Developmental changes in the activity of catechol-O-methyl transferase in rat and rabbit fetuses. Variations in the activity of catechol-O-methyltransferase (COMT) in peripheral organs in the brain of rat and rabbit fetus during development have been studied. The pattern of changes in COMT activity in rat fetus differed to a great extent according to the respective organs studied. In kidney and liver sharp declines occurred between days 18 and 20 and days 16 and 18 of fetal life respectively, followed by progressive increases up to onset of birth. Brain COMT of rat fetus declined progressively from day 16 of fetal life up to 0 hours after birth, while COMPT activity in adrenal and heart showed its maximum value at the 20th day of fetal life and at 0 hours after birth respectively. In the contrary, the developmental changes in activity of rabbit fetus were very similar in all the organs except in the adrenals, since it decreased between day 24 to 8 hours after birth in heart, liver, brain and kidney. In the adrenals an important increase could be seen between the 24th and 28th days of fetal life. Rat COMT activity during 4 and 8 hours of postnatal life in heart, liver and kidney declined from 0-hour value but it increased in the brain and adrenals. COMT in rabbit increased after birth in all the organs studied. The results suggest that metabolic degradation of catecholamines by 3-O-methylation in rat and rabbit fetus may have different developmental patterns to some extent according to the physiological status of the organ concerned. These species related differences for monoamine inactivation during fetal development may suggest a physiological role for COMT as a marker of the maturation of the autonomic nervous system.


Histochemical identification of acetylcholinesterase in dopaminergic nigrostriatal neurons. By combining histochemical procedures, evidence was obtained in the rat that acetylcholinesterase (AChE) is contained within perikarya of dopaminergic substantia nigra cells which project to the caudoputamen. Nigrostriatal neurons were identified by retrograde transport of horseradish peroxidase (HRP). Simultaneous incubation of substantia nigra sections for the presence of AChE and HRP demonstrated both reaction products in the same cell bodies. The catecholaminergic nature of these cells was determined by a loss of HRP and AChE reaction products subsequent to intranigral injection of 6-hydroxydopamine.


A survey of some active sheep pineal fractions and a discussion on the possible significance of pteridines in those fractions in in vitro and in vivo assays. Aqueous extracts of sheep pineals are separated on Sephadex G-25 fraction with antigonadotropic activity are ultrafiltered through the membrane UM 2. The UM 2 filtrate is subsequently filtered through the membrane UM 05. The actions of the different fractions on the anterior hypophysis and hypothalamus are discussed. The fractions which show an activity are further separated on Sephadex G-10. The active Sephadex G-10 fractions of the UM 05 filtrate acting on the anterior hypophysis in vitro are purified by electrophoresis and paper chromatography. After elution of different fluorescence bands the main inhibitory activity is found in a region, with the same Rf value as synthetic 6-biopterin. Gas liquid chromatography and mass spectrometry studies of the isolated fractions are carried out. The mass spectrum of an isolated compound from that fraction is identical with that of synthetic 6-biopterin. Thinlayer chromatography and the results of the Crithidia fasciculata test reveal that the isolated compound is probably identical with 6-L-erythrobiopterin. The activity of the active paper chromatography fraction (C4) is compared with the activity of three synthetic biopterin-preparations in vitro and in vivo.


Dose-dependent pharmacokinetics of alpha-methyl-p-tyrosine (alpha-MT) and comparison of catecholamine turnover rates after two doses of alpha-MT. Groups of rats were injected i.p. with 0.407 or 1.02 mmoles/kg of D,L-alpha-methyl-p-tyrosine methylester HCl (alpha-MT). The time-courses for alpha-MT in plasma and brain were followed together with the endogenous brain dopamine (DA) and noradrenaline (NA) contents. The elimination of alpha-MT from plasma and brain was markedly delayed after the high alpha-MT dose compared with the low dose. At 40 hours after the injection of 1.02 mmoles/kg of alpha-MT both plasma and brain levels were high, whereas no alpha-MT could be detected in plasma or brain at 16 hours after the lower dose. The brain catecholamines were decreased to very low values after the higher alpha-MT dose (DA 14% and NA 10% of controls at 8 and 24 hours respectively). There was no complete recuperation at 40 hours of any of the amines. After the lower alpha-MT dose, the DA concentration was back to control levels at 16 hours and NA at 12 hours. Between 16--40 hours after the high alpha-MT dose a majority of the rats showed prominent signs of sedation, weight loss and dehydration. No such signs were observed in rats receiving 0.407 mmoles/kg. During the first hour after the alpha-MT injection the declines of DA and NA respectively were almost identical for both alpha-MT doses. When the whole time-course (0--8 hours) after the high dose was considered, biphasic declines were obtained for both DA and NA, suggesting at least two different catecholamine pools. However, due to toxic effects after the high alpha-MT dose, turnover data have to be interpreted with caution.


The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists. The antidepressant drugs, imipramine (10 mg/kg s.c.), amitriptyline (10 mg/kg s.c.), mianserin (2 mg/kg i.p.), danitracen (3 mg/kg i.p.) or the vehicle were administered to rats twice a day for 4 or 10 days. Clonidine (0.5 mg/kg s.c.) induced in rats chronically treated with the compounds studied an increase in locomotor activity but, at the same time, did not affect or decreased this activity in rats chronically treated with the vehicle or a single dose of an antidepressant. This refers, in particular, to imipramine, amitriptyline and danitracen which have a similar effect. This effect, an increase in motility, was most pronounced and common for all the three drugs (after a 4- and 10-day treatment) when clonidine was administered 72 hours after the last dose of an antidepressant. Only in a few cases the amphetamine-induced hypermotility was enhanced by a chronic administration of antidepressants (a 4-day amitriptyline treatment, 72 hours after the last injection; a 4-day mianserin or danitracen treatment, 48 hours after the last injection). The results obtained seem to suggest that a chronic administration of the antidepressant drugs may cause a change in the sensitivity of the central noradrenaline receptors.


Trazodone, a central serotonin antagonist and agonist. We examined the effect of trazodone (TR), a non-tricyclic antidepressant drug with an unknown mechanism of action, as well as its supposed metabolites beta-(3-oxo-s-triazolo-[4, 3 a]-pyridin-2-yl-propionic acid (OTPA) and 1-(m-chlorophenyl)-piperazine (CPP) on the serotonin (5-HT) -system in a model of the hind limb flexor reflex of the spinal rat. When given alone at low doses (1 mg/kg) TR does not change the flexor reflex but counteracts its serotonergic stimulation induced by LSD, quipazine or fenfluramine. At higher doses (6--8 mg/kg), after a period of latency, it enhances the reflex; this effect is antagonized by the 5-HT receptor blockers (cyproheptadine, WA-335 and metergoline) but not by imipramine. From the two TR metabolites studied only CPP exerts an effect in the flexor reflex model. It considerably enhances (0.05--1 mg/kg) the reflex, this effect being antagonized by cyproheptadine, WA-335 and metergoline, but not by imipramine. Our findings indicate that TR has a double effect on the central 5-HT system: at low doses it acts as a 5-HT antagonist, whereas at higher ones--as a 5-HT agonist. The latter effect may be connected with formation of a metabolite, CPP, or a compound chemically related to CPP.


Familial occurrence of moya-moya disease: report of three Japanese families. Three Japanese families with moya-moya disease in six patients are presented. These six patients were among 49 cases of confirmed moya-moya disease in our experience, and the familial incidence was more than 12%. A relatively high familial incidence (7%) was found in the total Japanese series emphasising the important hereditary components in the pathogenesis of the disease.


Computerised tomography after recent severe head injury in patients without acute intracranial haematoma. Sixty patients with severe head injury who did not have an acute intracranial haematoma on CAT scanning are reviewed. The scans are correlated with the level of consciousness at the time of scanning and with the outcome six months after injury. The initial scan was interpreted as being normal in 38% of the cases. In the remainder the most common abnormalities were small ventricles and areas of mixed increased and decreased density interpreted as contusions. All the patients with small ventricles were under 20 years of age. Postmortem examinations were undertaken on 15 of the 19 fatal cases. There was evidence of a high intracranial pressure in 12, cerebral contusions were absent or minimal in 10, there was diffuse immediate impact damage to white matter in six, and there was moderate or severe hypoxic damage in four.


Wernicke's encephalopathy: a more common disease than realised. A neuropathological study of 51 cases. During a four year peirod, 51 cases of Wernicke's encephalopathy were diagnosed at necropsy, an incidence of 1.7% of all necropsies performed at the Royal Perth Hospital and by the Perth City coroner. Only seven had been diagnosed during life. Many of the patients died suddenly and unexpectedly, apparently as a result of haemorrhagic brainstem lesions, typical of acute Wernicke's encephalopathy, since no other cause of death was found. There was a high incidence of epilepsy and four patients were hypothermic. The diagnosis of Wernicke's encephalopathy may be missed at necropsy unless the brain is examined histologically. Cerebral atrophy and ventricular dilatation were common findings. This is a more common disease than is generally recognised, one which can be readily treated and, more importantly, prevented by adequate nutrition.


Ballistic elbow flexion movements in patients with amyotrophic lateral sclerosis. Patients with amyotrophic lateral sclerosis made stereotyped 20 degrees elbow flexion movements as rapidly as possible while surface EMG was recorded from biceps and triceps. The characteristic ballistic movement EMG pattern could be recognised in almost all the patients. The first agonist burst and the first antagonist burst, which are normally limited in duration, were prolonged in patients with clinical signs of pyramidal tract disease or alpha motor neurone disease or both. Prolongation of these components permits the muscles to generate sufficient forces to accomplish the movements.


Delayed cervical somatosensory potentials in cervical spondylosis. The cervical somatosensory evoked potential after median nerve stimulation was recorded in 14 patients with cervical spondylosis with radiculopathy and, in 10 cases, myelopathy. Four patients had normal potentials, five showed delayed potentials, and in five others no potential could be seen.


