clinical utility.