Slow cord dorsum potentials elicited by descending volleys in man. Human cord dorsum potential (CDP) was recorded from the posterior epidural space at the levels of cervical and lumbar enlargements, using epidural catheters as the recording electrodes, in 15 normal volunteers and six patients suffering from amyotrophic lateral sclerosis. In normal subjects the CDP elicited by descending volleys consisted of spike potentials followed by sharp negative and slow positive waves which were very similar to the P1, N1, and P2 potentials, respectively, of the CDP evoked segmentally. By contrast, in all patients with amyotrophic lateral sclerosis both the sharp negative and slow positive waves were absent in the CDP elicited by descending volleys, while the pattern of each component of the segmentally evoked CDP remained unchanged. Thus, the sharp negative and slow positive waves of human CDP elicited by descending volleys might reflect the activity of interneurones and primary afferent depolarisation respectively, produced by impulses through the corticospinal tract.


Effect of raising body temperature on visual and somatosensory evoked potentials in patients with multiple sclerosis. The effects of raising body temperature on the visual (VEP) and somatosensory (SEP) evoked potentials were observed in normal subjects and in patients with multiple sclerosis. The amplitude of the VEP was significantly reduced to the same degree after heating in normal subjects and in patients with multiple sclerosis but there was no effect on the latency of the potential. Changes in amplitude could not be related to reduction in acuity. In contrast, the cervical SEP was greatly disorganised after heating in many patients with multiple sclerosis while the only effect in normal subjects was to reduce the latency by increasing peripheral conduction velocity. These results suggest that heat caused conduction block in demyelinated axons in the sensory pathways of the cervical spinal cord.


Mental aspects of temporal lobe epilepsy. Follow-up of 74 patients after resection of a temporal lobe. Psychiatric disorders were investigated in 74 patients with drug-resistant temporal lobe epilepsy (complex partial epilepsy). In all cases unilateral anterior temporal lobectomy had been performed during the period 1960-69. At follow-up in 1970-71, 45 patients were free from seizures, and in a further group of 15 patients seizure frequency had been substantially reduced. There were four postoperative deaths. Six patients were psychiatrically normal and had no history of any such disorder. Behavioural disturbances were observed in 55 patients. Before operation 11 patients displayed schizophrenia-like psychoses, and nine others became psychotic during follow-up. Fourteen patients attempted suicide on one or more occasions. Half the patients had diminished sexual drive. Improvement in psychiatric status was clearly correlated with relief from seizures and, in those cases with only a few or no seizures after operation, led directly to social rehabilitation. The presence or absence of a psychiatric disorder was not useful as a criterion for or against surgery.


Pure agraphia: a discrete form of aphasia. A 62 year old, right handed man developed a pure agraphia as the result of a left temporal lobe stroke. Isolated writing disturbances persisted for seven months until he had a second cerebrovascular accident resulting in total aphasia and right hemiplegia. A CAT scan obtained four months after the first episode showed a localised dilatation of the posterior portion of the left Sylvian cistern and patchy areas of low absorption in the left temporal lobe. The report supports suggestions that localised damage to the language area can produce a pure agraphia as the sole detectable disorder of language organisation.


Remittent painful ophthalmoplegia: the Tolosa-Hunt syndrome? A report of seven cases and review of the literature. Seven patients with remittent painful ophthalmoplegia for which no specific local cause was found were seen during a period of five years. One had coincidental rheumatoid arthritis, and another had actinomycosis of the ipsilateral middle ear and contralateral parotid gland. The other five had no evidence of generalised autoimmune disease nor any other systemic disorder, two having separate episodes affecting each side. A history of relapsing and remitting painful ophthalmoplegia is suggestive of the Tolosa-Hunt syndrome, but it is rarely possible to confirm that the lesion in the cavernous sinus is the result of non-specific granulomatous infiltration so that the diagnosis remains one of exclusion. Carotid arteriography may show narrowing of the intracavernous part of the internal carotid artery. Orbital venography may also be helpful, particularly when the carotid arteriogram is normal. We believe that the Tolosa-Hunt syndrome is more common in England than is generally realised, but that its clinical features do not necessarily indicate a single pathological entity. Its recognition is important since the response to steroids, although not specific, is rapid in most patients, and the prognosis for complete recovery is relatively good.


Rigid spine syndrome.

Rigid spine syndrome. A patient is described with distinctive clinical features including childhood onset of non-progressive muscle weakness, limitation of flexion of the neck and spine, scoliosis, and joint contracture. Muscle biopsy and electromyography showed findings suggestive of a myopathic disorder. The combination of these distinctive clinical features is termed the rigid spine syndrome. Only six cases have been reported in the literature to date.


Cauda equina compression presenting as spontaneous priapism. Disturbance of autonomic function is an unusual feature of compression of the cauda equina. A 61 year old man who had complete occlusion of the lumbar spinal canal with compression of the cauda equina from a large centrally prolapsed disc, had spontaneous priapism, precipitated by walking and relieved by resting. This symptom was comparable to claudication by compression of cauda equina. It subsided completely after surgical removal of a prolapsed L4-5 disc.


Glial fibrillary acidic protein (GFAP): purification from human fibrillary astrocytoma, development and validation of a radioimmunoassay for GFAP-like immunoactivity. The extraction and purification of glial fibrillary acidic protein (GFAP) from human fibrillary cerebellar astrocytoma is described. Using an immunoperoxidase method, antisera raised to the protein showed specific staining of astrocytes in normal spinal cord and in tumours of astrocytic origin. A double antibody radioimmunoassay for GFAP in tissue extract was developed, the detection limit of the assay being 360 pg. Extracts of tissues other than brain or spinal cord did not cross-react significantly in the assay, neither did purified preparations of myelin basic and S-100 proteins. Levels of GFAP in normal CNS tissue were higest in spinal cord (1370 microgram/g wet weight) but a level of 3050 microgram/g wet weight was detected in a fibrillary astrocytoma.


Maturation of human skeletal muscle fibres in explant tissue culture. Human foetal skeletal muscle was grown in explant cultures and the development of myotubes was monitored morphologically and by the development of membrane potential and acetycholine sensitivity. Migration of uninucleate cells from the explants occurred in the first day of culture and formation of multinucleated myotubes took place between 7 to 10 days. Early myotubes were variable in appearance, being either flat and nonrefractile or narrow and cylindrical. Some cross-striated cells were observed. Resting membrane potentials were around -25mV and there was great variation in myotube sensitivity to acetylcholine. After about 6 weeks in culture most myotubes were of the refractile type. Many had hypolemmal nuclei and were cross-striated; some contracted spontaneously. All myotubes had developed high sensitivity to acetylcholine although there had been no increase in resting membrane potential.


Effect of tenotomy on self-reinnervated and randomly reinnervated soleus muscle of rat. The time course and degree of atrophic changes caused by tenotomy were compared in normal, self-reinnervated and randomly reinnervated soleus muscle 6 months after transsection and reunion of the nerve at different distances from the muscle. Comparison was made between the behaviour of Type I and Type II fibers, distinguished on the basis of histochemical myofibrillar ATPase and succinic dehydrogenase reactions. Cross-sectional areas of individual muscle fibers were measured using Quantimet 720 image analyser. Selective atrophy of Type I muscle fibers as determined by structural and histochemical changes was observed after tenotomy of normal, self-reinnervated and randomly reinnervated soleus muscles after transsection of the muscular branch of the tibial nerve, Type II muscle fibers in randomly reinnervated muscles were found to be relatively insensitive to tenotomy, as in normal muscle. In randomly reinnervated muscles after transsection and reunion of the sciatic nerve, tenotomy did not cause any visible structural and histochemical abnormalities although a decrease of muscle weight and cross-sectional surface area of fibers was noted. Since in these muscles Type II fibers increased to about 70% of the muscle fiber population, it is suggested that the increased percentage of Type II fibers seemed to prevent the atrophic changes in Type I fibers after tenotomy.


Neutralizing antibodies to canine distemper and measles virus in multiple sclerosis. Serum neutralizing antibody to canine distemper virus (CDV) was measured in 142 patients with multiple sclerosis (MS), an equal number of age and sex-matched normal controls, and 75 patients with other neurological disorders. An elevated antibody titer was found in the MS population compared to controls. Measles-neutralizing antibody was also found to be elevated in 128 patients with MS. The mean ratio of measles to CDV antibody was similar in the control and MS groups, but a wide range of measles to CDV ratios was found in individual patients and controls. No significant correlation was found between IgG levels and neutralizing antibody titers in MS sera. While the increased titer of measles and CDV antibody may represent a non-specific immunological response, these findings are also consistent with the hypothesis that CDV or a closely related measles virus may stimulate the increased level of measles and CDV antibodies found in MS sera.


A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis. In a combined histological, biochemical and histochemical study of the macroscopically normal white matter in multipe sclerosis 72% of samples were histologically abnormal. The significance of this fact in the interpretation of previous biochemical studies and in the design of future studies is discussed. The present study showed a significant elevation of the lysosomal enzyme beta-glucosaminidase in the microscopically normal white matter in MS as compared with controls. Studies on lysosomes separated from microscopically normal or mild to moderately gliosed white matter in multiple sclerosis showed an increase in lysosomal fragility. Histochemical study of the microscopically normal white matter in multiple sclerosis revealed an increase in the number of acid phosphate-containing cells as compared with normal and neurological control material. The significance of these findings is discussed and it is suggested that irrespective of the primary or secondary nature of these abnormalities, the white matter may be rendered more susceptible to the pathogenetic process in this disease.


Fatal lipid storage myopathy in an infant: case report and autopsy findings. The clinical presentation, muscle biopsy appearances and autopsy findings in a male infant dying at the age of 13 weeks with a lipid storage myopathy are described. The primary metabolic abnormality was not elucidated but was thought not to be carnitine deficiency.


Alcohol embryo- and fetopathy. Neuropathology of 3 children and 3 fetuses. Maternal chronic ethanol abuse during pregnancy causes malformations of the offspring. Three children (aged 6 months, 9 months, 4 1/2 years) and 3 fetuses (17th, 18th, and 20th gestational week) showed a wide spectrum of disorders ranging from severe dysraphic state, arhinencephaly, porencephaly, agenesis of corpus callosum, a range from hydranencephaly to microdysplasias (p.e. reduced gyration of dentate nucleus and inferior olives), and a range from gastrochisis or congenital heart defects to craniofacial dysmorphogenesis and palmar crease anomalies. The patterns of the cerebral malformations were not as uniform as the clinical phenotype of the alcohol embryopathy. The observations did not support the assumption that there exists a specific period for alcohol teratogenicity.


Intranervous regeneration. The study of motor axon reflexes. More than 1000 motor axon reflexes (ARs) have been studied. The AR often has a long latency and the first excited branch almost always has the fastest conduction velocity. Sometimes the potentials of the two branches are recorded at the same needle placement, giving the appearance in the EMG tracing of a coupling discharge. Stimulation of the axons in the muscle produces more ARs than stimulation of the nerve trunk. ARs are recorded in denervated muscles but never in normal subjects. All kinds of lower motor neuron lesions produce ARs. They are more frequent in the Charcot-Marie-Tooth syndrome and hereditary neuropathy with liability to pressure palsies where the axonal lesions are mainly located at the traditional sites of entrapment. The possibility of neurolysis in some of these cases has to be considered. Obstetrical brachial plexus palsies furnish many ARs linking two muscles, thus explaining the associated contractions in these cases.


Cellular responses to free grafting of the extensor digitorum longus muscle of the rat. The cellular and subcellular responses related to the survival or destruction and subsequent regeneration of muscle fibers within the freely grafted extensor digitorum longus muscle of the rat were examined by light and electron microscopy. A small number of fibers at the periphery of the grafts survived the initial ischemia but underwent denervation changes and accumulated lipid deposits. The majority of fibers in the grafts, however, became ischemic and underwent an intrinsic degeneration within 4 hours. Cell-mediated destruction of the degenerating fibers occurred as the grafts became revascularized. The basal laminae and some of the satellite cells were the only elements of the original fibers that persisted. Regeneration began at the periphery of the graft within three days after grafting and reached the center about three days later. After phagocytosis of the original fibers, presumptive myoblasts within the grafts differentiated into myoblasts and myotubes. The formation of myotubes followed a biphasic pattern of development comparable to that of normal fetal muscle. Although most of the myotubes were formed within the basal lamina remaining from the original fiber, there was also evidence for regeneration outside the basal lamina. Myotubes matured into muscle fibers which were essentially normal in apperance when examined up to 180 days after grafting. Some fibers, however, were atrophic, presumably due to a failure to become innervated, and some fibers were joined by myo-myous junctions. Pre-denervated grafts and Marcaine-treated grafts were also examined. There were more surviving fibers in pre-denervated grafts, and cell-mediated destruction of degenerating fibers proceeded more rapidly than in normal grafts. No surviving fibers were found in Marcaine-treated grafts. The changes in these grafts were otherwise similar to normal grafts. A schematic model of the spatial and temporal sequence of degeneration and regeneration within a free muscle graft is presented.


Bulbocavernosus reflex in patients with conus medullaris and cauda equina lesions. The clinical value and practical application of the electrically induced BC reflex was investigated in 40 patients with traumatic or compressive lesions of the conus medullaris or cauda equina. It was shown that the BC reflex was either absent or delayed depending upon the invovlement of the sacral 2--4 spinal and radicular segments. The latency of the BC reflex was normal in patients with mainly epiconus and lumbar cord involvement. The loss of the BC reflex in the acute period of traumatic lesions was an adverse prognostic sign while the presence of the reflex whether or not delayed, indicated a more benign final outcome of sphincter and sexual reflex disturbances. In chronic progressive compression, the latency of BC reflex was often delayed.


Fatty acid activation and transfer in blood cells of patients with muscular dystrophy. Two membrane-bound enzymes, concerned in repair of erythrocyte membranes, have been investigated in patients with muscular dystrophy. The activation of long-chain fatty acids is normal in erythrocytes from Duchenne patients, but increases two-fold in cells from myotonic dystrophy patients (congenital form). This alteration is not present in leucocytes. In all leucocytes tested palmitate was the preferred substrate while palmitoleate and linoleate were activated at a lower rate. In the erythrocytes the 3 fatty acids were activated at the same rate. Carnitine palmitoyltransferase was not significantly altered in erythrocytes of both groups of patients.


Muscle carnitine deficiency. Genetic heterogeneity. Two types of lipid storage myopathy have been associated with decreased content of carnitine in muscle. In "muscle carnitine deficiency", carnitine concentration is normal in serum, but reduced in muscle. In "systemic carnitine deficiency", apparently due to imparied synthesis of carnitine in the liver, carnitine content is low in both serum and muscle. We studied a woman with a corticosteroid-responsive, probably autosomal recessive, lipid storage myopathy. Carnitine therapy was ineffective and carnitine failed to correct the impaired fatty acid oxidation in muscle homogenates, in contrast to a previous case. Carnitine transport into skeletal muscle was normal. These observations suggest that ll cases of "muscle carnitine deficiency are not the same.


Regional cerebral blood flow measured by 133Xe inhalation in tracheostomized and laryngectomized men and women. The question of contamination of cerebral clearance curves utilized for measuring regional cerebral blood flow by radioactivity derived from the nasopharyngeal air passages following inhalation of 133Xe was tested in patients with chronic tracheostomy. The peak counts for head curves were 5--9% higher when 133Xe was inhaled via a face mask than when inhaled via the tracheal stoma. Calculated flow values using standard recommended start-fit-times were not significantly different between these two different methods. Present results indicate that neither overestimation of fast flow values due to contamination from rapid 133Xe washout recorded from the air passages nor the underestimation of slow flow due to contamination from 133Xe trapped in the air sinuses produced significant measurement errors. However, if earlier start-fit-times were used, flow values were artificially high, particularly for brain stem/cerebellar probes because of an initial rapid decline in the head desaturation curves due to an arterial peak believed to be derived from  the basilar artery.


Identification of glycosaminoglycans in nerve terminals. Synaptosomes were prepared using sucrose and Ficoll density-gradient-centrifugation procedures. Extraction of lipid-free material from both preparations with guanidinium chloride together with papain treatment released hexuronic-containing fractions. The glycosaminoglycan fractions (C1, C2, and C3) were isolated after ion-exchange chromatography. Chemical studies identified fraction C1 as a chondroitin sulphate proteoglycan whereas fractions C2 and C3 were characterised as hyaluronic acid and heparan sulphate. The relative yields of glycosaminoglycans (as compared with brain mitochondria) strongly suggest that these macromolecules form an integral component of nerve endings. The possible role of glycosaminoglycans in synaptosomes is also discussed.


[Effects of juxtafastigial stimulation on the rhythmic activity of Purkinje cells in harmaline-treated rats]. In the anaesthetized rat, harmaline induces an olivary activation which results in rhythmic complex-spike (CS) discharges of Purkinje cells (4--8/sec) in the vermian cortex. The temporal organization of the rhythmic CS activity was studied. While some Purkinje cells present long periods of continuous rhythmic activity, the rhythmic CS discharge of other cells is modulated by periodical suppression of activity, with a total cycle length of about 10 sec. This organization can be modified by electrical stimulation of the juxtafastigial region (JF). During periods without spontaneous rhythmical CS firing, single JF shocks produce a late reflex response (200--300 msec) of the Purkinje cells, which appears as a repetitive sequence of CS (up to 30) at the harmaline-like induced frequency. The response obtained is the same whether the electrical stimulus is single or given in succession at regular intervals; however, in order to obtain such an effect, the frequency of the JF stimulation has to be inferior to the rhythmic CS frequency produced by the drug. At a higher stimulation rate (10 c/sec, 3 sec) the JF-induced response of Purkinje cells is abolished and we observe the suppression--4 to 8 sec following stimulation - of any rhythmic CS activity. This experimental modulation of rhythmic activity of the Purkinje cells (inducement or suppression of the CS firing), controlled indirectly by the olivary system, reproduces the spontaneous fluctuations of the thythmicity under harmaline. A neurophysiological model is presented and the functional significance of the results is discussed.


Morphometric quantification of the cervical limb motor cells in controls and in amyotrophic lateral sclerosis. The limb motor cells of the C6 segment of the spinal cord were counted and correlated with quantified histological findings of biceps brachii muscles in controls and in cases of amyotrophic lateral sclerosis (ALS). In 12 controls the motor cells were divided into larger ones with a minimum diameter greater than 20 micron, and smaller cells. Total numbers of the larger motor cells decreased significantly in 11 of 12 cases of ALS and of the smaller cells in 4 cases. In 4 controls most of the constituents of the biceps brachii muscle were normal-sized fibers, while in ALS smaller fibers and interstitial connective tissue increased and hypertrophic fibers decreased in association with a decrease of normal-sized fibers. The correlation coefficients between total numbers of the larger or smaller motor cells and normal-sized fibers in ALS were 0.92 and 0.65 respectively, and the larger motor cells, correlating with muscular atrophy of the upper arm, were considered to be alpha motor cells. Although in ALS the larger motor cells decreased almost diffusely, there were segmental variations, similar to controls, in numbers of the motor cells per 500 micron thickness.


Glycogen accumulation in the central nervous system in the cerebro-hepato-renal syndrome. Report of a case with ultrastructural studies. We found marked accumulation of glycogen in the brain in one case of the cerebro-hepato-renal syndrome (CHRS). Glycogen in the form of beta-particles was deposited freely within the nucleus, perikaryon and cell processes of neurons and glial cells. The changes involved the gray matter diffusely but were more prominent in the cerebral cortex. The patient died at the age of 4 months after a clinical course characterized by severe hypotonia, seizures, and apneic episodes. Other neuropathologic findings were developmental malformations of the central nervous systen (CNS) (pachygyria, polymicrogyria, and hypoplasia of the inferior olives), white matter abnormalities (deficiency in myelination and diffuse accumulation of sudanophilic droplets within glial cells), clusters of peculiar "globoid" histiocytes with pleomorphic lipid inclusions, and microglial nodules in gray and white matter. This unusual combination of findings is regarded as characteristic of the CHRS.


[Paralysis of the 3d cranial nerves in diabetes and common oculomotor vascularization]. The purpose of this paper is to present explanations for various patterns of IIIrd cranial nerve involvement in diabetes mellitsus, based on its vascularisation. Three clinical cases of diabetes with numerous attacks of IIIrd nerve paralysis are reported. The following patterns were observed: (1) isolated; (2) associated with Vth nerve involvement and; (3) associated with invovlement of the Vth, IVth, VIth, and occasionally IInd and VIIth nerves. An anatomical study of IIIrd nerve vascularisation demonstrates three territories which could correspond to the 3 patterns of clinical expression. The arterial branches to the IIIrd nerve give off no collaterals in the posterior region of the circle of Willis. In the supra-cavernous region, vascularisation of the IIIrd nerve may be associated with that of the IVth. Eventually, vascularisation of the IIIrd nerve in the intracavernous region is associated with that of the Vth, IVth, VIth, and occasionally IInd and VIIth cranial nerves. Thus, a painless paralysis of the IIIrd nerve (isolated or associated only with an involvement of the IVth) would predictably be related to a vascular disturbance limited to the first or second portion of this nerve, whereas a painful paralysis of the IIIrd nerve, without or with associated involvement of other cranial nerves, would relate to a vascular distrubance in the intra-cavernous region. The anatomo-clinical relationships that have been presented: (1) support the vascular basis of IIIrd nerve paralysis in diabetes; (2) explain the various clinical patterns of IIIrd nerve involvement in that disorder and; (3) act as a model which can be applied to the study of ischemic pathology in other cranial nerves and other etiologies.


A longitudinal study of immunological parameters in multiple sclerosis. Cytotoxic antibodies. Complement-dependent gliotoxic antibody activity was determined in 22 patients with multiple sclerosis (MS) and 19 normal control persons. Peripheral blood serum was collected from MS patients at about 4-week intervals for one year, and the results of cytotoxicity tests correlated with the course of disease. For 10 MS patients with stable disease, complement-dependent cytotoxic antibodies directed against a noncytocidally infected mouse glial cell line (an as yet unidentified virus) were found in significantly higher than normal titer. For 12 MS patients with fluctuating clinical course, the gliotoxic antibody titer remained relatively constant before relapse. During relapse, the titer remained constant or dropped. With remission initially low titers increased appreciably.


Distribution of adrenaline-synthesizing enzyme activity in the human brain. A study of the distribution of phenylethanolamine-N-methyl-transferase (PNMT) activity in normal human brain is presented. After a preliminary dissection to separate brain tissue for formalin fixation and tissue designed for biochemical studies, the hemi-brain stem is cut in slices by hand and a cerebral hemisphere is cut on a cyromicrotome. "Punches" are made with an operating microscope. The dissection method was used to study the distribution of PNMT activity in 117 "punches" made on 21 slices obtained from 5 normal human brains. The caudo-rostral distribution of PNMT activity in C1 and C2 groups was found to be identical in each brain. The distribution of PNMT activity was found to be similar to that in the rat, but, in addition, important activity was found in the substantia nigra, internal pallidium and nucleus accumbens.


Hereditary canine spinal muscular atrophy. Hereditary canine spinal muscular atrophy is a newly recognized motor neuron disease occurring in Brittany Spaniels. The clinical manifestations, pattern of inheritance, electrodiagnostic findings, and muscle biopsies have features in common with human spinal muscular atrophy. Neuropathological examination discloses some loss of motor neurons in the spinal cord and brainstem. Many of the surviving motor neurons have neurofibrillary swellings in proximal axons, an abnormality similar to that which occurs early in the course of human amyotrophic lateral sclerosis. These axonal swellings are filled with maloriented skeins of neurofilaments. Since the proteins comprising neurofilaments are carried by slow axonal transport, their accumulation within axons suggest that the swellings may result from impaired slow transport, a hypothesis that can be tested in affected Brittany Spaniels. Hereditary canine spinal muscular atrophy is a new genetic, clinical, and pathological entity, and, at present, it appears to be the best currently available animal model of motor neuron disease.


Early and late mechanisms of increased vascular permeability following experimental cerebral infarction. Cerebral infarction was produced in rats by a combination of transient unilateral common carotid artery occlusion and systemic hypoxia. Horseradish peroxidase (HRP) and Evans blue were given 5 minutes prior to sacrifice to assess the integrity of the blood-brain barrier (BBB) at 1 minute, 30 minutes, and 2 hours following the ischemic insult. There was immediate permeability to HRP in the early (1 minute and 30 minutes) post-ischemic period, whereas, Evans blue was not seen until the late (1.5 to 2 hours) post-ischemic period. Ultrastructural examination showed two routes of barrier permeability to HRP. In the early post-ischemic period, HRP was transported by pinocytosis through endothelial cells in areas of brain containing ischemic neurons. In the late post-ischemic period, HRP diffusely leaked into the brain through the necrotic walls of vessels in areas of infarction. In contrast to previous reports, these results show that the BBB becomes permeable immediately following hypoxia-ischemia. In addition, this study shows that BBB permeability to HRP during cerebral ischemia occurs through two mechanisms: an active, energy-requiring permeability through enhanced pinocytosis within endothelial cells and a passive leakage of protein tracers through necrotic vessel walls.


Phagocytic astrocytes and neurons in old encephalomalacia. Cytoplasmic accumulation of hemosiderin was observed within astrocytes and neurons as well as in other phagocytes associated with old encephalomalacia. The first patient was 3 years old when she died with malnutrition and superimposed infection. A cortical infarct had been caused by an old thrombus in a small artery. The second case was a 9-year-old girl who had old encephalomalacia in the pineal region after extirpation of a pineoloma. The third patient was a 22-year-old man who had a cortical infarct from an embolus associated with chronic rheumatic endocarditis. Granules of hemosiderin had accumulated within the perikaryon of many astrocytes and other phagocytes in all cases, and in a few neurons in the second instance. Review of the literature reveals that cytoplasmic accumulation of particulate matter has been described infrequently with regard to neuroepithelial derivatives. Our findings indicate that astrocytes and neurons as well as derivations of mesenchyme may act as phagocytes of old blood.


The persistence and possible externalization of axonal debris during Wallerian degeneration. The sequence of changes in transected rat sciatic nerves were subjected to parallel ultrastructural and biochemical studies. Widespread granular disintegration of axoplasmic microtubules and neurofilaments occurred in the 24--72 hour interval following nerve transection. These changes were associated with a loss of neurofilament proteins and a marked enhancement of 53,000, 70--73,000 and 85,000 MW proteins in transected nerve. The emergence of prominent nerve proteins during the aftermath of axonal degeneration supports their derivation from axonal sources. These three proteins remained prominent components in transected nerves and comprised the major proteins found in 34-day transected nerves. Amorphous granular breakdown products from myelinated and unmyelinated nerve fibers were encountered with progressively decreasing frequency after 48 hours. This diminution of intracellular axonal debris was accompanied by the appearance and increasing prominence of amorphous granular deposits within the endoneurium of transected nerves. These endoneurial deposits became closely associated with collagen fibers and persisted as a prominent component in 34-, 80- and 120-day transected nerves. It is suggested that the amorphous endoneurial granular deposits arise in part from the externalization of granular axoplasmic breakdown products. Externalized axonal components could have important implications for tissue reaction to injury.


Pineocytoma with astrocytomatous differentiation. A pineocytoma with astrocytomatous differentiation in a 57-year-old man is reported. The histogenetic and oncogenetic implications of this neoplasm are briefly discussed.


Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons. The neurogenetic process leading to the formation of primary sensory neurons persists into adult life in the olfactory epithelium of mammals. The morphological stages of maturation and ageing of this exceptional neuron have been described both at light and electron microscopical levels. For descriptive purposes the neural elements have been classified as: (1) basal cells proper, (2) globose basal cells, and (3) neurons. Intermediate stages, however, have been identified. Autoradiographic observations complement the morphological studies and provide a time sequence of the morphological stages leading to the mature neurons. A typical columnar arrangement of the sensory neurons has been described. Furthermore, active and quiescent zones have been recognized in the neuroepithelium. In the active zones the neurogenetic process is vigorous, and the zones are characterized by the presence of immature elements. However, in the quiescent zones there exists a population of mature elements while immature neurons are sparse.


An ultrastructural study of transganglionic degeneration in the main sensory trigeminal nucleus of the rat. In adult rats subjected to unilateral transection of the infraorbital nerve, the main sensory trigeminal nucleus was studied by electron microscopy. Post-operative survival times varied between 2 and 60 days. A variety of ultrastructural alterations was observed from the sixth post-operative day onwards. These changes were in many respects similar to those seen in the course of Wallerian degeneration. Neurofilamentous boutons and axons were found 6-30 days post-operatively. Various types of dark boutons were observed between 7 and 30 days and axonal changes indicative of degeneration between 7 and 60 days post-operatively. Astrocytes and microglial cells contained degenerating structures 7-60 days post-operatively. The alterations observed in the present study are interpreted as related, at least in part, to the nerve cell degeneration and the nerve cell death previously shown to occur in the trigeminal ganglion after infraorbital nerve transection.


Paramembranous densities of 'C' terminal-motoneuron synapses in the spinal cord of the rat. A category of large boutons forming synapses with the soma and proximal dendrites of spinal motoneurons was studied in glutaraldehyde-fixed, non-osmicated tissue stained with uranyl acetate and lead citrate. The identity of these boutons with 'C' boutons was indicated by their shape, frequency and distribution as well as by the ultrastructural characteristics of the boutons and the associated postsynaptic structures. In contrast to previous descriptions based on osmicated tissue, this study demonstrates that paramembranous densities are a feature of 'C' terminal-motoneuron synapses.


Electron microscopic localization of [125I]alpha-bungarotoxin binding sites in the outer plexiform layer of the goldfish retina. Light and electron microscope autoradiography were performed on goldfish (Carassius auratus) retinas incubated in [125I]labelled alpha-bungarotoxin. The toxin was bound preferentially to membrane receptors in the inner and outer plexiform layers. Binding was suppressed by 10(-5) M nicotine or 10(-5) M native alpha-bungarotoxin. Electron microscopic analysis of the outer plexiform layer (OPL) strongly suggested that alpha-bungarotoxin binding sites were located on small bipolar cell dendritic processes that invaginated rod and cone synaptic terminals, and on large bipolar cell dendritic processes more proximally situated in the OPL. Large horizontal cell processes in the OPL and horizontal cell processes that invaginated rod and cone synaptic terminals did not appear to be labelled.


Location of interganglionic neurons in the stomatogastric system of the spiny lobster. The stomatogastric ganglion produces distinct and complex patterned output driving the mastication and filtration of food. It does so with a small number of neurons whose properties and interconnections have been extensively examined. The motor patterns are subject to modulation and integration by neurons of other ganglia. This paper reports a search for interneurons of the four interconnecting ganglia of this system, using cobalt chloride backfilling techniques. It was determined that only a small number of neurons may interconnect these ganglia: (1) In the stomatogastric ganglion there are two to three small neurons and six large neurons with neurites projecting anteriorly towards the other ganglia. (2) In the two commissural ganglia there are one to three small neurons whose neurites project to the primary input nerve of the stomatogastric ganglion. (3) In the oesophageal ganglion there are three small neurons whose location would allow them to play a co-ordinating role in the output of all four ganglia.


Endplates after esterase inactivation in vivo: correlation between esterase concentration, functional response and fine structure. Mouse sternomastoid muscles were incubated with diisopropylfluorophosphate (DFP) in vivo, and the time course of recovery was studied using histochemistry, EM autoradiography and physiology. We found that: (1) the ability of the muscle to sustain tetanus in response to nerve stimulation is eliminated when the esterases at the neuromuscular junctions are saturated with DFP. This ability is regained partially when less than 10% of the DFP-binding sites have recovered. (2) There is a positive correlation between the frequency of stimulation at which the tetanic response can be maintained and the extent of acetylcholinesterase (AChE) recovery. (3) Tetanic responses at fusion frequency (about 100 Hz) appear indistinguishable from controls with only about 25% of normal AChE. (4) Butyrylcholinesterase (BuChE) possibly of Schwann cell origin recovers more rapidly than does AChE. (5) The muscle shows fine structural changes involving Z band dissolution and the breakdown of sarcoplasmic reticulum within hours after esterase inactivation. (6) This myopathy reaches a peak at three days after esterase inactivation and is almost fully recovered by two weeks. (7) It can be eliminated if, at the time of esterase inactivation, the nerve is cut or the acetylcholine receptors at the endplate are inactivated by alpha-bungarotoxin. We suggest that the myopathy, seen after DFP, is mediated by Ca2+ fluxes due to prolonged action of acetylcholine (ACh) in the absence of esterases.


Chemotherapy as an adjunct in the initial management of cerebellar medulloblastomas. A preliminary report. Eight consecutive children with biopsy-proven cerebellar medulloblastoma were treated with a combination of whole neuraxis radiation and prolonged chemotherapy using vincristine and cyclophosphamide. There was no evidence of tumor recurrence in the follow-up period, which ranged from 16 months to 7 years and 8 months following diagnosis. Morbidity associated with this regimen has been infrequent and easily reversible.


Reconstitution of "totally" occluded internal carotid arteries: angiographic and technical considerations. The authors describe their experiences with five patients with delayed transient ischemic symptoms homolateral to internal carotid artery (ICA) occlusions. In each instance, initial arteriograms were interpreted as showing irreversible occlusions of these arteries in the neck and microvascular bypass procedures were contemplated. However, after repeat arteriographic evaluations with a modified injection technique, certain angiographic features were identified that suggested the mechanism of the symptoms in these patients and that their ICA's could be reconstituted in the neck. This was successfully accomplished in each patient with complete relief of ischemic symptoms. The angiographic technique employed and the arterial flow patterns identified in these patients are discussed. The details of the operative technique are described. It is concluded that routine arteriographic techniques may be inadequate to identify the reversible carotid occlusion. This may account for some of the confusion which surrounds the surgery of these vessels as well as the failure of extracranial-intracranial bypass to relieve recurrent ischemic symptoms in these individuals.


Nonvolumetric methods of detecting impaired intracranial compliance or reactivity: pulse width and wave form analysis. The authors have attempted to find a clinically reliable method of measuring intracranial pressure (ICP) compliance or reactivity that does not require volumetric manipulation. An analysis was undertaken of ICP, pulse widths and of the presence or absence of B waves, both experimentally in dogs and clinically in postoperative human patients. In both dogs and humans, ICP pulse width generally increased with increasing ICP and with increasing intracranial mass, and definitely increased with systolic arterial blood pressure. Nonetheless, ICP pulse width commonly failed to increase with increasing cerebral reactivity, and low ICP pulse width measurements were at times recorded in distinctly pathological situations. From the clinical study it was found that B waves were encountered more commonly in patients with increased ICP or increased ICP pulse width. However, the correlation between B waves alone or in combination with increased ICP or ICP pulse width and quantitative measurements of ICP reactivity was not significant. Mean reactivity and the range of reactivity measurements were almost identical in patient groups with and without B waves. For the time being the "ICP reserve test" remains the most accurate, the safest, and the most clinically useful method of quantitating ICP reserve.


Pulmonary shunt as a prognostic indicator in head injury. Severe head injury may cause momentary respiratory arrest. Resultant hypoxia would increase cerebral edema and adversely affect the quality of survival. This study examines the effect of hypoxemia on outcome. Pulmonary shunt was calculated as a convenient measurement of respiratory insufficiency in 86 severely  head-injured patients who underwent surgery. All samples were taken shortly after induction into anesthesia when controlled ventilation with high inspired-oxygen concentration had been established. In 39 patients who improved, mean pulmonary shunt was 8.9%. Twelve patients who survived with deficit showed a mean shunt of 13.6%, and in 35 patients who died, the mean initial shunt was 15.6%. No significant correlation was found between abnormal chest x-ray findings or the occurrence of hypertension and shunt percentage. The American Society of Anesthesiologists at-risk classification correlated grossly with the outcome. Early pulmonary shunt is a prognostic indicator in severe head injury and should be used in conjunction with the Glasgow Coma Scale in assessing outcome. Despite an apparently adequate respiratory pattern, all patients with severe head injury must be assumed to be hypoxic until proven otherwise. While hypoxemia may prove to be refractory in overwhelming injury, patients who score low on the Glasgow Coma Scale but who have relatively normal oxygen exchange may still survive with little deficit.


Results of urinary diversion in patients with myelomeningocele. Among 481 children with myelomeningocele seen at the North Carolina Baptist Hospital since 1949, 46 have undergone a urinary diversion procedure, as follows: ileal loop in 43; sigmoid loop in two; and transverse colon conduit in one. The indications for diversion were incontinence in 28, urinary infection or pyelonephritis in 27, and hydronephrosis, pyelocaliectasis, and reflux in 12 patients. No deaths resulted from the diversionary procedures. One patient required early surgical revision and seven patients required late surgical revision. Two patients have since died, 44 have been followed for an average of 7.9 years, 15 for more than 10 years. Overall, of 26 patients with normal prediversionary intravenous pyelograms (IVP's), 88% now have normal or nearly normal IVP's; of 14 patients with abnormal prediversionary IVP's, 79% now have normal, improved, or unaltered IVP's. Renal function has remained normal in all 44 patients, and renal calculi have developed in 10 patients. Ileal loop diversion appears to convert a high-pressure system into a low-pressure system, thereby helping to prevent further renal damage. This procedure tends to stabilize, rather than improve, urinary-tract function. For these children already so incapacitated by their basic disease, this goal is acceptable, particularly since it also provides continence and independence from parental nursing.


Analysis and measurement of some sources of variability in experimental spinal cord trauma. Experiments were performed on anesthetized cats to determine whether the variability that is common in experimental spinal cord injuries produced by the weight-drop technique can be reduced if a more accurate determination of the actual intensity of the insult to the cord is measured. In addition, determinations of the contribution of such variables as mass of drop-weight, impounder diameter, and animal weight to variability were made. It was found that of the three measures of intensity readily available from a strain gauge transducer, impulse (change in momentum of drop-weight) showed the highest correlation with the histologically determined extent of the lesion. It was shown that the mass of the drop-weight had a significant effect on lesion size even when the gram X centimeter quantification of the injury was constant. Animal weight and impounder diameter did not make a significant contribution to the variability of injury as determined by low-power microscopy.


Paraplegia due to posttraumatic pelvic arteriovenous fistula treated by surgery and embolization. Case report. A case is presented in which a posttraumatic pelvic arteriovenous fistula caused progressive paraplegia because of voluminous shunting into the epidural venous system. Surgical ligation and transcatheter embolization of major and minor arterial feeders decreased shunt flow sufficiently to permit direct embolization of the fistula by an injectable plastic. This combined approach may allow obliteration of unresectable acquired or congenital arteriovenous malformations.


Localized primary intracranial Ewing's sarcoma of the orbital roof. Case report. A rare case of a primary Ewing's sarcoma arising from the intracranial portion of the right orbital roof is presented. Clinical presentation was that of a rapidly growing tender exostosis, associated with headaches. History indicated that the tumor may have been present for more than 1 year. Skull x-rays showed marked diastasis of the coronal suture and a "mottled" appearance on the right frontal bone suggestive of a sarcoma. Bone scan further confirmed the presence of a malignant bone tumor. Computerized tomography scan showed the intracranial extension of the tumor and a follow-up scan allowed us to see the response of the tumor to therapy. Only two other cases with details as to intracranial localization were found in the literature.


Replacement of L-phenylalanine and L-leucine by alpha-hydroxy analogues in the diets of germfree rats. It has been suggested that the metabolic activity of the intestinal microflora is necessary for the utilization of the alpha-keto and alpha-hydroxy analogues of the essential amino acids. This role of the intestinal microflora has been examined by comparing weight gain of germfree and conventional rats in response to the substitution of one amino acid in the diet by its analogue. Using a completely defined liquid diet it was found that weight gain of germfree rats was well maintained and comparable to that of conventional rats when 1.5 M equivalents of DL-alpha-hydroxyisocaproic acid was substituted for L-leucine in the diet. Although weight gain was not fully maintained when 2.0 M equivalents of L-phenyllactate was substituted for L-phenylalanine, germfree and conventional rats showed similar weight gains. These results exclude an obligatory role for the flora in the utilization of these non-nitrogen containing analogues of L-phenylalanine and L-leucine.


Vitamin B6 dependence of selenomethionine and selenite utilization for glutathione peroxidase in the rat. The biological availability of selenium from sodium selenite and selenomethionine for glutathione peroxidase activity was studied. Rats were fed ad libitum for 2 weeks a basal diet deficient in both selenium and vitamin B6, and then for the subsequent 2 weeks the same diet supplemented with vitamin B6 (2.5 micrograms as pyridoxine-HCl/g diet) or selenium (2 microgram/g diet) or both. In the presence of vitamin B6, selenite and selenomethionine increased equally the glutathione peroxidase activity in both the liver and erythrocytes above that of selenium-unsupplemented controls. In the absence of vitamin B6, selenomethionine was less effective in the liver and ineffective in the erythrocytes while selenite was equally effective in both tissues and was as effective as in the presence of vitamin B6. These results indicate that selenite selenium is readily available for glutathione peroxidase induction as compared with selenomethionine, and establish that vitamin B6 is involved in the metabolism of selenomethionine to supply selenium for glutathione peroxidase.


Effect of food toxicants on voluntary wheel running in rats. Voluntary wheel running in rats in reaction to a dietary deficiency of iron or food toxicants of natural (dioscin) and environmental (cadmium) origins was used to develop a behavioral model by which rapid detection of food contaminants was accomplished following induction of spontaneous activity by techniques of feed restriction. High levels of voluntary wheel running in reference controls were followed by significant depressions in running activity in animals fed the dietary toxicants. Analyses of blood and liver tissues and depressions of testes size confirmed the presence of the insults to metabolism.


Effect of capsaicin on gastric acid secretion and mucosal blood flow in the rat. The effect of capsaicin, a pungent ingredient in capsicum fruit, upon gastric acid secretion and mucosal blood flow was assessed in the anesthetized rat. At each 15 minute interval, 0.3 ml saline solution, with or without various doses of pure synthetic capsaicin (the doses varied from 50 to 2,000 microgram/kg rat) was delivered into the gastric lumen via a gastric fistula. The gastric contents were withdrawn after 15 minutes for acid assay and replaced with a new saline solution. Capsaicin of increasing doses (up to 1,000 microgram/kg) progressively increased the acid output. Gastric inhibitors hexamethonium and atropine, completely abolished the acid secretion induced by capsaicin whereas secretin only partially reduced such a response. The systemic blood pressure was not affected by the capsaicin or the method employed. However, the aminopyrine clearance which was the indicator of the gastric mucosal blood flow increased in accordance with the increase in the acid output. It is suggested that the effect of capsaicin on the acid secretion and mucosal blood flow is by the release of endogenous gastric secretagogues which increase both tissue perfusion and the secretory activity.


Response of plasma levels of vitamin A to a dose of vitamin A as an indicator of hepatic vitamin A reserves in rats. Rats were fed diets deficient [-A] or sufficient [+A] (3 mg retinol equivalents/kg) in vitamin A, and without [-RA] or with [+RA] (12 mg/kg) retinoic acid supplementation for up to 33 days. Rats with plasma vitamin A levels ranging from 7 to 62 micrograms/dl were studied at intervals during progressive depletion of liver stores of vitamin A (expt. 2) and when liver stores were nearly exhausted (less than 10 micrograms/g) or replete (up to 100 micrograms/g) with vitamin A (expt. 1). A dose of retinyl acetate in corn oil (20 micrograms retinol equivalents) was administered by intubation directly into the stomach. The relative dose response (RDR), expressed as a percentage and defined as the absolute magnitude of the rise in plasma vitamin A levels 5 hours after the dose of retinyl acetate, divided by the plasma level of vitamin A attained after 5 hours, was determined for each rat and correlated over a wide range of vitamin A plasma and liver levels. An RDR above 50% invariably was associated with low plasma levels (10 to 30 micrograms/dl) and low liver stores (less than 10 micrograms/g) of vitamin A, whereas an RDR of less than 40% was associated with plasma levels above 30 micrograms/dl and liver stores ranging from 3 to 100 micrograms/g.


Effects of dietary vitamin A deficiency, retinoic acid and protein quantity and quality on serially obtained plasma and liver levels of vitamin A in rats. Rats were fed vitamin A-deficient diets either alone, supplemented with retinoic acid (RA), or of limited protein quality or quantity (7%rice or 7% casein protein); one group was fed 7% rice protein supplemented with vitamin A. Plasma and liver levels of vitamin A were determined serially. Plasma levels in rats fed otherwise adequate vitamin A-deficient diets remained above 30 micrograms/dl until liver reserves were below 10 micrograms/g tissue, at which point plasma levels decreased in some but not all rats while liver levels continued to decline (at a slower rate) to levels as low as 3 micrograms/g. Supplementation with RA caused an immediate and sustained reduction of 15 to 20 micrograms/dl in circulating vitamin A. At 7% dietary protein, plasma levels of vitamin A remained above 30 micrograms/dl when casein protein was fed or when the rice protein diet was supplemented with dietary vitamin A, but not when the rice protein diet was fed without an exogenous source of the vitamin. A scheme is proposed suggesting possible regulatory mechanisms that might control homeostatic levels of plasma vitamin A.


Dietary fat-dependent changes in hepatic cholesterogenesis and the activity of 3-hydroxy-3-methylglutaryl-CoA reductase in fasted-refed rats. Effects of various dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and sterol and fatty acid synthesis from [1-14C]acetate and [2-14C]mevalonate were examined in the liver from fasted-refed rats. Rats fasted for 2 days were refed a fat-free diet or diets containing various fats (tricaprylin, trilaurin, trimyristin, tristearin, camellia oil, or safflower oil) at the 10% level for 1, 3, or 7 days. The activity of HMG-CoA reductase was restored to about one-half of the pre-fasting levels in all groups after refeeding for 1 day and increased to above the pre-fasting levels after 3 days, with the exception of safflower oil, the rise was especially noticeable when fat-free, tricaprylin, and tristearin diets were fed. After 7 days, the activity of HMG-CoA reductase, except for rats refed tristearin, was decreased to levels that were far below those observed after 1 day-refeeding. This was particularly marked with tricaprylin, trilaurin, and camellia oil. The response of sterogenesis resembled that of the reductase. Dietary fat-dependent modification of fatty acid synthesis from [1-14C]acetate was first demonstrated after 7 days. Hepatic esterified cholesterol tended to accumulate and the deposition was marked after 3 days of refeeding. However, fat-dependent alterations of this parameter were remarkable on day 7. The concentration of plasma cholesterol also showed dietary fat-dependent changes after refeeding. Dietary fats appear to play an important role not only in the regulation of hepatic HMG-CoA reductase and sterol synthesis, but also in the overall processes of cholesterol dynamics.


Effect of mineral mixture in diet on protein intake regulation in the weanling rat. Weanling rats fed a choice of two diets varying only in protein concentration (10 and 60% casein) select a lower proportion of dietary energy as protein when the dietary minerals are supplied by a mineral mixture high in Na, K, and Cl but low in P and Cu (Hi Cl) than when the diets contain the Bernhart-Tomarelli (BT) mineral mixture. The addition of Na and/or K as acetate salts to the BT mineral mixture, to levels in the Hi Cl mixture, had no effect on regulation of protein intake. However, the addition of Na and/or K as chloride salts to the BT mineral mixture resulted in the rats selecting a protein concentration equivalent to the Hi Cl fed group. Weight gains and energy consumption were similar for all groups. It was therefore concluded that dietary chloride affects protein feeding behavior.


Protein quality of high-protein and low-protein milled rices in preschool children. High-protein (11.0%, IR480-5-9) and low-protein (7.1%, IR32) milled rices were compared with casein as a control when fed as the main source of dietary N to eight apparently normal Filipino children, 1.5 to 2.0 years of age. Daily diets were formulated to contain 250 mg N and 100 kcal/kg body weight. Apparent digestibility of 60.0% for high-protein rice was lower than for low-protein rice (66.2%), and higher values of 76.8 and 80.8% were obtained for the two casein control diets. Corresponding apparent retentions were similar for the two rices, at 23.4 and 26.9%, respectively, as compared to 25.0 and 38.6% for the two casein control diets. These results support previous data on children fed non-isonitrogenous rice-based diets indicating that an increase in protein content of milled rice results in only a slight decrease in its protein quality. The results were similar to those obtained with Peruvian children on a similar protocol.


Use of tritiated water for measurement of 24-hour milk intake in suckling lean and genetically obese (ob/ob) mice. A non-invasive method has been developed for measuring milk intake of suckling mice under physiological conditions. This method was used to determine whether genetically obese (ob/ob) mice are hyperphagic at 10 and 15 days of age. Lactating dams were injected with tritiated water (3H2O), which equilibrated in body water within 30 minutes. A constant specific activity of 3H2O was maintained over a 24-hour period by provision of 3H2O in drinking water. Tritium accumulation in body water of pups was proportional to their milk intake. After 24 hours, pups were removed from the dam, weighed, and blood samples (less than 10 microliters) obtained for assay of plasma 3H content by liquid scintillation counting. Body water content was computed from body weight. The composition of mouse milk taken from dams on days 10 and 15 of lactation was analyzed both volumetrically and gravimetrically. Water content was 68 to 69%; lipid content was 20% on day 10, 17% on day 15. At 10 days, mean milk intake was 0.96 ml, independent of litter size. At 15 days, intake per pup tended to decrease, from 1.4 to 0.8 ml, with increasing litter size. Using this method we have established that under physiological conditions ob/ob mice, which were identified as such at 4 to 5 weeks of age, do not have increased milk consumption at either 10 or 15 days of age.


Fetal skeletal malformations associated with moderate zinc deficiency during pregnancy. This study investigated the effects of moderate zinc deficiency on the development of rat fetal skeleton. Eighteen pregnant rats were fed zinc deficient diet (1.3 ppm) from days 3 to 15 of gestation. An additional 18 rats were pair fed the same diet supplemented with 100 ppm zinc and served as controls. The levels of zinc in plasma were determined on days 15 and 20 of gestation and in the amniotic fluid on day 20. The pregnant rats were killed on day 20 and fetuses were cleared and stained with alizarin red. The weight of zinc deficient fetuses was significantly less than that of controls. The uncleared, as well as stained zinc supplemented fetuses, showed no anomalies. The alizarin stained experimental fetuses showed severe anomalies of long bones, vertebrae, and ribs. The overall calcification of bones was also considerably less as compared to zinc supplemented controls. The zinc levels were significantly less in plasma (day 15) and amniotic fluid (day 20) of experimental dams. The results also indicated that although moderate zinc deficiency does not cause external craniofacial malformations, it severely affects the calcification and development of cranial bones.


Cancer mortality in oil refinery workers. The cancer mortality experience from 1964 to 1973 of employees of the Imperial Oil Limited was examined in a cohort study. Employees in jobs which exposed them on a daily basis to crude petroleum or its products, compared with nonexposed employees, were found to have more than three times the risk of esophageal and stomach cancer and about twice the risk of lung cancer. In the exposed group, increasing risks of both cancers occurred with increasing duration of employment. In the absence of more complete information on the similarity of the exposed and nonexposed employees, these results cannot be ascribed with certainty to a carcinogenic effect of petroleum. However, there was no other clear explanation for the results, and further study is required. When refinery workers were compared with nonrefinery workers without consideration of exposure to petroleum in either group, the refinery workers were found to have twice the risk of cancer of the intestines (including rectum) and other digestive organs. No relationship with duration of employment was evident. Although the increased intestinal cancer mortality in the refinery workers was not consistent, bias was not an obvious explanation for the observed relationship. Therefore, the presence on a refinery site of a carcinogen other than petroleum has not been ruled out, and further study is urged.


Urinary and plasma concentrations of nickel as indicators of exposure to nickel in an electroplating shop. The relationship between atmospheric exposure to nickel and urine and plasma nickel concentrations was studied by following four workers from an electroplating shop for one work week by daily measurements of the nickel concentration in workroom air with personal samplers and nickel concentrations in blood and urine samples collected before and after the work shift. The workroom air concentrations ranged from 0.03 to 0.16 mg/m3. The urinary and plasma nickel concentrations were higher in the samples taken after than before the work shift and a close positive correlation was found between the air nickel concentrations and the urine and plasma nickel concentrations, respectively. There was also a close correlation between urinary and plasma nickel concentrations. A slight accumulation of nickel occurred as judged from the increasing concentrations of nickel in the urine and plasma morning samples during the study week. This study indicates that both plasma and urine nickel concentrations may be used as biological indicators of exposure to soluble nickel compounds.


Harvester exposure to Zolone (phosalone) residues in peach orchards. This field study was undertaken to quantitate the exposures of peach pickers to pesticide residues. Five fields were harvested each for three days at decreasing post-application intervals. Aerosol and dermal exposure estimates indicated 98-99% of the workers' dose was dermal, predominantly to the hands and upper extremities. Estimates of dose correlated with measurements of foliar residues. Despite estimated dose rates of up to 14 mg/hr, the RBC cholinesterase in these workers may have been only slightly inhibited (circa 4%) when compared to an unexposed, control population. Comparisons of these results with earlier studies of parathion residues on citrus indicate a consistent pattern of worker exposure. However, a concern is raised over the efficacy of using existing foliar residue sampling methodologies for all other pesticides.


Significance of data collection. Viewpoint - academia. The academic view of the collection of data relating to the health of workers must reflect a concern for the value of the data for research purposes. Most routine data systems do not provide information of research quality, and often are not appropriate or sufficiently detailed to allow specific hypotheses to be tested. the cost of serving research purposes in such systems is likely to be prohibitive. However, the monitoring of illness in groups of employees can and should serve as a most valuable research resource when viewed as a screening and detection mechanism. Therefore, a data collection system should be carefully designed with research needs in mind, so that it will be appropriately sensitive and consistent.


Medically-related absenteeism: random or motivated behavior? The present study examined alternative measures of absence proneness related to organizationally-defined measures of absenteeism. A typical distinction among various types of absences is to separate medically-related absences from other types, since medically-related absences are believed to reflect random or unsystematic causes of behavior rather than voluntary choice behavior of the employee. The present study defined absence proneness as the degree to which individuals repeat their behavior. Three years of absence data for a sample of employees from one company were examined to discover the degree of absence proneness present in organizationally-defined forms of medically-related and voluntary absenteeism. In addition, a survey was administered to the sample to measure employee perceptions of work and non-work-related factors which were believed to be motivational determinants of absenteeism. A multiple discriminant analysis was developed in an attempt to classify employees to a survey designed to measure motivational determinants of absenteeism. The classification results supported the view that medically-related absenteeism has motivational determinants related to employee work and non-work preferences. Implications for management are discussed.


Critical analysis of the effectiveness of secondary prevention of occupational hearing loss. There is an unavoidable error margin associated with audiometric measurements. This error margin was used to set specificity and sensitivity criteria for repeated testing of hearing. The criteria were applied to the time growth function of occupational hearing loss for typical noise exposures. It is shown that monitoring audiometry can be an effective screening procedure only for the first five to ten years of exposure to a given noise environment. A strategy for effective secondary prevention of occupational hearing loss is outlined.


Instrumentation for measurement of sensory loss in the fingertips. Four aesthesiometers measuring fingertip sensation were fabricated, two for depth-sense perception and two for two-point discrimination. With the use of 20 normal subjects (10 female and 10 male) and seven subjects with vasospastic disturbance (three female and four male) comparisons were made to determine which of each pair of instruments was the more sensitive. The results indicated that instrument A is preferable to B in measuring depth-sense perception, and C is preferable to D in measuring two-point discrimination. Females appear to have more acute sensory perception than males. Female and male patients diagnosed as having "Raynaud's disease" show a loss in fingertip sensory perception.


Strength and fitness and subsequent back injuries in firefighters. This prospective investigation was done to evaluate five strength and fitness measurements and the subsequent occurrence of back injuries in 1652 firefighters for the years 1971 to 1974. The prospective measurements included flexibility, isometric lifting strength, bicycle ergometer exercise measurements of two-minute recovery heart rate, diastolic blood pressure at a heart rate of 160 beats per minute and watts of effort required to sustain heart rate at 160. Three fitness and conditioning groups were established by multivariate ranking and regression techniques (259 high, 266 low, and 1127 middle) and the subsequent back injuries were tabulated for the three groups. The results showed a graded and statistically significant protective effect for added levels of fitness and conditioning (least fit, 7.1% injured; middle fit, 3.2% jured; and most fit, 0.8% injured). It was concluded that physical fitness and conditioning of firefighters are preventive of back injuries and that further investigations are warranted to study other injuries and physical fitness in this physically active occupational group.


Prevalence of respiratory disease in a cotton compress and warehouse. A preliminary survey. A preliminary survey was undertaken to explore the relationship of respiratory symptoms and disease to work in a cotton compress and warehouse operation. A respiratory history was obtained from all 70 employees in a single cotton compress and warehouse complex. Sixteen of 70 employees (23%) had respiratory symptoms but none were typical of byssinosis. Fifteen of the 16 employees with positive respiratory symptoms were further studied by objective pulmonary function tests. Five of these 15 workers had abnormal results: one with an FEV1 decrement greater that 5% only, one with a ratio of FEV1, to FVC less than 70% only, and two with both abnormalities. One additional employee had an FEV1 of 73% predicted as his only abnormality.


Studies of respiratory cancer in high risk communities. Mortality from cancers of the respiratory tract show marked geographic variation within the U.S. This review describes the unusual patterns of these tumors, and traces how new clues to environmental and occupational determinants are being tested by epidemiologic studies in areas of the country where rates are high.


The problems of asbestosis in Spain.

The problems of asbestosis in Spain. About 50 cases of asbestosis have been descirbed in Spain from 1948 through 1974. Since 1975 the Instituto Territorial de Barcelona, Servicio Social de Higiene y Seguridad del Trabajo, has initiated a survey of all the industries with an asbestosis risk in the Barcelona area. Nearly 300 cases of asbestosis have been detected to date. Given the poor hygienic conditions of most of the industries, with an asbestosis risk, and the considerably large number of exposed people, it can easily be predicted that a rapid increase of the incidence of the disease in the years to come will occur. Most of the observed cases in Barcelona were from two fibrocement industries. Of a total of 1003 workers examined, 247 (about 25%) had asbestosis.


Median cleft face syndrome or frontonasal dysplasia: a case report with associated kidney malformation. The authors present a case of an 11-month-old girl with the medial cleft face syndrome and the following malformations: ocular hyperterolism, primary telecanthus, cleft nose with absent tip, broad nasal root, complete absence of the left upper lid, and abnormal hair-line implantation in the corresponding frontal region, high arched palate, neurosensorial deafness and agenesia of the right kidney. The authors propose that the  eyelid is responsible for the area of hair growth suppression around the eyes. This is the first case report of median cleft face syndrome associated with renal agenesia.


Rate and various aspects of eye infection resulting from congenital rubella. A study on the eyes of 39 embryos, which were removed from women who had contracted clinical or subclinical rubella during the first and beginning of the second trimester of gestation is presented. A virological and histological study was performed on the eyes. In four cases rubella virus was isolated from the eye tissues (10.3%) and in nine cases, histological evidence of rubella cataract was found (27.3%). These results suggest that the rubella infection, even in cases of subclinical infections in pregnant women in the first trimester, are highly dangerous (in our study--37.6%) to the eye of the fetus, and, therefore, early diagnosis is necessary in order to avoid the risk of the consequences of congenital rubella infections in the newborn.


Isolation of rubella virus from lens material in cases of congenital cataracts. Rubella virus cultures were carried on lens materials from seven cases of bilateral congenital cataracts and in one of them it was possible to isolate the virus. This case is one of those rare cases in which the virus was isolated.


Comparison and combination of recall and Background Interference Procedures for the Bender-Gestalt Test with brain-damaged and schizophrenic patients. The Bender-Gestalt Test was administered under standard, recall, Background Interference Procedure (BIP), and BIP-recall conditions to 20 brain-damaged and 20 schizophrenic male inpatients. Individual recall, BIP, and BIP-recall scores differentiated between the groups prior to controlling for IQ, but only recall and BIP-recall continued to discriminate once IQ was held constant. The use of difference scores corrected for standard copy performance (base level) resulted in improved diagnostic discrimination compared to difference scores alone. However, this procedure also produced a substantial multiple correlation with IQ and a consequent loss of group differentiation for the BIP difference score, while failing to yield an appreciable increase in predictive accuracy over individual scores for recall and BIP-recall. Nonetheless, a significant effect emerged independently of both recall and IQ for the BIP-recall score, suggesting that the BIP hypothesis may have merit within the context of memory functioning.


The diagnosis of brain-damage by the MMPI: a comprehensive evaluation. A number of research studies have proposed various methods for using the MMPI to identify brain dysfunction. This previous research has taken one of three major approaches. The present study compared the major approaches in a population consisting of 30 schizophrenic, 30 brain-damaged and 30 hospitalized normal patients. The results indicated that the most effective diagnosis device was the use of the Sc scale alone or in conjunction with the remaining clinical scales and the F scale. None of the organic scales or keys were able to match the performance of the Sc scale alone. The poor results obtained bring into question the use of these scales in any other setting without an extensive research validation. An alternate method that might be used to employ the MMPI in the diagnosis of brain dysfunction was suggested.


Superior oblique strengthening procedures in hypertropia I and II. Strengthening the paretic superior oblique has an effective role in the management of cyclovertical hypertropia. Resection of the tendon is safe and the reduction of the deviation is long lasting.


Alternate day esotropia.

Alternate day esotropia. A six-year-old girl was noted to develop alternate day esotropia three years following surgery for a moderate "v" esotropia. Many of the usual features of cyclic esotropia, including moderate hypermetropia, mild amblyopia, moderate to large deviation, a 48-hour cyclic pattern, and a high AC/C ratio were present. A therapeutic trial with strong miotics was unsuccessful. Saccadic velocity studies revealed no evidence of lateral rectus palsy. No fluctuations in pupillary size or response, refractive errors, accommodative amplitude, visual acuity, blood pressure, behavior, and the electroencephalographic pattern were noted. Following bimedial recession surgery, the eyes have remained straight and the cyclic pattern has been abolished for a two and one half year follow-up period. There is evidence to suggest that these patients are basically strabismic with cycles of remission.


Cross validation of the 2-8/8-2 MMPI code type for young adult psychiatric outpatients. Young adults attending a college student mental health center and obtaining 2 and 8 as their highest scale elevations (and not scale 7 as the third elevation) on the MMPI were compared to other patients at the center on 175 descriptors obtained from intake interviews. Those items which discriminated (chi2, p less than .05) 2-8/8-2 patients from others in the sample are presented in relationship to the descriptors obtained for this code type by other investigators. The statements generated by the Marks and Seeman interpretive system for adults were then reanalyzed by the Chi Square method to demonstrate the differential effect of statistical method upon code type interpretation. Although previously established correlates of 2-8/8-2 profiles were partially validated, a number of different descriptors emerge for males and females in this population. Questions are raised and discussed concerning methodologies for generating interpretive statements for various clinical populations.


The Mosher Forced Choice Guilt Scale as a measure of anxiety. Women divided into two levels of sex-guilt were administered the Word Association Test under three different conditions. In the first a confederate modeled sexual responses, in the second a confederate modeled nonsexual responses, and in the third condition no confederate was present. The results indicated that both low- and high-guilt women made significantly more sexual responses when exposed to the sexual model than in the nonsexual or no-model conditions. The results were interpreted as supporting an avoidant-anxiety conceptualization of guilt as opposed to Mosher's preservation of self-esteem view.


MMPI validity scales and behavioral disturbance in psychiatric inpatients. Sixty psychiatric inpatients were assigned to one of three groups on the basis of F and K MMPI validity scales. Staff ratings of patient behavior and recorded incidents of "acting-out" behavior were obtained for patients with: (a) "plea for help" validity profiles, (b) hyper-defensive profiles, and (c) average profiles. Patients with "plea for help" profiles were perceived as "acting-out" more frequently and engendering more feelings of frustration than patients in the other groups. These patients account for 77% of the incidents of inappropriate, destructive behavior and 83% of the seclusions in the patients sampled. Although the "plea for help" profile is considered invalid in some scoring systems, results suggest that this validity profile may be useful in treatment planning.


Studies on skin-electrode ERG in the closed-eye state. Electroretinograms (ERG) were recorded using contact lens electrode and periorbital skin electrode in the opened- and closed-eye states in 15 volunteers. The implicit times of a-wave and b-wave were almost equal between recordings by contact lens electrode and those by skin electrode, when the tested eye was opened. Implicit times were prolonged when tested in the closed-eye state. In the opened-eye state, the b-wave amplitude by skin electrode was decreased to an extent of about 40%, compared to that by contact lens electrode. If repetitional stimuli of higher intensities were employed and responses were averaged, clinically satisfactory ERGs were recordable with skin electrodes in the closed-eye state.


Correspondence between psychological reports based on the Mini-Mult and the MMPI. In order to assess the utility of the Mini-Mult with a university counseling center clientele, MMPI answer sheets of 10 students at the University of Miami Counseling Center were scored for both the MMPI and the Mini-Mult. Four judges completed psychological reports (Q-item questionnaires) based on the profiles. Correlations between judges' responses to MMPI and Mini-Mult profiles were calculated as an indication of the correspondence between the two tests. In addition, correlations between judges' responses to repeated presentations of MMPI profiles were calculated as an indication of the judges' reliability over time. The results do not support the use of the Mini-Mult with a university counseling center clientele.


Locus of control and behavior in treatment groups. Studied the Rotter Locus of Control scale for effective prediction of behavior in small groups. Subjects were 205 male VA Hospital patients participating in self-directed groups who completed the AGCT, Psychological and Somatic Symptom Scales, and Rotter's I-E measure of locus of control. Group behavior was measured through sociometry and a Group Member Evaluation form. Three hypotheses were not supported: (a) Persons scoring high in the direction of internal control (internals) will be more likely to act to influence their social environment; (b) internals will be more active than externals in gathering and processing information in group discussions, and (c) internals will be more self-directed and less susceptible to being influenced by others. Two hypotheses were supported: (a) externals will express more somatic and psychological complaints than internals, and (b) externals will be perceived as behaving more defensively than internals. In contrast, intelligence was correlated with a large number of group process measures. Locus of control and intelligence measures predict different kinds of behavior in groups.


Synthesis and antimicrobial evaluation of quaternary salts of 4-phenyl-1,2,3,6-tetrahydropyridine and 3,6-dimethyl-6-phenyl-tetrahydro-2H-1,3-oxazine. Fifteen predominantly alkyl bromide quaternary salts of 1-substituted 4-phenyl-1,2,3,6-tetrahydropyridine and 10 from 3,6-dimethyl-l-phenyltetrahydro-2H-1,3-oxazine were synthesized. None was effective against the parasitic protozoan Eimeria tenella and the helminth trichostrongyle nematode. Nearly all inhibited Gram-positive and Gram-negative bacteria; maximum efficiency was obtained with nonyl through dodecyl bromide salt derivatives. Antifungal effectiveness paralleled these results. The oxazinium salt analogs were inhibitory in an in vitro peridontal microorganism screen. The decyl bromide derivative at 0.05% in drinking water prevented dental plaque and reduced calculus deposition in rats but not in hamsters fed cariogenic diets. A 0.01% concentration of the tetrahydropyridinium analog caused increased plaque in rats compared to nonmedicated control animals.


Analysis of fludrocortisone acetate and its solid dosage forms by high-performance liquid chromatography. A newly developed reversed-phase high-performance liquid chromatographic assay and test method for determining content uniformity are described for fludrocortisone acetate. The method is stability indicating and separates most known degradation products and impurities. In addition, the method is simple, sensitive, accurate, and relatively free of interferences. The coefficient of variation for multiple weight assays is between 0.3 and 1.8%.


Dielectric constants of solid-liquid and liquid-liquid systems as a function of composition. The dielectric constant of a solid substance in the dissolved state may be found by using a solvent with a dielectric constant that remains invariable when the solid substance is dissolved. The slope values obtained from dielectric constant versus concentration plots of the solid substance in two solvents with different dielectric constants are extrapolated or interpolated. The dielectric constant of a solid substance in the dissolved state also can be found directly from the dielectric constants of solutions of the solid in one solvent at two concentrations. The dielectric constants are converted to polarizations, and the two values allow calculations of the polarizations of the solvent and solute separately. From the polarization of the solute, one can calculate its dielectric constant (in dissolved state). Such a procedure is correct only if the dielectric constant is concentration independent.


Acid dissociation and metal complex formation constants of penicillamine, cysteine, and antiarthritic gold complexes at simulated biological conditions. Ionization constants for acid functions of D-penicillamine, L-cysteine, thiomalic acid, and thioglucose were measured by pH titration at 37 degrees and 0.15 M ionic strength. Chelate formation constants for these ligands with calcium(II), iron(III), and gold(I) were then determined under the same conditions chosen to approximate the in vivo situation. Only iron(III) formed both 1:1 and 1:2 chelates with D-penicillamine, L-cysteine, and thiomalate; calcium formed weak and gold strong 1:1 complexes with all ligands studied. Because of precipitate formation, the stability constants for the systems thioglucose-iron(III), D-penicillamine-gold(I), and L-cysteine-gold(I) had to be determined indirectly with thiomalic acid as the competing ligand. The in vivo fate of antiarthritic gold(I) compounds remained uncertain, but gold(I) chelates probably persist as such for extended periods.


Predictability of warfarin dose requirements: theoretical considerations. The theoretical basis of the predictability of warfarin maintenance dose requirements was evaluated using computer-generated hypothetical patient responses to a 10-mg/day "loading" dose regimen. Correlations between these responses and projected maintenance dose requirements were evaluated statistically, and a significant relationship was identified.


Pharmacokinetics of topically applied pilocarpine in the albino rabbit eye. The temporal and spatial pattern of [3H]-pilocarpine nitrate distribution in the albino rabbit eye following topical administration was determined. A four-compartment caternary chain model describing this disposition corresponds to the precorneal area, the cornea, the aqueous humor, and the lens and vitreous. Simultaneous computer fitting of data from tissue corresponding to some compartments in the model supported the proposed model. Additional support was provided by the excellent correlation between predicted and observed values in multiple-dosing studies. Several important aspects of ocular drug disposition are evident from the model. The extensive parallel elimination at the absorption site gives rise to an apparent absorption rate constant that is one to two orders of magnitude larger than the true absorption rate constant. In addition, aqueous flow accounts for most of the drug removal. Thus, major effects on absorption and elimination, independent of the drug structure, suggest the possibility of similar pharmacokinetics for vastly different drugs.